Effects of Halothane on Mechanical Response of Skeletal Muscle from Malignant Hyperthermia Susceptible Patients

Abstract

The purpose of this investigation was to compare the effects of halothane on malignant hyperthermia (MH) and normal isolated muscle bundle performance during isometric contraction and relaxation phases. Mechanical parameters were measured: peak tension (PT), time to peak tension (TPT) and positive peak of isometric tension derivative (+dP/dtmax) characterized the contraction phase. Half-relaxation time (RT1/2) and negative peak of isometric tension derivative (-dP/dtmax) characterized the relaxation phase. The ratio R = (+dP/dtmax)/(-dP/dtmax) was used to study the coupling between contraction and relaxation under isometric condition. In normal muscle, halothane increased PT by nearly 40% without altering TPT. The +dP/dtmax value increased concomitantly with the -dP/dtmax values, thus no changes in R was observed. In MH muscle, PT was first potentiated (0.5-1.0 vol% halothane) and then depressed (2.0-3.0 vol% halothane). TPT and +dP/dtmax were not altered whereas RT1/2 increased progressively with concomitant decrease in -dP/dtmax, thus R increased by nearly 40%. The amplitude of MH muscle contracture with stepwise concentrations of halothane was correlated with the increase of RT1/2 and R, and the decrease of -dP/dtmax. These results suggest that halothane alters the relaxation phase more than the contraction phase in MH human skeletal muscle compared to normal muscle.

Effect of caffeine on intrinsic mechanical properties of normal and malignant hyperthermia‐susceptible muscle

“…Despite the higher resting calcium level in MHS muscle, similar mechanical properties exist. 7 A similar behavior has been described previously for halothane …”

“…Length and weight of the examined muscle bundles were not different between the 2 groups. Cross‐sectional area was calculated as the ratio of muscle weight (g), to maximum muscle length, assuming a muscle density of 1.06, as described previously (Table ) …”

“…In isolated muscle bundles not only can the baseline tension be measured, but, after electrical stimulation, other parameters that characterize the single twitch can also be recorded. These intrinsic mechanical properties in MHS skeletal muscle have rarely been investigated and compared with normal skeletal muscle …”

“…These intrinsic mechanical properties in MHS skeletal muscle have rarely been investigated and compared with normal skeletal muscle. 5 The purpose of this study was to investigate the intrinsic mechanical properties of MHS and MHN bundles in vitro. In MH muscle, altered calcium uptake and release may cause different intrinsic mechanical properties, even without exposure to triggering agents.…”

“…The effect of caffeine, a nonspecific activator of sarcoplasmic calcium release, was evaluated and was expected to affect contraction and relaxation, as previously shown for halothane. 5 We hypothesized that muscle bundles from MHS and MHN individuals have different intrinsic mechanical properties, and that this difference is greatly enhanced with exposure to caffeine.…”