Effects of halothane and isoflurane on carbon monoxide-induced relaxations in the rat aorta

BACKGROUND: Halothane and isoflurane previously were reported to attenuate endothelium-derived relaxing factor/nitric oxide-mediated vasodilation and cyclic guanosine monophosphate (cGMP) formation in isolated rat aortic rings. Carbon monoxide has many chemical and physiologic similarities to nitric oxide. This study was designed to investigate the effects of halothane and isoflurane on carbon monoxide-induced relaxations and cGMP formation in the isolated rat aorta. METHODS: Isometric tension was recorded continuously from endothelium denuded rat aortic rings suspended in Krebs-filled organ baths. Rings precontracted with submaximal concentrations of norepinephrine were exposed to cumulative concentrations of carbon monoxide (26-176 microM). This procedure was repeated three times, with anesthetics delivered 10 min before the second procedure. Carbon monoxide responses of rings contracted with the same concentration of norepinephrine (10(-6) M and 2 x 10(-6) M) used in the anesthetic-exposed preparations also were examined. The concentrations of cGMP were determined in denuded rings using radioimmunoassay. The rings were treated with carbon monoxide (176 microM, 30 s) alone, or carbon monoxide after a 10-min incubation with halothane (0.34 mM or 0.72 mM). To determine whether the sequence of anesthetic delivery influenced results, vascular rings pretreated with halothane were compared with nonpretreated rings. RESULTS: Carbon monoxide (26-176 microM) caused a dose-dependent reduction of norepinephrine-induced tension, with a maximal relaxation of 1.51 +/- 0.07 g (85 +/- 7% of norepinephrine-induced contraction). Halothane (0.34 mM and 0.72 mM) significantly attenuated the carbon monoxide-induced relaxations, but only the highest concentration of isoflurane (0.53 mM) significantly attenuated the carbon monoxide-induced relaxations. Carbon monoxide (176 microM) significantly increased cGMP content (+88.1 +/- 7.1%) and preincubation of the aortic rings with halothane (0.34 mM and 0.72 mM) inhibited this increase (-70.7 +/- 6.8% and -108.1 +/- 10.6%, respectively). When aortic rings and carbon monoxide were added simultaneously to Krebs solution equilibrated with halothane (0.72 mM), no inhibition of cGMP formation occurred. CONCLUSION: Carbon monoxide-induced endothelium-independent relaxations of rat aortic rings were decreased by clinically relevant concentrations of halothane and isoflurane. The carbon monoxide-induced elevations of cGMP were attenuated by halothane only when the anesthetic was incubated with aortic rings before carbon monoxide treatment. The possible clinical significance of the actions of the anesthetics on this endogenous vasodilator is yet to be determined.     

Delayed onset of malignant hyperthermia induced by isoflurane and desflurane compared with halothane in susceptible swine

BACKGROUND: Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether) is a new inhalational anesthetic currently under investigation for use in humans. Recently, the authors showed that desflurane is a trigger of malignant hyperthermia (MH) in susceptible swine. To date, there has been no in vivo comparison of the relative ability of inhalational anesthetics to trigger MH. The effects of desflurane, isoflurane, and halothane on six MH-susceptible purebred and six MH-susceptible mixed-bred Pietrain swine were examined. METHODS: The animals were exposed to 1 MAC and 2 MAC (if MH was not triggered after 1 MAC hour) doses of each of the three volatile anesthetics in random sequence at 7-10-day intervals and changes in end-tidal CO2, arterial blood gases, serum lactate, core and muscle temperature, blood pressure, and heart rate were measured. RESULTS: There was a statistical difference between anesthetics in the time required to trigger MH; halothane exposure resulted in the fastest onset of an MH episode (20 +/- 5 min), compared with isoflurane (48 +/- 24 min) and desflurane (65 +/- 28 min), both of which required significantly longer exposures. There was no statistical difference between the MH purebred and mixed-bred swine in the time required to trigger MH (defined as a PaCO2 of 70 mmHg) with a given agent, and time to triggering was also independent of the order of exposure to the three anesthetics. Malignant hyperthermia susceptibility was confirmed in ten surviving animals, by both in vivo succinylcholine challenge and in vitro contracture testing. CONCLUSIONS: Although all three volatile anesthetics triggered MH, exposure to halothane resulted in significantly shorter times to MH triggering when compared with desflurane and isoflurane.     

Effects of halothane and isoflurane on beta-adrenoceptor-mediated responses in the vascular smooth muscle of rat aorta

The present study was designed to investigate the consequences of a chronic diazepam (DZ) exposure (10 mg/kg/day) during the first 3 weeks of life on social behavior of adult male rats measured in a situation of restricted access to food, the diving-for-food model. The treatment had no long-term effects on the acquisition of social roles related to feeding. However, DZ-exposed rats were less efficient than controls in carrying food from the feeder to the cage during the 1st session but were able to adapt and improve their performances during the 2nd one. In the home cage, DZ-exposed rats were more aggressive toward conspecifics than controls and compensated for their deficit of food by stealing it from the others. These results suggest that an early DZ exposure has long-term consequences on social behavior of rats, possibly reflecting a reduction of the level of emotionality.     

Shortening velocity is different in longitudinal and circular muscle layers of the rabbit urethra

The aim of the study was to investigate whether the functional difference between circular and longitudinal muscles in the female rabbit urethra is reflected in their shortening properties and lactate dehydrogenase (LDH) activity. For mechanical experiments the preparations were chemically skinned to avoid influence of membrane-related mechanisms and to enable maximal activation. Force velocity relations and the maximal shortening velocity (v(max)) were determined using the isotonic quick-release method. The v(max) was three times higher in longitudinal muscle. LDH isoform pattern was determined on agarose gels. The M-subunit, favourable for lactate formation, constituted 70% of the total in both types of muscle. There was no difference in the LDH isoform pattern despite the marked difference in v(max). We conclude that the difference in v(max) reflects differences in the contractile machinery itself. These mechanical characteristics are advantageous for the role of the circular as a tonic muscle contracting during bladder filling, and the longitudinal as a phasic muscle active in opening up the urethra during micturition.     

Changing from isoflurane to desflurane toward the end of anesthesia does not accelerate recovery in humans

BACKGROUND: In an attempt to combine the advantage of the lower solubilities of new inhaled anesthetics with the lesser cost of older anesthetics, some clinicians substitute the former for the latter toward the end of anesthesia. The authors tried to determine whether substituting desflurane for isoflurane in the last 30 min of a 120-min anesthetic would accelerate recovery. METHODS: Five volunteers were anesthetized three times for 2 h using a fresh gas inflow of 2 l/min: 1.25 minimum alveolar concentration (MAC) desflurane, 1.25 MAC isoflurane, and 1.25 MAC isoflurane for 90 min followed by 30 min of desflurane concentrations sufficient to achieve a total of 1.25 MAC equivalent ("crossover"). Recovery from anesthesia was assessed by the time to respond to commands, by orientation, and by tests of cognitive function. RESULTS: Compared with isoflurane, the crossover technique did not accelerate early or late recovery (P > 0.05). Recovery from isoflurane or the crossover anesthetic was significantly longer than after desflurane (P < 0.05). Times to response to commands for isoflurane, the crossover anesthetic, and desflurane were 23 +/- 5 min (mean +/- SD), 21 +/- 5 min, and 11 +/- 1 min, respectively, and to orientation the times were 27 +/- 7 min, 25 +/- 5 min, and 13 +/- 2 min, respectively. Cognitive test performance returned to reference values 15-30 min sooner after desflurane than after isoflurane or the crossover anesthetic. Isoflurane cognitive test performance did not differ from that with the crossover anesthetic at any time. CONCLUSIONS: Substituting desflurane for isoflurane during the latter part of anesthesia does not improve recovery, in part because partial rebreathing through a semiclosed circuit limits elimination of isoflurane during the crossover period. Although higher fresh gas flow during the crossover period would speed isoflurane elimination, the amount of desflurane used and, therefore, the cost would increase.     

Long-term graft outcome is not necessarily affected by delayed onset of graft function and early acute rejection

Cytogenetic and molecular genetic investigations in cancer are important tools to address problems of oncogenesis and tumor progression, of classification, and of diagnosis of tumors. A combination of advanced molecular genetic, cytogenetic, and (immuno) histopathologic analysis will contribute significantly to the elucidation of the oncogenic steps that lead to immortalization and subsequent malignant behavior. In this review written on the occasion of Dr. Avery Sandberg's 75th anniversary, we will present a model for the pathogenesis of renal cell tumors based on a new cytomorphologic classification and our (cyto)genetic analysis of about 175 renal cell tumors, together with the accumulated data in the literature.     

Mathematical modelling of the contribution of mechanical inhomogeneity in the myocardium to contractile function

Earlier we developed a mathematical model of the cardiac muscle that allowed for inactivation through the effects of cooperativity of contractile proteins. In the present work we used the model to analyze the mechanical function of an inhomogeneous myocardium. To simulate the latter we chose, as the simplest sytstem, a duplex in which muscles with different mechanical properties were connected in series and in parallel. Numerical experiments showed that the basic effect due to the inhomogeneity consists in the non-additivity of the mechanical characteristics of the muscle, e.g., of the relationship between end-systolic length and end-systolic force (Les - Pes). As a rule, non-additivity consists in a negative inotropic effect. The analysis showed that the cause of non-additivity is redistribution of loads between muscles (in a parallel duplex), redistribution of lengths (in a serial duplex), changes in the rate of contraction of each muscle compared to contraction that when working separately, shifts in time to Les. Also, the model predicts that additional inactivation of contractile proteins in a muscle within a duplex against isolation is the substantial mechanism of enhanced non-additivity. Among the factors of inhomogeneity studied the basic determinants are difference in amplitudes between isometric tensions developed by each muscle in isolation and the asynchronism in the development of these tensions.     

Summation in autoshaping is affected by the similarity of the visual stimuli to the stimulation they replace.

Pigeons received autoshaping with 2 stimuli, A and B, presented in adjacent regions on a television screen. Conditioning with each stimulus was therefore accompanied by stimulation that was displaced from the screen whenever the other stimulus was presented. Test trials with AB revealed stronger responding if this displaced stimulation was similar to, rather than different from, A and B. For a further experiment the training just described included trials with A and B accompanied by an additional, similar, stimulus. Responding during test trials with AB was stronger if the additional trials signaled the presence rather than the absence of food. The results are explained with a configural theory of conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Actions of halothane and isoflurane on Purkinje fibers in the infarcted canine heart: conduction, regional refractoriness, and reentry

The actions of halothane (HAL) and isoflurane (ISO) on conduction and regional refractoriness were studied in infarcted canine hearts to compare their effects on reentry in vitro. In two anesthetic groups of 8 hearts, high and low dose effects were assessed using action potentials recorded from Purkinje fibers located in the nonischemic and ischemic regions. An extrastimulus technique was used to determine the relationship between delay of conduction of premature impulses into the more refractory ischemic region and induction of reentrant responses. At high doses (HAL 0.60 mM and ISO 0.64 mM, approximately 2.3 minimum alveolar anesthetic concentration [MAC]) both anesthetics decreased (P < or = 0.05) the effective refractory period for direct intracellular stimulation of nonischemic fibers (local ERP, initial control: 294 +/- 8 ms); the decrease with HAL (-29 +/- 6 ms) was smaller (P < or = 0.05) than with ISO (-50 +/- 7 ms). HAL and ISO also decreased (P < or = 0.05) the coupling interval of the earliest premature impulse which conducted into the infarct (system effective refractory period [SERP], control: 301 +/- 7 ms) by -31 +/- 11 and -44 +/- 8 ms, respectively. In contrast, the functional refractory period (FRP) in the ischemic region (control:354 +/- 4 ms) was increased by HAL (26 +/- 8 ms; P < or = 0.05) but decreased by ISO (-14 +/- 4 ms, P < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular hemodynamics and function in acute myocardial infarction: studies during the acute phase, convalescence and late recovery

The left ventricular hemodynamics of 70 patients with acute myocardial infarction were determined from measurements of pulmonary arterial end-diastolic pressure, cardiac index, mean arterial pressure and heart rate during the acute phase(first study, 5 hours after admission), 4 to 6 weeks later (second study, during convalescence) and in 35 percent of all subjects 6 to 12 months after the acute infarction (third study). Serial analysis of serum creatine kinase was carried out during the acute phase. The peak CK value normalized for body surface area was used as a rough index of the extent of the acute myocardial necrosis. The condition of all survivors of the acute stage improved. Patients with only slightly reduced left ventricular performance during the acute stage recovered to nearly normal during convalescence. The condition of patients with greatly reduced left ventricular function also improved but remained impaired during convalescence. In all patients the main changes in left ventricular hemodynamics occurred within the first 4 to 6 weeks; there was almost no further alteration during the following 9 months.     

Respiratory symptoms and cough reflex in populations exposed to different degrees of environmental pollution

BACKGROUND: Santiago is a city with a high degree of environmental pollution caused by particulate matter and ozone, producing adverse effects in the respiratory system. AIM: To compare respiratory symptoms and cough reflex in adults from Santiago and from a rural area with low levels of environmental pollution. SUBJECTS AND METHODS: One hundred twenty six non-smoker adults from Santiago and 116 from a rural area with low levels of pollution answered a respiratory symptom questionnaire. Of these 101 subjects from Santiago and 116 from the rural area inhaled doubling concentrations of capsaicin from 0.5 to 500 microM or until five coughs were elicited. The lowest concentration eliciting 2 or more coughs (CD2) or 5 or more coughs (CD5) was recorded. Levels of environmental particulate matter were also recorded in both locations. RESULTS: Levels of particulate matter were 102 +/- 41 and 64 +/- 24 micrograms/m3 in Santiago and the rural area respectively. People from Santiago had higher rates of throat clearing, cough and phlegm. CD2 geometric mean and confidence limits in Santiago and the rural area were 6.9 (5.2-7.4) and 2.8 (2.7-2.9) respectively (p < 0.001). No differences in CD5 were observed between both locations. Multivariate analysis disclosed the variable location (city) as the only independent predictor of respiratory symptoms. CONCLUSIONS: The increased CD2 found in Santiago suggests that the higher rates of respiratory symptoms related to air pollution can be associated to a decreased sensitivity of the cough reflex.     

Spine morphology of neurons in the avian forebrain is affected by rearing conditions

An area of the caudal forebrain of male zebra finches, the Archi-Neostriatum caudale (ANC), which is active during arousal (Bischof & Herrmann, 1986, 1988), shows rearing-dependent changes in neuron morphology (Rollenhagen & Bischof, 1991). We demonstrate here that rearing conditions also affect the shape of spines of one of the four ANC neuron types. This neuron type was examined in birds reared under five different conditions--in isolation (1), caged (2), in the aviary (3), and with social contact (4) or chasing (5) after an isolation period. Our results show that social experience determines the proportion of the three types of spines (thin, mushroom, and stubby) of the investigated neuron type. Rearing conditions and short social contact also affect the spine stem length of the thin spine type. Long-term isolation results in a reduction in number and elongation of shafts of thin spines, along with an increase of stubby-and mushroom-shaped spines. Short-term social contact or arousal enhances the number of mushroom-and thin-shaped spines and reduces the length of spine stems of thin spines. We suggest that isolation prevents the ANC neuron from reaching full development. The increase of mushroom and thin spine types due to social contact indicates that the stubby-shaped spines are replaced by, or transformed into, mushroom-shaped spines, and the mushroom-shaped spines are replaced by, or transformed into, thin spines. These results confirm and extend the experimental background for our hypothesis (Rollenhagen & Bischof, 1991) that social contact is necessary for development of normal morphology of ANC neurons.     

