Tachycardia-induced diastolic dysfunction and resting tone in myocardium from patients with a normal ejection fraction

Donald E. Selby, Bradley M. Palmer, Martin M. Lewinter, Markus Meyer

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67 Scopus citations

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)147-154
Number of pages8
JournalJournal of the American College of Cardiology
Volume58
Issue number2
DOIs
StatePublished - Jul 5 2011
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by a National Heart, Lung and Blood Institute Institutional Training Grant ( T32 HL07647 ) to the College of Medicine, University of Vermont; American Heart Association Scientist Development Grant 0730056N (to Dr. Meyer); and National Institutes of Health grants R01 HL089944 (to Dr. LeWinter) and R01 HL086902 (to Dr. Palmer). The authors have reported that they have no relationships to disclose.

Keywords

  • calcium
  • diastole
  • hypertrophy
  • tachycardia

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