Effects of sevoflurane, isoflurane, enflurane, and halothane on left ventricular diastolic performance in dogs

The effects of volatile anesthetics on active (ventricular relaxation) and passive (chamber stiffness) indices of diastolic function and on left ventricular filling rates in dogs were studied to determine how these agents affect left ventricular diastolic performance. Thirty-five mongrel dogs were randomly assigned to receive sevoflurane, isoflurane, enflurane, or halothane. Left ventricular pressure waveforms, phonocardiograms, and echocardiograms were recorded after administering the anesthetics at concentrations of 0% (control), 1%, 2%, and 3%. Ventricular relaxation was defined as the time constant of the decline in left ventricular pressure. Chamber stiffness was derived from the ventricular pressure-volume relationship during passive filling. Rapid filling rate, slow filling rate, and atrial filling rate were obtained from echocardiograms and phonocardiograms. No change in the time constant or in chamber stiffness was observed at any concentration of sevoflurane or isoflurane. However, the highest studied concentration of enflurane and halothane produced a significant increase in the time constant and in chamber stiffness. Rapid filling rate as well as atrial filling rate decreased significantly with the volatile anesthetics, especially with enflurane and halothane. Sevoflurane and isoflurane did not alter ventricular relaxation or chamber stiffness, but did affect diastolic function as manifested by their alteration of filling rates. In contrast, enflurane and halothane each prolonged ventricular relaxation and increased chamber stiffness. With the administration of the volatile anesthetics, the rapid filling rate decreased with the deterioration of diastolic function; in addition, atrial filling rates decreased and did not compensate for the reduction in early ventricular filling.     

Cardiovascular effects of acute changes in extracellular ionized calcium concentration induced by citrate and CaCl2 infusions in chronically instrumented dogs, conscious and during enflurane, halothane, and isoflurane anesthesia

To study the cardiovascular effects of low blood ionized calcium ion concentrations [Ca2+] induced by citrate infusion followed by high [Ca2+], induced by CaCl2 infusion awake and during enflurane (2.5% ET), halothane (1.2% ET), and isoflurane (1.6% ET) anesthesia, dogs were chronically instrumented to measure heart rate, aortic, left atrial, and left ventricular (LV) blood pressures, and cardiac output. In conscious dogs low [Ca2+] (decreased 0.35 mM); increased heart rate (HR) and mean aortic pressure (MAP) and decreased stroke volume (SV) and LV dP/dtmax. Low [Ca2+] increased HR during all three anesthetics and decreased LV dP/dtmax except during isoflurane anesthesia. Low [Ca2+] produced more hemodynamic depression during enflurane anesthesia than during anesthesia with halothane or isoflurane increasing left atrial pressure and decreasing MAP and SV. The differences seen were partially related to decreased systemic vascular resistance during halothane and isoflurane anesthesia. In conscious dogs following high [Ca2+] (increased 0.37 mM); only MAP and LV dP/dtmax increased. LVdP/dtmax was also increased by high [Ca2+] during all three anesthetics without a change in MAP. Cardiac output increased during halothane and isoflurane anesthesia but was unchanged during enflurane. It would appear that the hemodynamic sensitivity for the effects of changing [Ca2+] was enflurane greater than halothane greater than isoflurane greater than awake. The results suggest that the effects of changes in [Ca2+] induced by citrate and CaCl2 infusion are modified by the three volatile anesthetics.     

Comparative effects of halothane, enflurane, and isoflurane at equihypotensive doses on cardiac performance and coronary and renal blood flows in chronically instrumented dogs.

