Bezold-Jarisch reflex: Difference between revisions

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__NOTOC__
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{{SI}}
{{SI}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}; {{Rim}}; {{M.P}}


{{SK}} Bezold's reflex, Bezold-Jarisch response, Jarisch-Bezold reflex, BJR.
{{SK}} Bezold's reflex, Bezold-Jarisch response, Jarisch-Bezold reflex, BJR


==Overview==
==Overview==
The '''Bezold–Jarisch reflex''' involves a variety of cardiovascular and neurological processes which cause [[hypopnea]] (overly shallow breathing or an abnormally low [[respiratory rate]]) and  [[bradycardia]] (abnormally low resting [[heart rate]]).<ref name="pmid17567718">{{cite journal |author=Salo LM, Woods RL, Anderson CR, McAllen RM |title=Nonuniformity in the von Bezold-Jarisch reflex |journal=Am. J. Physiol. Regul. Integr. Comp. Physiol. |volume=293 |issue=2 |pages=R714–20 |year=2007 |month=August |pmid=17567718 |doi=10.1152/ajpregu.00099.2007 |url=http://ajpregu.physiology.org/cgi/pmidlookup?view=long&pmid=17567718}}</ref>. A cardiovascular depressor reflex involving a marked increase in [[vagal]] ([[parasympathetic]]) efferent discharge to the heart, elicited by stimulation of [[chemoreceptor]]s, primarily in the [[left ventricle]]. This causes a slowing of the heart beat ([[bradycardia]]) and dilatation of the peripheral blood vessels with resulting lowering of the [[blood pressure]]. <ref> A. von Bezold, Ludwig Hirt (1844-1907): Über die physiologischen Wirkungen des essigsauren Veratrine. Untersuchungen aus dem Physiologischen Laboratorium in Würzburg, 1867, 1: 73-122.</ref> <ref>A. Jarisch, C. Henze Über Blutdrucksenkung durch chemische Erregung depressorischer Nerven. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1937, 187: 706­-730.</ref> <ref>A. Jarisch Vom Herzen ausgehende Kreislaufreflexe. Archiv für Kreislaufforschung 1940, 7: 260-­274.</ref>
Bezold-Jarisch reflex is the occurrence of [[bradycardia]] and [[hypotension]] through a pathway involving cardiac receptors, [[medulla|medullary centers]] and [[vagus|vagal]] afferent nerves.<ref name="pmid11458703">{{cite journal| author=Aviado DM, Guevara Aviado D| title=The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes. | journal=Ann N Y Acad Sci | year= 2001 | volume= 940 | issue= | pages= 48-58 | pmid=11458703 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11458703  }} </ref> It results from cardiovascular depressor reflex involving a marked increase in [[vagal]] efferent discharge to the heart, elicited by stimulation of [[mechanoreceptor]]s, primarily in the [[left ventricle]]. This leads to [[bradycardia]] and dilatation of the peripheral blood vessels with resulting lowering of the [[blood pressure]]. <ref> A. von Bezold, Ludwig Hirt (1844-1907): Über die physiologischen Wirkungen des essigsauren Veratrine. Untersuchungen aus dem Physiologischen Laboratorium in Würzburg, 1867, 1: 73-122.</ref> <ref>A. Jarisch, C. Henze Über Blutdrucksenkung durch chemische Erregung depressorischer Nerven. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1937, 187: 706­-730.</ref> <ref>A. Jarisch Vom Herzen ausgehende Kreislaufreflexe. Archiv für Kreislaufforschung 1940, 7: 260-­274.</ref> Bezold-Jarisch reflex is responsible for 61% of [[bradyarrhythmia]] that occur within the first 60 minutes of inferoposterior [[myocardial infarction]].<ref>{{cite book|last=Goldman|first=Lee|title=Goldman: Goldman's Cecil Medicine|publisher=Saunders, an imprint of Elsevier Inc.|isbn=978-1-4377-1604-7|author2=Anderson, Jeffrey L.|edition=24th|chapter=ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION AND COMPLICATIONS OF MYOCARDIAL INFARCTION|page=444}}</ref> In addition, it is considered a good prognostic indicator of successful early [[reperfusion]] and [[coronary artery]] patency in the setting of [[thrombolysis]] after inferoposterior [[MI]].


==Historical Perspective==
==Historical Perspective==
It is named for [[Albert von Bezold]] and [[Adolf Jarisch Junior]].<ref>{{WhoNamedIt|synd|3165}}</ref>. The concept was originated by Bezold in 1867, later revised by Jarisch in 1937.<ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref>
Bezold-Jarisch reflex is named after [[Albert von Bezold]] and [[Adolf Jarisch]].<ref>{{WhoNamedIt|synd|3165}}</ref><ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref> The concept of this reflex originated by Bezold in 1867 after injecting experimental animals with intravenous injection of veratrum [[alkaloids]],<ref name="pmid11458703">{{cite journal| author=Aviado DM, Guevara Aviado D| title=The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes. | journal=Ann N Y Acad Sci | year= 2001 | volume= 940 | issue=  | pages= 48-58 | pmid=11458703 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11458703  }} </ref> and was later revised by Jarisch in 1937.<ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref> It was described as a variety of cardiovascular and neurological processes which cause [[hypopnea]] (overly shallow breathing or an abnormally low [[respiratory rate]]) and  [[bradycardia]] (abnormally low resting [[heart rate]]).<ref name="pmid17567718">{{cite journal |author=Salo LM, Woods RL, Anderson CR, McAllen RM |title=Nonuniformity in the von Bezold-Jarisch reflex |journal=Am. J. Physiol. Regul. Integr. Comp. Physiol. |volume=293 |issue=2 |pages=R714–20 |year=2007 |month=August |pmid=17567718 |doi=10.1152/ajpregu.00099.2007 |url=http://ajpregu.physiology.org/cgi/pmidlookup?view=long&pmid=17567718}}</ref>


