摘要:

Preservation of the arterial baroreflex response is important to restore cardiac output and blood pressure by reflex sympathetic nerve activation in the event of sudden hypotension caused by acute blood loss during surgery. However, the arterial baroreflex may be significantly attenuated by both anesthetics and hypotensive agents. In isoflurane-anesthetized dogs, the authors investigated the arterial baroreflex response 1) to bolus injections of sodium nitroprusside (SNP), prostaglandin E1(PGE1) and trimethaphan (TM); and 2) to rapid blood loss (5 ml/kg) before and during induced hypotension with SNP, PGE1, and TM by measuring mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Hypotension produced by both SNP and PGE1was accompanied by an increase in RSNA and HR. The increase in RSNA and HR following the SNP bolus injection was significantly greater than that following injection of PGE1(P< 0.05). Trimethaphan was associated with a decrease in RSNA and HR. Rapid blood loss resulted in the same degree of MAP reduction (20 ± 2 mmHg) before and during induced hypotension. Sensitivities of baroreflex, as evaluated by ratios of maximum changes in RSNA or HR to MAP (△RSNA/△MAP, △HR/△MAP), in response to rapid blood loss, were significantly suppressed during continuously induced hypotension, as compared with responses before induced hypotension. Despite the same degree of induced hypotension (70 ± 5 mmHg of MAP), △RSNA/△MAP and △HR/△MAP in response to rapid blood loss were significantly greater with PGE1than those with SNP (P< 0.05). Because of its sympathetic ganglion blocking action, arterial baroreflex sensitivity was suppressed by rapid blood loss during TM infusion. The authors conclude that induced hypotension with PGE1provides a greater margin of safety than that associated with SNP when acute blood loss occurs during isoflurane anesthesia. Trimethaphan is inferior to both PGE1and SNP in this respect.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). One mechanism suggested for this action is stimulation of release of endothelium-derived relaxing factor. The present study has tested this hypothesis. These studies were performed in 66 ventilated and perfused isolated rat lungs. There were three study protocols. Study 1 examined the effect on HPV of the inhibition of soluble guanylate cyclase by methylene blue (MB). In the presence or absence of MB, the lungs constricted to hypoxia with pulmonary artery pressure increases of 8.6 ± 0.2 cmH2O and 11.5 ± 0.4 cmH2O, respectively, and halothane, enflurane, and isoflurane caused a reversible 50% decrease in the pulmonary pressor response, but ace-tylcholine (ACh) was vasodilatory in the saline group and vasoconstrictor in the MB group. In Study II a dose–response curve was established for the potent stimulator (Sin 1) of the enzyme guanylate cyclase. In the presence of MB the dose–response curve for Sin 1 was shifted to the right with an increase in the ED50for Sin 1 from 44 μM for the control to 85 μM for the MB group. In Study III, baseline pulmonary artery pressure was increased with U46619, and the hypoxic pressor response was increased (28.9 ± 2.5 cmH2O), but halothane again caused a 50% decrease (11.0 ± 1.8 cmH2O) in the response to hypoxia. In summary, when soluble guanylate cyclase activity is inhibited by MB, the inhibition of hypoxic pulmonary vasoconstriction by halothane, isoflurane, or enflurane was unaltered, and release of endothelium-derived relaxing factor (EDRF) is therefore not an essential mechanism underlying this action.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Malignant hyperthermia (MH) can be triggered in swine either by stress or by certain anesthetic agents. In humans, MH commonly occurs in patients previously exposed uneventfully to triggering anesthetics. This variability in expressivity of the MH syndrome is a combination of unknown genetic and environmental factors. A hypothesis was tested that a fall in rectal temperature following general anesthesia can prevent the MH syndrome in susceptible patients. Nine littermate Pietrain pigs with MH were exposed to halothane after their rectal temperatures were stabilized at 35°, 36°, and 37° C during thiopental/nitrous oxide anesthesia. Thein vivoMH metabolic, cardiopulmonary, and contracture responses were attenuated at the lower rectal temperatures. The effect of varying temperatures on biopsies of skeletal muscle from these animals showed a marked decrease in contracture response to halothane when the muscle was cooled to 25° C. Studies on the Ca2+uptake process