Separation of primary and secondary cardiovascular events in systemic anaphylaxis.

Abstract

SUMMARY The purpose of this investigation was to differentiate primary cardiac participation in systemic anaphylaxis from a cardiac reaction secondary to respiratory distress. Hemocyaninsensitized guinea pigs were anesthetized with sodium pentobarbital and artifically ventilated. The chest was opened and the left ventricle cannulated. The electrocardiogram, bronchial resistance, arterial blood pressure, and left ventricular pressure and its first derivative were recorded. Following intravenous administration of antigen, the sinus rate increased by about 50-60 beats/ min, left ventricular dP/dt increased by a factor of 3, and mean arterial pressure doubled. Conduction disturbances occurred in all of the experiments and ventricular fibrillation in four of six. These changes were concomitant with a 4-fold rise in bronchial resistance. To separate the cardiac and respiratory components, antigen was administered directly into the left ventricle to expose the heart to antigen before the lungs. The intracardiac challenge resulted in increases in sinus rate and left ventricular and arterial pressures quantitatively similar to changes recorded from guinea pigs after the intravenous challenge. However, all these changes preceded the rise in bronchial resistance by 60 seconds. Arrhythmias occurred as frequently as with the intravenous challenge. Our findings show that by use of an appropriate route for administration of antigen, cardiovascular and respiratory components of systemic anaphylaxis can be separated. Our data also indicate that anaphylactic cardiovascular changes can be dissociated temporally into two sets of events: an initial primary cardiac reaction caused by intracardiac release of histamine and a subsequent cardiovasular reaction secondary to systemic release of mediator.SEVERE disturbances of cardiovascular function occur during systemic anaphylaxis in the guinea pig. 5 include sinus tachycardia, atrioventricular conduction block, increased ventricular automaticity, and histamine release. The similarities between the effects on the heart of anaphylaxis in vivo and in vitro led us to the conclusion that the guinea pig heart reacts as a primary target organ in systemic hypersensitivity reactions.3 However, because cardiac and respiratory events occur at the same time during systemic anaphylaxis, the possibility could not be excluded that certain cardiovascular changes were secondary to the effects of bronchospasm.The present investigation describes an experimental model in which injection of antigen directly into the left ventricle of sensitized guinea pigs permits identification of the primary cardiac effects of anaphylaxis in vivo. MethodsThirty-two Hartley guinea pigs of either sex were sensitized by two consecutive weekly intraperitoneal injections of 1 mg of alum-precipitated keyhole limpet hemocyanin (K.LH); 15-30 days after sensitization blood samples were taken by puncture of the retro-orbital plexus, and the serum level of anti-KLH anaphylactic antibody was determined by passive cutaneous anaphylaxi...

Acceleration of idioventricular rhythms by histamine in guinea pig heart: mediation by H2 receptors.

“…The mechanism by which histamine increases idioventricular rate probably involves two components: (1) an enhancement in automaticity of the original pacemaker, and (2) IN THE course of our studies on the cardiac effects of histamine we had become intrigued by the fact that histamine, whether exogenously administered or endogenously released, could induce ventricular dysrhythmias ranging from isolated multifocal ectopic beats to ventricular tachycardia and fibrillation. The severity of the arrhythmia was related to the amounts of histamine injected or released (Levi, 1972;Capurro and Levi, 1975;Levi and Capurro, 1975;Zavecz and Levi, 1977). The purpose of the present study was to investigate the mechanism of histamine-induced ventricular tachyarrhythmias by studying the influence of histamine on ventricular rhythmicity.…”

Cardiac dysfunction caused by purified human C3a anaphylatoxin.

“…The cardiac effects of C3a resemble those observed in sensitized guinea pig hearts upon challenge with the specific antigen; from a quantitative standpoint, however, the changes caused by C3a are of lesser intensity and shorter duration than those provoked by cardiac anaphylaxis (7,19,20). In the latter, sinus tachycardia is caused by the release of endogenous cardiac histamine, which has marked H2-mediated positive chronotropic effects (17,21).…”

“…1, with increasing doses (0. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Mg) C3a enhanced the sinus rate (by beats/min, equivalent to a 3%-30% increase), prolonged the P-R interval (by 3%-50%), decreased left ventricular contractile force (by 3%-32%), and diminished coronary flow rate (by 7%-30%).…”

Anaphylactic Reactions to Bee-Sting Challenges in Allergic Children Are Not Modified by Endogeneous Catecholamines

“…The benign natural history of allergy to Hymenoptera stings particularly observed in childhood (8 -1 1) requires more precise scrutiny before an individual child can be assigned to receive venom immunotherapy. Single (4, 12) or sequential sting challenges (13, 14) can be offered to estimate the patient's individual risk and thus to establish the necessity for venom immunotherapy.Various studies demonstrated a release of E, NE, and angiotensin 11 within several minutes after the onset of anaphylactic shock to maintain cardiovascular functions (15)(16)(17)(18). Van der Linden et al (12) made the same observation when investigating insect sting-allergic patients using stings fiom the insects in question.…”

“…Various studies demonstrated a release of E, NE, and angiotensin 11 within several minutes after the onset of anaphylactic shock to maintain cardiovascular functions (15)(16)(17)(18). Van der Linden et al (12) made the same observation when investigating insect sting-allergic patients using stings fiom the insects in question.…”