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Introdução: O prognóstico da parada cardiorrespiratória (PCR) em ritmo não chocável (assistolia/atividade elétrica sem pulso) é ruim e não melhorou significativamente nas últimas décadas. Embora a epinefrina seja o vasopressor recomendado, há evidências de que ela eleva o consumo de oxigênio, reduz a pressão de perfusão subendocárdica, causa grave disfunção miocárdica e piora a microcirculação cerebral durante a ressuscitação cardiopulmonar. Vasopressina foi muito estudada nos últimos anos e não se mostrou superior à epinefrina. Naloxona e terlipressina têm sido cogitadas como potenciais vasopressores no tratamento da PCR, entretanto há poucos estudos publicados e os resultados são controversos e inconclusivos. Objetivos: Avaliar os efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na PCR induzida por hipóxia e compará-las com o tratamento-padrão (epinefrina ou vasopressina). Métodos: Estudo experimental, randomizado, cego e controlado. Ratos Wistar adultos, machos, foram anestesiados, submetidos a traqueostomia e ventilados mecanicamente. A PCR foi induzida por obstrução da traqueia e mantida por 3,5 minutos. Em seguida, os animais foram ressuscitados de forma padronizada e randomizados em um dos grupos: placebo (n = 7), vasopressina (n = 7), epinefrina (n = 7), naloxona (n = 7) ou terlipressina (n = 21). Variáveis hemodinâmicas foram monitorizadas durante todo o experimento (via cateter intra-arterial e intraventricular) e mensuradas na base, no 10o (T10), 20o (T20), 30o (T30), 45o (T45) e 60o (T60) minutos pós-PCR. Amostras de sangue arterial foram coletadas para gasometria, hemoglobina, bioquímica e lactato em quatro momentos [base, 11o (T11), 31o (T31), e 59o (T59) minutos pós-PCR]. Resultados: Os grupos foram homogêneos e não houve diferença significativa entre eles nas variáveis de base. O retorno da circulação espontânea ocorreu em 57% dos animais no grupo placebo (4 de 7) e 100% nos demais grupos (p = 0,002). A ! sobrevida em 1 hora foi de 57% no grupo placebo, 71,4% no grupo epinefrina, 90,5% no grupo terlipressina e de 100% nos demais grupos. Comparado com o grupo epinefrina, o grupo terlipressina teve maiores valores de PAM no T10 (164 vs 111 mmHg; p = 0,02), T20 (157 vs 97 mmHg; p < 0,0001), T30 (140 vs 67 mmHg; p < 0,0001), T45 (117 vs 67 mmHg; p = 0,002) e T60 (98 vs 62 mmHg; p = 0,026). O lactato arterial no grupo naloxona foi significativamente menor quando comparado ao grupo epinefrina, no T11 (5,15 vs 8,82 mmol/L), T31 (2,57 vs 5,24 mmol/L) e T59 (2,1 vs 4,1 mmol/L)[p = 0,002]. Ao longo da 1a hora pós-PCR, o grupo naloxona apresentou o melhor perfil do excesso de bases (-7,78 mmol/L) quando comparado ao grupo epinefrina (-12,78 mmol/L; p = 0,014) e ao grupo terlipressina (-11,31 mmol/L; p = 0,024). Conclusões: Neste modelo de PCR induzida por hipóxia em ratos, terlipressina e naloxona foram eficazes como vasopressores na RCP e apresentaram melhor perfil metabólico que a epinefrina. A terlipressina resultou em uma maior estabilidade hemodinâmica na 1a hora pós-PCR comparada com a epinefrina ou a vasopressina. Os efeitos metabólicos favoráveis da naloxona não são explicados pelos valores da PAM / Introduction: The prognosis of cardiac arrest (CA) with nonshockable rhythm (asystole/pulseless electrical activity) is poor and not improved significantly in recent decades. Epinephrine is the most commonly used vasopressor, although there is evidence that its use correlates with myocardial dysfunction and worsens the cerebral microcirculation. Vasopressin has been widely studied in recent years and was not superior to epinephrine. Naloxone and terlipressin have been considered as potential vasopressors in the treatment of CA, however, there are few published studies and the results are controversial and inconclusive. Objectives: To evaluate the hemodynamic and metabolic effects of terlipressin or naloxone in CA induced by hypoxia and compare with standard treatment with epinephrine or vasopressin. Methods: Experimental, randomized, blinded and controlled trial. Adult male Wistar rats were anesthetized, the proximal trachea was surgically exposed, and a 14-gauge cannula was inserted 10 mm into the trachea to the larynx. They were mechanically ventilated and monitored. The CA was induced by tracheal obstruction and maintained for 3.5 minutes. Subsequently, the animals were resuscitated using standard maneuvers and randomized to one of groups: placebo (n=7), vasopressin (n=7), epinephrine (n=7), naloxone (n=7) or terlipressin (n=21). Hemodynamic variables were monitored throughout the study (intra-arterial and intra-ventricular catheter) and measured at baseline, in the 10th (T10), 20th (T20), 30th (T30), 45th (T45) and 60th (T60) minute post-cardiac arrest. Arterial blood samples were collected for hemoglobin, biochemistry, blood gases and lactate at four moments: baseline, 11th (T11), 31st (T31) and 59th (T59) minute post-cardiac arrest. Results: The groups were homogenous and there were no significant differences among them regarding the baseline variables. The return of spontaneous circulation (ROSC) occurred in 57% of the animals (4 of 7) in the placebo group and in 100% in the ! other groups (P=0.002). One-hour survival was 57% in the placebo