Synkopa wazowagalna – Patofizjologia i mechanizm

Synkopa wazowagalna
Patofizjologia i mechanizm

Synkopa wazowagalna jest najczęstszą formą omdlenia odruchowego, wynikającą z przejściowego globalnego niedokrwienia mózgu spowodowanego dysregulacją ciśnienia tętniczego i spadkiem mózgowego ciśnienia perfuzyjnego. Patofizjologia obejmuje złożony łuk odruchowy z częścią aferentną, aktywowaną przez bodźce takie jak stres czy ból, oraz częścią eferentną, prowadzącą do zwiększonej aktywności przywspółczulnej i wycofania współczulnej. W fazie przedomdleniowej obserwuje się spadek pojemności minutowej serca o 35-48% oraz wzrost oporu naczyniowego o 12-44% względem wartości wyjściowych, co skutkuje hipotensją i bradykardią, a w skrajnych przypadkach asystolią. Spektrum odpowiedzi hemodynamicznych obejmuje odpowiedź kardioinhibicyjną (znaczący spadek HR i kurczliwości) oraz wazodepresyjną (spadek ciśnienia tętniczego do nawet 80/20 mmHg bez istotnej zmiany HR), z dominacją mechanizmu zależną od wieku pacjenta.

Patofizjologia synkopy wazowagalnej

Synkopa wazowagalna (omdlenie wazowagalne) jest najczęstszą formą omdlenia odruchowego (refleksyjnego). Stanowi przejściową utratę świadomości spowodowaną globalnym niedokrwieniem mózgu, które wynika z nieprawidłowej regulacji ciśnienia tętniczego i ostatecznie prowadzi do spadku mózgowego ciśnienia perfuzyjnego.¹² Mechanizmy odpowiedzialne za ten stan są złożone i obejmują zarówno zmniejszenie pojemności minutowej serca, jak i spadek napięcia naczyniowego.³

Mechanizm refleksu wazowagalnego

Patofizjologię omdlenia wazowagalnego można rozpatrywać jako łuk odruchowy, składający się z części aferentnej (doprowadzającej) i eferentnej (odprowadzającej). Chociaż autonomiczny układ nerwowy pośredniczy w synkopie wazowagalnej, mechanizmy patofizjologiczne nie są w pełni poznane.⁴⁵

Część aferentna łuku odruchowego rozpoczyna się od bodźca wyzwalającego. Może nim być stres emocjonalny, ból, ale często pozostaje on niezidentyfikowany. Uważa się, że ten bodziec, zwykle w połączeniu z centralną hipowolemią (spowodowaną pionową pozycją ciała lub odwodnieniem), prowadzi do zwiększonej kurczliwości serca w warunkach stosunkowo niedostatecznie wypełnionej lewej komory. Może to aktywować mechanoreceptory w komorze, które przekazują sygnały za pośrednictwem włókien aferentnych nerwu błędnego do ośrodkowego układu nerwowego.⁶⁷

Zgodnie z teorią Bezolda-Jarischa, zmniejszenie obciążenia wstępnego komory stymuluje mechanoreceptory w dolno-tylnej części lewej komory, prowadząc do energicznego skurczu. Powoduje to zwiększone wyładowanie aferentne niezmielinizowanych włókien C z mechanoreceptorów komorowych, a ośrodkowy układ nerwowy odpowiada odruchowym wycofaniem aktywności współczulnej i zwiększonym wyładowaniem przywspółczulnym.⁸

Fazy odpowiedzi wazowagalnej

Pacjenci wrażliwi na test pochyleniowy przechodzą przez 4 fazy odruchu wazowagalnego:⁹¹⁰

Wczesna stabilizacja
Niestabilność krążeniowa (wczesna faza przedomdleniowa)
Końcowe niedociśnienie (późna faza przedomdleniowa)
Powrót do normalnego stanu

W trakcie fazy 2, zmienność ciśnienia tętniczego zwiększa się, występują regularne oscylacje o częstotliwości 0,1 Hz, znane jako fale Mayera.¹¹ W późnej fazie 3 dochodzi do spadku pojemności minutowej serca (35-48% od wartości wyjściowej) i konsekwentnego wzrostu oporu naczyniowego (12-44% od wartości wyjściowej).¹²

Część eferentna łuku odruchowego

Część eferentna łuku odruchowego jest lepiej poznana. Zwiększone wyładowanie nerwu błędnego (zwiększona aktywność przywspółczulna) w węźle zatokowym i przedsionkowo-komorowym powoduje zwolnienie częstości akcji serca. To spowolnienie może być znaczne, z asystolią trwającą nawet kilka sekund. Jednocześnie zmniejszona aktywność współczulna prowadzi do obniżenia napięcia naczyniowego zarówno w tętniczkach, jak i żyłkach.¹³

Rezultatem jest zmniejszone obciążenie wstępne, powrót żylny i objętość komór. Ponieważ pojemność minutowa serca jest iloczynem objętości wyrzutowej i częstości akcji serca, ten łuk odruchowy wpływa na oba czynniki w równaniu: spowalnia częstość akcji serca i zmniejsza objętość krwi krążącej. Prowadzi to do spadku średniego ciśnienia tętniczego. Autoregulacja mózgowa zapewnia stały przepływ krwi przez mózg w szerokim zakresie średniego ciśnienia tętniczego, ale gdy średnie ciśnienie tętnicze spada poniżej zdolności organizmu do autoregulacji, pacjent traci przytomność.¹⁴¹⁵

Mechanizmy hipotensji w synkopie wazowagalnej

W synkopie wazowagalnej występuje spektrum odpowiedzi hemodynamicznych:¹⁶

Odpowiedź kardiodepresyjna

Na jednym końcu spektrum znajduje się odpowiedź kardiodepresyjna (kardioinhibicyjna), charakteryzująca się znacznym spadkiem częstości akcji serca (efekt chronotropowy ujemny) i kurczliwości (efekt inotropowy ujemny), prowadzącym do zmniejszenia pojemności minutowej serca wystarczającego do wywołania utraty przytomności. Uważa się, że odpowiedź ta wynika głównie ze wzmocnienia napięcia przywspółczulnego.¹⁷¹⁸

Odpowiedź wazodepresyjna

Na drugim końcu spektrum znajduje się odpowiedź wazodepresyjna, spowodowana spadkiem ciśnienia tętniczego (do nawet 80/20 mmHg) bez znacznej zmiany częstości akcji serca. Zjawisko to występuje z powodu rozszerzenia naczyń krwionośnych, prawdopodobnie w wyniku wycofania napięcia układu współczulnego.¹⁹²⁰

Większość osób z omdleniem wazowagalnym ma mieszaną odpowiedź gdzieś pomiędzy tymi dwoma krańcami spektrum.²¹

Rola pojemności minutowej serca i oporu naczyniowego

Badania wykazały, że mechanizmy hipotensyjne różnią się w zależności od wieku pacjentów. U nastolatków i młodych dorosłych, postępująca hipotensja podczas faz 2 i 3 może być napędzana przez rozszerzenie naczyń lub spadającą pojemność minutową serca. Spadek pojemności minutowej jest wtórny do postępującego zmniejszenia objętości wyrzutowej, ponieważ krew gromadzi się w żyłach trzewnych.²²

U dorosłych spadek pojemności minutowej serca jest dominującym mechanizmem hipotensyjnym, ponieważ systemowy opór naczyniowy zawsze pozostaje powyżej poziomów wyjściowych.²³²⁴

Klasyczne badania nad omdleniem wazowagalnym, przeprowadzone na zdrowych młodych osobach, przeceniały rozszerzenie naczyń jako dominujący mechanizm hipotensyjny.²⁵ Wyniki nowszych badań wykazały, że zarówno zmniejszenie pojemności minutowej serca, jak i wycofanie napięcia naczynioskurczowego układu współczulnego przyczyniają się do rozwoju hipotensji w synkopie wazowagalnej.²⁶

Rola układu autonomicznego

Autonomiczny układ nerwowy reguluje funkcje fizjologiczne, które nie zależą od świadomości (trawienie, częstość akcji serca, ciśnienie krwi i inne). Składa się z dwóch podsystemów: współczulnego i przywspółczulnego (lub błędnego). Pierwszy stymuluje funkcje neurovegetatywne, podczas gdy drugi je hamuje.²⁷

Teoria żołądkowa

Pierwsze badania dotyczące patofizjologii omdlenia wazowagalnego wykazały, że zaangażowany jest paradoksalny i kompensacyjny odruch. Tak zwana „teoria komorowa” zakłada, że baroreceptory reagują na spadek ciśnienia krwi aktywacją układu współczulnego, powodując większą odpowiedź inotropową i chronotropową oraz obkurczenie naczyń obwodowych.²⁸

