Protective effect of calmodulin inhibitors on reperfusion injury.
Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Chlorpromazine and trifluoperazine, calmodulin inhibitors, were used to enhance myocardial preservation by preventing harmful effect of intracellular calcium accumulation. The experimental model used one-hour LAD coronary occlusion and subsequent two-hour reperfusion in 70 dogs divided into four groups. Reperfusion alone significantly increased regional myocardial blood flow and left ventricular enddiastolic pressure and significantly reduced infarct size, dp/dt max, V max, mean aortic pressure, cardiac index and index of left ventricular minute work. Phenothiazines, applied at the 30th minute of occlusion significantly reduced infarct size, left ventricular enddiastolic pressure and index of systemic resistance and significantly increased dp/dt max, V max, cardiac index and regional myocardial blood flow in ischemic and border zones. The physiological results tightly correlated with the biochemical results and ultrastructural findings. The present study suggests that phenothiazines can improve cardiac performance and preservation of myocytes by preventing calcium stimulatory effect on degradative enzymes and may represent a potential clinical tool in modifying myocardial injury induced by ischemia and reperfusion.
Gabauer
I
I
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, CSFR.
Slezák
J
J
Styk
J
J
Ziegelhöffer
A
A
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002746:Chlorpromazine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D014268:Trifluoperazine; D002746:Chlorpromazine