In order to compare equihypotensive effects of the three available volatile anesthetics, halothane, enflurane, and isoflurane, dogs were chronically instrumented for measurement of: arterial, left ventricular, and left atrial blood pressures; rate of rise of left ventricular blood pressure; myocardial wall thickening (pulsed Doppler); cardiac output (pulmonary artery electromagnetic flow meter); and coronary and renal blood flows (pulsed Doppler flow meters). All three anesthetics were administered on different days in random order to each dog (n = 10) at doses necessary to decrease mean arterial pressure to 70 and 45 mmHg and two intermediate arterial blood pressures. Changes in cardiac function and regional blood flows were compared to the awake resting state and between anesthetics using analysis of variance and paired t tests. All three anesthetics produced increases in heart rate and decreases in left ventricular dP/dt, myocardial thickening fraction, and stroke volume with the hypotension. The decreases in cardiac performance were similar among the anesthetics except at the high dose (mean arterial pressure = 45 mmHg). During this profound hypotension, cardiac performance was better maintained during isoflurane anesthesia and most depressed by enflurane anesthesia. Coronary and renal blood flows were well preserved with all three anesthetics even at mean arterial pressures of 45 mmHg. Our results suggest that isoflurane may be more beneficial than halothane or enflurane for producing profound intentional hypotension (less than 50 mmHg mean arterial pressure), although extrapolation from animal experiments to the clinical situation should be used with caution.     

Depression of atrial rate, atrioventricular nodal conduction, and cardiac contraction by diltiazem and volatile anesthetics in isolated hearts

The direct effects of isoflurane, halothane, and enflurane alone or combined with diltiazem were examined in 49 isolated perfused guinea pig hearts. Recording electrodes were placed in the right atrium and left ventricular septal wall to measure spontaneous atrial rate and atrioventricular conduction time (AVCT). The right atrium was paced at 3-7 Hz (n = 10) to examine rate-dependent effects on AVCT, Wenckebach's periodicity, and ventricular response rates with atrioventricular (AV) block. Isovolumetric left ventricular pressure (LVP) was measured with a saline-filled balloon placed through the mitral valve. Hearts were perfused with oxygenated Krebs-Ringer's solution at 55 mmHg equilibrated with low or high concentrations of isoflurane (0.7 and 1.5%), halothane (0.5 and 1%), or enflurane (1.1 and 2.2%). Hearts were also perfused with a low or high concentration of diltiazem (75 and 150 ng/ml) alone and during anesthetic exposure. Significant findings of combined exposure were as follows: 1) the low isoflurane, halothane, or enflurane concentration plus a low or high diltiazem concentration decreased LVP compared with control and diltiazem alone; low isoflurane plus the high diltiazem concentration decreased LVP more than isoflurane alone. The high isoflurane, halothane, or enflurane concentration plus the low or the high diltiazem concentration decreased LVP from control, anesthetics and diltiazem alone. Diltiazem plus halothane or enflurane decreased LVP more than diltiazem plus isoflurane. 2) Diltiazem plus low or high isoflurane, halothane, or enflurane concentrations decreased spontaneous atrial rate from control and the agents alone, except the high isoflurane concentration plus the low diltiazem concentration was not greater than that of isoflurane alone. Diltiazem plus halothane or enflurane decreased atrial rate more than diltiazem plus isoflurane. 3) Low and high diltiazem concentration plus low isoflurane, halothane, or enflurane concentrations did not prolong AVCT more than the individual agents alone, but low or high diltiazem plus high isoflurane, halothane, or enflurane concentrations increased AVCT more than each anesthetic alone. In nonpaced hearts, AV block occurred only with high diltiazem plus low enflurane (23%) concentrations and the high enflurane concentration (31%). 4) In hearts paced at 5 and 6 Hz, AVCT increased above controls during a low or high concentrations of diltiazem, during enflurane, and during the low or high concentration of diltiazem plus enflurane; AVCT increased more with the low concentration of diltiazem plus enflurane than with the low diltiazem concentration alone.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prolongation of the QT interval by volatile anesthetics in chronically instrumented dogs

