We read with great interest the study by De Hert and colleagues [1], which showed no difference in troponin C levels in patients undergoing cardiopulmonary bypass, who had received either volatile anaesthetic agents (desflurane or sevoflurane) or total intravenous anaesthesia (TIVA). The results by De Hert et al conflict with the results of previous studies, although not all these studies demonstrate a cardioprotective effect of volatile anaesthetic agents versus TIVA.

This is the first study, in which a strict minimal protocol of administration of volatile anaesthetic agents, was observed and which was continued throughout the operative period, until 10 minutes after the beginning of reperfusion. What may be responsible for the inability to reproduce the expected cardioprotective effect? Even though anaesthetic preconditioning has a solid experimental basis, its transfer to the clinical setting of cardiac surgery is difficult for many reasons: the confounding effect of concomitant medication, pre-existing disease, the low incidence of postoperative troponin release in the overall population and the lack of a homogenous cardioprotective protocol; all of these factors may have masked the positive effect of the volatile anaesthetic agents. In addition, as suggested in our study [2], anaesthetic preconditioning, is probably both time- and dose-dependent. However, there is no clear evidence in the literature about which dose of volatile anaesthetic agent is cardioprotective. Cardioprotection may also vary in relation to the patient and complexity of the operation. Furthermore, the dose of sevoflurane and enflurane (0.5 MAC), used in the present study, is lower than used in other studies.

A cardioprotective effect has been experimentally shown for opioids, especially with morphine and  remifentanil. This mechanism of cardioprotection is through their Gi-protein coupled receptors (GPCR) which may induce preconditioning by activation of PKC, GSK3b , PI3K and mitochondrial K_ATP channels [3]. Recently, the ability to induce postconditioning has been shown for morphine and remifentanil [4-5]. Propofol also has been shown to have a cardioprotective effect. This is thought to be mediated through:

 1) activation of several isoforms of PKC [6]

 2) reduction of intracellular calcium, of oxidative stress and of lipid peroxidation [7

 3) anti-arrhythmic effect [8-9]

 4) induction of postconditioning [10]

 5) preservation against endocrine manifestations of stress [11]

Despite the experimental data available, very little is known about the potential cardioprotective properties of intravenous anaesthetic agents. A cardioprotective effect of morphine and fentanyl, after cardiopulmonary bypass, has been shown by Murphy [12] and by Corcoran [7].

The results obtained by De Hert are not completely new. In contrast to the majority of the studies, Jacobsen et al. (cited by De Hert), in a retrospective analysis of 10 535 patients, showed no difference in the incidence of myocardial infarction or postoperative mortality in patients treated with either sevoflurane or propofol [13].

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Which explanation is then the more plausible: is the dose of volatile anaesthetic agents used too low?;  is there some important piece of information about preconditioning by volatile anaesthetic agents that we are yet unaware of?;  has the cardioprotective effect of TIVA been undervalued until now?; is it possible that in some groups of patients, TIVA may be protective, as much as volatile anaesthetic agents?

Until future studies can shed more light on this topic, we think that the article by De Hert, despite its unexpected results, adds an important piece of knowledge to the problem of the clinical application of anaesthetic preconditioning.