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

Diastolic dysfunction at high heart rates may be associated with incre ased myocardial energy consumption. Frequency-dependent changes of iso metric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various deg rees of diastolic dysfunction. MVO2 was determined by a new method whi ch was validated. When stimulation rate was increased from 40 to 200 m in(-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 f orce were 1.8 +/- 0.4 ml/min/100g and 15.9 +/- 3.0 mN/mm(2), respectiv ely. After addition of 30 mM 2,3-butanedione monoxime (BDM) to inhibit cross-bridges, resting MVO2 and resting force decreased by 46% (P<0.0 5) and 15% (P<0.01), respectively, indicating the presence of active f orce generation in unstimulated failing human myocardium. In each musc le preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r = 0.96 +/- 0.01). The strength of th ese correlations did not vary with the contribution of diastolic FTI t o total FTI, The ratio of activity related MVO2 to developed FTI, an i nverse 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, i n muscle preparations with disturbed diastolic function economy of con traction decreases with higher stimulation rates, depending on the ris e of diastolic force. (C) 1998 Academic Press