Prevention of cardiac events caused by surgical stress in aged rats: simultaneously activating β2-adrenoceptor and inhibiting β1-adrenoceptor

Increased plasma catecholamine levels are associated with a high risk of perioperative cardiac events in aged individuals undergoing non-cardiac surgical interventions. Given the different effects of beta(1)-adrenoreceptor (beta(1)AR) and beta(2)-adrenoreceptor (beta(2)AR) stimulation by catecholamine in cardiomyocytes, this study evaluated whether simultaneous inhibition of beta(1)AR and activation of beta(2)AR is better than separate application in reducing the risk of perioperative cardiac events in aged rats undergoing non-cardiac surgery. Male aged Sprague-Dawley (SD) rats were divided into five groups. Normal group received no treatment. Surgery group received an abdominal surgery with hypoxia. beta(-)(1) group, beta(+)(2) group and beta(-)(1)beta(+)(2) group received surgery and hypoxia with metoprolol (100 mg/kg.d), fenoterol (250 mu g/kg.d) or both, respectively. The drugs were given three days before surgery with treatment continued through post-surgical day 7. The results showed that simultaneous activation of beta(2)AR with a beta(2)AR agonist and inhibition of beta(1)AR with a selective beta(1)AR blocker normalized myocardial oxygen consumption, decreased myocardial damage, augmented cardiomyocyte survival, improved cardiac function, reduced the incidence of arrhythmia, thus decreasing the occurrence of cardiac events in perioperative aged rats undergoing non-cardiac surgery. The results demonstrated that combined use of beta(2)AR agonist and beta(1)AR blocker achieved better general effects than use of either one alone. Our results provide a new insight into preventing perioperative cardiac events for elderly patients undergoing surgical stress.