Search PubMed⌕ Search

Biomedical subjects

H Ording

Publications and source records attributed to H Ording.

18 recordsLinked to original sources
PubMed1992

Ca(2+)-ATPase and Na(+)-K(+)-ATPase content in skeletal muscle from malignant hyperthermia patients.

The purpose of this study was to determine the concentration of Ca(2+)-ATPase and Na(+)-K(+)-ATPase in biopsies from vastus lateralis muscle of 24 patients, who underwent a diagnostic contracture test for susceptibility to malignant hyperthermia (MH). Ca(2+)-ATPase was quantified as the Ca(2+)-dependent 32P incorporation in whole muscle homogenates. Na(+)-K(+)-ATPase was quantified as the [3H]ouabain-binding capacity in intact muscle samples. These methods avoid isolation of membranes, a procedure that may influence the results due to interindividual variation in recovery. The results show that both enzymes can be determined in (frozen) muscle biopsies weighing 50 mg. Neither the concentration of Ca(2+)-ATPase nor that of Na(+)-K(+)-ATPase differed in biopsies from subjects diagnosed as susceptible (MHS) or nonsusceptible (MHN) to MH. Our data support the view that changes in the concentration of Ca(2+)-ATPase and/or Na(+)-K(+)-ATPase do not play a primary role in the pathogenesis of MH.

Adult↗
PubMed1992

[Malignant hyperthermia].

Malignant hyperthermia (MH) is a life threatening complication following anaesthesia with potent inhalational agents and suxamethonium. The signs of MH are caused by increased metabolism and secondary stimulation of the sympathetic nervous system due to uncontrolled, high intracellular concentrations of calcium in skeletal muscle. The hyperthermia is secondary to the increased energy turnover. Calcium release from the sarcoplasmic reticulum is increased due to a low threshold for release and prolonged opening of the calcium channel upon normal stimulation. The gene encoding the calcium channel is localized on chromosome 19 in humans, and a substitution of cysteine for arginine has recently been described in one family with MH.

Calcium↗
PubMed1992

Sources of variability in halothane and caffeine contracture tests for susceptibility to malignant hyperthermia.

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed in 96 patients according to the protocol of the European MH Group. In addition, tests were performed with halothane 0.44 mmol l-1 and 0.66 mmol l-1, and caffeine 2 mmol l-1, each added as a single bolus dose to fresh specimens. For all tests the size of contractures were recorded, and for the diagnostic tests the halothane and caffeine threshold concentrations were determined (i.e. the minimal concentrations eliciting a contracture of 0.2 g). The caffeine specific concentration (CSC, i.e. the concentration increasing force 1.0 g) and the % increase with caffeine 2 mmol l-1 were calculated from the dose response curves. Various diagnostic criteria in use by the North American MH Group were applied, and diagnostic outcome compared with the result obtained by the protocol of the European MH Group. Thirty-five patients were susceptible to MH (MHS), 33 were non-susceptible (MHN), and 28 had equivocal results of the tests (MHE). Additional tests were made in 34 MHS, 32 MHN, and 26 MHE patients. Contractures elicited by bolus addition of halothane or caffeine were significantly larger than those observed following the same dose of drug added cumulatively (P less than 0.05). Contractures greater than or equal to 0.7 g following halothane 3% (bolus dose) were seen in 78% of MHS patients and 18% of MHN patients, A CSC less than 4 mmol l-1 was elicited in 86% of MHS and 30% of MHN patients, whereas an increase in force greater than or equal to 4% or greater than or equal to 7% was seen in 71% and 34% of MHS patients, respectively, and in none of the MHN patients. Using the criterion of greater than or equal to 0.7 g in the halothane test and greater than or equal to 4% increase in the caffeine test gave the best agreement between diagnostic outcome with the European and North American protocols: All 34 MHS patients (100%) were positive to one or more tests, but so were eight of 32 MHN patients (25%), giving an overall diagnostic agreement of 88%. We conclude that, in our laboratory, the results obtained with the two major protocols for investigation of MH susceptibility are not identical. Patients surviving fulminant MH, however, react abnormally to nearly all the tests. For validation and possibly further standardization of the tests each laboratory must investigate a large number of normal controls and as many patients surviving fulminant MH as possible.

