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PubMed1990

Attenuation of histamine-induced airway constriction by albuterol during halothane anesthesia.

The effect of albuterol (a beta 2 specific adrenergic agonist) on airway reactivity to histamine aerosol challenge was evaluated during halothane anesthesia and thiopental-fentanyl anesthesia in five Basenji Greyhound dogs. Responses to histamine aerosol challenges (0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/ml) were measured during thiopental-fentanyl anesthesia and during halothane anesthesia in the presence and absence of iv albuterol (2.5 micrograms/kg). Prior to aerosol challenges, baseline pulmonary resistance (RL) and dynamic compliance (Cdyn) did not differ in the four conditions. Albuterol significantly attenuated the pulmonary response to histamine during thiopental-fentanyl anesthesia. Although halothane itself significantly attenuated the pulmonary response to histamine, this response was further attenuated by the addition of albuterol. This study suggests that albuterol is effective in attenuating bronchoconstriction during both thiopental-fentanyl and halothane anesthesia. As the effects of albuterol and halothane on the airways are additive, beta-adrenergic agonists such as albuterol are the agents of choice to treat bronchospasm in patients anesthetized with inhalational anesthetics.

Albuterol↗
PubMed1990

Peripheral vascular effects of halothane and isoflurane in humans with an artificial heart.

The peripheral vascular effects of isoflurane and halothane were compared in five critically ill patients in whom a Jarvik-7 artificial heart had been implanted. The lungs of all patients were mechanically ventilated in the postoperative period and the patients were monitored with an arterial catheter and with catheters that had been surgically inserted into the right and left atria and into the pulmonary artery. Norepinephrine and epinephrine plasma concentrations were measured using a radioenzymatic assay. The Jarvik-7 settings were modified to render the artificial heart "preload independent" and to maintain cardiac output constant. Each patient was anesthetized twice using halothane and isoflurane at two different MAC levels, 1 and 1.5 (Datex vapour analyzer), with the interval between each anesthetic ranging from 12 to 26 h. Both anesthetics significantly decreased mean arterial pressure (from 100 +/- 11 mmHg to 66 +/- 13 mmHg for halothane and from 102 +/- 17 mmHg to 48 +/- 11 mmHg for isoflurane; mean +/- SD) and systemic vascular resistance index (from 27 +/- 11 Wood units/m2 to 18 +/- 6 Wood units/m2 for halothane and from 30 +/- 6 Wood units/m2 to 13 +/- 3 Wood units/m2 for isoflurane; mean +/- SD), but with isoflurane to a significantly greater extent than with halothane (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of halothane on human and rat hepatocyte cultures.

The aim of this study was to investigate direct cytotoxicity to human and rat hepatocytes in primary culture from halothane and compare it with that of isoflurane, which is known to be minimally metabolized and less toxic in vivo. Both human and rat parenchymal cells were isolated by the two-step collagenase perfusion method and after attachment to plastic were incubated with either volatile anesthetic for 24 h. All the cultures were maintained in 20% O2 condition and were not induced prior to anesthetic treatment. Temperature, atmosphere conditions, and anesthetic concentrations were kept constant during the study period. Evaluation of cytotoxicity was based on morphologic, biologic (determination of both extracellular and intracellular lactate dehydrogenase activity), and metabolic (protein synthesis and secretion) end points. Protein synthesis and secretion rates were found to be the most sensitive parameters in hepatocyte cultures from both species. Protein synthesis was inhibited by 18% and protein secretion by 50% in the presence of 1 and 1.25 mM halothane, respectively, in human cell cultures (P less than 0.05). With 1.25 mM halothane intracellular lactate dehydrogenase was also decreased; lactate dehydrogenase leakage and morphologic alterations were detected only beyond 5 mM halothane. By contrast, in rat hepatocyte cultures protein secretion was inhibited by 26% and protein synthesis by 20% in the presence of 0.1 and 0.75 mM halothane, respectively, whereas morphologic alterations and a 37% lactate dehydrogenase leakage increase were observed with the concentration of 1 mM (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Direct effect of halothane and isoflurane on the function of the sarcoplasmic reticulum in intact rabbit atria.

