Tension-time index, fatigue, and energetics in isolated rat diaphragm: a new experimental model

The tension-time index (TTI) has been used to estimate mechanical load, energy utilization, blood flow, and susceptibility to fatigue in contracting muscle. The TTI can be defined, for a rhythmically contracting muscle, as the product of average force development divided by maximum tetanic force times duty cycle [contraction time / (contraction + relaxation time)]. In this study, the TTI concept was applied to isolated diaphragm via a method that allowed TTI to be clamped at a predetermined value. The hypothesis tested was that, at constant TTI, muscle energetics and the extent of fatigue would vary with stimulation frequency. Isolated diaphragm strips were stimulated at 25, 50, 75, or 100 Hz for 4 min, one per second. Duty cycle was continuously adjusted to maintain TTI at 0.07, which was near the highest TTI tolerated for 4 min, at 20-Hz stimulation. At the end of the fatigue run, muscles were either immediately frozen for determination ATP, creatine, and creatine phosphate concentrations (n = 6) or stimulated for evaluation of low- and high-frequency fatigue (n = 5). Results demonstrated no difference in the extent of fatigue or in the final ATP and creatine phosphate concentrations between groups. Large within-run increases in duty cycle were required at low stimulation frequencies, but only small increases were required at the highest frequencies. The results demonstrate that, at a constant TTI, similar fatigue properties predominate at all stimulation frequencies with no clear distinction between high- and low-frequency fatigue. The method of clamping TTI during fatigue may be useful for evaluating energetics and contractile function between treatment groups in isolated muscle when treatment influences baseline contractile characteristics.