On the Functional Role of Gamma Synchronization in the Retinogeniculate System of the Cat.

Fast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies conducted under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multielectrode recordings of spiking activity in the retina and the LGN of both male and female cats, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were nonoscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent on halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision.SIGNIFICANCE STATEMENT Gamma rhythms have been proposed to be a robust encoding mechanism critical for visual processing. In the retinogeniculate system of the cat, many studies have shown gamma oscillations associated with responses to static stimuli. Here, we extend these observations to dynamic stimuli. An unexpected finding was that retinal gamma responses strongly depend on halothane concentration levels and are absent in the awake cat. These results weaken the notion that gamma in the retina is relevant for vision. Notably, retinal gamma shares many of the properties of cortical gamma. In this respect, oscillations induced by halothane in the retina may serve as a valuable preparation, although artificial, for studying oscillatory dynamics.

Predictive factors of the contracture test for diagnosing malignant hyperthermia in a Brazilian population sample: a retrospective observational study

Abstract Introduction Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features. Objective To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. Methods We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation). Results Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%). Conclusions Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.

Fatigue, depression, and physical activity in patients with malignant hyperthermia: a cross-sectional observational study

Abstract Background Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional. Objective The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression. Methods A cross-sectional observational study was carried out with three groups - 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity). Results There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9 ± 1.9 vs. 3.9 ± 2, t-test unpaired, p< 0.05). Conclusion We did not detect subjective fatigue in MH susceptible patients, although we reported protracted recovery after physical activity, which may alert us to further investigation requirements.

Predictive factors of the contracture test for diagnosing malignant hyperthermia in a Brazilian population sample: a retrospective observational study.

INTRODUCTION: Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features. OBJECTIVE: To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. METHODS: We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation). RESULTS: Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%). CONCLUSIONS: Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.

Fatigue, depression, and physical activity in patients with malignant hyperthermia: a cross-sectional observational study.

BACKGROUND: Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional. OBJECTIVE: The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression. METHODS: A cross-sectional observational study was carried out with three groups ... 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity). RESULTS: There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9.ß...ß1.9 vs. 3.9.ß...ß2, t-test unpaired, p.ß<.ß0.05). CONCLUSION: We did not detect subjective fatigue in MH susceptible patients, although we reported protracted recovery after physical activity, which may alert us to further investigation requirements.

Anesthesia for muscle biopsy to test susceptibility to malignant hyperthermia / Anestesia durante biópsia muscular para teste de suscetibilidade à hipertermia maligna

Abstract Introduction Malignant hyperthermia is an autosomal dominant pharmacogenetic disorder, characterized by hypermetabolic crisis triggered by halogenated anesthetics and/or succinylcholine. The standard method for diagnosing malignant hyperthermia susceptibility is the in vitro muscle contracture test in response to halothane-caffeine, which requires muscle biopsy under anesthesia. We describe a series of anesthetic procedures without triggering agents in malignant hyperthermia, comparing peripheral nerve block and subarachnoid anesthesia. Method We assessed the anesthetic record charts of 69 patients suspected of malignant hyperthermia susceptibility who underwent muscle biopsy for in vitro muscle contracture in the period of 7 years. Demographic data, indication for malignant hyperthermia investigation, in vitro muscle contracture test results, and surgery/anesthesia/recovery data were analyzed. Results Sample with 34 ± 13.7 years, 60.9% women, 65.2% of in vitro muscle contracture test positive. Techniques used: peripheral nerve blocks — lateral femoral and femoral cutaneous, latency 65 ± 41 min — (47.8%); subarachnoid anesthesia (49.3%), and total venous anesthesia (1.4%). There was 39.4% failure of peripheral nerve block and 11.8% of subarachnoid anesthesia. Adverse events (8.7%) occurred only with subarachnoid blockade (bradycardia, nausea, and transient neurological syndrome). All patients remained in the post-anesthesia care unit until discharge. Age and weight were significantly higher in patients with blockade failure (ROC cut-off point of 23.5 years and 59.5 kg) and blockade failure was more frequent in the presence of increased idiopathic creatine kinase. Conclusion Anesthesia with non-triggering agents has been shown to be safe in patients with malignant hyperthermia susceptibility. Variables such as age, weight, and history of increased idiopathic creatine kinase may be useful in selecting the anesthetic technique for this group of patients.

