Expression of active alpha(1B)-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 preconditio ning protection is not entirely clear and activation of alpha(1B)-adrenergi c receptors (AR) is believed to be involved, Transgenic mice expressing con stitutively 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 3 0- or 40-min periods of left coronary artery occlusion followed by 60-min r eperfusion, or ischemic preconditioning prior to sustained ischemia-reperfu sion. Risk and infarct zones were determined by staining with Evans blue an d triphenyltetrazolium, respectively, and quantitated digitally, Infarct zo ne and infarct size were not different between wild-type and transgenic mic e, nor was the ex-tent of reduction in infarct size by preconditioning isch emia (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 e xpression of constitutively active mutant alpha(1B)-AR in mice does not mim ic ischemic preconditioning to protect against ischemia-reperfusion injury. (C) 2000 Academic Press.