group, 71.4% in the epinephrine group, 90.5% in the terlipressin and 100% in the naloxone group. Compared with the epinephrine group, the terlipressin groups had a significantly higher MAP at the T10 (164 x 111 mmHg; P=0.02), T20 (157 x 97 mmHg; P<0.0001), T30 (140 x 67 mmHg; P=0.0001), T45 (117 x 67 mmHg; P=0.002) and T60 (98 x 62 mmHg; P= 0.026). The blood lactate in naloxone group was significantly lower when compared to epinephrine group in the T11 (5.15 x 8.82 mmol/L), T31 (2.57 x 5.24 mmol/L) and T59 (2.1 x 4.1)[P=0.002]. Along the first hour after cardiac arrest, the naloxone group showed the best profile of base excess (- 7.78 mmol/L) when compared to epinephrine (-12.78 mmol/L, P= 0.014) and terlipressin group (-11.31 mmol/L, P=0.024). Conclusions: In this model of CA induced by hypoxia in rats, terlipressin and naloxone were effective as vasopressors in resuscitation and had better metabolic profile compared to epinephrine. Terlipressin resulted in higher hemodynamic stability in the first hour after CA and significantly better than epinephrine or vasopressin. The favorable metabolic effects of naloxone are not explained by the values of MAP

INTRODUÇÃO: A segurança da administração de anestésicos locais com vasoconstritor em pacientes diabéticos submetidos à cirurgia oral não está bem fundamentada na literatura. OBJETIVO: Investigar a ocorrência de variação da glicemia nos períodos pré, trans e pós-operatório de exodontia de dentes superiores, sob anestesia local com lidocaína 2% sem e com adrenalina 1:100.000, em portadores de diabetes mellitus tipo 2. Secundariamente, avaliar os efeitos hemodinâmicos e o grau de ansiedade. MÉTODOS: Estudo prospectivo e randomizado com pacientes portadores de diabetes acompanhados na Unidade Clinica de Coronariopatia Crônica do Instituto do Coração do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo. A monitorização contínua da glicemia durante 24 horas foi realizada através do MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic). Os pacientes foram divididos em dois grupos: LSA - que recebeu 5,4 mL lidocaína 2% sem adrenalina e LCA - que recebeu 5,4 mL de lidocaína 2% com adrenalina 1:100.000. Os níveis de glicemia foram avaliados nas 24 horas (período basal) e nos tempos determinados: uma hora antes, durantes e até uma hora após a exodontia (período de procedimento). Os parâmetros hemodinâmicos foram avaliados por meio de um medidor de pressão arterial digital automático e o nível de ansiedade através de uma escala. RESULTADOS: Dos 400 pacientes avaliados, 70 foram incluídos no estudo, sendo 35 randomizados no grupo LSA e 35 no grupo LCA. A análise das médias da glicemia nos grupos LSA e LCA durante os períodos (basal e procedimento) não demonstrou diferença estatisticamente significativa (p=0,229 e p=0,811, respectivamente). Também não houve diferença significativa (p=0,748) na glicemia entre os grupos em cada tempo avaliado. Entretanto, nos dois grupos houve decréscimo significativo da glicemia (p < 0,001) ao longo dos tempos avaliados. Os grupos LSA e LCA não apresentaram diferenças significativas em relação à PAS (p=0,176), à PAD (p=0,913), à FC (p=0,570) e ao nível de ansiedade. CONCLUSÃO: A administração de 5,4mL de lidocaína 2% com adrenalina 1:100.000 não provocou alteração significativa da glicemia, parâmetros hemodinâmicos e nível de ansiedade em relação ao grupo sem vasoconstritor / INTRODUCTION: The safety of administration of local anesthetics with epinephrine for diabetic patients undergoing oral surgery is not well grounded in the literature. OBJECTIVE: To investigate the occurrence of variation of glucose in the pre, intra and postoperative extraction of upper teeth under local anesthesia with lidocaine 2% with and without 1:100.000 epinephrine in patients with type 2 diabetes mellitus. Secondly, to evaluate the hemodynamic effects and degree of anxiety. METHODS: A prospective randomized study of patients with diabetes attended in Coronary Chronic Clinics Unit, Heart Institute, Hospital das Clinicas in University of São Paulo Medical School. Continuous monitoring of blood glucose for 24 hours was performed using MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic) and the patients were divided into two groups: LSA - which received 5.4 mL of 2% lidocaine without epinephrine and LCA - which received 5.4 mL of 2% lidocaine with 1:100,000 epinephrine. Blood glucose levels were assessed at 24 hours (baseline period) and at certain times: one hour before, during, and up to one hour after oral surgery (procedure period). We evaluated the hemodynamic parameters through a digital automatic pressure meter and anxiety level was measured by the scale. RESULTS: Of 400 patients evaluated, 70 were included in these study, 35 were randomized in the LSA group and 35 in the group LCA. The analysis of mean glicemia in groups LSA and LCA during the baseline period and procedure showed no statistically significant difference (p = 0.229 and p = 0.811, respectively). There was no difference in blood glucose (p = 0.748) between the groups at each time evaluated. However, in both groups there was a significant decrease in blood glucose (p < 0.001) over the time periods studied. The groups showed no significant differences regarding SBP (p = 0.176), DBP (p = 0.913), HR (p = 0.570) and anxiety level. CONCLUSION: The administration of 5.4 mL of 2% lidocaine with epinephrine 1:100.000 caused no significant change in blood glucose, hemodynamic parameters and level of anxiety compared to the group without vasoconstrictor

