Mechanoelectrical feedback: role of beta-adrenergic receptor activation in mediating load-dependent shortening of ventricular action potential and refractoriness.
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 beta-adrenergic stimulation of a cAMP-sensitive K(+) current.


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 (MAPD(50) and MAPD(90)) and refractoriness were determined at low (9+/-3 mL) and high (39+/-4 mL) load before and after beta-adrenergic blockade. During control, the MAPD(50) decreased from 193+/-26 to 184+/-26 ms with increased load, as did the MAPD(90) (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 beta-adrenergic receptor. An increase in a cAMP-mediated K(+) current, possibly the slowly activating delayed rectifier I(Ks), may account in part for this form of mechanoelectrical coupling.
Lerman
B B
BB
Department of Medicine, Division of Cardiology, The New York Hospital-Cornell University Medical Center, New York, NY, USA.
Engelstein
E D
ED
Burkhoff
D
D
D000200:Action Potentials / Q000187:drug effects*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D004285:Dogs; D004594:Electrophysiology; D005246:Feedback / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D016276:Ventricular Function; D017725:Ventricular Pressure / Q000187:drug effects
D018759:Adrenergic Uptake Inhibitors; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D012110:Reserpine; D011433:Propranolol