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 β1-adrenoreceptor (β1AR) and β2-adrenoreceptor (β2AR) stimulation by catecholamine in cardiomyocytes, this study evaluated whether simultaneous inhibition of β1AR and activation of β2AR 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. β1- group, β2+ group, β2+ group and β1+β2+ group received surgery and hypoxia with metoprolol (100 mg/kg·d), fenoterol (250 μg/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 β2AR with a β2AR agonist and inhibition of β1AR with a selective β1AR 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 β2AR agonist and β1AR 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.