Resumo Introdução Hipertermia maligna é uma doença farmacogenética autossômica dominante, caracterizada por crise hipermetabólica desencadeada por anestésicos halogenados e/ou succinilcolina. O padrão para diagnóstico da suscetibilidade à hipertermia maligna é o teste de contratura muscular in vitro em resposta ao halotano-cafeína, para o qual é necessária biopsia muscular sob anestesia. Descrevemos uma série de anestesias sem agentes desencadeantes na hipertermia maligna e comparamos bloqueios de nervo periférico e anestesias subaracnóideas. Método Foram analisados os prontuários/fichas anestésicas de 69 pacientes suspeitos de susceptibilidade à hipertermia maligna, submetidos à biópsia muscular para teste de contratura muscular in vitro durante sete anos. Analisamos dados demográficos, indicação para investigação de hipertermia maligna, resultado do teste de contratura muscular in vitro e dados da cirurgia/anestesia/recuperação. Resultados Amostra com 34 ± 13,7 anos, 60,9% mulheres, 65,2% de teste de contratura muscular in vitro positivos. Técnicas empregadas: 47,8% bloqueios de nervo periférico (femoral e cutâneo femoral lateral, latência 65 ± 41 minutos), 49,3% anestesias subaracnóideas e 1,4% anestesia venosa total. Falha em 39,4% dos bloqueios de nervo periférico e 11,8% das anestesias subaracnóideas. Eventos adversos (8,7%) como bradicardia, náuseas e síndrome neurológica transitória só ocorreram com bloqueio subaracnóideo. Todos os pacientes permaneceram na sala de recuperação pós-anestésica até liberação. Idade e peso foram significativamente maiores nos pacientes com falha no bloqueio (ponto de corte da curva ROC de 23,5 anos e 59,5 Kg) e esta foi mais frequente na presença de aumento idiopático de creatinoquinase. Conclusão Anestesia com agentes não desencadeantes mostrou-se segura em pacientes suscetíveis à hipertermia maligna. Variáveis como idade, peso e antecedente de aumento idiopático de creatinoquinase podem ser úteis para selecionar a técnica anestésica nesse grupo.

[Anesthesia for muscle biopsy to test susceptibility to malignant hyperthermia]. / Anestesia durante biópsia muscular para teste de suscetibilidade à hipertermia maligna.

INTRODUCTION: Malignant hyperthermia is an autosomal dominant pharmacogenetic disorder, characterized by hypermetabolic crisis triggered by halogenated anesthetics and/or succinylcholine. The standard method for diagnosing malignant hyperthermia susceptibility is the in vitro muscle contracture test in response to halothane-caffeine, which requires muscle biopsy under anesthesia. We describe a series of anesthetic procedures without triggering agents in malignant hyperthermia, comparing peripheral nerve block and subarachnoid anesthesia. METHOD: We assessed the anesthetic record charts of 69 patients suspected of malignant hyperthermia susceptibility who underwent muscle biopsy for in vitro muscle contracture in the period of 7 years. Demographic data, indication for malignant hyperthermia investigation, in vitro muscle contracture test results, and surgery/anesthesia/recovery data were analyzed. RESULTS: Sample with 34±13.7 years, 60.9% women, 65.2% of in vitro muscle contracture test positive. Techniques used: peripheral nerve blocks - lateral femoral and femoral cutaneous, latency 65±41minutes - (47.8%); subarachnoid anesthesia (49.3%), and total venous anesthesia (1.4%). There was 39.4% failure of peripheral nerve block and 11.8% of subarachnoid anesthesia. Adverse events (8.7%) occurred only with subarachnoid blockade (bradycardia, nausea, and transient neurological syndrome). All patients remained in the post-anesthesia care unit until discharge. Age and weight were significantly higher in patients with blockade failure (ROC cut-off point of 23.5 years and 59.5kg) and blockade failure was more frequent in the presence of increased idiopathic creatine kinase. CONCLUSION: Anesthesia with non-triggering agents has been shown to be safe in patients with malignant hyperthermia susceptibility. Variables such as age, weight, and history of increased idiopathic creatine kinase may be useful in selecting the anesthetic technique for this group of patients.

