The effects of cocaine on the cardiovascular system in rats

Abstract

By Zhen-hin Chan, Biochemistry

Advisor: Andrew Norman

Presentation ID: PM_A27

Abstract: Cocaine abuse is a major worldwide problem with no approved medications. h2E2, a humanized monoclonal anti-cocaine antibody, is a potential pharmacotherapy which acts by forming a complex with cocaine that is too large to pass through the blood-brain barrier. By sequestering cocaine into the peripheral circulation, h2E2 increases cocaine concentrations in the plasma greater than 10-fold in both rats and mice. This dramatic increase in peripheral concentration could have toxic effects, which need to be elucidated prior to clinical trials. Therefore, we investigated the effect cocaine produces on the cardiovascular system. Blood pressure and heart rate in male rats were measured using the Kent Scientific CODA tail vein volume pressure monitoring system. A dose range of intravenous cocaine (0.1-0.5 mg/kg) was administered and preliminary results indicate a dose-dependent increase on mean arterial pressure and heart rate. In addition, a single dose of cocaine (0.5 mg/kg) produced increases in the cardiac output, heart rate, and ejection fraction of a male rat heart, as measured by echocardiography. Therefore, cocaine produces measurable effects on the cardiac system in rats. Now we will investigate whether h2E2 exacerbates or antagonizes the effects of cocaine on the cardiovascular system, an important milestone for the clinical development of h2E2.