Estudamos 62 pacientes, que com teste ergométrico positivo, manifestaram angina estável e estavam sob controle farmacológico. Todos apresentavam cinecoronariografia mostrando obstrução >70% em pelo menos uma das principais artérias coronárias. Objetivamos avaliar parâmetros eletrocardiográficos e de pressão arterial, durante procedimento odontológico restaurador sob anestesia local com e sem vasoconstritor em presença de doença arterial coronária. As idades variaram de 39 a 80, média de 58,7±8,8 anos, sendo 51 (82,3%) homens. Trinta pacientes foram randomizados para receber anestesia local com solução de lidocaína a 2% com adrenalina 1:100.000 e os demais para lidocaína a 2% sem vasoconstritor. Todos os pacientes foram submetidos à monitorização ambulatorial da pressão arterial (MAPA) e eletrocardiografia dinâmica por 24 horas, iniciados 2 horas antes do procedimento odontológico. Consideramos 3 períodos de registro: (1) basal - os 60 minutos que antecederam ao procedimento odontológico; (2) procedimento - desde o início da anestesia até o final do procedimento odontológico restaurador; (3) subseqüente completar das 24 horas. A análise de variância com medidas repetidas mostrou que houve elevação significativa da pressão arterial sistólica e diastólica do período basal para o procedimento nos dois grupos estudados (aproximadamente 14mmHg e 5 a 7mmHg) respectivamente, quando analisados separadamente e quando confrontados não apresentaram diferença de comportamento entre si. A freqüência cardíaca não se alterou nos dois grupos estudados. Depressão do segmento ST >1mm ocorreu em 10 (17,9%) pacientes; todos os eventos ocorreram no mínimo 2 horas após o término do procedimento odontológico. Extra - sístoles supra-ventriculares e/ou extra-sístoles ventriculares em número maior do que 10/hora estiveram presentes em 17 (30,4%) pacientes durante as 24 horas e durante o período do procedimento em 7 (12,5%), sendo 4 (13,8%) do grupo que recebeu anestesia sem adrenalina e 3 (11,1%) do grupo que recebeu anestesia com adrenalina e o teste Exato de Fisher não mostrou diferença entre os grupos. Concluímos que não houve diferença em relação ao comportamento de pressão arterial, freqüência cardíaca, evidência de isquemia e arritmias entre os grupos. O uso associado de vasoconstritor mostrou-se, portanto, seguro dentro dos limites do estudo. / We enrolled 62 patients with positive exercise stress test who presented with stable angina and were receiving drug therapy. All had a coronary angiography screening showing >70% obstruction in at least one of the main coronary arteries. The study aimed to compare electrocardiographic and blood pressure parameters during restorative dentistry procedure under local anesthesia, both with and without vasoconstrictor, in the presence of coronary artery disease. Ages ranged from 39 to 80, (mean ± SD) 58.7±8.8 years, 51 (82.3%) of them were male. Thirty patients were randomly assigned to receive 2% lidocaine local anesthesia with 1:100,000 epinephrine, the others receiving 2% lidocaine without vasoconstrictor. All the patients underwent ambulatory blood pressure and 24-hour Holter monitoring, beginning two hours ahead of the dental procedure. Recording were made during (1) baseline - 60-minute period before dental procedure began; (2) procedure - from beginning of anesthesia until the end of the procedure; and (3) subsequent 24-hour period. Analysis of variance with repeat measures showed significant diastolic and systolic blood pressure increases from baseline to the period of the procedure, in the two study groups (approximately 14 mm Hg, and 5 to 7 mm Hg, respectively); both in a separate analysis and in a comparative analysis no significant difference between them could be confirmed. Heart rate did not change in neither of the two groups. ST-segment >1 mm depression was detected in 10 (17.9%) patients; all these events occurred at least two hours after the end of the dentistry procedure. Premature supraventricular systoles and/or premature ventricular systoles in a greater number than 10/hour were seen in 17 (30.4%) patients in the 24-hours period after the procedure; during the procedure they occurred in 7 (12.5%) patients, of whom 4 (13.8%) were in the group without, and 3 (11.1%) in the group with vasoconstrictor. The Fisher\'s exact test revealed no difference between the groups. We concluded that there was no difference of blood pressure, heart rate, evidence of ischemia or arrhythmia episodes between the groups. Thus, the associated use of vasoconstrictor proved to be safe within the limits of this study