Adolescent↗
PubMed1991

Evaluation of 119 anaesthetics received after investigation for susceptibility to malignant hyperthermia.

A questionnaire was sent to the first 371 patients investigated for MH susceptibility at the Danish MH Register, in order to assess sequelae from the muscle biopsy and possible subsequent anaesthetic complications. The purpose was to evaluate both the safety of anaesthetizing MH-susceptible (MHS) patients without the use of trigger agents, and the safety of giving trigger agents to non-susceptible (MHN) patients. Eighty-eight per cent of patients alive replied to the questionnaire. Of these, 22% complained about discomfort at the site of the biopsy, 2% had experienced problems when needing a subsequent anaesthetic, and 0.9% had had trouble when applying for life or accident insurance. The median observation period for all patients following the muscle biopsy was 5.5 years (range 27 months-11 years). During this period, 36 MHS patients had been anaesthetized 52 times (28 general and 23 regional anaesthetics, data missing in one case) without any MH-related complications. None of the patients had received prophylactic dantrolene. Three MHE patients had received non-trigger anaesthetic agents on three occasions without development of MH. Thirty-five MHN patients had been anaesthetized 64 times, and 13 of these MHN patients had received trigger agents 26 times without any signs of MH. An estimate of the probability of clinical MH developing in MHN patients subsequently anaesthetized with trigger agents was found to be 0-24.7% (95% confidence limits), whereas the probability of clinical MH developing in MHS patients anaesthetized with non-trigger agents was 0-9.7% (95% confidence limits).

Adjuvants, Anesthesia↗
PubMed1990

Cytosolic free calcium concentrations in lymphocytes from malignant hyperthermia susceptible patients.

Halothane in concentrations exceeding 1.2 mmol litre-1 increased (P less than 0.05) the apparent intracellular concentration of calcium in lymphocytes from 12 patients being tested for susceptibility to malignant hyperthermia (MH) using the fluorescent Ca2+ indicator, fura2. There was no difference in [Ca2+]i between lymphocytes from patients found to be MH susceptible (n = 5) on in vitro contracture testing with halothane and caffeine and those from MH negative patients (n = 6). Thus determination of [Ca2+]i in lymphocytes after exposure to halothane could not be used as a diagnostic test for MH susceptibility.

Adult↗
PubMed1990

Influence of salbutamol on the in vitro muscle response to caffeine and halothane in malignant hyperthermia.

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed with halothane and caffeine in 34 patients, according to the protocol of the European MH Group. Additional halothane and caffeine tests were performed in the presence of salbutamol 50 micrograms/l. Contractures after exposure to halothane were seen only in MH-susceptible (MHS) patients (n = 16), and were not changed by salbutamol. Salbutamol did not influence the caffeine dose-response curves in any of the groups (n = 14 in the MH-non-susceptible (MHN) group). The caffeine threshold concentration was significantly increased by salbutamol in the MHS group.

Adult↗
PubMed1989

Pathophysiology of malignant hyperthermia.

Malignant hyperthermia (MH) is a pharmacogenetic disease in man and animals. It primarily involves skeletal muscle tissue, but other tissues might be affected to a lesser degree. Calcium homeostasis in muscle cells is upset in susceptible individuals, so that various agents and circumstances can increase the free, ionised intracellular calcium concentration to damaging levels. The primary defect is not known at present, but is believed to involve an abnormally sensitive calcium-induced calcium release mechanism. Thus small, localised increases in calcium concentration releases more calcium so that a vicious cycle is triggered. The increased calcium concentration causes multiple effects in the muscles by stimulating contraction and a hypermetabolic state, clinically observed as rigidity and fever. If demands on the homeostatic mechanisms to lower the calcium concentration become exhausted, and metabolism is insufficient to supply enough phosphocreatine and ATP, membrane potentials cannot be maintained, and permeability of the cell membranes increase. This causes loss of phosphate and H+ as well as K+ and Mg++, and later myoglobin and creatine kinase. Thereby oxidative metabolism is further impeded with formation of lactate as a result. The ensuing acidosis stimulates sympathetic innervation, resulting in tachycardia, high blood pressure, and vasoconstriction. Hyperkalemia causes arrhythmia. Dantrolene inhibits the release of calcium and can halt the process if given before depletion of the energy rich phosphates is too advanced.

