摘要:

BackgroundOpioids inhibit the rapid eye movement (REM) phase of sleep and decrease acetylcholine (ACh) release in medial pontine reticular formation (mPRF) regions contributing to REM sleep generation. It is not known whether opioids decrease ACh release by acting on cholinergic cell bodies or on cholinergic axon terminals. This study used in vivo microdialysis to test the hypothesis that opioids decrease ACh levels at cholinergic neurons in the laterodorsal tegmental nuclei (LDT) and LDT axon terminals in the mPRF.MethodsNine male cats were anesthetized with halothane, and ACh levels within the mPRF or LDT were assayed using microdialysis and high‐pressure liquid chromatography (HPLC). ACh levels were analyzed in response to dialysis of the mPRF and LDT with Ringer's solution (control), followed by dialysis with Ringer's solution containing morphine sulfate (MSO4) or naloxone. ACh in the mPRF also was measured during either dialysis delivery or intravenous infusion of remifentanil and during dialysis delivery of fentanyl.ResultsCompared with dialysis of Ringer's solution, micro‐dialysis with MSO4decreased ACh by 23% in the mPRF and by 30% in the LDT. This significant decrease in ACh was antagonized by naloxone. MSO4and fentanyl each caused a dose‐dependent decrease in mPRF ACh when delivered by dialysis. Remifentanil delivered by continuous intravenous infusion or by dialysis into the mPRF did not alter mPRF ACh.ConclusionsMorphine inhibits ACh at the cholinergic cell body region (LDT) and the terminal field in the mPRF. ACh in the mPRF was not altered by remifentanil and was significantly decreased by fentanyl. Thus, MSO4and fentanyl disrupt cholinergic neurotransmission in the LDT‐mPRF network known to modulate REM sleep and cortical electroencephalographic activation. These data are consistent with the possibility that inhibition of pontine cholinergic neurotransmission contributes to arousal state disruption by opioids.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundConventional cardiopulmonary resuscitation (CPR) includes 80‐100/min precordial compressions with intermittent positive pressure ventilation (IPPV) after very fifth compression. To prevent gastric insufflation, chest compressions are held during IPPV if the patient is not intubated. Elimination of IPPV would simplify CPR and might offer physiologic advantages, but compression‐induced ventilation without IPPV has been shown to result in hypercapnia. The authors hypothesized that application of continuous positive airway pressure (CPAP) might increase CO2elimination during chest compressions.MethodsAfter appropriate instrumentation and measurement of baseline data, ventricular fibrillation was induced in 18 pigs. Conventional CPR was performed as a control (CPRC) for 5 min. Pauses were then discontinued, and animals were assigned randomly to receive alternate trials of uninterrupted chest compressions at a rate of 80/min without IPPV, either at atmospheric airway pressure (CPRATM) or with CPAP (CPRCPAP). CPAP was adjusted to produce a minute ventilation of 75% of the animal's baseline ventilation. Data were summarized as mean +/− SD and compared with Student t test for paired observations.ResultsDuring CPR without IPPV, CPAP decreased PaCO2(55 +/− 28 vs. 100 +/− 16 mmHg) and increased SaO2(0.86 +/− 0.19 vs. 0.50 +/− 0.18%; P < 0.001). CPAP also increased arteriovenous oxygen content difference (10.7 +/− 3.1 vs. 5.5 +/− 2.3 ml/dl blood) and CO2elimination (120 +/− 20 vs. 12 +/− 20 ml/min; P < 0.01). Differences between CPRCPAPand CPRATMin aortic blood pressure, cardiac output, and stroke volume were not significant.ConclusionsMechanical ventilation may not be necessary during CPR as long as CPAP is applied. Discontinuation of IPPV will simplify CPR and may offer physiologic advantage.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia.MethodsCats were anesthetized with pentobarbital sodium and [Greek small letter alpha]‐chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs‐Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%.ResultsThe hypoxic ventilatory response was depressed in a dose‐dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.8%.ConclusionThe hypoxic ventilatory response is depressed by a high dose of halothane through a peripheral effect at the carotid body.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundRecently, a new structural family of potassium channels characterized by two pore domains in tandem within their primary amino acid sequence was identified. These tandem pore domain potassium channels are not gated by voltage and appear to be involved in the control of baseline membrane conductances. The goal of this study was to identify mechanisms of local anesthetic action on these channels.MethodsOocytes of Xenopus laevis were injected with cRNA from five cloned tandem pore domain baseline potassium channels (TASK, TREK‐1, TOK1, ORK1, and TWIK‐1), and the effects of several local anesthetics on the heterologously expressed channels were assayed using two‐electrode voltage‐clamp and current‐clamp techniques.ResultsBupivacaine (1 mM) inhibited all studied tandem pore potassium channels, with TASK inhibited most potently. The potency of inhibition was directly correlated with the octanol: buffer distribution coefficient of the local anesthetic, with the exception of tetracaine, to which TASK is relatively