RESUMEN
Critical value of oxygen tension (Po2) and cerebral blood flow in the striatum for seizure appearance during hyperbaric oxygenation (5 ATA) were determined in awake Wistar rats. Seizure activity was observed at Po2=1030±102 mm Hg. A relationship between brain Po2 and blood flow was revealed at different regimens of hyperbaric oxygenation using a mathematical model. Comparison of experimental data and mathematical model showed that seizure-inducing levels of Po2during hyperbaric oxygenation at 4, 5, and 6 ATA can be achieved after increasing blood flow by 1.5-3.0, 1.2-2.0, and 0.8-1.1, respectively.
Asunto(s)
Encéfalo/irrigación sanguínea , Oxigenoterapia Hiperbárica , Animales , Circulación Cerebrovascular/fisiología , Hemodinámica , Masculino , Modelos Teóricos , Ratas , Ratas Wistar , Convulsiones/fisiopatologíaRESUMEN
Breathing hyperbaric oxygen (HBO2), particularly at pressures above 3 atmospheres absolute, can cause acute pulmonary injury that is more severe if signs of central nervous system toxicity occur. This is consistent with the activation of an autonomic link between the brain and the lung, leading to acute pulmonary oxygen toxicity. This pulmonary damage is characterized by leakage of fluid, protein, and red blood cells into the alveoli, compatible with hydrostatic injury due to pulmonary hypertension, left atrial hypertension, or both. Until now, however, central hemodynamic parameters and autonomic activity have not been studied concurrently in HBO2, so any hypothetical connections between the two have remained untested. Therefore, we performed experiments using rats in which cerebral blood flow, electroencephalographic activity, cardiopulmonary hemodynamics, and autonomic traffic were measured in HBO2 at 5 and 6 atmospheres absolute. In some animals, autonomic pathways were disrupted pharmacologically or surgically. Our findings indicate that pulmonary damage in HBO2 is caused by an abrupt and significant increase in pulmonary vascular pressure, sufficient to produce barotrauma in capillaries. Specifically, extreme HBO2 exposures produce massive sympathetic outflow from the central nervous system that depresses left ventricular function, resulting in acute left atrial and pulmonary hypertension. We attribute these effects on the heart and on the pulmonary vasculature to HBO2-mediated central sympathetic excitation and catecholamine release that disturbs the normal equilibrium between excitatory and inhibitory activity in the autonomic nervous system.
Asunto(s)
Circulación Cerebrovascular/efectos de los fármacos , Oxigenoterapia Hiperbárica/efectos adversos , Lesión Pulmonar/inducido químicamente , Oxígeno/toxicidad , Animales , Electroencefalografía/efectos de los fármacos , Corazón/efectos de los fármacos , Paro Cardíaco/inducido químicamente , Hemodinámica/efectos de los fármacos , Oxigenoterapia Hiperbárica/métodos , Pulmón/efectos de los fármacos , Circulación Pulmonar/efectos de los fármacos , Ratas , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
The hypothesis that in conditions of hyperbaric oxygenation, nitric oxide (NO) modulates the vasodilatory effect of CO2 in the brain and thus accelerates the neurotoxic action of oxygen was verified experimentally. Conscious rats breathed atmospheric air or oxygen at 5 atm and blood flow in the striatum was measured before and after inhibition of carbonic anhydrase with acetazolamide, which causes retention of CO2 in the brain. Acetazolamide (35 mg/kg) increased blood flow in the animals when breathing air by 38 +/- 7.4% (p < 0.01), while preliminary inhibition of NO synthase with N(omega)-nitro-L-arginine-methyl ester (L-NAME, 30 mg/kg) significantly weakened its vasodilatory action. Inhibition of carbonic anhydrase in animals breathing hyperbaric oxygen at 5 atm prevented cerebral vasoconstriction, increased brain blood flow, and accelerated the development of oxygen convulsions. The vasodilatory effect of acetazolamide in hyperbaric oxygenation was significantly reduced in animals pretreated with the NO synthase inhibitor, such that the latent period of convulsions increased. The results obtained here provide evidence that in conditions of extreme hyperoxia, NO modulates the cerebral hyperemia developing in conditions of CO2 retention in the brain and accelerates the development of the neurotoxic actions of hyperbaric oxygen.
