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PubMed1975

Halothane and isometric contractions of isolated pregnant rat myometrium.

The effects of halothane on isometirc contractions of isolated pregnant uterine muscle strips were evaluated in tissue obtained from 13 midpregnant rats. Peak developed tension was depressed in a dose-related manner at halothane concentrations above 0.8 vol per cent, but was not affected at lower halothane concentrations. Time to peak tension was reduced 10-20 per cent, and relaxation time, 10 per cent, by halothane concentrations ranging up to 2.2 per cent. Total resting tension consisted of a passive component and a calcium-dependent component. In concentrations above 0.8 per cent, halothane rapidly removed 100 per cent of the calcium-dependent resting tension. At lower concentrations, halothane reduced it 50 per cent. The passive component of resting tension was unaffected by halothane. These actions of halothane can prevent postpartum hemostasis. They occur even with very low anesthetic concentrations and can be detected soon after introduction of anesthetic into the muscle bath. This indicates that the hemostatic hazards associated with the use of halothane for delivery may not be prevented by limiting the concentration of halothane or the duration of anesthetic exposure.

Anesthesia, Obstetrical↗
PubMed1982

Changes in lung membrane diffusing capacity for oxygen produced by halothane.

The effect of halothane on membrane diffusing capacity for O2 (DMO2) was measured in isolated left lower lobes of dog lungs using the sodium dithionite method. At 25 degrees C, halothane reduced DMO2 according to the regression equation: per cent control DMO2 = -4.85(per cent halothane) + 97.5 (r = -0.55, P = 0.0007). Although DMO2 was reduced from control by halothane administration, lung volume (VL) increased at higher halothane concentrations and tended to restore DMO2 by increasing surface area. There was a better correlation between the DMO2/VL ratios and per cent halothane: per cent (DMO2/VL) = -5.76 (per cent halothane) + 95.6 (r = -0.65, P = 0.00003). Effects of halothane on DMO2 and VL were reversible and were not influenced by gas mixing efficiency since argon dilution half-times over two decades were unchanged by halothane. It is unlikely that altered vascular recruitment affected the measured DMO2 since resistance to blood flow was unchanged. We conclude that halothane decreases DMO2 by either decreasing the physical diffusion coefficient (D') for O2 or decreasing the effective O2 solubility (alpha), or both, in the alveolar-capillary membrane.

Animals↗
PubMed1982

Sites of action of halothane on respiratory pattern and ventilatory response to CO2 in cats.

To assess the major sites of action of halothane on the control of breathing, the ventilatory response to CO2 was studied in 11 cats and partitioned into tidal volume and frequency response. In these cats artificial perfusion of the ponto-medullary region was applied. In essence, this technique allows one to deliver to the brainstem blood-gas tensions and anesthetic concentrations at predetermined levels which are independent from those in the systemic circulation; thus the central and peripheral effects of halothane and CO2 can be determined separately. In cats exposed both centrally and peripherally to halothane (1.0-1.6%) tachypnea was observed which disappeared when the blood perfusing the brainstem was purged of halothane. From these results is follows that the tachypnea is exclusively due to an action of halothane on structures in the brainstem. In these cats the extrapolated Paco2 at zero ventilation was significantly lower during general halothane anesthesia than during light chloralose-urethane anesthesia (P less than 0.05). In cats lightly anesthetized with chloralose-urethane, halothane (0.5-1.5%) was either administered centrally or peripherally. In these experiments the "overall" ventilatory CO2 sensitivity of both the peripheral and central chemorereflex pathways decreased significantly (P less than 0.01). However, the ratio between these two sensitivities remained the same (P less than 0.5). The extrapolated Paco2 at zero ventilation was not affected by halothane provided its concentration was below 1% (P less than 0.7). From these results we conclude that the depressant effect of halothane on ventilation originates centrally as well as peripherally. Furthermore, from the findings that the ratio of the CO2 sensitivities and the extrapolated Paco2 at zero ventilation remained constant, the authors argue that halothane acts on the processing part of the neural respiratory drive (integrating centers) rather than on the neural activity of the peripheral and central chemoreceptors per se. The peripheral effect is mainly on the neuromechanical link between integrating centers and respiratory movements.

