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 shortenin g action potential duration (APD). The mechanism governing this phenomenon is unknown. Because myocardial stretch increases intracellular cAMP, we hyp othesized that load-dependent chancres in myocardial excitability are media ted by beta -adrenergic stimulation of a cAMP-sensitive K+ current. Methods and Results-The effects of propranolol on load-induced changes in e lectrical 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) lo ad 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 less than or equal to0.04. Simil ar changes were observed in ventricular refractoriness. Treatment with prop ranolol completely abolished these load-induced effects. Myocardial catecho lamine 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 -adrenerggic recepto r. An increase in a cAMP-mediated K+ current, possibly the slowly activatin g delayed rectifier I-Ks, may account in part for this form of mechanoelect rical coupling.