The influence of volatile anesthetics on ventricular repolarization in vivo (QT interval) has not been studied in a systematic fashion. The purpose of this investigation was to characterize the electrocardiographic and hemodynamic actions of the volatile anesthetics halothane, isoflurane, and enflurane in chronically instrumented dogs. Because autonomic nervous system tone may influence ECG findings, experiments were completed with and without concomitant pharmacologic autonomic nervous system blockade. In six groups comprising 50 experiments with 21 instrumented dogs, anesthesia was mask-induced with nitrous oxide, oxygen, and one of the volatile anesthetics and maintained with the volatile anesthetic in 100% oxygen for 2 hours. Changes in the ECG and in hemodynamics were compared to the conscious state. In the absence of autonomic nervous system blockade, halothane and isoflurane significantly prolonged the QT interval (0.24 +/- 0.01 to 0.30 +/- 0.01 second and 0.22 +/- 0.01 to 0.28 +/- 0.01 second, respectively), whereas enflurane produced no change in ventricular repolarization (0.24 +/- 0.01 to 0.26 +/- 0.01 second). All of the volatile anesthetics increased the QT interval corrected for changes in basal heart rate (QTc), and all agents decreased intravascular pressure and dP/dt. Following autonomic nervous system blockade, halothane, isoflurane, and enflurane significantly increased the QT interval and QTc. The results demonstrate that ventricular repolarization is directly altered by the volatile anesthetics independent of changes in autonomic nervous tone. Whether or not such effects are additive with other congenital or acquired forms of QTc prolongation has yet to be examined. The present results indicate that caution should be used during the administration of volatile anesthetics to patients with abnormalities of the QT interval.     

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.     

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. II. Verapamil, enflurane, and isoflurane

The effects of enflurane and isoflurane on the cardiovascular system and cellular calcium kinetics are somewhat different. Consequently, the interaction with the calcium channel blocking drug, verapamil, may also differ. In order to compare the anesthetics, the authors studied the effects of two infusion doses of verapamil (which produced plasma levels of 90 and 180 ng X ml-1) on cardiovascular dynamics and regional blood flow in awake dogs. On two other days, in the same dogs, the effects of approximately 1.1 and 2 MAC enflurane and isoflurane were first studied and then the same verapamil dose regimens while the same anesthetic concentrations were maintained. Verapamil produced only increases in heart rate and the P-R interval in the awake animal. The high dose of both anesthetics markedly decreased mean aortic pressure and left ventricular rate of tension development (dP/dt), and increased heart rate. However, only enflurane also decreased myocardial segment length shortening and increased left atrial pressure. Neither anesthetic alone affected coronary or renal blood flow, while both increased carotid blood flow at the low dose. Verapamil infusion during 1.2 MAC enflurane was more depressant than during 1.2 MAC isoflurane, but the combination of verapamil with 2 MAC concentration of both anesthetics was equally depressant. Both doses of both anesthetics increased plasma verapamil levels compared with the same verapamil dosing regimen awake. When these results are compared with those previously reported for halothane, the effects of verapamil during all three anesthetics are more similar than different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular responses to acute loading with nifedipine alone and nifedipine plus propranolol during inhalation anesthesia in monkeys

The cardiovascular effects of the administration of nifedipine and nifedipine combined with propranolol were examined in 15 monkeys during 0.75 and 1.25 MAC of anesthesia with isoflurane, enflurane, or halothane. Hemodynamic variables measured included heart rate (HR), mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP), maximum rate of increase of the Left ventricular pressure (max LV dP/dt), and thermodilution cardiac output (CO). The infusion of nifedipine at a rate adequate to produce therapeutic blood levels during 0.75 MAC with each anesthetic decreased MAP and SVR, but had no effect on cardiac index (CI), max LV dP/dt, or HR. Increasing the anesthetic concentration from 0.75 to 1.25 MAC during nifedipine administration decreased HR and MAP in all groups and decreased CI with halothane and enflurane, but not with isoflurane. Addition of propranolol by infusion in amounts adequate to produce 75% beta-adrenergic blockade caused a further depression of CI, max LV dP/dt, HR, and MAP. However, the hemodynamic depression was significantly greater with halothane and enflurane than with isoflurane. Intravenous administration of calcium chloride (10 mg/kg) after calcium channel and beta-adrenergic blockade only partially reversed the hemodynamic depression that occurred with all three anesthetics. It was concluded that acute loading with nifedipine with and without propranolol exerts a greater cardiovascular depressant effect during enflurane or halothane anesthesia than during isoflurane anesthesia. The myocardial depressant effects of nifedipine and propranolol myocardial depressant effects of nifedipine and propranolol may be synergistic with the depressant effects of potent inhalation anesthetics.     

