Opioid/adrenergic interactions were studied to evaluate two hypotheses: (1) naloxone potentiates the effect of epinephrine on cardiac contractility by increasing circulating epinephrine concentrations; and (2) endogenous and exogenous opioids alter left cardiac nerve stimulationinduced norepinephrine release and cardiac function. A canine isolated heart-lung preparation was used for the first study. Plasma epinephrine was determined and myocardial epinephrine uptake was calculated during intravenous epinephrine infusion. Naloxone (4 mg) was given and the epinephrine infusion was repeated. Naloxone increased cardiac contractility, coronary blood flow, and the coronary sinus epinephrine concentration. When coronary blood flow was subsequently held constant (100% above resting), naloxone increased only contractility. This result indicated that the previously observed increase in coronary sinus epinephrine was flow dependent. Corticosterone (an uptake II blocker) was employed as a positive control. Corticosterone increased the contractile response to epinephrine, but unlike naloxone, corticosterone was accompanied by a clear decrease in myocardial epinephrine uptake. The stereospecificity of the response to naloxone was investigated and (+) naloxone equaled or exceeded (-) naloxone in potentiating the inotropic effect of epinephrine. In the second study, the left cardiac nerve was isolated and electrically stimulated in intact dogs. Norepinephrine overflow gradually declined during successive control stimulations. Pretreatment with naloxone (100 Mg/kg) prevented or delayed the decline. An intracoronary dynorphin 1-9 infusion (2 nmol/min/kg for 20 minutes) reduced both norepinephrine overflow and cardiac performance, and both effects were prevented by pretreatment with naloxone (100 /xg/kg) . To summarize, naloxone potentiated the inotropic effect of infused epinephrine without altering circulating epinephrine concentrations or myocardial epinephrine uptake. This effect of naloxone was not stereospecific and probably not mediated through a traditional opiate receptor. Endogenous and exogenous opioids inhibited the left cardiac nerve stimulation-induced norepinephrine overflow, suggesting that opiate receptors may regulate cardiac excitability by modulating norepinephrine release.

Os neurônios do grupamento catecolaminérgico C1, localizados na porção ventrolateral do bulbo, são classicamente conhecidos por seu envolvimento no controle cardiovascular. O modelo atual propõe que os neurônios C1 são recrutados em situações que ofereçam risco de vida aos indivíduos, desencadeando respostas generalizadas e estereotipadas em defesa da homeostase. Tais respostas envolvem ajustes cardiovasculares, imunológicos, neuroendócrinos, metabólicos, termorregulatórios e respiratórios. Ferramentas anatômicas e funcionais foram utilizadas para investigar se os neurônios C1 contribuem para os ajustes respiratórios induzidos pela hipóxia e pela hipercpania. Os resultados mostram que os neurônios C1 contribuem para a aumento da ventilação induzido pela hipóxia, mas não pela hiperpania, via aumento da frequência da respiratória. Além disso, demonstramos que o aumento da frequência respiratória promovido pela ativação do grupamento C1 depende da ativação de receptores glutamatérgicos, mas não adrenérgicos, localizados na região do complexo pré-Bötzinger. / The catecholaminergic C1 neurons, located in the rostral ventrolateral portion of the medulla, are classically known by their involvement in the cardiovascular control. Recent models suggest that C1 neurons are recruited in situations of life risk, triggering generalized and stereotyped responses to homeostasis. Such responses involve cardiovascular, immunologic, neuroendocrine, metabolic, thermoregulatory and respiratory adjustments. Thus, anatomic and functional tools were used to assess the contribution of C1 neurons to the respiratory adjustments induced by hypoxia and hypercapnia. The results show that these neurons contribute to the increase of ventilation induced by hypoxia, but not by hypercapnia, via an increase of the breathing frequency. Moreover, we demonstrated that increase of breathing frequency promoted by the activation of C1 neurons depend on the activation of glutamatergic receptors, but not adrenergic, located in the pre-Bötzinge complex.

Abstract not available

Abstract not available

Thesis (Ph. D.)--University of Chicago, 1939. / Lithoprinted. "List of references": p. 17-19.

Thesis (Ph. D.)--State University of New York at Binghamton, Department of Anthropology, 2008. / Includes bibliographical references.

