Left Ventricular Mechanical Unloading Restores Beta-2-Adrenergic Receptor mRNA Expression and Decreases Susceptibility to Ischemia and Reperfusion in the Failing Heart

Abstract

Objectives: Left ventricular (LV) mechanical unloading is known to reduce the hemodynamic demands of failing LV, resulting in improved myocyte contractility. This study was designed to examine effects of LV unloading on β-adrenergic receptor (BAR) expression and ischemic susceptibility to ischemia reperfusion. Methods: Five groups were studied: group 1 [unloading myocardial infarction (MI), n = 6], MI hearts 2 weeks after coronary ligation subjected to LV unloading by heterotopic heart transplantation for 2 weeks; group 2 (2-week MI, n = 6), MI hearts left for 2 weeks without unloading; group 3 (4-week MI, n = 6), MI hearts left for 4 weeks without unloading; group 4 (control, n = 6), normal (non-MI) hearts as a control with no interventions, and group 5 (unloading control, n = 5), normal (non-MI) hearts subjected to LV unloading for 2 weeks.Then, all hearts were isolated and subjected to 20 min of global ischemia and 60 min of reperfusion on Langendorff apparatus. LV pressures and coronary flow were measured throughout the experiment. Either total BAR density or β₂-adrenergic receptor (B2AR) mRNA expression in the noninfarcted myocardium was determined by radioligand binding assays or real-time quantitative RT-PCR, respectively. Results: LV unloading improved postischemic functional recovery (unloading MI vs. 2-week MI vs. 4-week MI: 74 ± 6 vs. 54 ± 5 vs. 51 ± 4%; p < 0.05 vs. unloading MI). LV unloading restored B2AR mRNA expression (unloading MI vs. 2-week MI vs. 4-week MI: 4.78 ± 0.21 vs. 2.80 ± 0.19 vs. 2.24 ± 0.17 × 10⁷ copy/µg total RNA; p < 0.05 vs. unloading MI). Conclusion: LV mechanical unloading restored B2AR mRNA expression and improved postischemic functional recovery.