Effects of surgical stress and volatile anesthetics on left ventricular global and regional function in patients with coronary artery disease. Evaluation by computer-assisted two-dimensional quantitative transesophageal echocardiography.

We investigated the effects of halothane, enflurane, and isoflurane on central hemodynamics and left ventricular global and regional function when used to control intraoperative hypertension in 39 patients with coronary artery disease. Left ventricular short-axis, midpapillary images were obtained by transesophageal echocardiography. Using a centerline algorithm, we analyzed left ventricular images for global area ejection fraction (GAEF) and segmental area ejection fraction (SAEF). The SAEF/GAEF ratio was calculated for each of eight segments. Measurements were performed after induction of anesthesia but before skin incision; 1 min after sternotomy; and during administration of the inhaled anesthetic. The increase in arterial blood pressure during sternotomy was due to an increase in vascular resistance accompanied by increases in heart rate and filling pressures while GAEF decreased. No changes in the SAEF/GAEF ratio appeared during sternotomy. The inhaled anesthetics restored arterial blood pressure by a similar decrease in vascular resistance. Isoflurane caused an increase in cardiac index that was not seen with halothane or enflurane (halothane vs isoflurane, P < 0.05). The GAEF was decreased by halothane but unaffected by isoflurane and enflurane (halothane vs enflurane; P < 0.05). Isoflurane induced a decrease in the SAEF/GAEF ratios of two segments corresponding to the inferolateral wall of the left ventricle that was, in one of these segments, significantly more pronounced compared with both halothane and enflurane. Halothane or enflurane did not cause any change in regional wall motion. We conclude that isoflurane is more likely to cause regional wall motion changes than halothane or enflurane in patients with coronary artery disease.     

Simultaneous evaluation of left ventricular end-systolic pressure-volume ratio and time constant of isovolumic pressure decline in dogs exposed to equivalent MAC halothane and isoflurane

The effects of 1.5, 2.0, and 2.5 MAC halothane (N = 8) and isoflurane (N = 6) upon systolic performance and isovolumic relaxation were evaluated in open chest dogs. Left ventricular internal volume was determined using piezoelectric crystals. Left ventricular end-systolic pressure-volume points were determined for a series of normal sinus beats during transient venae caval occlusions. The slope of the line formed by those points is a load-independent inotropic index (EES). Left ventricular pressure points during isovolumic relaxation were plotted for computing the time constant of isovolumic pressure decline (T). Both drugs dose-dependently decreased mean arterial blood pressure with no change in heart rate, end-diastolic pressure, or end-diastolic volume. Increasing halothane concentration decreased the values of EES, the maximum rate of rise of left ventricular pressure (dP/dtMAX), and systolic ejection fraction (SEF). Total systemic resistance was unchanged by halothane. Increasing isoflurane concentration decreased EES and dP/dtMAX. The EES was significantly larger (P less than 0.05) with 2.5 MAC isoflurane than 2.5 MAC halothane. The SEF was unchanged by increasing isoflurane. Total systemic vascular resistance was decreased by increasing isoflurane. Isovolumic relaxation was prolonged and became more load-dependent with increasing halothane concentration. Isoflurane did not alter T, but the load-dependency of T was increased by 2.5 MAC isoflurane. There were no differences in T or its load-dependency between drug groups. These results indicate that both anesthetics evoke load-independent negative inotropic effects. Systolic ejection fraction is maintained during isoflurane anesthesia by decreased systemic vascular resistance and less pronounced negative inotropic effects than equivalent MAC halothane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of volatile anesthetics on cardiac calcium channels