Orientador: Sebastião Araujo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T01:38:54Z (GMT). No. of bitstreams: 1 Ovalle_CarlosCezarIvoSant'Ana_D.pdf: 918971 bytes, checksum: 7890aba34116748396efbad3ac6c01f5 (MD5) Previous issue date: 2011 / Resumo: Fundamento: O papel de vasopressores não-adrenérgicos na ressuscitação cardiopulmonar (RCP) permanece controverso. Objetivo: O objetivo do estudo foi avaliar a eficácia da terlipressina (TP) vs. adrenalina (ADR) em aumentar a pressão de perfusão coronariana (PPCor) e o retorno da circulação espontânea (RCE) na RCP em suínos. Métodos: Sob anestesia ketamina/tiopental, fibrilação ventricular foi induzida em 44 porcos fêmeas imaturos, permanecendo não-assistida por 10min, seguido de 2min de RCP-manual (100 compressões/10 ventilações/min com ar). Os animais foram então alocados em quatro grupos, recebendo: 1) ADR (45?g/kg); 2) salina-placebo (10mL); 3) TP (20?g/kg); 4) TP (20?g/kg) + ADR (45?g/kg). Desfibrilação foi realizada 2min apos, observando-se os animais sobreviventes por um período de 30min. ECG, PA sistêmica, PAD e PEtCO2 foram monitorados continuamente. Resultados: A TP não diferiu do placebo quanto aos efeitos na PPC, com baixas taxas de RCE em ambos os grupos (1/11 vs. 2/11; p=NS). A ADR aumentou a PPC de 13 ± 12 para 54 ± 15mmHg (p<0,0001), efeito similar a TP+ADR (de 21 ± 10 para 45 ± 13mmHg; p<0,0001), com altas taxas de RCE/sobreviventes em ambos os grupos (10/11 vs. 9/11, respectivamente). Entre os sobreviventes, maior PAM foi observada no grupo TP+ADR vs. ADR (105 ± 19mmHg vs. 76 ± 21mmHg; p=0,0157). Conclusões: ADR e TP+ADR foram efetivas para aumentar a PPC/RCE neste modelo experimental, mas a TP isolada não foi diferente do placebo. Contudo, nos animais sobreviventes do grupo TP+ADR observou-se uma maior estabilidade hemodinâmica após a RCE, sugerindo que a TP possa ser uma medicação útil no manuseio da hipotensão pós-RCP / Abstract: Background: The role of non-adrenergic vasopressors during cardiopulmonary resuscitation (CPR) remains controversial. Objective: The aim of the study was to compare the efficacy of terlipressin (TP) vs. adrenaline (ADR) to increase coronary perfusion pressure (CPP) and the return of spontaneous circulation (ROSC) during CPR in pigs. Methods: Under ketamine/thiopental anesthesia, ventricular fibrillation was induced in 44 immature female pigs remaining non-assisted for 10min, followed by 2min of manual closed-chest CPR (100 thoracic compressions and 10 ventilation/min with air). The animals were then randomized into four groups, receiving: 1) ADR (45?g/kg); 2) saline-placebo (10mL); 3) TP (20?g/kg); 4) TP (20?g/kg) + ADR (45?g/kg). Defibrillation was attempted 2min later. Surviving animals were observed during 30min. EKG, systemic AP, RA pressure and PEtCO2 were continuously recorded. Results: TP was not different from placebo regarding their effects on CPP, with low ROSC rates in both groups (1/11 vs. 2/11, respectively; p=NS). ADR increased CPP from 13 ± 12 to 54 ± 15mmHg (p<0.0001), similar to TP+ADR (from 21 ± 10 to 45 ± 13mmHg; p<0.0001), with high rates of ROSC/survival in both groups (10/11 vs. 9/11, respectively). Among surviving animals, a greater MAP was recorded in TP+ADR when compared with ADR (105 ± 19mmHg vs. 76 ± 21mmHg; p=0.0157). Conclusions: ADR and TP+ADR were highly effective to increase CPP and ROSC in this experimental CPR model, but TP alone was not different from placebo. Moreover, surviving animals in TP+ADR group showed greater hemodynamic stability after ROSC, suggesting that TP could be a potential useful drug for post-CPR hypotension/shock management / Doutorado / Fisiopatologia Cirúrgica / Doutor em Ciências

