Shortening velocity of skeletal muscle from humans with malignant hyperthermia susceptibility: effects of halothane.

The aim of this investigation was to assess the effect of halothane on the velocity of shortening and lengthening of muscle from normal subjects and from patients with malignant hyperthermia susceptibility. Strips were mounted horizontally at optimal length in normal Krebs-Ringer's solution and mechanical parameters were obtained before and after exposure to 3 vol.% halothane. The maximun shortening velocity at zero load (V(max)) was determined by using Hill's characteristic equation. The contraction and relaxation indices were measured under isotonic and isometric conditions: maximum shortening and lengthening velocities (maxV(c) and maxV(r), respectively); isometric peak twitch tension; peak of the positive (+dP/dt(max)) and negative (-dP/dt(max)) twitch tension derivative; ratio R1=maxV(c)/maxV(r) and ratio R2=(+dP/dt(max))/(-dP/dt(max)). In normal muscle, halothane markedly increased V(max), maxV(c) and peak twitch tension by 30+/-10%, 30+/-5% and 40+/-15%, respectively. The maxV(r) values increased concomitantly with the maxV(c) values, such that no change in the ratio R1 was observed. Both +dP/dt(max) and -dP/dt(max) increased such that the ratio R2 did not vary. In malignant hyperthermia susceptibility muscle, halothane induced a significant decrease in V(max) (-30+/-10%) and maxV(r) (-45+/-15%) without changing maxV(c). The decrease in maxV(r) was greater than that of maxV(c), such that the ratio R1 increased significantly. Peak twitch tension and +dP/dt(max) remained unchanged whereas -dP/dt(max) decreased significantly; the ratio R2 increased by 40+/-10%. These results suggest that halothane alters the contractile properties of malignant hyperthermia susceptibility muscle.

A new noninvasive method to measure blood pressure: results of a multicenter trial.

BACKGROUND: Blood pressure (BP) monitoring with arterial waveform display requires an arterial cannula. We evaluated a new noninvasive device, Vasotrac (Medwave, Arden Hills, MN) that provides BP measurements approximately every 12-15 beats and displays pulse rate and a calibrated arterial waveform for each BP measurement. METHODS: Surgical and critically ill patients (n = 80) served as subjects for the study. BPs, pulse waveforms, and pulse rates measured via a radial artery catheter were compared with those obtained by the Vasotrac from the opposite radial artery. Data were analyzed to determine agreement between the two systems of measurement. RESULTS: Blood pressure measured noninvasively by the Vasotrac demonstrated excellent correlation (P<0.01) with BP measured via a radial arterial catheter (systolic r2 = 0.93; diastolic r2 = 0.89; mean r2 = 0.95). Differences in BP measured by the Vasotrac versus the radial arterial catheter were small. The mean+/-SD bias and precision were as follows: systolic BP 0.02+/-5.4 mm Hg and 3.9+/-3.7 mm Hg; diastolic BP -0.39+/-3.9 mm Hg and 2.7+/-2.8 mm Hg; mean BP -0.21+/-3.0 mm Hg and 2.1+/-2.2 mm Hg compared with radial artery measurements. The Vasotrac pulse rates were almost identical to those measured directly (r2 = 0.95). The Vasotrac BP waveform resembled those directly obtained radial artery pulsatile waveforms. CONCLUSIONS: In surgical and critically ill patients, the Vasotrac measured BP, pulse rate, and displayed radial artery waveform, which was similar to direct radial arterial measurements. It should be a suitable device to measure BP frequently in a noninvasive fashion.

ATX II, a sodium channel toxin, sensitizes skeletal muscle to halothane, caffeine, and ryanodine.

