Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

A rise in arterial PCO(2) stimulates breathing and sympathetic activity to the heart and blood vessels. In the present study, we investigated the involvement of the retrotrapezoid nucleus (RTN) and glutamatergic mechanisms in the Botzinger/C1 region (Botz/C1) in these responses. Splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded in urethane-anesthetized, sino-aortic-denervated, vagotomized, and artificially ventilated rats subjected to hypercapnia (end-expiratory CO(2) from 5% to 10%). Phrenic activity was absent at end-expiratory CO(2) of 4%, and strongly increased when end-expiratory CO(2) reached 10%. Hypercapnia also increased sSND by 103 +/- 7%. Bilateral injections of the GABA-A agonist muscimol (2 mM) into the RTN eliminated the PND and blunted the sSND activation (Delta = +56 +8%) elicited by hypercapnia. Injections of NMDA receptor antagonist AP-5 (100 mM), non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 100 mM) or metabotropic glutamate receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG; 100 mM) bilaterally into the Botz/C1 reduced PND (Delta = +43 +/- 7%, +52 +/- 6% or +56 +/- 11%, respectively). MCPG also reduced sSND (Delta = +41 +/- 7%), whereas AP-5 and DNQX had no effect. In conclusion, the increase in sSND caused by hypercapnia depends on increased activity of the RTN and on metabotropic receptors in the Botz/C1, whereas PND depends on increased RTN activity and both ionotropic and metabotropic receptors in the Botz/C1.

Contribution of excitatory amino acid receptors of the retrotrapezoid nucleus to the sympathetic chemoreflex in rats

In the present study, we evaluated the role of glutamatergic mechanisms in the retrotrapezoid nucleus (RTN) in changes of splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) elicited by central and peripheral chemoreceptor activation. Mean arterial pressure (MAP), sSND and PND were recorded in urethane-anaesthetized, vagotomized, sino-aortic denervated and artificially ventilated male Wistar rats. Hypercapnia (10% CO(2)) increased MAP by 32 +/- 4 mmHg, sSND by 104 +/- 4% and PND amplitude by 101 +/- 5%. Responses to hypercapnia were reduced after bilateral injection of the NMDA receptor antagonist D,L-2-amino-5-phosphonovalerate (AP-5; 100mm in 50 nl) in the RTN (MAP increased by 16 +/- 3 mmHg, sSNDby 82 +/- 3% and PND amplitudeby 63 +/- 7%). Bilateral injection of the non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione(DNQX; 100 mm in 50 nl) and the metabotropic receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG; 100mm in 50 nl) in the RTN did not affect sympathoexcitatory responses induced by hypercapnia. Injection of DNQX reduced hypercapnia-induced phrenic activation, whereas MCPG did not. In animals with intact carotid chemoreceptors, bilateral injections of AP-5 and DNQX in the RTN reduced increases in MAP, sSND and PND amplitude produced by intravenous injection of NaCN (50 mu g kg(-1)). Injection of MCPG in the RTN did not change responses produced by NaCN. These data indicate that RTN ionotropic glutamatergic receptors are involved in the sympathetic and respiratory responses produced by central and peripheral chemoreceptor activation.

Cardiopulmonary and acid-base effects of desflurane and sevoflurane in spontaneously breathing cats

The cardiopulmonary effects of desflurane and sevoflurane anesthesia were compared in cats breathing spontaneously. Heart (HR) and respiratory (RR) rates; systolic (SAP), diastolic (DAP) and mean arterial (MAP) pressures; partial pressure of end tidal carbon dioxide (PETCO(2)), arterial blood pH (pH), arterial partial pressure of oxygen (PaO(2)) and carbon dioxide (PaCO(2)); base deficit (BD), arterial oxygen saturation (SaO(2)) and bicarbonate ion concentration (HCO(3)) were measured. Anesthesia was induced with propofol (8 +/- 2.3 mg/kg IV) and maintained with desflurane (GD) or sevoflurane (GS), both at 1.3 MAC. Data were analyzed by analysis of variance (ANOVA), followed by the Tukey test (P < 0.05). Both anesthetics showed similar effects. HR and RR decreased when compared to the basal values, but remained constant during inhalant anesthesia and PETCO(2) increased with time. Both anesthetics caused acidemia and hypercapnia, but BD stayed within normal limits. Therefore, despite reducing HR and SAP (GD) when compared to the basal values, desflurane and sevoflurane provide good stability of the cardiovascular parameters during a short period of inhalant anesthesia (T20-T60). However, both volatile anesthetics cause acute respiratory acidosis in cats breathing spontaneously. (c) 2004 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Hemogasometria de eqüinos submetidos à obstrução experimental do duodeno, íleo e cólon maior

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of hypercapnic hyperpnea on recovery from isoflurane or sevoflurane anesthesia in horses

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Nucleus isthmi and control of breathing in amphibians

Despite recent advances, the mechanisms of neurorespiratory control in amphibians are far from understood. One of the brainstem structures believed to play a key role in the ventilatory control of anuran amphibians is the nucleus isthmi (NI). This nucleus is a mesencephalic structure located between the roof of the midbrain and the cerebellum, which differentiates during metamorphosis; the period when pulmonary ventilation develops in bullfrogs. It has been recently suggested that the NI acts to inhibit hypoxic and hypercarbic drives in breathing by restricting increases in tidal volume. This data is similar to the influence of two pontine structures of mammals, the locus coeruleus and the nucleus raphe magnus. The putative mediators for this response are glutamate and nitric oxide. Microinjection of kynurenic acid (an ionotropic receptor antagonist of excitatory amino acids) and L-NAME (a non-selective NO synthase inhibitor) elicited increases in the ventilatory response to hypoxia and hypercarbia. This article reviews the available data on the role of the NI in the control of ventilation in amphibians. (C) 2004 Elsevier B.V. All rights reserved.

Periaqueductal gray matter modulates the hypercapnic ventilatory response

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Brain monoaminergic neurons and ventilatory control in vertebrates

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The locus coeruleus and central chemosensitivity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CONTROL of THE CENTRAL CHEMOREFLEX BY A5 NORADRENERGIC NEURONS IN RATS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of a sidestream capnograph and a mainstream capnograph in mechanically ventilated dogs

Objective-To compare the ability of a sidestream capnograph and a mainstream capnograph to measure end-tidal CO2 (ETCO2) and provide accurate estimates of Paco(2) in mechanically ventilated dogs.Design-Randomized, double Latin square.Animals-6 healthy adult dogs.Procedure-Anesthesia was induced and neuromuscular blockade achieved by IV administration of pancuronium bromide. Mechanical ventilation was used to induce conditions of standard ventilation, hyperventilation, and hypoventilation. While tidal volume was held constant, changes in minute volume ventilation and Paco(2) were made by changing the respiratory rate. Arterial blood gas analysis was performed and ETCO2 measurements were obtained by use of either a mainstream or a sidestream capnographic analyzer.Results-A linear regression model and bias analysis were used to compare Paco(2) and ETCO2 measurements; ETCO2 measurements obtained by both capnographs correlated well with Paco(2). Compared with Paco(2), mainstream ETCO2 values differed by 3.15 +/- 4.89 mm Hg (mean bias +/- SD), whereas the bias observed with the sidestream ETCO2 system was significantly higher (5.65 +/- 5.57 mm Hg). Regardless of the device used to measure ETCO2, bias increased as Paco(2) exceeded 60 mm Hg.Conclusions and Clinical Relevance-Although the mainstream capnograph was slightly more accurate, both methods of ETCO2 measurement correlated well with Paco(2) and reflected changes in the ventilatory status. However, ETCO2 values > 45 mm Hg may inaccurately reflect the severity of hypoventilation as Paco(2) may be underestimated during conditions of hypercapnia (Paco(2) > 60 mm Hg).