[Profile of malignant hyperthermia susceptibility reports confirmed with muscular contracture test in Brazil]. / Perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular no Brasil.

BACKGROUND AND OBJECTIVES: Malignant hyperthermia is an autosomal dominant hypermetabolic pharmacogenetic syndrome, with a mortality rate of 10%-20%, which is triggered by the use of halogenated inhaled anesthetics or muscle relaxant 10%-20% succinylcholine. The gold standard for suspected susceptibility to malignant hyperthermia is the in vitro muscle contracture test in response to halothane and caffeine. The determination of susceptibility in suspected families allows the planning of safe anesthesia without triggering agents for patients with known susceptibility to malignant hyperthermia by positive in vitro muscle contracture test. Moreover, the patient whose suspicion of malignant hyperthermia was excluded by the in vitro negative muscle contracture test may undergo standard anesthesia. Susceptibility to malignant hyperthermia has a variable manifestation ranging from an asymptomatic subject presenting a crisis of malignant hyperthermia during anesthesia with triggering agents to a patient with atrophy and muscle weakness due to central core myopathy. The aim of this study is to analyze the profile of reports of susceptibility to malignant hyperthermia confirmed with in vitro muscle contracture test. METHOD: Analysis of the medical records of patients with personal/family suspicion of malignant hyperthermia investigated with in vitro muscle contracture test, after given written informed consent, between 1997 and 2010. RESULTS: Of the 50 events that motivated the suspicion of malignant hyperthermia and family investigation (sample aged 27±18 years, 52% men, 76% white), 64% were investigated for an anesthetic malignant hyperthermia crisis, with mortality rate of 25%. The most common signs of a malignant hyperthermia crisis were hyperthermia, tachycardia, and muscle stiffness. Susceptibility to malignant hyperthermia was confirmed in 79.4% of the 92 relatives investigated with the in vitro muscle contracture test. CONCLUSION: The crises of malignant hyperthermia resembled those described in other countries, but with frequency lower than that estimated in the country.

Profile of malignant hyperthermia susceptibility reports confirmed with muscular contracture test in Brazil / Perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular no Brasil

Abstract Background and objectives: Malignant hyperthermia is an autosomal dominant hypermetabolic pharmacogenetic syndrome, with a mortality rate of 10%-20%, which is triggered by the use of halogenated inhaled anesthetics or muscle relaxant succinylcholine. The gold standard for suspected susceptibility to malignant hyperthermia is the in vitro muscle contracture test in response to halothane and caffeine. The determination of susceptibility in suspected families allows the planning of safe anesthesia without triggering agents for patients with known susceptibility to malignant hyperthermia by positive in vitro muscle contracture test. Moreover, the patient whose suspicion of malignant hyperthermia was excluded by the in vitro negative muscle contracture test may undergo standard anesthesia. Susceptibility to malignant hyperthermia has a variable manifestation ranging from an asymptomatic subject presenting a crisis of malignant hyperthermia during anesthesia with triggering agents to a patient with atrophy and muscle weakness due to central core myopathy. The aim of this study is to analyze the profile of reports of susceptibility to malignant hyperthermia confirmed with in vitro muscle contracture test. Method: Analysis of the medical records of patients with personal/family suspicion of malignant hyperthermia investigated with in vitro muscle contracture test, after given written informed consent, between 1997 and 2010. Results: Of the 50 events that motivated the suspicion of malignant hyperthermia and family investigation (sample aged 27 ± 18 years, 52% men, 76% white), 64% were investigated for an anesthetic malignant hyperthermia crisis, with mortality rate of 25%. The most common signs of a malignant hyperthermia crisis were hyperthermia, tachycardia, and muscle stiffness. Susceptibility to malignant hyperthermia was confirmed in 79.4% of the 92 relatives investigated with the in vitro muscle contracture test. Conclusion: The crises of malignant hyperthermia resembled those described in other countries, but with frequency lower than that estimated in the country.