BACKGROUND: The function or expression of subtypes of the sodium ion (Na+) channel is altered in biopsies or cultures of skeletal muscle from many persons who are susceptible to malignant hyperthermia (MH). ATX II, a specific Na+ channel toxin from a sea anemone, causes delayed inactivation of the channel similar to that seen in cell cultures of MH muscle. ATX II was added to skeletal muscle to determine whether altered Na+ channel function could increase the sensitivity of normal skeletal muscle to agents (halothane, caffeine, ryanodine) to which MH muscle is hypersensitive. METHODS: Studies were performed of fiber bundles from the vastus lateralis muscle of persons who were deemed not MH susceptible (MH-) or MH susceptible (MH+) according to the MH diagnostic test and of strips of diaphragm muscle from rats. Preparations in a tissue bath containing Krebs solution were connected to a force transducer. ATX II was introduced 5 min before halothane, caffeine, or ryanodine. RESULTS: ATX II increased the magnitude of contracture to halothane in preparations from most MH-, but not MH+, human participants. After ATX II treatment, preparations from 9 of 24 MH- participants generated contractures to halothane, 3%, that were of the same magnitude as those from MH+ participants. Preparations from four of six ATX II-treated healthy participants also gave responses of the same magnitude as those of MH-susceptible participants to a graded halothane challenge (0.5-3%). The contractures to bolus doses of halothane in specimens from male participants were more than three times larger than the contractures in specimens from female participants. In rat muscle, ATX II increased the magnitude of contracture to caffeine (2 mM) and decreased the time to produce a 1-g contracture to ryanodine (1 microM). CONCLUSIONS: ATX II, which causes delayed inactivation of the Na+ channel in cell cultures similar to that reported in cultures of MH+ skeletal muscle, increased the sensitivity of normal muscle to three agents to which MH+ muscle is hypersensitive. The increased sensitivity to halothane, 3%, occurred in most (79%), but not all, MH- participants, and this effect was most evident in male participants. Therefore, abnormal function of the Na+ channel, even if it is a secondary event in MH, may contribute to a positive contracture test result for MH.

Halothane induces calcium release from human skinned masseter muscle fibers.

BACKGROUND: An increase in masseter muscle tone in response to halothane or succinylcholine anesthesia (or both) can be observed in healthy persons. Thus the authors compared the fiber-type halothane and succinylcholine sensitivities in human masseter and vastus lateralis muscles. METHODS: Masseter and vastus lateralis muscle segments were obtained from 13 and 9 healthy persons, respectively. After chemical skinning of a single fiber and loading the sarcoplasmic reticulum with Ca++ 0.16 microM solution, halothane (0.5-4 vol% bubbled in the incubating solution), succinylcholine (0.1 microM to 10 mM), or both sensitivities were defined as the concentration inducing more than 10% of the maximum tension obtained by application of 16 microM Ca++ solution. The myofilament response to Ca++ was studied with and without halothane by observing the isometric tension of skinned masseter fibers challenged with increasing concentrations of Ca++. Muscle fiber type was determined by the difference in strontium-induced tension measurements. RESULTS: A significant difference in halothane sensitivity was found between type 1 masseter fibers (0.6+/-0.2 vol%; mean +/- SD) versus type 1 (2.7+/-0.6 vol%) and type 2 vastus lateralis muscle (2.5+/-0.4 vol%). Succinylcholine did not induce Ca++ release by the sarcoplasmic reticulum. In the masseter muscle, 0.75 vol% halothane decreased the maximal activated tension by 40% but did not change the Ca++ concentration that yields 50% of the maximal tension. CONCLUSIONS: The very low halothane threshold for Ca++ release from the masseter muscle usually could be counteracted by a direct negative inotropic effect on contractile proteins. However, halothane may increase the sensitivity of the sarcoplasmic reticulum Ca++ release to succinylcholine-induced depolarization, leading to an increase in masseter muscle tone.

-The clinical use of the cuffed oropharyngeal airway (COPA)-. / Utilisation clinique du COPA (cuffed oropharyngeal airway).

OBJECTIVE: To assess the performance of the COPA device during general anaesthesia. STUDY DESIGN: Prospective, clinical, open study. PATIENTS: Eighty patients scheduled for short elective surgical procedures under general anaesthesia not requiring tracheal intubation. METHOD: After premedication (midazolam, atropine), anaesthesia was induced with propofol (154 +/- 40 mg = 2.47 +/- 0.8 mg.kg-1) and alfentanil (1.14 +/- 0.43 mg). The COPA device was inserted in a fashion similar to a Guedel airway device. The device was evaluated on the following criteria: correct choice of COPA size, ease of insertion, ability to obtain or maintain patent airway. Adverse reactions were noted, such as coughing, nausea, regurgitation, inhalation, and sore throat. The overall rating of the COPA as a "hand free device" was evaluated on the basis of excellent, good, fair, and poor. RESULTS: Insertion of the device was easy and in 70 cases successful on the first attempt. Jaw thrust on head tilt was necessary in half the cases. No patient necessitated intubation because of hypoxaemia or airway obstruction. Adverse reactions occurred in few cases and consisted of sore throat (always moderate) in 10% of the cases. COPA was evaluated as excellent or good in 80% of the cases. CONCLUSION: COPA is a convenient device for airway management in fasting patients undergoing general anaesthesia for elective surgery in the supine position, in whom tracheal intubation is not indicated.