In order to investigate how volatile anesthetics affect cardiac calcium channels, the effects of halothane, enflurane, and isoflurane on the specific binding of [3H]-nitrendipine to bovine heart sarcolemmal membranes were studied. All three anesthetics added in liquid form inhibited [3H]-nitrendipine binding in a dose-dependent manner, and more interestingly, the order of inhibition by these volatile anesthetics roughly followed that of their anesthetic potencies. The partial pressures, calculated using the gas/water partition coefficients of halothane, enflurane, and isoflurane which inhibited [3H]-nitrendipine binding by 30% at 37 degrees C were about 1.48 x 10(-2) atm. (1.48%), 4.89 x 10(-2) atm. (4.89%) and 2.76 x 10(-2) atm. (2.76%), respectively. One mmol/l halothane altered not only the maximal binding (Bmax) from 189 f mol/mg protein to 136 f mol/mg protein, but also the dissociation constant (Kd) from 0.074 nmol/l to 0.18 nmol/l. Halothane was also added to the reaction mixture in the gaseous form with air. The partial pressure of halothane needed to bring about 30% inhibition was 0.82 x 10(-2) (0.82%), a value almost similar to that for halothane added in the liquid form. These results indicate that all three volatile anesthetics have direct effects on cardiac calcium channels, and that the magnitude of the effects depends on their anesthetic potencies.     

Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane, and enflurane in the chronically instrumented dog

The systemic and coronary hemodynamic effects of desflurane were compared to those of isoflurane, halothane, and enflurane in chronically instrumented dogs. Since autonomic nervous system function may significantly influence the hemodynamic actions of anesthetics in vivo, a series of experiments also was performed in the presence of pharmacologic blockade of the autonomic nervous system. Eight groups comprising a total of 80 experiments were performed on 10 dogs instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. Systemic and coronary hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.25 and 1.75 MAC desflurane, isoflurane, halothane, and enflurane. Desflurane (+79 +/- 12% change from control) produced greater increases in heart rate than did halothane (+44 +/- 12% change from control) or enflurane (+44 +/- 9% change from control) at 1.75 MAC. Desflurane preserved mean arterial pressure to a greater degree than did equianesthetic concentrations of isoflurane. This result was attributed to a smaller effect on peripheral vascular resistance as compared to isoflurane and greater preservation of myocardial contractility as evaluated by peak positive left ventricular dP/dt and the rate of increase of ventricular pressure at 50 mmHg (dP/dt50) compared to other volatile anesthetics. Increases in diastolic coronary blood flow velocity (+19 +/- 6 and +35 +/- 12% change from control at 1.75 MAC, respectively) and concomitant decreases in diastolic coronary vascular resistance (-41 +/- 12 and -58 +/- 6% change from control at 1.75 MAC, respectively) were produced by desflurane and isoflurane. In the presence of autonomic nervous system blockade, the actions of desflurane and isoflurane were nearly identical with the exception of coronary vasodilation. After autonomic nervous system blockade, isoflurane increased coronary blood flow velocity, but desflurane did not. Furthermore, both desflurane and isoflurane continued to produce less depression of myocardial contractility than did halothane and enflurane. In summary, at equianesthetic concentrations, desflurane and isoflurane produced similar hemodynamic effects; however, in the absence of drugs that inhibit autonomic reflexes, desflurane had less negative inotropic activity and produced less decrease in arterial pressure. The coronary vasodilator actions of desflurane and isoflurane within the limitations of this model were not similar. When the increase in heart rate and rate-pressure product produced by desflurane were prevented in dogs with autonomic nervous system blockade, desflurane produced no change in coronary blood flow velocity.     

Effects of halothane, isoflurane and enflurane on isolated rat heart muscle

Since the effects in the intact organism are complicated by central as well as peripheral effects, we compared the direct cardiac effects of three commonly used inhalational anaesthetics--halothane, isoflurane and enflurane--on isolated heart muscle. Concentration-response curves for inotropic, chronotropic and ventricular automaticity effects of halothane, isoflurane and enflurane (0.1-2% v/v) on electrically stimulated left atria, right atria and right ventricles of the rat were obtained. All three inhalational anaesthetics significantly decreased contractile force; the inhibitory concentration 50 (IC50) of enflurane was 0.55 +/- 0.06% v/v, significantly lower than halothane (0.96 +/- 0.08% v/v) and isoflurane (0.67 +/- 0.05% v/v). Similar results were obtained on atrial nomotopic rate. Halothane, isoflurane and enflurane produced negative chronotropic effects in this preparation. On the other hand, halothane and isoflurane significantly reduced the ventricular ectopic automaticity. However enflurane (0.3, 0.5, 1% v/v) increased ventricular rate. There were statistically significant differences between the IC50 values of atrial and ventricular rate for halothane and isoflurane. These results indicate: (a) direct negative inotropic and chronotropic effects for the three inhalational anaesthetics tested; (b) anti-dysrhythmic actions for halothane and isoflurane; and (c) dysrhythmogenic effects of enflurane.     

