Porcine malignant hyperthermia: Halothane effects on force generation in skeletal muscles

Abstract

Halothane-induced malignant hyperthermia (MH) is thought to result from a defect in the regulation of cytosolic calcium concentration in MH-susceptible (MHS) skeletal muscle. Such a defect might be expected to alter the time course of contractile responses. To test this hypothesis, isolated intact cell bundles from external intercostal and common digital extensor muscles of normal and MHS pigs were stimulated electrically to elicit twitch and tetanic tension in the presence and absence of halothane (2.5%). Time intervals measured for both twitches and tetani were (1) the latent period between the stimulus and tension increase, (2) the time to peak tension, and (3) the half-relaxation time. In contrast to previous reports, halothane had no effect on any measured time course parameter of twitches of either type of normal or MHS muscle, nor did the twitches of MHS and normal muscles differ in any parameter in the absence of halothane. However, the tetanic tension relaxation in both types of MHS muscle was markedly slowed by halothane, whereas in normal muscles there was little change. The slower rate of relaxation induced by halothane in MHS muscles suggests that halothane, either directly or indirectly, enhances the release or slows the removal of calcium in intact MHS muscles following maximal activation. This slowed tetanus relaxation could be of use in identification of MHS individuals.

Malignant hyperthermia: Effects of sarcoplasmic reticulum Ca2+ pump inhibition

“…This is consistent with observations of a greater twitch-to-tetanus ratio in MHS muscles. 7,9 Our findings of no difference in peak tension and twitch time-to-peak and halfrelaxation time were also consistent with previous observations on muscles from adult pigs. 7,10 Further, our results supported the general similarity of mechanical responses in piglet and adult muscles.…”

“…This difference was consistent with the previously documented higher twitch-totetanus ratio in MHS as compared with normal muscles. 7,9 In spite of this difference in tension at low frequencies, the degree of fusion at each stimulus frequency was not significantly different between the two muscle types at 36°C (see Fig. 2A).…”

“…For example, elevated resting [Ca 2+ ] and/or delayed RyR closing should prolong twitch and tetanus relaxation of MHS muscles; however, this has not been observed in the absence of drugs. 7,10 We hypothesized that a difference in twitch relaxation between MHS and normal muscles might become evident if Ca 2+ removal by the SR Ca 2+ pump was compromised.…”

Myoplasmic calcium regulation in myotubes from horses with recurrent exertional rhabdomyolysis

“…First, horses affected with RER have faster twitch and tetanus time courses than unaffected horses, 4 whereas a difference in time course is not found in MH porcine muscle, compared with unaffected porcine muscle. 34 In addition, the rate of calcium release from, the apparent dissociation constant (K d ) for ryanodine binding to, and the caffeine sensitivity of ryanodine binding to isolated SR vesicles is not different in RER, compared with control equine muscle. 19 This is in contrast to enhanced calcium release from, and high affinity for ryanodine binding to, SR vesicles from MH-affected muscle, compared with unaffected pig 13 or human 35 muscles.…”