Bezold-Jarisch reflex: Difference between revisions
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==Overview== | ==Overview== | ||
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 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== | ||
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> | 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.<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 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. | Below is an image that illustrates the physiology of Bezold-Jarisch reflex. | ||
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===Reperfusion=== | ===Reperfusion=== | ||
* Bezold-Jarisch reflex can occur in acute inferior [[MI]] after [[thrombolysis]]. | * 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> | * 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=== | ===Vasovagal Syncope=== | ||
* Prolonged upright posture results in some degree of pooling of blood in the [[lower extremities]] that can lead to diminished intracardiac volume. | * 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]]. | * Inappropriate Bezold- Jarisch reflex must be suspected in the setting of unexplained [[syncope]] and should be investigated by [[tilt table test]]. | ||
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==Causes== | ==Causes== | ||
===Life Threatening Causes=== | ===Life Threatening Causes=== | ||
* [[Myocardial infarction|Inferoposterior myocardial infarction]] | * [[Myocardial infarction|Inferoposterior myocardial infarction]] | ||
===Common Causes=== | ===Common Causes=== | ||
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|-bgcolor="LightSteelBlue" | |-bgcolor="LightSteelBlue" | ||
| '''Drug Side Effect''' | | '''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]], [[pramipexole]], [[prazosin]], [[Prostacyclin|prostacyclin(PGI2)]], [[serotonin receptor agonist]], [[cholecystokinin|systemic cholecystokinin]], [[tamsulosin]], [[thiazole|thiazole derivatives]], [[tricyclic antidepressants]], [[zotepine]] | |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" | |-bgcolor="LightSteelBlue" | ||
| '''Ear Nose Throat''' | | '''Ear Nose Throat''' | ||
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{{Reflist|2}} | {{Reflist|2}} | ||
[[Category: | {{WikiDoc Help Menu}} | ||
{{WikiDoc Sources}} | |||
[[CME Category::Cardiology]] | |||
[[Category:Cardiovascular diseases]] | [[Category:Cardiovascular diseases]] | ||
[[Category:Reflexes]] | [[Category:Reflexes]] | ||
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[[Category:Signs and symptoms]] | [[Category:Signs and symptoms]] | ||
[[Category:Emergency medicine]] | [[Category:Emergency medicine]] | ||
Latest revision as of 05:01, 15 March 2016
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.
Clinical Implications
Bezold-Jarisch reflex plays a role in the following clinical conditions:
- Bradycardia, hypotension and gastrointestinal symptoms with inferoposterior myocardial infarction
- Exertional syncope in aortic stenosis
- Neurohumoral activation in chronic heart failure
- Reperfusion induced bradycardia and hypotension during coronary catheterization
- Therapeutic benefits of digitalis
- Vasovagal syncope[7]
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.
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.
Causes
Life Threatening Causes
Common Causes
- Chronic heart failure
- Coronary catheterization
- Digitalis
- Exertional syncope in aortic stenosis
- Inferoposterior myocardial infarction
- Serotonin receptor agonists
- Nitrate
- Vasovagal syncope[7]
Causes by Organ System
Causes by Organ System developed by WikiDoc.org, Copyleft 2013
Causes in Alphabetical Order
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References
- ↑ 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.
- ↑ 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.
- ↑ A. Jarisch, C. Henze Über Blutdrucksenkung durch chemische Erregung depressorischer Nerven. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1937, 187: 706-730.
- ↑ A. Jarisch Vom Herzen ausgehende Kreislaufreflexe. Archiv für Kreislaufforschung 1940, 7: 260-274.
- ↑ 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.
- ↑ Template:WhoNamedIt
- ↑ 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.
- ↑ 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) - ↑ 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.
- ↑ Katz, Arnold M. (2001). Physiology of the heart (3. ed. ed.). Philadelphia [u.a.]: Lippincott Williams & Wilkins. p. 595. ISBN 0-7817-1548-2.
- ↑ Linden R.J. Function of Cardiac Receptors. Circulation. 1973; 48: 463-480
- ↑ 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.
- ↑ eMedicine - Syncope : Article by M Silvana Horenstein, MD
- ↑ Tsai T. & Greengrass R. (2007). Textbook of Regional Anesthesia and Acute Pain Management: Spinal Anesthesia. (A. Hadzic, Ed.). New York: McGraw Hill Medical.
- ↑ Malinowska B. Godlewski G, Schlicker E. FUNCTION OF NOCICEPTIN AND OPIOID OP4 RECEPTORS IN THE REGULATION OF THE CARDIOVASCULAR SYSTEM, 2002, Bialystok, Poland