RICIN DEPRESSES CARDIAC-FUNCTION IN THE RABBIT HEART

Ricin, a toxic glycoprotein from the castor bean, causes myocardial he morrhage and a decrease in blood pressure, We studied the effects of r icin on myocardial function in the isolated rabbit heart, Rabbits were given 0.22 mu g/kg of ricin iv and 48 hr later, the heart was isolate d and retrogradely perfused through the aorta with Tyrode's solution. A latex balloon was inserted into the left ventricle and isovolumic le ft ventricular function curves were generated. Left ventricular develo ped pressure (LVDP), heart rate, coronary artery flow, left ventricula r end diastolic pressure, myocardial oxygen consumption, oxygen extrac tion (a - vO(2)), and contractility (+dp/dt) were measured over a rang e of left ventricular volumes. Dose-response curves to isoproterenol ( 10(-9)-10(-8) M) and phenylephrine (10(-9)-10(-6) M) were also obtaine d. Compared to the control group, ricin pretreatment markedly decrease d ventricular compliance (p < 0.01), diminished maximum left ventricul ar developed pressure (p < 0.05), and reduced maximal +dp/dt (p < 0.05 ). Myocardial oxygen consumption, heart rate, electrocardiographic PR, QRS, and QT intervals were not different in control and ricin treatme nt groups. Ricin did not significantly alter the inotropic or chronotr opic responses to isoproterenol and phenylephrine. The results from th e binding studies showed that ricin neither reduced beta-adrenergic re ceptor numbers nor altered the dissociation constant. Thus, ricin redu ced both systolic (LVDP and +dp/dt) and diastolic (compliance) left ve ntricular functions, perhaps due to increased vascular permeability, w ithout altering responses to the alpha- and beta-adrenoceptor agonists phenylephrine and isoproterenol. (C) 1996 Academic Press, Inc.