RESUMEN
We examined the influence of two clinically relevant concentrations (1 and 2 MAC (minimum alveolar concentration)) of halothane and sevoflurane on both efflux and reverse modes of Na+-Ca2+ exchange (NCX) in enzymatically dissociated adult rat cardiac myocytes. We hypothesised that a volatile anaesthetic-induced decrease in myocardial contractility is mediated by a reduction in intracellular calcium concentration ([Ca2+]i) via inhibition of NCX. Cells were exposed to cyclopiazonic acid and zero extracellular Na+ and Ca2+ to block sacroplasmic reticulum (SR) re-uptake and NCX efflux, respectively. As [Ca2+]i increased under these conditions, extracellular Na+ was rapidly (< 300 ms) reintroduced in the presence or absence of a volatile anaesthetic to selectively promote Ca2+ efflux via NCX. Other cells exposed to cyclopiazonic acid and ryanodine to inhibit SR Ca2+ re-uptake and release were Na+ loaded in zero extracellular Ca2+. The reintroduction of extracellular Ca2+ was used to selectively activate Ca2+ influx via NCX. Compared to controls, both 1 and 2 MAC halothane as well as sevoflurane reduced NCX-mediated efflux. The reduction in NCX-mediated influx was concentration dependent, but comparable between the two anaesthetics. Both anaesthetics at each concentration also shifted the relationship between extracellular Na+ (or extent of Na+ loading) and NCX-mediated efflux (or influx) to the right. These data indicate that despite inhibition of NCX-mediated Ca2+ efflux, volatile anaesthetics produce myocardial depression. However, the inhibition of NCX-mediated Ca2+ influx may contribute to decreased cardiac contractility. The overall effect of volatile anaesthetics on the [Ca2+]i profile is likely to be determined by the relative contributions of influx vs. efflux via NCX during each cardiac cycle.
Asunto(s)
Anestésicos por Inhalación/farmacología , Calcio/metabolismo , Halotano/farmacología , Éteres Metílicos/farmacología , Miocardio/metabolismo , Intercambiador de Sodio-Calcio/metabolismo , Sodio/metabolismo , Animales , Antiarrítmicos/farmacología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Corazón/efectos de los fármacos , Corazón/fisiología , Indoles/farmacología , Masculino , Microscopía Confocal , Miocardio/citología , Ratas , Ratas Sprague-Dawley , Rianodina/farmacología , Retículo Sarcoplasmático/efectos de los fármacos , Retículo Sarcoplasmático/metabolismo , SevofluranoRESUMEN
We studied the renovascular action of adenosine on isolated perfused rat 10 min after drug injections. Adenosine was applied intraarterially as a single bolus injection in logarithmically increasing doses (0.3-30 microg). Adenosine treatment induced a biphasic vascular-response, namely, an initial vasoconstriction followed by a long-lasting vasodilation. Pretreatment with 0.1. 0.3, or 1.0 mM theophylline or quinidine (2 microg/ml) significantly depressed both components of the adenosine response. The vasoconstrictor response to adenosine was not affected by either 0.5 or 1.0 microg/ml dihydroergocristine. whereas the vasodilatory response was dose-dependently reduced. The biphasic response to adenosine was markedly depressed by 10 microg/ml indomethacin and was augmented by combining this agent with quinidine. We studied the possible roles of the platelet activating factor (PAF) and nitric oxide-cGMP systems in the renovascular actions of adenosine. Tebokan (a PAF antagonist) antagonized both components of the response, but methylene blue (MM) reduced only the pressory part Electron-microscopic examination of kidneys exposed for 15 min to MM showed some acute degenerative alterations and constriction in the glomeruli. From these findings, we conclude that the P1/A1, and P2x purinoceptors, the prostaglandins, PAF, and the NO-cGMP systems have a share in the renovascular actions of adenosine.
Asunto(s)
Adenosina/farmacología , Circulación Renal/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Femenino , Guanosina Monofosfato/fisiología , Técnicas In Vitro , Riñón/efectos de los fármacos , Riñón/ultraestructura , Masculino , Óxido Nítrico/fisiología , Factor de Activación Plaquetaria/farmacología , Prostaglandinas/fisiología , Ratas , Ratas Sprague-Dawley , Receptores Purinérgicos/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
Totally 25 cases without any fetal anomaly, 10 with polyhydramnios, 10 with oligohydramnios and 5 with normal volume of amniotic fluid were taken into consideration. Their amnion covering the placenta and umbilical cord were examined under electron microscope. In the group with polyhydramnios the microvilli facing the amniotic cavity were denser in certain regions. The intercellular space was widened and the terminal bars were opened. Within the cells the number of vesicles were increased and there were large cysternas within these vesicles. It was postulated that the large cysternas found in the basal and apical parts of the cell were composed of macropinocytotic vesicles of the basal membrane. In the group with oligohydramnios the microvilli on the apical side were diminished. The intercellular space of the lateral side was narrowed. The electron density of the basal lamina was increased. The cellular structures were apparently reduced having just a few vesicles and lipid granules. Both in polyhydramnios and oligohydramnios the amniotic epithelium cells covering the placenta and umbilical cord are responsible for the transfer of the fluid into the amniotic cavity. Possibly they control the amount of fluid by reducing or increasing its passage.