Animals↗
PubMed1984

Elimination of nitrous oxide accelerates elimination of halothane: reversed second gas effect.

The effect of nitrous oxide on the elimination of halothane was studied in 10 patients ranging in age from 20 to 50 years. After establishing a stable baseline (inspired halothane concentration: 0.85%, end-tidal halothane concentration: 0.75%), halothane administration was stopped and the rate of decrease in alveolar concentration of halothane (FE/ FE0 , FE: measured end-tidal concentration of halothane; FE0 : the endtidal concentration immediately preceding the cessation of halothane administration) was measured continuously. The rate of decrease in FE/ FE0 was more rapid when nitrous oxide (70%) is discontinued abruptly and replaced by the same concentration of nitrogen (Part 2) than when the nitrous oxide is continued (Part 1). One minute and a half after the cessation of halothane administration, FE/ FE0 was 0.38 +/- 0.05 (mean +/- SD) in Part 2 and 0.45 +/- 0.04 in Part 1 (P less than 0.01). In Part 2, the fall in the alveolar concentration of halothane was accompanied by a decrease in alveolar carbon dioxide from 4.27 +/- 0.01% to 4.16 +/- 0.01% at 1.5 min and an increase in the mean expired tidal volume from 522 +/- 39 ml to 557 +/- 29 ml. The authors conclude that the elimination of nitrous oxide accelerates the elimination of halothane both by dilution and by an increased expired ventilation.

Adult↗
PubMed1985

The cardiovascular and metabolic effects of halothane in normoxic and hypoxic newborn lambs.

Oxygen consumption, cardiac output, and tissue oxygen delivery were measured in normoxic and hypoxic 1-3-day-old lambs during the following six conditions: 1) (control) paralysis with pancuronium and controlled ventilation with room air; 2) paralysis, controlled ventilation and hypoxia (PaO2 = 30 +/- 3 mmHg, [SD]); 3) paralysis, controlled ventilation with room air and 0.5 MAC halothane; 4) paralysis, controlled ventilation, hypoxia, and 0.5 MAC halothane; 5) paralysis, controlled ventilation with room air, and 1 MAC halothane; and 6) paralysis, controlled ventilation, hypoxia, and 1 MAC halothane. During normoxia, 0.5 and 1 MAC halothane decreased total body oxygen consumption, cardiac output, and arterial blood pressure. One-half MAC halothane had no effect on blood flow to any organ except muscle, whose flow decreased 64%. One MAC halothane decreased blood flow to the brain, heart, kidney, muscle, and gut. Both concentrations of halothane decreased serum catecholamine levels below control values and prevented hypoxia from increasing catecholamine levels. Hypoxia decreased the oxygen consumption about 40% from the immediately previous normoxic value, whether the animals were anesthetized or not. Tissue oxygen delivery followed changes in blood flow. The cardiac output, arterial blood pressure, and heart rate of anesthetized, hypoxic animals were not different from those in the previous normoxic condition. Halothane did not prevent redistribution of blood flow to the heart and brain of hypoxic animals, nor did halothane prevent hypoxic pulmonary vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of halothane on medullary inspiratory neurons of the cat.