Animals↗
PubMed1989

Influence of propranolol on the in vitro response to caffeine and halothane in malignant hyperthermia-susceptible muscle.

In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were performed with halothane and caffeine in 27 patients according to the protocol of the European MH Group. Additional halothane and caffeine tests were performed in the presence of propranolol 80 micrograms/l. Contractures after exposure to halothane were seen only in MH-susceptible (MHS) patients (n = 12), and were not affected by propranolol. In contrast, propranolol shifted the caffeine dose-response curve to the right and significantly increased the caffeine threshold in the MHS group. Propranolol did not influence the caffeine results in the normal response group group (n = 12). It is concluded that beta-blockers should be discontinued before investigation for MH susceptibility.

Anesthesia↗
PubMed1988

Use of vecuronium and doxapram in patients susceptible to malignant hyperthermia.

Neuromuscular blockade was obtained with vecuronium 108 micrograms kg-1 in 44 patients undergoing diagnostic muscle biopsy as part of an investigation of malignant hyperthermia (MH) susceptibility. At the termination of anaesthesia doxapram 1.43 mg kg-1 was given in an attempt to antagonize postoperative respiratory depression. Rectal, muscle and skin temperatures, blood lactate concentration and venous PCO2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the protocol of the European MH Group. Twenty patients were susceptible to MH (MHS), 19 were MH non-susceptible (MHN) and five MH equivocal (MHE). No adverse effects of the drugs were observed. There were no differences between the three groups in rectal or muscle temperature, blood lactate concentration or venous PCO2 at any time. Doxapram did not prevent an increase in postoperative PCO2. It is concluded that vecuronium and doxapram may be safely administered to patients susceptible to MH.

Adult↗
PubMed1987

A new infusion design for atracurium and vecuronium.

An infusion technique, designed to reduce the duration of period of no response to nerve stimulation following atracurium (Group I) and vecuronium (Group 2), was studied in 30 patients during neurolept anaesthesia. For intubation a combination of a small bolus injection of the relaxant (ED50) and a continuous infusion were administered. The tactile response to nerve stimulation was used to quantify the degree of relaxation and to adjust the speed of infusion. On the other arm the mechanical twitch was recorded blindly for control. Good to excellent intubation conditions were obtained in 4.3 min with atracurium and in 4.0 min with vecuronium. The total dose given for intubation was 0.36 mg kg-1 atracurium (0.24-0.49 mg kg-1) and 0.064 mg kg-1 vecuronium (0.046-0.084 mg kg-1). The period of no response was zero in seven patients in Group I and in four patients in Group 2. In the remaining patients in Group I the period of no response ranged from 5.0-25.0 min, median 10.9 min, and in Group 2 from 2.5-15.6 min, median 9.5 min. At the time of extubation the train-of-four ratio was 0.71 and 0.72 in Group I and 2, respectively. It is concluded that it is possible to achieve a stable, adjustable, and easily reversible block with this technique, even during surgery of short duration.

Adult↗
PubMed1986

Atracurium and its antagonism by neostigmine (plus glycopyrrolate) in patients susceptible to malignant hyperthermia.

Forty patients undergoing diagnostic muscle biopsy as part of investigation for malignant hyperthermia (MH) were given atracurium 0.45 +/- 0.10 mg kg-1 for muscle paralysis. The neuromuscular blockade was antagonized with neostigmine 2.4 +/- 0.4 mg given with glycopyrrolate 0.47 +/- 0.09 mg. Rectal, muscle and skin temperatures and blood lactate concentration and venous Pco2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the regimen of the European MH Group. Fifteen patients were susceptible to MH (MHS), 19 were MH-negative (MHN) and six were MH-equivocal (MHE). No side effects of the drugs were noted. There were no differences between the three groups of patients in any of the measurements.