==Physiology==
==Physiology==
* Bezold-Jarisch reflex is the occurrence of [[bradycardia]] and [[hypotension]] through a pathway involving cardiac receptors, [[medulla|medullary centers]] and [[vagus|vagal]] afferent nerves.  Bezold-Jarisch reflex originates from inhibitory mechanoreceptors that are located in the left [[ventricle]], particularly in the inferoposterior wall. The stimulation of these receptors occurs in the context of stretching and contraction of a poorly filled ventricle. Once stimulated, these mechanoreceptors stimulate [[parasympathetic]] pathways and inhibits the [[sympathetic pathways]]. The result of this [[reflex]] is a constellation of [[bradycardia]], [[vasodilation]] and [[hypotension]] in addition to increase [[renin]] and [[vasopressin]] release.<ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref>
Bezold-Jarisch reflex is the occurrence of [[bradycardia]] and [[hypotension]] through a pathway involving cardiac receptors, [[medulla|medullary centers]] and [[vagus|vagal]] afferent nerves.<ref name="pmid11458703">{{cite journal| author=Aviado DM, Guevara Aviado D| title=The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes. | journal=Ann N Y Acad Sci | year= 2001 | volume= 940 | issue= | pages= 48-58 | pmid=11458703 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11458703  }} </ref> Bezold-Jarisch reflex originates from inhibitory mechanoreceptors that are located in the left [[ventricle]], particularly in the inferoposterior wall. The stimulation of these receptors occurs in the context of stretching and contraction of a poorly filled ventricle. Once stimulated, these mechanoreceptors stimulate [[parasympathetic]] pathways and inhibits the [[sympathetic pathways]]. The result of this [[reflex]] is a constellation of [[bradycardia]], [[vasodilation]] and [[hypotension]] in addition to increase [[renin]] and [[vasopressin]] release.<ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref>
 
Below is an image that illustrates the physiology of Bezold-Jarisch reflex.
[[Image:Bezold-Jarisch_reflex.png|500px|center|Physiology of Bezold-Jarisch reflex]]


==Clinical Implications==
==Clinical Implications==
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* [[Vasovagal syncope]]<ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref>
* [[Vasovagal syncope]]<ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref>


===Acute Posterior Myocardial Infarction===
===Acute Inferoposterior Myocardial Infarction===
Bezold-Jarisch reflex is responsible for 61% of bradyarrhythmia that occur within the first hour of posterior MI. It is hypothesized that this reflex is a protective refelx that vasodilate the coronary arteries in the setting of posterior ischemia associated with coronary spasm.<ref>Linden, Function of Cardiac Receptors. Circulation. 1973;   48: 463-480</ref>
* Bezold-Jarisch reflex is responsible for 61% of [[bradyarrhythmia]] that occur within the first 60 minutes of [[MI]],<ref>{{cite book|last=Goldman|first=Lee|title=Goldman: Goldman's Cecil Medicine|publisher=Saunders, an imprint of Elsevier Inc.|isbn=978-1-4377-1604-7|author2=Anderson, Jeffrey L.|edition=24th|chapter=ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION AND COMPLICATIONS OF MYOCARDIAL INFARCTION|page=444}}</ref> and it explains the occurrence of [[AV block|AV node block]] in the context of acute posterior or inferior myocardial infarction.<ref>{{cite book|last=Katz|first=Arnold M.|title=Physiology of the heart|year=2001|publisher=Lippincott Williams & Wilkins|location=Philadelphia [u.a.]|isbn=0-7817-1548-2|page=595|edition=3. ed.}}</ref>
* It is hypothesized that this reflex is a protective reflex that vasodilates the [[coronary arteries]] in the setting of posterior infarction associated with coronary vasospasm.<ref>Linden R.J. Function of Cardiac Receptors. Circulation. 1973; 48: 463-480</ref> [[Bradycardia]] in this setting may be treated with [[atropine]].
 