insensitive. The approximate 50% inhibitory concentrations of TASK were 709 [micro sign]M mepivacaine, 222 [micro sign]M lidocaine, 51 [micro sign]M R(+)‐ropivacaine, 53 [micro sign]M S(‐)‐ropivacaine, 668 [micro sign]M tetracaine, 41 [micro sign]M bupivacaine, and 39 [micro sign]M etidocaine. Local anesthetics (1 mM) significantly depolarized the resting membrane potential of TASK cRNA‐injected oocytes compared with saline‐injected control oocytes (tetracaine 22 +/− 6 mV vs. 7 +/− 1 mV, respectively, and bupivacaine 31 +/− 7 mV vs. 6 +/− 4 mV).ConclusionsLocal anesthetics inhibit tandem pore domain baseline potassium channels, and they could depolarize the resting membrane potential of cells expressing these channels. Whether inhibition of these channels contributes to conduction blockade or to the adverse effects of local anesthetics remains to be determined.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundMild hypothermia, a promising therapy being evaluated for various clinical situations, may suppress the formation of reactive oxygen species during reperfusion and may ameliorate microcirculatory perfusion failure (the “no‐reflow phenomenon”).MethodsIsolated rat livers underwent 30 min of perfusion, 2.5 h of ischemia, and 3 h of reperfusion. The temperature was maintained at 34 [degree sign]C (mild hypothermia, n = 5) or 38 [degree sign]C (normothermia, n = 6) for all three periods by perfusion of a modified Krebs Henseleit solution, air surface cooling, or both. A third group of livers was normothermic before and during ischemia and mildly hypothermic during reperfusion (reperfusion hypothermia, n = 6). Control livers had 3 h of perfusion at normothermia. Chemiluminescence (a measure of the generation of reactive oxygen species) and hepatic vascular resistance were monitored simultaneously to evaluate the effect of temperature on the formation of reactive oxygen species and the development of no reflow. Also measured were thiobarbituric acid reactive species and lactate dehydrogenase, as indicators of oxidative stress and cell injury.ResultsMild hypothermia decreased formation of reactive oxygen species and postischemic increases in vascular resistance. Reperfusion hypothermia also decreased postischemic increases in vascular resistance, but not as effectively as did mild hypothermia. Levels of thiobarbituric acid reactive species were lower for reperfusion hypothermia than for mild hypothermia at only 0 and 30 min of reperfusion. Lactate dehydrogenase was significant only at 0 min of reperfusion for the normothermic group. Oxygen consumption did not change.ConclusionThe prevention of hepatic vascular injury by suppression of oxidative stress may be an important protective mechanism of mild hypothermia.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe authors compared the lung injury in rabbits that occurred after tracheal instillation of human breast milk (HBM) acidified to pH 1.8 with hydrochloric acid (HCl), HBM at its native pH (7.0), and HBM acidified with gastric juice to pH 1.8 and 3.0.MethodsThe alveolar‐to‐arterial oxygen tension gradient and dynamic compliance were recorded before and hourly for 4 h after intratracheal instillation of 0.8 ml/kg HBM acidified with HCl (pH 1.8), HBM at its native pH (7.0), HBM acidified with gastric juice (pH 1.8 or 3.0), or 5% dextrose solution acidified with gastric juice (pH 1.8) as a control in 30 adult rabbits. The circulating neutrophil count and phagocyte oxidant activity were determined before and 1 and 4 h after instillation.ResultsThe alveolar‐to‐arterial oxygen tension gradient increased and dynamic compliance decreased significantly in all groups after instillation of HBM compared with baseline values and those in the control group. The severity of the lung injury after instillation of HBM at all pH values (1.8, 3.0, and 7.0) and after acidification with gastric juice or HCl was similar. The circulating neutrophil count increased steadily for 4 h after instillation (P < 0.013), whereas spontaneous phagocyte oxidant burst activity peaked at 1 h (P < 0.007) and returned to baseline by 4 h after instillation.ConclusionsThe severity of the lung injury after tracheal instillation of 0.8 ml/kg HBM in rabbits is similar at pH values between 1.8 and 7.0 after acidification with HCl or gastric juice. Tracheal instillation of HBM increases the circulating neutrophil count and phagocyte oxidant burst activity.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundInhalation anesthetics depress breathing dose dependently. The authors studied the dynamics of ventilation on changes in end‐tidal sevoflurane partial pressure. To learn more about the mechanisms of sevoflurane‐induced respiratory depression, the authors also studied its influence on the dynamic ventilatory response to carbon dioxide.MethodsExperiments were performed in cats anesthetized with [Greek small letter alpha] chloralose‐urethane. For protocol 1, step changes in end‐tidal sevoflurane partial pressure were applied and inspired ventilation was measured. Breath‐to‐breath inspired ventilation was related to the sevoflurane concentration in a hypothetical effect compartment based on an inhibitory sigmoid Emax model. For protocol 2, step changes in the end‐tidal partial pressure of carbon dioxide were applied at 0, 0.5, and 1% end‐tidal sevoflurane. The inspired ventilation‐end‐tidal partial pressure of carbon