Mechanoelectrical Feedback

Abstract

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 β-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 (MAPD 50 and MAPD 90 ) and refractoriness were determined at low (9±3 mL) and high (39±4 mL) load before and after β-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 β-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.