Asunto(s)
Encéfalo/fisiología , Dióxido de Carbono/metabolismo , Óxido Nítrico/fisiología , Oxígeno/efectos adversos , Presión , Acetazolamida/farmacología , Animales , Encéfalo/efectos de los fármacos , Inhibidores de Anhidrasa Carbónica/farmacología , Cuerpo Estriado/irrigación sanguínea , Cuerpo Estriado/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Electroencefalografía/métodos , Inhibidores Enzimáticos/farmacología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The activation of autonomic afferents (achieved through the vagus nerve (VN) electrical stimulation) on CNS O2 toxicity and cardiovascular function was investigated. In conscious rabbits at 5 ATA 02, prodromal signs of CNS O2 toxicity and convulsion latency were determined with and without vagus nerve (VN) stimulation. EEG, ECG and respiration were also recorded. In rabbits at 5 ATA, sympathetic overdrive and specific patterns on the EEG (synchronization of slow-waves), ECG (tachycardia) and respiration (respiratory minute volume increase) preceded motor convulsions. Vagus nerve stimulation increased parasympathetic component of autonomic drive and significantly delayed prodromal signs of oxygen toxicity and convulsion latency. Autonomic afferent input to the brain is a novel target for preventing CNS toxicity in HBO2.
Asunto(s)
Electroencefalografía , Epilepsia/inducido químicamente , Epilepsia/fisiopatología , Oxígeno/toxicidad , Estimulación del Nervio Vago , Nervio Vago/fisiopatología , Animales , ConejosRESUMEN
The hypothesis that decreases in brain blood flow during respiration of hyperbaric oxygen result from inactivation of nitric oxide (NO) by superoxide anions (O2(-)) is proposed. Changes in brain blood flow were assessed in conscious rats during respiration of atmospheric air or oxygen at a pressure of 4 atm after dismutation of O2(-) with superoxide dismutase or suppression of NO synthesis with the NO synthase inhibitor L-NAME. I.v. administration of superoxide dismutase increased brain blood flow in rats breathing air but was ineffective after previous inhibition of NO synthase. Hyperbaric oxygenation at 4 atm induced decreases in brain blood flow, though prior superoxide dismutase prevented hyperoxic vasoconstriction and increased brain blood flow in rats breathing hyperbaric oxygen. The vasodilatory effect of superoxide dismutase in hyperbaric oxygenation was not seen in animals given prior doses of the NO synthase inhibitor. These results provide evidence that one mechanism for hyperoxic vasoconstriction in the brain consists of inactivation of NO by superoxide anions, decreasing its basal vasorelaxing action.
Asunto(s)
Encéfalo/irrigación sanguínea , Hiperoxia/fisiopatología , Óxido Nítrico/metabolismo , Superóxidos/metabolismo , Vasoconstricción , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depuradores de Radicales Libres/farmacología , Oxigenoterapia Hiperbárica , Masculino , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Superóxido Dismutasa/farmacologíaRESUMEN
Studies on conscious rats with inhibition of NO synthase were used to assess the dynamics of brain blood flow and EEG traces during hyperbaric oxygenation at 4 or 5 atm. Oxygen at a pressure of 4 atm induced cerebral vasoconstriction in intact animals and decreased blood flow by 11-18% (p < 0.05) during 60-min exposure to hyperbaric oxygenation. Paroxysmal EEG activity and oxygen convulsions did not occur in rats at 4 atm of O2. At 5 atm, convulsive activity appeared on the EEG at 41 +/- 1.9 min, and blood flow decreased significantly during the first 20 min; blood flow increased by 23 +/- 9%, as compared with controls, (p < 0.01) before the appearance of convulsions on the EEG. Prior inhibition of NO synthase I (NOS I) and NO synthase III (NOS III) with N(omega)-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) or inhibition only of NOS I with 7-nitroindazole (7-NI, 50 mg/kg) prevented the development of hyperoxic hyperemia and paroxysmal spikes on the EEG during hyperbaric oxygenation at 5 atm. These results show that hyperbaric oxygen induces changes in cerebral blood flow which modulate its neurotoxic action via nitric oxide synthesized both in neurons and in cerebral vessels.
Asunto(s)
Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Oxigenoterapia Hiperbárica/efectos adversos , Óxido Nítrico Sintasa/efectos de los fármacos , Oxígeno/toxicidad , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Cuerpo Estriado/irrigación sanguínea , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/enzimología , Electroencefalografía , Endotelio Vascular/metabolismo , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo I , Óxido Nítrico Sintasa de Tipo III , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Convulsiones/inducido químicamente , Vasoconstricción/efectos de los fármacosRESUMEN
The data obtained demonstrated that NO restrains ET-1 production and blunts ET-1-mediated basal cerebrovascular tone. Local hyperoxygenation of the brain tissue decreases NO availability, supeoxide production, suppresses NO-mediated vascular tone and facilitates ET-1-mediated vasoconstriction.