Aktywność współczulna i przywspółczulna

Gwałtowne przerwanie aktywności nerwowej współczulnej do naczyń mięśni szkieletowych, reprezentujące wycofanie współczulne, jest uważane za ważny krok w rozszerzeniu naczyń, które prowadzi do hipotensji.²⁹

Zmniejszenie aktywności współczulnej koreluje bezpośrednio ze średnim ciśnieniem tętniczym, podczas gdy aktywność przywspółczulna, mierzona analizą spektralną zmienności rytmu serca, pozostaje poniżej poziomu bazowego. Sugeruje to, że współczulna kontrola całkowitego oporu obwodowego jest dominującym mechanizmem odpowiedzialnym za omdlenie wazowagalne.³⁰

Jądro pasma samotnego pnia mózgu jest aktywowane bezpośrednio lub pośrednio przez bodziec wyzwalający, co prowadzi do jednoczesnego wzmocnienia napięcia układu przywspółczulnego (błędnego) i wycofania napięcia układu współczulnego.³¹

Neurohumoralne mechanizmy synkopy wazowagalnej

Potencjalne zdarzenia neurohumoralne, które uczestniczą w reakcjach wazowagalnych, są złożone i pozostają słabo poznane. Lepsze zrozumienie tych mechanizmów może prowadzić do bardziej specyficznych strategii terapeutycznych w przyszłości.³²

Aktywność neuroendokrynna odgrywa rolę w odruchu, prawdopodobnie jako mechanizm ochronny, i zaczyna się od uwolnienia wazopresyny, a następnie epinefryny. Wysokie poziomy epinefryny mają efekt rozszerzający naczynia na mięśnie szkieletowe, sprzyjając pewnemu spadkowi ciśnienia tętniczego.³³

Inne potencjalne mechanizmy obejmują zaangażowanie centralnych dróg serotoninergicznych i uwalnianie endogennych opioidów lub katecholamin.³⁴ Nieprawidłowe wydzielanie pewnych katecholamin, szczególnie epinefryny, lub reniny, endogennych peptydów opioidowych, wazopresyny, serotoniny lub endoteliny może przyczyniać się do patogenezy omdlenia wazowagalnego.³⁵

Głęboka hipotensja obserwowana w synkopie wazowagalnej była uważana za związaną z głębokim rozszerzeniem naczyń w mięśniach szkieletowych w wyniku stymulacji cholinergicznej.³⁶

Czynniki genetyczne i psychologiczne

Współzależność aspektów psychologicznych i synkopy wazowagalnej jest obecnie dobrze udokumentowana.³⁷ Zaburzenia serotoniny mogą odgrywać rolę w omdleniu neurogiennym. Uogólnione zaburzenia lękowe, zaburzenia paniki, depresja i uzależnienie od alkoholu występują częściej u pacjentów z omdleniami.³⁸

Wykazano, że pacjenci z omdleniem wazowagalnym często mają krewnego pierwszego stopnia, który również jest dotknięty tym schorzeniem. Chociaż udział genetyczny w synkopie wazowagalnej był przedmiotem dyskusji, niektóre dowody sugerują, że istnieje jeden główny składnik genetyczny: receptory adrenergiczne.³⁹

Badania wykazały związek między dodatnim testem pochyleniowym u pacjentów z omdleniami a obecnością polimorfizmów w dwóch receptorach adrenergicznych: Arg389Gly beta-1 i Arg347Cys alfa-1a.⁴⁰

Teorie patofizjologiczne

Istnieją dwie główne teorie fizjologiczne próbujące wyjaśnić występowanie omdlenia wazowagalnego:⁴¹

Teoria centralna

Według teorii centralnej van Lieshouta i współpracowników, odruch jest wyzwalany przez aktywację ośrodków korowo-podkorowych, z udziałem nekohormonów i neuroprzekaźników, które prowadzą do odruchu bradykardii-hipotensji z powodu takich czynników jak ból, strach lub emocje.⁴²

Teoria obwodowa

Teoria obwodowa Oberga i Thorena zakłada, że odruch jest wyzwalany przez stymulację mechanoreceptorów sercowych w lewej komorze, przedsionkach serca i łuku aorty, a także obwodowych chemoreceptorów naczyniowych z powodu przedłużonego utrzymywania pionowej pozycji ciała.⁴³

Te dwie teorie i inne mniej popularne pokazują, że mechanizm patofizjologiczny zespołu wazowagalnego wciąż nie jest w pełni określony. Dlatego wciąż testowane są nowe, bardziej zaawansowane metody analizy omdleń w poszukiwaniu lepszego zrozumienia ich mechanizmów.⁴⁴

Inne teorie i podejścia

Rola neuropeptydu Y

W patogenezie synkopy wazowagalnej ważną rolę odgrywa dysregulacja autonomicznego układu nerwowego. Upośledzone uwalnianie neuropeptydu Y (NPY) może odgrywać rolę w patogenezie omdlenia wazowagalnego. Inne hormony naczyniozwężające, takie jak endotelina-1 (ET-1) i angiotensyna (ANG), również mogą być zaangażowane w patomechanizmy.⁴⁵

Odruch trójdzielno-sercowy

Niedawno zaproponowano, że odruch trójdzielno-sercowy, wcześniej znany jako odruch oczno-sercowy, może być mechanizmem omdlenia wazowagalnego. Patofizjologia odruchu hipotensja/bradykardia odpowiedzialnego za omdlenie wazowagalne nie jest w pełni zrozumiała. Zarówno mechanizmy centralne, jak i obwodowe zostały zasugerowane w jego patogenezie, jednak ich względny wkład nie jest w pełni wyjaśniony.⁴⁶⁴⁷

Teoria obrony serca

Według teorii obrony serca, odruch wazowagalny wydaje się być mechanizmem ochronnym przed nadmierną aktywnością współczulną, a serce jest najbardziej wrażliwym narządem w tych warunkach. Jest to jedyna teoria unifikująca, która może wyjaśnić występowanie odruchu wazowagalnego i jego związane z nim selektywne korzyści, zarówno podczas stresu ortostatycznego, jak i emocjonalnego.⁴⁸

Implikacje kliniczne i terapeutyczne

Zrozumienie dominującego mechanizmu synkopy wazowagalnej ma kluczowe znaczenie dla określenia odpowiedniej strategii terapeutycznej. Pacjenci z dominującym komponentem wazodepresyjnym mogą korzystać z terapii mających na celu rozszerzenie objętości osocza lub promowanie zwężenia naczyń, podczas gdy interwencje ukierunkowane na bradykardię mogą być rozważane u osób z dominującym profilem kardioinhibicyjnym.⁴⁹

Dokumentowanie asystolii podczas spontanicznego zdarzenia nie oznacza, że jest to mechanizm dominujący, ponieważ asystolia może wystąpić po tym, jak wazodepresja już wywołała utratę przytomności.⁵⁰

Rola stymulacji serca

Terapia za pomocą stymulatora może być skuteczna u niektórych, ale nie u wszystkich pacjentów. Nie jest to zaskakujące, jeśli weźmiemy pod uwagę, że stymulacja jest prawdopodobnie skuteczna w przypadku odruchu asystolicznego, ale nie ma roli w zwalczaniu niedociśnienia, które często jest dominującym odruchem w synkopie wazowagalnej.⁵¹

Niedawne badanie z wykorzystaniem implantowanego rejestratora pętlowego jako standardu referencyjnego wykazało, że tylko około połowa pacjentów miała zarejestrowaną przerwę asystoliczną w momencie spontanicznego omdlenia, która ewentualnie mogłaby skorzystać ze stymulatora serca.⁵²

Kardioneuroablacja

Denerwacja autonomiczna serca została początkowo przeprowadzona przez endokardialne identyfikowanie pletury zwoików nerwowych nasierdziowych i ich ablację, bazując na celach neuromodulacji dla migotania przedsionków, z zachęcającymi wczesnymi wynikami. Istnieją ograniczone, ale rosnące dowody na to, że kardioneuroablacja może pomóc pacjentom z ciężkimi objawowo nawracającymi omdleniami wazowagalnymi z wyraźnym komponentem asystolicznym.⁵³

Istnieje ryzyko oferowania niewłaściwego leczenia w przypadku schorzenia głównie związanego z układem naczyniowym, co może wyjaśniać niski wskaźnik odpowiedzi na kardioneuroablację u niektórych pacjentów.⁵⁴

Podsumowując, istnieją zachęcające wyniki z systematycznych serii przypadków przemawiających za kardioneuroablacją. Wysoko wyselekcjonowana, bardzo objawowa grupa pacjentów z dominującym omdleniem kardioinhibicyjnym może odnieść korzyści z tej procedury, albo przez całkowite zniesienie omdleń, albo przez wydłużenie prodromów na tyle, aby zapobiec urazom.⁵⁵

Podsumowanie patofizjologii

Synkopa wazowagalna jest złożonym zjawiskiem fizjologicznym, które obejmuje interakcje między układem sercowo-naczyniowym a autonomicznym układem nerwowym. Główne mechanizmy obejmują:

