RESUMO
It is now well established that the pathophysiology of the malignant hyperthermia (MH) syndrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium [( Ca2+]i). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China X Pietrain). After determination of resting concentrations of [Ca2+]i and [Mg2+]i, each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+]i and [Mg2+]i were determined by means of ion-selective microelectrodes. The resting [Ca2+]i in normal muscle fibers was 0.11 +/- 0.01 microM (mean +/- SEM), whereas in the MH muscles the resting [Ca2+]i was 0.36 +/- 0.01 microM. In neither group was the resting [Ca2+]i modified by MgSO4. This cumulative dose of MgSO4 (100 mg/kg) was not able to prevent the induction of an MH episode by 2% halothane. Although MgSO4 did not directly decrease [Ca2+]i, it did attenuate the increase in [Ca2+]i associated with the syndrome from 7.29 +/- 0.43 microM in untreated animals to 0.84 +/- 0.03 microM in MgSO4 pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4 pretreatment. Baseline measurements of [Mg2+]i were not different in control and MH-susceptible muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cálcio/metabolismo , Sulfato de Magnésio/uso terapêutico , Hipertermia Maligna/prevenção & controle , Músculos/efeitos dos fármacos , Animais , Cálcio/análise , Dantroleno/farmacologia , Suscetibilidade a Doenças , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Halotano/farmacologia , Sulfato de Magnésio/sangue , Sulfato de Magnésio/farmacocinética , Hipertermia Maligna/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Microeletrodos , Músculos/metabolismo , Especificidade da Espécie , SuínosRESUMO
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle triggered when susceptible subjects are exposed to volatile anesthetic agents and/or depolarizing muscle relaxants. We have used Ca2+ selective microelectrodes to measure in vivo the intracellular free [Ca2+] in skeletal muscle of MH susceptible swine before and after the administration of dantrolene. We have investigated the effectiveness of this muscle relaxant in preventing clinical MH and the relationship between the resting intracellular free [Ca2+] and the probability of inducing the MH syndrome. The resting intracellular free [Ca2+] was 0.41 +/- 0.01 microM (M +/- SEM), which agrees with our previous measurements in susceptible swine. The administration of 0.5, 1, 2, 2.5 and 3 mg/Kg Dantrolene, reduced the intracellular free [Ca2+] to 0.31, 0.21, 0.09, 0.08, 0.08 microM respectively. The 0.5 mg/Kg dose induced a moderate decrease of [Ca2+]i and failed to prevent the MH syndrome after exposure to halothane (2%). The 1 mg/Kg dose produced a further reduction in [Ca2+]i and was sufficient to prevent the clinical syndrome in 2 out of 3 animals. The 2.5 mg/Kg dose was uniformly protective in all animals. These results suggest that the mechanism by which dantrolene protects susceptible animals exposed to triggering agents is by reducing the intracellular free [Ca2+] in skeletal muscle.
Assuntos
Cálcio/metabolismo , Dantroleno/farmacologia , Hipertermia Maligna/prevenção & controle , Músculos/efeitos dos fármacos , Anestésicos/efeitos adversos , Animais , Suscetibilidade a Doenças , Feminino , Masculino , Hipertermia Maligna/fisiopatologia , Potenciais da Membrana/efeitos dos fármacos , Microeletrodos , Músculos/metabolismo , SuínosRESUMO
Percutaneous catheterization of the radial artery appears to be a simple and safe alternative to catheterization of the umbilical artery for monitoring critically ill neonates. This avoids the serious and potentially fatal complications associated with use of the umbilical arterial catheter, and it is also applicable to monitoring of neonates in whom the umbilical artery is no longer patent. We observed no serious sequelae in cannulation of the radial artery and think that the technique should be used more widely.