Asunto(s)
Encéfalo/irrigación sanguínea , Endotelinas/fisiología , Hiperoxia/fisiopatología , Óxido Nítrico/fisiología , Vasoconstricción/fisiología , Animales , Masculino , Ratas , Ratas WistarAsunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Isquemia Encefálica/metabolismo , Inhibidores Enzimáticos/administración & dosificación , Indometacina/administración & dosificación , Quinacrina/administración & dosificación , Telencéfalo/enzimología , Animales , Química Encefálica/efectos de los fármacos , Isquemia Encefálica/patología , Ratas , ATPasa Intercambiadora de Sodio-Potasio , Telencéfalo/patologíaRESUMEN
The physiological role of extracellular superoxide dismutase (SOD3) has received insufficient study. We investigated the hypothesis that SOD3, which neutralizes superoxide anions (O2(-)) in the intercellular space of the brain, prevents the inactivation of nitric oxide (NO) and is thus involved in regulating cerebral vascular tone. Local brain blood flow was measured in the striatum of anesthetized rats during administration of various combinations of a SOD mimetic, a SOD inhibitor, an NO donor, and an NOS inhibitor into the striatum using a Hamilton syringe. In normal conditions, SOD3 was found to minimize O2(-) levels, protecting endogenously produced NO at a sufficient level to maintain cerebral vascular tone and reactivity. SOD3 was found to increase the vasodilatory effect of endogenously produced NO in the brain. SOD3 was found to neutralize superoxide anions produced in the brain during respiration of 100% O2 and to maintain basal NO levels and its vasodilatory potential in normobaric hyperoxia.
Asunto(s)
Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Circulación Cerebrovascular/fisiología , Superóxido Dismutasa/metabolismo , Animales , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/enzimología , Vasos Sanguíneos/fisiología , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Cuerpo Estriado/irrigación sanguínea , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/fisiología , Inhibidores Enzimáticos/farmacología , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/fisiología , Hiperoxia/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Ratas , S-Nitroso-N-Acetilpenicilamina/farmacología , Superóxido Dismutasa/antagonistas & inhibidores , Superóxidos/metabolismo , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaAsunto(s)
Adaptación Fisiológica , Oxigenoterapia Hiperbárica/efectos adversos , Óxido Nítrico/fisiología , Animales , Animales Recién Nacidos , Arginina/farmacología , Encéfalo/metabolismo , Síndromes de Neurotoxicidad , Donantes de Óxido Nítrico/farmacología , Nitroglicerina/farmacología , Ratas , Ratas WistarRESUMEN
Physiological role of extracellular superoxide dismutase (SOD3) remains obscure. We tested the hypothesis that SOD3 regulates the equilibrium between superoxide (O2-) and nitric oxide (NO), thereby controlling vascular tone and cerebrovascular reactivity. In anesthetized rats local blood flow was measured in the striatum after intracerebral delivery of SOD-mimetic, SOD-inhibitor, NO-donor and NOS-inhibitor by microdialysis. We have found that SOD3 minimizes O2- levels preserving NO availability at resting conditions. SOD3 promotes NO mediated vasodilatation by scavenging O2- and basal SOD3 levels is able to inactivate O2- produced by 100% oxygen breathing preserving vasodilator effect of NO.
Asunto(s)
Circulación Cerebrovascular/efectos de los fármacos , Óxido Nítrico/metabolismo , Superóxido Dismutasa/farmacología , Superóxidos/metabolismo , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Ratas , Superóxido Dismutasa/metabolismo , Vasodilatación/efectos de los fármacosRESUMEN
Hyperbaric oxygenation modulates cerebral blood flow affecting the development of oxygen convulsions. Before hyperbaric oxygenation-induced convulsions in rats the initial decrease in blood flow gave place to hyperemia, Po(2) increased. In rats receiving cyclooxygenase inhibitor indomethacin no convulsions were observed, blood flow and Po(2)were lower than in controls. Our results indicate that indomethacin prevents hyperemia and alleviates oxygen convulsions under conditions of hyperbaric oxygenation.
Asunto(s)
Inhibidores de la Ciclooxigenasa/farmacología , Oxigenoterapia Hiperbárica/efectos adversos , Hiperemia/prevención & control , Indometacina/farmacología , Convulsiones/inducido químicamente , Convulsiones/prevención & control , Telencéfalo/irrigación sanguínea , Telencéfalo/efectos de los fármacos , Animales , Inhibidores de la Ciclooxigenasa/uso terapéutico , Indometacina/uso terapéutico , Masculino , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Convulsiones/tratamiento farmacológicoRESUMEN
We tested a hypothesis that the cerebral blood flow (CBF) is reduced at hyperbaric oxygen due to inactivation of nitric oxide (NO) by superoxide anions (O2). In our experiments, the CBF was measured under hyperbaric oxygenation (HBO) 4ATA after inhibition of NO synthesis and inactivation of O2. The CBF was reduced at HBO exposure. Inhibition of NO--synthase type I and III (NOS) by L-NAME in the air caused the same decreasing of the CBF as at 4 ATA HBO. Hyperbaric vasoconstriction was diminished after NOS inhibition. Intravenous injection of superoxide dismutase (CuZn SOD) increased the CBF in the air and HBO exposure. This effect disappeared at preliminary NOS inhibition. These data suggest that inactivation of NO by O2 is a more effective mechanism of HBO vasoconstriction.