The effect of halothane on the electrical activity of inspiratory neurons of the nucleus tractus solitarius (NTS) was studied in decerebrate, paralyzed, mechanically ventilated cats. Simultaneous recording of the activity of the neurons of the NTS and the phrenic nerve was done to identify the inspiratory neurons. Cells whose firing activity was synchronous with that of the phrenic nerve were considered inspiratory neurons. Administration of 1% and 1.5% halothane in oxygen induced a dose-dependent depression of the cell activity (spikes/s) with the cervical vagi intact or severed. Five and ten minutes after inhalation of 1% halothane, the cell activity (mean +/- SE) expressed as per cent of the control was 55.3 +/- 9 and 27 +/- 7, respectively (P less than 0.001), before bilateral cervical vagotomy. The corresponding values for 1.5% halothane were 25 +/- 10.1 and 5.6 +/- 3, respectively. Upon termination of halothane administration, the cell activity gradually returned toward the control level. The cell response to halothane was not affected by bilateral cervical vagotomy. Hypercapnia produced by inhalation of 5% CO2 increased the cell activity, but halothane caused profound depression of the cells even in the presence of hypercapnia. Based on these results, it may be concluded that: halothane has inhibitory effects on the activity of the inspiratory neurons of the NTS; and halothane-induced respiratory depression has a central component and that the NTS may serve as a site of action of halothane for its respiratory depressant effect.

Animals↗
PubMed1987

Depth of halothane anesthesia potentiates citrate-induced ionized hypocalcemia and adverse cardiovascular events in dogs.

The purpose of this study was to determine if depth of halothane anesthesia contributed to the adverse cardiovascular effects of citrate-induced ionized hypocalcemia. Six mongrel dogs were monitored with arterial, central venous, and pulmonary artery flow-directed catheters. Measured end-tidal halothane assured a constant depth of anesthesia, while controlled ventilation and arterial blood gas analysis provided constant acid-base status. Each dog received sodium citrate (USP Fenwal) equivalent to fresh frozen plasma, 1.0 ml.kg-1.min-1, during both deep (D) and light (L) halothane anesthesia. Three dogs received the infusion during L halothane anesthesia first; after a 1-h stabilization period (2.5 h after first infusion) they received a second equivalent infusion during D halothane anesthesia. Three other dogs were studied first with D, then with L halothane. Mean expired halothane (+/- SEM) for group D was 1.52 +/- 0.08%, for group L, 0.85 +/- 0.07%. Significantly greater adverse cardiovascular effects were seen during D halothane anesthesia; four of the six dogs that received citrate during D halothane anesthesia required cessation of the infusion or suffered cardiac arrest. All six infusions during L halothane anesthesia were tolerated. In both groups, significant reductions in ionized calcium [Ca++] (P less than 0.0001) and mean arterial pressure (MAP) (P less than 0.005) were observed; greater reductions in both parameters occurred in group D (P less than 0.0036-0.0005). In group D, but not in group L, cardiac output was depressed compared to baseline (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1988

Comparative coronary vascular reactivity and hemodynamics during halothane and isoflurane anesthesia in swine.

To assess the dose-response effects of isoflurane and halothane anesthesia on hemodynamics and coronary artery reactivity, the authors studied myocardial hyperemic responses following brief single artery flow arrests in 21 open chest, isocapnic swine in which arterial blood pressures and cardiac outputs were recorded. A specially designed Doppler probe was used to measure the peak and time course of coronary blood flow velocity in the left anterior descending coronary artery (LAD) after 15-s LAD occlusions. The ratio of peak velocity of blood flow to resting velocity (coronary reserve), relative repayment of flow debt, and duration of hyperemic responses were studied. Surgery was performed at MAC end-tidal concentrations ([Et]isoflurane = 1.45%. [Et]halothane = 1.25%) of isoflurane (n = 7) or halothane (n = 7), and recordings were made after 15-min steady state [Et]agent at 0.5, 1, 1.25, 1.5, 1.75, 2 MAC, and further 0.5 MAC increments until the demise of each animal. To compare coronary reactivity at similar coronary pressures, an aortic snare was used to elevate arterial pressures in a third group of halothane anesthesized pigs (n = 7) to those in the previously studied isoflurane group at each MAC level. There were three major differences between halothane and isoflurane. First, cardiac depression (reduction in arterial pressure, cardiac output, and stroke volume) was less with isoflurane compared with halothane anesthesia. Second, with halothane anesthesia, there was a marked decrease in coronary reactivity independent of coronary perfusion pressures with marked, dose-dependent reductions in both coronary reserve and relative flow repayment. During isoflurane anesthesia, coronary reactivity and coronary reserve was well preserved within physiologic limits up to 1.75 MAC [Et]. Third, halothane anesthesized pigs died in cardiac collapse at much lower agent concentrations than with isoflurane (no animals survived 1.75 MAC halothane, whereas all animals survived 2.5 MAC isoflurane). Therefore, pigs anesthesized with isoflurane had greater coronary reserve, better preserved cardiac function, and greater tolerance to increasing agent concentration than pigs anesthesized with halothane.

Anesthesia, Inhalation↗
PubMed1988

The effect of halothane on the free intracellular calcium concentration of isolated rat heart cells.

The free intracellular calcium concentration of suspensions of isolated rat heart cells was monitored during sequential exposures to halothane and caffeine to evaluate cellular mechanisms of the negative inotropic effect of halothane. The calcium-sensitive, fluorescent dye quin2 was used as the indicator of free intracellular calcium. The acute addition of halothane in concentrations greater than or equal to 0.062 mM (0.19 vol%) to suspensions of quiescent rat heart cells at 37 degrees C caused a transient (approximately 1.5 min) increase in free intracellular calcium concentration. The intracellular calcium concentration after the decay of this transient was not detectably different from that prior to the addition of halothane. Neither the reduction of extracellular calcium from 1 mM to 100 nM, nor the prior addition of verapamil (5 microM) decreased this halothane-induced calcium transient. The transient was completely blocked by the prior addition of 10 mM caffeine, which depletes the sarcoplasmic reticulum of calcium. Also, the prior addition of halothane caused a reduction in the calcium transient due to caffeine. The depression of the caffeine-induced calcium transient by halothane was independent of the time interval (up to 4 min) between the additions of halothane and caffeine. These results indicate that halothane causes a net loss of calcium from the sarcoplasmic reticulum of quiescent rat heart cells. Thus, halothane has a direct effect at the sarcoplasmic reticulum, probably an enhancement of calcium release, which may explain its depression of myocardial contractility.

Aminoquinolines↗
PubMed1989

Comparison of the effects of halothane on skinned myocardial fibers from newborn and adult rabbit. I. Effects on contractile proteins.

The effect of halothane on maximal and submaximal Ca2+-activated tension development of the contractile proteins of newborn and adult cardiac muscle from rabbits was determined. Right ventricular muscle was removed from newborn and adult rabbits, and the sarcolemma was disrupted (skinned) by homogenization. Fiber bundles were dissected from the homogenate and mounted on tension transducers. Fiber bundles were alternately immersed in relaxing solution [( Ca2+] less than 10(-9) M) and contracting solutions (various [Ca2+] from 10(-5.6) to 10(-3.8) M), which were saturated with 100% N2 alone or with three concentrations of halothane-N2 mixture. In the absence of halothane, newborn skinned myocardial fibers were slightly more sensitive to submaximal Ca2+ concentrations than were adult myocardial fibers. [Ca2+] required for 50% maximum tension were 10(-5.43) M and 10(-5.31) M, respectively (P less than 0.05). Halothane (1-3%) decreased the maximal Ca2+-activated tension (at [Ca2+] = 10(-3.8) M) similarly in adult and newborn myocardial fibers in a dose-dependent fashion. Tension was reduced by 5.9% for each 1% increase in halothane concentration. Halothane also decreased the sensitivity of adult myocardial skinned fibers to submaximal Ca2+ concentrations (10(-5.6) M to 10(-5.0) M) by shifting the Ca2+-tension response curve to the right. Only 3% halothane decreased the sensitivity of newborn myocardial skinned fibers to Ca2+. The authors conclude that halothane causes less depression of Ca2+ activation of the contractile proteins in newborn than adult rabbit myocardium and that this effect of halothane cannot account for greater negative inotropy of halothane in the newborn.

Animals↗
PubMed1989

The effect of halothane, isoflurane, and verapamil on ischemic-isolated rabbit renal tubules.

The effects of the volatile anesthetics halothane and isoflurane, and the calcium entry blocker verapamil, were studied in isolated rabbit renal tubules under nonischemic and simulated ischemic conditions. Isolated rabbit renal tubules were subjected to zero (control), 30 (I-30), or 60 (I-60) minutes of simulated ischemia following the method of Weinberg. Following the ischemic period, tubules were reoxygenated in a Gilson respirometer (simulated reperfusion) and treated with either halothane (1%) or isoflurane (1%) in the controls and at I-30, or halothane (1%, 2%, 4%) or verapamil (5 microM, 15 microM, 30 microM) at I-60. Tubules were analyzed for lactate dehydrogenase (LDH) release (measuring cell membrane integrity), intracellular potassium and adenosine triphosphate (ATP), and oxygen consumption (cellular respiratory rate). In nonischemic tubules, exposure to 1% isoflurane caused significantly reduced LDH release compared with that released by controls, indicating cell membrane protection, whereas 1% halothane had no effect on these cells. With 30 min of ischemia, 1% isoflurane was associated with significantly higher cellular LDH release and lower ATP concentration, suggesting increased cellular damage. Halothane (1%) was associated with only an increased ATP concentration in tubules exposed to 30 min of ischemia. Following 60 min of ischemia, halothane (4%) decreased LDH release by 45% (29.2 +/- 2.3% vs. 47.0 +/- 9.6% without halothane). Tubules exposed to halothane also had higher intracellular potassium and ATP concentrations, and increased respiratory rates. Halothane (2%) was less protective and only increased the ATP concentration. The release of LDH was not statistically different with or without 2% halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1989

Age and gender influence halothane-associated hepatotoxicity in strain 13 guinea pigs.

The factors of age and gender, which have been linked to development of fulminant halothane hepatitis in humans, were evaluated in a guinea pig model of acute halothane-associated hepatotoxicity. Since nitrous oxide is commonly coadministered with halothane and has been shown to exacerbate halothane-associated liver injury in rats; this combination of anesthetics was also evaluated in guinea pigs. Male and female strain 13 guinea pigs (300-1000 g) were exposed to 1% v/v halothane and 39% O2 for 4 h with a balance of either 60% N2 or 60% N2O. Both animal age, as determined by body weight, and gender proved to be factors in the model with older (approximately 6.2 +/- 1.0 month) guinea pigs of both sexes, demonstrating significantly greater elevations in plasma ALT and a greater incidence of centilobular necrosis versus younger (approximately 3.1 +/- 0.6 month) animals. Older females showed a greater hepatotoxic response than older males. There were no significant differences in halothane plasma metabolite levels between older and younger animals of either gender. The addition of nitrous oxide affected neither plasma concentrations of halothane metabolites nor the degree of resultant hepatic injury. Older (approximately 5-6 month) male guinea pigs, from a strain (inbred Hartley) previously shown to be resistant to the halothane lesion, did not develop centrilobular necrosis following halothane exposure even though they generated plasma metabolite concentrations equivalent to those generated by strain 13 animals. The lack of differences in the biotransformation of halothane between groups indicates that other intrinsic factors must be involved in the observed variations in susceptibility to hepatic injury.

Aging↗
PubMed1990

The effect of halothane on morphine disposition: relative contributions of the liver and kidney to morphine glucuronidation in the dog.

The present study determined the effect of halothane on the disposition of morphine by defining the effect of halothane anesthesia on the systemic, renal, and hepatic clearance of the parent compound, morphine, and on the generation of the primary metabolite, morphine-3-glucuronide (M3G) in the dog. Unlabeled morphine, 3H-morphine, and 14C-morphine were simultaneously administered into the portal vein, femoral vein, and renal artery, respectively, first during pentobarbital anesthesia and second during halothane (1.5 MAC) anesthesia; blood samples were taken for estimation of unlabeled plasma morphine and M3G concentrations by high performance liquid chromatography (HPLC). 3H- and 14C-morphine concentrations and corresponding M3G concentrations were determined by dual-channel liquid scintillation counting of the eluant corresponding to the appropriate peak on the HPLC. The portal clearance of morphine was not altered by halothane. However, intravenous (iv) morphine clearance (CLs) decreased (P less than 0.05) by 40% from 963 +/- 131 to 579 +/- 91 ml/min during halothane anesthesia, accompanied by an increase (P less than 0.05) in half-life from 78 +/- 8 to 106 +/- 8 min. The reduction in CLs of morphine occurred putatively on the basis of a halothane-induced decrease in hepatic blood flow, whereas morphine metabolism, reflected by morphine portal (intrinsic) clearance, was not significantly decreased by halothane. There was no significant effect of halothane on the partial metabolic clearance of morphine to M3G, and the ratio of area under the plasma concentration-time curve (AUC)-M3G to AUC unchanged morphine was not significantly altered by halothane, indicating that morphine glucuronidation is unaffected by halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Glutathione depletion enhances subanesthetic halothane hepatotoxicity in guinea pigs.

Reduced glutathione has a potential role in protecting the liver against the reactive acyl acid chloride intermediate generated during the oxidative biotransformation of halothane. Glutathione is also important in maintaining the integrity of an injured cell. Thus, the effect of decreased hepatic glutathione concentrations on covalent binding of halothane metabolic intermediates to hepatic protein and lipid and the resultant hepatic injury were investigated in male, outbred Hartley guinea pigs. The animals were injected with either 1.6 g.kg-1 dl-buthionine-S,R-sulfoximine to deplete hepatic glutathione or vehicle-control solution 24 h before exposure to 0.1% (subanesthetic) halothane for 4 h (fractional inspired oxygen tension = 0.40). Buthionine sulfoximine pretreatment depleted liver glutathione concentrations by 85% at the time of halothane exposure, without affecting the degree of halothane biotransformation or causing hepatic injury. Glutathione depletion caused a significant increase in the level of organic fluorine covalently bound to hepatic protein but not lipid after halothane exposure. Glutathione-depleted animals also exhibited a significant enhancement of hepatotoxicity after halothane exposure; plasma isocitrate dehydrogenase activity was 25-fold greater than the increase observed 48 h after exposure in animals treated with vehicle plus halothane, and the incidence and severity of hepatic injury were significantly greater, as observed by light microscopic examination of tissue 96 h after exposure. These findings are in agreement with a previously proposed mechanism of halothane-associated hepatotoxicity in guinea pigs and indicate that hepatic glutathione status may play an important role in the susceptibility of patients to halothane-induced liver injury.

Animals↗
PubMed1994

Effects of halothane and isoflurane on ventilation and occlusion pressure.

