REVIEW ARTICLE
Rationale for Propofol Use in Cardiac Surgery
Lukasz J. Krzych, MD, PhD,* Dariusz Szurlej, MD, PhD,† and Andrzej Bochenek, MD, PhD*
P
ROPOFOL IS A COMMONLY USED intravenous anes-thetic agent. Chemically, propofol is a lipophilic, sterically hindered alkylated phenol that is a very weak acid.1,2 Pharma-cokinetic and pharmacodynamic properties make propofol a useful drug in everyday anesthesia with rapid and clear emer-gence, precise control of the level of sedation, and lack of cumulative effects even after prolonged administration.1-4 Al-though the terminal half-life of propofol is long, recovery is rapid because of the slow mobilization from the highly li-pophilic tissue compartment.1-4The indications for propofol use include the induction and maintenance of anesthesia for most surgical procedures, and it can be extended into the postoperative setting or intensive care unit for sedation. Rapid redistribution and elimination make propofol valuable for short procedures and ambulatory sur-gery.1-4Moreover, the agent possesses antiemetic, antipruritic, and anticonvulsant properties.1-4
Propofol is also widely used in subjects with cardiac dis-ease.3,4An anesthetic drug for cardiac surgery should provide intraoperative amnesia, analgesia, and hemodynamic stability with minimal direct myocardial depression and rapid recovery; ideally, with weak inotropic support.4Pharmacokinetic prop-erties of propofol favor its use in clinical practice in cardiac surgery patients.3-5The induction of anesthesia with an opioid-benzodiazepine/etomidate combination followed by a mainte-nance infusion of propofol supplemented with an inhalation agent or opioid analgesic or both as needed are considered acceptable for patients undergoing routine cardiac surgery.3 Apart from general anesthesia, major indications for propofol use are sedation during painful procedures (eg, cardioversion), sternal wound debridement, central venous catheter insertion, and transesophageal echocardiography (Table 1).3,4
Propofol is safely administered to patients with cirrhosis and renal failure, with no impairment in its clearance.1However, in comparison with other agents, the induction dose of propofol has a relatively higher prevalence of respiratory depression, short-lived apnea, and arterial blood pressure (estimated even at
30%-40%) decrease.1-3 Although propofol has a negative im-pact on systemic blood pressure in cardiac surgery patients,6-9 clinical studies have shown that the agent, in combination with an opioid and adequate intravenous fluid supplementation, is a safe option for such procedures.5The other unpleasant effect of propofol is pain on injection, which can be dealt with either by a prior injection of a small amount of local anesthetic (eg, lidocaine) or by mixing it in the same syringe.1-4The previously mentioned effects are age, but not sex, dependent; the dose should be reduced in elderly patients and increased in chil-dren.1-5,10Obesity has no influence on the clinical duration of the effects of propofol (Table 2).2
A major concern is the propofol infusion syndrome (PRIS), which is rare but may be fatal if not identified early.11-14The review by Wysowski and Pollock11reported 36 cases of PRIS, including 15 pediatric and 21 adult patients, described in the literature from 1989 to 2005; and Kam and Cardone12found 61 patients with PRIS, 32 pediatric and 29 adult cases, described up to 2006. PRIS is characterized by metabolic acidosis, li-pemic plasma, hepatomegaly, rhabdomyolysis, and electrocar-diographic changes (eg, right bundle-branch block, acute bra-dycardia leading to asystole, and other cardiac arrhythmias), with no structural cardiac lesions or abnormalities in contrac-tility on echocardiography.1-5,12,13 Vasile et al14 suggested 2 groups of mechanisms directly related to the occurrence of PRIS, namely priming and triggering factors. The first group stems from severe critical illness (eg, multiple-organ failure) and central nervous system activation, resulting in the produc-tion of catecholamines and glucocorticosteroids.12,13 PRIS is believed to be triggered by a dose of propofol exceeding 4 mg/kg/h, time of infusion longer than 48 hours, and implemen-tation of concomitant infusions of endogenous catecholamines and steroids.12,13PRIS should be considered a potential serious adverse effect in high-risk cardiac surgery patients who often require catecholamine support and prolonged mechanical ven-tilation with long-lasting sedation.