Made available in DSpace on 2014-07-29T15:25:14Z (GMT). No. of bitstreams: 1 Tese de doutorado Luiza Cristina Lacerda Jacomini.pdf: 1113139 bytes, checksum: 6f7dbdd64a41cff3100ce05df4ddcf61 (MD5) Previous issue date: 2010-08-05 / Lacerda Jacomini, LC. Investigation on dysautonomia, epinephrine and norepinephrine-evoked pain, and effect of beta-blocker in fibromyalgia and systemic lupus erythematosus. 2010, 169 p. Doctoral thesis - Universidade Federal de Goiás, Goiânia. Dysautonomia is a condition in which an altered autonomic function affects the health in an adverse way. The present study aims: to search for the presence of epinephrine and norepinephrine-evoked pain; to evaluate the cardiovascular autonomic function and the effect of propranolol in women with fibromyalgia (FM), systemic lupus erythematosus (SLE) and controls (CTR). For each objective a separate research was developed, including a clinical trial. Epinephrine and norepinephrine-evoked pain were diagnosed when the subcutaneous injections containing these substances (10 micrograms/ 0.1 mL saline solution) induced greater pain than the saline solution did (n=7). Autonomic function was assessed through the standard Ewing tests battery, through heart rate responses to Valsalva maneuver, deep breathing, standing and blood pressure responses to ortostatism and to hand grip (n=7). Functional symptoms related to autonomic manifestations were checked. In a randomized, double-blind, placebo-controlled, crossover clinical trial with 6 women with FM, SLE and CTR, propranolol (80 mg/day po/4 weeks) was added to the usual schedule of prescribed medicines and its effect was examined regarding: pain, fatigue, tender points, blood pressure, heart rate, health related quality of life (SF-36) and fibromyalgia impact questionnaire. Epinephrine-evoked pain was diagnosed in SLE and FM groups and norepinephrine-evoked pain was diagnosed in FM group. Epinephrine and norepinephrine-evoked pain intensity has a trend to be greater in FM patients when compared to healthy CTR. FM and SLE patients had an elevated number of functional symptoms related to autonomic manifestations. Cardiovascular autonomic function was altered in FM and SLE groups. Parasympathetic cardiovascular autonomic function tests were mainly abnormal in SLE patients while in FM patients both, parasympathetic and sympathetic tests were abnormal. Propranolol reduced tender points count and the number of symptoms related to autonomic manifestations in FM group. Four in six patients presented significant improvement in health related quality of life evaluated by SF-36. These results suggest that FM belong to the group of sympathetically maintained pain syndromes. The study demonstrates that FM and SLE patients have cardiovascular autonomic function alterations which can be detected by simple, standardized, non-invasive and inexpensively methodology and that propranolol has a potential benefit in FM treatment. / Lacerda Jacomini, LC. Pesquisa de disautonomia, dor evocada por adrenalina e noradrenalina e efeito de beta-bloqueador na fibromialgia e no lupus eritematoso sistêmico. 2010, 169 p. Tese de doutorado - Universidade Federal de Goiás, Goiânia. Disautonomia é uma condição na qual a função autonômica alterada afeta a saúde de modo adverso. Os objetivos do presente estudo foram: pesquisar a presença de dor evocada por adrenalina (AD) e por noradrenalina (NA), avaliar a função autonômica cardiovascular e o efeito do propranolol, em mulheres com fibromialgia (FM), lupus eritematoso sistêmico (LES) e controles (CTR). Para cada objetivo foi desenvolvida uma etapa de estudo, sendo incluído um ensaio clínico. A dor evocada por AD ou NA foi diagnosticada quando estas substâncias produziram dor maior que soro fisiológico quando injetadas (10 microgramas/ 0,1 mL de soro fisiológico), via subcutânea (n=7). A função autonômica foi testada usando-se a bateria de testes de Ewing (respostas da frequência cardíaca à manobra de Valsalva, respiração profunda e ao ortostatismo e respostas da pressão arterial ao ortostatismo e à preensão sustentada) (n=7). Foram pesquisados sintomas funcionais relacionados às manifestações autonômicas. No ensaio-clínico randomizado, duplo-cego, placebo controlado e cruzado em grupos de 6 mulheres com LES, FM e CTR, o propranolol (80 mg/dia, via oral/4 semanas) foi adicionado ao esquema terapêutico das pacientes e seu efeito avaliado segundo as variáveis: dor, fadiga, tender points, pressão arterial, frequência cardíaca, qualidade de vida e questionário do impacto da FM. A dor evocada por AD ocorreu nos grupos FM e LES comparada ao CTR e, por NA ocorreu no grupo FM. Os escores de dor evocada por AD e por NA, no grupo FM, tiveram uma tendência a serem maiores do que os do grupo CTR. Pacientes com FM e com LES apresentaram elevado número de sintomas funcionais relacionados a manifestações autonômicas. A função autonômica cardiovascular estava alterada no LES e na FM. No grupo LES, os testes de função parassimpática tiveram frequência maior de respostas anormais e no grupo FM estavam alterados tanto os da função parassimpática como da simpática. O propranolol reduziu o número de tender points e de sintomas funcionais relacionados a manifestações autonômicas no grupo FM. Quatro em 6 pacientes do grupo FM apresentaram melhora significativa na qualidade de vida avaliada pelo SF-36. Os resultados sugerem que a FM faz parte do grupo de doenças com dor simpaticamente mantida. O estudo demonstrou que as pacientes com LES e FM têm alterações da função autonômica cardiovascular detectáveis por metodologia simples, padronizada, não invasiva e de baixo custo e que o propranolol tem um benefício potencial no tratamento da FM.

