North American Journal of Medical Sciences

: 2013  |  Volume : 5  |  Issue : 11  |  Page : 631--636

Anaphylactic shock: Kounis hypersensitivity-associated syndrome seems to be the primary cause

Nicholas G Kounis1, George D Soufras2, George Hahalis3,  
1 Department of Medical Sciences, Patras Highest Institute of Education and Technology, Patras, Greece
2 Department of Cardiology, 'Saint Andrews' State General Hospital, Patras, Greece
3 Department of Cardiology, University of Patras Medical School, Rio, Patras, Greece

Correspondence Address:
Nicholas G Kounis
Queen Olgas Square, 7 Aratou Street, Patras 26221


Experiments have shown that anaphylaxis decreases cardiac output; increases left ventricular end diastolic pressure; induces severe early acute increase in respiratory resistance with pulmonary interstitial edema; and decreases splanchnic, cerebral, and myocardial blood flow more than what would be expected from severe arterial dilation and hypotension. This is attributed to the constrictive action of inflammatory mediators released during anaphylactic shock. Inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet-activating factor (PAF), and a variety of cytokines and chemokines constitute the pathophysiologic basis of Kounis hypersensitivity-associated acute coronary syndrome. Although the mechanisms of anaphylactic shock still remain to be elucidated, myocardial involvement due to vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome should be always considered. Searching current experimental and clinical literature on anaphylactic shock pathophysiology, causality, clinical appearance, and treatment via PubMed showed that differentiating global hypoperfusion from primary tissue suppression due to mast cell mediator constrictive action on systemic arterial vasculature is a challenging procedure. Combined tissue suppression from arterial involvement and peripheral vasodilatation, perhaps, occur simultaneously. In cases of anaphylactic shock treatment targeting the primary cause of anaphylaxis together with protection of coronary vasculature and subsequently the cardiac tissue seems to be of paramount importance.

How to cite this article:
Kounis NG, Soufras GD, Hahalis G. Anaphylactic shock: Kounis hypersensitivity-associated syndrome seems to be the primary cause.North Am J Med Sci 2013;5:631-636

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Kounis NG, Soufras GD, Hahalis G. Anaphylactic shock: Kounis hypersensitivity-associated syndrome seems to be the primary cause. North Am J Med Sci [serial online] 2013 [cited 2021 Jun 24 ];5:631-636
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It is generally believed, that during anaphylactic shock, the observed myocardial damage and ventricular dysfunction is the result of depression of cardiac output due to coronary hypoperfusion from systemic vasodilation, leakage of plasma and volume loss due to increased vascular permeability, and reduced venous return. It has been reported that during anaphylactic shock circulating blood volume may decrease by as much as 35% within 10 min due to transfer of intravascular fluid to extravascular space. [1] Furthermore, severe vasodilation resistant to epinephrine and responding only to other potent vasoconstrictors has been also reported. [2]

This effective shift of fluid volume is countered by compensatory vasopressor mechanisms involving the release of epinephrine and norepinephrine together with activation of angiotensin system. [3] The ensuing increase in catecholamines might produce varied effects. Some patients during anaphylactic episodes experience maximum peripheral vasoconstriction due to increased vascular resistance while others have decreased systemic vascular resistance. The variable effects of internal compensatory mechanisms might explain why epinephrine injections sometimes fail to help acute and severe allergy. Furthermore, the endogenous catecholamine release which can be enhanced by therapeutic administration can have an adverse effect in myocardium, including ischemic chest pain and electrocardiographic changes even in the absence of existing coronary disease. [4],[5] Indeed, platelets from patients suffering from angina pectoris are more sensitive to increased endogenous serum epinephrine levels and therefore are prone to get activated and aggregate in order to induce thrombotic events. [6] In anaphylactic shock, experiments with ovalbumin-sensitized guinea pigs [7] have shown that left ventricular end diastolic pressure raises within 3 min following antigen challenge; while, contemporarily, cardiac output declines by 90%. These have forced the researchers to conclude that the view of registered anaphylactic cardiac damage might be due to peripheral vasodilatation should be definitively excluded. Other recent experimental findings [8] have shown that during anaphylactic shock the cerebral blood flow decreases more than what would be expected from severe arterial hypotension. This was attributed to the early and direct action of anaphylactic mediators on cerebral vessels. Concurrent changes in airway-lung mechanics, such as respiratory resistance and reactance response to ovalbumin-induced anaphylactic shock in allergic rats have been also studied. [9] It was found that an early increase in respiratory resistance followed by a decrease in respiratory reactance consistent with initial acute bronchoconstriction occurs and this is followed by pulmonary capillary leakage into smaller airspaces.

