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.
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 3vol% 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/dt(max)) and negative (-dP/dt(max)) twitch tension derivative; ratio R1 = maxVc/ maxVr and ratio R2= (+ dP/dt(max)) (-dP/dt(max)).Results: In MHN muscle, halothane markedly increased maxVc and maxVr, so that the ratio R1 was unchanged. Both + dP/dt(max) and -dP/dt(max) 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/ dt(max) remained unchanged whereas -dP/dt(max) 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. (C) 2002 Editions scientifiques et medicales Elsevier SAS.
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 (Vmax) 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 (maxVc and maxVr, respectively); isometric peak twitch tension; peak of the positive (+dP/dtmax) and negative (−dP/dtmax) twitch tension derivative; ratio R1=maxVc/maxVr and ratio R2=(+dP/dtmax)/(−dP/dtmax). In normal muscle, halothane markedly increased Vmax, maxVc and peak twitch tension by 30±10%, 30±5% and 40±15%, respectively. The maxVr values increased concomitantly with the maxVc values, such that no change in the ratio R1 was observed. Both +dP/dtmax and −dP/dtmax increased such that the ratio R2 did not vary. In malignant hyperthermia susceptibility muscle, halothane induced a significant decrease in Vmax (−30±10%) and maxVr (−45±15%) without changing maxVc. The decrease in maxVr was greater than that of maxVc, such that the ratio R1 increased significantly. Peak twitch tension and +dP/dtmax remained unchanged whereas −dP/dtmax decreased significantly; the ratio R2 increased by 40±10%. These results suggest that halothane alters the contractile properties of malignant hyperthermia susceptibility muscle.