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EFFECT OF DILTIAZEM, VERAPAMIL AND DANTROLENE ON THE CONTRACTILITY OF ISOLATED MALIGNANT HYPERPYREXIA‐SUSCEPTIBLE HUMAN SKELETAL MUSCLE
Author(s) -
Foster P. S.,
Hopkinson K. C.,
Denborough M. A.
Publication year - 1989
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1989.tb01518.x
Subject(s) - diltiazem , dantrolene sodium , dantrolene , verapamil , malignant hyperthermia , skeletal muscle , medicine , halothane , muscle contracture , endocrinology , caffeine , pharmacology , nifedipine , anesthesia , chemistry , calcium , anatomy
SUMMARY 1. Diltiazem (10 μmol/L) and verapamil (10 μmol/L) inhibited the hypercontractility induced by 3% halothane and 2 mmol/L caffeine in malignant hyperpyrexia susceptible (MHS) muscle. Diltiazem also inhibited 80 mmol/L KCl contractures. 2. Like the skeletal muscle relaxant dantrolene sodium (6 μmol/L), diltiazem not only prevented but reversed the abnormal contractures induced by halothane and caffeine. 3. The effect on caffeine contractures of diltiazem and dantrolene in combination was additive. 4. The ability of diltiazem and verapamil to inhibit the hypercontractility of MHS muscle suggests that Ca 2+ influx across the transverse tubular membrane may be important in the aetiology of the malignant hyperpyrexia syndrome. 5. These results also suggest an abnormality in transverse tubule—sarcoplasmic reticulum communication.