Orientadores: Francisco Carlos Groppo, Maria Cristina Volpato / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-24T14:56:00Z (GMT). No. of bitstreams: 1 Burga-Sanchez_Jonny_M.pdf: 1446024 bytes, checksum: 5abbf4456cb67b444d465cc424ab2baa (MD5) Previous issue date: 2014 / Resumo: A associação a carreadores tem sido proposta visando prolongar o efeito anestésico, além de reduzir a toxicidade de vários anestésicos locais, incluindo a articaína (ATC). O objetivo do estudo foi avaliar in vitro o efeito da ATC livre ou associada a diferentes concentrações de epinefrina ou 2-hidroxipropil-?-ciclodextrina (HP-?-CD) sobre a viabilidade celular de queratinócitos humanos imortalizados (HaCaT). Foi avaliado também o efeito do metabissulfito de sódio, principal antioxidante e componente das soluções anestésicas comerciais, sobre a viabilidade das citadas células. A microscopia eletrônica de varredura (MEV) foi utilizada para avaliar as características físicas dos cristais da ATC, da HP-?-CD e do complexo de inclusão liofilizado de ATC/HP-?-CD. As células HaCaT foram expostas às formulações de ATC em diferentes concentrações desde 0.1% até 4%, associadas ou não a epinefrina 1:50.000, 1:100.000 e 1:200.000, ou em associação com HP-?-CD; em tempos de 10, 30, 60 e 240 min. As células viáveis foram quantificadas pelo método do MTT após os períodos de exposição e comparadas a um grupo controle sem tratamento. A avaliação celular qualitativa foi realizada por microscopia de fluorescência pelo método de coloração Live/Dead®. A análise estatística foi realizada por two-way ANOVA (teste de Tukey, p>0.05). Os resultados revelaram que a toxicidade da ATC depende da concentração e do tempo de exposição, sendo que quando complexada com HP-?-CD ou associada à epinefrina 1:200.000, houve tendência a diminuir a toxicidade avaliada inicialmente. Da mesma forma, os adjuvantes como a epinefrina, o metabissulfito de sódio e a HP-?-CD sozinhos mostraram biocompatibilidade nas concentrações empregadas neste estudo. Concluímos que a associação da ATC com a HP-?-CD bem como à epinefrina 1:200.000 diminuiu a toxicidade do anestésico local quando avaliado nas concentrações mais baixas. Entretanto, a associação destes adjuvantes não melhorou o perfil de toxicidade da ATC quando avaliado em concentrações clínicas usuais de 2 e 4% / Abstract: The association with carriers has been proposed to prolong the anesthetic effect and reduce the toxicity of several local anesthetics including articaine (ATC). The aim of this study was to assess the in vitro effect of ATC associated with different concentrations of epinephrine or 2-hydroxypropyl-?-cyclodextrin (HP-?-CD) on cell viability in immortalized human keratinocyte cells cultures (HaCaT). It was also evaluated the effect of sodium metabisulphite, major antioxidant component of commercial anesthetic solutions, on the viability of cited cells. The scanning electron microscopy (SEM) was used to assess the physical characteristics of ATC crystals, HP-?-CD and ATC/HP-?-CD lyophilized inclusion complex. The HaCaT cells were exposed to different formulations of ATC in concentrations from 0.1% to 4%, associated or not with epinephrine 1:50.000, 1:100.000 and 1:200.000, or in formulation with HP-?-CD; in 10, 30, 60 and 240 min time exposure. Vital HaCaT cells were quantified by the MTT method after exposure periods and compared to an untreated control group. Cells were assessed qualitatively by fluorescent microscopy using the staining Live/Dead® method. Statistical analysis was performed by two-way ANOVA (Tukey test, p> 0.05). The results showed that toxicity of ATC depends on the concentration and exposure time, and when complexed with HP-?-CD or associated with epinephrine 1:200.000, there was a tendency to decrease the toxicity initially evaluated. Likewise, adjuvants such as epinephrine, sodium metabisulphite and HP-?-CD alone showed biocompatibility in concentrations used in this study. In conclusion, the association of ATC with HP-?-CD as well as epinephrine 1:200.000 decreased local anesthetic toxicity when lower concentrations of ATC are used. However, the combination of adjuvants did not improve the toxicity profile of ATC when used in clinical usual concentrations of 2 and 4% / Mestrado / Farmacologia, Anestesiologia e Terapeutica / Mestre em Odontologia