Resumo Justificativa e objetivo: Hipertermia maligna é uma síndrome farmacogenética hipermetabólica, autossômica dominante, com mortalidade entre 10%-20%, desencadeada por uso de anestésico inalatório halogenado ou relaxante muscular succinilcolina. O padrão-ouro para pesquisa de suscetibilidade à hipertermia maligna é o teste de contratura muscular in vitro em resposta ao halotano e à cafeína. A determinação da suscetibilidade nas famílias suspeitas permite planejar anestesias seguras sem agentes desencadeantes para os pacientes confirmados como suscetíveis à hipertermia maligna pelo teste de contratura muscular in vitro positivo. Além disso, o paciente no qual a suspeita de hipertermia maligna foi excluída pelo teste de contratura muscular in vitro negativo pode ser anestesiado de forma convencional. Suscetibilidade à hipertermia maligna tem manifestação variável, desde indivíduo assintomático que apresenta crise de hipertermia maligna durante anestesia com agentes desencadeantes, até paciente com atrofia e fraqueza muscular por miopatia central core disease. O objetivo deste trabalho é analisar o perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular in vitro. Método: Análise das fichas de notificação dos pacientes com suspeita pessoal/familiar de hipertermia maligna investigados com teste de contratura muscular in vitro, após assinatura do termo de consentimento, entre 1997-2010. Resultados: Dos 50 eventos que motivaram a suspeita de hipertermia maligna e a investigação familiar (amostra com 27 ± 18 anos, 52% homens, 76% brancos), 64% foram investigados por crise de hipertermia maligna anestésica, com mortalidade de 25%. Sinais mais comuns da crise de hipertermia maligna foram hipertermia, taquicardia e rigidez muscular. Suscetibilidade à hipertermia maligna foi confirmada em 79,4% dos 92 parentes investigados com teste de contratura muscular in vitro. Conclusão: Crises de hipertermia maligna assemelharam-se às descritas em outros países, porém com frequência inferior à estimada no país.

Molecular dynamics simulation study of the effect of halothane on mixed DPPC/DPPE phospholipid membranes.

We report results of a molecular dynamics simulation study of the effect of one general anesthetic, halothane, on some properties of mixed DPPC/DPPE phospholipid membranes. This is a suitable model for the study of simple, two-phospholipid membrane systems. From the simulation runs, we determined several membrane properties for five different molecular proportions of DPPC/DPPE. The effect of halothane on the studied membrane properties (area per lipid molecule, density of membrane, order parameter, etc.) was rather small. The distribution of halothane is not uniform through the bilayer thickness. Instead, there is a maximum of anesthetic concentration around 1.2 nm from the center of the membrane. The anesthetic molecule is located close to the phospholipid headgroups. The position of the halothane density maximum depends slightly on the DPPC/DPPE molar proportion. Snapshots taken over the plane of the membrane, as well as calculated two-dimensional radial distribution functions show that the anesthetic has no preference for either phospholipid (DPPC or DPPE). Our results indicate that this anesthetic molecule has only small effects on DPPC/DPPE mixed membranes. In addition, halothane displays no preferential location around DPPC or DPPE. This is probably due to the hydrophobic nature of halothane and to the fact that the chosen phospholipids have the same hydrophobic tails.

Experimental assessment of a myocyte-based multiscale model of cardiac contractile dysfunction.

Cardiac contractile dysfunction (CD) is a multifactorial syndrome caused by different acute or progressive diseases which hamper assessing the role of the underlying mechanisms characterizing a defined pathological condition. Mathematical modeling can help to understand the processes involved in CD and analyze their relative impact in the overall response. The aim of this study was thus to use a myocyte-based multiscale model of the circulatory system to simulate the effects of halothane, a volatile anesthetic which at high doses elicits significant acute CD both in isolated myocytes and intact animals. Ventricular chambers built using a human myocyte model were incorporated into a whole circulatory system represented by resistances and capacitances. Halothane-induced decreased sarco(endo)plasmic reticulum Ca2+ (SERCA2a) reuptake pump, transient outward K+ (Ito), Na+-Ca2+ exchanger (INCX) and L-type Ca2+ channel (ICaL) currents, together with ryanodine receptor (RyR2) increased open probability (Po) and reduced myofilament Ca2+ sensitivity, reproduced equivalent decreased action potential duration at 90% repolarization and intracellular Ca2+ concentration at the myocyte level reported in the literature. In the whole circulatory system, model reduction in mean arterial pressure, cardiac output and regional wall thickening fraction was similar to experimental results in open-chest sheep subjected to acute halothane overdose. Effective model performance indicates that the model structure could be used to study other changes in myocyte targets eliciting CD.

Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy / Reação atípica à anestesia em distrofia muscular de Duchenne/Becker

Abstract Background and objectives Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Case report Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040 IU.L-1 (normal 174 IU.L-1). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. Conclusion On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia.

Resumo Justificativa/objetivos Distrofia muscular de Duchenne/Becker afeta a musculatura esquelética e leva a fraqueza muscular progressiva e risco de reações atípicas anestésicas após exposição à succinilcolina ou halogenados. O objetivo do presente relato é descrever investigação e diagnóstico de paciente com distrofia muscular de Becker e revisar os cuidados necessários na anestesia. Relato de caso Paciente masculino, 14 anos, encaminhado por hiperCKemia (aumento crônico dos níveis séricos de creatinoquinase - CK), com valores de CK de 7.779-29.040 UI.L-1 (normal 174 UI.L-1). Apresentou discreto atraso da aquisição de marcos motores (sentou aos nove meses, andou aos 18). Antecedente de transplante hepático. No exame neurológico apresentava dificuldade para andar nos calcanhares, levantar miopático (apoiava mãos nas coxas para ficar de pé), palato arqueado alto, hipertrofia de panturrilhas, escápulas aladas, hipotonia muscular global e arreflexia. Havia insuficiência respiratória restritiva leve na espirometria (capacidade vital forçada: 77% do previsto). O teste de contratura muscular in vitro em resposta ao halotano e à cafeína foi normal. Estudo da distrofina muscular por técnica de Western blot mostrou redução da distrofina (20% do normal) para ambos os anticorpos (C e N-terminal), e permitiu o diagnóstico de distrofia muscular de Becker. Conclusão Na avaliação pré-anestésica, história de atraso do desenvolvimento motor, bem como sinais clínicos e/ou laboratoriais de miopatia, deve motivar avaliação neurológica, com o objetivo de diagnosticar miopatias subclínicas e planejar cuidados necessários para prevenir complicações anestésicas. Distrofia muscular de Duchenne/Becker, apesar de não conferir suscetibilidade aumentada à HM, pode levar a reações atípicas fatais na anestesia.

Tiopental altera a resposta nociceptiva de ratos jovens em longo prazo / Thiopental alters long term nociceptive response of young rats

The objective of this study was to evaluate the long term nociceptive response determined by use of two general anesthetics, one intravenous and the other inhalatory, in young animals. In the first experiment, the animals of 21 days of age were divided into control (saline) and thiopental (35 mg/kg, i.p.) groups. In the second experiment, rats of the same age were divided in two groups ­ halothane (2%) and control. In experiment 1, there was difference between groups ­ reduction of tail-flick latency in the group thiopental (P< 0.05). In experiment 2, there were no differences between groups or interaction between time versus group (F(1,19)=0.11 for groups, P>0.05; F(1,19)=0.032 for the interaction, P>0.05). The results obtained in this study showed that halothane did not alter the nociceptive response in young animals. However, the thiopental induced hyperalgesic response in rats. (AU)

O objetivo desse estudo foi avaliar a resposta nociceptiva a longo prazo relacionada ao uso de dois anestésicos gerais ­ um intravenoso e outro inalatório, em animais jovens. No primeiro experimento, os animais de 21 dias de idade foram divididos nos grupos controle (solução salina) e tiopental sódico (35 mg/kg, i.p.). No segundo experimento, animais de mesma idade foram divididos em dois grupos ­ halotano (2%) e controle. No Experimento 1, houve redução da latência de retirada da cauda no grupo tiopental (P<0,05). No Experimento 2, não houve diferença entre os grupos ou interação entre grupo x tempo (F(1,19)=0,11 para grupos, P>0,05; F(1,19)=0,032 para a interação, P>0,05). Os resultados obtidos nesse estudo demonstraram que o halotano não altera a resposta nociceptiva em animais jovens. Entretanto, o tiopental induziu resposta hiperalgésica nestes ratos.(AU)