The negative inotropic effect of halothane and isoflurane on potentiated-state contractions of isolated rabbit atria in a normal Ca2+ (2.5 mM) medium was compared with the force depression in low Ca2+ media without an anesthetic. When this comparison was made in the presence of 1 microM ryanodine so that the force of contraction was dependent only upon transsarcolemmal Ca2+ influx with no Ca2+ contribution from the sarcoplasmic reticulum (SR), the force of contraction was depressed equally by 0.6% halothane in a normal Ca2+ medium and by a 1.5 mM Ca2+ medium without the anesthetic. Similarly, 1.0% halothane or 1.5% isoflurane and a 1.0 mM Ca2+ medium were equally depressant as were 2.4% isoflurane and a 0.5 mM Ca2+ medium. In the absence of ryanodine, where the atrial contractile activity is largely dependent on Ca2+ released from the SR, 0.6% halothane in the normal Ca2+ medium depressed contractile force by 32%, whereas the force was depressed by only 16% in the 1.5 mM Ca2+ medium without the anesthetic. Similar results were obtained when the effects of 1.0% halothane and of 1.0 mM Ca2+ were compared. In contrast, the force of contraction measured in the absence of ryanodine was not at all inhibited by 1.5% isoflurane and minimally (11%) inhibited by 2.4% isoflurane. Consequently, the force depression by isoflurane was less than that found in the low Ca2+ media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in normovolemic and hypovolemic cirrhotic rats.

The effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in cirrhotic rats that were either normovolemic or hypovolemic following hemorrhage were characterized. Rats received at random either ketamine (30 mg/kg iv, 1.5 mg.kg-1.min-1 iv), halothane, enflurane, or isoflurane (1 MAC). Conscious rats were considered the control group. Four weeks before hemodynamic studies bile duct ligation was performed in all rats to induce cirrhosis. Hemodynamic measurements were performed using the radioactive microsphere method 1 h after the onset of anesthesia and 30 min after hemorrhage. Anesthetized rat lungs were mechanically ventilated with room air. Before hemorrhage cardiac index was higher in conscious rats and in rats receiving isoflurane than in the other groups (P less than 0.001). Hepatic arterial blood flow was similar in conscious rats and in those receiving isoflurane or halothane and was higher than in those receiving ketamine or enflurane. The lowest splanchnic and portal venous tributary blood flows were observed in rats receiving enflurane. After hemorrhage cardiac index was significantly less than before hemorrhage in all groups, except in rats receiving enflurane. After hemorrhage portal venous tributary blood flow decreased significantly in all groups except in enflurane group. During halothane and enflurane anesthesia hepatic arterial blood flow and hepatic arterial fraction of cardiac output decreased (P less than 0.01) and they were maintained in the other groups. After hemorrhage hepatic arterial fraction of cardiac output in conscious rats was higher than in those receiving ketamine, halothane, or enflurane (P less than 0.05) and was similar to those receiving isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of halothane and isoflurane on postischemic "stunned" myocardium in the dog.

Short periods of coronary artery occlusion are known to produce prolonged periods of ventricular dysfunction. The effects of halothane or isoflurane on contractility and metabolism in postischemic "stunned" myocardium were studied in an open-chest canine model in which the left anterior descending artery (LAD) was occluded for 15 min and then reperfused. Regional function in the LAD and circumflex artery (CIRC) areas were measured with sonomicrometry, and metabolic data were determined from simultaneous arterial and venous measurements of oxygen and lactate. Halothane and isoflurane produced equivalent decreases in systolic shortening in both normal (CIRC) and stunned (LAD) areas of the heart. Furthermore, the amount of depression was similar with either halothane or isoflurane. Halothane 0.75 MAC significantly decreased systolic shortening in both the LAD region (from 38.8 +/- 25.9% to 11.0 +/- 21.8%) and in the CIRC region (from 116.7 +/- 24.7% to 87.5 +/- 23.3%). At equivalent MAC concentrations of isoflurane, the values were 42.5 +/- 45.7 to -7.0 +/- 49.9% in the LAD region and 91.5 +/- 11.9% to 66.9 +/- 23.9% in the CIRC area. At 1.5-MAC halothane, systolic shortening in the LAD region decreased from 47.9 +/- 47.2% to -0.6 +/- 20.3% and in the CIRC area from 114.6 +/- 16.8% to 76.0 +/- 18.7%. Isoflurane at 1.5 MAC produced significant decreases, from 23.4 +/- 54.5% to -15.6 +/- 27.1% in the LAD region and from 94.4 +/- 33.2% to 61.3 +/- 28.2 in the CIRC area.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effects of halothane, enflurane, and isoflurane on calcium current in isolated canine ventricular cells.