Effects of veratridine on mechanical responses of human malignant hyperthermic muscle fibers.

BACKGROUND: To determine if alteration in the function of the sodium channel may in turn modify halothane-induced changes in mechanical responses of muscle bundles from patients susceptible to malignant hyperthermia (MH). METHODS: Mechanical responses of muscle bundles from 12 MH-susceptible and 20 MH non-susceptible patients were measured prior to and during administration of halothane alone and in the presence of 10 microM veratridine, an inhibitor of sodium channel inactivation. Peak tension (PT), time to peak tension (TPT), positive peak of isometric tension derivative (+dP/dtmax) were used to characterize the inotropic state. Analysis of relaxation process was performed using half relaxation time (RT 1/2) and the negative peak of isometric tension derivative (-dP/dtmax). The ratio (R) = (+dP/dtmax)/(-dP/dtmax) was used to measure the coupling between contraction and relaxation under isometric condition. RESULTS: Veratridine significantly enhanced the 0.5, 1, 2 and 3 vol% halothane-induced contracture and induced a negative inotropic effect in MH-susceptible muscle bundles. R increased by nearly 90% indicating that the combined effects were more pronounced in the relaxation phase. In MH non-susceptible muscle, veratridine did not significantly enhance the effects of halothane. CONCLUSIONS: These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of an inhibitor of sodium channel inactivation.

Identification of heterozygous and homozygous individuals with the novel RYR1 mutation Cys35Arg in a large kindred.

BACKGROUND: Malignant hyperthermia (MH) is a potentially fatal, often autosomal dominant, disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalational anesthetics. In this article, the authors describe a malignant hyperthermia susceptible (MHS) kindred in which both parents of the proband are MHS and are first-degree cousins. Haplotype analysis in this kindred with chromosome 19 linked markers revealed that the proband and another sibling were homozygous for the affected RYR1 allele. METHODS: Eighteen members of this large pedigree were investigated, with a clinical examination for signs of a myopathy, a caffeine halothane contracture test, a histo-enzymologic study on the muscle biopsies, and linkage analysis on genomic DNA isolated from family blood samples. RYR1 cDNA was amplified by polymerase chain reaction and was cloned and sequenced, facilitating mutation detection. RESULTS: Linkage analysis demonstrated linkage between RYR1-linked markers and MH susceptibility in this family. DNA sequencing identified a T to C transition at nucleotide position 103, resulting in the substitution of an arginine for cysteine 35, representing the most N-terminal mutation reported to date in the RYR1 gene. This mutation segregates fully with the MHS trait, generating a lod score of 4.65 in favor of linkage to MHS at a recombination frequency of 0.0. CONCLUSIONS: The proband in this kindred is the first reported homozygote to have presented with an MH episode. The homozygotes in this pedigree do not have an overt myopathy. The sensitivity of muscle samples to caffeine clearly distinguished the two homozygotes from other heterozygous-susceptible individuals. No clear differentiation was observed with the halothane contracture results.

Isoform-dependent effects of halothane in human skinned striated fibers.

BACKGROUND: Reports of the effects of halothane on isoform contractile proteins of striated muscles are conflicting. To determine whether halothane affects cardiac and skeletal contractile proteins differently, the authors examined the effects of two doses of halothane (0.44 and 1.26 mM, equivalent to 0.75 and 2.25 vol%, respectively) on the Ca++ sensitivity and maximal force in human skinned cardiac, type I (slow twitch), and type II (fast twitch) skeletal muscle fibers. METHODS: Left ventricular muscle strips and skeletal muscle biopsy specimens were obtained from eight and ten patients undergoing cardiac and orthopedic surgery, respectively. Sarcolemma and sarcoplasmic reticulum were destroyed with ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus Brij 58. Ca++ sensitivity was studied by observing the isometric tension developed by skinned fibers challenged with increasing concentrations of Ca++. Muscle fiber type was determined in each skeletal fiber by the difference in strontium-induced tension measurements. RESULTS: Halothane shifted the Ca++ tension curves toward higher Ca++ concentrations and increased the Ca++ concentrations for half-maximal activation in both cardiac and type I skeletal muscle fibers (from 1.96 microM and 1.06 microM under control conditions to 2.92 microM and 1.71 microM in presence of 0.75 vol% halothane, respectively) without changing the slope of this relationship (Hill coefficient). In contrast, no significant effect was observed in type II fibers. Halothane also decreased the maximal activated tension in the three groups of fibers with a lesser effect in type II fibers. CONCLUSIONS: Halothane decreases Ca++ sensitivity and maximal force in human skinned cardiac and type I fibers at 20 degrees C. It is concluded that the negative inotropic effects of halothane depend on contractile proteins isoforms.

