MALIGNANT HYPERTHERMIA - EFFECTS OF SARCOPLASMIC-RETICULUM CA2+ PUMP INHIBITION

In porcine malignant hyperthermia-susceptible (MHS) skeletal muscles, calcium release is abnormal and resting calcium may be elevated. Thus MHS muscles may have prolonged twitch relaxation and lower fusion freq uencies, which would be augmented by inhibition of sarcoplasmic reticu lum (SR) Ca2+ adenosine triphosphatase (ATPase) activity; bundles of i ntact muscle cells from MHS and normal pigs were used to investigate t his possibility. Cooling and low-frequency stimulation, in combination , enhanced twitch fusion and prolonged twitch relaxation significantly more in MHS than in normal muscles (e.g., 34 +/- 4% versus 16 +/- 4% fusion, and 82.4 +/- 9.4 ms versus 43.2 +/- 7.8 ms half-relaxation tim e, for MHS and normal muscles, respectively). Similarly, inhibition of the SR Ca2+ ATPase by cyclopiazonic acid resulted in significantly gr eater twitch fusion in MHS muscles. These results were consistent with predicted effects of enhanced SR Ca2+ release and/or elevated resting calcium in MHS muscles and indicate that cooling during a malignant h yperthermia crisis could actually increase the force of muscle contrac tures. (C) 1998 John Wiley & Sons, Inc.