Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure

M. R. Wolff, P. P. De Tombe, Y. Harasawa, D. Burkhoff, S. Bier, W. C. Hunter, G. Gerstenblith, D. A. Kass

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Abstract

The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3±2.9 days and compared with a separate control group (n=8). Studies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29±0.94 versus 2.71±0.98 mm Hg/ml, p<0.01) and lowered end-systolic stiffness at a matched stress (956.1±123.5 versus 1,401.7±431.7 g/cm2, p<0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3±3.9 versus 21.9±7.6 ml, p<0.01). Inotropic response to increased heart rate and exogenous β-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1±1.1 versus 2.9±1.4 ml O2 · mm Hg-1 · ml-1 · 100 g left ventricle-1, p<0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation- contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure.

Original languageEnglish (US)
Pages (from-to)516-529
Number of pages14
JournalCirculation Research
Volume70
Issue number3
DOIs
StatePublished - 1992

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Keywords

  • canine heart failure model
  • cardiomyopathy
  • contractility
  • diastole
  • force-frequency
  • pacing tachycardia
  • pressure-volume relations
  • β-adrenergic receptors

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