In vitro human masseter muscle hypersensitivity: a possible explanation for increase in masseter tone.

To determine whether a difference in fiber-type caffeine and Ca2+ sensitivities exists between human masseter and vastus lateralis skeletal muscle, we compared the fiber-type caffeine sensitivities in chemically skinned muscle fibers from 13 masseter and 18 vastus lateralis muscles. Caffeine sensitivity was defined as the threshold concentration inducing > 10% of the maximal tension obtained after the fiber was loaded with a 1.6 x 10(-2) mM Ca2+ solution for 30 s. Significant difference in the mean caffeine sensitivity was found between type I masseter fibers [2.57 +/- 1.32 (SD) mM] vs. type I (6.02 +/- 1.74 mM) and type II vastus lateralis fibers (11.25 +/- 3.13 mM). Maximal Ca(2+)-activated force per cross-sectional area was significantly different between masseter and vastus lateralis fibers. However, the Ca2+ concentration corresponding to half-maximal tension (pCa50) was not significantly different between type I masseter (pCa50 5.9 +/- 0.02) and type I vastus lateralis muscle (pCa50 6.01 +/- 0.08). These results suggest that the increase in caffeine sensitivity of masseter muscle reflects the presence of a low reactivity threshold of the sarcoplasmic reticulum.

Evaluation of the Augustine Guide for difficult tracheal intubation.

Successful tracheal intubation with Augustine Guide (Augustine Medical, Inc., Eden Prairie, MN) in patients with normal airways has recently been described. There are no studies describing Augustine Guide (AG) use in patients with difficult airways. Accordingly, we studied AG intubation in a population of patients with expected difficult airways due to cervical spine pathology, limited mouth opening, obesity, facial trauma or deformity due to previous operation or radiation and in patients with unexpectedly difficult airways. A total of 44 patients were studied. The AG was used as a primary intubating tool in patients with known difficult airways (n = 36) and as a secondary intubating tool in patients with unexpected inability to intubate using conventional direct laryngoscopy (n = 8). Airway difficulty was predicted by history and physical examination. Intubations were performed under general anaesthesia in 40 of the 44 patients studied. In four patients with predictably difficult airways, topical anaesthesia and sedation were used. Backup methods to achieve intubation were available. Thirty-two of the 36 with known or suspected difficult airways were classified as Mallampati Class III or IV. In the remaining eight patients the preoperative examination suggested an easy airway; however, after induction of general anaesthesia, their laryngeal inlet could not be seen using direct laryngoscopy. Using the AG, all were intubated successfully (36/44 at the first attempt, in 8/44 repositioning of the AG to allow successful laryngeal entry of the stylet was necessary). There were no failures or complications secondary to AG use. This study shows that the AG is a useful device for oral tracheal intubation in patients with known or unexpectedly difficult airways.

[Cervicofacial cellulitis of dental origin and tracheal intubation]. / Cellulites cervico-faciales d'origine dentaire et intubation trachéale.

OBJECTIVES: To evaluate the difficulty of intubation in relation with the localisation and spread of cervico-facial cellulitis of odontogenic origin and to recognize the optimal technique of intubation in such circumstances. STUDY DESIGN: Prospective clinical open study. PATIENTS: Hundred patients, including 16 children, undergoing surgical drainage of a cervico-facial cellulitis of odontogenic origin under general anesthesia were studied. METHODS: Difficulty of intubation was evaluated with the following four criteria: active mouth opening in the awake patient, Mallampati's classifying system, presence of trismus, clinical and radiological control of localisation and extension of the cellulitis (mandibular, maxillar or mouth floor). In case of a foreseen difficult intubation, a fibrescope was used in the awake patient. Otherwise the endotracheal tube was inserted after administration of propofol (3 mg.k-1) and alfentanil (10 to 20 micrograms.kg-1). A Cormack's grading was performed during intubation. RESULTS: Mouth opening depended on the localisation of the cellulitis. Trismus occurred more often with mandibular than maxillary localisations. Trismus and a Mallampati's class > 2 were associated with difficulty in intubation (Cormack's grade > 2), except in maxillary localisations. CONCLUSIONS: The localisation of cellulitis of odontogenic origin is responsible for the difficulty grade of intubation. Awake fibreoptic intubation should be systematically performed in patients with a floor of the mouth cellulitis to reduce the risk of rupture of the abscess by a laryngoscope blade. As trismus associated with mandibular localisations is not relieved by general anaesthesia, awake fibreoptic endotracheal intubation should be preferred.

