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(Circulation. 1999;99:2402-2407.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Inotropic and Sympathetic Responses to the Intracoronary Infusion of a ß₂-Receptor Agonist

A Human In Vivo Study

Gary E. Newton, MD; Eduardo R. Azevedo, MD; John D. Parker, MD

From the Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.

Correspondence to John D. Parker, MD, Cardiovascular Division, Mount Sinai Hospital, 600 University Ave, Suite 1609, Toronto, Ontario M5G 1X5 Canada. E-mail jdp{at}inforamp.net

Background—On the basis of the presence of ß₂-receptors within the sympathetic nervous system, ß₂-stimulation may increase cardiac sympathetic outflow. We addressed the hypothesis that sympathoexcitatory ß₂-receptors are present in the human left ventricle.

Methods and Results—The ß₂-agonist salbutamol was infused into the left coronary artery in 3 groups of patients: group 1 (n=9, no ß-blocker therapy), group 2 (n=7, ß₁-selective blockade with atenolol), and group 3 (n=6, nonselective ß-blockade with nadolol). Left ventricular +dP/dt in response to increasing concentrations of salbutamol was measured in all groups, and cardiac norepinephrine spillover was measured in group 1. There were no systemic hemodynamic changes in any group. Salbutamol resulted in a 44±6% increase in +dP/dt in group 1, a 25±6% increase in group 2 (P<0.05 versus group 1), and no increase in group 3. Salbutamol also resulted in a 124±37% increase in cardiac norepinephrine spillover in group 1 (P<0.05).

Conclusions—Evidence that salbutamol increased norepinephrine release from cardiac sympathetic nerves was provided by the observations that atenolol suppressed the salbutamol inotropic response, demonstrating that this response was mediated in part by ß₁-receptors and that salbutamol also resulted in an increase in cardiac norepinephrine spillover. This result provides in vivo evidence, in humans, for the role of sympathoexcitatory cardiac ß₂-receptors.

Key Words: salbutamol • atenolol • nadolol • ventricles • norepinephrine

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