Ts. Etchrivi et al., Shortening velocity of skeletal muscle from humans with malignant hyperthermia susceptibility: effects of halothane, EUR J PHARM, 388(1), 2000, pp. 107-113
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 f
rom patients with malignant hyperthermia susceptibility. Strips were mounte
d horizontally at optimal length in normal Krebs-Ringer's solution and mech
anical parameters were obtained before and after exposure to 3 vol.% haloth
ane. The maximum shortening velocity at zero load (V-max) was determined by
using Hill's characteristic equation. The contraction and relaxation indic
es were measured under isotonic and isometric conditions: maximum shortenin
g 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 increa
sed 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 m
alignant hyperthermia susceptibility muscle, halothane induced a significan
t 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 tha
t 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. (C
) 2000 Elsevier Science B.V. All rights reserved.