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. CONCLUSIONS: The results indicate that desflurane, sevoflurane, and isoflurane depress left atrial contractility, delay relaxation, reduce chamber stiffness, preserve reservoir and conduit function, and impair left atrial-left ventricular coupling in vivo.     

Volatile anesthetic effects on left ventricular relaxation in swine

The effects of halothane (0.5, 1.0, and 1.5%; n = 10), enflurane (1.0, 2.0, and 3.0%; n = 8), and isoflurane (0.75, 1.5, and 2.25%; n = 8) on isovolumic relaxation were studied in open-chest swine. The time constant for isovolumic left ventricular pressure decline, T, was determined at each anesthetic concentration at the intrinsic heart rate and during atrial pacing to 150 beats per min. The effect of increased left ventricular afterload on T was investigated by partial occlusion of the thoracic aorta to raise the left ventricular systolic pressure to baseline in the presence of volatile anesthetics, and 20% above baseline in the absence of volatile anesthetics. Heart rate and left ventricular systolic pressure decreased substantially with all three anesthetics, whereas left ventricular end-diastolic pressure increased (by 3-4 mmHg). Relaxation time constants increased with all three anesthetics at the intrinsic heart rate; when the heart rate was controlled by pacing, T increased in the halothane and enflurane, but not in the isoflurane, experiments. T was significantly prolonged (by 30-100%) by partial aortic occlusion in the presence of anesthetic, but not in the control measurements. T did not change significantly in the isoflurane experiments when atrial pacing was employed with partial aortic occlusion. The volatile anesthetics, particularly halothane, seem to impair the relaxation process of the left ventricle; further investigation of the mechanisms of this interference, such as anesthetic effects on intracellular calcium movement and total left ventricular load, is warranted.     

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.     

Alteration of left ventricular diastolic function by desflurane, isoflurane, and halothane in the chronically instrumented dog with autonomic nervous system blockade

The effects of the new volatile anesthetic desflurane on three indices of left ventricular diastolic function were examined and compared to those produced by equianesthetic concentrations of isoflurane and halothane. Diastolic function has been shown to significantly influence systolic performance, but the effects of volatile anesthetics on diastolic function have not been extensively examined. Since autonomic nervous system function may significantly influence hemodynamic actions of anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Three groups comprising a total of 23 experiments were performed using 11 dogs instrumented for measurement of aortic and left ventricular pressure, rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, and cardiac output. Systemic hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.0 and 1.5 MAC desflurane, isoflurane, or halothane. Ventricular relaxation was described using invasively derived time constants of isovolumetric relaxation with zero (To) or nonzero (Tn) assumptions of asymptotic decay. Chamber and myocardial stiffness the viscoelastic properties of the ventricle, were described using exponential relationships relating ventricular pressure to segment length and end-diastolic pressure to Lagrangian strain, respectively. Desflurane produced a significant (P less than 0.05) and dose-dependent increase in isovolumetric relaxation as a evaluated by both time constants (To, 22.2 +/- 2.0 during control to 33.9 +/- 3.5 ms at 1.5 MAC; Tn, 33.1 +/- 1.6 during control to 45.1 +/- 4.3 ms at 1.5 MAC). Similar degrees of prolongation of isovolumetric relaxation were produced by isoflurane (Tn, 35.6 +/- 1.5 during control to 47.1 +/- 2.9 ms at 1.5 MAC) and halothane (Tn, 31.7 +/- 2.2 during control to 42.3 +/- 3.9 ms at 1.5 MAC). Halothane also caused an increase in regional passive chamber stiffness (Kp, 0.46 +/- 0.07 during control to 0.88 +/- 0.17 mm-1 at 1.5 MAC) indicating a decrease in ventricular compliance. No changes in chamber stiffness were observed with desflurane or isoflurane. In addition, no significant changes in myocardial stress-strain relationships as evaluated by nonlinear elastic coefficients, alpha (gain) and beta (myocardial stiffness), were observed with any anesthetic. Although the effects of volatile anesthetics on systolic function could not be entirely excluded from the analysis, the results indicated that desflurane, isoflurane, and halothane produce equivalent degrees of prolongation of isovolumetric relaxation. Halothane also caused a decrease in compliance during passive filling as evaluated by chamber stiffness, but no change in compliance was observed at end diastole as assessed by stress-strain relationships.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Effects of halothane and isoflurane on left ventricular diastolic function during surgical stress in patients with coronary artery disease