Aktywację części aferentnej łuku odruchowego przez różne bodźce wyzwalające
Przetwarzanie sygnałów w ośrodkowym układzie nerwowym, szczególnie w jądrze pasma samotnego
Aktywację części eferentnej, powodującą zwiększone napięcie przywspółczulne i zmniejszone napięcie współczulne
Rozszerzenie naczyń i/lub bradykardię, prowadzące do hipotensji
Zmniejszenie przepływu krwi przez mózg poniżej progu autoregulacji, powodujące omdlenie

Względny udział komponentu wazodepresyjnego i kardioinhibicyjnego różni się w zależności od wieku i indywidualnych czynników. U młodszych pacjentów rozszerzenie naczyń może odgrywać większą rolę, podczas gdy u starszych dorosłych dominującym mechanizmem hipotensyjnym jest często spadek pojemności minutowej serca.⁵⁶

Zrozumienie tych złożonych mechanizmów jest kluczowe dla właściwej diagnozy i leczenia pacjentów z omdleniem wazowagalnym, a dalsze badania mogą prowadzić do bardziej ukierunkowanych i skutecznych strategii terapeutycznych.⁵⁷

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Materiały źródłowe

#1 Vasovagal Episode – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470277/
A vasovagal episode or vasovagal syncope is the most common form of reflex syncope. Reflex syncope describes any form of syncopal episode caused by a failure in the autoregulation of blood pressure, and ultimately, a drop in cerebral perfusion pressure resulting in a transient loss of consciousness. The mechanisms responsible for this are complex and can both depression of cardiac output as well as decreased vascular tone. […] The mechanisms responsible for this are complex and involve both depression of cardiac output as well as a decrease in vascular tone. […] It is helpful to think about the pathophysiology of vasovagal syncope as a reflex arc, with an afferent limb and an efferent limb. Although the autonomic nervous system mediates vasovagal syncope, pathophysiological mechanisms are not completely understood. The afferent limb of the reflex arc begins with a trigger. Although this trigger may be emotional stress or pain, it is often unidentifiable. It is believed that this trigger, usually in combination with central hypovolemia (from upright posture or dehydration) results in increased cardiac contractility in the setting of a relatively underfilled left ventricle. This may trigger mechanoreceptors in the ventricle that signal via vagal afferents to the central nervous system.
#2 Syncope: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/811669-overview
Syncope occurs as a consequence of global cerebral hypoperfusion. Brain parenchyma depends on adequate blood flow to provide a constant supply of glucose, the primary metabolic substrate. Brain tissue cannot store energy in the form of the high-energy phosphates found elsewhere in the body; consequently, a cessation of cerebral perfusion lasting only 3-5 seconds can result in syncope. […] Cerebral perfusion is maintained relatively constant by an intricate and complex feedback system involving cardiac output (CO), systemic vascular resistance (SVR), mean arterial pressure (MAP), intravascular volume status, cerebrovascular resistance with intrinsic autoregulation, and metabolic regulation. A clinically significant defect in any one of these systems or subclinical defects in several of them may cause syncope.
#3 Vasovagal Episode – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470277/
A vasovagal episode or vasovagal syncope is the most common form of reflex syncope. Reflex syncope describes any form of syncopal episode caused by a failure in the autoregulation of blood pressure, and ultimately, a drop in cerebral perfusion pressure resulting in a transient loss of consciousness. The mechanisms responsible for this are complex and can both depression of cardiac output as well as decreased vascular tone. […] The mechanisms responsible for this are complex and involve both depression of cardiac output as well as a decrease in vascular tone. […] It is helpful to think about the pathophysiology of vasovagal syncope as a reflex arc, with an afferent limb and an efferent limb. Although the autonomic nervous system mediates vasovagal syncope, pathophysiological mechanisms are not completely understood. The afferent limb of the reflex arc begins with a trigger. Although this trigger may be emotional stress or pain, it is often unidentifiable. It is believed that this trigger, usually in combination with central hypovolemia (from upright posture or dehydration) results in increased cardiac contractility in the setting of a relatively underfilled left ventricle. This may trigger mechanoreceptors in the ventricle that signal via vagal afferents to the central nervous system.
#4 Vasovagal Episode – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470277/
A vasovagal episode or vasovagal syncope is the most common form of reflex syncope. Reflex syncope describes any form of syncopal episode caused by a failure in the autoregulation of blood pressure, and ultimately, a drop in cerebral perfusion pressure resulting in a transient loss of consciousness. The mechanisms responsible for this are complex and can both depression of cardiac output as well as decreased vascular tone. […] The mechanisms responsible for this are complex and involve both depression of cardiac output as well as a decrease in vascular tone. […] It is helpful to think about the pathophysiology of vasovagal syncope as a reflex arc, with an afferent limb and an efferent limb. Although the autonomic nervous system mediates vasovagal syncope, pathophysiological mechanisms are not completely understood. The afferent limb of the reflex arc begins with a trigger. Although this trigger may be emotional stress or pain, it is often unidentifiable. It is believed that this trigger, usually in combination with central hypovolemia (from upright posture or dehydration) results in increased cardiac contractility in the setting of a relatively underfilled left ventricle. This may trigger mechanoreceptors in the ventricle that signal via vagal afferents to the central nervous system.
#5 Vasovagal Syncope: A Review of Current and Future Strategies – touchCARDIOLOGY
https://touchcardio.com/syncope/journal-articles/vasovagal-syncope-a-review-of-current-and-future-strategies/
Vasovagal syncope is common, and while it is usually associated with a benign prognosis, it results in significant physical and psychological morbidity for affected individuals. Despite comprehensive understanding of the underlying pathophysiology, there have been few definitive therapeutic advances until recent randomized, controlled trials in pharmacotherapy, pacing and cardioneuroablation. […] Despite advances in the understanding of the pathophysiology of VVS, significant uncertainty remains. Individuals with VVS represent a heterogenous patient population, and different mechanisms are likely to contribute. These mechanisms are still not fully understood. Therefore, determining dominant mechanisms and modifying therapies accordingly is not always possible. In this review, we first describe the pathophysiology of the condition and discuss an approach for evaluating patients with VVS, emphasising holistic, multifaceted care.
#6 Vasovagal Episode – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470277/
A vasovagal episode or vasovagal syncope is the most common form of reflex syncope. Reflex syncope describes any form of syncopal episode caused by a failure in the autoregulation of blood pressure, and ultimately, a drop in cerebral perfusion pressure resulting in a transient loss of consciousness. The mechanisms responsible for this are complex and can both depression of cardiac output as well as decreased vascular tone. […] The mechanisms responsible for this are complex and involve both depression of cardiac output as well as a decrease in vascular tone. […] It is helpful to think about the pathophysiology of vasovagal syncope as a reflex arc, with an afferent limb and an efferent limb. Although the autonomic nervous system mediates vasovagal syncope, pathophysiological mechanisms are not completely understood. The afferent limb of the reflex arc begins with a trigger. Although this trigger may be emotional stress or pain, it is often unidentifiable. It is believed that this trigger, usually in combination with central hypovolemia (from upright posture or dehydration) results in increased cardiac contractility in the setting of a relatively underfilled left ventricle. This may trigger mechanoreceptors in the ventricle that signal via vagal afferents to the central nervous system.
#7 What is the mechanism of vasovagal syncope? | Medcrine Academy
https://medcrine.com/mechanism-of-vasovagal-syncope
A vasovagal syncope is a condition that causes fainting in some individuals. It is a syndrome of cardiac slowing with hypotension (low blood pressure) that occurs in some individuals who experience intense emotional disturbances. The vasovagal reaction consists of vasodilatation and bradycardia. During a prolonged standing period, the vasovagal reaction is triggered by a reduction of the central blood volume because of pooling in the lower body veins. The muscle vasodilator system may become activated, and at the same time, the vagal cardioinhibitory center transmits strong signals to the heart to slow the heart rate markedly. The arterial pressure falls rapidly, which reduces blood flow to the brain and causes the person to lose consciousness. The resultant arterial hypotension is sensed in the carotid sinus baroreceptors, and afferent fibers from these receptors trigger autonomic signals that increase cardiac rate and contractility. However, pressure receptors in the wall of the left ventricle respond by sending signals that trigger paradoxical bradycardia and decreased contractility, resulting in suddenly marked hypotension. The nucleus tractus solitarii of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of the parasympathetic nervous system (vagal) tone and withdrawal of sympathetic nervous system tone.
#8
https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/syncope/