BACKGROUND: Isoflurane has been said to be more ventilatory depressant than halothane. However, data for comparing the respiratory effects of halothane and isoflurane in humans are insufficient at this time. The aim of this study was to extend our understanding of the nature of the central, as opposed to peripheral, ventilatory effect of halothane and isoflurane by comparing them at two concentrations. METHODS: Twenty patients were randomly assigned to receive halothane (n = 10) or isoflurane (n = 10). The patients were studied the day before surgery and during anesthesia immediately before surgery. Ventilatory effects were analyzed in terms of breathing pattern, end-tidal carbon dioxide pressure (PETCO2) and inspiratory occlusion pressure. After anesthetic induction and orotracheal intubation with thiopental and succinylcholine patients were allowed to breathe halothane or isoflurane in oxygen spontaneously at 1.2 (low) and 2.0 (high) minimum alveolar concentration (MAC) applied in random order. Inspiratory active impedance during anesthesia was also measured. RESULTS: Significant reduction of minute ventilation between awake and low MAC states was observed for isoflurane (-34.4%; P < 0.001) but not for halothane. Inspiratory occlusion pressure at 100 ms increased significantly between awake and low MAC states, from 1.43 +/- 0.89 to 2.67 +/- 1.05 cmH2O (P < 0.05) for halothane, representing an 87% increase, whereas a nonsignificant increase (16%) was observed for isoflurane. Both anesthetics showed a dose-related ventilatory depressant effect, not attributable to changes in mechanical properties, reflected by significant reductions in minute ventilation (P < 0.001), tidal volume (P < 0.001), and inspiratory occlusion pressure at 100 ms (P < 0.05) and increases in respiratory rate (P < 0.001) and end-tidal carbon dioxide pressure (P < 0.01) when concentration was increased. However, at the higher concentration a significantly greater reduction of minute ventilation (P < 0.01) was observed for isoflurane (-25.6%) than for halothane (-9.4%). We did not observe differences in respiratory rate between the two anesthetics. Significant differences in inspiratory occlusion pressure wave were observed, characterized by a concave-upward tendency for isoflurane and for high concentration. CONCLUSIONS: Our study confirms the stronger ventilatory depression induced by isoflurane compared with that induced by halothane and indicates that halothane at 1.2 MAC induces significantly less ventilatory depression than expected.

Adult↗
PubMed1995

The effects of halothane on cardiovascular responses in the neuraxis of cats. Influence of background anesthetic state.

BACKGROUND: This study examined the effects of halothane on arterial pressure after central nervous system (CNS) pressor site stimulation in anesthetized cats, cats rendered unconscious by midcollicular transection, and conscious cats. METHODS: Two anesthetized groups and two nonanesthetized groups were used. Cats were anesthetized with either alpha-chloralose and urethane or pentobarbital. Nonanesthetized groups were cats with midcollicular transections or conscious cats with chronically implanted electrodes. Stimulating electrodes were placed into vasomotor areas of the hypothalamus (HYP), reticular formation (RF), and medulla, and arterial pressure responses to increasing stimulus currents were examined during different halothane concentrations. Two groups of cats were also anesthetized with either pentobarbital or urethane and underwent bilateral carotid artery occlusion. RESULTS: Stimulation at each CNS site produced increases in arterial pressure and heart rate. Halothane attenuated pressor responses evoked by stimulation of all loci in all groups of cats. The inhibition by halothane on these cardiovascular responses was greatest at HYP and RF sites, while the medulla was more resistant to the effects of halothane in the anesthetized animals. Midcollicular transection decreased this medullary resistance. The inhibition of pressor responses by halothane was also greater in pentobarbital-than chloralose urethane-anesthetized animals. In contrast, pressor responses elicited by bilateral carotid occlusion were attenuated by halothane similarly in both anesthetic groups. Reticular formation stimulation in conscious animals resulted in "altering responses" in addition to pressor effects, both of which were attenuated by halothane. CONCLUSIONS: Modulation of CNS cardiovascular control centers contribute to halothane-induced hemodynamic alterations. Baseline anesthesia, CNS stimulation site, and the suprabulbar system influence the effects of halothane.

Anesthesia↗
PubMed1995

Halothane reduces focal ischemic injury in the rat when brain temperature is controlled.

