Haemodynamic pattern of formyl-leurosine induced acute cardiovascular depression in the dog.
High incidence of cardiovascular collapses during clinical treatments with the cytostatic Vinca derivative formyl-leurosine (F-leurosine) prompted efforts to analyse in experimental models the haemodynamic mechanisms underlying the cardiodepression induced by large doses of the drug. A variety of cardiovascular variables was measured in 38 dogs narcotized with sodium pentobarbital. It was found that i.v. administration of F-leurosine (2 mg/kg) elicits, after a very short latency (less than 5 min), considerable decreases of arterial and pulmonary blood pressure, ventricular contractile force, cardiac output, ventricular filling pressure, coronary blood flow, and myocardial O2 consumption. Calculated systemic and pulmonary vascular resistance increased, while coronary resistance did not change. The later phase of F-leurosine action (greater than 1 hour) was associated with a permanent circulatory depression, a compromised coronary autoregulatory capacity, and serious histological injuries in the heart. Autonomic blocking drugs could not prevent these effects. It is concluded that the F-leurosine-induced rapid primary (pharmacologic) depression is followed by toxic manifestations of a more serious, secondary cardiac damage caused by the direct action of the drug cellular membranes.
D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects; D012770:Shock, Cardiogenic / Q000139:chemically induced*; D014748:Vinca Alkaloids / Q000009:adverse effects* / Q000494:pharmacology
D001337:Autonomic Agents; D014748:Vinca Alkaloids; C016463:formyl-leurosine