Propofol has been suggested as a useful adjunct to cardiople-gic solutions because of its potential protective effect on the heart mediated by a decrease in ischemia-reperfusion injury in clinically relevant concentrations.15 Nevertheless, clinicians should be aware that cardiopulmonary bypass (CPB) alters its concentration by hemodilution, reduces clearance caused by changes in renal and hepatic blood flow, changes in unbound compared with bound drug, absorption by CPB apparatus, and hypothermia.6,7,15
Therefore, the authors have attempted to describe a rationale for propofol use in cardiac surgery. The aim of the article is to summarize data from the literature regarding the impact of the From the *1st Department of Cardiac Surgery and †Department of
Cardiac Anesthesia and Postoperative Intensive Care, Medical Uni-versity of Silesia, Katowice, Poland.
Address reprint requests to Lukasz J. Krzych, MD, PhD, 1st Depart-ment of Cardiac Surgery, Medical University of Silesia, 47 Ziolowa Street, 40-635 Katowice, Poland. E-mail:l.krzych@wp.pl
© 2009 Elsevier Inc. All rights reserved. 1053-0770/09/2306-0022$36.00/0 doi:10.1053/j.jvca.2009.05.001
Key words: propofol, cardiac surgery, coronary artery bypass graft surgery
agent on the heart, vessels, and blood, including the inflammatory system.
PROPOFOL AND THE HEART
Myocardial Contractility
The influence of propofol on the heart has been investigated in several studies. Its negative effect on myocardial contractil-ity and hemodynamic status has been revealed both in animal and human (in vitro) models.16-26The negative inotropic impact was found in nonfailing (nonischemic) and failing (acute isch-emic) myocardium in a dose-dependent manner, but only at concentrations higher than those typically used in clinical prac-tice.24,25A decrease in cardiac function was measured by sev-eral hemodynamic parameters, including left ventricular end-systolic pressure, end-diastolic length and end-systolic shortening,24 myocardial contractility, and a decrease in mean arterial pres-sure.25 Alterations in left ventricular preload, afterload, and regional chamber stiffness with impaired early-diastolic left ventricular filling26and wall-thickening fraction of the myocar-dium also were found (Table 3).26
Direct myocardial and coronary vascular responses to propo-fol were studied by Stowe et al.27 They found that propofol moderately depressed cardiac function and markedly attenuated autoregulation by causing coronary vasodilatation. In this ex-perimental in vitro study,27at concentrations below 10mol/L, no significant changes were observed; beyond 50 mol/L, propofol caused progressive but differential decreases in heart rate, atrioventricular conduction time (leading to atrioventric-ular dissociation), left ventricatrioventric-ular pressure, ⫹LVdP/dTmax (change in the maximal positive derivative of left ventricular pressure), percent oxygen extraction, and myocardial oxygen consumption of isolated hearts.
The adverse effects of propofol in elderly and high-risk patients or those with impaired left ventricular ejection fraction are more pronounced in quantity compared with persons with a preserved cardiac function and lower perioperative risk.22,28 Nevertheless, no impact on the requirement for inotropic sup-port at the termination of CPB was found during propofol anesthesia,29,30and the simultaneous administration of calcium
chlorate during the induction of anesthesia may diminish the negative influence of propofol on cardiac function.31
Molecular Mechanisms
Previous observations depicted multiple possible biologic mechanisms linking propofol with cardiac depression including a decrease in sympathetic activity, vasodilatory effect, and modifications of ␣- and -adrenoceptor binding and L-type calcium cardiac inhibition.32-36In an experimental study on rat papillary muscle, Zhou et al32found that propofol acted as a calcium channel blocker and had a direct impact on calcium channel proteins to diminish voltage-dependent L-type calcium current. Another explanation for propofol’s impact on the heart included the antagonism of -adrenoreceptor binding and al-teration in receptor responsiveness to catecholamines in a dose-dependent (ranged from 25 to 200 mol/L) and competitive manner.33Lejay et al34 showed that at a concentration of 45 mol/L, the agent abolished the positive effect of ␣- but not -adrenoreceptor stimulation. Supportive data were published by Sprung et al35who found that the impact of propofol was reversible with-adrenergic stimulation and mediated by re-duced calcium uptake into the sarcoplasmic reticulum. As far as adrenergic-receptor competition is concerned, the addition of propofol to dopamine may prevent dopamine-induced apopto-sis while maintaining positive inotropy by improving dopam-ine-mediated diastolic function after ischemia.36
Besides the above results from in vitro studies, the clinical evidence for propofol use in cardiac surgery patients is limited. The small number of in vivo studies, especially in humans, is a serious limitation. However, propofol has shown no significant negative inotropic effect in the clinically used concentra-tions.34,37
Table 1. Indications for Propofol Use in Cardiac Patients
Fast-track anesthesia; induction and maintenance
Sedation in cardiac ICU patients Sedation during transesophageal
echocardiography
Arterial/venous catheterization Sedation for cardioversion Sternal (other) wound
debridement Abbreviation: ICU, intensive care unit.