The above experimental findings in heart, brain, and lungs show that coronary vasoconstriction cerebral vasospasm and bronchoconstriction are the initial events during anaphylactic shock. These findings together with clinical observations according to which anaphylactic myocardial damage responds to myocardial infarction protocol treatment and not only to fluid replacement, might have profound implications in pathophysiology of anaphylactic shock and also clinical and therapeutic implications as far as Kounis hypersensitivivity-associated syndrome is concerned. [10],[11],[12],[13]

 Kounis Syndrome: The Hypersensitivity Coronary Disorder

The association of allergic, anaphylactic, and anaphylactoid reactions with acute coronary events had been observed more than 6 decades ago and cases of allergic myocardial infarction were published in 1965. [14] However, a detailed description of the allergic angina syndrome, which could progress to acute allergic myocardial infarction, was not described until 1991. [15] Following this initial description, other researchers emphasizing the existence and association of this syndrome with coronary inflammation and vasospastic angina gave recognition, name, attention, and emergence to this life-threatening clinical phenomenon. [16],[17] Today allergic angina and allergic myocardial infarction, [18] that are referred to as 'Kounis syndrome', are ubiquitous diseases affecting from pediatric to geriatric patients, involving numerous and continuously increasing causes, with broadening clinical manifestations and covering a wide spectrum of mast cell activation disorders. It has been repeatedly stated that Kounis syndrome is not a rare disease but a rarely diagnosed condition. [19] Kounis syndrome is regarded as nature's own experiment and magnificent natural paradigm which might have profound clinical and therapeutic implications and may shed light on potential therapeutic strategies that may apply to the area of interference with plaque erosion or rupture and primary as well as secondary prevention of acute coronary and cerebrovascular events. [20] The number of causes that have been implicated to induce Kounis syndrome is increasing rapidly. These include various drugs, environmental exposures, and several conditions. [21] The most recent offender was Anisakis simplex. [22] Other recent offenders include scombroid syndrome, [23] which is also called histamine fish poisoning; gelofusin substance; [24] latex exposure; [25] losartan; [26] systemic mastocytosis; and mast cell activation syndromes. [27] Anisakis simplex is a common fish parasite which can sensitize humans and induce anisakiasis and Kounis syndrome. On the other hand, fish flesh contains the aminoacid histidine and when fish is infected by gram negative bacteria which contain the enzyme histidine decarboxylase, this enzyme converts histidine to histamine which induces Kounis syndrome. The gelofusin substance is a bovine gelatin administered to maintain intravascular volume. Gelofusin is component of various vaccines for children and constitutes the main cause of sensitization to children. It should be always remembered the "kiss of death" [21] and the "dog licking". [21] "The kiss of death" occurs when a person after consumption of shellfish or peanuts kisses or exhales allergens during oral contact with a person who happens to be allergic to these substances. Furthermore a dog, who receives antibiotic such as penicillin for any infection, can be very dangerous when he or she, in a gesture of compliance licks his penicillin allergic master or other associates. Kounis syndrome is manifesting with three variants: Coronary artery spasm, myocardial infarction, and stent thrombosis. [28] The currently used bare metal coronary