Sevoflurane Alters Right Ventricular Performance But Not Pulmonary Vascular Resistance in Acutely Instrumented Anesthetized Pigs

Sevoflurane Alters Right Ventricular Performance But Not Pulmonary Vascular Resistance in Acutely Instrumented Anesthetized Pigs François Kerbaul, MD, PhD,* Maurice Bellezza, MD,* Choukri Mekkaoui, PhD,* Horéa Feier, MD,* Catherine Guidon, MD,* Joanny Gouvernet, MD,† Pierre-Henri Rolland, PhD,* François Gouin, MD, PhD,* Thierry Mesana, MD, PhD,* and Frédéric Collart, MD* Objective: Although the effects of halogenated agents on both normal and diseased left ventricles have been widely studied, the influence of these anesthetic agents on right ventricular (RV) performance remains less well characterized. This study was undertaken to examine the effects of 2 different concentrations of sevoflurane on RV function, and coronary and pulmonary hemodynamics in acutely instrumented anesthetized pigs. Design: Prospective experimental study. Setting: Laboratory of experimental research in a university teaching hospital. Subjects: Anesthetized pigs. Interventions: Regional RV function in 10 pigs was determined from pressure segment length loop analysis, global RV function from stroke work versus end-diastolic pressure relation, right coronary blood flow, and pulmonary vascular resistance (PVR), without and then with 2.6% (minimum

alveolar concentration [MAC]) and 3.9 % (1.5 MAC) end-tidal sevoflurane concentrations. Main Results: Sevoflurane preserved inflow systolic shortening and RV regional external work, but significantly depressed outflow systolic shortening (p < 0.05). Global RV stroke work was depressed to 72% ⴞ 12% and 61% ⴞ 10% of baseline value, respectively, with 1 and 1.5 MAC of sevoflurane (p < 0.05), but without alteration of PVR. Right coronary blood flow decreased dose dependently. Conclusions: Sevoflurane causes significant depression of global RV function associated with a qualitatively different effect on inflow and outflow tracts, without any modification of PVR. © 2006 Elsevier Inc. All rights reserved.

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ple shortening fraction in the assessment of RV regional contractility.

INCE THE INTRODUCTION OF HALOTHANE, the effects of the halogenated agents on both the normal and diseased left ventricle (LV) have been widely studied.1-3 In contrast, the influence of these volatile anesthetic agents on determinants of right ventricular (RV) function remain less well characterized. Morphologically different from the LV, the crescentshaped RV is comprised of 2 parts, inflow and outflow tracts. These regions differ embryologically, anatomically, and in response to inotropic stimulation, and normally contract and relax sequentially.4,5 This concept of sequential or asynchronous contraction of the RV free wall from inflow to outflow tract complicates analysis of the variations of systolic shortening of the 2 regions, and has been emphasized in several studies.4,6-8 Sevoflurane is one of the most recently introduced inhalation anesthetic agents. Its effects on LV function have been the focus of 1 study in chronically instrumented dogs, and were almost identical to those induced by isoflurane.1 With regard to RV contraction, a previous investigation9 indicated that sevoflurane exerts similar effects of systolic segment shortening in both the RV inflow and outflow tracts in sheep, but did not evaluate completely regional and global RV performance. Therefore, the present study was designed to assess the effects of sevoflurane at clinically relevant concentrations (1 and 1.5 minimum alveolar concentration [MAC]) on regional global RV performance, as well as coronary and pulmonary hemodynamics, in anesthetized pigs, using pressure-dimension segment length loops, global RV stroke work, and pulmonary vascular resistance (PVR). The authors attempted to address 2 important aspects of cardiac physiology in this study design: regional differences within the RV free wall (inflow v outflow tract) and superiority of pressure/dimension analysis over sim-

KEY WORDS: anesthetized pigs, coronary hemodynamics, regional and global performance, right ventricular function

METHODS The study design was reviewed and approved by the animal ethics review board of the Faculty of Medicine. All procedures were in accordance with the Guiding Principles in the Care and Use of Animals of the American Physiological Society.