===Reperfusion===
* Bezold-Jarisch reflex can occur in acute inferior [[MI]] after [[thrombolysis]]. In fact, it is a prognostic sign for early reperfusion as it occurs in 94% of cases of successful early thrmobolysis in inferior MI.
* In addition, it is a prognostic factor for coronary patency as it occurs in 89% of patent [[right coronary artery]] characterized by a [[TIMI flow grade]] of 3.<ref name="pmid12862298">{{cite journal| author=Chiladakis JA, Patsouras N, Manolis AS| title=The Bezold-Jarisch reflex in acute inferior myocardial infarction: clinical and sympathovagal spectral correlates. | journal=Clin Cardiol | year= 2003 | volume= 26 | issue= 7 | pages= 323-8 | pmid=12862298 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12862298  }} </ref>
 
===Vasovagal Syncope===
* Prolonged upright posture results in some degree of pooling of blood in the [[lower extremities]] that can lead to diminished intracardiac volume. This phenomenon is exacerbated if the individual is [[Dehydration|dehydrate]]d. The resultant arterial hypotension is sensed in the [[carotid sinus]] [[baroreceptors]], and [[efferent nerve fiber|efferent fibers]] from these receptors trigger [[sympathetic]] autonomic signals that increase cardiac rate and [[contractility]]. However, pressure receptors in the wall and [[trabeculae]] of the underfilled [[left ventricle]] may then sense the stretching and contraction of the poorly filled ventricle, activating high-pressure [[C-fiber]] afferent nerves from these receptors. They may respond by activating the [[parasympathetic system]] that triggers paradoxical [[bradycardia]] and decreased contractility, resulting in additional and relatively sudden arterial [[hypotension]]. Hence, Bezold-Jarisch reflex results from the stimulation of [[vagus|vagal]] afferent pathways in response to [[sympathetic]] overactivity.
* Inappropriate Bezold- Jarisch reflex must be suspected in the setting of unexplained [[syncope]] and should be investigated by [[tilt table test]].


Prolonged upright posture results in some degree of pooling of blood in the [[lower extremities]] that can lead to diminished intracardiac volume. This phenomenon is exacerbated if the individual is [[Dehydration|dehydrate]]d. The resultant arterial hypotension is sensed in the [[carotid sinus]] [[baroreceptors]], and [[efferent nerve fiber|efferent fibers]] from these receptors trigger autonomic signals that increase cardiac rate and [[contractility]]. However, pressure receptors in the wall and [[trabeculae]] of the underfilled [[left ventricle]] may then sense stimuli, activating high-pressure [[C-fiber]] afferent nerves from these receptors. They may respond by sending signals that trigger paradoxical [[bradycardia]] and decreased contractility, resulting in additional and relatively sudden arterial [[hypotension]].
Below is an image that illustrates the mechanism of Bezold-Jarisch reflex in syncope.
[[Image:BJR 2.jpg|500px|center|Mechanism of Bezold-Jarisch reflex in syncope]]
<br clear="left"/>


The Bezold–Jarisch reflex is responsible for the [[sinus bradycardia]] that commonly occurs within the first 60 minutes following an acute myocardial infarction,<ref>{{cite book|last=Goldman|first=Lee|title=Goldman: Goldman's Cecil Medicine|publisher=Saunders, an imprint of Elsevier Inc.|isbn=978-1-4377-1604-7|author2=Anderson, Jeffrey L.|edition=24th|chapter=ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION AND COMPLICATIONS OF MYOCARDIAL INFARCTION|page=444}}</ref> and explains the occurrence of AV node block in the context of acute posterior or inferior myocardial infarction.<ref>{{cite book|last=Katz|first=Arnold M.|title=Physiology of the heart|year=2001|publisher=Lippincott Williams & Wilkins|location=Philadelphia [u.a.]|isbn=0-7817-1548-2|page=595|edition=3. ed.}}</ref> Bradycardia in this setting may be treated with [[atropine]].
===Medication Effect===
* [[Digitalis]]
* [[Nitrate]]
* [[Serotonin receptor agonist]]<ref>[http://www.emedicine.com/ped/topic2188.htm eMedicine - Syncope : Article by M Silvana Horenstein, MD<!-- Bot generated title -->]</ref>


It usually occurs in nitrate therapy and use of [[serotonin]] [[agonists]].<ref>[http://www.emedicine.com/ped/topic2188.htm eMedicine - Syncope : Article by M Silvana Horenstein, MD<!-- Bot generated title -->]</ref> The Bezold–Jarisch reflex has also been suggested as a possible cause of profound bradycardia and circulatory collapse after spinal anesthesia.<ref>Tsai T. & Greengrass R. (2007). ''Textbook of Regional Anesthesia and Acute Pain Management: Spinal Anesthesia.'' (A. Hadzic, Ed.). New York: McGraw Hill Medical.</ref>
===Anesthesia===
Also, it is one of the complications of interscalene brachial plexus block.
* The Bezold–Jarisch reflex has also been suggested as a possible cause of profound bradycardia and circulatory collapse after [[spinal anesthesia]].<ref>Tsai T. & Greengrass R. (2007). ''Textbook of Regional Anesthesia and Acute Pain Management: Spinal Anesthesia.'' (A. Hadzic, Ed.). New York: McGraw Hill Medical.</ref>
* Also, it is one of the complications of interscalene brachial plexus block.


