We read with interest the letter of Drs. Xia and Luo regarding our recent article on the cardioprotective effects of volatile anesthetic agents in elderly high-risk coronary artery patients. 1The authors propose an interesting hypothesis, which is that the use of propofol as sedation in the postoperative period on the intensive care unit may have added to the cardioprotective effects observed with sevoflurane and desflurane. Postischemic reperfusion is associated with an acute inflammatory response, involving a number of mediators, which ultimately may trigger cardiomyocyte death within the first hours after reperfusion. Drs. Xia and Luo propose that the potential of propofol in reducing cytokines and reactive oxygen species induced myocardial injury during reperfusion is responsible for the additional cardioprotective effect. It should be noted, however, that in our study, propofol administration was only started after arrival in the intensive care unit. This implies that in the sevoflurane and desflurane groups, during the first period of reperfusion (from the opening of the proximal anastomoses until the end of the operation), anesthesia was still obtained with the volatile anesthetic. If the beneficial effects of propofol during the first 2 h of reperfusion are assumed to be of major importance in the cardioprotective effects observed in the sevoflurane and desflurane groups, one would expect this effect also to be present in the propofol group, which was not the case in our study protocol.
Different research groups have demonstrated that propofol has antioxidant activity and may even inhibit tumor necrosis factor α–induced human (umbilical vein) endothelial cell apoptosis, 2but the clinical relevance of these properties for myocardial protection remains to be established. Until now, all data published on the cardioprotective effects of propofol were obtained at higher concentrations than those used in clinical practice. For example, the cardioprotective effects observed by Ko et al. 3were obtained at propofol concentrations of 100 μm. Similarly, in the study of Xia et al. 4in isolated rat hearts, the enhanced ischemic tolerance of middle-aged rats was observed with a propofol perfusion at 12 μg/ml during the first 15 min of reperfusion, which was subsequently reduced to 5 μg/ml. Ebel et al. , 5on the contrary, found no effect of propofol on reperfusion injury when it was administered at concentrations of 1 μg/ml.
The pathophysiology of myocardial reperfusion injury is extremely complex, with several pathways involved, ultimately resulting in myocardial dysfunction. As such, it is conceivable that different therapeutic interventions may act at different levels and have an additive cardioprotective effect. In addition to their pharmacologic preconditioning effect, volatile anesthetics also seem to have cardioprotective effects when administered only during the reperfusion period. 6,7Although the underlying mechanisms for these effects remain to be elucidated, there is now evidence that a reduction in postischemic adhesion of neutrophils may be involved. 8,9At the moment, it remains an open question how all these experimental observations may translate to clinical pathophysiology and even more to clinical treatment of myocardial ischemia–reperfusion injury.
Therefore, although it is conceptually attractive, the hypothesis proposed by Drs. Xia and Luo lacks experimental and clinical evidence. To date, there are indeed no published data available supporting the hypothesis that the administration of propofol as a sedative in the intensive care unit contributes to the cardioprotective effects of peri-operatively administered sevoflurane and desflurane. Elucidation of this question would require a study protocol comparing sedation in the intensive care unit with propofol to another sedative agent without antioxidant properties.