Animal Preparation After a 12-hour fasting period with free access to water, 10 pietrin pigs (mean weight, 70 kg) were premedicated with ketamine (20 mg/kg intramuscularly [IM]), midazolam (0.1 mg/kg IM), and atropine (0.25 mg IM) and placed in the supine position. Anesthesia was induced with midazolam, 0.1 mg/kg , plus sufentanil, 0.5 ␮g/kg, and were maintained with intravenous infusions of sufentanil, 0.5 ␮g/kg/h, and midazolam, 0.15 mg/kg/h. Muscle paralysis was achieved with vecuronium bromide, 1 mg/kg, and was maintained with an infusion of vecuronium at 2 mg/kg/h after a tracheostomy had been performed. The lungs were mechanically ventilated via a No. 9 cuffed tracheostomy tube (Tracheosoft Lanz, 101-70 ID; Malinckrodt Medical, Athlone Ireland) with a Servo ventilator B 900 (Siemens, Elema, Sweden) initially set to deliver forced inspiratory oxygen (FIO2) of 0.4, tidal volume between 12 and 15

From the *Laboratoire d’Hémodynamique et de Mécanique Cardiovascular (LHMCV) and †LERTIM, Faculté de Médecine, Hôpital Timone adultes, Marseille, France. Address reprint requests to François Kerbaul, MD, PhD, Département d’Anesthésie-Réanimation, Hôpital Timone adultes, 264 rue saint Pierre, 13005 Marseille cedex 05, France. E-mail: [email protected] © 2006 Elsevier Inc. All rights reserved. 1053-0770/06/2002-0013$32.00/0 doi:10.1053/j.jvca.2005.05.017

Journal of Cardiothoracic and Vascular Anesthesia, Vol 20, No 2 (April), 2006: pp 209-216

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Fig 1. Surgical instrumentation of the right ventricle in a pig. Ao, aorta; RV, right ventricle; IVC, inferior vena cava; PA, pulmonary artery.

mL/kg, and respiratory rate adjusted to maintain partial pressure of carbon dioxide in arterial blood (PaCO2) in the range of 35 to 40 mmHg. Positive end-expiratory pressure of 5 cmH2O was used to prevent atelectasis. Sevoflurane was administered with a vaporizer adapted to the ventilator. Inspired and expired fractions of oxygen, carbon dioxide, and sevoflurane were measured with an infrared spectrophotometer (Ultima II; Datex, Helsinki, Finland). Sodium chloride (0.9% at 10 mL/kg/h) was infused into the left internal jugular vein during surgery. Temperature was maintained at 38°C to 39°C with an electrical heating pad. A fluid-filled catheter was placed in the aortic arch through the right carotid artery for systemic

arterial blood pressure and arterial blood sampling. A balloon-tipped flow-directed pulmonary artery catheter (Model 131H-7F; Baxter Edwards, Irvine, CA) was inserted through the left internal jugular vein and positioned under pressure control in a branch of the pulmonary artery for measurement of mean pulmonary arterial pressure (Ppa), occluded pulmonary arterial pressure (Ppao), and central core temperature. After exposure with a midline sternotomy, the heart was suspended in a pericardial cradle. A solid-state micromanometer catheter (Millar Instruments, Houston, TX) was introduced into the RV through the right internal jugular vein. One hydraulic occluder was placed around the inferior vena cava (IVC) to achieve transient modifications of RV preload. Two pairs of piezoelectric crystals were implanted in the RV to determine segment shortening via a sonomicrometer (Triton Technology, San Diego, CA). One set was placed in the region of the inflow tract, and 1 set in the region of the outflow tract. These crystals were placed intramyocardially, 1.5 cm apart, and were aligned parallel to the principal shortening axis in each region, as determined by Meier et al10 (Fig 1). An intramyocardial electrocardiogram (ECG) was recorded from the crystal leads and used for timing of cardiac events. A 24-mm ultrasonic flow probe (Transonic Systems, Ithaca, NY) was placed around the main pulmonary artery. A 3-mm ultrasonic flow probe (Transonic Systems) was placed around the right coronary artery 1 cm above the first right marginal artery to measure right coronary blood flow. Flow probes were connected to a transit-time flowmeter device (T101; Transonic Systems). Hemodynamic data were obtained after steady-state instrumentation (1 hour after the end of surgical preparation). Arterial pH, partial pressure of carbon dioxide (PCO2), and partial pressure of oxygen (PO2) were determined every 2 hours immediately after drawing the samples with an automated analyzer (ABL 500; Radiometer, Copenhagen, Denmark). Intravenous lidocaine, 1 mg/kg, was systematically added to prevent ventricular arrhythmias during implantation of sonomicrometric crystals.