[[Image:BJR.jpg|frame|left|400px|Distribution of opioid OP4 receptors involved in the regulation of cardiovascular function. Various locations of OP4 receptors as suggested by functional studies are shown. Excitatory neurons are represented by solid lines, inhibitory neurons are represented by dotted lines. Abbreviations: CVLM - caudal ventrolateral medulla; NAmb - nucleus ambiguus; NTS - nucleus tractus solitarii; PVN - paraventricular nucleus; RVLM - rostral ventrolateral medulla.<ref>[http://www.jpp.krakow.pl/journal/archive/0902/articles/01_article.html Malinowska B. Godlewski G, Schlicker E. FUNCTION OF NOCICEPTIN AND OPIOID OP4 RECEPTORS IN THE REGULATION OF THE CARDIOVASCULAR SYSTEM, 2002, Bialystok, Poland]</ref>]]
Below is an image that illustrates the distribution of opioid OP4 receptors involved in the regulation of cardiovascular function.
<br clear="left"/>
[[Image:BJR.jpg|center|500px|Distribution of opioid OP4 receptors involved in the regulation of cardiovascular function. Various locations of OP4 receptors as suggested by functional studies are shown. Excitatory neurons are represented by solid lines, inhibitory neurons are represented by dotted lines. Abbreviations: CVLM - caudal ventrolateral medulla; NAmb - nucleus ambiguus; NTS - nucleus tractus solitarii; PVN - paraventricular nucleus; RVLM - rostral ventrolateral medulla.<ref>[http://www.jpp.krakow.pl/journal/archive/0902/articles/01_article.html Malinowska B. Godlewski G, Schlicker E. FUNCTION OF NOCICEPTIN AND OPIOID OP4 RECEPTORS IN THE REGULATION OF THE CARDIOVASCULAR SYSTEM, 2002, Bialystok, Poland]</ref>]]
[[Image:BJR 2.jpg|400px|left|frame|thumb]]
<br clear="left"/>
<br clear="left"/>