Effects of exposure to halothane, isoflurane, and sevoflurane on embryo viability and gestation in female mice / Efeitos da exposição ao halotano, isofluorano, e sevofluorano na viabilidade embrionária e gestação em fêmeas de camundongos

Although the negative effects of inhalation anaesthetics on fertility have been known for a while, the stages during the reproductive cycle at which these effects occur and the mechanisms of action are largely unknown. This study aimed to evaluate the effects of acute exposure of female mice to halothane, isoflurane, and sevoflurane prior to mating. BALB/c female mice (n=160) were allocated in groups of 20 to halothane (HG), isoflurane (IG), sevoflurane (SG), and oxygen/sham (SH) treatment groups and their respective control groups (CGs). The mice were exposed to 1 minimum alveolar concentration (MAC) of the corresponding anaesthetic or oxygen for 4 h/day over 5 consecutive days. Two days after exposure, females were mated with males (ratio 2:1 female/male) for five consecutive days. Every morning, females were checked for the presence of vaginal plugs. Half of the females that exhibited plugs were euthanised 72 h later for embryo evaluation. The remaining females were euthanised on the 14th day of pregnancy for foetal evaluation. A low number of morulae and total embryos (morulae + blastocysts) were observed in the HG (P 0.05). The number of implantations was lower in the HG (6.0) compared with the IG (11.8) and SG (12.4) (P 0.05). Exposure to halothane is not recommended for use in female mice prior to mating procedures because it leads to decreased embryo production...(AU)

Embora os efeitos negativos dos anestésicos inalatórios na fertilidade já foram descritos há algum tempo, os estágios durante o ciclo reprodutivo em que estes efeitos ocorrem bem como os mecanismos de ação ainda permanecem desconhecidos. Os objetivos deste estudo foram avaliar os efeitos da exposição aguda em fêmeas de camundongos ao halotano, isofluorano, e sevofluorano prévio ao acasalamento. Fêmeas de camundongos BALB/c (n=160) foram alocadas em grupos de 20 aos tratamentos halotano (HG), isofluorano (IG), sevofluorano (SG), oxigênio (SH), e seus respectivos grupos controle (CGs). As fêmeas de camundongos foram expostas a uma concentração alveolar mínima (CAM) do anestésico correspondente ou a oxigênio por 4 horas diárias durante 5 dias consecutivos. Após dois dias do fim da exposição às fêmeas foram acasaladas com os machos (proporção 2:1 fêmea/macho) durante 5 dias consecutivos. A cada manhã, as fêmeas foram avaliadas para a observação da presença de plug vaginal. Metade das fêmeas que exibiam plug foram submetidas à eutanásia após 72 horas para avaliação embrionária. As fêmeas restantes foram eutanasiadas no 14º dia de gestação para avaliação fetal. No HG foi observado um menor número de mórulas e embriões totais (mórulas + blastocistos) (P 0,05). O número de implantações foi menor no HG (6,0) comparado ao IG (11,8) e SG (12,4) (P 0,05). A exposição ao halotano não...(AU)

Juan César García: social medicine as project and endeavor / Juan César García: a medicina social como projeto e realização

This paper analyses some aspects of the trajectory of the Argentinian physician and sociologist Juan César García (1932-1984) in the field of Latin American Social Medicine. Three dimensions constituting his basic orientations are highlighted: the elaboration of systematic and reflective social thought; a critical attitude in questioning teaching and professional practices; a commitment to the institutionalization and dissemination of health knowledge.

O artigo analisa aspectos da trajetória de Juan César García (1932-1984), médico e sociólogo argentino, no campo da medicina social latino-americana. Destaca três dimensões que constituem as suas orientações básicas no campo da saúde: a elaboração de um pensamento sobre o social, sistemático e reflexivo; uma atitude crítica na problematização do ensino e das práticas profissionais; um compromisso com a institucionalização e divulgação do saber sanitário.