stents are made from metal platform which is stainless steel containing nickel, chromium, titanium, manganese, and molybdenum. In the drug eluting coronary stents the metal platform is covered by the polymer coating with impregnated antiproliferative drugs. All these components constitute an antigenic complex that applies continuous, persistent, repetitive, and chronic inflammatory irritation on the arterial intima lasting as long as the antigens stay present. That is why some unexpected, peculiar, bizarre, strange, surprising, extraordinary, and astonishing reports are appearing in the medical literature. According to these reports, patients with implanted stents who accidentally developed an allergic reaction elsewhere in the human body from various causes are prone to develop, contemporarily intrastent thrombosis culminating in deadly anaphylactic cardiac shock. Indeed, such stent thrombosis has been associated with allergic symptoms such as glottis edema, cold sweat, and tongue enlargement followed flavonate-propyphenasone administration a week after stent implantation, [29] intravenous administration of the non-anionic contrast material iopromide during routine excretory urography, [30] nonsteroidal anti-inflammatory agent acemetacine manifesting as type III variant, [31] and anaphylaxis after insect and larvae stings. [32] Even the astonishing event that allergy to clopidogrel, the drug given to prevent stent thrombosis, has induced itself stent thrombosis. [33] The incidence of anaphylaxis with cardiovascular features is about eight per 100,000 population in both Europe and USA. [34],[35] Cardiovascular symptoms are more common in events occurring in the operating room and are associated mainly with muscle relaxants and latex. [36] In a cohort including children from 3 to 14 years, the incidence of anaphylaxis with cardiovascular symptoms including hypotension, tachycardia, and cardiac arrest was 20.5%. [37] In a study on 29 fatalities from Hymenoptera stings, the performed autopsy in 12 fatalities revealed 11 with cardiac disease, 10 of which had coronary heart disease. [38] So far, there are 20 published cases of anaphylactic shock associated with Kounis syndrome. These cases include patients who did not respond to antianaphylactic treatment, but required additional myocardial infarction protocol therapy. This clinical evidence, together with experimental findings, supports the view that anaphylactic shock is the result of depression of cardiac output due to coronary hypoperfusion from vasoconstrictive action of anaphylactic mediators on the coronary tree and not only from systemic vasodilation. Type I and type II variants of Kounis syndrome [21] include such patients with normal or nearly normal coronary arteries and patients with culprit, but quiescent preexisting atheromatous disease in whom the acute release of anaphylactic mediators can induce either coronary artery spasm or coronary artery spasm together with plaque erosion or rupture culminating in acute myocardial infarction with anaphylactic cardiac shock.

 Experimental Evidence

In a recent experiment in rats, [39] it was shown that vascular resistance responses to anaphylactic shock were characterized by considerable increase in portal venous resistance, initial transient decrease in hepatic artery and splanchnic vascular resistances, and absence of a significant increase in splanchnic vascular resistances in the early stage. This opposes to the general belief that anaphylactic shock is the result of diminished vascular resistance leading to vasodilation and fluid extravasation. The increased portal venous resistance is attributed to anaphylaxis-released vasoactive mediators which constrict portal veins in isolated perfused rat livers. [40]