==Causes==
==Causes==
===Life Threatening Causes===
* [[Myocardial infarction|Inferoposterior myocardial infarction]]
===Common Causes===
* [[Chronic heart failure]]
* [[Coronary catheterization]]
* [[Digitalis]]
* [[Syncope|Exertional syncope]] in [[aortic stenosis]]
* [[MI|Inferoposterior myocardial infarction]]
* [[Serotonin receptor agonist]]s
* [[Nitrate]]
* [[Vasovagal syncope]]<ref name="pmid6826948">{{cite journal| author=Mark AL| title=The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. | journal=J Am Coll Cardiol | year= 1983 | volume= 1 | issue= 1 | pages= 90-102 | pmid=6826948 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6826948  }} </ref>
===Causes by Organ System===
{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | [[Aortic stenosis]], [[arrhythmias]], [[Bradbury-Eggleston syndrome]], [[carotid sinus hypersensitivity]], [[chronic heart failure]], [[coronary catheterization]], [[PCI|coronary reperfusion]], [[digitalis]], [[bleeding|excessive bleeding]], [[hypertrophic cardiomyopathy]], [[myocardial infarction|inferior wall myocardial infarction]], [[myocarditis]], [[pericarditis]], [[prinzmetal's angina]], [[radiofrequency catheter ablation]], [[temporary cardiac pacing]], [[vasovagal syncope]]
|-
|-bgcolor="LightSteelBlue"
| '''Chemical/Poisoning'''
|bgcolor="Beige"| [[Food poisoning]], [[Grayanotoxin|grayanotoxin-contaminated honey]]
|-
|-bgcolor="LightSteelBlue"
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| [[Excessive sweating]]
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| [[ACE inhibitor]], [[acetophenazine]], [[adriamycin]], [[aliskiren|aliskiren (direct renin inhibitor)]], [[alpha blockers]], [[ARB]], [[BNP]], [[calcium channel blocker]], [[cannabinoid]], [[triazole|central 3-amino-1,2,4-triazole(ATZ)]], [[clonidine]], [[codeine withdrawal]], [[colchicine toxicity]], [[deoxycorticosterone|deoxycorticosterone acetate]], [[digitalis]], [[dihydrocapsaicin]], [[disulfiram|disulfiram toxicity]], [[dobutamine]], [[ketanserin]], L-S-nitrosocysteine, [[MAO inhibitors]], [[mibefradil]], [[nandrolone]], [[nitrates]], [[sodium nitroprusside]],  [[ondansetron]], [[biguanide|phenylbiguanide]], piperamide analogue, [[pramipexole]], [[prazosin]], [[Prostacyclin|prostacyclin(PGI2)]], [[serotonin receptor agonist]], [[cholecystokinin|systemic cholecystokinin]], [[tamsulosin]], [[thiazole|thiazole derivatives]], [[tricyclic antidepressants]], [[zotepine]]
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| [[Wolfram's disease]]
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| [[Acute pancreatitis]], [[addisonian crisis]], [[Addison's disease]],  [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency]], [[congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase  deficiency]], [[diabetes insipidus]], [[diabetes mellitus type 2]], [[diabetic ketoacidosis]], [[hyperosmolar non-ketotic diabetic coma]], [[multiple endocrine neoplasia]],  [[panhypopituitarism]], [[pheochromocytoma]], [[hypoaldosteronism|pseudohypoaldosteronism type 1]], [[Waterhouse-Friederichsen syndrome]], [[Wolfram's disease]], [[CAH|X-Linked congemital adrenal hyperplasia]]
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| [[Dihydrocapsaicin]], [[excessive sweating]], [[grayanotoxin|grayanotoxin-contaminated honey]], [[heat stroke]], [[malnutrition]], [[marijuana]], [[veratridine]]
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Acute pancreatitis]], [[diarrhea]], [[dysentery]], [[food poisoning]], [[hyperemesis gravidarum]], [[vomiting]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency]], [[congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase  deficiency]], [[cystinosis]], [[Riley-Day syndrome|familial dysautonomia]], [[Fanconi syndrome]], [[multiple endocrine neoplasia]], [[pseudohypoaldosteronism|pseudohypoaldosteronism type 1]], [[Riley-Day syndrome]], [[Shy-Drager syndrome]], [[Wolfram's disease]], [[CAH|X-Linked congenital adrenal hyperplasia]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| [[Coronary catheterization]], [[PCI|coronary reperfusion]], [[dialysis]], [[anesthesia|high spinal blockade]], [[anesthesia|interscalene brachial plexus block]], [[pyrexia]], [[radiofrequency catheter ablation]], [[severe dehydration]], [[surgery|surgery in prone position]], [[temporary cardiac pacing]], [[vomiting]], [[radiation injury|whole-body acute irradiation]]
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| [[Dysentery]], [[endotoxins]], [[Guillain-Barre syndrome]], [[HIV/AIDS]], [[pyrexia]]
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| [[Bradbury-Eggleston syndrome]], [[cannabinoid]], [[dementia with Lewy bodies]], [[Riley-Day syndrome|familial dysautonomia]], [[Guillain-Barre syndrome]], [[panhypopituitarism]], [[autonomic neuropathy|paraneoplastic autonomic neuropathy]], [[parkinson's disease]], [[Riley-Day syndrome]], [[Shy-Drager syndrome]], [[vasovagal syncope]], [[veratridine]]
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
|bgcolor="Beige"| [[Anorexia nervosa]], [[vitamin B12 deficiency]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| [[Hyperemesis gravidarum]]
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| [[autonomic neuropathy|Paraneoplastic autonomic neuropathy]]
|-
|-bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
|bgcolor="Beige"| [[cocaine|Cocaine overdose]], [[colchicine toxicity]], [[disulfiram|disulfiram toxicity]], [[marijuana]]
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| [[Anorexia nervosa]]
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
|bgcolor="Beige"| [[Cystinosis]], [[dialysis]], [[Fanconi syndrome]], [[renal failure]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
|bgcolor="Beige"| [[Anaphylaxis]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| [[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency]], [[congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase  deficiency]]
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| [[bleeding|Excessive bleeding]], [[anesthesia|interscalene brachial plexus block]]
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| [[Aging]], [[dieting|excessive dieting]], [[excessive sweating]], [[physical exercise|exercise training]], [[sitting|prolonged upright posture]], [[severe dehydration]]
|-
|}
<font color="white">Causes by Organ System developed by WikiDoc.org, Copyleft 2013</font>
===Causes in Alphabetical Order===
{{col-begin|width=80%}}
{{col-break|width=33%}}
*[[ACE inhibitor]]
*[[Acetophenazine    ]]
*[[Acute pancreatitis ]]
*[[Addisonian crisis ]]
*[[Addison's disease]]
*[[Adriamycin]]
*[[Aging]]
*[[Aliskiren|Aliskiren (direct renin inhibitor)]]
*[[Alpha blockers]]
*[[Anaphylaxis]]
*[[Angiotensin II receptor antagonist]]
*[[Anorexia nervosa]]
*[[Aortic stenosis ]]
*[[Arrhythmias]]
*[[BNP]]
*[[Bradbury-Eggleston syndrome]]
*[[Calcium channel blocker]]
*[[Cannabinoid]]
*[[Carotid sinus hypersensitivity]]
*[[triazole|Central 3-amino-1,2,4-triazole(ATZ)]]
*[[Chronic heart failure]]
*[[Clonidine ]]
*[[cocaine|Cocaine overdose]]
*[[codeine|Codeine withdrawal]]
*[[Colchicine toxicity ]]
*[[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency]]
*[[Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase  deficiency]]
*[[Coronary catheterization]]
*[[PCI|Coronary reperfusion]]
*[[Cystinosis ]]
*[[Dementia with Lewy bodies]]
*[[Deoxycorticosterone|Deoxycorticosterone acetate]]
*[[Diabetes insipidus]]
*[[Diabetes mellitus type 2]]
*[[Diabetic ketoacidosis]]
{{col-break|width=33%}}
*[[Dialysis]]
*[[Diarrhea]]
*[[Digitalis]]


*[[Dihydrocapsaicin]]


==References==
*[[disulfiram|Disulfiram toxicity]]
{{Reflist|2}}
 
*[[Dobutamine]]
 
*[[Dysentery]]
 
*[[Endotoxins]]
 
*[[bleeding|Excessive bleeding]]
 
*[[dieting|Excessive dieting]]
 
*[[Excessive sweating]]
 
*[[exercise|Exercise training]]
 
*[[Riley-Day syndrome|Familial dysautonomia]]
 
*[[Fanconi syndrome]]
 
*[[Food poisoning ]]
 
*[[Grayanotoxin|Grayanotoxin-contaminated honey]]
 
*[[Guillain-Barre syndrome]]
 
*[[Heat stroke]]
 
*[[anesthesia|High spinal blockade]]
 
*[[HIV/AIDS]]
 
*[[Hyperemesis gravidarum]]
 
*[[Hyperosmolar non-ketotic diabetic coma]]
 