Adult↗
PubMed1986

Ketanserin and malignant hyperthermia in pigs.

Four Danish landrace pigs susceptible to MH were challenged with halothane and suxamethonium on six occasions after pretreatment with the serotonin-S2 antagonist ketanserin 0.4 mg/kg (three animals) or 4 mg/kg (three animals). The animals developed typical MH on all occasions despite the pretreatment. Dantrolene remains the only specific drug for prevention and treatment of MH.

Animals↗
PubMed1985

Precurarization with vecuronium and pancuronium in awake, healthy volunteers: the influence on neuromuscular transmission and pulmonary function.

The influence of pretreatment with pancuronium and vecuronium on the neuromuscular transmission was compared in 24 healthy, awake, non-premedicated volunteers using train-of-four (TOF) nerve stimulation and measurement of respiratory frequency, vital capacity, inspiratory force and peak expiratory flow (PEF). The subjects were randomly allocated to one of three groups. Each subject received one dose of pancuronium and one dose of vecuronium: Group I pancuronium 0.01 mg/kg and vecuronium 0.005 mg/kg; Group II pancuronium 0.01 mg/kg and vecuronium 0.01 mg/kg and Group III pancuronium 0.01 mg/kg and vecuronium 0.015 mg/kg intravenously. The median TOF ratio decreased significantly in Groups I and II following both pancuronium and vecuronium. The TOF ratio following vecuronium in Group II was significantly lower compared to the TOF ratio following vecuronium in Group I. Only PEF decreased significantly in Group I following pancuronium and in Group II following both pancuronium and vecuronium. There was no significant difference between Group I and Group II regarding the number of subjects with signs or symptoms of partial neuromuscular blockade. Following vecuronium 0.005 mg/kg, one subject was unable to swallow and the twitch height decreased to 0.25. In Group II one subject was unable to lift her head and had difficulty in swallowing following pancuronium 0.01 mg/kg. Only four subjects entered Group III because of an unacceptably high frequency of signs and symptoms of partial neuromuscular blockade and a decrease in median TOF ratio to 0.64 following vecuronium. The subjects felt it difficult to swallow, and one subject could just sustain head lift for 10 s following vecuronium 0.015 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Consciousness↗
PubMed1985

Dose-response curves for vecuronium during halothane and neurolept anaesthesia: single bolus versus cumulative method.

The purpose of this study was to compare the incremental, cumulative dose method and the single bolus injection technique for construction of dose-response curves for vecuronium. Dose-response curves were determined in 77 patients divided into four groups according to the anaesthetic given and the method used for construction of dose-response curves. The regression lines corresponding to the four dose-response curves were found to be parallel. For vecuronium ED50 during neurolept anaesthesia was found to be 28 micrograms kg-1 with the single bolus injection technique and 35.2 micrograms kg-1 with the incremental, cumulative dose method (P less than 0.05). During halothane anaesthesia, ED50 was found to be 25.7 micrograms kg-1 and 26.2 micrograms kg-1, respectively (P greater than 0.05). Potentiation of vecuronium by halothane was found with the cumulative method only. It is concluded that the incremental, cumulative dose method is not suitable for potency determinations of vecuronium.

Adult↗
PubMed1985

Edrophonium and neostigmine for reversal of the neuromuscular blocking effect of vecuronium.

The effect of edrophonium for reversal of the non-depolarizing neuromuscular blockade produced by a continuous infusion of vecuronium was compared to that of neostigmine in 20 adult patients during neurolept anaesthesia. When antagonism was attempted at 10% twitch height recovery, reversal time to a train-of-four ratio of 0.7 was significantly shorter following neostigmine 0.04 mg/kg than after edrophonium 0.75 mg/kg (9.8 min and 18.7 min, respectively) but the same after edrophonium 1.5 mg/kg (10.3 min). There was no statistically significant difference in reversal time between neostigmine 0.04 mg/kg given at 10% twitch height and edrophonium 0.75 mg/kg given at 25% twitch height recovery (6.0 min). Additional doses of atropine were necessary following edrophonium 1.5 mg/kg.

Adult↗