The effect of calcium on cardiac anaphylaxis in guinea-pig Langendorff heart preparations

Abstract

This study was designed to determine the effects of different calcium concentrations on the perfused isolated guinea-pig heart preparation subjected to cardiac anaphylaxis. Following challenge both physiological and biochemical effects were determined on hearts from guinea-pigs previously sensitized to ovalbumin. Perfusion media containing either 1,2.54 or 5 mM of calcium was used. In comparison to nonsensitized controls challenged to ovalbumin, challenged sensitized hearts (CSH) perfused with 1 mM Ca2+ showed an initial increase in dF/dt, a prolonged rise in H.R. and depressed coronary flow. Raising the calcium concentration to either 2.54 or 5 mM in CSH preparations resulted in a marked increase in the release of lactate dehydrogenase (LDH) into the coronary effluent and depressed coronary flow. Perfusing CSH preparations with increasingly higher calcium concentrations more often produced severe tachyarrhythmias and fibrillation. The highest level of histamine released into the coronary effluent occurred immediately following challenge and then declined exponentially over the next 20 min. Both challenge and the administration of histamine induced an immediate but transient increase in H.R., a rise in dF/dt, and LDH release. The infusion of histamine produced an increase in coronary flow, but on porcine tubular coronary arterial segments only a direct constricting effect was obtained. The prior administration of cimetidine (10(-5) M) attenuated the rise in LDH and dF/dt in CSH and nonsensitized preparations infused with histamine (3 micrograms). However, although cimetidine did not affect the decreased coronary flow in CSH preparations, it initially attenuated the rise in coronary flow in preparations infused with histamine. These results suggest that calcium enhances the likelihood of tachyarrhythmias in cardiac anaphylaxis. The release of LDH in histamine-infused preparations and those CSH preparations perfused with 2.54 and 5 mM calcium-containing media also suggests the possibility that calcium enhances the damaging effects on the myocardial cell in cardiac anaphylaxis.