*[[Hypertrophic cardiomyopathy]]
 
*[[myocardial infarction|Inferior wall myocardial infarction]]
 
*[[anesthesia|Interscalene brachial plexus block]]
 
*[[Ketanserin]]
 
*L-S-nitrosocysteine
 
*[[Malnutrition]]
 
*[[MAO inhibitors]]
 
*[[Marijuana]]
 
*[[Mibefradil]]
 
*[[Multiple endocrine neoplasia]]
 
*[[Myocarditis]]
 
*[[Nandrolone]]
 
*[[Nitrates]]
 
*[[Ondansetron]]
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*[[Panhypopituitarism    ]]
 
*[[autonomic neuropathy|Paraneoplastic autonomic neuropathy]]
 
*[[Parkinson disease ]]
 
*[[Pericarditis]]
 
*Phenylbiguanide
 
*[[Pheochromocytoma ]]
 
*Piperamide analogue
 
*[[Pramipexole]]
 
*[[Prazosin]]
 
*[[Prinzmetal's angina ]]
 
*[[sitting|Prolonged upright posture]]
 
*[[Prostacyclin|Prostacyclin(PGI2)]]
 
*[[Pseudohypoaldosteronism|Pseudohypoaldosteronism type 1]]
 
*[[Pyrexia]]
 
*[[Radiofrequency catheter ablation]]
 
*[[Renal failure]]
 
*[[Riley-Day syndrome]]
 
*[[Serotonin receptor agonist]]
 
*[[Severe dehydration]]
 
*[[Shy-Drager syndrome]]
 
*[[Sodium nitroprusside]]
 
*[[surgery|Surgery in prone position]]
 
*[[cholecystokinin|Systemic cholecystokinin]]
 
*[[Tamsulosin]]
 
*[[Temporary cardiac pacing]]
 
*[[thiazole|Thiazole derivatives]]
 
*[[Tricyclic antidepressants]]
 
*[[Vasovagal syncope]]
 
*[[Veratridine]]
 
*[[Vitamin B12 deficiency]]
 
*[[Vomiting]]
 
*[[Waterhouse-Friederichsen syndrome]]
 
*[[radiation injury|Whole-body acute irradiation]]
 
*[[Wolfram's disease ]]
 
*[[CAH|X-Linked congenital adrenal hyperplasia]]


[[Category:Cardiovascular diseases]]
*[[Zotepine ]]
[[Category:Reflexes]]
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==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


{{Circulatory system pathology}}
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[[CME Category::Cardiology]]


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[[Category:Cardiology]]
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[[Category:Emergency medicine]]
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Latest revision as of 05:01, 15 March 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Rim Halaby, M.D. [3]; Mugilan Poongkunran M.B.B.S [4]

Synonyms and keywords: Bezold's reflex, Bezold-Jarisch response, Jarisch-Bezold reflex, BJR

Overview

Bezold-Jarisch reflex is the occurrence of bradycardia and hypotension through a pathway involving cardiac receptors, medullary centers and vagal afferent nerves.[1] It results from cardiovascular depressor reflex involving a marked increase in vagal efferent discharge to the heart, elicited by stimulation of mechanoreceptors, primarily in the left ventricle. This leads to bradycardia and dilatation of the peripheral blood vessels with resulting lowering of the blood pressure. [2] [3] [4] Bezold-Jarisch reflex is responsible for 61% of bradyarrhythmia that occur within the first 60 minutes of inferoposterior myocardial infarction.[5] In addition, it is considered a good prognostic indicator of successful early reperfusion and coronary artery patency in the setting of thrombolysis after inferoposterior MI.

Historical Perspective

Bezold-Jarisch reflex is named after Albert von Bezold and Adolf Jarisch.[6][7] The concept of this reflex originated by Bezold in 1867 after injecting experimental animals with intravenous injection of veratrum alkaloids,[1] and was later revised by Jarisch in 1937.[7] It was described as a variety of cardiovascular and neurological processes which cause hypopnea (overly shallow breathing or an abnormally low respiratory rate) and bradycardia (abnormally low resting heart rate).[8]

Physiology

Bezold-Jarisch reflex is the occurrence of bradycardia and hypotension through a pathway involving cardiac receptors, medullary centers and vagal afferent nerves.[1] Bezold-Jarisch reflex originates from inhibitory mechanoreceptors that are located in the left ventricle, particularly in the inferoposterior wall. The stimulation of these receptors occurs in the context of stretching and contraction of a poorly filled ventricle. Once stimulated, these mechanoreceptors stimulate parasympathetic pathways and inhibits the sympathetic pathways. The result of this reflex is a constellation of bradycardia, vasodilation and hypotension in addition to increase renin and vasopressin release.[7]

Below is an image that illustrates the physiology of Bezold-Jarisch reflex.

Physiology of Bezold-Jarisch reflex
Physiology of Bezold-Jarisch reflex

Clinical Implications

Bezold-Jarisch reflex plays a role in the following clinical conditions:

Acute Inferoposterior Myocardial Infarction

  • Bezold-Jarisch reflex is responsible for 61% of bradyarrhythmia that occur within the first 60 minutes of MI,[9] and it explains the occurrence of AV node block in the context of acute posterior or inferior myocardial infarction.[10]
  • It is hypothesized that this reflex is a protective reflex that vasodilates the coronary arteries in the setting of posterior infarction associated with coronary vasospasm.[11] Bradycardia in this setting may be treated with atropine.

