Further assessment of the protective effect of calmodulin inhibitors against reperfusion injury after acute coronary occlusion in the dog.

Abstract

OBJECTIVE:

To re-evaluate the suitability of chlorpromazine and trifluoperazine to prevent postischemic reperfusion injury of the myocardium.

DESIGN:

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.

SETTING:

Experimental study.

ANIMALS:

Seventy adult mongrel dogs.

INTERVENTIONS:

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

MAIN 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.

• Authors: I Gabauer, J Slezak, J Styk, A Ziegelhöffer
• Journal: The Canadian journal of cardiology (Can J Cardiol) 1994 Jan-Feb Vol. 10 Issue 1 Pg. 125-32 ISSN: 0828-282X [Print] England
• PMID: 8111666 (Publication Type: Journal Article)

Chemical References

• Calmodulin
• Trifluoperazine
• Chlorpromazine

Topics

• Animals
• Calmodulin (therapeutic use)
• Chlorpromazine (pharmacology)
• Coronary Circulation (drug effects)
• Dogs
• Hemodynamics (drug effects)
• Myocardial Reperfusion Injury (metabolism, pathology, physiopathology, prevention & control)
• Myocardium (metabolism, pathology, ultrastructure)
• Trifluoperazine (pharmacology)