Intermittent left bundle branch block revealed during anaesthesia.

Intermittent left bundle branch block is uncommon. During anaesthesia,, left bundle branch block may be related to hypertension or tachycardia and its occurrence makes the diagnosis of acute myocardial ischaemia or infarction difficult. Patients with intermittent left bundle branch block often develop established left bundle branch block, which may represent an earlier state of ischaemic heart disease. Cardiological investigation of our patient after operation did not point towards an organic cause of intermittent left bundle branch block.

Halothane and isoflurane decrease calcium sensitivity and maximal force in human skinned cardiac fibers.

BACKGROUND: Reports of the direct effects of volatile anesthetics on cardiac myofibrils, studied in various mammalian species but not in humans, have conflicted. To determine whether volatile anesthetics directly affect cardiac contractile proteins in humans, we examined the effects of various equianesthetic doses of halothane (0.46, 0.83, and 1.23 mM, equivalent to 0.75, 1.50, and 2.25%, respectively) and isoflurane (0.63, 1.22, and 1.93 mM, equivalent to 1.15, 2.30, and 3.50%, respectively) on the Ca2+ sensitivity and maximal force in human skinned cardiac fibers. METHODS: Left ventricular muscle strips were obtained from seven patients undergoing cardiac surgery. Sarcolemma was disrupted with EGTA (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid), and sarcoplasmic reticulum was destroyed with EGTA plus BRIJ 58 detergent. Ca2+ sensitivity was studied by observing the isometric tension developed by skinned fiber bundles challenged with solutions of increasing Ca2+ concentrations expressed in pCa (where pCa = -log10[Ca2+]). Maximal force was measured with a pCa 4.8 solution. RESULTS: Both anesthetics shifted the pCa-tension curves toward higher Ca2+ concentrations and decreased pCa for half-maximal activation in a dose-dependent and reversible fashion (from 5.71 for control to 5.56 and 5.55 for 1 MAC halothane and isoflurane, respectively) without changing the slope of this relationship (Hill coefficient). No differences between agents were observed at equianesthetic concentrations. The two agents also decreased the maximal activated tension in a dose-dependent fashion (-27 and -28% vs. control for 2 MAC halothane and isoflurane, respectively). CONCLUSIONS: The current study indicates that halothane and isoflurane decrease Ca2+ sensitivity and maximal force in human skinned cardiac fibers at 20 degrees C. If these effects extend to higher temperatures, they may contribute to the negative inotropic effect of these agents.

[Lack of sensitivity to per-anesthetic malignant hyperthermia in 32 patients who developed neuroleptic malignant syndrome]. / Absence de sensibilité à l'hyperthermie maligne peranesthésique chez 32 patients ayant développé un syndrome malin des neuroleptiques.

The aim of this study was to verify whether a relationship exists between neuroleptic malignant syndrome (NMS) and anaesthetic-induced malignant hyperthermia (MH) or not. The in vitro halothane-caffeine tests were performed on muscle tissue obtained from 32 patients with documented NMS episodes. The diagnosis of NMS relied on Levenson's criteria. The results, expressed in accordance with the criteria of the European MH Group, defined 29 subjects as MH non-susceptible. Three patients were classified as MH equivocal. These findings demonstrate the lack of any link between NMS and MH. Therefore, patients with a history of NMS are not likely to be at risk of developing MH and special measures against MH are not required for anaesthesia in these patients.

Viability criterion of muscle bundles used in the in vitro contracture test in patients with neuromuscular diseases.

We have compared the viability criteria of muscle bundles used in the in vitro contracture test for susceptibility to malignant hyperthermia (MH) in a group of 28 patients with various neuromuscular diseases (NMD) and 93 MH-related family patients. In the patients with NMD, this standard test gave one positive, six equivocal and 21 negative results. Compared with MH-related family patients, muscle bundles used had significantly smaller resting membrane potentials and smaller predrug twitch tension amplitudes. Some results from the group with NMD were obtained with muscles which were damaged, more rapidly deteriorating, non-standard or both, and should not be taken to indicate that the patients have the genetic trait for MH. The in vitro contracture test is not always relevant for myopathic muscle (especially dystrophic muscle) and this could explain the lack of specificity for MH.