Introdução: O prognóstico da parada cardiorrespiratória (PCR) em ritmo não chocável (assistolia/atividade elétrica sem pulso) é ruim e não melhorou significativamente nas últimas décadas. Embora a epinefrina seja o vasopressor recomendado, há evidências de que ela eleva o consumo de oxigênio, reduz a pressão de perfusão subendocárdica, causa grave disfunção miocárdica e piora a microcirculação cerebral durante a ressuscitação cardiopulmonar. Vasopressina foi muito estudada nos últimos anos e não se mostrou superior à epinefrina. Naloxona e terlipressina têm sido cogitadas como potenciais vasopressores no tratamento da PCR, entretanto há poucos estudos publicados e os resultados são controversos e inconclusivos. Objetivos: Avaliar os efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na PCR induzida por hipóxia e compará-las com o tratamento-padrão (epinefrina ou vasopressina). Métodos: Estudo experimental, randomizado, cego e controlado. Ratos Wistar adultos, machos, foram anestesiados, submetidos a traqueostomia e ventilados mecanicamente. A PCR foi induzida por obstrução da traqueia e mantida por 3,5 minutos. Em seguida, os animais foram ressuscitados de forma padronizada e randomizados em um dos grupos: placebo (n = 7), vasopressina (n = 7), epinefrina (n = 7), naloxona (n = 7) ou terlipressina (n = 21). Variáveis hemodinâmicas foram monitorizadas durante todo o experimento (via cateter intra-arterial e intraventricular) e mensuradas na base, no 10o (T10), 20o (T20), 30o (T30), 45o (T45) e 60o (T60) minutos pós-PCR. Amostras de sangue arterial foram coletadas para gasometria, hemoglobina, bioquímica e lactato em quatro momentos [base, 11o (T11), 31o (T31), e 59o (T59) minutos pós-PCR]. Resultados: Os grupos foram homogêneos e não houve diferença significativa entre eles nas variáveis de base. O retorno da circulação espontânea ocorreu em 57% dos animais no grupo placebo (4 de 7) e 100% nos demais grupos (p = 0,002). A ! sobrevida em 1 hora foi de 57% no grupo placebo, 71,4% no grupo epinefrina, 90,5% no grupo terlipressina e de 100% nos demais grupos. Comparado com o grupo epinefrina, o grupo terlipressina teve maiores valores de PAM no T10 (164 vs 111 mmHg; p = 0,02), T20 (157 vs 97 mmHg; p < 0,0001), T30 (140 vs 67 mmHg; p < 0,0001), T45 (117 vs 67 mmHg; p = 0,002) e T60 (98 vs 62 mmHg; p = 0,026). O lactato arterial no grupo naloxona foi significativamente menor quando comparado ao grupo epinefrina, no T11 (5,15 vs 8,82 mmol/L), T31 (2,57 vs 5,24 mmol/L) e T59 (2,1 vs 4,1 mmol/L)[p = 0,002]. Ao longo da 1a hora pós-PCR, o grupo naloxona apresentou o melhor perfil do excesso de bases (-7,78 mmol/L) quando comparado ao grupo epinefrina (-12,78 mmol/L; p = 0,014) e ao grupo terlipressina (-11,31 mmol/L; p = 0,024). Conclusões: Neste modelo de PCR induzida por hipóxia em ratos, terlipressina e naloxona foram eficazes como vasopressores na RCP e apresentaram melhor perfil metabólico que a epinefrina. A terlipressina resultou em uma maior estabilidade hemodinâmica na 1a hora pós-PCR comparada com a epinefrina ou a vasopressina. Os efeitos metabólicos favoráveis da naloxona não são explicados pelos valores da PAM / Introduction: The prognosis of cardiac arrest (CA) with nonshockable rhythm (asystole/pulseless electrical activity) is poor and not improved significantly in recent decades. Epinephrine is the most commonly used vasopressor, although there is evidence that its use correlates with myocardial dysfunction and worsens the cerebral microcirculation. Vasopressin has been widely studied in recent years and was not superior to epinephrine. Naloxone and terlipressin have been considered as potential vasopressors in the treatment of CA, however, there are few published studies and the results are controversial and inconclusive. Objectives: To evaluate the hemodynamic and metabolic effects of terlipressin or naloxone in CA induced by hypoxia and compare with standard treatment with epinephrine or vasopressin. Methods: Experimental, randomized, blinded and controlled trial. Adult male Wistar rats were anesthetized, the proximal trachea was surgically exposed, and a 14-gauge cannula was inserted 10 mm into the trachea to the larynx. They were mechanically ventilated and monitored. The CA was induced by tracheal obstruction and maintained for 3.5 minutes. Subsequently, the animals were resuscitated using standard maneuvers and randomized to one of groups: placebo (n=7), vasopressin (n=7), epinephrine (n=7), naloxone (n=7) or terlipressin (n=21). Hemodynamic variables were monitored throughout the study (intra-arterial and intra-ventricular catheter) and measured at baseline, in the 10th (T10), 20th (T20), 30th (T30), 45th (T45) and 60th (T60) minute post-cardiac arrest. Arterial blood samples were collected for hemoglobin, biochemistry, blood gases and lactate at four moments: baseline, 11th (T11), 31st (T31) and 59th (T59) minute post-cardiac arrest. Results: The groups were homogenous and there were no significant differences among them regarding the baseline variables. The return of spontaneous circulation (ROSC) occurred in 57% of the animals (4 of 7) in the placebo group and in 100% in the ! other groups (P=0.002). One-hour survival was 57% in