Positive inotropic effects of the beta2-adrenoceptor agonist terbutaline in the human heart: Effects of long-term beta1-adrenoceptor antagonist treatment

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Abstract

Objectives. This study was conducted to determine whether activation of cardiac beta2-adrenoceptors increases contractility in humans and whether this is affected by long-term beta1-adrenoceptor antagonist treatment. Background. Coexistence of beta1- and beta2-adrenoceptors in the human heart is generally accepted. The functional importance of cardiac beta2-adrenoceptors for increases in contractility in humans, however, has not been completely established. Methods. We studied 1) the beta-adrenoceptor subtype mediating positive inotropic effects of the beta2-adrenoceptor agonist terbutaline in vitro (on right atrial and left ventricular preparations from nonfailing human hearts) and increases in contractility (by measurement of systolic time intervals) in vivo in seven healthy male volunteers; and 2) in vivo whether long-term treatment of volunteers with the beta1-adrenoceptor antagonist bisoprolol affects terbutaline-induced increases in contractility. Results. In vitro terbutaline caused a concentration-dependent increase in atrial and ventricular adenylate cyclase activity and force of contraction. Terbutaline effects were antagonized only by the beta2-adrenoceptor antagonist ICI 118,551, indicating that they were mediated by beta2-adrenoceptor stimulation. In vivo intravenous infusions of terbutaline (dose range 25 to 300 ng/kg body weight per min for 15 min) dose dependently increased heart rate and shortened the pre-ejection period and heart rate-corrected electromechanical systole (QS2) time. These effects are mediated predominantly by beta2-adrenoceptor stimulation because they were only marginally affected by the beta1-adrenoceptor antagonist bisoprolol (1 × 10 mg orally), either given 2 h before infusion or long term for 3 weeks. Conclusions. Stimulation of cardiac beta2-adrenoceptors in humans causes not only in vitro but also in vivo positve inotropic effects. Long-term beta1-adrenoceptor antagonist treatment does not considerably affect beta2-adrenoceptor-mediated in vivo increases in contractility. Thus, it may be possible to treat patients with chronic heart failure and long-term beta1-adrenoceptor antagonist therapy with beta2-adrenoceptor agonists if immediate inotropic support is needed. © 1994.

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APA

Schäfers, R. F., Adler, S., Daul, A., Zeitler, G., Vogelsang, M., Zerkowski, H. R., & Brodde, O. E. (1994). Positive inotropic effects of the beta2-adrenoceptor agonist terbutaline in the human heart: Effects of long-term beta1-adrenoceptor antagonist treatment. Journal of the American College of Cardiology, 23(5), 1224–1233. https://doi.org/10.1016/0735-1097(94)90615-7

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