Reperfusion

  • Bezold-Jarisch reflex can occur in acute inferior MI after thrombolysis. In fact, it is a prognostic sign for early reperfusion as it occurs in 94% of cases of successful early thrmobolysis in inferior MI.
  • In addition, it is a prognostic factor for coronary patency as it occurs in 89% of patent right coronary artery characterized by a TIMI flow grade of 3.[12]

Vasovagal Syncope

  • Prolonged upright posture results in some degree of pooling of blood in the lower extremities that can lead to diminished intracardiac volume. This phenomenon is exacerbated if the individual is dehydrated. The resultant arterial hypotension is sensed in the carotid sinus baroreceptors, and efferent fibers from these receptors trigger sympathetic autonomic signals that increase cardiac rate and contractility. However, pressure receptors in the wall and trabeculae of the underfilled left ventricle may then sense the stretching and contraction of the poorly filled ventricle, activating high-pressure C-fiber afferent nerves from these receptors. They may respond by activating the parasympathetic system that triggers paradoxical bradycardia and decreased contractility, resulting in additional and relatively sudden arterial hypotension. Hence, Bezold-Jarisch reflex results from the stimulation of vagal afferent pathways in response to sympathetic overactivity.
  • Inappropriate Bezold- Jarisch reflex must be suspected in the setting of unexplained syncope and should be investigated by tilt table test.

Below is an image that illustrates the mechanism of Bezold-Jarisch reflex in syncope.

Mechanism of Bezold-Jarisch reflex in syncope
Mechanism of Bezold-Jarisch reflex in syncope


Medication Effect

Anesthesia

  • The Bezold–Jarisch reflex has also been suggested as a possible cause of profound bradycardia and circulatory collapse after spinal anesthesia.[14]
  • Also, it is one of the complications of interscalene brachial plexus block.

Below is an image that illustrates the distribution of opioid OP4 receptors involved in the regulation of cardiovascular function.

Distribution of opioid OP4 receptors involved in the regulation of cardiovascular function. Various locations of OP4 receptors as suggested by functional studies are shown. Excitatory neurons are represented by solid lines, inhibitory neurons are represented by dotted lines. Abbreviations: CVLM - caudal ventrolateral medulla; NAmb - nucleus ambiguus; NTS - nucleus tractus solitarii; PVN - paraventricular nucleus; RVLM - rostral ventrolateral medulla.[15]
Distribution of opioid OP4 receptors involved in the regulation of cardiovascular function. Various locations of OP4 receptors as suggested by functional studies are shown. Excitatory neurons are represented by solid lines, inhibitory neurons are represented by dotted lines. Abbreviations: CVLM - caudal ventrolateral medulla; NAmb - nucleus ambiguus; NTS - nucleus tractus solitarii; PVN - paraventricular nucleus; RVLM - rostral ventrolateral medulla.[15]


Causes

Life Threatening Causes

Common Causes

Causes by Organ System

Cardiovascular Aortic stenosis, arrhythmias, Bradbury-Eggleston syndrome, carotid sinus hypersensitivity, chronic heart failure, coronary catheterization, coronary reperfusion, digitalis, excessive bleeding, hypertrophic cardiomyopathy, inferior wall myocardial infarction, myocarditis, pericarditis, prinzmetal's angina, radiofrequency catheter ablation, temporary cardiac pacing, vasovagal syncope
Chemical/Poisoning Food poisoning, grayanotoxin-contaminated honey
Dental No underlying causes
Dermatologic Excessive sweating
Drug Side Effect ACE inhibitor, acetophenazine, adriamycin, aliskiren (direct renin inhibitor), alpha blockers, ARB, BNP, calcium channel blocker, cannabinoid, central 3-amino-1,2,4-triazole(ATZ), clonidine, codeine withdrawal, colchicine toxicity, deoxycorticosterone acetate, digitalis, dihydrocapsaicin, disulfiram toxicity, dobutamine, ketanserin, L-S-nitrosocysteine, MAO inhibitors, mibefradil, nandrolone, nitrates, sodium nitroprusside, ondansetron, phenylbiguanide, piperamide analogue, pramipexole, prazosin, prostacyclin(PGI2), serotonin receptor agonist, systemic cholecystokinin, tamsulosin, thiazole derivatives, tricyclic antidepressants, zotepine
Ear Nose Throat Wolfram's disease
Endocrine Acute pancreatitis, addisonian crisis, Addison's disease, congenital adrenal hyperplasia due to 21-hydroxylase deficiency, congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency, diabetes insipidus, diabetes mellitus type 2, diabetic ketoacidosis, hyperosmolar non-ketotic diabetic coma, multiple endocrine neoplasia, panhypopituitarism, pheochromocytoma, pseudohypoaldosteronism type 1, Waterhouse-Friederichsen syndrome, Wolfram's disease, X-Linked congemital adrenal hyperplasia
Environmental Dihydrocapsaicin, excessive sweating, grayanotoxin-contaminated honey, heat stroke, malnutrition, marijuana, veratridine
Gastroenterologic Acute pancreatitis, diarrhea, dysentery, food poisoning, hyperemesis gravidarum, vomiting
Genetic Congenital adrenal hyperplasia due to 21-hydroxylase deficiency, congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency, cystinosis, familial dysautonomia, Fanconi syndrome, multiple endocrine neoplasia, pseudohypoaldosteronism type 1, Riley-Day syndrome, Shy-Drager syndrome, Wolfram's disease, X-Linked congenital adrenal hyperplasia
Hematologic No underlying causes
Iatrogenic Coronary catheterization, coronary reperfusion, dialysis, high spinal blockade, interscalene brachial plexus block, pyrexia, radiofrequency catheter ablation, severe dehydration, surgery in prone position, temporary cardiac pacing, vomiting, whole-body acute irradiation
Infectious Disease Dysentery, endotoxins, Guillain-Barre syndrome, HIV/AIDS, pyrexia
Musculoskeletal/Orthopedic No underlying causes
Neurologic Bradbury-Eggleston syndrome, cannabinoid, dementia with Lewy bodies, familial dysautonomia, Guillain-Barre syndrome, panhypopituitarism, paraneoplastic autonomic neuropathy, parkinson's disease, Riley-Day syndrome, Shy-Drager syndrome, vasovagal syncope, veratridine
Nutritional/Metabolic Anorexia nervosa, vitamin B12 deficiency
Obstetric/Gynecologic Hyperemesis gravidarum
Oncologic Paraneoplastic autonomic neuropathy
Ophthalmologic No underlying causes
Overdose/Toxicity Cocaine overdose, colchicine toxicity, disulfiram toxicity, marijuana
Psychiatric Anorexia nervosa
Pulmonary No underlying causes
Renal/Electrolyte Cystinosis, dialysis, Fanconi syndrome, renal failure
Rheumatology/Immunology/Allergy Anaphylaxis
Sexual Congenital adrenal hyperplasia due to 21-hydroxylase deficiency, congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency
Trauma Excessive bleeding, interscalene brachial plexus block
Urologic No underlying causes
Miscellaneous Aging, excessive dieting, excessive sweating, exercise training, prolonged upright posture, severe dehydration

