1 The cardiovascular effects of (-)-cis-diltiazem, an optical isomer of diltiazem, were studied in the isolated atrium and aortic strip. (-)-cis-Diltiazem (30,pM or more) increased the developed tension of the rat left atrium, while (+ )-cis-diltiazem (1 ,UM or more) decreased it.2 (-)-cis-Diltiazem (1 to 100pM) decreased the rate of spontaneous beating in the right atrium as did (+ -cis-diltiazem. 3 The potency of the positive inotropic action of (-)-cis-diltiazem was almost the same as that of ouabain in the rat left atrium, but in the guinea-pig left atrium it was considerably weaker than that of ouabain.4 In both endothelium-intact and endothelium-denuded aortic strips, (-)-cis-diltiazem relaxed the Ca2 -induced contraction. In the endothelium-intact rat aortic strip depolarized by 15mM KC1, Bay K 8644, a calcium channel agonist, increased the contractile force, whereas (-)cis-diltiazem did not. 5 These results indicate that (-)-cis-diltiazem has a positive inotropic action in isolated atria in rats and guinea-pigs, but the mode of positive inotropic action of (-)-cis-diltiazem is different from that of ouabain or Bay K 8644.

According to the receptor binding assay, not only i9-adrenergic receptors but also ai adrenergic receptors exist on the myocardial cell membrane (1, 2). During ischemia, re leased catecholamines activate (3-adrenergic receptors and make the myocardial damage worse (3). There are reports indicating that 8-adrenergic blocking agents, such as pro pranolol, can reduce the myocardial injury caused by ischemia (4-6). Either norepi nephrine or epinephrine released during ischemia affects both 8 and ai -adrenergic receptors. In the recent studies, stimulation of a1 -adrenergic receptors of the myocardium activates phosphoinositide metabolism, lead ing to an increase in the intracellular calcium ion concentration (7). The increased calcium ions can produce a positive inotropism (8), cardiac arrhythmia (9). In addition, norepi nephrine induces cardiac hypertrophy through a,-adrenergic receptors (10). In the non ischemic normal myocardium, ai -adrenergic stimulation plays an important role in many physiological processes. In the ischemic myocardium, in which an energy deficiency has occurred, however, the stimulated ai adrenergic receptors may extend the in fluence of ischemia on the myocardium, be cause of activation of energy consuming pro cesses. A selective a,-adrenergic blocking agent can inhibit the activation of phospho inositide metabolism including the intracel lular calcium ion movement (11). Nayler et al. (12) have been reported that prazosin exerts a protective effect on the ischemic myocar dium under some in vitro conditions. How ever, it is still unclear whether an ai -ad renergic blocking agent directly protects the myocardium from ischemic damage in vivo. The present study, therefore, was undertaken to examine whether an al -adrenergic block ing agent, bunazosin, possesses a protective effect on the ischemic myocardium.* To whom reprint requests should be addressed .Materials and Methods Forty healthy mongrel dogs of either sex weighing 7-18 kg were anesthetized with sodium pentobarbital (30 mg/kg, i.v.), and endotracheally intubated and ventilated with a respirator. A left thoracotomy was performed between the fourth and fifth ribs to expose the left ventricular wall. A main trunk of the left anterior descending coronary artery (LAD) was dissected free from the adjacent tissues at a distal portion to the first diagonal branch, and it was loosely encircled with a 2-0 silk thread ligature. Ischemia was initiated by ligating the LAD. An ischemic region of the myocardium was assessed by visible cyanosis and the elevation of the ST segment of the ECG, which was introduced by a wire elec trode attached on the surface of the left ven tricular wall. Heart rate was counted from the ECG taken in the standard limb lead II. Arteri al blood pressures were measured via cannula introduced into the left femoral artery. Coro nary blood flow was measured by an elec tromagnetic flow probe positioned just proxi mal to the ligature.After a 60-min stabilization period, either saline or bunazosin (0.3 mg/kg) was injected i.v. ov...