Orientadores: Jose Ranali, Darceny Zanetta Barbosa / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-04T04:03:18Z (GMT). No. of bitstreams: 1 Oliveira_PatriciaCristinede_D.pdf: 14172731 bytes, checksum: a824d5516bc922567d636ef268423166 (MD5) Previous issue date: 2005 / Resumo: Este estudo avaliou a variação de parâmetros cardiovasculares em 15 portadores de DAC aguda com angina instável e infarto agudo do miocárdio prévio, submetidos a tratamento odontológico sob anestesia local com epinefrina e felipressina. MAPA e ECG foram usados para avaliar a pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), freqüência cardíaca (FC), extrassístoles ventriculares (EV) e supraventriculares (ESV), depressão e elevação do segmento SI. Adicionalmente foram avaliados a alteração na troponina I (Tn-I), a saturação de oxigênio (Sp02) com oxímetro de pulso, o grau de ansiedade (através da Escala de Ansiedade Dental de Corah - EADC) e a sensação dolorosa (pela Escala de dor de 11 pontos em caixa - EC), em quatro fases: 0- basal, monitoramento com holter por 24 horas; 1 ¿ simulação do atendimento odontológico, holter por 24 horas, MAPA por 5 horas, oxímetro de pulso por 1 hora que corresponde ao período do atendimento odontológico; 2 e 3 - similar à fase 1 porém com atendimento odontológico que constituiu de anestesia local infiltrativa vestibular e submucosa palatina com 1,8mL de lidocaína 2% com adrenalina 1:100.000 ou de prilocaína 3% com felipressina 0,03Ul/mL seguida de raspagem periodontal. As soluções anestésicas foram distribuídas de forma aleatória em cada uma das fases, em um estudo cruzado, cego para o atendimento e duplo-cego para a análise dos dados. As fases 2 e 3 foram acompanhadas por um cardiologista no período correspondente ao do atendimento odontológico. Antes do início das sessões, aplicou-se a EADC e, após o atendimento odontológico (fases 2 e 3), aplicou-se a EC. Os dados de ansiedade, dor, PAS, PAD e FC foram avaliados pelo teste de Wilcoxon pareado com nível de significância de 5%, ou com fator de correção de Bonferroni para os casos de três (a= 0,016) ou quatro (a= 0,0125) testes, e as variáveis do ECG pelo teste exato de Fisher (u= 0,05). A PAS apresentou diferença significante durante o atendimento odontológico com epinefrina e a Sp02 foi diferente com tendência de apresentar menor valor na fases inicial do estudo (Fase 1). Não foram encontradas diferenças significantes entre as fases para EV, ESV, depressão de ST, Tn-I, ansiedade e dor. Pode-se concluir que a epinefrina e a felipressina tiveram tendência de alterar a PAS, PAD e Sp02 embora somente a epinefrina tenha influenciado de forma significante. Porém este aumento não foi suficiente para induzir alterações eletrocardiográficas no grupo de pacientes avaliados, podendo-se dizer que ambas as soluções, na dose e concentração utilizadas, são bem toleradas por portadores de DAC aguda o tipo AI e IAM prévio, não contra-indicando, portanto o atendimento - deste grupo de pacientes / Abstract: The purpose of this study was to evaluate the changes of cardiovascular parameters in 15 volunteers with acute CAD (instable angina and previous myocardial infarction) during dental treatment under local anesthesia with epinephrine and felypressine. Ambulatory monitoring (BPAM) and ECG were utilized to evaluate systolic (SBP) and diastolic (OBP) blood pressures, heart rate (HR), ventricular (VA) and supraventricular arrhythmias (SVA), ST depression and ST elevation, and SpO2(by pulse oximeter), troponin I (Tn-I), anxiety (by Corah's Dental Anxiety Scale - CDAE) and painful sensibility (by The 11-point Box Scale - BS-11), in 4 phases: 0- baseline, 24 hours holter monitoring; 1 - dental treatment simulation, 24 hours holter, 5 hours MAPA, 1 hour pulse oximeter, corresponding the dental treatment; 2 and 3 - similar to phase 1, more dental treatment with periodontal scaling, made under maxillary and palatine local anesthesia using 1.8ml of 2% lidocaine with 1:100.000 epinephrine (Epi) or 3% prilocaine supplemented 0,03 IUlml of felypressine (Fel), in a double blind cross-over study. Phases 2 and 3 were looked closely by a cardiologist. The COAE was applied at the beginning of the sections and after the dental treatment (phases 2 and 3) was applied the BS-11. The anxiety date, painful sensibility, SBP, DBP and HR were evaluated by Wilcoxon test (5% levei of significance or Bonferroni correction factor for the cases of three, u= 0.016 or four, u= 0.0125 tests) and the data of ECG were analyzed by Fisher test (u= 0.05). The SBP presented significant difference during dental treatment with epinephrine and SpO2was different with tendency to showed lowers values in phase 1. Significant differences were not found among the phases for VA, SVA, ST depression, Tn-I, anxiety and painful sensation. It can be concluded that epinephrine and felypressine resulted changes in SBP, OBP and SpO2, but only' epinephrine caused significant difference. However the SBP did not increased sufficiently to cause ECG alterations in this group, and both of them, in utilized doses and concentrations are well tolerated by patients with acute CAD (instable angina and myocardial infarction), it did not presented absolute contraindications to dental treatment in this grou / Doutorado / Farmacologia, Anestesiologia e Terapeutica / Doutor em Odontologia

