Inotropic Effects of Prostaglandin E 2 on Isolated Cardiac Tissue

Abstract

Summary

Prostaglandin E₂ (PGE₂) was studied for its effects on the contractile force of electrically driven or spontaneously beating rabbit left and right atrial preparations, as well as on human atrial appendages obtained from patients undergoing open-heart surgical procedures. A concentration of 2.84 μM produced a reproducible biphasic inotropic action on rabbit left atrial preparations characterized by a transient negative inotropic phase (—18.5%) followed by a sustained positive inotropic effect (+38.7%). A qualitatively similar inotropic response was observed using spontaneously beating rabbit right atria, although no significant chronotropic response was noted in these experiments. Human atrial appendage failed to respond to PGE₂ under the conditions used.

The negative and positive inotropic effects of PGE₂ on left atria are not significantly attenuated by classical cholinergic or beta-adrenergic blocking agents. Reserpine pretreatment in vivo also failed to modify the positive inotropic response, although the negative inotropic phase was significantly attenuated. Bretylium and diphenhydramine significantly attenuated but did not completely inhibit the positive inotropic phase. The antihistamine also produced a highly significant inhibition of the negative inotropic effect. Phenoxybenzamine failed to antagonize the positive inotropic response, although it reduced the magnitude of the negative inotropic effect.

An apparent tachyphylactic response to PGE₂ was observed in the rabbit atria experiments, as evidenced by failure to produce a normal inotropic effect upon rechallenging the tissues with PGE₂ following a prior response to an earlier dose.

The data suggest that a classical cholinergic, beta- or alpha-adrenergic, or catecholamine releasing mechanism is not involved in mediating the biphasic inotropic responses of rabbit left atria to a 2.84 μM concentration of PGE₂. A possible histaminergic mechanism may be operative, but is not proved, because of known nonspecific actions of the histamine antagonist used.