Table 2. Side Effects of Propofol
Vasodilatation with arterial blood pressure decrease
PRIS
Respiratory depression with apnea Histamine release
Pain on injection Venous thrombosis/
phlebitis Excitatory phenomena Hypertriglyceridemia
Table 3. Propofol and the Cardiovascular System
Myocardial contractility
Negative inotropic effect
2 Left ventricular loading (2 LVESP, 2 LVEDP, 2 SF, 2WT)
2 HR
Electrophysiology No impact on QTc interval
2 HR and 2 HRV (2 SA conduction) Atrial fibrillation inhibition (2 AV conduction,
His-Purkinje system inhibition) Molecular
mechanisms
2 Sympathetic activity
␣- and -adrenoceptor response modification L-type calcium cardiac inhibition
Receptors’ sensitivity modulation Cardioprotective
effects
2 Oxidative stress (2 plasma inflammatory cytokine levels, 2 oxygen-free radicals, 2 lipid peroxidation, 2 chemotactic activity, 2 leukocyte infiltration) 2 Ischemia-reperfusion injury 2 Cardiac troponin I concentration
Vessels Arterial dilatation (pulmonary and peripheral) Venous dilatation (pulmonary and peripheral) Abbreviations: 2, decrease; LVESP, left ventricular end-systolic pressure; LVEDP, left ventricular end-diastolic pressure; SF, shorten-ing fraction; WT, wall thickenshorten-ing; HR, heart rate; HRV, heart rate variability; AV, atrioventricular; SA, sinus atrial; QTc, control QT in-terval.
Electrophysiology
Propofol has an impact on electrophysiologic findings in patients. Numerous studies revealed that during both the induc-tion and maintenance of total intravenous anesthesia, propofol significantly shortened the QT interval.38-43 Additional data suggested that propofol infusion may prolong the corrected QT (QTc) interval but only in subjects with a normal QTc interval, whereas it can be shortened in patients with a prolonged QTc interval at baseline.18However, the effects of the agent on the QT interval are generally too small to be clinically significant and to be identified in an intraoperative electrocardiogram.44 This is consistent with a study that showed no influence of propofol on QTc in healthy children (Table 3).45
Propofol infusion is also believed to decrease both heart rate and heart rate variability, predominantly by a reduction in cardiac parasympathetic tone.25,27,46-52Wu et al52found in an experimental study that the atrioventricular conduction interval may be lengthened by propofol in a dose-dependent and age-related manner, even at low concentrations (3 mol/L). At higher concentrations, propofol significantly prolonged the atrioventricular conduction interval (10 mol/L and more), slowed conduction through the atrial tissue (SA interval) and the His-Purkinje system (HV interval), decreased the sponta-neous heart rate, and prolonged the AV Wenckebach cycle length (all at concentrations of 30mol/L and higher).52These findings are consistent with in vivo studies of Cervigón et al53 who reported that anesthesia with propofol may slow atrial fibrillation and Owczuk et al54 who revealed a decrease in P-wave dispersion after propofol anesthesia.
Taking the previously described data into account, clinicians should be cautious of propofol’s electrophysiologic influence on patients with delayed or blocked conduction in the heart. Propofol can be a reasonable choice for cardiac surgery patients with atrial fibrillation, but it should be used with caution during cardioversion because of hypotension and an increase in energy required for successful effect of the procedure.3
PROPOFOL AND THE INFLAMMATORY SYSTEM
Cardiopulmonary bypass is one of the acknowledged causes of a complex systemic inflammatory response during cardiac surgery, and it may contribute to postoperative complications and even multiple-organ dysfunction.55-57 Inflammation, as a result of cellular oxidative stress and myocardial injury, is mediated by several agents including interleukins 6, 8, and 10; high-sensitivity C-reactive protein; tumor necrosis factor ␣; and the release of other inflammatory agents.55-57Thus, results suggesting that propofol has antioxidative properties58-64 and may be of great importance because of its ability to reduce ischemia-reperfusion injury in coronary artery bypass graft (CABG) surgery patients.