the placebo group, 71.4% in the epinephrine group, 90.5% in the terlipressin and 100% in the naloxone group. Compared with the epinephrine group, the terlipressin groups had a significantly higher MAP at the T10 (164 x 111 mmHg; P=0.02), T20 (157 x 97 mmHg; P<0.0001), T30 (140 x 67 mmHg; P=0.0001), T45 (117 x 67 mmHg; P=0.002) and T60 (98 x 62 mmHg; P= 0.026). The blood lactate in naloxone group was significantly lower when compared to epinephrine group in the T11 (5.15 x 8.82 mmol/L), T31 (2.57 x 5.24 mmol/L) and T59 (2.1 x 4.1)[P=0.002]. Along the first hour after cardiac arrest, the naloxone group showed the best profile of base excess (- 7.78 mmol/L) when compared to epinephrine (-12.78 mmol/L, P= 0.014) and terlipressin group (-11.31 mmol/L, P=0.024). Conclusions: In this model of CA induced by hypoxia in rats, terlipressin and naloxone were effective as vasopressors in resuscitation and had better metabolic profile compared to epinephrine. Terlipressin resulted in higher hemodynamic stability in the first hour after CA and significantly better than epinephrine or vasopressin. The favorable metabolic effects of naloxone are not explained by the values of MAP

The primary goal of my thesis research was to characterize the basis for the hypersensitive response of glycogen phosphorylase to catecholamine stimulation in primary culture diabetic cardiomyocytes. Toward this goal, I have investigated several key regulatory sites in this signaling pathway which could promote the hypersensitive activation of phosphorylase. Specifically, I investigated (1) which adrenergic receptors are involved in mediating the hypersensitive response of glycogen phosphorylase to epinephrine stimulation; (2) whether the presence of fatty acid metabolites affects phosphorylase activation; (3) whether the hypersensitive response of phosphorylase results from altered signal transduction through the β-adrenergic receptor system or from a post-receptor defect; and (4) the potential role for phosphorylase kinase in mediating the hypersensitive response of phosphorylase to catecholamine stimulation. The basis for adrenergic receptor mediation of the catecholamine-induced activation of glycogen phosphorylase was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. Cells derived from diabetic animals exhibited a hypersensitive response to epinephrine stimulation which was apparent 3 hours after cell isolation and was further enhanced upon maintenance of the myocytes in culture for 24 hours. Normal cells initially lacked the hypersensitive response to epinephrine stimulation although upon maintenance of these cells in culture for 24 hours, the hypersensitive response was acquired in vitro. To assess alpha- and beta- adrenergic mediation of the response, normal and diabetic cardiomyocytes were incubated with propranolol, a β-receptor antagonist, prior to direct α1receptor stimulation with phenylephrine. Both normal and diabetic myocytes failed to undergo activation of phosphorylase in 3 or 24 hour cell cultures. In addition, the effects of epinephrine on phosphorylase activation were completely inhibited by propranolol whereas prazosin, an α-receptor antagonist, was unsuccessful. This data suggests that the hypersensitive response of glycogen phosphorylase in normal and diabetic cardiomyocytes is solely mediated through β-adrenergic receptor activation. Since the accumulation of various fatty acid metabolites can affect certain enzymes and signal transduction pathways within the cell, the potential effect of various fatty acid metabolites on phosphorylase activation was investigated. To determine the potential effects of fatty acid metabolites on phosphorylase activation in cultured cardiomyocytes, normal and alloxan-diabetic cells were incubated with either carnitine or palmitoylcarnitine prior to stimulation with epinephrine. Pretreatment of cardiomyocytes with or without carnitine or palmitoylcarnitine for 3 or 24 hours before epinephrine stimulation failed to alter phosphorylase activation. The addition of exogenous carnitine in the absence and presence of insulin was also unsuccessful in attenuating the hypersensitive phosphorylase activation response in 3 and 24 hour, normal and alloxan-diabetic derived cardiomyocytes. To determine if carnitine palmitoyltransferase 1 (CPT-1) activity was responsible for the hypersensitive response of phosphorylase in the diabetic myocytes, both normal and diabetic myocytes were maintained for 3 and 24 hours in the absence and presence of etomoxir, a CPT-1 inhibitor. Subsequent activation of phosphorylase by epinephrine in normal and diabetic myocytes was unaltered in the presence of etomoxir. Collectively, these data fail to support a critical role for fatty acid metabolite involvement in the hypersensitive activation of glycogen phosphorylase in acute, alloxan-diabetic cardiomyocytes. To assess potential G-protein involvement in the response, normal and diabetic-derived myocytes were incubated with either cholera or pertussis toxin prior to hormonal stimulation. Pretreatment of cardiomyocytes with cholera toxin resulted in a potentiated response to epinephrine stimulation whereas pertussis toxin did not affect the activation of this signaling