Cardioprotective effects of amlodipine on ischemia and reperfusion in two experimental models.
The cardioprotective effect of amlodipine, a long-acting dihydropyridine derivative, was studied in 2 experimental models of ischemia and reperfusion. Isolated and blood-perfused feline hearts were made globally ischemic for 60 minutes and then reperfused for 60 minutes. Alterations of left ventricular developed pressure and compliance were monitored in both amlodipine-treated hearts and saline-treated control animals. Changes in perfusion pressure indicated that amlodipine significantly reduced myocardial oxygen consumption and coronary vascular resistance. Furthermore, a progressive increase in resting left ventricular diastolic pressure indicated that amlodipine, administered before the onset of global ischemia, attenuated the development of ischemic contracture. Return of contractile function 60 minutes after reperfusion and maintenance of tissue concentrations of electrolytes were significantly better in the amlodipine-treated group than in the control animals. In intact canine hearts, regional myocardial ischemia was induced for 90 minutes, followed by 6 hours of reperfusion. Although the hemodynamic variables and the size of the region of risk did not differ significantly between treated animals and control animals, the infarct size was significantly smaller in the amlodipine-treated group than in the control animals, and a gradual reduction in coronary blood flow was observed in the control group that was prevented in the amlodipine group. A comparison of these findings with those observed with oxygen radical scavengers also is discussed. A detailed report of these studies was published in The American Journal of Cardiology (1989;64:101I-116I). This review is included here to maintain continuity of the symposium for the convenience of the reader.
Hoff
P T
PT
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Tamura
Y
Y
Lucchesi
B R
BR
D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002415:Cats; D003327:Coronary Disease / Q000188:drug therapy*; D004285:Dogs; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine