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Am J Physiol Heart Circ Physiol 282: H949-H955, 2002. First published November 1, 2001; doi:10.1152/ajpheart.00741.2001
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Vol. 282, Issue 3, H949-H955, March 2002

Cardiac overexpression of A1-adenosine receptor protects intact mice against myocardial infarction

Zequan Yang1,*, Rachael J. Cerniway2,*, Anne M. Byford2, Stuart S. Berr3, Brent A. French1,3, and G. Paul Matherne2

Cardiovascular Research Center, Departments of 1 Biomedical Engineering, 2 Pediatrics, and 3 Radiology, University of Virginia Health System, Charlottesville, Virginia 22908

Previous studies have shown that high-level (300-fold normal) cardiac overexpression of A1-adenosine receptors (A1-ARs) in transgenic (TG) mice protects isolated hearts against ischemia-reperfusion injury. However, this high level of overexpression is associated with bradycardia and increased incidence of arrhythmia during ischemia in intact mice, which interfered with studies to determine whether this line of TG mice might also be protected against myocardial infarction (MI) in vivo. For these studies, we therefore selected a line of TG mice that overexpresses the A1-AR at more moderate levels (30-fold normal), which affords cardioprotection in the isolated heart while minimizing bradycardia and arrhythmia during ischemia in intact mice. Wild-type (WT; n = 10) and moderate-level A1-AR TG (n = 10) mice underwent 45 min of left anterior descending coronary artery occlusion, followed by 24-h reperfusion. Infarct size and region at risk were determined by triphenyltetrazolium chloride and phthalo blue staining, respectively. Infarct size (% region at risk) in WT mice was 52 ± 3%, whereas overexpression of A1-ARs in the TG mice markedly reduced infarct size to 31 ± 3% (P < 0.05). Furthermore, contractile function (left ventricular ejection fraction) as determined by cardiac magnetic resonance imaging 24 h after MI was better preserved in TG vs. WT mice. Cardiac overexpression of A1-ARs reduces infarct size by 40% and preserves cardiac function in intact mice after MI.

ischemia-reperfusion; cardioprotection; transgenic mice; magnetic resonance imaging

* Z. Yang and R. J. Cerniway contributed equally to this work.




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