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 trifluoperazine to prevent postischemic reperfusion injury of the myocardium.


METHODS
Acute occlusion (60 mins) and subsequent reperfusion (120 mins) of the left anterior descendent coronary artery with monitoring of hemodynamic, morphological and biochemical variables of the heart.


METHODS
Experimental study.


METHODS
Seventy adult mongrel dogs.


METHODS
Chlorpromazine (15 mg/kg body weight) or trifluoperazine (2 mg/kg body weight) given intravenously 30 mins after the onset of occlusion.


RESULTS
Reperfusion alone increased the regional bloodflow and left ventricular end-diastolic pressure (P < 0.05 to 0.01), and reduced the size of the occluded area. Reperfusion also decreased the dp/dtmax, Vmax, mean aortic pressure, cardiac index, etc, but failed to improve cardiac ultrastructure and metabolism. Chlorpromazine or trifluoperazine 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/dtmax, Vmax, cardiac index and regional bloodflow in the ischemic and border zones of the left ventricle. Moreover, these drugs preserved, to a certain extent, the metabolism of the myocardium and its ultrastructure.


CONCLUSIONS
In spite of their considerable preventive effect, neither chlorpromazine nor trifluoperazine provided a complete prevention of reperfusion injury to the myocardium.
Gabauer
I
I
Institute for Heart Research, Slovak Academy of Sciences, Braislava.
Slezak
J
J
Styk
J
J
Ziegelhöffer
A
A
D000818:Animals; D002147:Calmodulin / Q000627:therapeutic use*; D002746:Chlorpromazine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D014268:Trifluoperazine; D002746:Chlorpromazine