title: Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart.
abstract: BACKGROUND
  Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear.
  
  
  RESULTS
  Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping.
  
  
  CONCLUSIONS
  Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.
authors.affiliation: Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Sung
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mills
authors.forename: Jan
authors.initials: J
authors.lastname: Schettler
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Narayan
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D018780:Body Surface Potential Mapping / Q000379:methods*; D004548:Elasticity; D005246:Feedback; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D010496:Pericardium / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013307:Streptomycin / Q000494:pharmacology; D013314:Stress, Mechanical; D013318:Stroke Volume; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure
chemical_list: D013307:Streptomycin