Background: The effects of inhalation anesthetics on left ventricular (LV) systolic function are well documented, while the effects of these agents on LV diastolic function have mainly been evaluated in animal studies, with conflicting results.
Methods: We investigated the effects of halothane and isoflurane, when used to control the stress response to sternotomy in 33 patients with coronary artery disease (CAD). LV early diastolic relaxation and end-diastolic stiffness were evaluated from mitral Doppler flow profiles, transesophageal two-dimensional echocardiography, and central hemodynamic measurements. Measurements were performed a) after induction of anesthesia, b) after volume loading, c) prior to surgery and d) during surgery, 10 min after introduction of the inhalation anesthetic. The effects of the anesthetics on Doppler indices reflecting early diastolic relaxation, and on the left ventricular end-diastolic pressure-area (LVED P/A) relationship, were studied.
Results: When data obtained during surgical stress were compared to the control situation, we found an increase in the LV filling pressures in both groups, while only the isoflurane group showed an increase in heart rate. An increase in end-systolic LV area and decreased fractional area change was present in the halothane group, while an increase in LV end-diastolic area, and similar changes in the mitral Doppler indices (decreases of deceleration rate and time of early diastolic filling), indicating an impairment of early diastolic relaxation, was present in both groups. Isoflurane induced a displacement of the LVED P/A relationship leftwards from the baseline LVED P/A curve.
Conclusion: Both halothane and isoflurane impair early diastolic relaxation in patients with CAD, when used to control intraoperative surgical stress. In contrast to halothane, isoflurane induced a change in the LVED P/A relationship, suggestive of an increased LVED stiffness.     

Isoflurane, but Not Halothane, Improves Indices of Diastolic Performance in Dogs with Rapid Ventricular, Pacing-induced Cardiomyopathy

Background: The left ventricular (LV) mechanical effects of isoflurane and halothane were examined in dogs with rapid LV pacing-induced cardiomyopathy. These experiments tested the hypothesis that isoflurane and halothane differentially enhance indices of diastolic performance in dogs with moderate LV dysfunction.

Methods: Eight dogs were chronically instrumented for measurement of LV and aortic pressures, subendocardial segment length, and cardiac output. Contractility was quantified by preload recruitable stroke work (Mw). Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), segment lengthening velocities and time-velocity integrals during early filling (dL/dtE and TVI-E) and atrial systole (dL/dtA and TVI-A), and a regional chamber stiffness constant (Kp). Hemodynamics and LV function were recorded in the conscious state before pacing. The left ventricles of the dogs were then continuously paced at ventricular rates between 220 and 240 beats *symbol* min sup -1 for 10 plus/minus 1 days and monitored on a daily basis. After the development of moderate LV dysfunction, pacing was temporarily discontinued, and dogs were studied in sinus rhythm in the conscious state and after 20 min equilibration at 1.1, 1.4, and 1.7 minimum alveolar concentration isoflurane and halothane on separate days.

Results: Chronic rapid pacing increased baseline (sinus rhythm) heart rate, LV end-diastolic pressure, and end-diastolic segment length and decreased mean arterial pressure, LV systolic pressure, and cardiac output. Mw decreased and tau and Kp increased, consistent with LV systolic and diastolic dysfunction. Reductions in dL/dtE /dL/dt sub A and TVI-E/A occurred, which indicated that LV filling was more dependent on atrial systole. In dogs with cardiomyopathy, isoflurane and halothane increased heart rate and decreased mean arterial pressure, LV systolic pressure, LV end-diastolic pressure, cardiac output, Mw, and Kp. Decreases in LV end-diastolic pressure were more pronounced in dogs anesthetized with 1.1 minimum alveolar concentration isoflurane compared with halothane. Halothane-induced decreases Mw were greater than those observed with equi-minimum alveolar concentration isoflurane. A reduction in tau and increases in TVI-E/TVI-A and the ratio of early to total LV filling were observed with isoflurane. In contrast, halothane caused dose-related reductions in dL/dtE, dL/dt sub A, TVI-E, and TVI-A, and did not improve the ratios of these variables.     