Prognostic factors for perioperative pulmonary events among patients undergoing upper abdominal surgery

CONTEXTO E OBJETIVO: Associações significativas entre cirurgia do abdome superior e eventos pulmonares do período perioperatório foram investigadas em pacientes com condições pulmonares pré-operatórias submetidos a anestesia geral. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo cujos dados foram retirados de banco de dados obtidos prospectivamente de forma protocolada, de 1 de janeiro de 1999 a 31 de dezembro de 2004, em hospital universitário terciário. MÉTODOS: Estudados 3107 pacientes com mais de 11 anos, American Society of Anesthesiologists (ASA) I, II, III, com cirurgia de abdome superior sob anestesia geral, enviados à sala de recuperação. Condições pré-operatórias analisadas por regressão logística foram: idade, sexo, estado físico ASA, insuficiência cardíaca congestiva, asma, doença pulmonar obstrutiva crônica, insuficiência respiratória e hábito de fumar. Os resultados estudados, ou variáveis dependentes, incluíram eventos intra- e pós-operatórios: broncoespasmo, hipoxemia, hipercapnia, intubação prolongada e secreção de vias aéreas. RESULTADOS: Dos 3.107 pacientes: 1.540 eram homens, 1.649 mulheres, tinham média de 48 anos, 1088 ASA I, 1402 ASA II, 617 ASA III, com insuficiência cardíaca havia 80, asma, 82, doença pulmonar obstrutiva, 122, insuficiência respiratória, 21, hábito de fumar, 428. Pela regressão logística, sexo feminino (p < 0.001), idade maior que 70 anos (p < 0.01), hábito de fumar (p < 0.001) e doença pulmonar obstrutiva crônica (p < 0.02) influenciaram significativamente o desenvolvimento de eventos pulmonares, principalmente hipoxemia e broncospasmo, em ambos os períodos, mas não nos mesmos pacientes. Asma e insuficiência cardíaca não se associaram com eventos pulmonares na sala de recuperação. CONCLUSÃO: em cirurgia do abdome superior sob anestesia geral, sexo feminino, idade maior que 70 anos, hábito de fumar e doença pulmonar obstrutiva crônica foram fatores de risco independentes para a ocorrência de eventos pulmonares intra- e pós-operatórios.

Anestesia intravenosa total utilizando propofol ou propofol/cetamina em cadelas submetidas à ovariossalpingohisterectomia

Objetivou-se avaliar os efeitos cardiorrespiratório e analgésico da infusão contínua com propofol e propofol/cetamina em cadelas pré-medicadas com atropina e xilazina, submetidas a ovariossalpingohisterectomia (OSH). em seis cadelas (GP) a indução anestésica foi realizada com propofol (5mg kg-1 iv), seguido da manutenção anestésica com o mesmo fármaco em infusão contínua intravenosa na taxa inicial de 0,4mg kg-1.min-1. Outras seis cadelas (GPC) receberam a associação de propofol (3,5mg kg-1 iv) e cetamina (1mg kg-1 iv) como indução anestésica. Depois, foi feita manutenção anestésica em infusão contínua intravenosa inicial com 0,28mg kg-1.min-1 e 0,06mg kg-1.min-1 de propofol e cetamina, respectivamente. Os seguintes parâmetros foram mensurados durante a anestesia a cada 10 minutos: freqüências cardíaca (FC) e respiratória (f), pressão arterial sistólica, média e diastólica (PA), concentração final expirada de CO2 (EtCO2), volume minuto (VM), pressão parcial de gás carbônico (PaCO2), pressão parcial de oxigênio (PaO2), saturação de oxigênio na hemoglobina (SatO2), pH, bicarbonato, glicemia e temperatura retal (T). Observou-se redução da pressão arterial média entre 20 e 40 minutos de anestesia no GP. Ocorreu redução da temperatura, hipercapnia e acidose respiratória em ambos os grupos durante a anestesia. A PaO2, o bicarbonato e a glicose aumentaram de forma significativa apenas no GPC durante a anestesia. Houve necessidade de aumentar em 50 e 20% a taxa de infusão de propofol no GP e GPC respectivamente para anestesia cirúrgica satisfatória. Dessa forma, ambos os protocolos mostraram-se seguros e suficientes do ponto de vista de anestesia cirúrgica para realização da OSH em cadelas, desde que a ventilação assistida ou controlada seja instituída quando necessária e a velocidade de infusão do propofol seja 0,6 e 0,34mg kg-1.min-1 nos grupos GP e GPC, respectivamente.

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Central leptin replacement enhances chemorespiratory responses in leptin-deficient mice independent of changes in body weight

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)