Cooper P, Meddings J B
Department of Anesthesia, University of Calgary, Canada.
Biochim Biophys Acta. 1991 Nov 4;1069(2):151-6. doi: 10.1016/0005-2736(91)90117-q.
Malignant hyperthermia (MH) is a rare but serious complication of general anesthesia that potentially carries a high mortality and morbidity. It is associated with excessive release of calcium into skeletal muscle following exposure to certain drugs, including the volatile general anesthetics. Since these are recognized membrane fluidizing agents it has been speculated that this condition might represent a generalized defect in membrane physical properties either at rest or inducible by fluidizing agents. If this hypothesis were found to be correct, malignant hyperthermia might conveniently be detected by examining membrane physical properties of easily accessible cells rather than the cumbersome method of muscle biopsy currently employed. To test this hypothesis we identified patients proven to be susceptible to MH by muscle biopsy and a cohort of patients not susceptible to MH as defined by negative muscle biopsy testing. Erythrocytes were isolated from both groups and membrane physical properties examined using conventional, widely available, steady-state fluorescence polarization techniques. Erythrocyte membranes were evaluated with multiple probes both in the basal condition and following fluidization with either increasing temperature or two concentrations of a fluidizing alcohol. We report, contrary to previous publications, that no discernable differences were detectable between MH-positive or negative patients. Thus, we find no evidence for a generalized membrane defect in MH and conclude that the determination of erythrocyte membrane physical properties, by these techniques, are of no use in the preoperative screening for this disorder.
恶性高热(MH)是全身麻醉中一种罕见但严重的并发症,具有较高的潜在死亡率和发病率。它与接触某些药物(包括挥发性全身麻醉剂)后骨骼肌中钙的过度释放有关。由于这些药物被认为是膜流化剂,因此有人推测这种情况可能代表静息时或由流化剂诱导的膜物理性质的普遍缺陷。如果这一假设被证明是正确的,那么通过检查易于获取的细胞的膜物理性质,而不是目前采用的繁琐的肌肉活检方法,可能会方便地检测出恶性高热。为了验证这一假设,我们确定了经肌肉活检证实对MH易感的患者以及经肌肉活检检测为阴性所定义的对MH不易感的一组患者。从两组患者中分离出红细胞,并使用常规的、广泛可用的稳态荧光偏振技术检查膜物理性质。在基础状态下以及在温度升高或两种浓度的流化醇流化后,用多种探针评估红细胞膜。与之前的出版物相反,我们报告称,MH阳性或阴性患者之间未检测到明显差异。因此,我们没有发现MH存在普遍膜缺陷的证据,并得出结论,通过这些技术测定红细胞膜物理性质对该疾病的术前筛查没有用处。