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)     

Differential effects of halothane,enflurane, isoflurane,and sevoflurane on the hemodynamics and metabolism in the perfused rat liver in fasted rats

The effects of volatile anesthetics on hepatic hemodynamics and metabolism were studied using isolated liver perfusion. The liver was isolated from overnight-fasted male Sprague-Dawley rats and placed in a recirculating perfusion-aeration system. The liver was perfused through the portal vein at a constant pressure of 12 cmH₂O. Four volatile anesthetics, halothane, enflurane, isoflurane, and sevoflurane, were administered at concentrations identical to 1 and 2 times the minimal alveolar concentration (MAC). All the anesthetics maintained hepatic flow and decreased hepatic oxygen consumption. Among the anesthetics tested, isoflurane produced the largest decrease in hepatic oxygen consumption. At 2 MAC, the percent decrease in oxygen consumption by isoflurane was significantly greater than that by halothane. The increase in lactate concentration in the recirculating perfusate was significantly enhanced by the volatile anesthetics, and the enhancement was less remarkable in the isofluranetreated group than in the enflurane-or sevoflurane-treated groups. These results indicate that volatile anesthetics alter hepatic carbohydrate metabolism but maintain hepatic blood flow when the perfusion pressure is kept constant. Isoflurane exerts exceptional influence on hepatic oxygen consumption and lactate production, and may be preferable for operations that limit the oxygen supply to the liver.     

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.     

The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs.

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary-to-systemic blood flow ratio effects of sevoflurane,isoflurane, halothane,and fentanyl/midazolam with 100% oxygen in children with congenital heart disease

The cardiovascular effects of volatile anesthetics in children with congenital heart disease have been studied, but there are limited data on the effects of anesthetics on pulmonary-to-systemic blood flow ratio (Qp:Qs) in patients with intracardiac shunting. In this study, we compared the effects of halothane, isoflurane, sevoflurane, and fentanyl/midazolam on Qp:Qs and myocardial contractility in patients with atrial (ASD) or ventricular (VSD) septal defects. Forty patients younger than 14 yr old scheduled to undergo repair of ASD or VSD were randomized to receive halothane, sevoflurane, isoflurane, or fentanyl/midazolam. Cardiovascular and echocardiographic data were recorded at baseline, randomly ordered 1 and 1.5 mean alveolar anesthetic concentration (MAC) levels, or predicted equivalent fentanyl/midazolam plasma levels. Ejection fraction (using the modified Simpson's rule) was calculated. Systemic (Qs) and pulmonary (Qp) blood flow was echocardiographically assessed by the velocity-time integral method. Qp:Qs was not significantly affected by any of the four regimens at either anesthetic level. Left ventricular systolic function was mildly depressed by isoflurane and sevoflurane at 1.5 MAC and depressed by halothane at 1 and 1.5 MAC. Sevoflurane, halothane, isoflurane, or fentanyl/midazolam in 1 or 1.5 MAC concentrations or their equivalent do not change Qp:Qs in patients with isolated ASD or VSD. IMPLICATIONS: Sevoflurane, halothane, isoflurane, and fentanyl/midazolam do not change pulmonary-to-systemic blood flow ratio in children with atrial and ventricular septal defects when administered at standard anesthetic doses with 100% oxygen.     

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.     

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.     

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 volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle: investigation in isolated systemic resistance arteries

BACKGROUND: Volatile anesthetic actions on intracellular Ca2+ stores (ie., sarcoplasmic reticulum [SR]) of vascular smooth muscle have not been fully elucidated. METHODS: Using isometric force recording method and fura-2 fluorometry, the actions of four volatile anesthetics on SR were studied in isolated endothellum-denuded rat mesenteric arteries. RESULTS: Halothane (> or = 3%) and enflurane (> or = 3%), but not isoflurane and sevoflurane, increased the intracellular Ca2+ concentration ([Ca2+]i) in Ca2+-free solution. These Ca2+-releasing actions were eliminated by procaine. When each anesthetic was applied during Ca2+ loading, halothane (> or = 3%) and enflurane (5%), but not isoflurane and sevoflurane, decreased the amount of Ca2+ in the SR. However, if halothane or enflurane was applied with procaine during Ca2+ loading, both anesthetics increased the amount of Ca2+ in the SR. The caffeine-induced increase in [Ca2+], was enhanced in the presence of halothane (> or = 1%), enflurane (> or = 1%), and isoflurane (> or = 3%) but was attenuated in the presence of sevoflurane (> or = 3%). The norepinephrine-induced increase in [Ca2+], was enhanced only in the presence of sevoflurane (> or = 3%). Not all of these anesthetic effects on the [Ca2+]i were parallel with the simultaneously observed anesthetic effects on the force. CONCLUSIONS: In systemic resistance arteries, the halothane, enflurane, isoflurane, and sevoflurane differentially influence the SR functions. Both halothane and enflurane cause Ca2+ release from the caffeine-sensitive SR. In addition, both anesthetics appear to have a stimulating action on Ca2+ uptake in addition to the Ca2+-releasing action. Halothane, enflurane, and isoflurane all enhance, while sevoflurane attenuates, the Ca2+-induced Ca2+-release mechanism. However, only sevoflurane stimulates the inositol 1,4,5-triphosphate-induced Ca2+ release mechanism. Isoflurane and sevoflurane do not stimulate Ca2+ release or influence Ca2+ uptake.     