and on Ca2+channel-Ca2+release properties of isolated sarcoplasmic reticulum (SR) membranes showed that increasing incubation temperatures from 25° to 38° C increased the Ca2+uptake rate by the SR Ca2+pump and also increased the probability of Ca2+-induced Ca2+opening of a Ca2+channel and the release of stored Ca2+. This study indicates that temperature can have a marked effect on the expressivity of the MH defect at the whole animal, isolated tissue, and fragmented membrane levels of organization. Since many surgical patients' temperatures decrease after induction and anesthesia, this may explain one environmental factor that determines the incidence, rate, and magnitude of the MH syndrome.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Using magnetic resonance spectroscopy, the authors tested whether cerebral concentrations of inhaled anesthetics do not increase proportionately at inspired concentrations exceeding 3% 1) because anesthetics bind to and saturate specific sites in the brain or 2) because anesthetic-induced depression of ventilation limits the increase in alveolar anesthetic partial pressure. New Zealand White rabbits were anesthetized with methohexital, 70% nitrous oxide, and local infiltration of 1% lidocaine. Cerebral concentrations of anesthetic were determined from19F spectra acquired with nuclear magnetic resonance (NMR). Inspired, end-tidal, and arterial anesthetic concentrations, and end-tidal and arterial partial pressure of carbon dioxide were measured. Blood/gas partition coefficients were determined and used to convert arterial anesthetic concentration to partial pressures. In seven spontaneously breathing animals, halothane (1%; n = 5) or isoflurane (0.8%; n = 2) was administered at a constant inspired concentration for 20 min; NMR spectra were acquired between 10 and 20 min. Thereafter, the inspired concentration was increased and the process repeated until apnea occurred. Two additional rabbits were anesthetized with isoflurane and studied similarly but with higher inspired concentrations during mechanical ventilation. In spontaneously breathing animals, ventilatory depression occurred, documented by marked increases in PaCO2, and cerebral concentrations of anesthetic did not increase proportionately at inspired concentrations exceeding 3%. In contrast to an absence of a correlation of inspired and cerebral concentrations during spontaneous ventilation, arterial and cerebral concentrations correlated linearly during both spontaneous and mechanical ventilation (R2> 0.969). These results are consistent with depression of ventilation, rather than binding to specific cerebral sites as an explanation for the nonlinear relationship between cerebral and inspired anesthetic concentrations.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Cerebral blood volume (CBV = cerebral plasma volume [CPV] + cerebral red cell volume [CRBCV]) is one determinant of intracranial pressure. In an effort to quantitate the effects of anesthetics and Paco2on CBV, the authors measured cerebral plasma volume (CPV) in normocapnic (Paco2≈ 42 mmHg) and hypocapnic (Paco2= 22 mmHg) rats receiving 1 MAC doses of isoflurane or halothane, or given an approximately equivalent dose of pentobarbital. All animals were paralyzed, their lungs mechanically ventilated, and body temperature kept normal throughout the study. CPV was measured using14C-labeled dextran, a large (70,000 molecular weight [M.W.]), nondiffusible compound that was given intravenously and allowed to circulate for ≈5 min. The experiments then were terminated by freezing the brainsin situwith liquid N2poured into a funnel affixed to the exposed calvarium. Isotope concentrations in solubilized brain and in plasma were determined by scintillation counting, and CPV was calculated as the ratio between these values. CPV during both hypocapnic and normocapnic pentobarbital anesthesia was less than with either volatile agent. During normocapnia, CPV for pentobarbital = 2.1 ± 0.26 ml/100 g (mean ± SD, n = 8), compared with 2.96 ± 0.44 ml/100 g (n = 9) and 3.06 ± 0.44 ml/100 g (n = 9) for halothane and isoflurane, respectively. There were no differences in CPV between the two volatile agents during normocapnia. However, during hypocapnia, CPV in isoflurane-anesthetized animals decreased to 2.29 ± 0.43 ml/100 g, as compared with 2.68 ± 0.36 ml/100 g with halothane (P< 0.05) and 1.86 ± 0.33 ml/100 g for pentobarbital (not significantvs.isoflurane,P< 0.01 for pentobarbitalvs.halothane). The magnitude of these differences—particularly the changes produced by Paco2—appears to be smaller than previously published differences in cerebral blood flow (CBF), which supports suggestions that it may be invalid to equate changes in CBF with changes in brain blood volume or intracranial pressure.