Ricin depresses cardiac function in the rabbit heart.
Ricin, at toxic glycoprotein from the castor bean, causes myocardial hemorrhage and a decrease in blood pressure. We studied the effects of ricin on myocardial function in the isolated rabbit heart. Rabbits were given 0.22 micrograms/kg of ricin i.v. and 48 hr later, the heart was isolated and retrogradely perfused through the aorta with Tyrode's solution. A latex balloon was inserted into the left ventricle and isovolumic left ventricular function curves were generated. Left ventricular developed pressure (LVDP), heart rate, coronary artery flow, left ventricular end diastolic pressure, myocardial oxygen consumption, oxygen extraction (a - vO2), and contractility (+dp/dt) were measured over a range of left ventricular volumes. Dose-response curves to isoproterenol (10(-9)-10(-8) M) and phenylephrine (10(-9)-10(-6) M) were also obtained. Compared to the control group, ricin pretreatment markedly decreased ventricular compliance (p < 0.01), diminished maximum left ventricular 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 treatment groups. Ricin did not significantly alter the inotropic or chronotropic responses to isoproterenol and phenylephrine. The results from the binding studies showed that ricin neither reduced beta-adrenergic receptor numbers nor altered the dissociation constant. thus, ricin reduced both systolic (LVDP and +dp/dt) and diastolic (compliance) left ventricular functions, perhaps due to increased vascular permeability, without altering responses to the alpha- and beta-adrenoceptor agonists phenylephrine and isoproterenol.
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Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Hsu
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CH
Patterson
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Thadani
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Robinson
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004082:Dihydroalprenolol / Q000378:metabolism; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D012276:Ricin / Q000633:toxicity*; D016277:Ventricular Function, Left / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D012276:Ricin; D011433:Propranolol; D007545:Isoproterenol