Anesthesia and analgesia
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Anesthesia and analgesia · Jan 2003
One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model.
We tested the hypothesis that one-lung ventilation (OLV) with high tidal volumes (VT) and zero positive end-expiratory pressure (PEEP) may lead to ventilator-induced lung injury. In an isolated, perfused rabbit lung model, VT and PEEP were set to avoid lung collapse and overdistension in both lungs, resulting in a straight pressure-time (P-vs-t) curve during constant flow. Animals were randomized to (a) nonprotective OLV (left lung) (n = 6), with VT values as high as before randomization and zero PEEP; (b) protective OLV (left lung) (n = 6), with 50% reduction of VT and maintenance of PEEP as before randomization; and (c) control group (n = 6), with ventilation of two lungs as before randomization. The nonprotective OLV was associated with significantly smaller degrees of collapse and overdistension in the ventilated lung (P < 0.001). Peak inspiratory pressure values were higher in the nonprotective OLV group (P < 0.001) and increased progressively throughout the observation period (P < 0.01). The mean pulmonary artery pressure and lung weight gain values, as well as the concentration of thromboxane B(2), were comparatively higher in the nonprotective OLV group (P < 0.05). A ventilatory strategy with VT values as high as those used in the clinical setting and zero PEEP leads to ventilator-induced lung injury in this model of OLV, but this can be minimized with VT and PEEP values set to avoid lung overdistension and collapse. ⋯ One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure (PEEP) is injurious in the isolated rabbit lung model. A ventilatory strategy with tidal volumes and PEEP set to avoid lung overdistension and collapse minimizes lung injury during one-lung ventilation in this model.
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Anesthesia and analgesia · Jan 2003
Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: the effects on agonist enhancement, direct activation, and inhibition.
At clinically relevant concentrations, ethers, alcohols, and halogenated alkanes enhance agonist action on the gamma-aminobutyric acid(A) (GABA(A)) receptor, whereas nonhalogenated alkanes do not. Many anesthetics also directly activate and/or inhibit GABA(A) receptors, actions that may produce important behavioral effects; although, the effects of nonhalogenated alkane anesthetics on GABA(A) receptor direct activation and inhibition have not been studied. In this study, we assessed the abilities of two representative nonhalogenated alkanes, cyclopropane and butane, to enhance agonist action, directly activate, and inhibit currents mediated by expressed alpha(1)beta(2)gamma(2L) GABA(A) receptors using electrophysiological techniques. Our studies reveal that cyclopro- pane and butane enhance agonist action on the GABA(A) receptor at concentrations that exceed those required to produce anesthesia. Neither nonhalogenated alkane directly activated nor inhibited GABA(A) receptors, even at concentrations that approach their aqueous saturated solubilities. These results strongly suggest that the behavioral actions of nonhalogenated alkane anesthetics do not result from their abilities to enhance agonist actions, directly activate, or inhibit alpha(1)beta(2)gamma(2L) GABA(A) receptors and are consistent with the hypothesis that electrostatic interactions between anesthetics and their protein binding sites modulate GABA(A) receptor potency. ⋯ When normalized to either their in vivo anesthetic potencies or hydrophobicities, cyclopropane and butane are 1-1.5 orders of magnitude less potent enhancers of agonist action on alpha(1beta2gamma2L) GABA(A) receptors than isoflurane. Additionally, cyclopropane and butane fail to directly activate or inhibit receptors, even at near aqueous saturating concentrations. Thus, it is unlikely that either enhancement or inhibition of the most common GABA(A) receptor subtype in the brain accounts for the behavioral activities of cyclopropane and butane.
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Anesthesia and analgesia · Jan 2003
Volatile anesthetics reduce agonist affinity at nicotinic acetylcholine receptors in the brain.
In previous studies we and others have demonstrated that the activation of nicotinic acetylcholine receptors (nAChRs) is inhibited by subanesthetic concentrations of volatile anesthetics. The mechanism by which activation is inhibited is unknown. Studies of the evolutionarily related nAChRs from the electric fish Torpedo have suggested that volatile anesthetics alter the affinity of the agonist for the receptor. We studied the effect of two volatile anesthetics, isoflurane and sevoflurane, on equilibrium binding of the high-affinity nicotinic agonist epibatidine to nicotinic receptors from mouse brain. We studied binding to male and female brain separately, because sex differences in nicotine responses have been reported. Male and female brains have equal epibatidine binding without anesthetic. Isoflurane and sevoflurane reduce the binding of [(3)H]epibatidine to male and female nicotinic receptors, but only at concentrations at and above those required for anesthesia. The 50% inhibitory concentration for isoflurane inhibition of [(3)H]epibatidine binding to male brain was 0.58 +/- 0.07 mM and to female brain was 1.62 +/- 0.30 mM. The 50% inhibitory concentration for sevoflurane inhibition of [(3)H]epibatidine binding to male brain was 0.77 +/- 0.05 mM and to female brain was 0.77 +/- 0.04 mM. There was no statistically significant difference in the effect of either drug between sexes (P > 0.05). Although there is a slight decrease in agonist affinity at anesthetic concentrations, the marked reductions in nAChR function at subanesthetic concentrations cannot be attributed to changes in agonist affinity. ⋯ Volatile anesthetics reduce the activation of nicotinic acetylcholine receptors by an unknown mechanism. We have demonstrated that although isoflurane and sevoflurane inhibit agonist affinity, the concentrations required are too large to be responsible for the dynamic changes observed.
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Anesthesia and analgesia · Jan 2003
Hemodilution does not alter arterial baroreflex control of heart rate in anesthetized dogs.
The cardiovascular effects of acute normovolemic hemodilution (ANH) are characterized by increased cardiac output and decreased systemic vascular resistance. However, whether arterial baroreflex function is altered by ANH remains undetermined. We assigned 23 anesthetized, mechanically ventilated dogs to mild ANH (hemoglobin, 7-8 g/dL; n = 11) or profound ANH (hemoglobin, 4-5 g/dL; n = 12) achieved by phlebotomy and simultaneous exchange with lactated Ringer's solution at 1:3 ratio to maintain constant central venous pressure and pulmonary artery occluded pressure. Baroreflex sensitivity was assessed by measurements of RR intervals of the electrocardiogram and mean arterial blood pressure (MAP) through a femoral artery catheter. Baroreflex responses were triggered by bolus IV injections of phenylephrine (25-75 micro g) and nitroprusside (50-100 micro g). The linear portion of the baroreflex curves relating RR intervals and MAP were used to determine baroreflex sensitivities. Compared with the predilution period, both ANH groups had significant increases in cardiac output and decreases in systemic vascular resistance (P < 0.01), whereas MAP and heart rate (HR) remained unchanged. However, no significant difference was detected between pre-ANH and post-ANH baroreflex sensitivities in either group. Our results indicate that arterial baroreflex control of HR is preserved during ANH to a hemoglobin concentration of 4-5 g/dL in anesthetized dogs. ⋯ Acute normovolemic hemodilution may be preoperatively used to minimize the requirement of allogeneic blood products during major surgery. We found that baroreflex function is preserved during mild (hemoglobin concentration, 7-8 g/dL) and profound hemodilution (hemoglobin concentration, 4-5 g/dL) in pentobarbital-anesthetized dogs.