title: Mechanoelectrical feedback: role of beta-adrenergic receptor activation in mediating load-dependent shortening of ventricular action potential and refractoriness.
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 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.
authors.affiliation: Department of Medicine, Division of Cardiology, The New York Hospital-Cornell University Medical Center, New York, NY, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Lerman
authors.forename: E D
authors.initials: ED
authors.lastname: Engelstein
authors.forename: D
authors.initials: D
authors.lastname: Burkhoff
mesh_terms: 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
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D012110:Reserpine; D011433:Propranolol