In an experimental study, propofol anesthesia was directly related to a significant decrease in oxidative activity measured by malondialdehyde levels in plasma and pulmonary lavage.58 In a study by Corcoran et al,59it was found that in patients undergoing CABG surgery, clinically relevant concentrations of propofol attenuated free radical-mediated and inflammatory components of myocardial reperfusion injury including modu-lation of serum concentration of malondialdehyde; systemic
concentrations of interleukins 4, 6, 8, and 10; and systemic leukocyte functions. In several investigations,60-63an antioxi-dative effect of propofol was shown via mechanisms involving decreases in neutrophil infiltration, plasma inflammatory cyto-kine levels, oxygen free-radicals production, and lipid peroxi-dation. In vitro studies also showed that propofol depresses the immunologic reaction to bacterial challenge as well as chemo-tactic activity.5
There are some supplementary data indicating that propofol may also protect erythrocytes against both oxidative and phys-ical stress, suggesting its efficacy and usefulness as an antiox-idant.64 In the latter study,64propofol increased erythrocytes’ membrane fluidity, thereby increasing their resistance to phys-ical and hemodynamic stress. Moreover, the protective effect of propofol on oxidation in red blood cell membranes was en-hanced by another antioxidant, ascorbic acid.64
Hypertriglyceridemia is common in propofol-treated pa-tients,1,3,4,65,66 and may be associated with the PRIS occur-rence.11-13In a study by Oztekin et al,67propofol was found to increase triglycerides and very low-density lipoprotein concen-trations, but not glucose concentrations a few hours after CABG surgery. Repeated measures of the lipid profile could become a valuable marker for monitoring this side effect.
CARDIOPROTECTIVE EFFECTS OF PROPOFOL
Propofol is believed to possess a cardioprotective effect that derives in part from its antioxidant properties and free radical scavenging properties.68 These properties were described in several studies.69-74Zou et al69and Xia et al70reported the role of propofol in the reduction of cardiac troponin I concentration in clinical investigations. Myocardial protection by the agent may involve the activation of protein kinase C.74-77It is sug-gested that propofol increases the sensitivity of myofibrillar actomyosin ATPase to calcium by increasing intracellular pH via the protein kinase C– dependent activation of Na⫹-H⫹ ex-change.75,76In diabetic cardiomyocytes, propofol was found to decrease myofilament Ca2⫹ sensitivity via a protein kinase C–nitric oxide synthase– dependent pathway.77Supplementary data revealed that infusion of the agent significantly reduced the number of in vitro apoptotic cells71or prevented dopamine-induced apoptosis of the heart cells after ischemia in an animal model.37
On the basis of registry data from 10,535 surgical procedures comparing the influence of sevoflurane and propofol anesthesia on clinical outcomes, Jakobsen et al concluded that propofol anesthesia may be superior in patients with severe ischemia, cardiovascular instability, or in acute/urgent surgery because of its cardioprotective properties.73 The 30-day mortality was comparable among all patients from the sevoflurane and propo-fol groups (2.84% v 3.3%, p⫽ 0.18) as well as in a subgroup of subjects with unstable angina (5.48% v 4.8%, p⫽ 0.58) or recent myocardial infarction (4.91% v 4.72%, p ⫽ 0.93). Sevoflurane anesthesia resulted in a decrease in mortality in patients with stable angina and no history of myocardial infarc-tion compared with the propofol group (2.28% v 3.14%, p⫽ 0.01).78In the cited study,78propofol anesthesia had its most important beneficial influence on 30-day mortality in urgent CABG procedures (16.23 v 8.19%, p⫽ 0.03).
outcome advantage of propofol in a multicenter prospective randomized study in 150 CABG surgery patients by Tritapepe et al.79 The postoperative concentration of troponin I was 2 times higher in anesthetized subjects from the propofol group (median⫽ 5.5 ng/dL) compared with patients from the desflu-rane group (median⫽ 2.5 ng/dL).79Moreover, patients receiv-ing a volatile anesthetic had a reduced need for postoperative inotropic support (32% v 41.3% in the propofol group, p ⫽ 0.04). Consistent findings relating to differences between propofol and sevoflurane anesthesia were shown by De Hert et al17 in a group of 20 coronary artery surgery patients. They reported that for the sevoflurane group, troponin I concentra-tions remained below the cutoff value of 2 ng/mL throughout the 36-hour observation period, but, in the propofol group, an elevation in troponin I concentrations was found 12 hours after CPB, with a peak at 24 hours followed by a decrease in the next 12 hours.17 Kohro et al74 found that the administration of propofol may also hamper previously reported cardioprotective effects of inhalation anesthetics (eg, isoflurane and sevoflurane) as well.