In vitro anesthetic washin and washout via bubble oxygenators: influence of anesthetic solubility and rates of carrier gas inflow and pump blood flow

The uptake and elimination of volatile anesthetic agents administered to patients under conditions of hemodilution and hypothermia during cardiopulmonary bypass have not been determined. To define the limitations imposed by oxygenators, we defined washin and washout curves for volatile anesthetic agents administered to bubble oxygenators primed with diluted blood (without connection to a patient). There was rapid equilibration of anesthetic partial pressure between delivered gas and blood (85-90% within 16 minutes). Increasing the gas inflow to the oxygenator from 3 to 12 L/min hastened washin and washout slightly, while increasing the pump blood flow from 3 to 5 L/min had no effect. Rates of washin and washout of anesthetics differed as a function of their blood/gas solubilities: enflurane greater than isoflurane greater than halothane during washin; isoflurane greater than enflurane greater than halothane during washout. However, these differences were small. Oxygenator exhaust partial pressures of anesthetic correlated with simultaneously obtained blood partial pressures, suggesting that monitoring exhaust gas may be useful clinically.     

Local application of 133Xenon for measurement of regional cerebral blood flow (rCBF) during halothane, enflurane, and isoflurane anesthesia in humans

It is well known that halothane causes an increase in cerebral blood flow (CBF). In this study the effects of halothane, enflurane, and isoflurane on regional cerebral blood flow (rCBF) in humans were determined in the presence of 70% N2O at a combined MAC concentration of 1.5. CBF was determined in 24 patients from the washout of locally applied 133Xenon with the use of an external scintillation. All 24 patients (control n = 6, halothane n = 6, enflurane n = 6, and isoflurane n = 6) were undergoing neurosurgical procedures. All patients were anesthetized with thiopental, fentanyl, droperidol, and 70% N2O in oxygen and paralyzed with pancuronium. The measurements were performed after the dura had been opened and before definitive surgery. The first measurement was done in the absence of any volatile agent, and the wash-out curve was registered for 6 min. The second measurement was done after one of the volatile agents had been added for at least 20 min and had reached a concentration of 0.58% for halothane, 1.14% for enflurane, or 1.0% for isoflurane in the expiratory gases in order to obtain about 1.5 MAC with each volatile anesthetic. The anesthetic concentrations were measured with the Engstr?m multigas analyzer EMMA. The physiologic variables changed very little throughout the period of observation. Body temperature, heart rate, blood pressure, PaCO2, and PaO2 were stable. Ephedrine was used to maintain a stable arterial pressure. At approximately 1.5 MAC, halothane (plus N2O) increased rCBF to nearly three times (166%) the control value, while enflurane induced only a slight increase (35%) in rCBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of Adenosine Triphosphate-sensitive Potassium Channels in Coronary Vasodilation by Halothane, Isoflurane, and Enflurane

Background: Halothane, isoflurane, and enflurane cause coronary vasodilation and cardiac depression. This study was performed to assess the role of adenosine triphosphate (ATP)-sensitive potassium channels (K (ATP) channels) in these effects.

Methods: Twenty-five thoracotomized dogs were anesthetized with fentanyl and midazolam. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs. One reservoir was supplied with arterial blood free of a volatile anesthetic, and the second reservoir was supplied with arterial blood equilibrated in an oxygenator with a 1 minimum alveolar concentration of either halothane (0.9%, n = 10), isoflurane (1.4%, n = 28), or enflurane (2.2%, n = 7). Coronary blood flow (CBF) was measured using a Doppler flow transducer, and segmental shortening (SS) was measured with ultrasonic crystals. Responses to the volatile anesthetics were assessed under control conditions, during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 micro gram/min), and after cessation of glibenclamide (recovery). The effectiveness of glibenclamide was verified from inhibition of coronary vasodilator responses to the KATP channel opener cromakalim without effect on those to the KATP channel-independent vasodilators, sodium nitroprusside and acetylcholine.