Effects of halothane, enflurane, and isoflurane on coronary blood flow autoregulation and coronary vascular reserve in the canine heart

To investigate the effects of volatile anesthetics on coronary blood flow (CBF) autoregulation and coronary vascular reserve, studies were performed on chronically instrumented dogs, awake and during the administration of 1.0 MAC halothane, enflurane, and isoflurane. Coronary pressure-flow plots were generated by measuring left anterior descending coronary artery blood flow while varying coronary inflow pressure with a hydraulic occluder. Autoregulation was quantitated by two measures: the slope of the horizontal "autoregulated" portion of the pressure-flow relationship and the autoregulation index (ArI) of Norris. Slope values (ml.min-1.mmHg-1 +/- SD) were: awake, 0.243 +/- 0.043; halothane, 0.414 +/- 0.044; enflurane, 0.587 +/- 0.187; and isoflurane, 0.795 +/- 0.246. The increase in slope was statistically significant only for halothane and isoflurane (P less than .05). The ArI approaches 1.0 when autoregulation is perfect, and approaches zero or is a negative number when autoregulation is absent. The authors found ArI values of: awake, 0.55; halothane, -0.08; enflurane, -0.01; isoflurane, -0.02. These values indicate good autoregulation while awake, but impaired autoregulation with all three anesthetics (P less than .05). Coronary vascular reserve was calculated, at a diastolic coronary pressure of 40 mmHg, as the difference between resting flow and flow during maximal coronary vasodilation induced by intracoronary adenosine. Coronary vascular reserve, maximal coronary conductance, and coronary zero-flow pressure were not significantly altered by these anesthetics. The authors conclude that 1.0 MAC enflurane, halothane, and isoflurane mildly disrupt CBF autoregulation, increasing CBF out of proportion to myocardial demands. Under the conditions of this study, these anesthetics do not affect maximal CBF or coronary vascular reserve.     

Alteration of canine left ventricular diastolic function by intravenous anesthetics in vivo. Ketamine and propofol.

Diastolic function has been shown to influence overall cardiac performance significantly, but the effect of intravenous anesthetics on diastolic function has not been previously characterized in vivo. The effects of ketamine and propofol on two indices of left ventricular diastolic function were examined in chronically instrumented dogs. Because autonomic nervous system function may significantly influence the systemic hemodynamic actions produced by intravenous anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups comprising a total of 14 experiments were performed using 7 dogs instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, and cardiac output. Systemic hemodynamics and diastolic function were recorded and evaluated in the conscious state and after a 20-min equilibration at 25-, 50-, and 100-mg.kg-1.h-1 infusion doses of ketamine or propofol. Ventricular relaxation was described using the time constant of isovolumetric relaxation (tau) assuming a nonzero asymptote of ventricular pressure decay. Regional chamber stiffness, an index of passive ventricular filling, was described using an exponential equation relating segment length to ventricular pressure between minimum ventricular pressure and the onset of atrial systole.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anesthetics and Automaticity of Dominant and Latent Pacemakers in Chronically Instrumented Dogs: IV. Dysrhythmias after Sinoatrial Node Excision

Background: Subsidiary atrial pacemakers assume control after sinoatrial (SA) node excision, and anesthetic-catecholamine interactions can produce severe bradycardia during isoflurane anesthesia. We hypothesized that epinephrine enhances atrial, atrioventricular junctional, and ventricular dysrhythmias after SA node excisions in dogs and that inhalation anesthetics would facilitate such dysrhythmias.

Methods: In eight dogs, SA nodes were excised and epicardial electrodes implanted at the atrial appendages, at the His bundle, and along the sulcus terminalis. Site of the earliest atrial activation and incidences of nonatrial beats were determined in the conscious state, with methylatropine, with epinephrine, and during halothane, isoflurane, or enflurane anesthesia.

Results: After SA node excision, a stable, regular subsidiary atrial pacemaker rhythm resulted. Epinephrine and halothane shifted the site of earliest activation to more remote atrial sites. Epinephrine-induced ventricular escape was increased by all anesthetics tested, but atropine prevented ventricular escape. Epinephrine-induced His bundle (atrioventricular junctional) and premature ventricular beats were increased by halothane and enflurane. After SA node excision, ventricular escape occurred as a result of epinephrine-anesthetic interactions, especially during anesthesia with isoflurane.