In another experiment, [41] left ventricular pressure, coronary artery, and coronary vein pressures and coronary flow were directly and simultaneously measured before and after ovalbumin challenge in both antigen-sensitized and in nonsensitized rat hearts with induced coronary flow reduction. The authors determined maximum increasing rate of left ventricular pressure (dp/dtmax) during isovolumic contractions for the assessment of left ventricular contractility without changes in preload. They applied also the cross-circulated blood perfusion method, which permits analysis of left ventricular mechanical work in the excised heart under more physiological conditions. They concluded that coronary vasoconstriction inducing myocardial ischemia, during anaphylaxis, is the main and major contributory factor for the ensuing ventricular dysfunction. Furthermore, in the studies with ovalbumin-sensitized guinea pigs, [7] it was shown that soon after antigen administration, electrocardiogram showed signs of acute myocardial ischemia, cardiac output was decreased by 90%, left ventricular end diastolic pressure was raised indicating pump failure, and arterial blood pressure was increased. Blood pressure started declining steadily after 4 min. It was concluded that the rapid increase in left ventricular end diastolic pressure suggests that volume loss due to an increase in vascular permeability and decreased venous return were unlikely to have been the primary causes of the documented depression in cardiac output. It was concluded that the view of registered anaphylactic cardiac damage might be due to peripheral vasodilatation should be definitively excluded. [7] In another experiment, [42] passively sensitized guinea pigs with anti-albumin rabbit serum and challenged with albumin, showed heart rate and left ventricular end diastolic pressure markedly increased; while coronary flow, aortic flow, left ventricular developed pressure, and dp/dtmax profoundly decreased. When specific platelet-activating factor (PAF) antagonist was administered, the increased heart rate and left ventricular end diastolic pressure as well as the decrease in coronary and aortic flow, left ventricular developed pressure and dp/dtmax were all inhibited in a dose dependent manner. PAF is mast cell mediator deriving from mast cell degranulation in anaphylaxis and its neutralization by its antagonist results in inhibition of primary events of anaphylaxis on coronary blood flow and other parameters. In isolated guinea pig, hearts undergoing anaphylaxis after an intra-aortic injection of antigen, [43] a prompt and prolonged decrease in coronary blood flow, an abrupt heart rate increase that peaked within 2 min, and a transient increase in ventricular contractile force followed by a prolonged decrease were observed. These findings are in accordance with those from other reports that anaphylactic cardiac damage may be dissociated temporarily into two sets of events: Initial primary cardiac reaction caused by the intracardiac release of histamine and a subsequent cardiovascular reaction secondary to the systemic release of mediators. [44]

In the study of Davidson, [8] it was found that anaphylactic shock decreases cerebral blood flow more than what would be expected from severe arterial hypotension. The authors of this paper concluded that, in anaphylactic shock, severe impairment of the cerebral blood flow takes place which could not be explained by the level of arterial hypotension. In these experiments, with use of rat model of anaphylaxis, the tissue oxygen partial pressure decreased very rapidly, as early as 1 min following the onset of anaphylaxis and this was attributed to the early and direct action of anaphylactic mediators on cerebral vessels. Indeed, mast cell mediators such as histamine, chymase, and leukotrienes can induce cerebral artery spasm and PAF can reduce cerebral blood flow leading to postischemic hypoperfusion. Therefore, cerebral ischemia and brain injury following anaphylactic shock could be due to direct action of anaphylactic mediators on the cerebral arterial system and not solely due to arterial hypotension. Another experimental study [45] has shown that antigen challenge in the small isolated mesenteric and coronary arteries from the sensitized guinea pig is followed by anaphylactic contraction but not relaxation. The released NO from the endothelium of small arteries, during the antigen challenge, contributes to the development of hypotension or redistribution of blood during anaphylaxis. However, the contracting products of cyclooxygenase pathway are very important for the development of the small artery constriction in anaphylactic shock and counteract the development of the relaxation and hypotension. The authors of this study concluded that arterial contraction induced by anaphylaxis could be partially attenuated by the endothelium-derived NO and enhanced by the cyclooxygenase products in the small coronary and mesenteric arteries. All the above experimental evidence supports the view that the primary target of the released anaphylactic mediators is the arterial vasculature resulting in damage of the corresponding myocardial or brain tissue and the bronchial tree responding with severe early and acute bronchoconstriction.

