Cardioprotective effects of amlodipine in animal models of ischemia and reperfusion.
The protective effect of amlodipine was studied in isolated blood-perfused cat hearts made globally ischemic for 60 min followed by reperfusion for 60 min. Ischemia-induced alterations of left ventricular developed pressure and compliance were monitored. Amlodipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml of oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). When administered before the onset of global ischemia, amlodipine decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 min after reperfusion, was improved significantly in amlodipine-treated hearts compared to controls and there was better maintenance of the tissue concentration of Na+, Ca2+, and K+. In a canine model of regional myocardial ischemia (6 h) followed by reperfusion, amlodipine at 150 microg/kg, administered 15 min before reperfusion (90 min), reduced infarct size expressed as a percentage of the area at risk (34.5 +/- 3.8% vs. 45.9 +/- 2.8%, p = 0.027). We conclude that amlodipine reduces myocardial ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen demand as well as by positively influencing transmembrane Ca2+ fluxes during ischemia and reperfusion.
Lucchesi
B R
BR
Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI 48109-0626, USA.
Hoff
P T
PT
Tamura
Y
Y
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D017311:Amlodipine