Neutrophils playa key role in the systemic inflammatory response which may lead to serious tissue injury and multiple organ dysfunction. In this setting, activated neutrophils, largely in response to tumour necrosis factor-alpha (TNF-α), secrete reactive oxidants, granule proteases and bioactive lipids, as well as pro-inflammatory cytokines, emphasising the importance of these cells as targets for anti-inflammatory therapies. There are, however, only a few currently available agents that directly modulate neutrophil pro-inflammatory responses in clinical practice, with corticosteroids being relatively ineffective against these cells. Although, the anti-inflammatory potential of cAMP-elevating agents has been recognised, the exact molecular/biochemical mechanisms which underlie the anti-inflammatory actions of epinephrine and related β-agonists with neutrophils, have not been established. Epinephrine treatment of neutrophils resulted in increased intracellular cAMP and dose-related inhibition of both superoxide production and elastase release, which was potentiated by the type 4 phosphodiesterase inhibitor, rolipram, further supporting a cAMP-mediated effect. Although epinephrine did not affect the release of Ca2+ from neutrophil intracellular stores, the rate of clearance of cytosolic Ca2+ was accelerated by this agent. In the setting of decreased efflux and a reduction in store-operated influx of Ca2+, these effects of epinephrine are compatible with enhancement of the cAMP-dependent Ca2+ sequestering/resequestering endo-membrane Ca2+-ATPase. Epinephrine therefore down-regulates the pro-inflammatory activation of neutrophils by cAMP-mediated enhancement of the clearance of cytosolic Ca2+. Comparison of the effects of 4 selective (fenoterol, formoterol, salbutamol and salmeterol) and 3 non-selective (epinephrine, norepinephrine and isoproterenol) β-adrenoreceptor agonists, on the pro-inflammatory activities of human neutrophils, demonstrated that the agents tested clearly differ with respect to anti-inflammatory potential. Epinephrine, isoproterenol, fenoterol and formoterol significantly increased intracellular concentrations of cAMP in neutrophils, an activity which was paralleled by inhibition of the production of reactive oxidants and release of elastase from FMLP-activated cells. Salbutamol and salmeterol on the other hand, did not cause significant suppression of the pro-inflammatory activities of these cells. The effect of norepinephrine was intermediate between these two groups. The inhibitory effects of βagonists are mediated via β2-adrenergic receptors on the neutrophil membrane. The relationship between activation of NAOPH oxidase, alterations in membrane potential and triggering of Ca2+ fluxes in human phagocytes has been investigated using neutrophils from 4 subjects with chronic granulomatous disease (CGO). Activation of CGO neutrophils was accompanied by a prolonged increase in cytosolic Ca2+, occurring in the setting of trivial membrane depolarisation and accelerated influx of Ca2+. This was associated with hyperactivity of the cells with excessive elastase release, which was attenuated by the type 4 phosphodiesterase inhibitor, rolipram. These findings support the involvement of NAOPH oxidase in regulating membrane potential and Ca2+ influx in activated neutrophils, and may explain the disordered inflammatory responses, and granuloma formation, which are characteristic of CGO. Store-operated influx of Ca2+ into activated neutrophils is stringently regulated, presumably to prevent hyperactivation of the cells. The major contributors to this physiologic, anti-inflammatory process are NAOPH oxidase which, by its membrane depolarising actions excludes extracellular Ca2+, and the plasma membrane and endomembrane Ca2+-ATPases, which mediate clearance of store-derived cation. Subsequent influx of the cation, through store-operated Ca2+ channels is controlled by the relatively slow, restraining, membrane repolarising action of the Na+/Ca2+ exchanger, enabling efficient diversion of incoming cation into stores. / Thesis (DPhil (Immunology))--University of Pretoria, 2005. / Immunology / unrestricted