Table 1. Hemodynamic Data Sevoflurane Measurement

Baseline

1 MAC

1.5 MAC

Heart rate (bpm) Mean arterial pressure (mmHg) Mean Ppa (mmHg) Ppao (mmHg) PVR (dynes · sec · cm⫺5) RV systolic pressure (mmHg) RV end-diastolic pressure (mmHg) Fractional systolic shortening (inflow) Fractional systolic shortening (outflow) Cardiac output (L/min) Stroke volume (mL) dP/dt max (mmHg/sec) Right coronary blood flow (mL/min) Right coronary vascular resistances (mmHg/mL/min)

114 ⫾ 27 96 ⫾ 22 19 ⫾ 5 9⫾3 200 ⫾ 76 32 ⫾ 10 2⫾3 0.12 ⫾ 0.05 0.11 ⫾ 0.03 4.0 ⫾ 0.9 38 ⫾ 6 504 ⫾ 140 96 ⫾ 33 1.6 ⫾ 0.5

107 ⫾ 25 74 ⫾ 19* 18 ⫾ 3 9⫾3 192 ⫾ 51 27 ⫾ 9* 2⫾3 0.12 ⫾ 0.05 0.07 ⫾ 0.04*‡ 3.6 ⫾ 0.9* 33 ⫾ 8* 398 ⫾ 190* 77 ⫾ 32* 1.6 ⫾ 0.6

102 ⫾ 26 58 ⫾ 22*† 16 ⫾ 3* 8⫾5 208 ⫾ 50 23 ⫾ 6*† 4⫾3 0.10 ⫾ 0.04 0.06 ⫾ 0.04*‡ 3.0 ⫾ 0.3*† 30 ⫾ 6* 278 ⫾ 78* 57 ⫾ 24*† 1.7 ⫾ 0.6

NOTE. Values represent mean ⫾ SD. Sevoflurane 1 MAC and 1.5 MAC, respectively, 2.6% and 3.9% end-tidal sevoflurane concentrations. Abbreviations: MAC, minimum alveolar concentration; Mean Ppa, mean pulmonary arterial pressure; Ppao, pulmonary artery occlusion pressure; PVR, pulmonary vascular resistances; RV, right ventricular. *p ⬍ 0.05 v baseline. †p ⬍ 0.05 v SEV 1 MAC. ‡p ⬍ 0.05 v inflow fractional systolic shortening.

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Fig 2. Representative regional segment length and pressure measurements (pig 4) obtained from the right ventricle (RV) inflow and outflow tracts during 1 beat in the absence (A) and presence (B) of 1.5 minimal alveolar anesthetic concentration of sevoflurane. X-axis represents time in milliseconds. During sevoflurane administration, inflow contracted first, and onset of shortening and occurrence of maximal systolic shortening was different by 25 to 30 msec between inflow and outflow tracts. (Color version of figure is available online.)

