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.