PROPOFOL AND THE BRAIN
Neurologic deterioration after CPB including complications of stroke, transient ischemic attacks or cognitive dysfunction is frequent.80The results of longitudinal assessment of neurocog-nitive function after CABG surgery revealed that the incidence of cognitive decline occurred in more than half the patients (53%) at discharge and remained after 5 years (46%).80 More-over, cognitive function at discharge was a major predictor of cognitive decline at 5 years.80The etiology of neuropsycho-logic deterioration is complex and includes microemboliza-tion, altered cerebral perfusion, temperature perturbations, cerebral edema, blood-brain barrier dysfunction, and a gen-eralized or localized inflammatory response.81
Proper perioperative management is required to reduce neu-rologic decline. The current literature describes several poten-tial neuroprotective interventions including perioperative propofol administration.81It has been suggested that the neu-roprotective effect of propofol is attributed to its global and regional (at brain level) antioxidative properties that were men-tioned earlier;68however, its role is believed to be beneficial only in limiting the size of cerebral damage rather than the incidence of infarction.3,81 The protective role of the de-creased cerebral mean arterial pressure caused by vasodila-tation has been neglected.81Propofol’s protective effect may be mediated by microembolic delivery reduction by way of decreasing cerebral blood flow,81 but this has not yet been confirmed in clinical trials (Table 4).
The decrease in cerebral metabolic rate and oxygen con-sumption during propofol infusion on CPB may potentially be of some importance. It was revealed that in patients undergoing CABG surgery, induction with propofol resulted in a 51% decrease in cerebral blood flow, a 36% reduction of cerebral metabolic rate and oxygen consumption, and a 25% decrease in cerebral perfusion pressure.82-84 Newman et al85 described a significant reduction in cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate in response to propofol anesthesia during nonpulsatile normothermic and hypothermic phases of CPB. Burst-suppression doses of propofol during
moderate hypothermic CPB were also found to decrease cere-bral blood flow by 35% and cerecere-bral oxygen consumption by 10%.86
Roach et al,87however, reported no association between a reduction in cerebral metabolic suppression or a reduction in cerebral blood flow and neurologic or neuropsychologic dys-function after propofol anesthesia during CPB. By using a battery of neurologic and neuropsychologic tests in 225 pa-tients, they showed that, compared with a sufentanil group, patients in the propofol-sufentanil group tended to have an even higher incidence of adverse neurologic outcomes on postoper-ative days 1 and 2 (40% v 25%, p⫽ 0.06) and at 5 to 7 days (18% v 8%, p⫽ 0.07). These differences resolved after 50 to 70 days (6.2% v 6.2%, p⫽ 0.8).87The incidence of neuropsy-chologic deficits was comparable between the propofol and sufentanil groups (91% v 92%, p⫽ 0.73 at days 5-7, and 52%
v 47% at days 50-70, p⫽ 0.58, respectively), and neither the
severity nor the prevalence or neuropsychologic outcomes dif-fered among patients.87
In view of the previously described information, the clinical relevance of propofol use to prevent cognitive deterioration in cardiac surgery needs to be confirmed in larger prospective studies. The lack of neuroprotection in some studies may be caused by the fact that either propofol has no neuroprotective effects or that appropriate perioperative treatment diminishes any protective impact of the agent significantly (eg, proper oxygenation, glucose control, arterial filters and membrane oxygenators, and concomitant volatile anesthesia).3,81,85,87 Moreover, the methodology of the cited studies varies signifi-cantly and presents a serious limitation to reaching a conclu-sion.
VASCULAR EFFECTS OF PROPOFOL
From a cardiac surgeon’s point of view, the influence of propofol on the biologic tissues used for vascular grafts (CABG) and vasoregulation is crucial. Early postoperative graft failure attributed to spontaneous contraction or spasm requires improvements in preventative strategies and effective treatment. Thus, the potential vasodilating effect of propo-fol88-97may be crucial during the perioperative period. Unfor-tunately, there is still a discrepancy between the number of animal investigations and clinical studies concerning the influ-ence of propofol on systemic vasoregulation.88-97
Animal Studies
The well-known hypotensive effect of propofol may be mediated via multiple mechanisms including its action on pe-ripheral vasculature (arterial and venous vasodilatation) as well as a decrease in myocardial contractility, resetting of baroreflex
Table 4. Propofol and the Brain
EEG burst suppression 2 Oxidative stress 2 Cerebral metabolic rate
and oxygen consumption
2 Cerebral blood flow and cerebral blood flow velocity
2 Cerebral perfusion pressure
Microembolic delivery reduction
activity, and inhibition of the sympathetic nervous system outflow.5,19,49,88-90 The primary cause of reduction in blood pressure differs between individual studies.88-91
Data from the literature raise questions about the molecular background of vasodilatation caused by propofol, and information published about this issue is inconsistent. A number of articles confirm that vasodilatation is endothelium-dependent and uses the activation of numerous endothelial agents.88,90,95,98However, some contradictory data revealed that the effect is mediated in an endo-thelium-independent manner.92,93,99It was also found that propofol may cause significant vasodilatation in both endothelium-intact and endothelium-denuded tissue.89,100,101Thus, further investiga-tions focused on potential mechanisms of the anesthetic are needed.