Experimental Protocol Initial surgical preparation was performed in 10 pigs that underwent measurements of regional, global RV function, and right coronary artery flow under baseline conditions and during transient vena cava occlusion induced via inflation of the IVC occluder for approximately 10 seconds. Autonomic blockade was induced after surgery with atropine (2 mg/kg), propranolol (3 mg/kg), and hexamethonium (20 mg/kg), administered over 10 minutes. Then continuous infusions of atropine (0.1 mg/kg/h), propranolol (0.5 mg/ kg/h), and hexamethonium (4 mg/kg/h) were added to minimize the effects of cardiac autonomic tone on sequential RV contraction.6 Pigs were also randomly assigned to receive 2.6% (1 MAC) and 3.9% (1.5 MAC) end-tidal sevoflurane concentrations 1 hour after the beginning of pharmacologic autonomic blockade.11 Measurements were made 30 minutes after exposure of each concentration with 10 minutes of a stable state. Stable state was assessed according to stable heart rate, systemic arterial and pulmonary pressures, cardiac output, and end-tidal PCO2. At the end of each study, each animal was sacrificed by intravenous injection of potassium chloride, under deep intravenous anesthesia.

Hemodynamic Measurements Pressure segment length loops were recorded during 10-second occlusions of the IVC while mechanical ventilation was suspended.

One IVC short occlusion (⬍10 sec) was performed under each experimental condition to avert repetitive and prolonged systemic arterial hypotension and inadequate coronary perfusion. Hemodynamic data were digitized at 200 Hz and recorded with a data acquisition system consisting of a power personal computer (Pentium, 1 gHz), a 16-bit high-speed analog-to-digital converter, and custom software developed using the LabView programming language (National Instruments Corp, Austin, TX).

Hemodynamic Data Analysis Hemodynamic data, including pressure, segment length, segment shortening, and pulmonary and right coronary artery flow were all determined under steady-state conditions during dynamic IVC occlusion without (baseline) and with 2.6% and 3.9% end-tidal sevoflurane (1 MAC and 1.5 MAC) concentrations. Adequacy of autonomic blockade was demonstrated by the absence of significant variation of heart rate during abrupt decreases in venous return. End-diastole was defined as the point corresponding to the beginning of the sharp upslope in the expanded RV pressure tracings. End-systole was defined as the point of maximum negative RV dP/dt max. Systolic shortening was defined as the difference between end-diastolic and end-systolic segment length, divided by end-diastolic segment length. Dynamic IVC occlusion data were analyzed as follows. Individual cardiac cycles were automatically identified from the intramyocardial ECG signal. Regional external

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Fig 3. Effects of sevoflurane on end-diastolic and end-systolic segment lengths of right ventricular free wall (inflow region) and outflow region. Values are presented as mean ⴞ SD. *Significantly (p < 0.05) different from baseline.

work was defined as the mean area of each pressure segment length loop recorded during each cardiac cycle under IVC occlusion. The area of the pressure segment length loop recorded during each cardiac cycle was plotted against its corresponding end-diastolic segment length to derive the preload recruitable stroke work relationship from both the inflow and outflow tracts.12 The slope of the preload recruitable stroke

Fig 4. tions.

work relationship has been used as a reproducible index of regional RV contractility, whereas the length axis intercept corresponds to the enddiastolic segment length at which no external work would be performed.13 Global RV stroke work was determined as the instantaneous product of the stroke volume (determined by integration of the pulmonary blood flow waveform during ejection using the pulmo-

Recordings show representative cardiac dimensions, right ventricular pressure, and cardiac output recorded under baseline condi-

SEVOFLURANE CAUSES SIGNIFICANT DEPRESSION OF GLOBAL RV FUNCTION

Fig 5.

213

Recordings show representative cardiac dimensions, right ventricular pressure, and cardiac output recorded under sevoflurane.

nary artery flow probe) and RV pressure over each cardiac cycle during IVC occlusion. Right coronary vascular resistance (CVR) and PVR were derived from the following formulas:

a Pentium power personal computer (2 gHz) with Statistica software (StatSoft Inc, Tulsa, OK).

