(Circulation. 1997;96:1305-1312.)
© 1997 American Heart Association, Inc.
Articles |
Is Calcium a Mediator of Infarct Size Reduction With Preconditioning in Canine Myocardium?
From the Heart Institute, Hospital of the Good Samaritan, and Department of Medicine, Section of Cardiology, University of Southern California, Los Angeles.
Correspondence to Karin Przyklenk, PhD, Heart Institute/Research, Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA 90017.
Background The cellular mechanisms by which brief episodes of ischemia protect or "precondition" the heart and limit infarct size caused by a later period of sustained coronary artery occlusion remain unresolved. We propose that calcium may be an important mediator in eliciting this cardioprotection.
Methods and Results To test this hypothesis, anesthetized dogs received a 15-minute intracoronary infusion of 20 mmol/L CaCl2 or saline before undergoing 1 hour of coronary occlusion and 4 hours of reperfusion (protocol 1). Collateral blood flow during occlusion was measured with radiolabeled microspheres, area at risk of infarction (AR) was delineated by injection of blue dye, and area of necrosis (AN) was determined by tetrazolium staining. AN/AR was reduced from 20±5% in the saline-treated controls to 9±3% in CaCl2-treated dogs (P<.05). Additional animals underwent 10 minutes of preconditioning ischemia or a comparable waiting period before the 1-hour test occlusion (protocol 2). Administration of 5-(N,N-dimethyl)-amiloride (an inhibitor of calcium influx via Na+-H+ and Na+-Ca2+ exchange) before the preconditioning stimulus attenuated the protective effect of ischemic preconditioning: AN/AR was 12±1%, larger than the value of 4±1% observed in preconditioned dogs that received saline (P<.05) and comparable to the values of 12±3% and 14±3% seen in saline- and dimethylamiloride-treated controls.
Conclusions Brief intracoronary infusion of CaCl2 mimicked, whereas treatment with dimethylamiloride blocked, infarct size reduction with preconditioning, thereby implicating calcium as a mediator of preconditioning in this canine model.
Key Words: calcium • ischemia • myocardial infarction • signal transduction
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