title: Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction.
abstract: OBJECTIVE
  The purpose of this study is to evaluate tachycardia-induced relaxation abnormalities in myocardium from patients with a normal ejection fraction.
  
  
  BACKGROUND
  Diastolic dysfunction and left ventricular (LV) hypertrophy are closely linked. Tachycardia can induce heart failure symptoms in otherwise asymptomatic patients. To study the effects of tachycardia on myocardial contractility and relaxation, we evaluated the effects of increasing pacing rates in myocardial biopsy samples obtained from patients with a normal ejection fraction.
  
  
  METHODS
  LV biopsy samples were obtained during coronary bypass surgery. Myocardial strip preparations were electrically paced at rates from 60 to 180 beats/min. Diastolic resting tone was assessed by cross-bridge deactivation. Calcium transporting systems were functionally examined, and myofilament calcium sensitivity was studied.
  
  
  RESULTS
  Incomplete relaxation developed in 7 preparations, with increased diastolic tension development at increasing pacing rates. This was absent in the remaining 7 preparations. Incomplete relaxation was found to be associated with increased LV mass and left atrial volume. Cross-bridge deactivation showed that these preparations also had a significant resting tone. Additional functional analyses suggest that incomplete relaxation is associated with disproportionately elevated cellular calcium loads due to a reduced sarcolemmal calcium extrusion reserve.
  
  
  CONCLUSIONS
  Tachycardia-induced incomplete relaxation was associated with increased LV mass and left atrial volumes. We also found a disproportionately increased calcium load at high rates and a substantial resting tone due to diastolic cross-bridge cycling. These observations may play a role in reduced exercise tolerance and tachycardia-induced diastolic dysfunction.
authors: Cardiology Division and Department of Physiology, University of Vermont College of Medicine, Burlington, Vermont 05401, USA.
authors: Donald E
authors: DE
authors: Selby
authors: Bradley M
authors: BM
authors: Palmer
authors: Martin M
authors: MM
authors: LeWinter
authors: Markus
authors: M
authors: Meyer
mesh_terms: D000368:Aged; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications; D003971:Diastole / Q000502:physiology*; D015444:Exercise; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D013610:Tachycardia / Q000378:metabolism* / Q000628:therapy; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000473:pathology*
chemical_list: D002118:Calcium