CVR(dyne ⁄ sec ⁄ cm⫺5) ⫽ Mean arterial pressure (systemic arterial blood pressure 关mmHg兴) ⫺ RV end-diastolic pressure 共mmHg) ⁄ coronary blood flow (mL ⁄ min)

Table 1 shows steady-state hemodynamic data under each experimental condition. Sevoflurane induced dose-dependent decreases in mean arterial pressure and right coronary blood flow, with no change in CVR. Cardiac output, stroke volume, dP/dt max, and RV systolic pressure were significantly depressed by both concentrations. Pulmonary vascular resistances were not modified. Sevoflurane had different effects on regional function within the RV (Table 1; Figs 2 and 3). Figures 4 through 6 depict recordings that show representative cardiac output, RV pressure, and cardiac dimensions obtained under baseline conditions, sevoflurane administration, and during transient IVC occlusion. Figure 2 depicts representative regional segment length and pressure tracings before and during administration of 1.5 MAC sevoflurane. Inflow and outflow contractions were similar at baseline. During sevoflurane administration, the in-

(1)

⫺5

PVR (dyne ⁄ sec ⁄ cm ) ⫽ Mean Ppa (mmHg) ⫺ Ppao (mmHg) ⫻ 80 ⁄ cardiac output (L ⁄ min)

Statistical Analysis Hemodynamic and metabolic variables were analyzed by analysis of variance (ANOVA) for repeated measures. When significance of a factor was p ⬍ 0.05, a Scheffe post hoc test was performed to compare specific situations. Slopes and intercepts of composite preload recruitable stroke work relations were compared with the Student t test. Data are expressed as mean (⫾SD). All analyses were performed with

RESULTS

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Fig 6. sion.

Recordings show representative cardiac dimensions, right ventricular pressure, and cardiac output recorded during IVC occlu-

flow tract contracted first, and onset of shortening and occurrence of maximal systolic shortening was different by 25 to 30 msec between the inflow and outflow tracts (Fig 2). Outflow systolic shortening remained depressed, whereas inflow systolic shortening remained constant. Outflow end-diastolic and systolic segment lengths were also greater at 1 and 1.5 MAC than at baseline (Fig 3). Table 2 summarizes the derived indices of systolic function during the control period and under deep

sevoflurane anesthesia. Outflow regional external work was reduced, respectively, to 67% ⫾ 18% and 51% ⫾ 16% of the baseline value under 2.6% and 3.9% end-tidal sevoflurane concentrations (Fig 7). Global RV stroke work was depressed to 72% ⫾ 12% and 61% ⫾ 10% of the baseline value, respectively, with 1 and 1.5 MAC of sevoflurane. No significant difference was shown between metabolic parameters during the experiment (Table 3).

Table 2. Derived Indices of Contractile Function Sevoflurane Measurement

Regional PRSW relation slope inflow (mmHg) Regional PRSW relation slope outflow (mmHg) Regional PRSW relation intercept inflow (mm) Regional PRSW relation intercept outflow (mm) Regional external work inflow (N/m) Regional external work outflow (N/m) Global RV stroke work (N/m)

Baseline

1 MAC

1.5 MAC

11.2 ⫾ 1.6 11.0 ⫾ 1.5 8.5 ⫾ 2.2 7.9 ⫾ 2.1 54 ⫾ 35 43 ⫾ 32 64 ⫾ 33

9.1 ⫾ 1.8 9.4 ⫾ 0.9* 7.1 ⫾ 1.5 8.4 ⫾ 2.0 48 ⫾ 30 29 ⫾ 18* 46 ⫾ 22*

8.5 ⫾ 1.2* 7.4 ⫾ 1.1*† 7.6 ⫾ 1.6 9.6 ⫾ 2.5 41 ⫾ 27 22 ⫾ 12* 39 ⫾ 15*

NOTE. Values represent mean ⫾ SD. Sevoflurane 1 MAC and 1.5 MAC, respectively, 2.6% and 3.9% end-tidal sevoflurane concentrations. Abbreviations: MAC, minimum alveolar concentration; PRSW, preload recruitable stroke work; RV, right ventricular. *p ⬍ 0.05 v baseline. †p ⬍ 0.05 v sevoflurane 1 MAC.