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Supraventricular tachydysrhythmias are a commonly encountered clinical problem after cardiothoracic surgery. Current choices for acute drug therapy of these dysrhythmias include intravenous verapamil as well as esmolol, but no data yet exist comparing the relative negative dromotropic (atrioventricular [A-V] nodal blocking) and negative inotropic effects of these agents. The purpose of this study was to compare the effects of esmolol with those of verapamil on systemic hemodynamics, coronary blood flow, and cardiac contractility at doses that produce a similar ventricular response rate in an animal model of a supraventricular tachydysrhythmia. Rapid electrical stimulation (800 impulses/min) of the left atrium in 14 dogs resulted in a rapid and irregularly irregular ventricular rhythm. Esmolol or verapamil were administered by bolus and then infusion to incrementally slow the average ventricular rate. Regional myocardial contractility was measured using the end-systolic pressure-length relationship (Ees). At drug doses that produced similar decreases in ventricular rate, esmolol produced a greater decrease in contractility (Ees: 284 ± 46 to 40 ± 22 mmHg/mm, LV dp/dt:2,400 ± 450 to 1,360 ± 450 mmHg/sec) compared with that following verapamil (Ees: 297 ± 57 to 116 ± 25 mmHg/mm, LV dp/dt: 2,040 ± 580 to 1,950 ± 520 mmHg/sec). This was accompanied by a modest decrease in cardiac output in the esmolol group (2,880 ± 940 to 2,290 ± 730 ml/min) compared with an unchanged cardiac output as ventricular rate slowed in verapamil-treated animals. Stroke volume increased significantly in the verapamil-treated animals (10.9 ± 4.0 to 18.5 ± 4.6 ml), but remained unchanged following esmolol. Neither drug produced adverse effects on perfusion pressure nor left anterior descending coronary blood flow in the doses employed in this model. The differential effects of esmolol and verapamil on contractility may have important implications when used to control the ventricular response to supraventricular tachydysrhythmias in the presence of impaired ventricular function.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Serotonin was administered intrathecally onto cat spinal cords to evaluate the pharmacology by which it suppresses noxiously evoked activity of wide-dynamic-range (WDR) neurons in the spinal dorsal horn. Doses of 500, 1000 and 2000 μg serotonin produced significant suppression of the mean noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord (21, 44, and 69% at 30 min, respectively). The dose-dependent effects were partially reversed by the intravenous administration of the serotonin antagonist methysergide (1 or 2 mg). Intravenous administration of the alpha 2-adrenergic antagonist yohimbine (0.5 or 1.0 mg/kg) produced a significant antagonism of the effects of serotonin. In contrast to the effects of methysergide and yohimbine, intravenous administration of naloxone or the alpha 1-antagonist corynanthine had no effect upon the suppressive effects of serotonin. The combination of low-dose serotonin and low-dose clonidine produced a supraadditive effect (30% at 30 min). These data support the concept that noradrenergic systems, possibly through an alpha 2-adrenergic mechanism, are involved in the modulation of spinal WDR neurons by serotonin.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effect of halothane on the response of small isolated mesenteric capacitance veins to exogenous norepinephrine and electrically induced endogenous norepinephrine release was studied. The role of extra- and intracellular Ca2+in norepinephrine-induced contractions was also examined. Two-millimeter-long segments from the second-order branch of the mesenteric vein were stretched to twice their resting diameter, and the generated tension was measured with a force transducer. Dose-dependent effects of norepinephrine on generated tension were examined before and after exposure to 0.75 and 1.5% halothane. (These concentrations produced perfusate halothane concentrations of 0.31 and 0.49 mM respectively.) Norepinephrine produced an increase in the basal vessel tension along with a superimposed rhythmic oscillation in tension. Although the magnitude of the tension increase was not affected by either concentration of halothane, the amplitude