 Clinical Evidence

There are, currently, patients with anaphylactic cardiac shock who do not respond to intravenous fluid administration and antiallergic therapy, but required coronary event treatment protocol. The following reports have been published this year. In a patient with Hymenoptera sting-induced Kounis syndrome complicated with anaphylactic shock, [46] urgent coronary angiography revealed acute coronary thrombosis and the patient recovered with intra-aortic balloon pump assistance and myocardial infarction treatment. In another patient, [47] who was stung by multiple wasps and developed type I variant of Kounis syndrome with anaphylactic shock and myocardial ischemia, treatment with 2 l of normal saline, adrenaline, hydrocortisone, and antihistamines did not have any immediate effect and the patient recovered in a later stage with vasopressors and myocardial infarction protocol treatment. In an atopic female nurse [48] with previous atopic eczema, asthma, and allergy to milk protein; who suffered an anaphylactic reaction, hemodynamic status was unresponsive to intravenous administration of fluids such as Ringer's acetate and antiallergic treatment with adrenaline and corticosteroids. Her condition was complicated with pulmonary congestion with reduced ejection fraction. The patient recovered with myocardial infarction protocol treatment. It was commented that hemodynamic disturbance was most probably due to myocardial stunning leading to reduced cardiac output rather than due to fluid extravasation. In a patient with per-operative anaphylactic shock due to gelofusin infusion [24] treatment with metaraminol and epinephrine worsened the hypotension and the cardiac output was lost. The patient recovered gradually with intravenous antihistamines, steroids, and inotropic support. Finally, in a patient with stent thrombosis following snake bite, [49] which today is regarded as anaphylactic consequence, the patient was not responding to inotropes and fluid expansion but he recovered with thrombolysis and other acute myocardial infarction protocol treatment.


Although the mechanisms of anaphylactic shock still remain to be elucidated, bronchial and myocardial involvement with early severe bronchoconstriction and vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome respectively should be always considered. Combined bronchoconstriction with interstitial edema and tissue suppression from arterial involvement and peripheral vasodilatation, perhaps, occur simultaneously. Therefore, in any case of anaphylactic shock combined treatment targeting the primary cause of anaphylaxis together with protection of lung and cardiac tissue seems to be of paramount importance. More studies and more experience are needed to determine the importance of mediators of anaphylaxis in myocardial pathobiology.


1Fisher MM. Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse. Anaesth Intensive Care 1986;14:17-21.
2Schummer W, Schummer C, Wipperman J, Fuchs J. Anaphylactic shock: Is vasopressin the drug of choice? Anesthesiology 2004;101:1025-7.
3van der Linden PW, Struyvenberg A, Kraaijenhagen RJ, Hack CE, van der Zwang JK. Anaphylactic shock after insect-sting challenge in 138 persons with a previous insect-sting reaction. Ann intern Med 1993;118:161-8.
4Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539-48.
5Brown SG. Cardiovascular aspects of anaphylaxis: Implications for treatment and diagnosis. Curr Opin Allergy Clin Immunol 2005;5:359-64.
6Wallén NH, Held C, Rehnqvist N, Hjemdahl P. Effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls. Eur Heart J 1997;15:807-15.
7Felix SB, Baumann G, Berdel WE. Systemic anaphylaxis - separation of cardiac reactions from respiratory and peripheral vascular events. Res Exp Med (Berl) 1990;190:239-52.
8Davidson J, Zheng F, Tajima K, Barthel G, Alb I, Tabarna A, et al. Anaphylactic shock decreases cerebral blood flow more than what would be expected from severe arterial hypotension. Shock 2012;38:429-35.
9Barthel G, Zheng F, Demoulin B, Davidson J, Montémont C, Gaburro J, et al. Biphasic airway-lung response to anaphylactic shock in Brown Norway rats. Respir Physiol Neurobiol 2013;189:47-51.
10Biteker M. Current understanding of Kounis syndrome. Expert Rev Clin Immunol 2010;6:777-88.
11Lopez PR, Peiris AN. Kounis syndrome. South Med J 2010;103:1148-55.
12Gázquez V, Dalmau G, Gaig P, Gómez C, Navarro S, Mercé J. Kounis syndrome: Report of 5 cases. J Investig Allergol Clin Immunol 2010;20:162-5.
13Ridella M, Bagdure S, Nugent K, Cevik C. Kounis syndrome following beta-lactam antibiotic use: Review of literature. Inflamm Allergy Drug Targets 2009;8:11-6.
14Zosin P, Miclea F, Munteanu M. Allergic myocardial infarction. Rum Med Rev 1965;19:26-8.
15Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: The concept of allergic angina. Br J Clin Pract 1991;45:121-8.
16Rich MW. Is vasospastic angina an inflammatory disease? Am J Cardiol 2005;96:1612.
17Zavras GM, Papadaki PJ, Kokkinis CE, Kalokairinov K, Kouni SN, Batsolaki M, et al. Kounis syndrome secondary to allergic reaction following shellfish ingestion. Int J Clin Pract 2003;57:622-4.
18Sinkiewicz W, Sobañski P, Bartuzi Z. Allergic myocardial infarction. Cardiol J 2008;15:220-5.
19Biteker M, Duran NE, Biteker FS, Civan HA, Kaya H, Gökdeniz T, et al. Allergic myocardial infarction in childhood: Kounis syndrome. Eur J Pediatr 2010;169:27-9.
20Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): A natural paradigm? Int J Cardiol 2006;110:7-14.
21Kounis NG. Coronary hypersensitivity disorder: The Kounis syndrome. Clin Ther 2013;35:563-71.
22Barbarroja-Escudero J, Rodriguez-Rodriguez M, Sanchez-Gonzalez MJ, Antolin-Amerigo D, Alvarez-Mon M. Anisakis simplex: A new etiological agent of Kounis syndrome. Int J Cardiol 2013;167:e187-9.
23Coppola G, Caccamo G, Bacarella D, Corrado E, Caruso M, Cannavò MG, et al. Vasospastic angina and scombroid syndrome: A case report. Acta Clin Belg 2012;67:222-5.
24Shah G, Scadding G, Nguyen-Lu N, Wigmore T, Chenzbraun A, Wechalekar K, et al. Peri-operative cardiac arrest with ST elevation secondary to gelofusin anaphylaxis-Kounis syndrome in the anaesthetic room. Int J Cardiol 2013;164:e22-6.
25Marcoux V, Nosib S, Bi H, Brownbridge B. Intraoperative myocardial infarction: Kounis syndrome provoked by latex allergy. BMJ Case Rep 2013;2013.
26Josefsson J, Fröbert O. Losartan-induced coronary artery spasm. BMJ Case Rep 2012;2012.
27González-de-Olano D, Matito A, Sánchez-López P, Sánchez-Muñoz L, Morgado JM, Teodósio C, et al. Mast cell-related disorders presenting with Kounis syndrome. Int J Cardiol 2012;161:56-8.
28Kounis NG, Mazarakis A, Tsigkas G, Giannopoulos S, Goudevenos J. Kounis syndrome: A new twist on an old disease. Future Cardiol 2011;7:805-24.
29Patanè S, Marte F, Di Bella G, Chiofalo S, Currò A, Coglitore S. Acute myocardial infarction and Kounis syndrome. Int J Cardiol 2009;134:e45-6.
30Kogias JS, Papadakis EX, Tsatiris CG, Hahalis G, Kounis GN, Mazarakis A, et al. Kounis syndrome: A manifestation of drug-eluting stent thrombosis associated with allergic reaction to contrast material. Int J Cardiol 2010;139:206-9.
31Greif M, Pohl T, Oversohl N, Reithmann C, Steinbeck G, Becker A. Acute stent thrombosis in a sirolimus eluting stent after wasp sting causing acute myocardial infarction: A case report. Cases J 2009;2:7800.
32Akyel A, Murat SN, Cay S, Kurtul A, Ocek AH, Cankurt T. Late drug eluting stent thrombosis due to acemetacine: Type III Kounis syndrome: Kounis syndrome due to acemetacine. Int J Cardiol 2012;155:461-2.
33Karabay CY, Can MM, Tanboða IH, Ahmet G, Bitigen A, Serebruany V. Recurrent acute stent thrombosis due to allergic reaction secondary to clopidogrel therapy. Am J Ther 2011;18:e119-22.
34Helbling A, Hurni T, Mueller UR, Pichler WJ. Incidence of anaphylaxis with circulatory symptoms: A study over a 3-year period comprising 940,000 inhabitants of the Swiss Canton Bern. Clin Exp Allergy 2004;34:285-90.
35Yocum MW, Butterfield JH, Klein JS, Volcheck GW, Schroeder DR, Silverstein MD. Epidemiology of anaphylaxis in Olmsted County: A population-based study. J Allergy Clin Immunol 1999;104:452-6.
36Ben-Shoshan M, Clarke AE. Anaphylaxis: Past, present and future. Allergy 2011;66:1-14.
37Serbes M, Can D, Atlihan F, Günay I, Asilsoy S, Altinöz S. Common features of anaphylaxis in children. Allergol Immunopathol (Madr) 2013;41:255-60.
38Mueller UR. Cardiovascular disease and anaphylaxis. Curr Opin Allergy Clin Immunol 2007;7:337-41.
39Zhang W, Shibamoto T, Tanida M, Wang M, Sun L, Kurata Y. Rat hepatic and splanchnic vascular responses to anaphylactic shock, compared with hemorrhagic or vasodilator-induced shock. In Vivo 2013;27:485-93.
40Cui S, Shibamoto T, Takano H, Zhang W, Kurata Y. Leukotrienes and cyclooxygenase products mediate anaphylactic venoconstriction in ovalbumin sensitized rat livers. Eur J Pharmacol 2007;576:99-106.
41Kuda Y, Kurata Y, Wang M, Tanida M, Shibamoto T. Major contribution of vasospasm-induced coronary blood flow reduction to anaphylactic ventricular dysfunction assessed in isolated blood-perfused rat heart. Cardiol J 2013.
42Tosaki A, Koltai M, Braquet P, Szekeres L. Possible involvement of platelet activating factor in anaphylaxis of passively sensitised, isolated guinea pig hearts. Cardiovasc Res 1989;23:715-22.
43Levi R. Cardiac anaphylaxis: Models, mediators, mechanisms, and clinical considerations. In: Marone G, Lichtenstein LM, Condorelli M, Fauci AS, editors. Human Inflammatory Disease Clinical Immunology, Vol. 1. Toronto: Decker; 1988. p. 93-105.
44Zavecz JH, Levi R. Separation of primary and secondary cardiovascular events in systemic anaphylaxis. Circ Res 1977;40:15-9.
45Laukeviciene A, Ugincius P, Korotkich I, Lazauskas R, Kevelaitis E. Anaphylaxis of small arteries: Putative role of nitric oxide and prostanoids. Medicina (Kaunas) 2010;46:38-44.
46Gangadharan V, Bhatheja S, Al Balbissi K. Kounis syndrome - An atopic monster for the heart. Cardiovasc Diagn Ther 2013;3:47-51.
47Mukta V, Chandragiri S, Das AK. Allergic myocardial infarction. N Am J Med Sci 2013;5:157-8.
48Kajander OA, Virtanen MP, Sclarovsky S, Nikus KC. Iatrogenic inverted takotsubo syndrome following intravenous adrenaline injections for an allergic reaction. Int J Cardiol 2013;165:e3-5.
49Satish R, Kanchan R, Yashawant R, Ashish D, Kedar R. Acute MI in a stented patient following snake bite-possibility of stent thrombosis - A case report. Indian Heart J 2013;65:327-30.