Expression of active α(1B)-adrenergic receptors in the heart does not alleviate ischemia reperfusion injury

Ischemic preconditioning reduces infarct size and improves cardiac function ha various species, including mice. The mechanism for ischemic preconditioning protection is not entirely clear and activation of α(1B)-adrenergic receptors (AR) is believed to be involved. Transgenic mice expressing constitutively active mutant α(1B)-AR in the heart have enhanced α(1B)-AR activity and therefore can be used to test the role of α(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 extent 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 α(1B)-AR activity by cardiac-specific expression of constitutively active mutant α(1B)-AR in mice does not mimic ischemic preconditioning to protect against ischemia-reperfusion injury. (C) 2000 Academic Press.