of the oscillations was reduced. Ryanodine (a blocker of Ca2+release from the sarcoplasmic reticulum), like halothane, decreased the amplitude of the oscillations, but did not affect overall tension development. In the Ca2+-free medium the contractile response to norepinephrine was greatly attenuated as compared to control, whereas the oscillatory behavior was completely abolished. Norepinephrine release was examined indirectly by measuring the increase in tension during electric field stimulation. Response to endogenously released norepinephrine was significantly decreased by exposure to halothane 1.5% (0.49 mM) and blocked by pretreating the vessel with phentolamine. At concentrations used clinically, halothane did not affect overall developed tension in response to exogenously applied norepinephrine. However, 1.5% (0.49 mM) halothane decreased both sarcoplasmic-reticulum-dependent oscillations in tension and electrically induced release of endogenous norepinephrine.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effects of iv succinylcholine (SCh) on cerebral blood flow (CBF), the electroencephalogram (EEG), muscle afferent activity (MAA), electromyographic activity (EMG), and Paco2were tested in six halothane-anesthetized dogs (1.0 MAC) more than 1 h after a 10-min period of complete cerebral ischemia. All dogs received treatments of both iv SCh (1.0 mg · kg−1) and saline placebo in a random sequence. Fasciculations and substantial increases in EMG activity were observed in all dogs following SCh administration. At the onset of fasciculations, there was an increase in MAA to a peak value of 353 ± 74% of control (mean ± SE; n = 5 for MAA; n = 6 for all other variables) at the 1-min measurement point. Thereafter, MAA gradually declined toward control values. There were delayed increases in Paco2throughout the 45-min study period, achieving values of 106 ± 1% to 118 ± 4% of control (an increase in Paco2of 2–7 mmHg). Despite the increases in MAA and Paco2, there were no significant increases in CBF during the study. The control EEG 1·h after complete cerebral ischemia, but immediately before administering the drug treatments, consisted predominantly of a delta rhythm, denoting cerebral dysfunction. In one dog, SCh administration produced transient attenuation of the delta rhythm, a change consistent with cerebral stimulation. In the remaining five dogs, SCh had no effect on the EEG. Treatment with saline placebo did not affect any variable measured. The authors conclude that, in the electrically dysfunctioning brain (e.g., as occurs following resuscitation from complete cerebral ischemia), the cerebral (i.e., CBF and EEG) response to iv SCh is attenuated when compared to the previously reported response in normal brain.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

An aqueous suspension of n-butyl p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally and around ulnar nerves in dogs. The suspension consisted of 10% BAB and 0.025% polysorbate in 0.9% NaCl. Sensory effects were tested by electrical stimulation. Three epidural injections were given, and the dogs were killed after 21 days. The increase in stimulation threshold was comparable to the effect of lidocaine in a concentration between 0.5% and 1%. Increased sensory threshold lasted for days, whereas no long-lasting motor effects were observed. Pathomorphologic changes were found primarily in the dorsal spinal nerve roots, although slight changes were also found in the ventral spinal roots. White matter degeneration was found only in the lumbar dorsal columns. This result suggested Wallerian degeneration in the dorsal spinal nerves and was at variance with recently published data on epidural BAB. No changes were observed in the ulnar nerves. The authors demonstrated that the pathomorphologic changes were induced by the BAB suspension and not by the suspending additive polysorbate 80. It was postulated that the suspension of BAB, which contains particles of a median size of 15 μm, was mainly confined to the dorsal epidural space where neurolytic changes in axons of the dorsal spinal nerve roots and dorsal columns are induced. This may explain the long-lasting sensory effects seen in intractable cancer pain patients after epidural BAB administration. More research is necessary to define the distribution of BAB in nervous tissue after its epidural administration and to better characterize toxicity, neurolytic effects, and regeneration of nervous tissue after BAB administrations.

ISSN:0003-3022    

出版商:OVID    

年代:1990

数据来源: OVID