Causes by Organ System developed by WikiDoc.org, Copyleft 2013

Causes in Alphabetical Order

References

  1. 1.0 1.1 1.2 Aviado DM, Guevara Aviado D (2001). "The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes". Ann N Y Acad Sci. 940: 48–58. PMID 11458703.
  2. A. von Bezold, Ludwig Hirt (1844-1907): Über die physiologischen Wirkungen des essigsauren Veratrine. Untersuchungen aus dem Physiologischen Laboratorium in Würzburg, 1867, 1: 73-122.
  3. A. Jarisch, C. Henze Über Blutdrucksenkung durch chemische Erregung depressorischer Nerven. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1937, 187: 706­-730.
  4. A. Jarisch Vom Herzen ausgehende Kreislaufreflexe. Archiv für Kreislaufforschung 1940, 7: 260-­274.
  5. Goldman, Lee; Anderson, Jeffrey L. "ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION AND COMPLICATIONS OF MYOCARDIAL INFARCTION". Goldman: Goldman's Cecil Medicine (24th ed.). Saunders, an imprint of Elsevier Inc. p. 444. ISBN 978-1-4377-1604-7.
  6. Template:WhoNamedIt
  7. 7.0 7.1 7.2 7.3 7.4 Mark AL (1983). "The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart". J Am Coll Cardiol. 1 (1): 90–102. PMID 6826948.
  8. Salo LM, Woods RL, Anderson CR, McAllen RM (2007). "Nonuniformity in the von Bezold-Jarisch reflex". Am. J. Physiol. Regul. Integr. Comp. Physiol. 293 (2): R714–20. doi:10.1152/ajpregu.00099.2007. PMID 17567718. Unknown parameter |month= ignored (help)
  9. Goldman, Lee; Anderson, Jeffrey L. "ST SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION AND COMPLICATIONS OF MYOCARDIAL INFARCTION". Goldman: Goldman's Cecil Medicine (24th ed.). Saunders, an imprint of Elsevier Inc. p. 444. ISBN 978-1-4377-1604-7.
  10. Katz, Arnold M. (2001). Physiology of the heart (3. ed. ed.). Philadelphia [u.a.]: Lippincott Williams & Wilkins. p. 595. ISBN 0-7817-1548-2.
  11. Linden R.J. Function of Cardiac Receptors. Circulation. 1973; 48: 463-480
  12. Chiladakis JA, Patsouras N, Manolis AS (2003). "The Bezold-Jarisch reflex in acute inferior myocardial infarction: clinical and sympathovagal spectral correlates". Clin Cardiol. 26 (7): 323–8. PMID 12862298.
  13. eMedicine - Syncope : Article by M Silvana Horenstein, MD
  14. Tsai T. & Greengrass R. (2007). Textbook of Regional Anesthesia and Acute Pain Management: Spinal Anesthesia. (A. Hadzic, Ed.). New York: McGraw Hill Medical.
  15. Malinowska B. Godlewski G, Schlicker E. FUNCTION OF NOCICEPTIN AND OPIOID OP4 RECEPTORS IN THE REGULATION OF THE CARDIOVASCULAR SYSTEM, 2002, Bialystok, Poland


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