Results: Under control conditions, the volatile anesthetics caused pronounced increases in CBF (isoflurane > halothane = enflurane), and decreases in SS (enflurane > halothane = isoflurane). Glibenclamide blunted significantly (and reversibly) the increases in CBF, but it had no effect on the decreases in SS.     

Desflurane, Sevoflurane, and Isoflurane Affect Left Atrial Active and Passive Mechanical Properties and Impair Left Atrial-Left Ventricular Coupling In Vivo: Analysis Using Pressure-Volume Relations

Background: The effects of volatile anesthetics on left atrial function in vivo have not been described. The authors tested the hypothesis that desflurane, sevoflurane, and isoflurane alter left atrial mechanics evaluated with invasively derived pressure-volume relations.

Methods: Barbiturate-anesthetized dogs (n = 24) were instrumented for measurement of aortic, left atrial, and left ventricular pressures (micromanometers) and left atrial volume (orthogonal sonomicrometers). Left atrial contractility and chamber stiffness were assessed with end-systolic and end-reservoir pressure-volume relations, respectively, obtained from differentially loaded diagrams. Relaxation was determined from the slope of left atrial pressure decline after contraction. Stroke work and reservoir function were assessed by A and V loop areas, respectively. Left atrial-left ventricular coupling was determined by the ratio of left atrial contractility and left ventricular elastance. Dogs received 0.6, 0.9, and 1.2 minimum alveolar concentration desflurane, sevoflurane, or isoflurane in a random manner, and left atrial function was determined after 20-min equilibration at each dose.

Results: Desflurane, sevoflurane, and isoflurane decreased heart rate, mean arterial pressure, and maximal rate of increase of left ventricular pressure and increased left atrial end-diastolic, end-systolic, and maximum volumes. All three anesthetics caused dose-related reductions in left atrial contractility, relaxation, chamber stiffness, and stroke work. Administration of 0.6 and 0.9 minimum alveolar concentration desflurane, sevoflurane, and isoflurane increased V loop area. All three anesthetics decreased the ratio of stroke work to total left atrial pressure-volume diagram area, increased the ratio of conduit to reservoir volume, and reduced left atrial contractility-left ventricular elastance to equivalent degrees.     

Effect of age on the solubility of volatile anesthetics in human tissues

To determine the effect of age on the solubility of volatile anesthetics in human tissues, the authors measured the solubilities of isoflurane, enflurane, halothane, and methoxyflurane in vitro at 37 degrees C in 35 postmortem human tissue specimens. Specimens were taken from neonates, and young (20-50 yr), middle-aged (50-70 yr), and elderly adults (greater than 70 yr). Brain/gas, heart/gas, and liver/gas partition coefficients for all four anesthetics increased significantly (P less than 0.05) between birth and adulthood, although brain/gas partition coefficients in young adults tended to be higher than those in middle-aged and elderly adults. Heart/gas and liver/gas partition coefficients tended to increase with aging. Muscle/gas partition coefficients for the four anesthetics increased linearly with age. Fat/gas partition coefficients did not change significantly with age. Tissue/blood solubilities for the four anesthetics were of the same order of magnitude for a given tissue and age group. Tissue/blood solubilities for enflurane were 30% lower than those for isoflurane in the same tissue and age group. In summary: the solubility of volatile anesthetics in human tissues increases with age; the lower solubility of anesthetics in neonates partially explains the more rapid increase of alveolar and tissue anesthetic partial pressures in neonates; despite the higher blood solubility of enflurane, its lower tissue solubility may explain a rate of recovery comparable with that of isoflurane.     

