doi: 10.1161/hc2901.091397
(Circulation. 2001;104:486.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Mechanoelectrical Feedback
Role of ß-Adrenergic Receptor Activation in Mediating Load-Dependent Shortening of Ventricular Action Potential and Refractoriness
From the Department of Medicine, Division of Cardiology, The New York Hospital–Cornell University Medical Center, and the Division of Circulatory Physiology, College of Physicians and Surgeons, Columbia University, New York, NY.
Reprint requests to Bruce B. Lerman, MD, Division of Cardiology, The New York Hospital–Cornell Medical Center, 525 E 68th St, Starr-409, New York, NY 10021. E-mail blerman{at}med.cornell.edu
Background—— Augmented preload increases myocardial excitability by shortening action potential duration (APD). The mechanism governing this phenomenon is unknown. Because myocardial stretch increases intracellular cAMP, we hypothesized that load-dependent changes in myocardial excitability are mediated by ß-adrenergic stimulation of a cAMP-sensitive K+ current.
Methods and Results—— The effects of propranolol on load-induced changes in electrical excitability were studied in 7 isolated ejecting canine hearts. LV monophasic APD at 50% and 90% repolarization (MAPD50 and MAPD90) and refractoriness were determined at low (9±3 mL) and high (39±4 mL) load before and after ß-adrenergic blockade. During control, the MAPD50 decreased from 193±26 to 184±26 ms with increased load, as did the MAPD90 (238±28 to 233±28 ms), P
0.04. Similar changes were observed in ventricular refractoriness. Treatment with propranolol completely abolished these load-induced effects. Myocardial catecholamine depletion with reserpine in 2 hearts also abolished changes in MAPD and excitability in response to increased preload.
Conclusions—— Increases in ventricular load mediate a decrease in ventricular APD and refractoriness through activation of the ß-adrenergic receptor. An increase in a cAMP-mediated K+ current, possibly the slowly activating delayed rectifier IKs, may account in part for this form of mechanoelectrical coupling.
Key Words: arrhythmias • electrophysiology • tachyarrhythmias • tachycardia
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