Central hydrogen sulphide mediates ventilatory responses to hypercapnia in adult conscious rats.

AIM: Hydrogen sulphide (H2S) is endogenously produced and plays an important role as a modulator of neuronal functions; however, its modulatory role in the central CO2 chemoreception is unknown. The aim of the present study was to assess the role of endogenously produced H2S in the ventilatory response to hypercapnia in adult conscious rats. METHODS: Cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) inhibitors (aminooxyacetate: AOA and propargylglycine: PAG respectively) and a H2S donor (sodium sulphide: Na2S) were microinjected into the fourth ventricle (4V). Ventilation (V̇(E)), oxygen consumption (V̇O2) and body temperature were recorded before (room air) and during a 30-min CO2 exposure (hypercapnia, 7% CO2). Endogenous H2S levels were measured in the nucleus tractus solitarius (NTS). RESULTS: Microinjection of Na2S (H2S donor), AOA (CBS inhibitor) or PAG (CSE inhibitor) did not affect baseline of the measured variables compared to control group (vehicle). In all experimental groups, hypercapnia elicited an increase in V̇(E). However, AOA microinjection, but not PAG, attenuated the ventilatory response to hypercapnia (P < 0.05), whereas Na2S elicited a slight, not significant, enhancement. Moreover, endogenous H2S levels were found higher in the NTS after hypercapnia (P < 0.05) compared to room air (normoxia) condition. CONCLUSION: There are a few reports on the role of gaseous transmitters in the control of breathing. Importantly, the present data suggest that endogenous H2S via the CBS-H2S pathway mediates the ventilatory response to hypercapnia playing an excitatory role.

Central ventilatory control in the South American lungfish, Lepidosiren paradoxa: contributions of pH and CO(2).

Lungfish represent a probable sister group to the land vertebrates. Lungfish and tetrapods share features of respiratory control, including central, peripheral and intrapulmonary CO(2) receptors. We investigated whether or not central chemoreceptors in the lungfish, L. paradoxa, are stimulated by CO(2) and/or pH. Ventilation was measured by pneumotachography for diving animals. The fourth cerebral ventricle was equipped with two catheters for superfusion. Initially, two control groups were compared: (1) catheterized animals with no superfusion and (2) animals superfused with mock CSF solutions at pH = 7.45; PCO(2) = 21 mmHg. The two groups had virtually the same ventilation of about 40 ml BTPS kg(-1) h(-1) (P > 0.05). Next, PCO(2) was increased from 21 to 42 mmHg, while pH(CSF) was kept at 7.45, which increased ventilation from 40 to 75 ml BTPS kg(-1) h(-1). Conversely, a decrease of pH(CSF) from 7.45 to 7.20 (PCO(2) = 21 mmHg) increased ventilation to 111 ml BTPS kg(-1) h(-1). Further decreases of pH(CSF) had little effect on ventilation, and the combination of pH(CSF) = 7.10 and PCO(2) = 42 mmHg reduced ventilation to 63 ml BTPS kg(-1) h(-1).

Components to the acid-base related ventilatory drives in the South American lungfish Lepidosiren paradoxa.

Lungfish are closely related to terrestrial vertebrates (tetrapoda). Like tetrapods, the South American lungfish (Lepidosiren paradoxa) has central chemoreceptors involved in regulation of acid-base status. However, no data were available on peripheral CO(2)/[H(+)] receptors. Therefore, we tested the hypothesis that such receptors exist by measuring the ventilatory responses during a 5h exposure to combined aquatic/gas phase hypercarbia 7% (approximately 49 mmHg). Normocarbic control ventilation was 22 ml BTPS kg(-1)h(-1), and hypercarbia increased ventilation to 175 ml BTPS kg(-1)h(-1) at 5h. This procedure was repeated with the modification that normocarbic mock CSF (pH 7.45; P(CO2) = 20.7 mmHg) was applied to superfuse the cerebral ventricular system during the last 2h of the experiment. This served to eliminate the hypercarbic stimulus to the central chemoreceptors, while possible responses from peripheral chemoreceptors would remain intact. Peripheral receptors were detected, since ventilation became reduced to 62 ml BTPS kg(-1)h(-1) (P<0.05), which exceeds the initial normocarbic control ventilation (P<0.05). Based on this, the peripheral contribution accounted for 20% of the total response to hypercarbia, similar to the contribution of these receptors in man.

Efeito do ultra-som e do d-pantenol na regeneracao tegumentar / Effect of ultrasound and dexpanthenol on wound healing