Effects of exposure to halothane, isoflurane, and sevoflurane on embryo viability and gestation in female mice / Efeitos da exposição ao halotano, isofluorano, e sevofluorano na viabilidade embrionária e gestação em fêmeas de camundongos

Although the negative effects of inhalation anaesthetics on fertility have been known for a while, the stages during the reproductive cycle at which these effects occur and the mechanisms of action are largely unknown. This study aimed to evaluate the effects of acute exposure of female mice to halothane, isoflurane, and sevoflurane prior to mating. BALB/c female mice (n=160) were allocated in groups of 20 to halothane (HG), isoflurane (IG), sevoflurane (SG), and oxygen/sham (SH) treatment groups and their respective control groups (CGs). The mice were exposed to 1 minimum alveolar concentration (MAC) of the corresponding anaesthetic or oxygen for 4 h/day over 5 consecutive days. Two days after exposure, females were mated with males (ratio 2:1 female/male) for five consecutive days. Every morning, females were checked for the presence of vaginal plugs. Half of the females that exhibited plugs were euthanised 72 h later for embryo evaluation. The remaining females were euthanised on the 14th day of pregnancy for foetal evaluation. A low number of morulae and total embryos (morulae + blastocysts) were observed in the HG (P 0.05). The number of implantations was lower in the HG (6.0) compared with the IG (11.8) and SG (12.4) (P 0.05). Exposure to halothane is not recommended for use in female mice prior to mating procedures because it leads to decreased embryo production...

Embora os efeitos negativos dos anestésicos inalatórios na fertilidade já foram descritos há algum tempo, os estágios durante o ciclo reprodutivo em que estes efeitos ocorrem bem como os mecanismos de ação ainda permanecem desconhecidos. Os objetivos deste estudo foram avaliar os efeitos da exposição aguda em fêmeas de camundongos ao halotano, isofluorano, e sevofluorano prévio ao acasalamento. Fêmeas de camundongos BALB/c (n=160) foram alocadas em grupos de 20 aos tratamentos halotano (HG), isofluorano (IG), sevofluorano (SG), oxigênio (SH), e seus respectivos grupos controle (CGs). As fêmeas de camundongos foram expostas a uma concentração alveolar mínima (CAM) do anestésico correspondente ou a oxigênio por 4 horas diárias durante 5 dias consecutivos. Após dois dias do fim da exposição às fêmeas foram acasaladas com os machos (proporção 2:1 fêmea/macho) durante 5 dias consecutivos. A cada manhã, as fêmeas foram avaliadas para a observação da presença de plug vaginal. Metade das fêmeas que exibiam plug foram submetidas à eutanásia após 72 horas para avaliação embrionária. As fêmeas restantes foram eutanasiadas no 14º dia de gestação para avaliação fetal. No HG foi observado um menor número de mórulas e embriões totais (mórulas + blastocistos) (P 0,05). O número de implantações foi menor no HG (6,0) comparado ao IG (11,8) e SG (12,4) (P 0,05). A exposição ao halotano não...

Modelagem hierárquica Bayesiana na avaliação de curvas de crescimento de suínos genotipados para o gene halotano / Hierarchical Bayesian modeling for the evaluation of growth curves of pigs genotyped for the halothane gene

Para avaliar a influência do gene halotano sobre a curva de crescimento de suínos, bem como sua interação com o sexo do animal, foi proposta uma modelagem hierárquica Bayesiana. Nesta abordagem, os parâmetros dos modelos não-lineares de crescimento (Logístico, Gompertz e von Bertalanffy) foram estimados conjuntamente com os efeitos de sexo e genótipos do gene halotano. Foram utilizados 344 animais F2(Comercial x Piau) pesados ao nascer, aos 21, 42, 63, 77, 105 e 150 dias. O modelo Logístico foi aquele que apresentou melhor qualidade de ajuste por apresentar menor DIC (Deviance Information Criterion) que os demais. As amostras das distribuições marginais a posteriori para as diferenças entre as estimativas dos parâmetros do modelo Logístico indicaram que o peso dos machos à idade adulta com genótipo heterozigoto (HalNn) foi superior ao dos homozigotos (HalNN). A título de comparação, também foi considerada a abordagem frequentista tradicional, baseada em dois passos distintos, a qual, por apresentar um menor poder de discernimento estatístico, não mostrou diferenças significativas.(AU)

