Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations

Abstract

Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min(-1) (n = 7), developed force decreased from 16.5 +/- 4.3 to 7.9 +/- 2.9 mN/mm(2) (P<0.01), diastolic force increased from 15.9 +/- 3.2 to 22.0 +/- 3.0 mN/mm(2) (P<0.01), and total MVO2 increased from 2.6 +/- 0.6 to 4.7 +/- 0.9 ml/min/100 g (P<0.025), Resting MVO2 and resting force were 1.8 +/- 0.4 ml/min/100g and 15.9 +/- 3.0 mN/mm(2), respectively. After addition of 30 mM 2,3-butanedione monoxime (BDM) to inhibit cross-bridges, resting MVO2 and resting force decreased by 46% (P<0.05) and 15% (P<0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r = 0.96 +/- 0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI, The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force. (C) 1998 Academic Press