Asunto(s)
Circulación Cerebrovascular , Óxido Nítrico/metabolismo , Oxígeno/farmacología , Superóxidos/metabolismo , Vasoconstricción , Animales , Inhibidores Enzimáticos/farmacología , Oxigenoterapia Hiperbárica , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Ratas , Superóxido Dismutasa/farmacologíaRESUMEN
Hyperbaric oxygen (HBO2) causes CO2 retention in the brain that leads to the increase in cerebral blood flow (CBF) by poorly understood mechanisms. We have tested the hypothesis that NO is implicated in CBF-responses to hypercapnia under hyperoxic conditions. Alert rats were exposed to HBO2 at 5 ata and blood flow in the striatum measured by H2 clearance every 10 min. Acetazolamide, the inhibitor of carbonic anhydrase, was used to increase brain PCO2. CBF responses to acetazolamide administration (30 mg/kg, i.p.) were assessed in rats breathing air at 1 ata or oxygen at 5 ata with and without NOS inhibition (L-NAME, 30 mg/kg, i.p.). In rats breathing air, acetazolamide increased CBF by 34 +/- 7.4% over 30 min and by 28 +/- 12% over 3 hours while NOS inhibition with L-NAME attenuated acetazolamide-induced cerebral vasodilatation. HBO2 at 5 ata reduced CBF during the first 30 min hyperoxia, after that CBF increased by 55 +/- 19% above pre-exposure levels. In acetazolamide-treated animals, no HBO, induced vasoconstricton was observed and striatal blood flow increased by 53 +/- 18% within 10 min of hyperbaric exposure. After NOS inhibition, cerebral vasodilatation in response to acetazolamide during HBO2 exposure was significantly attenuated. The study demonstrates that NO is implicated in acetazolamide (CO2)-induced cerebral hyperemia under hyperbaric oxygen exposure.
Asunto(s)
Dióxido de Carbono/fisiología , Cuerpo Estriado/efectos de los fármacos , Óxido Nítrico/fisiología , Oxígeno/toxicidad , Vasodilatación/efectos de los fármacos , Acetazolamida/farmacología , Animales , Inhibidores de Anhidrasa Carbónica/farmacología , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Cuerpo Estriado/irrigación sanguínea , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Presión , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/fisiopatologíaRESUMEN
High pressure oxygen evokes a cerebral vasoconstriction and diminishes cerebral blood flow with the aid of mechanisms which are not yet sufficiently studied. We were checking a hypothesis that the hyperbaric oxygen (HBO2) inactivates cerebral nitrogen oxide (NO), interrupts its basal relaxing effect, and evokes a vasoconstriction. In our experiments, HBO2 decreased cerebral blood flow depending on the pressure. Inhibiting the NO-synthase weakened basal vasorelaxation in breathing with atmosphere air and eliminated the vasoconstriction in exposure to the HBO2. Inactivation of O2 prevented the HBO2-induced vasoconstriction. The data obtained reveal that diminishing of cerebral blood flow in HBO is related to the NO inactivation and weakening of its basal vasorelaxing effect. Possible mechanisms of the NO inactivation may involve its reaction with oxygen and superoxide anion which lead to diminishing of the tissue NO concentration and weakening of its vasorelaxing effect.
Asunto(s)
Circulación Cerebrovascular/fisiología , Óxido Nítrico/fisiología , Oxígeno/farmacología , Vasoconstricción/fisiología , Anestesia , Animales , Inhibidores Enzimáticos/farmacología , Óxido Nítrico/biosíntesis , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Presión , Ratas , Ratas Sprague-Dawley , Ratas Wistar , VigiliaRESUMEN
The goal of work was to reveal changes in microcirculation of the rat brain and the role of nitric oxide (NO) in development of seizures at hyperbaric oxygen exposure. The Wistar rats with implanted paired platinum electrodes in left and right striatum were used for experiments. The latency of seizures was defined by the EEG, the cerebral blood flow (CBF) was measured by hydrogen clearance. One group of animals was exposed to a 5-ata oxygen, while the others before oxygen treatment were injected with: Nw-nitro-L-arginine methyl ester (L-NAME), blockator of constitutive NO synthase; 7-nitroindozol (7NI), specific inhibitor of neural NO synthase. The latency of seizures was 41 +/- 1.9 min at 5 ata oxygen exposure. CBF was decreased to 10-14% but before seizures it increased to 23 +/- 9%. L-NAME and 7NI prevented development of hyperoxygen hyperemia and onset of seizures. The results indicate occurrence of hyperbaric oxygen changes of the CBF that modulate neurotoxic effects of NO in neurons as well as in cerebral vessels.