A hierarchical Bayesian modeling was used to evaluate the influence of halothane gene and its interaction with sex on pig´s growth curves. Under this approach, the parameters from growth models (Logistic, Gompertz and von Bertalanffy) were estimated jointly with the effects of halothane gene and sex. A total of 344 F2 (Commercial x Piau) animals were weighted at birth, 21, 42, 63, 77, 105 and 150 days in life. The Logistic model has presented the best fit based on DIC (Deviance Information Criterion). Thus, the samples from marginal posterior distributions for the differences between the parameters estimates of Logistic model have indicated that the maturity weight of males with heterozygous genotypes (HalNn) was superior to males with homozygous genotypes (HalNN). In order to realize a comparison with the traditional methodology, the frequentist approach based on two distinct steps also was used, but there was not identified significant differences between growth curve parameter estimates from each group (combinations of halothane genotypes and sex).(AU)

Effect of the halothane genotype on intramuscular fat deposition in swine.

Intramuscular fat (IMF) content has been identified as an important factor in determining the quality of pork. Previous studies have suggested that IMF deposition may be associated with the presence of the halothane (HAL) gene. This study aimed to evaluate the effect of the HAL gene on IMF deposition in crossbred pigs of commercial lines, which were killed at a slaughterhouse under official inspection. The genotype of the HAL gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. IMF was analyzed from longissimus dorsi samples. Among all animals analyzed, 42.36% were of the HalNN genotype and 57.64% were of the HalNn genotype. The average IMF content of all samples was 2.14%. Variation in IMF between genotypes was evaluated by analysis of variance. No significant difference in IMF deposition, which could be based on the presence of the halothane allele, was observed, at least in heterozygotes.

The effects of volatile anesthetics on the extracellular accumulation of [(3)H]GABA in rat brain cortical slices.

GABA is an inhibitory neurotransmitter that appears to be associated with the action of volatile anesthetics. These anesthetics potentiate GABA-induced postsynaptic currents by synaptic GABAA receptors, although recent evidence suggests that these agents also significantly affect extrasynaptic GABA receptors. However, the effect of volatile anesthetics on the extracellular concentration of GABA in the central nervous system has not been fully established. In the present study, rat brain cortical slices loaded with [(3)H]GABA were used to investigate the effect of halothane and sevoflurane on the extracellular accumulation of this neurotransmitter. The accumulation of [(3)H]GABA was significantly increased by sevoflurane (0.058, 0.11, 0.23, 0.46, and 0.93 mM) and halothane (0.006, 0.012, 0.024, 0.048, 0072, and 0.096 mM) with an EC50 of 0.26 mM and 35 µM, respectively. TTX (blocker of voltage-dependent Na(+) channels), EGTA (an extracellular Ca(2+) chelator) and BAPTA-AM (an intracellular Ca(2+) chelator) did not interfere with the accumulation of [(3)H]GABA induced by 0.23 mM sevoflurane and 0.048 mM halothane. SKF 89976A, a GABA transporter type 1 (GAT-1) inhibitor, reduced the sevoflurane- and halothane-induced increase in the accumulation of GABA by 57 and 63 %, respectively. Incubation of brain cortical slices at low temperature (17 °C), a condition that inhibits GAT function and reduces GABA release through reverse transport, reduced the sevoflurane- and halothane-induced increase in the accumulation of [(3)H]GABA by 82 and 75 %, respectively, relative to that at normal temperature (37 °C). Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce GABA release through reverse transport, abolished the sevoflurane and halothane effects on the accumulation of [(3)H]GABA. The effect of sevoflurane and halothane did not involve glial transporters because ß-alanine, a blocker of GAT-2 and GAT-3, did not inhibit the effect of the anesthetics. In conclusion, the present study suggests that sevoflurane and halothane increase the accumulation of GABA by inducing the reverse transport of this neurotransmitter. Therefore, volatile anesthetics could interfere with neuronal excitability by increasing the action of GABA on synaptic and extrasynaptic GABA receptors.