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BRITISH JOURNAL OF ANAESTHESIA

The old Latin saying ‘nomen est omen’ suggests that a name is indicative of, or notorious for, its true but hidden nature. Likewise, current clinical evidence on organ protection elicited by ether-derived inhalation agents (‘anaesthetic preconditioning’) appears volatile or, to say the least, not fully convincing. In this issue of the British Journal of Anaesthesia, Piriou and colleagues report on sevoflurane preconditioning in patients undergoing on-pump coronary artery bypass graft (CABG) surgery. Despite some postoperative functional improvement, the primary outcome measure troponin I and some molecular markers of an effective preconditioning process in the heart remained unaffected. These rather disappointing results conflict, at least in part, with previous more promising clinical reports – 6 and call for clarification. Motivated by the work of Verdouw and colleagues and Reimer and colleagues, Murry and colleagues described for the first time in 1986 the phenomenon termed ‘ischaemic preconditioning’ in canine myocardium. Since then, this potent endogenous protective mechanism has been confirmed in almost all species, including man. 11 A few years later, in 1993, late preconditioning, which reflects a second delayed window of protection occurring 12–96 h after initiation of preconditioning, was described. 13 This second window of protection is the result of transcriptional reprogramming, depending on de novo protein synthesis and is of particular clinical relevance, as it is nearly 30 times longer than the first window, which lasts for only 2–3 h. Today, we know that cardiac preconditioning can be elicited more safely by pharmacological means than by brief ischaemic hits. This is of particular relevance for the already jeopardized diseased heart. Two anaesthesia research groups independently reported the preconditioningmimicking effects of isoflurane in 1997, and isofluraneinduced delayed protection was first reported in 2003 in a rabbit model. Recently, molecular evidence of delayed preconditioning after sevoflurane inhalation even at subanaesthetic concentrations (,0.5 MAC) was also reported in humans. Extensive experimental work aimed at elucidating the complex signalling cascade involved in anaesthetic-induced preconditioning has so far deciphered many, but not all, of the underlying mysteries of tissue protection by ether-derived inhalation agents. 11 18 Unlike most other preconditioning-inducing agents, which must be administered directly into the coronary arteries to be effective without serious side-effects, ether-derived agents can be safely inhaled and thus act systemically providing total body protection. In sharp contrast to the striking overwhelming evidence of cardioprotection by ether-derived inhalation agents in the experimental setting, are the results from predominantly smaller clinical studies. Meta-analyses evaluating ether-derived inhalation agent protection in patients undergoing CABG surgery recently concluded that there is only some protection with respect to cardiac function and troponin release but no evidence of reduced risk of myocardial infarction or cardiovascular mortality. 20 Although the proof of concept for anaesthetic preconditioning was demonstrated in on-pump CABG patients in a placebocontrolled randomized trial, many questions with respect to the optimal protective protocol still need to be answered. Julier and colleagues, as opposed to Piriou and colleagues, used a rather higher sevoflurane concentration (4 vol.% corresponding to 2 MAC) given for 10 min with a vaporizer attached to the cardiopulmonary bypass circuit. As with Piriou’s findings, this study showed improved cardiac function, as determined by reduced perioperative plasma NT-proBNP levels, and for the first time translocation of protein kinase C (a key molecular mechanism in preconditioning) in human myocardium in response to sevoflurane, but no perioperative reduction in cardiac necrosis markers. Conversely, other studies have reported a significant decrease in myocardial necrosis markers in patients undergoing on-pump CABG 3 and more recently aortic valve surgery if sevoflurane or desflurane was used throughout surgery. Other groups recently reported similar results. 6 22