FURTHER ASSESSMENT OF THE PROTECTIVE EFFECT OF CALMODULIN INHIBITORS AGAINST REPERFUSION INJURY AFTER ACUTE CORONARY-OCCLUSION IN THE DOG

OBJECTIVE: To re-evaluate the suitability of chlorpromazine and triflu operazine to prevent postischemic reperfusion injury of the myocardium . DESIGN: Acute occlusion (60 mins) and subsequent reperfusion (120 mi ns) of the left anterior descendent coronary artery with monitoring of hemodynamic, morphological and biochemical variables of the heart. SE TTING: Experimental study. ANIMALS: Seventy adult mongrel dogs. INTERV ENTIONS: Chlorpromazine (15 mg/kg body weight) or trifluoperazine (2 m g/kg body weight) given intravenously 30 mins after the onset of occlu sion. MAIN RESULTS: Reperfusion alone increased the regional bloodflow and left ventricular end-diastolic pressure (P<0.05 to 0.01), and red uced the size of the occluded area. Reperfusion also decreased the dp/ dt(max), V(max), mean aortic pressure, cardiac index, etc, but failed to improve cardiac ultrastructure and metabolism. Chlorpromazine or tr ifluoperazine induced a further reduction (P<0.05 to 0.01) in infarct size, left ventricular end-diastolic pressure and systemic resistance index, and caused an increase in dp/dt(max), V(max), cardiac index and regional bloodflow in the ischemic and border zones of the left ventr icle. Moreover, these drugs preserved, to a certain extent, the metabo lism of the myocardium and its ultrastructure. CONCLUSIONS: In spite o f their considerable preventive effect, neither chlorpromazine nor tri fluoperazine provided a complete prevention of reperfusion injury to t he myocardium.