Vasovagal syncope, also known as neurocardiogenic syncope, is commonly described using the Bezold-Jarisch reflex model, where a reduction in ventricular preload stimulates mechanoreceptors in the inferoposterior part of the left ventricle leading to a vigorous contraction. This causes an increased afferent discharge of the unmyelinated C fibers from the ventricular mechanoreceptors and the central nervous system responds with reflex sympathetic withdrawal and increased parasympathetic output. These signals cause vasodilation, hypotension and bradycardia. This ineffective reflex response causes venous pooling in the periphery or splanchnic regions or both with paradoxical vasodilation leading to further hypotension and loss of consciousness. […] Other potential mechanisms include involvement of central serotonergic pathways and release of endogenous opioids or catecholamines. Vaddadi et al described 2 phenotypes in patients with recurrent vasovagal syncope, both associated with reduced norepinephrine availability: 1 phenotype with low pressure (systolic blood pressure less than 100 mm Hg) and low tyrosine hydroxylase levels; and 1 phenotype with normal pressure (systolic blood pressure greater than 100 mm Hg) and increased norepinephrine reuptake.
#9 Pathophysiology of the vasovagal response
https://pmc.ncbi.nlm.nih.gov/articles/PMC5984661/
In part I of this study, we found that the classical studies on vasovagal syncope, conducted in fit young subjects, overstated vasodilatation as the dominant hypotensive mechanism. […] This has allowed us to analyze in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. All tilt-sensitive patients appear to progress through 4 phases: (1) early stabilization, (2) circulatory instability, (3) terminal hypotension, and (4) recovery. The physiology responsible for each phase is discussed. […] In adults a fall in cardiac output is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels. […] Careful analysis of continuous BP recordings (and other derived variables) during orthostatic stress allowed us to divide the sequence of hemodynamic events leading to vasovagal syncope into 4 phases: phase 1: early stabilization; phase 2: circulatory instability (early presyncope); phase 3: terminal hypotension (late presyncope) and syncope; phase 4: recovery.
#10 The Pathophysiology of the Vasovagal Response
https://touroscholar.touro.edu/nymc_fac_pubs/1906/
In part I of this study, we found that the classical studies on vasovagal syncope, conducted in fit young subjects, overstated vasodilatation as the dominant hypotensive mechanism. […] This has allowed us to analyze in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. […] All tilt-sensitive patients appear to progress through 4 phases: (1) early stabilization, (2) circulatory instability, (3) terminal hypotension, and (4) recovery. The physiology responsible for each phase is discussed. […] In teenagers and young adults, progressive hypotension during phases 2 and 3 can be driven by vasodilatation or falling cardiac output. The fall in cardiac output is secondary to a progressive decrease in stroke volume because blood is pooled in the splanchnic veins. […] In adults a fall in cardiac output is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels.
#11 Pathophysiology of the vasovagal response
https://pmc.ncbi.nlm.nih.gov/articles/PMC5984661/
The increase in BP variability consists of regular oscillations at a frequency of 0.1 Hz, known as Mayer waves. […] Late phase 3 was marked by a fall in CO (35%48% from baseline) and a consistent increase in SVR (12%44% from baseline). Therefore, in adults the fall in CO was the dominant hypotensive mechanism, because SVR always remained above baseline levels. […] The data support our previous conclusion that in the classical Barcroft papers, major vasodilatation (~40%) was overstated as the dominant hypotensive mechanism of vasovagal syncope. […] The mechanism for recovery is more likely the effect of increased venous return on stroke volume (Frank-Starling relationship) than the reversal of a cardioinhibitory reflex.
#12 Pathophysiology of the vasovagal response
https://pmc.ncbi.nlm.nih.gov/articles/PMC5984661/
The increase in BP variability consists of regular oscillations at a frequency of 0.1 Hz, known as Mayer waves. […] Late phase 3 was marked by a fall in CO (35%48% from baseline) and a consistent increase in SVR (12%44% from baseline). Therefore, in adults the fall in CO was the dominant hypotensive mechanism, because SVR always remained above baseline levels. […] The data support our previous conclusion that in the classical Barcroft papers, major vasodilatation (~40%) was overstated as the dominant hypotensive mechanism of vasovagal syncope. […] The mechanism for recovery is more likely the effect of increased venous return on stroke volume (Frank-Starling relationship) than the reversal of a cardioinhibitory reflex.
#13 Vasovagal Episode – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470277/
The efferent limb of the reflex arc is better understood. Increased vagal firing (increased parasympathetic activity) at the sinus node and the atrioventricular node causes a decrease in heart rate. This decrease in heart rate can be profound, with asystole that can be several seconds long. At the same time, decreased sympathetic activity results in decreased vascular tone in both arterioles and venules. The results in decreased preload, venous return, and ventricular volume. Since cardiac output is the product of stroke volume and heart rate, this reflex arc affects both factors in the equation: slowing the heart rate and decreasing the amount of volume. This results in a drop in the patient’s mean arterial pressure. Cerebral autoregulation results in constant cerebral blood flow over a wide range of mean arterial pressures, but when the mean arterial pressure falls below the body’s ability to autoregulate, the patient loses consciousness. Typically, if the patient falls or is laid supine, the increase in circulating blood volume from the lower extremities combined with the decreased work necessary to get blood to the brain (i.e., the heart does not have to pump „uphill” against gravity) will cause the patient to regain consciousness rapidly.
#14 Vasovagal Episode – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470277/
The efferent limb of the reflex arc is better understood. Increased vagal firing (increased parasympathetic activity) at the sinus node and the atrioventricular node causes a decrease in heart rate. This decrease in heart rate can be profound, with asystole that can be several seconds long. At the same time, decreased sympathetic activity results in decreased vascular tone in both arterioles and venules. The results in decreased preload, venous return, and ventricular volume. Since cardiac output is the product of stroke volume and heart rate, this reflex arc affects both factors in the equation: slowing the heart rate and decreasing the amount of volume. This results in a drop in the patient’s mean arterial pressure. Cerebral autoregulation results in constant cerebral blood flow over a wide range of mean arterial pressures, but when the mean arterial pressure falls below the body’s ability to autoregulate, the patient loses consciousness. Typically, if the patient falls or is laid supine, the increase in circulating blood volume from the lower extremities combined with the decreased work necessary to get blood to the brain (i.e., the heart does not have to pump „uphill” against gravity) will cause the patient to regain consciousness rapidly.
#15 Vasovagal syncope – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/vasovagal-syncope/symptoms-causes/syc-20350527
Vasovagal syncope occurs when the part of your nervous system that regulates heart rate and blood pressure overreacts to a trigger. […] During a vasovagal syncope episode, your heart rate slows, and the blood vessels in your legs widen. This allows blood to pool in your legs, which lowers your blood pressure. The drop in blood pressure and slowed heart rate quickly reduce blood flow to your brain, and you faint.
#16 Reflex syncope – Wikipedia
https://en.wikipedia.org/wiki/Reflex_syncope
Reflex syncope is divided into three types: vasovagal, situational, and carotid sinus. […] The underlying mechanism involves the nervous system slowing the heart rate and dilating blood vessels, resulting in low blood pressure and thus not enough blood flow to the brain. […] Regardless of the trigger, the mechanism of syncope is similar in the various vasovagal syncope syndromes. The nucleus tractus solitarii of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of parasympathetic nervous system (vagal) tone and withdrawal of sympathetic nervous system tone. […] This results in a spectrum of hemodynamic responses: On one end of the spectrum is the cardioinhibitory response, characterized by a drop in heart rate (negative chronotropic effect) and in contractility (negative inotropic effect) leading to a decrease in cardiac output that is significant enough to result in a loss of consciousness. It is thought that this response results primarily from enhancement in parasympathetic tone.
#17 Reflex syncope – Wikipedia
https://en.wikipedia.org/wiki/Reflex_syncope
Reflex syncope is divided into three types: vasovagal, situational, and carotid sinus. […] The underlying mechanism involves the nervous system slowing the heart rate and dilating blood vessels, resulting in low blood pressure and thus not enough blood flow to the brain. […] Regardless of the trigger, the mechanism of syncope is similar in the various vasovagal syncope syndromes. The nucleus tractus solitarii of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of parasympathetic nervous system (vagal) tone and withdrawal of sympathetic nervous system tone. […] This results in a spectrum of hemodynamic responses: On one end of the spectrum is the cardioinhibitory response, characterized by a drop in heart rate (negative chronotropic effect) and in contractility (negative inotropic effect) leading to a decrease in cardiac output that is significant enough to result in a loss of consciousness. It is thought that this response results primarily from enhancement in parasympathetic tone.
#18 Pacing for Vasovagal Syncope | AER Journal
https://www.aerjournal.com/articles/pacing-vasovagal-syncope-0?language_content_entity=en
