Gallant E M, Foldes F F, Rempel W E, Gronert G A
Anesth Analg. 1985 Jun;64(6):601-6.
We have investigated the hypothesis that the calcium antagonist verapamil might be useful for prevention or treatment of malignant hyperthermia (MH) in MH-susceptible (MHS) swine. MH episodes were triggered in four groups of four swine with halothane alone or combined with succinylcholine (SCh) and, with and without verapamil. MH episodes were reversed by therapy with dantrolene and NaHCO3 in all groups. Verapamil did not alter MH episodes triggered by halothane alone or combined with SCh. The dantrolene-NaHCO3 requirements for reversal of MH were greater for the groups receiving halothane-SCh, but did not differ in groups pretreated with and without verapamil. In vitro verapamil (25 microM) did not reduce responses of intact muscle fibers to halothane and, in fact, exaggerated some halothane-induced responses. High concentrations of verapamil (0.5 mM) caused contractures in MHS but not in normal muscles. Neither our in vivo nor in vitro results support the use of verapamil in the treatment of MH. Further, doses of dantrolene used to reverse these MH episodes, although admittedly small (1-2 mg/kg), did not produce myocardial depression when used in combination with verapamil.
我们研究了钙拮抗剂维拉帕米可能有助于预防或治疗易患恶性高热（MH）的猪的恶性高热这一假说。在四组每组四只猪中，单独使用氟烷或联合琥珀酰胆碱（SCh）触发MH发作，且一组使用维拉帕米，另一组不使用。所有组的MH发作均通过丹曲林和碳酸氢钠治疗得以逆转。维拉帕米并未改变单独使用氟烷或联合SCh触发的MH发作。接受氟烷-SCh的组逆转MH所需的丹曲林-碳酸氢钠剂量更大，但在预先使用和未使用维拉帕米的组之间并无差异。体外实验中，维拉帕米（25微摩尔）并未降低完整肌纤维对氟烷的反应，实际上，还放大了一些氟烷诱导的反应。高浓度的维拉帕米（0.5毫摩尔）在易患恶性高热的猪的肌肉中引起挛缩，但在正常肌肉中未出现。我们的体内和体外实验结果均不支持使用维拉帕米治疗恶性高热。此外，用于逆转这些MH发作的丹曲林剂量，尽管确实较小（1 - 2毫克/千克），但与维拉帕米联合使用时并未产生心肌抑制作用。