Effects of the agent on arterial and venous tissue showed the changes to be dose dependent. In a study by Stowe et al,27 propofol, administered at the highest concentration (100mol/L), increased coronary flow by 57%⫾ 10%, decreased myocardial oxygen consumption by 37%⫾ 5%, and increased oxygen deliv-ery/myocardial oxygen consumption ratio by 150%⫾ 15%. Be-tween concentrations of 100mol/L and 1 mmol/L, coronary flow was maximally increased and myocardial oxygen consumption was maximally decreased by the agent. In endothelium-intact arterial rings precontracted with PGF2a, propofol did not change vascular smooth muscle tone in low concentrations (1mol/L-10 mol/L), but at high concentrations (100 mol/L-100 mmol/L) it produced a significant relaxation compared to endothelium-de-nuded rings.90
There is some evidence suggesting a quantitative role of vascular diameter during the process of relaxation.91Coughlan et al investigated the influence of propofol in canine coronary arteries and showed that small arteries showed greater vasodi-latation (at similar concentrations) than larger arteries. Vaso-dilating properties of propofol were more pronounced in distal than in proximal vessels.91
Human Studies
The impact of propofol on the vessels seems comparable in animals and humans, but the issue of the underlying mechanism is still controversial. In a study by Klockgether-Radke et al,92 propofol administered at high concentrations (100 g/mL) caused an endothelium-independent relaxation on porcine and human coronary artery segments to a similar extent (⫺32% up to⫺49% and ⫺11% to ⫺67%, respectively). Wallestedt et al94
investigated the relaxant effects of propofol on smooth muscle tonus in human omental arteries and veins, and found that propofol induced relaxation of both vessels in an endothelium-independent manner. Contradictory data showed that propofol-related relaxation may be endothelium-dependent in omental and radial arteries and omental veins,95,97and Moreno et al96 found that the vasodilatation after propofol administration was similar in intact and denuded endothelium mesenteric rings. Pulmonary Vasoregulation
Park et al89 showed that propofol also promoted marked vasodilatation in pulmonary arteries. In the endothelium-intact aortic and pulmonary artery rings, the initial vasodilatation at the propofol concentration between 30 and 100mol/L showed gradual and partial recovery over 15 minutes, and, at a con-centration of 300mol/L, it caused sustained relaxation. More-over, endothelium-denuded rings and L-NAME pretreated endothelium-intact rings showed constant and sustained vaso-dilatation with all propofol concentrations.89The propofol ve-hicle had no dilating effect on vascular rings and indomethacin pretreatment decreased relaxation, the latter suggesting a me-diating role of endothelium in the process.89 Similar findings relating to the underlying mechanism were reported on a ca-nine102and rat model.103Moreover, the vasorelaxing response to propofol was seen in extrapulmonary but not in intrapulmo-nary arteries.103 Contradictory information was revealed by Horibe et al,104who found that propofol caused dose-dependent and endothelium-independent pulmonary vasorelaxation.
CONCLUSIONS
In summary, for cardiac anesthesia, propofol is useful for the induction and maintenance of anesthesia, and sedation as well, mainly because of its favorable pharmacokinetic properties. How-ever, the benefits of its use are still theoretic, and outcome advan-tages in cardiac surgical patients are unconvincing. Clinicians should be aware of serious adverse effects of propofol including hemodynamic instability, respiratory depression, and PRIS. Al-though propofol seems to be a promising vasodilator for the treatment of perioperative spasm of coronary artery grafts, there is a paucity of epidemiologic data regarding cardiac and neuropro-tective effects of the agent. Further investigations are required to explore the molecular mechanisms of propofol more precisely and to extend indications for its use in cardiac anesthetic practice.
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