SEVOFLURANE CAUSES SIGNIFICANT DEPRESSION OF GLOBAL RV FUNCTION

Fig 7. Representative pressure segment length loops of the outflow area obtained by constriction of the inferior vena cava during a single experiment, without (A) and with (B) 1.5 maximum allowable concentration of end-tidal sevoflurane (B). Note that loop area (ie, external work) is approximately 49% lower with high-dose sevoflurane than under baseline conditions.

215

respond to 1 and 1.5 MAC in combination with opiates, which reduce the anesthetic requirement.11,15 Reduction of systolic segment shortening by sevoflurane 2% and 4% has been previously shown in sheep, but regional, global RV function and coronary hemodynamics were not completely explored.9 Therefore the present study design attempted to address 2 important aspects of cardiac physiology: regional differences within the RV free wall (inflow v outflow tract) and superiority of pressure/dimension analysis over simple shortening fraction in the assessment of RV regional contractility. The study found a significant decrease of outflow fractional systolic shortening under sevoflurane, without any effect on the inflow tract. Autonomic blockade with atropine, propranolol, and hexamethonium was performed to minimize the effects of cardiac autonomic tone on sequential RV contraction, which modifies the sequential contraction pattern of the RV.6 Differential effects of isoflurane and halothane on RV inflow and outflow tracts have already been shown,6,16 different from those found by Fujita et al9 in sheep. These discrepancies could be explained by the anatomic and physiologic differences of these 2 regions. The RV inflow tract develops from the ventricular portion of the primitive cardiac tube, and the RV outflow tract arises from the bulbus.4,7 This concept of sequential or asynchronous contraction of the RV free wall from inflow to outflow tracts has been examined under a variety of conditions, including administration of volatile anesthetics,6,8,9,16 which found it to be dynamic (ie, the magnitude of asynchrony varies substantially under different conditions). Although the global mechanical significance of this phenomenon remains uncertain, what is clear is that both in experimental animals and human beings asynchrony of the RV free wall in combination with factors such as blood inertia could influence RV ejection and filling. Other causes could be due to differences in autonomic nervous system tone, and loading conditions.9,17,18 A variability in myocardial responsiveness to adrenergic and cholinergic stimulation could be implicated, and indicate that when the cardiac autonomic system is blocked, reflex responses did not offset the negative inotropy of sevoflurane in the outflow tract, but they did in the RV inflow tract. This could be corroborated in that the outflow tract in mammals demonstrates a more prominent positive inotropic response to catecholaminergic stimulation (cardiotonic drugs).8 Another reason could be due to disparities between experimental conditions (different orientation of ultra-

DISCUSSION

This study was undertaken to assess the effects of 2 different concentrations of sevoflurane on RV performance and pulmonary hemodynamics in 10 acutely instrumented anesthetized pigs. Sevoflurane induced a significant depression of global RV function with differential effects on inflow and outflow tracts, and no modification of PVR. Regional RV function was determined from pressure segment length loops and preload recruitable stroke work relations, which seem to be heart rate and load independent.1,14 Global RV function was determined as the instantaneous product of the stroke volume and RV pressure over each cardiac cycle during IVC occlusion. Sevoflurane concentrations studied cor-

Table 3. Arterial Blood Gas, pH, and body temperature at baseline and after exposure to sevoflurane Sevoflurane Measurement

Baseline

1 MAC

1.5 MAC

pH PaO2 (mmHg) PaCO2 (mmHg) Body temperature (°C)

7.40 ⫾ 0.06 177 ⫾ 45 35 ⫾ 5 38.4 ⫾ 0.8

7.42 ⫾ 0.05 168 ⫾ 52 34 ⫾ 6 38.1 ⫾ 0.8

7.38 ⫾ 0.05 188 ⫾ 55 38 ⫾ 5 38 ⫾ 0.9

NOTE. Values represent mean ⫾ SD. Sevoflurane 1 MAC and 1.5 MAC, respectively, 2.6% and 3.9% end-tidal sevoflurane concentrations.