BACKGROUND: Previous work has demonstrated that rats anesthetized with halothane during focal cerebral ischemia have better histologic and neurologic outcome than do rats undergoing the same insult when awake. The purpose of this experiment was to determine whether this difference persists when brain temperature is held similar in halothane-anesthetized and awake experimental groups. METHODS: Two ischemia experiments were performed. In both, the middle cerebral artery was occluded for 90 min. Temperature was monitored from a radiotelemetered thermistor implanted in the cerebral cortex. Four days after ischemia, infarct volume and neurologic function were assessed. In experiment 1, brain temperature was not controlled in awake rats. Temperature in rats anesthetized with halothane, approximately 1 minimum alveolar concentration, was regulated by servomechanism by surface heating or cooling to replicate the temperature profiles generated by awake animals. To address methodologic issues regarding infarct volume analysis, a subset of nine rats was examined for the effect of the histologic staining technique and the mathematical modeling algorithms used for computation of infarct volume values. In experiment 2, the brain temperature of awake and halothane-anesthetized rats was maintained normothermic (38.0 degrees C) throughout ischemia and early recirculation. RESULTS: In experiment 1 no difference between groups was observed for cortical (halothane 146 +/- 95 mm3 and awake 126 +/- 108 mm3; P = 0.64) or subcortical (halothane 110 +/- 48 mm3 and awake 100 +/- 66 mm3; P = 0.66) infarct volume. Neurologic function was also similar between groups. Total infarct volume was approximately 11% greater when histologic sections were stained with hematoxylin and eosin than when they were stained with nitro blue tetrazolium, although volumes correlated closely between the two techniques (r2 = 0.996). Analysis by orthogonal or frustum projection from two-dimensional planimetric areas to three-dimensional volumes resulted in nearly identical values (r2 = 0.999). In experiment 2, halothane-anesthetized rats experienced a 46% reduction in cortical infarct volume (halothane 106 +/- 97 mm3 and awake 197 +/- 103 mm3; P = 0.03). The incidence of hemiparesis was reduced in the anesthetized group (P = 0.03). CONCLUSIONS: When brain temperature was maintained normothermic throughout the focal ischemic insult, a neurologic and histologic protective effect for halothane anesthesia was observed. This effect of halothane was not sufficient to persist when large variations in brain temperature were allowed. Regulation of brain temperature is a critical factor in the determination of the effects of anesthetics on focal ischemic brain damage.

Animals↗
PubMed1995

Analysis of halothane effects on myocardial force-interval relationships at anesthetic concentrations depressing twitches but not tetanic contractions.

BACKGROUND: Tetanic contractions in rat myocardium depend solely on cellular Ca2+ uptake, whereas twitches depend on Ca2+ release from the sarcoplasmic reticulum. Because halothane may cause loss of sequestered Ca2+, the anesthetic was tested for its differential effects on twitch and tetanic forces. The in vitro effects of halothane on the twitch force-interval relationship were then evaluated, using a mathematical model that relates twitch contractile force to the Ca2+ content of intracellular compartments. METHODS: Isometric contractile force was measured in paced (0.4 Hz) rat atrial preparations. The sarcoplasmic reticulum was functionally eliminated using ryanodine (10(-6) M), abolishing twitches. Rapid pacing (20 Hz, 10 s) caused tetanic contractions. The effects of identical halothane exposures on twitches and tetanic contractions were compared. Ca2+ compartment model parameters were extracted from twitch force-interval data, according to a previously employed quantitative procedure. RESULTS: Halothane (0.5-1%) depressed normal twitches, but not tetanic contractions. The anesthetic decreased the amplitude of the steady-state twitch force-frequency relationship, and accelerated the course of mechanical recovery. Halothane (0.5-1%) also accelerated the decay constant for the decline in amplitude of a series of rest-potentiated contractions. The modeling showed that a 20-30% decrease in the recirculating fraction of activator Ca2+ accounts for 0.5% halothane-induced negative inotropy and acceleration of the decay constant. CONCLUSIONS: The differential effect of halothane on twitches and tetanic contractions implies that a functioning sarcoplasmic reticulum is required for halothane-induced negative inotropy. The effects of halothane on the force-interval relationship suggest that halothane reduces the sequestered pool of activator Ca2+.

Anesthetics, Inhalation↗