In Reply:—

We appreciate the interest of Drs. Ansley and Xia regarding our study on the preservation of myocardial function by sevoflurane in coronary surgery patients. 1Transient myocardial dysfunction after coronary bypass surgery is a well known phenomenon, 2but its pathophysiologic mechanisms still are not fully elucidated. Although its causes are multifactorial, reperfusion injury is thought to play an important role.

Recently, increasing evidence has indicated that anesthetic agents may have a potential beneficial role in the prevention and/or treatment of reperfusion injury. Volatile anesthetics have been shown to directly precondition or indirectly enhance ischemic preconditioning, resulting in protection of the myocardium, with the adenosine triphosphate– regulated potassium channel playing an important role. Central to the pathogenesis of ischemia–reperfusion injury is the production of free radicals. Several reports have demonstrated that propofol may enhance antioxidant capacity, and this property has been claimed to protect the myocardium. However, data on this subject are essentially experimental, and, to date, few studies have demonstrated a potential beneficial effect of anesthetic agents in myocardial stunning in the clinical situation.

For the volatile anesthetics, the beneficial effects were demonstrated on both functional hemodynamic parameters and biochemical markers of myocardial damage. For propofol, the evidence of a myocardial protective effect is mainly circumstantial. Several studies have, indeed, demonstrated that propofol increases the antioxidant capacity of erythrocytes and tissue. However, the possible implications of this increase in antioxidant capacity for preservation of tissue function remain to be demonstrated.

Ebel et al.  3found no protective effect of propofol (at clinically relevant concentrations) against myocardial reperfusion injury, but Ko et al.  4demonstrated that propofol at higher concentrations (100 μm) attenuated mechanical, biochemical, and histologic changes caused by myocardial ischemia and reperfusion. In a recent publication, Ansley et al.  5observed that high-dose propofol (a 2–2.5-mg/kg bolus followed by a continuous infusion of 200 μg · kg−1· min−1) enhances erythrocyte antioxidant capacity during cardiopulmonary bypass in humans. Erythrocyte antioxidant capacity with low-dose propofol or isoflurane anesthesia, on the contrary, was similar.

Ansley and Xia related this increased antioxidant capacity in the high-dose propofol group to improved myocardial function (higher cardiac index) 12 h postoperatively. However, the cardiac index in the low-dose propofol group was similar, despite the difference observed in the antioxidant capacity. It seems, therefore, that the suggested relation between improved cardiac function with propofol and its antioxidant properties is not supported by the data presented. Instead, it seems more likely that differences in cardiac loading conditions are responsible for the observed differences in cardiac index between the isoflurane and propofol groups.

In our study, 1propofol was administered by means of a target-controlled infusion system, which was set to achieve a target plasma propofol concentration of 2–4 μg/ml. This plasma concentration is far beyond the concentration at which Ansley and Xia have observed “cardioprotective” effects (12 μg/ml). Still, it is the concentration that is clinically applied in patients with compromised cardiac function, which is not the case for concentrations up to 12 μg/ml. From a clinical point of view, the agents that have potential beneficial effects on ischemia–reperfusion injury should also exert their action at clinically relevant concentrations.

Under the conditions of our study, sevoflurane at clinically relevant concentrations protected against the transient myocardial dysfunction related to coronary surgery, whereas propofol did not (lower cardiac index until the end of the operation). The suggestion that the title of our article, “Sevoflurane but Not Propofol Preserves Myocardial Function in Coronary Surgery Patients,” is misleading is therefore not correct. The data and conclusions clearly refer to clinically relevant concentrations and do not comment on possible properties at concentrations that are much higher than those used in clinical practice.

De Hert SG, ten Broecke PW, Mertens E, Van Sommeren EW, De Blier IG, Stockman BA, Rodrigus IE: Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. A nesthesiology 2002; 97: 42–9
Breisblatt WM, Stein KL, Wolfe CJ, Follansbee WP, Capozzi J, Armitage JM, Hardesty RL: Acute myocardial dysfunction and recovery: a common occurrence after coronary bypass surgery. J Am Coll Cardiol 1990; 15: 1261–9
Ebel D, Schlack W, Comfère T, Preckel B, Thämer V: Effect of propofol on reperfusion injury after regional ischaemia in the isolated rat heart. Br J Anaesth 1999; 83: 903–8
Ko SH, Yu CW, Lee SK, Choe H, Chung MJ, Kwak YG, Song HS: Propofol attenuates ischemia-reperfusion injury in the isolated rat heart. Anesth Analg 1997; 85: 719–24
Ansley DM, Sun J, Visser WA, Dolman J, Godin DV, Garnett ME, Qayumi AK: High dose propofol enhances red cell antioxidant capacity during CPB in humans. Can J Anaesth 1999; 46: 641–8