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sonic crystals, variations of species, potential use of lidocaine), which could have influenced ventricular conduction and sequential contraction. Sevoflurane caused dose-dependent decrease in right coronary artery blood flow, probably due to a reduction in cardiac output, a decrease in perfusion pressure, and a possible reduction in myocardial oxygen demand. This reduction in myocardial oxygen demand was a probability, because right coronary blood flow was reduced in conjunction with a decrease in global RV stroke work. In contrast to isoflurane,16 CVR remained unchanged, which could represent a balance of 2 opposing triggers: the decrease in systemic perfusion pressure and the potential decrease in myocardial oxygen consumption. Any statement on the direct effect of sevoflurane on right coronary vasomotor tone would have required measurement of coronary sinus oxygen tension and calculation of myocardial oxygen extraction. Although RV contractility decreased with sevoflurane, PVR was not modified. This confirms a previous study showing that sevoflurane did not modify pulmonary vascular tone either during hyperoxia or in hypoxia.19 However, even if PVR represents the opposition to continuous forward flow, it ignores the pulsatile component of RV afterload as assessed by pulmonary arterial impedance spectrum analysis.20

Limitations of the Study This anesthetic protocol was close to those used in clinical settings. Accordingly, all measurements were taken after acute surgical preparation with general anesthesia. Although it must be taken into consideration that anesthesia and acute surgical preparation may alter normal physiologic responses, this is what is expected in patients. Accordingly, close attention was paid to hemostasis, body temperature, fluid replacement, and control of metabolic parameters such as PaO2, PaCO2, and pH. Given that the inflow and outflow tracts may not be shortening or lengthening at the same time, applying a fixed marker based on events such as the ECG R wave and peak negative dP/dt could not necessarily reflect the same mechanical event in each area. A way to address this problem could be perhaps to examine the shortening patterns of each area individually and characterize drug-induced changes in the relative timing of regional events. These findings suggest that in the clinical setting of cardiac anesthesia, concentrations of sevoflurane higher than 1 MAC will depress global RV function. Further animal studies are required to investigate the effect of this anesthetic agent on acute RV dysfunction after acute pressure overload, such as pulmonary artery constriction or embolism.

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11. Manohar M: Regional brain flow and cerebral cortical O2 consumption during sevoflurane anesthesia in healthy isocapnic swine. J Cardiovasc Pharmacol 8:1268-1275, 1986 12. Greyson C, Xu Y, Cohen J, et al: Right ventricular dysfunction persists following brief right ventricular pressure overload. Cardiovasc Res 34:281-288, 1997 13. Chow E, Foppiano L, Farrar DJ: Regional contractile performance during acute ischemia in porcine right ventricle. Am J Physiol 263:H135-H140, 1992 14. Harkin CP, Pagel PS, Kersten JR, et al: Direct negative inotropic and lusitropic effects of sevoflurane. Anesthesiology 81:156-167, 1994 15. Katoh T, Ikeda K: The effects of fentanyl on sevoflurane requirements for loss of consciousness and skin incision. Anesthesiology 88:18-24, 1998 16. Priebe HJ: Differential effects of isoflurane on regional right and left ventricular performances, and on coronary systemic, and pulmonary hemodynamics in the dog. Anesthesiology 66:262-272, 1987 17. Priebe HJ: Adverse effects of halothane in a canine model of acute right ventricular hypertension. Anesthesiology 71:885-892, 1989 18. Priebe HJ: Effects of halothane on global and regional biventricular performances and on coronary hemodynamics before and during right coronary artery stenosis in the dog. Anesthesiology 78:541552, 1993 19. Kerbaul F, Bellezza M, Guidon C, et al: Effects of sevoflurane on hypoxic pulmonary vasoconstriction in anaesthetized piglets. Br J Anaesth 85:440-445, 2000 20. Heerdt PM, Gandhi CD, Dickstein ML: Disparity of isoflurane effects on left and right ventricular afterload and hydraulic power generation in swine. Anesth Analg 87:511-521, 1998