Estudar os efeitos dos tratamentos com ultra-som (US) e d-pantenol (d-p) na reparacao tegumentar em ratos por meio de analise histoetrica e histopatologica. Metodo: foram utilizados 50 ratos wistar, anestesiados por Thionembutal sodico (50 mg/kg), dos quais foi retirado 1cm2 de pele na rehiao dorsal, sendo que 25 foram submetidos a tratamento diario por 7 dias e 25 por 14 dias. Os grupos experimentais (n=5) foram: controle (C), gel (G), US (3MHz, 0,1 W/cm2, 1 minuto, modo continuo), d-p na concentracao de (10 por cento) e US+d-p. seccoes de 6 um de espessura da lesao foram procesados para coloracao em Hematoxilina-Eosina. A re-epitelizacao e o numero de fibroblastos e leucocitos foram obtidos num processador de imagens (Software Imagem Pro-Plus) e analisados pelo teste ANOVA, seguido de Tukey para comparacao da medias. Resultados: a re-epitelizacao dos grupos US(1869,6+-238,4 um) e US+d-p(2167,7+-232 um) foi maior (p<-0,05) em relacao ao C(987,7+-146,8 um), mas nao diferiram entre si. O numero de fibroblastos no grupo US (419+-37) com sete dias de tratamento foi significativamente maior em relacao aos demais grupos: (C:250+-17), (d-p:296+-49) e (US+d-p:274+-18). No grupo US, tratado por sete dias, a media de leucocitos (134+-15) foi menor (p<-0,05) em relacao ao C (253+-37), d-p (222+-29) e US+d-p (153+-14), evidenciando seu efeito na fase inicial do processo inflamatorio. Conclusoes: o US acelera o processo de reparo, bem como associado ao d-p. Porem, essa associacao dos tratamentos, US+d-p, n'ao mostrou resultados significativos em relacao ao tratamento com US isolado

An assessment of dead space in pulmonary ventilation of the toad Bufo schneideri.

The respiratory cycles of Rana and Bufo has been disputed in relation to flow patterns and to the respiratory dead-space of the buccal volume. A small tidal volume combined with a much larger buccal space motivated the "jet steam" model that predicts a coherent expired flow within the dorsal part of the buccal space. Some other studies indicate an extensive mixing of lung gas within the buccal volume. In Bufo schneideri, we measured arterial, end-tidal and intrapulmonary PCO(2) to evaluate dead-space by the Bohr equation. Dead-space was also estimated as: V(D)=(total ventilation-effective ventilation)/f(R), where total ventilation and f(R) were measured by pneumotachography, while effective ventilation was derived from the alveolar ventilation equation. These approaches were consistent with a dead space of 30-40% of tidal volume, which indicates a specific pathway for the expired lung gas.

Acid-base regulation in the South American lungfish Lepidosiren paradoxa: effects of prolonged hypercarbia on blood gases and pulmonary ventilation.

The South American lungfish (Lepidosiren paradoxa) has well-developed lungs and highly reduced gills. To evaluate acid-base regulation, we applied hypercarbia while blood gases and pulmonary ventilation were measured for up to 48 h. Dorsal aortic blood was analyzed, and pulmonary ventilation was measured by pneumotachography. Two protocols were used: (1) normocarbia (control) followed by aquatic hypercarbia (7% CO2 approximately 49 mmHg), gas phase normocarbic; and (2) normocarbia (control) followed by combined aquatic/gas phase hypercarbia (7% CO2). Normocarbic values were pHa~7.5, Paco2 approximately 17 mmHg, and [HCO-3]pl approximately 22 mM. For protocol 1, the first hour of exposure increased Paco2 from 17.0 to 37.4 mmHg, and pHa fell to 7.21 and remained there for the rest of the experiment. At 3 h, pulmonary ventilation reached sixfold the normocarbic value but then decreased. For protocol 2, combined gas phase/water hypercarbia had a large effect on acid-base status. Thus, Paco2 increased gradually to 74 mmHg (pHa=7.15) at 48 h. At 3 h, ventilation reached a sixfold increase relative to normocarbic control but then rose further to a 60-fold peak at 6 h, followed by a gradual decline. As in some salamanders and air-breathing teleosts, there was no evidence of active extracellular modulation bicarbonate.

Effects of acute temperature changes on aerial and aquatic gas exchange, pulmonary ventilation and blood gas status in the South American lungfish, Lepidosiren paradoxa.

Lungfish (Dipnoi) are probably sister group relative to all land vertebrates (Tetrapoda). The South American lungfish, Lepidosiren paradoxa, depends markedly on pulmonary gas exchange. In this context, we report on temperature effects on aquatic and pulmonary respiration, ventilation and blood gases at 15, 25 and 35 degrees C. Lung ventilation increased from 0.5 (15 degrees C) to 8.1 ml BTPS kg(-1) min(-1) (35 degrees C), while pulmonary O(2)-uptake increased from 0.06 (15 degrees C) to 0.73 ml STPD kg(-1) min(-1) (35 degrees C). Meanwhile aquatic O(2)-uptake remained about the same ( approximately 0.01 ml STPD kg(-1) min(-1)) at all temperatures. Concomitantly, the pulmonary gas exchange ratio (R(E)) rose from 0.11 (15 degrees C) to 0.62 (35 degrees C), because a larger fraction of total CO(2) output became eliminated by the lung. Accordingly, PaCO(2) rose from 13 (15 degrees C) to 37 mm Hg (35 degrees C), leading to a significant decrease of pHa at higher temperature (pHa=7.58-15 degrees C; 7.33-35 degrees C). The acid-base status of L. paradoxa was characterized by a generally low pH (7.4-7.5), high bicarbonate level (20-25 mM) and PaO(2) ( approximately 80 mm Hg). The increased dependence on the lung at higher temperature parallels data for amphibians. Further, the effects of bimodal gas exchange on temperature-dependent acid-base regulation closely resemble those of anuran amphibians.