Combined depressant effects of diltiazem and volatile anesthetics on contractility in isolated ventricular myocardium

Because the volatile anesthetics depress the entry of calcium (Ca) into myocardial cells and also alter release of intracellular Ca stores, additional pharmacologic blockade of Ca entry could potentially enhance anesthetic-induced depression. The depressant effects of the calcium entry blocker diltiazem combined with the volatile anesthetics halothane, enflurane, or isoflurane were investigated in isolated guinea pig papillary muscle. Muscle contractions were studied in normal Tyrode solution after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz. Anesthetics were studied in the presence of 0.1 and 1 microM diltiazem, which depressed tension to approximately 85 and 55% of control at 2-3 Hz, respectively; depression at the higher concentration was frequency-dependent. Depressant effects of enflurane were determined as previously done for equianesthetic concentrations (approximately 1 and 2 MAC) of halothane and isoflurane. At all stimulation rates, 1.7 and 3.5% enflurane depressed peak tension and dT/dt-max to approximately 73 and 50% of the mean control-recovery value, respectively. After control measurements of contractile characteristics, effects of 0.1 microM diltiazem were determined alone and then with the addition of halothane (0.75 or 1.5%), isoflurane (1.3 or 2.5%), or enflurane (1.7 or 3.5%), respectively. Recovery from anesthetic was then determined in the continued presence of diltiazem. After rest and at rates less than or equal to 0.5 Hz, equianesthetic concentrations of these volatile agents caused similar depression in the presence of diltiazem. At 3 Hz stimulation rate, 1.3% isoflurane caused significantly less contractile depression than did 1.7% enflurane or than 0.75% halothane. At 2-MAC concentrations, differences among the anesthetics were more apparent: 2.5% isoflurane depressed peak tension and dT/dt-max less than did halothane at 1-3 Hz stimulation rates, and depressed dT/dt-max less than 3.5% enflurane at 2-3 Hz. Similar frequency-dependent differences in depression by approximately 2 MAC anesthetics were observed in the presence of 1 microM diltiazem. The patterns of depressant action by the volatile anesthetics were similar to those previously observed in the absence of diltiazem. Furthermore, when the volatile anesthetic depression of contractions was combined with the depression due to diltiazem-induced blockade of Ca entry, the resulting contractile depression did not differ significantly from a prediction that assumed simply additive effects.     

Anesthetics and automaticity in latent pacemaker fibers: I. Effects of halothane, enflurane, and isoflurane on automaticity and recovery of automaticity from overdrive suppression in Purkinje fibers derived from canine hearts

Knowledge of arrhythmic or antiarrhythmic actions of anesthetics on automaticity of latent pacemaker fibers has relevance to the intraoperative management of patients with bradyarrhythmia due to sinus node dysfunction or heart block. The authors determined the effects of halothane, enflurane, and isoflurane on automaticity and recovery of automaticity from overdrive suppression in canine Purkinje fibers derived from normal hearts. Purkinje fibers were superfused with a modified Krebs' solution (37 degrees C) containing epinephrine (2 or 15 microM) and equilibrated with a 97% O2-3% CO2 gas mixture (control). Transmembrane action potentials (AP) were recorded using standard microelectrode techniques. Purkinje fibers were then exposed to anesthetics at vaporizer settings of 0.75 or 1.5% (halothane), 1.75 or 3.5% (enflurane), and 1 or 2% (isoflurane), which were equivalent to measured superfusate concentrations of 0.22 or 0.47 mM (halothane), 0.44 or 0.94 mM (enflurane), and 0.28 or 0.53 mM (isoflurane). Compared to control, there was no significant effect of either concentration of the anesthetics on upstroke (phase 0) depolarization, AP amplitude or duration (50% repolarization), or maximum diastolic potential. All three anesthetics increased spontaneous rate. The increase in rate with all three anesthetics was due to enhanced diastolic depolarization (rate dV/dt, phase-4 depolarization). Recovery times from overdrive suppression were determined after 30 or 60 s of pacing at drive cycle lengths of 800, 500, and 400 ms and only at higher anesthetic concentrations. Recovery of automaticity was shortened by halothane only in slowly paced fibers exposed to the lower concentration of epinephrine. Under all other conditions recovery times were not affected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)