dioxide data were analyzed using a two‐compartment model of the respiratory controller, which consisted of a fast peripheral and slow central compartment. Values are the mean +/− SD.ResultsIn protocol 1, the effect‐site half‐life of respiratory changes caused by alterations in end‐tidal sevoflurane partial pressure was 3.6 +/− 1.0 min. In protocol 2, at 0.5% sevoflurane, the central and peripheral carbon dioxide sensitivities decreased to 43 +/− 20% and 36 +/− 18% of control. At 1% sevoflurane, the peripheral carbon dioxide sensitivity decreased further, to 12 +/− 13% of control, whereas the central carbon dioxide sensitivity showed no further decrease.ConclusionsSteady state inspired ventilation is reached after 18 min (i.e., 5 half‐lives) on stepwise changes in end‐tidal sevoflurane. Anesthetic concentrations of sevoflurane have, in addition to an effect on pathways common to the peripheral and central chemoreflex loops, a selective effect on the peripheral chemoreflex loop. Sevoflurane has similar effects on ventilatory control in humans and cats.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundStimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate‐induced depressions of nociceptive transmission at the level of the spinal cord.MethodsAnesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2).ResultsThe responses (mean +/− SD) elicited by the 1.9‐cm2stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10‐mg/kg dose (to 11 +/− 4% of control values compared with saline; P < 0.05). In contrast, when the 18‐cm2stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159 +/− 36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42 +/− 24% of control values; P < 0.05) than was observed with the smaller stimulus.ConclusionsDoses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid‐induced depression of descending inhibitory influences triggered by spatial summation.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAn increase in intracellular calcium concentration ([Ca2+]i) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic‐induced increases in [Ca2+]iconflict.MethodsChanges in [Ca2+]iwere measured using fura‐2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 [micro sign]M isoflurane. To define the causes of an increase in [Ca2+]i, slices were studied in Ca2+‐freemedium, in the presence of Ca2+‐channelblockers, and in the presence of the Ca2+‐releaseinhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2‐dichlorohexafluorocyclobutane. Single‐dose experiments in CA1 neurons in hippocampal slices with halothane (360 [micro sign]M) and in acutely dissociated CA1 neurons with halothane (360 [micro sign]M) and isoflurane (445 [micro sign]M) also were performed.ResultsIsoflurane at 0.5, 1, and 2 minimum alveolar concentrations increased basal [Ca2+]iin cortical slices in a dose‐dependent manner (P < 0.05). This increase was not altered by Ca2+‐channelblockers or Ca2+‐freemedium but was reduced 85% by azumolene. The nonanesthetic 1,2‐dichlorohexafluorocyclobutane did not increase [Ca2+] (i). In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca (2+)]iby 15 nM (P < 0.05). Halothane increased [Ca2+]iin dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately 30 nM (P < 0.05).Conclusions(1) Isoflurane and halothane reversibly increase [Ca2+]iin isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+]iis caused primarily by release from intracellular stores. (3) Increases in [Ca2+]ioccur with anesthetics but not with the nonanesthetic 1,2‐dichlorohexafluorocyclobutane.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundCardiac output (CO) is likely to influence the pharmacokinetics of anesthetic drugs and should be accounted for in pharmacokinetic models. The influence of CO on the pharmacokinetic parameters of alfentanil in pigs was evaluated using compartmental and recirculatory models.MethodsTwenty‐four premedicated pigs were evaluated during halothane (0.6‐2%) anesthesia. They were assigned randomly to one of three groups. One group served as control. In the other groups, the baseline CO was decreased or increased by 40% by pharmacologic intervention (propranolol or dobutamine). Boluses of alfentanil (2 mg) and indocyanine green (25 mg) were injected into the right atrium. Blood samples were taken for 150 min from the right atrium and aortic root. Arterial concentration‐time curves of indocyanine green and alfentanil were analyzed using compartmental models (two‐stage and mixed‐effects approach) and a recirculatory model, which can describe lung uptake and early distribution.ResultsThe CO of individual pigs varied from 1.33 to 6.44 l/min. Three‐compartmental modeling showed that CO is a determinant of the central compartment volume (V1, r2= 0.54), fast peripheral compartment volume (V2, r2= 0.29), steady state distribution volume (Vss, r2= 0.29), fast distribution clearance (Cl12, r2= 0.39), and elimination clearance (Cl10, r2= 0.51). Recirculatory modeling showed that CO is a determinant of total distribution volume (r2= 0.48), elimination clearance (r2= 0.54), and some distribution clearances. The pulmonary distribution volume was independent of CO.ConclusionsCardiac output markedly influences the pharmacokinetics of alfentanil in pigs. Therefore, accounting for CO enhances the predictive value of pharmacokinetic models of alfentanil.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID