ABSTRACT
OBJECTIVE: To assess whether halothane exposure could influence contraction-relaxation coupling of human skeletal muscle with malignant hyperthermia susceptibility. STUDY DESIGNED: Laboratory investigation. MATERIAL AND METHODS: Muscle biopsies from 14 patients, including six classified as susceptible to MH (MHS) and eight as classified as non-susceptible (MHN) according to criteria of the European MH group. Mechanical parameters of strips were obtained before and after 3 vol% halothane exposure. The contraction and relaxation parameters were measured under isotonic and isometric conditions: maximum shortening and lengthening velocities (respectively maxVc and maxVr); peak of the positive (+dP/dtmax) and negative (-dP/dtmax) twitch tension derivative; ratio R1 = maxVc/maxVr and ratio R2 = (+dP/dtmax) (-dp/dtmax). RESULTS: In MHN muscle, halothane markedly increased maxVc and maxVr, so that the ratio R1 was unchanged. Both +dP/dtmax and -dP/dtmax increased such that the ratio R2 did not vary. In MHS muscle, halothane induced a significant decrease in maxVr (p < 0.05) without changes in maxVc, so that the ratio R1 increased significantly. +dP/dtmax remained unchanged whereas -dP/dtmax decreased significantly; the ratio R2 increased (p < 0.05). CONCLUSION: Our results indicated that, in MHN muscle the contractility property is improved with halothane exposure. In MHS muscle, halothane caused an impairment of relaxation. The mechanical abnormalities observed in this study might be related to sarcoplasmic reticulum dysfunction in MH diseases.
Subject(s)
Anesthetics, Inhalation/pharmacology , Halothane/pharmacology , Malignant Hyperthermia/physiopathology , Muscle, Skeletal/physiology , Humans , In Vitro Techniques , Isotonic Contraction/drug effects , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle Relaxation/drug effects , Muscle, Skeletal/drug effectsABSTRACT
The aim of this investigation was to assess the effect of halothane on the velocity of shortening and lengthening of muscle from normal subjects and from patients with malignant hyperthermia susceptibility. Strips were mounted horizontally at optimal length in normal Krebs-Ringer's solution and mechanical parameters were obtained before and after exposure to 3 vol.% halothane. The maximun shortening velocity at zero load (V(max)) was determined by using Hill's characteristic equation. The contraction and relaxation indices were measured under isotonic and isometric conditions: maximum shortening and lengthening velocities (maxV(c) and maxV(r), respectively); isometric peak twitch tension; peak of the positive (+dP/dt(max)) and negative (-dP/dt(max)) twitch tension derivative; ratio R1=maxV(c)/maxV(r) and ratio R2=(+dP/dt(max))/(-dP/dt(max)). In normal muscle, halothane markedly increased V(max), maxV(c) and peak twitch tension by 30+/-10%, 30+/-5% and 40+/-15%, respectively. The maxV(r) values increased concomitantly with the maxV(c) values, such that no change in the ratio R1 was observed. Both +dP/dt(max) and -dP/dt(max) increased such that the ratio R2 did not vary. In malignant hyperthermia susceptibility muscle, halothane induced a significant decrease in V(max) (-30+/-10%) and maxV(r) (-45+/-15%) without changing maxV(c). The decrease in maxV(r) was greater than that of maxV(c), such that the ratio R1 increased significantly. Peak twitch tension and +dP/dt(max) remained unchanged whereas -dP/dt(max) decreased significantly; the ratio R2 increased by 40+/-10%. These results suggest that halothane alters the contractile properties of malignant hyperthermia susceptibility muscle.