Vasovagal syncope (VVS) is due to a common autonomic reflex involving the cardiovascular system. It is associated with bradycardia (cardioinhibitory response) and/or hypotension (vasodepressor response), likely mediated by parasympathetic activation and sympathetic inhibition. […] The exact mechanism underlying and triggering the vasovagal reflex continues to be studied and debated, but inputs causing the reflex are manifold. Afferent signals from the peripheral vagus (and perhaps from central locations), processed in the nucleus tractus solitarius, elicit an efferent, phasic, abrupt and rapidly reversible parasympathetic response, causing transient relative sinus bradycardia, sinus arrest or paroxysmal atrioventricular (AV) block. […] There can be impairment of ventricular contractility, with consequent reduction in cardiac output, and changes in cerebrovascular autoregulation.
#19 Reflex syncope – Wikipedia
https://en.wikipedia.org/wiki/Reflex_syncope
On the other end of the spectrum is the vasodepressor response, caused by a drop in blood pressure (to as low as 80/20) without much change in heart rate. This phenomenon occurs due to dilation of the blood vessels, probably as a result of withdrawal of sympathetic nervous system tone. […] The majority of people with vasovagal syncope have a mixed response somewhere between these two ends of the spectrum. […] Vasovagal syncope may be part of an evolved response, specifically, the fight-or-flight response.
#20 Pacemaker for vasovagal syncope: good for few
https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-2/Pacemaker-for-vasovagal-syncope-good-for-few-Title-Pacemaker-for-vasovagal-s
Vasovagal syncope refers to a reflex response that, when triggered, gives rise to vasodilatation and bradycardia, although the contribution of both to systemic hypotension and cerebral hypoperfusion may differ considerably. […] It is valuable to assess the relative contribution of cardioinhibition and vasodepression before embarking on treatment as there are different therapeutic strategies for the two aspects. […] Among those settings, cardiac pacing may be reserved to those patients with cardioinhibitory vasovagal syncope with a frequency 5 attacks per year or severe physical injury or accident and age 40. […] In order to limit the vasodepressor component of the vasovagal reflex, dual-chamber pacemaker with rate-hysteresis features are usually preferred even though formal comparison studies among modes of pacing have not yet been performed.
#21 Reflex syncope – Wikipedia
https://en.wikipedia.org/wiki/Reflex_syncope
On the other end of the spectrum is the vasodepressor response, caused by a drop in blood pressure (to as low as 80/20) without much change in heart rate. This phenomenon occurs due to dilation of the blood vessels, probably as a result of withdrawal of sympathetic nervous system tone. […] The majority of people with vasovagal syncope have a mixed response somewhere between these two ends of the spectrum. […] Vasovagal syncope may be part of an evolved response, specifically, the fight-or-flight response.
#22 The Pathophysiology of the Vasovagal Response
https://touroscholar.touro.edu/nymc_fac_pubs/1113/
In part I of this study, we found that the classical studies on vasovagal syncope, conducted in fit young subjects, overstated vasodilatation as the dominant hypotensive mechanism. […] This has allowed us to analyze in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. […] All tilt-sensitive patients appear to progress through 4 phases: (1) early stabilization, (2) circulatory instability, (3) terminal hypotension, and (4) recovery. […] The physiology responsible for each phase is discussed. […] In teenagers and young adults, progressive hypotension during phases 2 and 3 can be driven by vasodilatation or falling cardiac output. […] The fall in cardiac output is secondary to a progressive decrease in stroke volume because blood is pooled in the splanchnic veins. […] In adults a fall in cardiac output is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels.
#23 Pathophysiology of the vasovagal response
https://pmc.ncbi.nlm.nih.gov/articles/PMC5984661/
In part I of this study, we found that the classical studies on vasovagal syncope, conducted in fit young subjects, overstated vasodilatation as the dominant hypotensive mechanism. […] This has allowed us to analyze in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. All tilt-sensitive patients appear to progress through 4 phases: (1) early stabilization, (2) circulatory instability, (3) terminal hypotension, and (4) recovery. The physiology responsible for each phase is discussed. […] In adults a fall in cardiac output is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels. […] Careful analysis of continuous BP recordings (and other derived variables) during orthostatic stress allowed us to divide the sequence of hemodynamic events leading to vasovagal syncope into 4 phases: phase 1: early stabilization; phase 2: circulatory instability (early presyncope); phase 3: terminal hypotension (late presyncope) and syncope; phase 4: recovery.
#24 Hemodynamic Mechanism of Vasovagal Syncope
https://www.jstage.jst.go.jp/article/ihj1960/37/3/37_3_361/_article
Vasovagal syncope is a common clinical problem, however the hemodynamic mechanism is not clearly understood. […] The aim of the present study was to investigate the circulatory control mechanism of vasovagal syncope provoked by the head-up tilt test. […] The effect of head-up tilt resembled that of hypovolemia. […] During vasovagal syncope, the heart rate and blood pressure fell precipitously and significantly, the cardiac index was reduced from 2.220.43 to 1.510.32 liters/min/m2 (p value0.05) and the systemic vascular resistance index decreased from 3, 689859 to 1, 999543.9 dynes s cm5/m2 (p value0.05). […] The results of our study showed that both reduction of cardiac output and withdrawal of sympathetic vasoconstriction tone contribute to the development of hypotension in vasovagal syncope.
#25 Pathophysiology of the vasovagal response
https://pmc.ncbi.nlm.nih.gov/articles/PMC5984661/
The increase in BP variability consists of regular oscillations at a frequency of 0.1 Hz, known as Mayer waves. […] Late phase 3 was marked by a fall in CO (35%48% from baseline) and a consistent increase in SVR (12%44% from baseline). Therefore, in adults the fall in CO was the dominant hypotensive mechanism, because SVR always remained above baseline levels. […] The data support our previous conclusion that in the classical Barcroft papers, major vasodilatation (~40%) was overstated as the dominant hypotensive mechanism of vasovagal syncope. […] The mechanism for recovery is more likely the effect of increased venous return on stroke volume (Frank-Starling relationship) than the reversal of a cardioinhibitory reflex.
#26 Hemodynamic Mechanism of Vasovagal Syncope
https://www.jstage.jst.go.jp/article/ihj1960/37/3/37_3_361/_article
Vasovagal syncope is a common clinical problem, however the hemodynamic mechanism is not clearly understood. […] The aim of the present study was to investigate the circulatory control mechanism of vasovagal syncope provoked by the head-up tilt test. […] The effect of head-up tilt resembled that of hypovolemia. […] During vasovagal syncope, the heart rate and blood pressure fell precipitously and significantly, the cardiac index was reduced from 2.220.43 to 1.510.32 liters/min/m2 (p value0.05) and the systemic vascular resistance index decreased from 3, 689859 to 1, 999543.9 dynes s cm5/m2 (p value0.05). […] The results of our study showed that both reduction of cardiac output and withdrawal of sympathetic vasoconstriction tone contribute to the development of hypotension in vasovagal syncope.
#27 Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors – Medwave
http://viejo.medwave.cl/link.cgi/English/Updates/Supplements/6842.act?ver=sindiseno
Vasovagal syncope is a type of orthostatic intolerance. This term is used to refer to a syncope that results from reflex mechanisms associated with inappropriate vasodilation and variable degrees of bradycardia. […] The autonomic nervous system regulates physiological functions that do not depend on consciousness (digestion, heart rate, blood pressure, and etcetera). It consists of two subsystems: the sympathetic and the parasympathetic system (or vagal). The first one stimulates neurovegetative functions while the second one depresses them. […] The first studies to investigate the pathophysiology of the vasovagal syncope showed that a paradoxical and compensatory reflex was involved. The so-called „ventricular theory” postulates that the baroreceptors react to the decrease of blood pressure with an activation of the sympathetic nervous system, causing a greater inotropic and chronotropic response as well as peripheral vasoconstriction.
#28 Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors – Medwave
http://viejo.medwave.cl/link.cgi/English/Updates/Supplements/6842.act?ver=sindiseno
Vasovagal syncope is a type of orthostatic intolerance. This term is used to refer to a syncope that results from reflex mechanisms associated with inappropriate vasodilation and variable degrees of bradycardia. […] The autonomic nervous system regulates physiological functions that do not depend on consciousness (digestion, heart rate, blood pressure, and etcetera). It consists of two subsystems: the sympathetic and the parasympathetic system (or vagal). The first one stimulates neurovegetative functions while the second one depresses them. […] The first studies to investigate the pathophysiology of the vasovagal syncope showed that a paradoxical and compensatory reflex was involved. The so-called „ventricular theory” postulates that the baroreceptors react to the decrease of blood pressure with an activation of the sympathetic nervous system, causing a greater inotropic and chronotropic response as well as peripheral vasoconstriction.
#29 Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors – Medwave
http://viejo.medwave.cl/link.cgi/English/Updates/Supplements/6842.act?ver=sindiseno
The abrupt interruption of sympathetic nerve activity to the vasculature of skeletal muscles, representing a sympathetic withdrawal, has been considered an important step for the vasodilation that leads to hypotension. […] This reduction in sympathetic activity directly correlated with the mean arterial blood pressure, while the parasympathetic activity, measured by spectral analysis, of the heart rate variability remained below the baseline, suggesting that the sympathetic control of total peripheral resistance was the predominant mechanism responsible for vasovagal syncope. […] The interrelation of psychological aspects and vasovagal syncope is now well documented. […] It has been well demonstrated that patients with vasovagal syncope frequently have a first-degree relative who is also affected. Although genetic participation in the vasovagal syncope has been debated, some evidence suggests that there is one major genetic component: the adrenergic receptors. Studies have shown an association between positive tilt test in patients with syncope and the presence of polymorphisms in two adrenergic receptors, the Arg389Gly of beta-1 and the Arg347Cys of the alpha-1a.