pathway. To determine if the enhanced response of phosphorylase activation resulted from an alteration in adenylyl cyclase activation, the cells were challenged with forskolin. After 3 hours in primary culture, diabetic cardiomyocytes exhibited a hypersensitive response to forskolin stimulation relative to normal cells. However, after 24 hours in culture, both normal and diabetic myocytes responded identically to forskolin challenge. The present data suggest that a cholera toxin sensitive G-protein mediates the hypersensitive response of glycogen phosphorylase to catecholamine stimulation in diabetic cardiomyocytes. This response, which is present in alloxan-diabetic cells, and is induced in vitroin normal cardiomyocytes, is primarily due to a defect at a post-receptor site. To assess the role of phosphorylase kinase in the hypersensitive activation of glycogen phosphorylase in the diabetic heart, phosphorylase kinase activity was measured initially in perfused hearts (to optimize the assay parameters) and subsequently in primary culture cardiomyocytes. Results from these experiments demonstrate that the present method for measuring phosphorylase kinase activity is a reliable indicator of the enzyme's activity in the heart, although the assay conditions must be further optimized before this system can be applied to the measurement of phosphorylase kinase activity in primary cultured cardiomyocytes.

v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...

Estudamos 62 pacientes, que com teste ergométrico positivo, manifestaram angina estável e estavam sob controle farmacológico. Todos apresentavam cinecoronariografia mostrando obstrução >70% em pelo menos uma das principais artérias coronárias. Objetivamos avaliar parâmetros eletrocardiográficos e de pressão arterial, durante procedimento odontológico restaurador sob anestesia local com e sem vasoconstritor em presença de doença arterial coronária. As idades variaram de 39 a 80, média de 58,7±8,8 anos, sendo 51 (82,3%) homens. Trinta pacientes foram randomizados para receber anestesia local com solução de lidocaína a 2% com adrenalina 1:100.000 e os demais para lidocaína a 2% sem vasoconstritor. Todos os pacientes foram submetidos à monitorização ambulatorial da pressão arterial (MAPA) e eletrocardiografia dinâmica por 24 horas, iniciados 2 horas antes do procedimento odontológico. Consideramos 3 períodos de registro: (1) basal - os 60 minutos que antecederam ao procedimento odontológico; (2) procedimento - desde o início da anestesia até o final do procedimento odontológico restaurador; (3) subseqüente completar das 24 horas. A análise de variância com medidas repetidas mostrou que houve elevação significativa da pressão arterial sistólica e diastólica do período basal para o procedimento nos dois grupos estudados (aproximadamente 14mmHg e 5 a 7mmHg) respectivamente, quando analisados separadamente e quando confrontados não apresentaram diferença de comportamento entre si. A freqüência cardíaca não se alterou nos dois grupos estudados. Depressão do segmento ST >1mm ocorreu em 10 (17,9%) pacientes; todos os eventos ocorreram no mínimo 2 horas após o término do procedimento odontológico. Extra - sístoles supra-ventriculares e/ou extra-sístoles ventriculares em número maior do que 10/hora estiveram presentes em 17 (30,4%) pacientes durante as 24 horas e durante o período do procedimento em 7 (12,5%), sendo 4 (13,8%) do grupo que recebeu anestesia sem adrenalina e 3 (11,1%) do grupo que recebeu anestesia com adrenalina e o teste Exato de Fisher não mostrou diferença entre os grupos. Concluímos que não houve diferença em relação ao comportamento de pressão arterial, freqüência cardíaca, evidência de isquemia e arritmias entre os grupos. O uso associado de vasoconstritor mostrou-se, portanto, seguro dentro dos limites do estudo. / We enrolled 62 patients with positive exercise stress test who presented with stable angina and were receiving drug therapy. All had a coronary angiography screening showing >70% obstruction in at least one of the main coronary arteries. The study aimed to compare electrocardiographic and blood pressure parameters during restorative dentistry procedure under local anesthesia, both with and without vasoconstrictor, in the presence of coronary artery disease. Ages ranged from 39 to 80, (mean ± SD) 58.7±8.8 years, 51 (82.3%) of them were male. Thirty patients were randomly assigned to receive 2% lidocaine local anesthesia with 1:100,000 epinephrine, the others receiving 2% lidocaine without vasoconstrictor. All the patients underwent ambulatory blood pressure and 24-hour Holter monitoring, beginning two hours ahead of the dental procedure. Recording were made during (1) baseline - 60-minute period before dental procedure began; (2) procedure - from beginning of anesthesia until the end of the procedure; and (3) subsequent 24-hour period. Analysis of variance with repeat measures showed significant diastolic and systolic blood pressure increases from baseline to the period of the procedure, in the two study groups (approximately 14 mm Hg, and 5 to 7 mm Hg, respectively); both in a separate analysis and in a comparative analysis no significant difference between them could be confirmed. Heart rate did not change in neither of the two groups. ST-segment >1 mm depression was detected in 10 (17.9%) patients; all these events occurred at least two hours after the end of the dentistry procedure. Premature supraventricular systoles and/or premature ventricular systoles in a greater number than 10/hour were seen in 17 (30.4%) patients in the 24-hours period after the procedure; during the procedure they occurred in 7 (12.5%) patients, of whom 4 (13.8%) were in the group without, and 3 (11.1%) in the group with vasoconstrictor. The Fisher\'s exact test revealed no difference between the groups. We concluded that there was no difference of blood pressure, heart rate, evidence of ischemia or arrhythmia episodes between the groups. Thus, the associated use of vasoconstrictor proved to be safe within the limits of this study

INTRODUÇÃO: A segurança da administração de anestésicos locais com vasoconstritor em pacientes diabéticos submetidos à cirurgia oral não está bem fundamentada na literatura. OBJETIVO: Investigar a ocorrência de variação da glicemia nos períodos pré, trans e pós-operatório de exodontia de dentes superiores, sob anestesia local com lidocaína 2% sem e com adrenalina 1:100.000, em portadores de diabetes mellitus tipo 2. Secundariamente, avaliar os efeitos hemodinâmicos e o grau de ansiedade. MÉTODOS: Estudo prospectivo e randomizado com pacientes portadores de diabetes acompanhados na Unidade Clinica de Coronariopatia Crônica do Instituto do Coração do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo. A monitorização contínua da glicemia durante 24 horas foi realizada através do MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic). Os pacientes foram divididos em dois grupos: LSA - que recebeu 5,4 mL lidocaína 2% sem adrenalina e LCA - que recebeu 5,4 mL de lidocaína 2% com adrenalina 1:100.000. Os níveis de glicemia foram avaliados nas 24 horas (período basal) e nos tempos determinados: uma hora antes, durantes e até uma hora após a exodontia (período de procedimento). Os parâmetros hemodinâmicos foram avaliados por meio de um medidor de pressão arterial digital automático e o nível de ansiedade através de uma escala. RESULTADOS: Dos 400 pacientes avaliados, 70 foram incluídos no estudo, sendo 35 randomizados no grupo LSA e 35 no grupo LCA. A análise das médias da glicemia nos grupos LSA e LCA durante os períodos (basal e procedimento) não demonstrou diferença estatisticamente significativa (p=0,229 e p=0,811, respectivamente). Também não houve diferença significativa (p=0,748) na glicemia entre os grupos em cada tempo avaliado. Entretanto, nos dois grupos houve decréscimo significativo da glicemia (p < 0,001) ao longo dos tempos avaliados. Os grupos LSA e LCA não apresentaram diferenças significativas em relação à PAS (p=0,176), à PAD (p=0,913), à FC (p=0,570) e ao nível de ansiedade. CONCLUSÃO: A administração de 5,4mL de lidocaína 2% com adrenalina 1:100.000 não provocou alteração significativa da glicemia, parâmetros hemodinâmicos e nível de ansiedade em relação ao grupo sem vasoconstritor / INTRODUCTION: The safety of administration of local anesthetics with epinephrine for diabetic patients undergoing oral surgery is not well grounded in the literature. OBJECTIVE: To investigate the occurrence of variation of glucose in the pre, intra and postoperative extraction of upper teeth under local anesthesia with lidocaine 2% with and without 1:100.000 epinephrine in patients with type 2 diabetes mellitus. Secondly, to evaluate the hemodynamic effects and degree of anxiety. METHODS: A prospective randomized study of patients with diabetes attended in Coronary Chronic Clinics Unit, Heart Institute, Hospital das Clinicas in University of São Paulo Medical School. Continuous monitoring of blood glucose for 24 hours was performed using MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic) and the patients were divided into two groups: LSA - which received 5.4 mL of 2% lidocaine without epinephrine and LCA - which received 5.4 mL of 2% lidocaine with 1:100,000 epinephrine. Blood glucose levels were assessed at 24 hours (baseline period) and at certain times: one hour before, during, and up to one hour after oral surgery (procedure period). We evaluated the hemodynamic parameters through a digital automatic pressure meter and anxiety level was measured by the scale. RESULTS: Of 400 patients evaluated, 70 were included in these study, 35 were randomized in the LSA group and 35 in the group LCA. The analysis of mean glicemia in groups LSA and LCA during the baseline period and procedure showed no statistically significant difference (p = 0.229 and p = 0.811, respectively). There was no difference in blood glucose (p = 0.748) between the groups at each time evaluated. However, in both groups there was a significant decrease in blood glucose (p < 0.001) over the time periods studied. The groups showed no significant differences regarding SBP (p = 0.176), DBP (p = 0.913), HR (p = 0.570) and anxiety level. CONCLUSION: The administration of 5.4 mL of 2% lidocaine with epinephrine 1:100.000 caused no significant change in blood glucose, hemodynamic parameters and level of anxiety compared to the group without vasoconstrictor