The effects of halothane, enflurane, and isoflurane on voltage-dependent Ca2+ channel current (ICa) were compared in canine ventricular cells by the whole-cell voltage-clamp technique. ICa was elicited in each cell by progressively depolarizing pulses, from -80 or -40 mV to more positive membrane potentials. The peak amplitude and inactivation rate of the inward current were analyzed before, during, and after the external application of equianesthetic concentrations (0.5, 1.0, and 2.0 MAC) of halothane, enflurane, or isoflurane. The concentrations of these agents in the Krebs' solution were as follows (percentage in the gas phase): halothane 0.36, 0.68, and 1.50%; isoflurane 0.50, 1.00, and 1.90%; and enflurane 0.66, 1.36, and 2.39%. Halothane, enflurane, and isoflurane rapidly reduced peak ICa amplitude at all voltages studied, resulting in a depression of the entire current-voltage relationship for ICa activation. This depression was concentration-dependent and completely reversible upon wash-out of the anesthetic agents. Quantitatively, the three anesthetic agents produced a similar inhibition of peak ICa at approximately equianesthetic concentrations. Inactivation of ICa during 200-ms depolarizing pulses was not affected by two lower concentrations of the anesthetic agents, but was accelerated by the highest concentration of enflurane used. These findings suggest that the negative inotropic and chronotropic actions of halothane, enflurane, and isoflurane on the ventricular myocardium are related, at least in part, to their inhibition of ICa at the sarcolemma. However, since all three anesthetic agents depressed ICa amplitude similarly, their quantitatively different effects on cardiac performance are due most likely to differences in actions at other cellular sites.

Animals↗
PubMed1991

Percutaneous loss of desflurane, isoflurane, and halothane in humans.

We studied the percutaneous losses of the new inhaled anesthetic, desflurane (I-653), and of isoflurane and halothane during anesthetic administration and elimination in seven healthy male volunteers. Anesthesia was induced and maintained with midazolam, thiopental, and fentanyl. We administered 70% N2O for 30 min, and then administered 2% desflurane, 0.4% isoflurane, and 0.2% halothane concurrently with 65% N2O for 30 min. Inspired, end-tidal, and mixed-expired gas samples were collected during administration of the volatile agents and for 5-7 days of elimination. The right arm and hand of each subject was enclosed in a sealed glass cylinder having a port at each end, one for sampling and both for flushing with N2 after anesthetic administration and every 15 min thereafter. We sampled gases from the cylinder during administration and for the 150 min of elimination and analyzed their anesthetic concentrations by gas chromatography. The surface area of the enclosed portion of the arm was measured, and the total body surface area was calculated. All values were normalized to (i.e., divided by) the end-tidal (alveolar) concentration at the end of administration. During administration, percutaneous loss of halothane was 3.5 times that of desflurane and 2 times that of isoflurane. During elimination, the loss of halothane was 6 times and 2 times greater than the loss of desflurane and isoflurane, respectively. Percutaneous loss of halothane significantly exceeded that of isoflurane. The elimination values included an estimate of elimination after 150 min. The percutaneous loss of each anesthetic was 2- to 3-fold greater during elimination than administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Isoflurane, and not halothane, increases mesenteric blood flow supplying esophageal ileocoloplasty.

Regional ischemia may induce anastomotic leakage or stenosis after esophageal reconstruction using retrosternal interposition of an ileocolic graft. These complications may be related to systemic or local hemodynamic alterations. This study was designed to evaluate the influence of inhalational anesthetic agents on the intestinal circulation supplying these ileocolic grafts. Seven patients (age 30 +/- 5 yr, mean +/- standard deviation [SD]) were studied in the immediate postlaparotomy period. Miniaturized Doppler implantable microprobes were sutured to the single artery supplying the graft and connected to an 8-MHz pulsed Doppler flowmeter. Continuous fentanyl infusion (300 micrograms.h-1) was maintained throughout the study. Measurements were performed at the end of four 30-min periods, which were, successively: first control; isoflurane or halothane anesthesia; second control; and isoflurane or halothane anesthesia. Isoflurane and halothane were administered in cross sequence with end-tidal concentration of 0.8% and 0.5%, respectively, to induce equipotent anesthesia. Both anesthetics induced similar decreases in mean systemic arterial pressure (MAP), cardiac output (CO), and systemic vascular resistance. During isoflurane, mean mesenteric blood flow (MBFm) supplying the graft was increased (+38%; P less than 0.05), and the mesenteric vascular resistance index (MVRI; -44%; P less than 0.05) was decreased, leading to an increase in the MBFm/CO ratio (P less than 0.05). Halothane changed neither the MBFm nor the MBFm/CO ratio, despite a mild decrease in MVRI (-14%; P less than 0.05). Diastolic blood flow velocity increased significantly (2.3 +/- 0.9 vs. 0.8 +/- 0.3 cm.s-1, P less than 0.05) only with isoflurane, suggesting a local vasodilation not observed with halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Direct comparative effects of halothane, enflurane, and isoflurane on oxygen supply and demand in isolated hearts.

The authors examined the direct myocardial and coronary vascular responses to isoflurane, enflurane, and halothane and compared their effects on attenuating autoregulation of coronary flow (CF) as assessed by changes in the O2 supply-demand relationship. The effects of these anesthetics on left ventricular pressure (LVP), CF, percentage of O2 extraction, O2 delivery (DO2), and myocardial O2 consumption (MVO2) were examined in 47 isolated guinea pig hearts perfused at constant pressure. An increase in DO2 from control relative to MVO2 was used to indicate attenuation of autoregulation, and a decrease in MVO2 relative to DO2 to indicate a reduction of myocardial work and O2 utilization. Each heart was exposed to 0.51, 0.70, and 1.20 vol% halothane (n = 16); 0.91, 1.41, and 2.04 vol% enflurane (n = 16); or 0.45, 0.87, and 1.22 vol% isoflurane (n = 15). Adenosine (2 mM) was given to test maximal CF in arrested and in paced hearts. Mean results for increasing concentrations of each agent were as follows: LVP (average control 92 +/- 5 mmHg) (standard error of mean [SEM]) decreased by 15%,* 25%,* and 34%* with halothane; 13%,* 24%,* and 34%* with enflurane; and only 3%, 7%, and 13%* with isoflurane (*P less than 0.05 vs. controls). CF (control 6.1 +/- 0.3 ml.min-1.g-1) was not altered significantly with halothane or enflurane but increased by 6%, 9%, and 16%* with isoflurane and maximally by 86 +/- 7%* with adenosine. The percentage of O2 extraction (control 69.2 +/- 1.8%) decreased by 9%,* 16%,* and 22%* with halothane; 7%,* 15%,* and 22%* with enflurane; and only 1%, 4%, and 7%* with isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Regional and global myocardial circulatory and metabolic effects of isoflurane and halothane in patients with steal-prone coronary anatomy.

The use of isoflurane in patients with coronary artery disease remains controversial because of the possibility of "coronary steal". In this study, the effects of isoflurane and halothane on global and regional myocardial blood flow and metabolism were compared, and the relationship between steal-induced myocardial ischemia and the administered volatile anesthetic was investigated in 40 patients with steal-prone coronary anatomy undergoing elective coronary artery bypass operations. The patients were randomly assigned to receive either isoflurane or halothane (0.5 MAC inspired concentration) immediately after induction with fentanyl (50 micrograms/kg). Hemodynamic measurements and blood samples were obtained at preinduction, postintubation, preincision, poststernotomy, at 60 min after beginning isoflurane or halothane, and precannulation (a total of 238 study events). Throughout the study, heart rate was kept constant by atrial pacing at approximately postintubation values while arterial pressure was maintained within 10% of postintubation values with fluid administration or phenylephrine infusion. Overall, systemic hemodynamic changes observed during the study were similar in the two groups. Myocardial ischemic episodes were defined as a new electrocardiographic ST-segment shift of greater than or equal to 0.1 mV, new echocardiographic regional wall motion abnormalities (RWMA) and/or myocardial lactate production (MLP). A total of 18 new ischemic episodes were detected in 15 patients (7 episodes during isoflurane in 7 patients and 11 during halothane in 8 patients). Ten (56%) episodes were related to acute hemodynamic abnormalities, whereas 8 (44%) were random and unrelated to changes. Seven episodes were detected by echocardiography (38%), 6 by MLP (33%) and 1 by ECG (6%) only, whereas concomitant echocardiographic abnormalities and MLP were observed during 2 episodes (11%), echocardiographic and ECG during 1 (6%), and ECG and MLP during 1 other (6%). Ratios of regional to global coronary venous flow, coronary vascular resistance, myocardial oxygen content, and lactate extraction, along with hemodynamic data obtained during these episodes, do not support coronary steal for the development of myocardial ischemia. We conclude that in patients with steal-prone coronary anatomy anesthetized with fentanyl, neither isoflurane nor halothane administered at concentrations used in the current study is likely to cause myocardial ischemia by the coronary steal mechanism.

Adult↗
PubMed1991

Comparison of halothane, enflurane, and isoflurane with nitrous oxide on contractility and oxygen supply and demand in isolated hearts.

The authors' aim was to examine direct cardiac responses to isoflurane, enflurane and halothane, as altered during mild hypoxia by the substitution of nitrogen (N2) for oxygen (O2), and additionally by the substitution of nitrous oxide (N2O) for N2. Heart rate, atrioventricular conduction time, left ventricular pressure (LVP), peak positive and negative derivatives of LVP (dLVP/dtmax), coronary flow, O2 delivery (DO2), percent O2 extraction, and myocardial O2 consumption (MVo2) were examined in 47 isolated guinea pig hearts. Changes in the ratio of DO2 to MVO2 indicated the relationship of autoregulation of coronary flow to myocardial O2 utilization. Each heart was first exposed to 96% O2 and then randomly exposed to 48% N2 and 48% N2O alone and with three equivalent concentrations of one of three volatile anesthetics: isoflurane (n = 15), halothane (n = 16), or enflurane (n = 16). Results were as follows: 1) N2 alone significantly decreased LVP, +dLVP/dtmax and -dLVP/dtmax, DO2 and MVO2; increased coronary flow; and produced no change in heart rate, atrioventricular conduction time, percent O2 extraction, or the DO2/MVO2 ratio. 2) Compared to N2, N2O alone only produced additional significant decreases in LVP and +dLVP/dtmax. 3) In the presence of N2 or N2O, each volatile anesthetic caused significant stepwise decreases in heart rate, LVP, +dLVP/dtmax and -dLVP/dtmax, MVO2, and percent O2 extraction; no additional change in coronary flow or DO2; and a stepwise increase in the DO2/MVO2 ratio. The effects of halothane and enflurane were generally greater than those of isoflurane. 4) Each volatile anesthetic caused an additive, parallel depression of LVP and percent O2 extraction as a function of MAC with N2O compared to N2. This study demonstrates that the direct negative inotropic effects of halothane and enflurane are more pronounced than those of isoflurane and are accompanied by a greater reduction in O2 utilization by halothane and enflurane than by isoflurane in the presence of mild hypoxia alone or with the addition of N2O. The study also demonstrates that N2O accentuates the negative inotropic effects of volatile anesthetics during reduced O2.

Animals↗
PubMed1992

Differential effects of halothane, enflurane, and isoflurane on Ca2+ transients and papillary muscle tension in guinea pigs.

These studies were designed to examine the effects of inhalational anesthetics on rapid changes in myocardial intracellular Ca2+ and Ca2+ sensitivity of the contractile apparatus. The effects of halothane, enflurane, and isoflurane on rapid changes in intracellular Ca2+ (Ca2+ transients as measured with bioluminescent protein aequorin) and contractile characteristics were compared in guinea pig right ventricular papillary muscles. In addition to examination of their potencies at equianesthetic concentrations, the effects of these agents on alterations in Ca2+ sensitivity at myofilaments were also investigated. The negative inotropic effects of halothane (0.65 and 1.15%) and enflurane (1.0 and 2.2%) were dose-dependent and closely related to a decrease in Ca2+ transients. In the presence of isoflurane (0.77 and 1.6%), the contractile force decreased in a dose-dependent manner, but the decrease was significantly less as compared to that with equianesthetic concentrations of halothane and enflurane. An additional feature observed in the presence of isoflurane was a dissociation between intracellular Ca2+ availability and contractile force. Although the magnitude of the Ca2+ transients did not change when the percentage of isoflurane was increased from 0.77 to 1.6, the contractile force decreased. Because of these findings, the effects of halothane (1.2%), enflurane (2.2%), and isoflurane (1.6%) on the relationship between intracellular Ca2+ and tension developed in the papillary muscle were examined in order to assess myofibrillar responsiveness to Ca2+. The results indicate that only isoflurane slightly but significantly shifted the Ca2+/isometric tension curve toward higher intracellular Ca2+ concentrations; no differences were observed in the absence and presence of equianesthetic concentrations of halothane and enflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Coronary microcirculation during halothane, enflurane, isoflurane, and adenosine in dogs.

We investigated the effects of clinically administered volatile anesthetics and of adenosine on the microvasculature of the in situ beating canine heart. Thirteen dogs were studied during general anesthesia with an opioid (piritramide), which was infused throughout the experiments. Measurements were obtained in each animal at control (piritramide only) and during hypotension (mean arterial pressure 60 mmHg) induced by halothane, enflurane, isoflurane, and adenosine. Using epiillumination and fluorescence microscopy, 354 arterial microvessels with diameters from 20 to 450 microns were examined through all experimental periods. Hypotension by halothane, enflurane, isoflurane, and adenosine reduced coronary vascular resistance by 13%, 23%, 40%, and 85%, respectively. Coronary venous PO2 was unchanged from control with halothane (+/- 0%) and enflurane (+7%) and significantly increased with isoflurane (+16%) and adenosine (+65%). Left ventricular blood flow decreased significantly during halothane (-35%) and enflurane (-23%); was unchanged from control during isoflurane (-9%); but significantly increased during adenosine (+397%). Coronary arterial and arteriolar diameters increased with all hypotensive agents. Vasodilation was least with halothane, intermediate with enflurane and isoflurane, and most pronounced with adenosine. Diameters increased considerably more in vessels with initial diameters below 100 microns as opposed to larger vessels. Calculation of microvascular segmental resistances revealed that the maximum conductance changes during volatile anesthetics were located in the vessel segments visualized by microscopy, i.e., in vessels larger than 20 microns. However, this was not the case with adenosine. We conclude that volatile anesthetics induce coronary vasodilation by preferentially acting on vessels with diameters from 20 microns to approximately 200 microns, whereas adenosine, in addition, has a pronounced impact on the small precapillary arterioles.

Adenosine↗
PubMed1992

Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells.

The effects of halothane (0.75% and 1.5%) and isoflurane (2.6%) on macroscopic Ca2+ and K+ channel currents (ICa and IK, respectively) were investigated in voltage-clamped vascular muscle cells from the canine coronary artery. Single coronary arterial cells were dialyzed with K+ glutamate solution and superfused with Tyrode's solution for measurement of IK (n = 45). Stepwise depolarization from a holding potential of -60 mV to beyond -30 mV elicited an outward, slowly inactivating IK that had a macroscopic slope conductance of 18 nS. IK was reduced 75% by 10 mM 4-aminopyridine, a K+ channel antagonist. Compared to 4-aminopyridine, halothane at 0.75% and 1.5% reduced peak IK amplitude only by 14 +/- 2% and 36 +/- 3%, respectively. At approximately equianesthetic concentrations, 2.6% isoflurane suppressed IK less than did 1.5% halothane, reducing peak amplitude by 15 +/- 3%. In other sets of experiments, cells were dialyzed with 120 Cs(+)-glutamate solution and superfused with 10 mM BaCl2 or CaCl2 solutions to isolate ICa (n = 39) pharmacologically. Under these conditions, progressive depolarizing steps from -60 mV elicited a small inward current, which was potentiated 3.4-fold by equimolar substitution of Ba2+ for Ca2+ in the external solution and was blocked by 1 microM nifedipine. This inward current, which resembled L-type ICa, was blocked 37 +/- 4% and 70 +/- 4% in the presence of 0.75% and 1.5% halothane, respectively. Isoflurane (2.6%) also decreased ICa by 55 +/- 5%. It appears that while halothane and isoflurane suppress both IK and ICa, these anesthetics preferentially reduce ICa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Halothane, enflurane, and isoflurane attenuate both receptor- and non-receptor-mediated EDRF production in rat thoracic aorta.

EDRF (endothelium-derived relaxing factor) is a cellular and intercellular messenger that activates soluble guanylate cyclase. In blood vessels it is released from the endothelium and causes relaxation of vascular smooth muscle. Halothane previously has been shown to attenuate EDRF-induced vasodilation elicited by the receptor-mediated vasodilators acetylcholine and bradykinin and to alter muscarinic receptor activity. We examined and compared the effects of the inhaled anesthetics halothane, enflurane, and isoflurane on endothelium-dependent vasodilation and tested the hypothesis that these agents inhibit EDRF-mediated vasodilation solely through inhibition of endothelial cell receptor-mediated EDRF release. Isolated rat thoracic aortic rings were mounted for isometric tension recording and preconstricted with phenylephrine. Cumulative dose-response curves were obtained to methacholine, a receptor-mediated endothelium-dependent dilator; to A23187, a nonreceptor-mediated endothelium-dependent dilator; and to sodium nitroprusside, a direct-acting endothelium-independent dilator before, during, and after inhalational anesthetic exposure. Both receptor-mediated and non-receptor-mediated endothelium-dependent relaxation by methacholine and A23187, respectively, were significantly (P less than 0.01 to P less than 0.05) and reversibly attenuated by halothane, enflurane, and isoflurane at 2 MAC and by isoflurane at 1 MAC. Endothelium-independent relaxation by sodium nitroprusside, an agent that acts directly on the vascular smooth muscle cell to activate guanylate cyclase, was unaffected by any of the anesthetics at any concentration tested. Indomethacin had no significant effect on the inhibition of endothelium-dependent vasodilation by these inhalational anesthetics. We conclude that halothane, enflurane, and isoflurane inhibit endothelium-dependent vasodilation; that isoflurane is more potent than halothane and enflurane in this regard.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Left ventricular hypertrophy in rabbits does not exaggerate the effects of halothane on the intracellular components of cardiac contraction.

Inhalational anesthetics and ventricular hypertrophy have adverse effects on cardiac muscle contraction. The effects of 1, 2, and 3% halothane on the contractile protein and sarcoplasmic reticulum, but not the sarcolemma, were examined in normal left ventricular tissue from rabbits that underwent a sham surgical procedure (n = 5) and in left ventricular hypertrophied tissue from surgically induced aortic coarctation (n = 7). Muscle samples were mechanically "skinned" to disrupt the sarcolemma. Fiber bundles were mounted in photodiode transducers and bathed in a series of solutions designed to examine the contractile protein [Ca2+]-tension responses or to examine Ca2+ storage by and release from the sarcoplasmic reticulum. Hill equation analysis of the [Ca2+]-tension relationship of the contractile protein was performed. Compared to normal muscle, hypertrophied muscle was associated with an 8.2% decrease in the [Ca2+] necessary for 50% maximum tension (more sensitive to Ca2+) (P less than 0.001) and an increase in the slope constant of 23% (P less than 0.001). In normal and hypertrophied tissue, each 1% of halothane incrementally decreased the contractile protein response to maximal [Ca2+] by 5% (P less than 0.01), increased the [Ca2+] at 50% maximum tension by 5% (P less than 0.01), and had no effect on the slope of the Hill equation. Halothane also inhibited Ca2+ storage by the sarcoplasmic reticulum. In normal muscle, 1, 2, and 3% halothane decreased the stored Ca2+ to 42, 22, and 9%, respectively, of Ca2+ storage without halothane (P less than 0.001). However, hypertrophied muscle demonstrated slightly less depression (P less than 0.05 by analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

AMPA receptor competitive antagonism reduces halothane MAC in rats.

Various subtypes of receptors have been identified for glutamate, an excitatory neurotransmitter. Previous studies have shown that antagonism of glutamate at the NMDA receptors reduces minimum alveolar concentration (MAC) for volatile anesthetics. NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline) is a selective antagonist at the glutamatergic AMPA receptor. The purpose of this experiment was to determine whether AMPA receptor antagonism influences halothane MAC in the rat. Sprague-Dawley rats were anesthetized with halothane in 50% O2/balance N2, tracheally intubated and the lungs were mechanically ventilated. Increasing doses of NBQX were intravenously infused in three groups while the control group was infused with vehicle (D5W). Halothane MAC was then determined by the tail-clamp method. Halothane MAC was log-linearly related to plasma NBQX concentrations (MAC = 0.125 (In plasma concentration NBQX) + 1.035, r2 = 0.77). A maximal 58% reduction of halothane MAC was achieved with an NBQX loading dose of 42 mg/kg followed by a continuous infusion rate of 36 mg x kg-1 x h-1 (control = 1.02 +/- 0.07%; NBQX = 0.43 +/- 0.12%; P < .01). Larger doses of NBQX were not possible because of the poor aqueous solubility of this compound. In a separate experiment, awake rats were randomly assigned to groups based on the dose of NBQX infused. Pa(CO2) and mean arterial pressure were measured at time 0 and at 5 and 30 min after start of NBQX infusion. The infusion was then stopped. Time until recovery of the righting reflex was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