#30 Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors – Medwave
http://viejo.medwave.cl/link.cgi/English/Updates/Supplements/6842.act?ver=sindiseno
The abrupt interruption of sympathetic nerve activity to the vasculature of skeletal muscles, representing a sympathetic withdrawal, has been considered an important step for the vasodilation that leads to hypotension. […] This reduction in sympathetic activity directly correlated with the mean arterial blood pressure, while the parasympathetic activity, measured by spectral analysis, of the heart rate variability remained below the baseline, suggesting that the sympathetic control of total peripheral resistance was the predominant mechanism responsible for vasovagal syncope. […] The interrelation of psychological aspects and vasovagal syncope is now well documented. […] It has been well demonstrated that patients with vasovagal syncope frequently have a first-degree relative who is also affected. Although genetic participation in the vasovagal syncope has been debated, some evidence suggests that there is one major genetic component: the adrenergic receptors. Studies have shown an association between positive tilt test in patients with syncope and the presence of polymorphisms in two adrenergic receptors, the Arg389Gly of beta-1 and the Arg347Cys of the alpha-1a.
#31 Reflex syncope – Wikipedia
https://en.wikipedia.org/wiki/Reflex_syncope
Reflex syncope is divided into three types: vasovagal, situational, and carotid sinus. […] The underlying mechanism involves the nervous system slowing the heart rate and dilating blood vessels, resulting in low blood pressure and thus not enough blood flow to the brain. […] Regardless of the trigger, the mechanism of syncope is similar in the various vasovagal syncope syndromes. The nucleus tractus solitarii of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of parasympathetic nervous system (vagal) tone and withdrawal of sympathetic nervous system tone. […] This results in a spectrum of hemodynamic responses: On one end of the spectrum is the cardioinhibitory response, characterized by a drop in heart rate (negative chronotropic effect) and in contractility (negative inotropic effect) leading to a decrease in cardiac output that is significant enough to result in a loss of consciousness. It is thought that this response results primarily from enhancement in parasympathetic tone.
#32 Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation – UpToDate
https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation
Vasovagal syncope is the most common cause of syncope in patients of all ages, and its diagnosis may usually be made by taking a careful history detailing the features of symptomatic events and identifying well-known triggers; however, a classic history is not always present, especially in older individuals. […] Understanding the pathophysiology involved in reflex syncope is essential to understanding its clinical manifestations and prevention strategies. Both neural (arterial and cardiac baroreceptor, including carotid sinus reflexes) and endogenous neuroendocrine pathways are thought to be involved. […] The potential neurohumoral events that participate in vasovagal reactions are complex and remain poorly understood; better understanding may be expected to lead to more specific therapeutic strategies in the future.
#33 Vasovagal Syncope: A Review of Current and Future Strategies – touchCARDIOLOGY
https://touchcardio.com/syncope/journal-articles/vasovagal-syncope-a-review-of-current-and-future-strategies/
Neuroendocrine activity plays a part in the reflex probably as a protective mechanism and begins with vasopressin release, followed by epinephrine. High epinephrine levels have a vasodilatory effect on skeletal muscle, favouring some fall in BP. […] The different heart rate and BP behaviours during orthostasis can be classified into collapse patterns, which are described and later modified by the Vasovagal Syncope International Study (VASIS). […] The two main interventions that can be offered under certain conditions are pacemaker therapy and cardioneuroablation (CNA). […] Cardiac autonomic denervation was initially undertaken by endocardial identification of epicardial ganglionated plexi and their ablation, building upon neuromodulation targets for atrial fibrillation with encouraging early results. Subsequently, there has been limited but growing evidence that cardioneuroablation may help patients with severely symptomatic recurrent VVS with a pronounced asystolic component.
#34
https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/syncope/
Vasovagal syncope, also known as neurocardiogenic syncope, is commonly described using the Bezold-Jarisch reflex model, where a reduction in ventricular preload stimulates mechanoreceptors in the inferoposterior part of the left ventricle leading to a vigorous contraction. This causes an increased afferent discharge of the unmyelinated C fibers from the ventricular mechanoreceptors and the central nervous system responds with reflex sympathetic withdrawal and increased parasympathetic output. These signals cause vasodilation, hypotension and bradycardia. This ineffective reflex response causes venous pooling in the periphery or splanchnic regions or both with paradoxical vasodilation leading to further hypotension and loss of consciousness. […] Other potential mechanisms include involvement of central serotonergic pathways and release of endogenous opioids or catecholamines. Vaddadi et al described 2 phenotypes in patients with recurrent vasovagal syncope, both associated with reduced norepinephrine availability: 1 phenotype with low pressure (systolic blood pressure less than 100 mm Hg) and low tyrosine hydroxylase levels; and 1 phenotype with normal pressure (systolic blood pressure greater than 100 mm Hg) and increased norepinephrine reuptake.
#35 Neurally Mediated Syncope | Vanderbilt Autonomic Dysfunction Center
https://www.vumc.org/autonomic-dysfunction-center/neurally-mediated-syncope
Inappropriate secretion of some catecholamines, particularly epinephrine, or of renin, endogenous opioid peptides, vasopressin, serotonin, or endothelin may contribute to the pathogenesis of NMS. […] The profound hypotension observed in NMS was thought to be related to profound vasodilation in skeletal muscle resulting from cholinergic stimulation. […] They postulated that cerebral ischemia in areas regulating cardiovascular function could initiate NMS. Results of some studies raise the possibility that abnormalities within the CNS, either functional or structural, play a pivotal role in the pathogenesis of NMS.
#36 Neurally Mediated Syncope | Vanderbilt Autonomic Dysfunction Center
https://www.vumc.org/autonomic-dysfunction-center/neurally-mediated-syncope
Inappropriate secretion of some catecholamines, particularly epinephrine, or of renin, endogenous opioid peptides, vasopressin, serotonin, or endothelin may contribute to the pathogenesis of NMS. […] The profound hypotension observed in NMS was thought to be related to profound vasodilation in skeletal muscle resulting from cholinergic stimulation. […] They postulated that cerebral ischemia in areas regulating cardiovascular function could initiate NMS. Results of some studies raise the possibility that abnormalities within the CNS, either functional or structural, play a pivotal role in the pathogenesis of NMS.
#37 Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors – Medwave
http://viejo.medwave.cl/link.cgi/English/Updates/Supplements/6842.act?ver=sindiseno
The abrupt interruption of sympathetic nerve activity to the vasculature of skeletal muscles, representing a sympathetic withdrawal, has been considered an important step for the vasodilation that leads to hypotension. […] This reduction in sympathetic activity directly correlated with the mean arterial blood pressure, while the parasympathetic activity, measured by spectral analysis, of the heart rate variability remained below the baseline, suggesting that the sympathetic control of total peripheral resistance was the predominant mechanism responsible for vasovagal syncope. […] The interrelation of psychological aspects and vasovagal syncope is now well documented. […] It has been well demonstrated that patients with vasovagal syncope frequently have a first-degree relative who is also affected. Although genetic participation in the vasovagal syncope has been debated, some evidence suggests that there is one major genetic component: the adrenergic receptors. Studies have shown an association between positive tilt test in patients with syncope and the presence of polymorphisms in two adrenergic receptors, the Arg389Gly of beta-1 and the Arg347Cys of the alpha-1a.
#38 Evaluation of Syncope | AAFP
https://www.aafp.org/pubs/afp/issues/2005/1015/p1492.html/1000
Situational syncope is related to micturition, defecation, coughing, or gastrointestinal stimulation. The history is diagnostic. The mechanism involves a similar vagal stimulation in addition to the decreased venous return associated with the Valsalva maneuver. […] Abnormal serotonin metabolism may play a role in neurally mediated syncope, and generalized anxiety disorder, panic disorder, major depression, and alcohol dependence have been reported more commonly in patients with syncope.
#39 Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors – Medwave
http://viejo.medwave.cl/link.cgi/English/Updates/Supplements/6842.act?ver=sindiseno