Symmetry of bone mineral density in the hips is not affected by age

To assess the symmetry of bone mineral density (BMD) of the hips, we used dual photon absorptiometry (DPA) to asses BMD in 266 normal Chinese women in the bilateral femoral neck, trochanter and Ward's triangle regions. Linear regression analysis of the results showed excellent correlation between the hips. The correlation coefficients for the femoral neck, trochanter and Ward's triangle regions were 0.899, 0.892 and 0.935 respectively, and the standard errors of the estimate (S.E.E.) were 0.029, 0.027 and 0.022 g cm-2 respectively. Pooling the BMD data of corresponding regions (n = 532), the correlation coefficient was 0.813 for femoral neck versus trochanter, 0.889 for femoral neck versus Ward's triangle, and 0.833 for trochanter versus Ward's triangle. Further analysis showed mean correlation coefficients of 0.854 for elderly subjects (age > or = 65 years, n = 51) and 0.887 for younger subjects (age < 65 years, n = 215). In conclusion, assessment of left or right hip BMD may be used to represent the BMD of the contralateral hip and can reduce both the cost and radiation exposure during mass screening for osteoporosis.     

Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice

We studied the effect of alterations in the level of myocardial beta-adrenergic receptor kinase betaARK1) in two types of genetically altered mice. The first group is heterozygous for betaARK1 gene ablation, betaARK1(+/-), and the second is not only heterozygous for betaARK1 gene ablation but is also transgenic for cardiac-specific overexpression of a betaARK1 COOH-terminal inhibitor peptide, betaARK1(+/-)betaARKct. In contrast to the embryonic lethal phenotype of the homozygous betaARK1 knockout (Jaber, M., Koch, W. J., Rockman, H. A., Smith, B., Bond, R. A., Sulik, K., Ross, J., Jr., Lefkowitz, R. J., Caron, M. G., and Giros, B. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 12974-12979), betaARK1(+/-) mice develop normally. Cardiac catheterization was performed in mice and showed a stepwise increase in contractile function in the betaARK1(+/-) and betaARK1(+/-)betaARKct mice with the greatest level observed in the betaARK1(+/-)betaARKct animals. Contractile parameters were measured in adult myocytes isolated from both groups of gene-targeted animals. A significantly greater increase in percent cell shortening and rate of cell shortening following isoproterenol stimulation was observed in the betaARK1(+/-) and betaARK1(+/-)betaARKct myocytes compared with wild-type cells, indicating a progressive increase in intrinsic contractility. These data demonstrate that contractile function can be modulated by the level of betaARK1 activity. This has important implications in disease states such as heart failure (in which betaARK1 activity is increased) and suggests that betaARK1 should be considered as a therapeutic target in this situation. Even partial inhibition of betaARK1 activity enhances beta-adrenergic receptor signaling leading to improved functional catecholamine responsiveness.     

Structure and function of the rabbit bladder altered by chronic obstruction or cystitis

In a prospective 5-year-study the development of adiposity was tested in a population group consisting of about 30,000 persons. It was shown that during the time of investigation the population decreased in its total number, the consumption of easily digestible carbohydrates and meat, however, increased. As it was established in 1968, the proportion of the adipose persons (more than 20% of the Broca-weight) and the percental average deviation from the Broca-weight (calculated in decennium classes) was more than in the comparable population groups in the GDR. Contrary to expectation the examination further showed that on an average men exhibited a trend to the increase in weight, but on the average women decreased in weight. In all age groups (with the exception of the 60- to 69-year-old persons) the proportion of obese persons was significantly lower in 1973 than in 1968. Unchangedly adipose are the diabetics who also have a by far higher average weight than the healthy population and who up to now do not reveal an inclination to the decrease in weight. With 2.9% the average frequency of diabetes is also adequately high.     

Gastric secretion, mucosal erosions and porto-systemic gastrin gradients as influenced by different degrees of stress in the rat

Gastric fistula rats (n = 79) were either left as unstressed (fistula closed) controls or gastric secretion, microcirculation (MBF), mucosal stress ulcers were studied in secretory rats subjected to zero (= freely movements allowed), mild, severe restraint stress for 8 h. In all rats gastrin in portal vein and aorta was measured in addition after discontinuation of either protocol. Acid secretion and MBF are progressively reduced by increasing stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Serum gastrin (controls - aorta 53+/- SEM 5, portal vein 73 +/- 9 pg/ml) rises sharply in portal and systemic blood with institution of acid diversion via the outside (zero stress - 136 +/- 21, 398 +/- 98 pg/ml), but declines with increasing stress (severe stress - 82 +/- 16, 101 +/- 27 pg/ml) despite otherwise identical experimental conditions. It is concluded that (1) acid secretion rate and MBF are lowered by stress, but stress ulcers are associated with either increased acidity (mild stress) or peptic activity (severe stress) of gastric juice in the absence of elevated gastrin, (2) enhanced sodium fluxes via gastric lumen and lower acid suggest disruption if mucosal barrier by severe stress, and (3) restraint stress ulcers may be the expression of a combination of disturbances, mainly of metabolic and endocrine nature.     

Role of preischemic glycogen depletion in the improvement of postischemic metabolic and contractile recovery of ischemia-preconditioned rat hearts

BACKGROUND: Ischemic preconditioning (IPC) attenuates acidosis during prolonged ischemia and improves contractile and metabolic parameters during subsequent reperfusion. Glycogen depletion induced by IPC is proposed as a potential mechanism. METHODS AND RESULTS: We studied the influence of manipulations of preischemic glycogen levels (Pre-G, micromol glucose/g wet wt) on contractile and metabolic (via 31P-nuclear magnetic resonance) parameters during 30 minutes of ischemia and recovery in four groups of isovolumic rat hearts: First, control (Con, n=18, mean Pre-G, 21.5+/-0.8); second, after two 5-minute IPC periods (IPC, n=12, Pre-G, 11.3+/-0.7); third, a control group in which Pre-G was depleted by glucose-free, acetate perfusion (Con-LowG, n=9, Pre-G, 7.9+/-1.2); and fourth, an IPC group in which Pre-G was raised by glucose and lactate perfusion such that Pre-G was similar to Con (IPC-HiG, n=11, Pre-G, 20+/-1.4). Manipulation of Pre-G significantly altered the pH fall during 30 minutes of ischemia (Con, 5.76+/-.03, Con-LowG, 6.26+/-.07; IPC-HiG, 5.91+/-.02, IPC, 6.05+/-.09). IPC-HiG hearts had significantly worse metabolic recovery (PCr, 70+/-7 versus 91+/-3% initial; IPC-HiG versus IPC, P<.05) and contractile recovery (end-diastolic pressure, 52+/-5 versus 29+/-5 mm Hg, P<.05) than IPC hearts but better recovery than Con (%PCr, 56+/-6% and end-diastolic pressure, 72+/-6 mm Hg). An ischemic rise in intracellular magnesium occurred and was atttenuated in preconditioned hearts. CONCLUSIONS: Pre-G levels before ischemia influence but are not the sole determinants of the extent of acidosis during prolonged ischemia and of metabolic and contractile recovery during reperfusion in control and preconditioned hearts.     

Preservation of the ration of cerebral blood flow/metabolic rate for oxygen during prolonged anesthesia with isoflurane, sevoflurane, and halothane in humans

BACKGROUND: In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2) was determined every 20 min during anesthesia lasting more than 4h in patients. METHODS: Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference. RESULTS: CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21 +/- 4, 20 +/- 3, and 21 +/- 5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P<0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). AT 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45 +/- 8) was significantly (P<0.01) greater than those in the halothane (32 +/- 8) and sevoflurane (31 +/- 8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC. CONCLUSIONS: These results demonstrate that CBF/CMRO2 ratio is markedly increased above normal and maintained during prolonged inhalation of volatile anesthetics in humans. It is impossible to determine whether these data indicate a stable CBF or whether CBF and CMRO2 are changing in parallel during the observation period. The unchanging electroencephalographic pattern suggests that the former possibility is more likely and that the increase of CBF produced by volatile anesthetics is maintained over time without decay, which has been reported in several animal studies. It also is suggested that isoflurane possesses greater capability to maintain global CBF relative to CMRO(2) than does halothane or sevoflurane. time.)