Nitric oxide inhibition intensifies the depressant effect of cocaine on the left ventricular function in anaesthetized pigs

Background Myocardial ischaemia and left ventricular dysfunction have been described in cocaine users. Whether nitric oxide (NO) inhibition may potent iate the effects of cocaine on coronary circulation and ventricular functio n is still unknown. Materials and methods In order to test this hypothesis, 38 pentobarbital-an aesthetized pigs were instrumented for systolic blood pressure, coronary bl ood flow, left ventricular dp/dt, cardiac output, left ventricular end-dias tolic and end-systolic lengths and shortening fraction. The pigs were rando mized into three groups: control group: i.v. saline (n = 5); group 1: i.v. cocaine, 10 mg kg(-1) over 20 min (n = 17); group 2: the same doses of coca ine 30 min after i.c. L-NAME 20 mug/kg min(-1) infusion (n = 16). In order to know whether the observed effects were specific of NO inhibition, in fiv e pigs i.c. l-arginine was simultaneously infused with L-NAME, in five pigs i.c. NTG, an endothelial-independent vasodilator, was simultaneously infus ed with L-NAME before cocaine was administered, and in nine additional pigs the proximal left anterior descending (LAD) flow was reduced to around 20% of the basal value by means of a mechanical occluder before cocaine was ad ministered. Results Cocaine i.v did not change the coronary blood flow, while it induce d a significant reduction in cardiac output, left ventricular dp/dt and sho rtening fraction (15 +/- 4-8 +/- 4%, P < 0.05). When cocaine was administer ed after L-NAME infused i.c. during 30 min, a significantly more severe red uction of the shortening fraction (12 +/- 3-4 +/- 2%, P < 0.0001) was induc ed; this effect was abolished by simultaneous perfusion of l-arginine i.c. NTG. The results when cocaine was administered after the 20% LAD flow reduc tion by mechanical occluder did not differ from those of cocaine alone. Conclusions NO inhibition intensifies the cocaine-induced left ventricular dysfunction.