Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents

Objectives. We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans. Background. The mechanisms underlying postischemic LV dysfunction are largely unknown. Methods. Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. Zn 50 patients undergoing coronary stenting for 77 +/- 5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 mu g/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 mu g/kg of the alpha(1)-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline. Results. Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34 +/- 9% to 45 +/- 8% and to 49 +/- 8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34 +/- 6%), as in control subjects. Conclusions. LV dysfunction occurs after PTCA as described in animal models after ischemia, Alpha blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha-and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction. (C)1998 by the American College of Cardiology.