The abrupt interruption of sympathetic nerve activity to the vasculature of skeletal muscles, representing a sympathetic withdrawal, has been considered an important step for the vasodilation that leads to hypotension. […] This reduction in sympathetic activity directly correlated with the mean arterial blood pressure, while the parasympathetic activity, measured by spectral analysis, of the heart rate variability remained below the baseline, suggesting that the sympathetic control of total peripheral resistance was the predominant mechanism responsible for vasovagal syncope. […] The interrelation of psychological aspects and vasovagal syncope is now well documented. […] It has been well demonstrated that patients with vasovagal syncope frequently have a first-degree relative who is also affected. Although genetic participation in the vasovagal syncope has been debated, some evidence suggests that there is one major genetic component: the adrenergic receptors. Studies have shown an association between positive tilt test in patients with syncope and the presence of polymorphisms in two adrenergic receptors, the Arg389Gly of beta-1 and the Arg347Cys of the alpha-1a.
#40 Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors – Medwave
http://viejo.medwave.cl/link.cgi/English/Updates/Supplements/6842.act?ver=sindiseno
The abrupt interruption of sympathetic nerve activity to the vasculature of skeletal muscles, representing a sympathetic withdrawal, has been considered an important step for the vasodilation that leads to hypotension. […] This reduction in sympathetic activity directly correlated with the mean arterial blood pressure, while the parasympathetic activity, measured by spectral analysis, of the heart rate variability remained below the baseline, suggesting that the sympathetic control of total peripheral resistance was the predominant mechanism responsible for vasovagal syncope. […] The interrelation of psychological aspects and vasovagal syncope is now well documented. […] It has been well demonstrated that patients with vasovagal syncope frequently have a first-degree relative who is also affected. Although genetic participation in the vasovagal syncope has been debated, some evidence suggests that there is one major genetic component: the adrenergic receptors. Studies have shown an association between positive tilt test in patients with syncope and the presence of polymorphisms in two adrenergic receptors, the Arg389Gly of beta-1 and the Arg347Cys of the alpha-1a.
#41 The complexity of hemodynamic response to the tilt test with and without nitroglycerine provocation in patients with vasovagal syncope | Scientific Reports
https://www.nature.com/articles/s41598-018-32718-2
The physiological mechanism of vasovagal syncope is still not fully understood. There are some theories explaining its etiology, but the principal cause remains unknown. […] The autonomic malfunction causing reflex syncope is either a vasodepressive response (loss of sympathetic vasoconstrictive tone with lowering of blood pressure) or cardio-depressive response (active parasympathetic stimulation leading to bradycardia or asystole) resulting in impaired cerebral perfusion. […] The pathophysiology of neurocardiogenic syncope is heterogeneous. The experience gained so far and assessment of the results of tilt test show that a short pause in cerebral perfusion (lasting 68s) or a decrease in systolic blood pressure (sBP) down to 60mmHg or less is associated with syncope. […] There are two physiological theories attempting to explain the occurrence of vasovagal syncope. According to the central theory by van Lieshout and al., the reflex is triggered by activation of the cortical-subcortical centers, participated by necrohormones and neurotransmitters which lead to the bradycardia-hypotension reflex due to factors such as pain, fear or emotions. The peripheral theory by Oberg and Thoren assumes that the reflex is triggered by stimulation of the cardiac mechanoreceptors in the left ventricle, cardiac atria and aortic arch as well as peripheral vascular chemoreceptors due to prolonged maintenance of upright body position. […] These two and other less popular theories show that the pathophysiological mechanism of vasovagal syndrome is still not fully determined. Therefore applications of new, more advanced methods for syncope analysis are continuously tested in search for better understanding of its mechanisms.
#42 The complexity of hemodynamic response to the tilt test with and without nitroglycerine provocation in patients with vasovagal syncope | Scientific Reports
https://www.nature.com/articles/s41598-018-32718-2
The physiological mechanism of vasovagal syncope is still not fully understood. There are some theories explaining its etiology, but the principal cause remains unknown. […] The autonomic malfunction causing reflex syncope is either a vasodepressive response (loss of sympathetic vasoconstrictive tone with lowering of blood pressure) or cardio-depressive response (active parasympathetic stimulation leading to bradycardia or asystole) resulting in impaired cerebral perfusion. […] The pathophysiology of neurocardiogenic syncope is heterogeneous. The experience gained so far and assessment of the results of tilt test show that a short pause in cerebral perfusion (lasting 68s) or a decrease in systolic blood pressure (sBP) down to 60mmHg or less is associated with syncope. […] There are two physiological theories attempting to explain the occurrence of vasovagal syncope. According to the central theory by van Lieshout and al., the reflex is triggered by activation of the cortical-subcortical centers, participated by necrohormones and neurotransmitters which lead to the bradycardia-hypotension reflex due to factors such as pain, fear or emotions. The peripheral theory by Oberg and Thoren assumes that the reflex is triggered by stimulation of the cardiac mechanoreceptors in the left ventricle, cardiac atria and aortic arch as well as peripheral vascular chemoreceptors due to prolonged maintenance of upright body position. […] These two and other less popular theories show that the pathophysiological mechanism of vasovagal syndrome is still not fully determined. Therefore applications of new, more advanced methods for syncope analysis are continuously tested in search for better understanding of its mechanisms.
#43 The complexity of hemodynamic response to the tilt test with and without nitroglycerine provocation in patients with vasovagal syncope | Scientific Reports
https://www.nature.com/articles/s41598-018-32718-2
The physiological mechanism of vasovagal syncope is still not fully understood. There are some theories explaining its etiology, but the principal cause remains unknown. […] The autonomic malfunction causing reflex syncope is either a vasodepressive response (loss of sympathetic vasoconstrictive tone with lowering of blood pressure) or cardio-depressive response (active parasympathetic stimulation leading to bradycardia or asystole) resulting in impaired cerebral perfusion. […] The pathophysiology of neurocardiogenic syncope is heterogeneous. The experience gained so far and assessment of the results of tilt test show that a short pause in cerebral perfusion (lasting 68s) or a decrease in systolic blood pressure (sBP) down to 60mmHg or less is associated with syncope. […] There are two physiological theories attempting to explain the occurrence of vasovagal syncope. According to the central theory by van Lieshout and al., the reflex is triggered by activation of the cortical-subcortical centers, participated by necrohormones and neurotransmitters which lead to the bradycardia-hypotension reflex due to factors such as pain, fear or emotions. The peripheral theory by Oberg and Thoren assumes that the reflex is triggered by stimulation of the cardiac mechanoreceptors in the left ventricle, cardiac atria and aortic arch as well as peripheral vascular chemoreceptors due to prolonged maintenance of upright body position. […] These two and other less popular theories show that the pathophysiological mechanism of vasovagal syndrome is still not fully determined. Therefore applications of new, more advanced methods for syncope analysis are continuously tested in search for better understanding of its mechanisms.
#44 The complexity of hemodynamic response to the tilt test with and without nitroglycerine provocation in patients with vasovagal syncope | Scientific Reports
https://www.nature.com/articles/s41598-018-32718-2
The physiological mechanism of vasovagal syncope is still not fully understood. There are some theories explaining its etiology, but the principal cause remains unknown. […] The autonomic malfunction causing reflex syncope is either a vasodepressive response (loss of sympathetic vasoconstrictive tone with lowering of blood pressure) or cardio-depressive response (active parasympathetic stimulation leading to bradycardia or asystole) resulting in impaired cerebral perfusion. […] The pathophysiology of neurocardiogenic syncope is heterogeneous. The experience gained so far and assessment of the results of tilt test show that a short pause in cerebral perfusion (lasting 68s) or a decrease in systolic blood pressure (sBP) down to 60mmHg or less is associated with syncope. […] There are two physiological theories attempting to explain the occurrence of vasovagal syncope. According to the central theory by van Lieshout and al., the reflex is triggered by activation of the cortical-subcortical centers, participated by necrohormones and neurotransmitters which lead to the bradycardia-hypotension reflex due to factors such as pain, fear or emotions. The peripheral theory by Oberg and Thoren assumes that the reflex is triggered by stimulation of the cardiac mechanoreceptors in the left ventricle, cardiac atria and aortic arch as well as peripheral vascular chemoreceptors due to prolonged maintenance of upright body position. […] These two and other less popular theories show that the pathophysiological mechanism of vasovagal syndrome is still not fully determined. Therefore applications of new, more advanced methods for syncope analysis are continuously tested in search for better understanding of its mechanisms.
#45 The role of neuropeptide Y in the pathogenesis of vasovagal syncope | ECE2022 | European Congress of Endocrinology 2022 | Endocrine Abstracts
https://www.endocrine-abstracts.org/ea/0081/ea0081p528
The role of neuropeptide Y in the pathogenesis of vasovagal syncope […] In the pathogenesis, a dysregulation of autonomic nervous system is playing an important role. […] The impaired release of NPY may play a role in pathogenesis of VVS. Other vasoconstrictive hormones, such as ET-1 and ANG, can be involved in pathomechanisms, too.
#46 KoreaMed Synapse
https://synapse.koreamed.org/articles/1084314
