To the Editor:—

We read with interest the article recently published by Dr. De Hert et al. , 1“Effects of Propofol, Desflurane, and Sevoflurane on Recovery of Myocardial Function after Coronary Surgery in Elderly High-risk Patients.”1In this study, the authors observed that sevoflurane or desflurane anesthesia in combination with continuous intravenous propofol sedation for 4 h postoperatively better preserved cardiac mechanics than using propofol alone for anesthesia and postoperative sedation in elderly high-risk patients. These approaches were also associated with significantly reduced plasma concentrations of cardiac troponin I, a sensitive marker for myocardial cellular damage. This is very interesting. This anesthetic “cocktail,” especially when further modified, may prove to be a promising approach. Unexpectedly, however, the authors have not appreciated the potential contribution propofol may have made to the manifested additional cardiac protection seen in the sevoflurane and the desflurane groups in their study.

Postischemic reperfusion can result in further damage to the myocardium through an acute inflammatory response mediated by cytokines, neutrophils, macrophages, and reactive oxygen species. These events can trigger cardiomyocyte death through either necrosis or apoptosis. Recent study has shown that apoptosis of coronary endothelial cells, which peaked at 1 h of reperfusion, precedes cardiac myocyte apoptosis in ischemia–reperfusion injury. 2Apoptosis spreads radially to the surrounding cardiac myocytes. After 2 h of reperfusion, apoptotic cardiac myocytes assumed a more homogeneous distribution around the vessels. 2This suggests that reperfusion induces the release of soluble proapoptotic mediators from endothelial cells that promote myocyte apoptosis. 2Our recent study shows that propofol can significantly reduce tumor necrosis factor (TNF) α–induced human endothelial cells apoptosis when applied at a clinically relevant low concentration of 12.5 μm (approximately 2 μg/ml), although most significant effect is manifested at a propofol concentration of 50 μm or greater. *Propofol’s inhibition of TNF-α–induced human endothelial cell apoptosis is attributable, at least in part, to its antioxidant property. This is because the low concentration of hydrogen peroxide significantly enhanced TNF-α–induced human endothelial cell apoptosis, while propofol prevented this synergistic effect between hydrogen peroxide and TNF-α and significantly attenuated hydrogen peroxide and TNF-α–induced human endothelial cell apoptosis (unpublished data, Luo and Xia et al. , Wuhan, Hubei Province, China, October 2003, Propofol Dose-dependently Reduces TNF-α Induced Human Umbilical Vein Endothelial Cell Apoptosis: Effects on bcl-2 and bax Expression And Nitric Oxide Generation).

It is well known that endogenous antioxidant capacity decreases with aging. Interestingly, propofol, when applied at a clinically achievable high dose primarily during ischemia and the early phase of reperfusion followed by a relatively low dose during reperfusion, seems able to provide better cardiac protection against ischemia injury in hearts from middle-aged rats than from young rats. 3Taken together, we suggest that the potential of propofol in reducing cytokines and reactive oxygen species–induced (coronary) endothelial cell and myocyte injury during reperfusion should have contributed, in part, to the attenuated myocardial cellular damage seen in the sevoflurane and the desflurane groups in the study of De Hert et al.  1 

It should be noted that postoperative recovery was relatively eventful in the desflurane group as compared with the sevoflurane group in the study of De Hert et al.  1This is likely because desflurane anesthesia could significantly enhance both local and systemic oxidative stress. 4Although a small amount reactive oxygen species produced by volatile anesthetics (including desflurane) before ischemia may serve to trigger anesthetic preconditioning, 5a significant amount of reactive oxygen species that could be produced by desflurane during ischemia and reperfusion is obviously detrimental. Therefore, it is reasonable for us to speculate that postoperative recovery in the desflurane group could have been otherwise more eventful if propofol were not supplemented as a sedative during the first several hours after reperfusion.

De Hert SG, Cromheecke S, ten Broecke PW, Mertens E, De Blier IG, Stockman BA, Rodrigus IE, Van der Linden PJ: Effects of propofol, desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients. A nesthesiology 2003; 99: 314–23
Scarabelli T, Stephanou A, Rayment N, Pasini E, Comini L, Curello S, Ferrari R, Knight R, Latchman D: Apoptosis of endothelial cells precedes myocyte cell apoptosis in ischemia/reperfusion injury. Circulation 2001; 104: 253–6
Xia Z, Godin DV, Ansley DM: Propofol enhances ischemic tolerance of middle-aged rat hearts: Effects on 15-F(2t)-isoprostane formation and tissue antioxidant capacity. Cardiovasc Res 2003; 59: 113–21
Allaouchiche B, Debon R, Goudable J, Chassard D, Duflo F: Oxidative stress status during exposure to propofol, sevoflurane and desflurane. Anesth Analg 2001; 93: 981–5
Kevin LG, Novalija E, Riess ML, Camara AK, Rhodes SS, Stowe DF: Sevoflurane exposure generates superoxide but leads to decreased superoxide during ischemia and reperfusion in isolated hearts. Anesth Analg 2003; 96: 949–55