Fiber-type caffeine sensitivities in skinned muscle fibers from humans susceptible to malignant hyperthermia.

BACKGROUND: The response to contracture tests may depend upon the relative proportion of muscle fiber types within the muscle specimen. To determine whether a difference in fiber-type caffeine sensitivities exists between malignant hyperthermia susceptible (MHS) and malignant hyperthermia-nonsusceptible (MHN) skeletal muscle, we compared the fiber-type caffeine sensitivities in chemically skinned muscle fibers dissected from vastus lateralis muscle from 15 MHS and 16 MHN patients. METHODS: Muscle fiber type was determined in each fiber by the difference in strontium-induced tension measurements and in 36 fibers, after contracture testing, by ATPase enzyme histochemistry. Caffeine sensitivity was defined as the threshold concentration inducing more than 10% of the maximal tension obtained with a calcium 1.6 x 10(-2) mM solution. RESULTS: Significant difference in the mean (+/- SD) caffeine sensitivity was found between type I MHS fibers (2.63 +/- 0.85 mM) versus type II MHS fibers (3.47 +/- 1.2 mM) and between type I MHN fibers (5.89 +/- 1.8 mM) versus type II MHN fibers (10.46 +/- 2.6 mM). The mean (+/- SD) caffeine sensitivities for a given muscle fiber type (I or II) were different between groups of MHS and MHN patients. Both type I and II MHS fibers had significantly lower caffeine sensitivities, and this increase in caffeine sensitivity was significantly smaller in type I than in type II fiber. CONCLUSIONS: The current study indicates that a truly MHS patient cannot have a false-negative result solely related to abnormal type II fibers contained in a given muscle strip. Although the occurrence of a very high proportion of type I fibers in MHN human muscle could result in a false-positive contracture outcome, such an occurrence is expected to be rare.

Effect of Bay K 8644 on the magnitude of isoflurane and halothane contracture of skeletal muscle from patients susceptible to malignant hyperthermia.

Isoflurane has a lesser ability than halothane to induce contracture in malignant hyperthermia (MH) muscle in vitro. This does not necessarily imply that isoflurane is not as potent an MH trigger as halothane in vivo. A hypothesis was tested that in vitro treatment with Bay K 8644, an activator of both the dihydropyridine receptors as well as the sodium channels of the T-tubules, potentiates isoflurane-induced MH-susceptible skeletal muscle contracture. In addition to the usual halothane-caffeine test, other muscle bundles were exposed to 10 microM Bay K 8644-halothane and equipotent anesthetic concentrations (expressed in multiple minimum alveolar concentration [MAC]) of isoflurane either alone or combined with Bay K 8644. In 14 MH-susceptible muscle bundles, the mean maximum contracture induced by 2 MAC isoflurane was 0.20 +/- 0.22 g (mean +/- SD), and this value was significantly less than that obtained with 2 MAC halothane (0.68 +/- 0.40 g). Bay K 8644 did not induce muscle contracture on its own but consistently enhanced both the 0.5 MAC isoflurane and halothane to the same maximal isometric tension (1.09 +/- 0.35 g and 1.11 +/- 0.37 g, respectively). Such an effect was not observed in the MH-nonsusceptible group. Under the conditions of this in vitro study, 0.5 MAC isoflurane appears to be as potent as halothane in inducing muscle contracture in skeletal muscle bundles from individuals susceptible to MH.

Is resting membrane potential a possible indicator of viability of muscle bundles used in the in vitro caffeine contracture test?

In 22 patients susceptible to and 34 patients not susceptible to malignant hyperthermia, we examined which muscle conditions may influence the degree of sensitivity of skeletal muscle to the in vitro caffeine contracture test: predrug resting membrane potential, predrug twitch tension, and maximum contracture induced by 32 mM caffeine in two caffeine tests performed respectively at 30 and 75 min after biopsy. No differences in the measured variables were observed between the first and the second caffeine tests in the 34 patients susceptible to malignant hyperthermia. The first caffeine test was found to be positive in all of the 22 patients susceptible to malignant hyperthermia. However, in eight patients, the second caffeine test was negative and the muscle fibers were found to be significantly depolarized. Resting membrane potential was -73.4 +/- 7.9 mV before the first caffeine test and -65.8 +/- 8.8 mV before the second test. We suggest that when time-induced partial depolarization of malignant hyperthermia-susceptible fibers occurs, fibers may become less sensitive to caffeine.