A vasovagal reaction is defined as the 'development of hypotension and bradycardia associated with the typical clinical manifestations of pallor, sweating and weakness’ […] The pathophysiology of the hypotension/bradycardia reflex responsible for vasovagal syncope is not completely understood. Central as well as peripheral mechanisms have been implicated in its pathogenesis: however their relative contribution is not fully elucidated. Recently, trigeminocardiac reflex, previously known as oculocardiac reflex, may serve as syncope. […] In this article, we would like to review new mechanism of vasovagal syncope and hope to be of help to manage the syncopal patients.
#47
https://koreascience.kr/article/JAKO201203939211339.page
A vasovagal reaction is defined as the 'development of hypotension and bradycardia associated with the typical clinical manifestations of pallor, sweating and weakness’. […] The pathophysiology of the hypotension/bradycardia reflex responsible for vasovagal syncope is not completely understood. Central as well as peripheral mechanisms have been implicated in its pathogenesis: however their relative contribution is not fully elucidated. […] Recently, trigeminocardiac reflex, previously known as oculocardiac reflex, may serve as syncope.
#48
https://link.springer.com/article/10.1007/s10286-017-0446-2
Many observations suggest that typical (emotional or orthostatic) vasovagal syncope (VVS) is not a disease, but rather a manifestation of a non-pathological trait. […] Under the heart defense theory, the vasovagal reflex seems to be a protective mechanism against sympathetic overactivity and the heart is the most vulnerable organ during this condition. This appears to be the only unifying theory able to explain the occurrence of the vasovagal reflex and its associated selective advantage, during both orthostatic and emotional stress.
#49
https://link.springer.com/article/10.1007/s10286-023-01005-0
The gradual slowing of the pulse has always been recognized as a prominent sign in vasovagal syncope (VVS). For a long time in history this seemed the sole mechanism to explain the circulatory arrest in VVS. […] It was not until the discovery of the sphygmomanometer that vasodilatation was identified as a coinciding mechanism contributing to the fall in blood pressure (BP) in VVS. […] Lewis concludes that the cause of syncope is mainly vasomotor and not vagal and redefined the term vasovagal in the context of syncope to emphasize the duality of the reflex. […] Although some signs of cardioinhibition may be seen in nearly all cases, the relative impact of cardioinhibition declines with age with the most prolonged asystolic response among the younger individuals. […] Refractory VVS cases with dominant vasodepressive subtypes could benefit from therapies aiming to expand plasma volume or to promote vasoconstriction while interventions targeting bradycardia may be considered in those with a dominant cardioinhibitory profile.
#50
https://link.springer.com/article/10.1007/s10286-023-01005-0
Documenting asystole during a spontaneous event does not mean that it is the dominant mechanism, as the asystole may occur after vasodepression has already provoked loss of consciousness. […] The major driver for the overall increased DC in VVS consisted of a higher prevalence of frequent short-lasting deceleration runs in VVS. […] Interestingly, a recent study of the same group suggested that DC findings might help to predict treatment response to invasive cardioneuroablation (CNA) procedures in cases with refractory VVS. […] It is likely that treating all cases with refractory VVS with CNA carries a huge risk of offering a wrong treatment in a mainly vasomotor condition, thus probably explaining the low response rate. […] Deceleration capacity is a promising candidate to phenotype VVS subtypes, but the proof of the pudding will need further multicenter validation studies.
#51 Pacemaker for vasovagal syncope: good for few
https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-2/Pacemaker-for-vasovagal-syncope-good-for-few-Title-Pacemaker-for-vasovagal-s
It seems that pacing therapy might be effective in some but not in all patients. […] This is not surprising if we consider that pacing is probably efficacious for asystolic reflex but has no role in combating hypotension which is frequently the dominant reflex in vasovagal syncope. […] A recent study using the Implantable Loop Recorder as reference standard showed that only about half of the patients had an asystolic pause recorded at the time of spontaneous syncope which might eventually benefit from a pacemaker. […] Nevertheless, recent data showed that the mechanism of tilt-induced syncope was frequently different from that of the spontaneous syncope recorded with the Implantable Loop Recorder.
#52 Pacemaker for vasovagal syncope: good for few
https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-2/Pacemaker-for-vasovagal-syncope-good-for-few-Title-Pacemaker-for-vasovagal-s
It seems that pacing therapy might be effective in some but not in all patients. […] This is not surprising if we consider that pacing is probably efficacious for asystolic reflex but has no role in combating hypotension which is frequently the dominant reflex in vasovagal syncope. […] A recent study using the Implantable Loop Recorder as reference standard showed that only about half of the patients had an asystolic pause recorded at the time of spontaneous syncope which might eventually benefit from a pacemaker. […] Nevertheless, recent data showed that the mechanism of tilt-induced syncope was frequently different from that of the spontaneous syncope recorded with the Implantable Loop Recorder.
#53 Vasovagal Syncope: A Review of Current and Future Strategies – touchCARDIOLOGY
https://touchcardio.com/syncope/journal-articles/vasovagal-syncope-a-review-of-current-and-future-strategies/
Neuroendocrine activity plays a part in the reflex probably as a protective mechanism and begins with vasopressin release, followed by epinephrine. High epinephrine levels have a vasodilatory effect on skeletal muscle, favouring some fall in BP. […] The different heart rate and BP behaviours during orthostasis can be classified into collapse patterns, which are described and later modified by the Vasovagal Syncope International Study (VASIS). […] The two main interventions that can be offered under certain conditions are pacemaker therapy and cardioneuroablation (CNA). […] Cardiac autonomic denervation was initially undertaken by endocardial identification of epicardial ganglionated plexi and their ablation, building upon neuromodulation targets for atrial fibrillation with encouraging early results. Subsequently, there has been limited but growing evidence that cardioneuroablation may help patients with severely symptomatic recurrent VVS with a pronounced asystolic component.
#54
https://link.springer.com/article/10.1007/s10286-023-01005-0
Documenting asystole during a spontaneous event does not mean that it is the dominant mechanism, as the asystole may occur after vasodepression has already provoked loss of consciousness. […] The major driver for the overall increased DC in VVS consisted of a higher prevalence of frequent short-lasting deceleration runs in VVS. […] Interestingly, a recent study of the same group suggested that DC findings might help to predict treatment response to invasive cardioneuroablation (CNA) procedures in cases with refractory VVS. […] It is likely that treating all cases with refractory VVS with CNA carries a huge risk of offering a wrong treatment in a mainly vasomotor condition, thus probably explaining the low response rate. […] Deceleration capacity is a promising candidate to phenotype VVS subtypes, but the proof of the pudding will need further multicenter validation studies.
#55 Vasovagal Syncope: A Review of Current and Future Strategies – touchCARDIOLOGY
https://touchcardio.com/syncope/journal-articles/vasovagal-syncope-a-review-of-current-and-future-strategies/
In summary, there are encouraging results from systematic case series data in support of CNA. A highly selected, very symptomatic group of patients with dominant cardioinhibitory VVS could benefit from CNA, by either completely abolishing syncope, or extending the prodrome long enough to prevent injury.
#56 The Pathophysiology of the Vasovagal Response
https://touroscholar.touro.edu/nymc_fac_pubs/1906/
In part I of this study, we found that the classical studies on vasovagal syncope, conducted in fit young subjects, overstated vasodilatation as the dominant hypotensive mechanism. […] This has allowed us to analyze in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. […] All tilt-sensitive patients appear to progress through 4 phases: (1) early stabilization, (2) circulatory instability, (3) terminal hypotension, and (4) recovery. The physiology responsible for each phase is discussed. […] In teenagers and young adults, progressive hypotension during phases 2 and 3 can be driven by vasodilatation or falling cardiac output. The fall in cardiac output is secondary to a progressive decrease in stroke volume because blood is pooled in the splanchnic veins. […] In adults a fall in cardiac output is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels.
#57 Vasovagal Syncope: A Review of Current and Future Strategies – touchCARDIOLOGY
https://touchcardio.com/syncope/journal-articles/vasovagal-syncope-a-review-of-current-and-future-strategies/
Vasovagal syncope is common, and while it is usually associated with a benign prognosis, it results in significant physical and psychological morbidity for affected individuals. Despite comprehensive understanding of the underlying pathophysiology, there have been few definitive therapeutic advances until recent randomized, controlled trials in pharmacotherapy, pacing and cardioneuroablation. […] Despite advances in the understanding of the pathophysiology of VVS, significant uncertainty remains. Individuals with VVS represent a heterogenous patient population, and different mechanisms are likely to contribute. These mechanisms are still not fully understood. Therefore, determining dominant mechanisms and modifying therapies accordingly is not always possible. In this review, we first describe the pathophysiology of the condition and discuss an approach for evaluating patients with VVS, emphasising holistic, multifaceted care.