Deleterious Effects of Low and Medium Doses of Clonidine on Left Ventricular Function in Diabetic Rats

Abstract

During the perioperative period, α‐2 receptor agonists have been suggested to reduce cardiovascular (CV) risk by decreasing catecholamine‐induced cardiac stress. Diabetics have a higher incidence of perioperative CV complications due to autonomic dysfunction and hemodynamic instability. The potential benefits of clonidine, an α‐2 receptor agonist, in maintaining CV homeostasis in diabetics during the perioperative period are unknown. In this study, we evaluated with echocardiography the effects of clonidine (250, 50 and 10 µg/kg, IP) on the CV status of streptozotocin (STZ)‐induced diabetic and control (CT) rats while under anesthesia. The oxidative‐stress markers MDA and 4‐HAE were also measured in cardiac and aortic homogenates after 1‐hour incubation with clonidine (0.1, 1.0 and 10 µg/ml). Heart rate was reduced by clonidine in diabetic rats and CT. In contrast, high (250 µg/kg) and medium (50 µg/kg) clonidine doses did not affect stroke volume, cardiac output, or ejection fraction in either diabetic rats or CT. In diabetic, but not in CT, low (10 µg/kg) and medium (50 µg/kg) clonidine doses increased left ventricular end‐systolic and diastolic volumes by 80% and 50 %, respectively (n= 6, P<0.05). Clonidine did not alter MDA or 4‐HAE levels in cardiac and aortic homogenates from either diabetic rats or CT, suggesting that oxidative stress is not modified by acute clonidine incubation. Our results indicate that low and medium clonidine doses have a deleterious effect on ventricular function in diabetic rats, possibly because the negative cardiac inotropic and chronotropic effects outweigh the reductions in afterload that are secondary to α‐2 receptor activation by the drug.