Effect of cocaine on cardiac biochemical functions

The role of cocaine in cardiac ischemia and subsequent reversible and irrev ersible pathologic changes is well established. Nevertheless, the mechanism s leading to cardiac injury and irreversible cellular changes remain elusiv e. Reactive oxygen species (ROSs) are the critical mediators of cellular da mage during ischemia-reperfusion. To explore the response of cardiac oxidat ive stress parameters to intravenous (i.v.) And intraperitoneal (i.p.) coca ine exposure, cardiac total glutathione (GSH, GSSG), malonaldialdehyde (MDA ), Mn-superoxide dismutase (Mn-SOD), catalase (CAT), GSH-peroxidase (GSH-px ), and GSH s-transferase (GST) were measured, along with biochemical and hi stologic markers indicative of cardiac injury. Repeated i.p. cocaine exposu re produced significant impairment in cardiac integrity, demonstrated by in creased circulating lactate (2.4-fold; p < 0.0001), creatine kinase (2.2-fo ld; p < 0.0001), and creatinine levels (1.7-fold; p < 0.0001). Infiltration of neutrophils into myocardial cavities also was evident. These changes pa ralleled increases in cardiac MDA (25%; p < 0.04), GSSG (55%; p < 0.001), p rotein carbonyls (23%; p < 0.05), and Mn-SOD (23%; p < 0.05) levels, indica tive of oxidative stress, decreases in GSH (35%; p < 0.01), adenosine triph osphate (ATP; 26%; p < 0.04), GSH-px (28%; p < 0.03), CAT (32%; p < 0.01), and GST (50%; p < 0.001) levels. Intravenous cocaine administration also ha d similar effects on cardiac oxidative stress measures. In conclusion, our data indicate that cocaine administration compromised the heart's antioxida nt defense system.