Importance of fasting in the lymphocyte calcium test for malignant hyperthermia.

Anaesthetic-induced increases in cytoplasmic free Ca2+ have been reported to be greater in lymphocytes from malignant hyperthermia (MH) susceptible patients than in those from controls, suggesting that this may be the basis for a less invasive test for MH susceptibility. In the present study the cytoplasmic Ca2+ concentrations of lymphocytes were monitored with indo-1 in 14 control subjects (nine fasted and five nonfasted) and five fasted MH susceptible and three fasted nonsusceptible patients, diagnosed by the halothane and caffeine contracture tests. No relationship was observed between MH susceptibility and Ca2+ concentrations in lymphocytes in the absence or presence of halothane. There was, however, a relationship in control subjects between fasting and the response of lymphocytes to halothane, with the halothane-induced Ca2+ increase being considerably larger in nonfasted subjects.

The importance of calcium ions for in vitro malignant hyperthermia testing.

Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine.

Caffeine and halothane contracture testing in swine using the recommendations of the North American Malignant Hyperthermia Group.

Caffeine and halothane contracture testing is widely used to detect malignant hyperthermia (MH) susceptibility. The accuracy and reliability of the 3% halothane test and the incremental caffeine test, as recommended by the North American MH Group, were assessed in 11 swine (five MHS, six control). Nine swine were tested twice, 4-6 weeks apart. Accuracy of the in vitro diagnosis was also assessed by in vivo anesthetic challenge. Of all muscle bundles from MH-susceptible swine, 65% reacted positively to 3% halothane and 70% to 2 mM caffeine. Only 35% had a positive caffeine-specific concentration, and 25% developed an increase in baseline tension greater than or equal to 7% at 2 mM caffeine. However, when only the most positive response to 3% halothane or to 2 mM caffeine was used (a minimum of three fresh muscle strips is recommended), these two tests were highly sensitive and specific. In control swine one of 30 muscle bundles reacted positively to 3% halothane. A positive caffeine-specific concentration developed in one of 25 control muscle bundles exposed to caffeine. The variability in the results of these tests mandated that at least three muscle bundles be used for each test. Nonviable muscle bundles could not be relied upon to provide accurate results. In this porcine model, MH susceptibility could be detected by performing the Caffeine Halothane Contracture Test (CHCT) according to the guidelines of the North American MH Group. However, only the 3% halothane test and the response to 2 mM caffeine produced adequate diagnostic results in this breed of swine.

Effect of platelet activating factor (PAF) on blood flow distribution in the spontaneously hypertensive rat.

A dose-dependent decrease in mean arterial blood pressure was produced in spontaneously hypertensive rats by intravenous PAF infusion. Heart rate was monitored, while cardiac index and regional blood flow were quantitated during maintenance of the PAF-induced hypotension using the radioactive microsphere method. Our results suggest that PAF administration is associated with specific changes in vascular resistance, since estimated blood flow was decreased to certain organs or tissues, but remained unchanged in others. Therefore, the hypotension observed during PAF infusion is dose-dependent, and is contributed to by decreases in vascular resistance in specific organs.

Effect of caloric restriction on cardiac reactivity and beta-adrenoceptor concentration.

The effect of a 21-day program of caloric restriction on cardiac reactivity and beta-adrenoceptor number was investigated in male Sprague-Dawley rats. Rats on the restricted diet (Restricted) exhibited significant decreases in body weight, epididymal fat pad, and retroperitoneal fat pad weight as well as the percent of body fat represented by these adipose tissue depots when compared with rats fed ad libitum (Fed). Fed rats exhibited significantly increased total heart weight and total heart protein, but the percent cardiac protein and ratio of heart weight to body weight were similar in Fed and Restricted rats. Isolated atria from Fed and Restricted rats developed similar chronotropic and inotropic responses over a range of isoproterenol concentrations. Although total beta-adrenoceptor number (fmol/heart) was greater in Fed rats, the concentration of beta-adrenoceptors (fmol/mg protein) was remarkably similar regardless of the dietary regimen. Therefore, despite significant decreases in body weight, body fat, and heart weight, the myocardium of Restricted rats maintained the capability of responding to isoproterenol as that of Fed rats, the mechanism of which is at least partially mediated through maintenance of beta-adrenoceptor concentration.