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Correspondence |
Renmin Hospital, Wuhan University, China, E-mail: zhengyuan_xia{at}yahoo.com
To the Editor:
We applaud Rodriguez-Lopez et al.1 for conducting a study in a clinically relevant large animal model detailing that propofol, when applied in a clinically relevant dose, reduces the systemic inflammatory response, renal superoxide anion production, and subsequent lipid peroxidation during aortic surgery compared to the volatile anesthetic sevoflurane. In their study, the inflammatory cytokine tumour necrosis factor-
(TNF-) increased significantly and progressively at 15 min after aortic declamping, reaching peak concentrations after 72 hr in the sevoflurane group. In contrast, post-ischemic serum concentrations of TNF- were significantly lower in the propofol group. Propofol attenuation of serum levels of TNF- may prove beneficial in pathological conditions, for example in patients with diabetes2 and during cardiac surgery involving cardiopulmonary bypass,3 when levels of TNF- are increased.
Tumour necrosis factor- can stimulate up-regulation of inducible nitric oxide synthase (iNOS) activity and nitric oxide production in human endothelial cells, which can be accompanied by a burst production of intracellular reactive oxygen species, such as superoxide anion,4 in excess of the endogenous antioxidant defense. Both nitric oxide and superoxide anion are highly reactive and unstable radicals that can react rapidly to form peroxynitrite, a cytotoxic compound. This reaction is approximately three times faster than the dismutation of superoxide anion by the superoxide dismutase. Increased peroxynitrite formation may not only cause further enhanced oxidative stress as commented on by Rodriguez-Lopez et al.,1 it may also create a condition of cellular stress called "nitrosative stress" which can be estimated by measuring the production of nitrotyrosine. Nitrosative stress has been shown to cause severe hypotension, profound vasodilatation, cardiac depression and multiple organ failure in various models of septic shock. On day seven, renal iNOS protein expression was significantly higher in the sevoflurane group relative to the propofol group, accompanied by elevated superoxide anion production, in the study of Rodriguez-Lopez et al. Therefore, nitrosative stress could have been apparent in the sevoflurane group, at least in the kidney, and possibly in other organs as well. However, their study was not designed to assess nitrosative stress, nor were related hemodynamic data presented.
Propofol has been reported to reduce endotoxin-induced increase of iNOS expression, nitrotyrosine formation and lung injury,5 and attenuate postoperative myocardial injury in patients compared to isoflurane.6 However, additional factors such as the duration of postoperative mechanical ventilation and postoperative management must be considered to fully ascertain potential outcome benefits related to propofol treatment for the indication studied by Rodriguez-Lopez et al.1
Footnotes
Accepted for publication August 29, 2006.
References
1 Rodriguez-Lopez JM, Sanchez-Conde P, Lozano FS, et al. Laboratory investigation: effects of propofol on the systemic inflammatory response during aortic surgery. Can J Anesth 2006; 53: 701–10.
2 Makino N, Maeda T, Sugan M, Satoh S, Watanabe R, Abe N. High serum TNF-alpha level in type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells. J Diabetes Complications 2005; 19: 347–55.[Medline]
3 Tomasdottir H, Hjartarson H, Ricksten A, Wasslavik C, Bengtsson A, Ricksten SE. Tumor necrosis factor gene polymorphism is associated with enhanced systemic inflammatory response and increased cardiopulmonary morbidity after cardiac surgery. Anesth Analg 2003; 97: 944–9.
4 Deshpande SS, Angkeow P, Huang J, Ozaki M, Irani K. Rac1 inhibits TNF-alpha-induced endothelial cell apoptosis: dual regulation by reactive oxygen species. FASEB J 2000; 14: 1705–14.
5 Gao J, Zeng BX, Zhou LJ, Yuan SY. Protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats. Br J Anaesth 2004; 92: 277–9.
6 Xia Z, Huang Z, Ansley DM. Large-dose propofol during cardiopulmonary bypass decreases biochemical markers of myocardial injury in coronary surgery patients: a comparison with isoflurane. Anesth Analg 2006; 103: 527–32.
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