POSTISCHEMIC LEFT-VENTRICULAR DYSFUNCTION IS ABOLISHED BY ALPHA-ADRENERGIC BLOCKING-AGENTS

Objectives. We sought to evaluate the efficacy of alpha-adrenergic blo cking agents in counteracting left ventricular (LV) dysfunction occurr ing after transient ischemia in humans. Background. The mechanisms und erlying postischemic LV dysfunction are largely unknown. Methods. Perc utaneous 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 transeso phageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 mu g/kg body weight of the al pha-blocker phentolamine intracoronarily, 15 patients received 600 mu g/kg of the alpha(1)-blocker urapidil intravenously, 10 patients recei ved the combination of phentolamine and 1.2 mg of propranolol intracor onarily, and 10 patients received saline. Results. Fifteen minutes aft er successful coronary dilation, significant contractile dysfunction o ccurred in previously ischemic and nonischemic myocardium. LV dysfunct ion was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coron ary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34 +/- 9% to 45 +/- 8% an d to 49 +/- 8%, respectively (p < 0.05). After the administration of p ropranolol combined with phentolamine, LV dysfunction remained unchang ed (34 +/- 6%), as in control subjects. Conclusions. LV dysfunction oc curs after PTCA as described in animal models after ischemia, Alpha bl ockers abolished LV, macrocirculatory and microcirculatory dysfunction , whereas the alpha-blocker effect was prevented by combining alpha-an d beta-blockers. The evidence of diffuse rather than regional dysfunct ion, together with the opposite effects of alpha- and beta-blockade, s upports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction. (C)1998 by the American College of Cardiology.