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

Abstract

SUMMARY To evaluate the ability of histamine to induce ventricular arrhythmias, we studied the effects of histamine on ventricular rhythmicity in the isolated guinea pig heart with complete atrioventricular conduction block. As a function of dose (0.1-30 pg), histamine enhanced the idioventricular rate by increasing the rate of firing of the original pacemaker and also by causing the sudden appearance of faster idioventricular rhythms that coincided with changes in pacemaker site. Anaphylaxis in the isolated guinea pig heart with complete atrioventricular conduction block caused histamine release and acceleration of idioventricular rate. The effects of histamine on idioventricular rhythmicity were not attenuated by the histamine Hi receptor antagonist chlorpheniramine, but were antagonized by the Hi receptor antagonist cimetidine. Moreover, the selective Hi agonist 4-methylhistamine (4MeH) accelerated the idioventricular rate, whereas 2-(2-thiazolyl) ethylamine (ThEA), at doses selective for Hi receptor activation, did not. The effects of histamine on idioventricular rhythmicity were not modified by the /J-adrenergic blocker pindolol. 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. We chose as an experimental model the isolated mammalian heart with complete atrioventricular conduction block. In this preparation idioventricular rate is not influenced by atrial pacemakers. MethodsMale Hartley guinea pigs weighing 300-400 g were stunned by a blow to the base of the skull. The heart was quickly excised and mounted in a Langendorff apparatus (Levi, 1972) and was perfused at constant pressure (40 cm H 2 O) with oxygenated Ringer's solution at 37°C. The ionic composition of the Ringer's solution was (in mM): Na + , 160; Cl~, 164; K + , 5.6; Ca ++ , 2.2; HC0J, 5.9; glucose, 5.5 The apex of the heart was connected by a nylon thread to a force-displacement transducer (model FT03B, Grass Instruments). Isometric ventricular contractions were displayed on a pen recorder (model R511, Beckman Instruments, Inc.). A bipolar surface electrogram, recorded from the right atrium and the left ventricle, was displayed on another channel of the pen recorder.Following an equilibration period of 30-45 minutes, the right atrium was cut open and a ligature (5-0 surgical...

Chronotropic cardiac effects of histamine in the conscious dog with chronic atrioventricular block: interactions with the autonomic nervous system

“…Here again, for the reasons given above, it seems unlikely, though not impossible, that catecholamine release is involved. Unlike the results reported by Levi and Zavecz [37] obtained on the His bundle of the guinea pig, albeit with doses higher than those ,used here, our results do not evidence the presence of histamine receptors in the His bundle of the dog. As observed at the level of the sinoatrial node, a negative chronotropic effect of histamine occurs in some animals at the level of the His bundle after blockade of only the beta-adrenoceptors with pindolol.…”

Histamine modification of spontaneous rate and rhythm in infarcted canine ventricle

“…Histamine causes arrhythmogenic alterations in impulse formation (automaticity) in normal guinea-pig ventricular myocardium [3] and in diseased human atrial muscle [4] via stimulation of cardiac H:receptors. On the other hand, arrhythmogenic alterations in impulse propagation (i.e.…”

The effects of cimetidine on histamine atrial chronotropic receptor activity

“…Another group [12] measured mechanical and electrical activity in guinea pig right ventricles and left and right atria that were treated with histamine, cimetidine, and diphenhydramine, however very high concentrations of eimetidine and diphenhydramine were used. There was another study in which the positive inotropic response of ventricular preparations to histamine was reported to be initiated by the H2-receptors; however, a negative inotropic effect was unmasked after the positive inotropic response was blocked with metiamide or cimetidine [13].This group reported also that histamineinduced idioventricular chronotropic responses that could be antagonized by cimetidine occurred in atrioventricular-blocked isolated guinea pig hearts [ 14].…”