Expression of active α1B-adrenergic receptors in the heart does not alleviate ischemic reperfusion injury

Ischemic preconditioning reduces infarct size and improves cardiac function in various species, including mice. The mechanism for ischemic preconditioning protection is not entirely clear and activation of alpha(1B)-adrenergic receptors (AR) is believed to be involved, Transgenic mice expressing constitutively active mutant alpha(1B)-AR in the heart have enhanced alpha(1B)-AR activity and therefore can be used to test the role of alpha(1B)-AR in ischemic preconditioning. Wild-type and transgenic mice were subjected to 30- or 40-min periods of left coronary artery occlusion followed by 60-min reperfusion, or ischemic preconditioning prior to sustained ischemia-reperfusion. Risk and infarct zones were determined by staining with Evans blue and triphenyltetrazolium, respectively, and quantitated digitally, Infarct zone and infarct size were not different between wild-type and transgenic mice, nor was the ex-tent of reduction in infarct size by preconditioning ischemia (wild-type mice: 45+/-3 to 18+/-3%, transgenic mice: 46 +/- 3 to 19 +/- 2% of the left ventricle, both P<0.01). Ventricular function was similar between wild-type and transgenic mice with or without ischemia-reperfusion injury. In conclusion, enhanced alpha(1B)-AR activity by cardiac-specific expression of constitutively active mutant alpha(1B)-AR in mice does not mimic ischemic preconditioning to protect against ischemia-reperfusion injury. (C) 2000 Academic Press.