Effect of Diltiazem on Myocardial and Microvascular Stunning in Open Chest Dog

Abstract

Background：Post-ischemic myocardial dysfunction (myocardial stunning is known to be associated with low reflow phenomenon or the reduction of coronary vasodilatory reserve. However, it remains controversial whether a relationship between myocardial stunning and post-ischemic impairment of coronary flow reserve exists. With increased influx of calcium into myocardial cells precipitated by ischemia and reperfusion known to be involved not only in the progression of myocardial tissue damage but also in the pathogenesis of postischemic myocardial dysfunction and impaired coronary vasodilatory reserve, it has been hypothesized that calcium channel blockers exert protective effects on post-ischemic myocardial dysfunction and microvascular dysfunction. Purpose：To investigate the effects of diltiazem, a calcium channel blocker, on post-ischemic myocardial dysfunction and coronary vasodilatory reserve, vehicle or diltiazem was administered before brief coronary artery occlusion in open chest dogs. Peak coronary flow and myocardial contractile function were measured after intracoronary infusion of endothelium-dependent vasodilator acetylcholine and endotheliumindependent vasodilator adenosine. The parameters measured before and after reperfusion in control dogs and diltiazem-treated dogs were compared. Method：Open chest dogs (n＝17 underwent 20 minutes occlusion of left circumflex artery followed by reperfusion for 60 minutes；the subjects were divided into two groups (n＝10 in control group and n＝7 in diltiazem group. Diltiazem dogs received diltiazem (0.2 mg/kg intravenuously 15 minutes before coronary occlusion. Control dogs received vehicle-a saline solution. Coronary blood flow was measured with electromagnetic flow probe. Coronary flow reserve was determined by peak coronary flow after intracoronary infusion of acetylcholine (ACH, 0.01 ug/kg and adenosine (ADE, 1.5 mg/kg； it was also determined by reactive hyperemia (RH measured after coronary occlusion for 20 seconds at baseline and 30 and 60 minutes after reperfusion. Segmental left ventricular function was assessed by 2-D echocardiography at the level of mid-papillary muscle, and changes of left ventricular function was