Source: David C. Warltier, M.D., Ph.D.; Judy R. Kersten, M.D.; Paul S. Pagel, M.D., Ph.D.; Garrett J. Gross, Ph.D. ANESTHESIOLOGY 2002;97:1-3

"Reviewer":  R. Prasad, MD

Comments:

• There were 7 articles on preconditioning that all appear to be very interesting.
• However, since I don't do any cardiac anesthesia, I thought I'd just summarize the editorial written on the special "section on anesthetic preconditioning"

• Background
• Volatile agents may have important cardioprotective properties against myocardial ischemia and reperfusion injury.
• Protection against reversible and irreversible myocardial injury was not easily explained by simple alterations in myocardial oxygen supply and demand
• In contrast, previous clinical investigations had not found evidence for a preferred anesthetic in patients with CAD. Thus, early lab findings went largely unresolved with the appearance of having few if any direct implications for humans.
• More recently, economical incentives to reduce lengths of stay (instead of scientific investigation to improve outcome!) --> advocation of shorter-acting drugs that allow patients to earlier extubations and ICU/hospital discharges. That is, high-dose opioid technique --> primarily volatile anesthetic technique for CABG.
• Resulted in anecdotal observations of fewer intraoperative ischemic events, less frequent need for pharmacological or mechanical circulatory support
• Ischemic Preconditioning (IPC)
• Single or multiple brief periods of ischemia can be protective against subsequent prolonged ischemic insult
• IPC results in finite periods in which the myocardium is protected. An early phase or window of IPC persists for 1 to 2 h before “disappearing” and then reoccurring 24 h later. This second or late window of preconditioning may last for as long as 3 days.
• Mechanism(s): A variety of ligands and multiple receptors coupled to G proteins are primarily responsible for activation of an intracellular signal transduction pathway that involves protein kinase C, mitogen-activated protein kinases, protein tyrosine kinases, reactive oxygen species, and nitric oxide synthase. Central to this process is the role of the mitochondrial adenosine triphosphate-sensitive potassium (KATP) channel. Opening of this channel is critical for the beneficial cardioprotective effects of IPC.
• Anesthetic Preconditioning (APC)
• Volatile anesthetics have been shown to directly precondition or indirectly enhance IPC, resulting in cardioprotection against myocardial infarction with the KATP channel playing an important role
• Pharmacological preconditioning produced by volatile agents, including isoflurane, desflurane, and sevoflurane, is remarkably similar to IPC and shares many of the same signal transduction elements
• In this issue:
• Zaugg et al. (pp 4–14 and 15–23) provide additional evidence that mitochondrial KATP channels are critical to APC by volatile agents and also demonstrate that certain intravenous anesthetics may have deleterious effects on preconditioning produced by KATP channel openers. Cardiac sarcolemmal KATP channels may also be modulated by volatile anesthetics. 
• Kwok et al. (pp. 50–6 and 57–65) demonstrate that isoflurane may not directly alter sarcolemmal KATP channels but instead potentiates opening of the channel by other agonists. Other results from this laboratory show that the action of isoflurane on the KATP channel requires endogenous mediators, most likely PKC.
• de Klaver et al. (pp. 24–32) suggests that APC is not limited to cardiomyocytes, but protection against vascular smooth muscle and endothelial cell death by isoflurane and halothane is also possible.
• Hanouz et al. (pp. 33–41) confirm that desflurane is cardioprotective, and this agent may act via multiple mechanisms that ultimately converge on the mitochondrial KATP channel. These investigators further demonstrate that adenosine and - and -adrenergic receptors may also be involved in APC signal transduction. 
• A small clinical investigation by De Hert et al. (pp. 42–9) has suggested that volatile anesthetics are cardioprotective in humans. This study demonstrates that sevoflurane-anesthetized patients had reduced cardiac enzyme release and improved left ventricular function after coronary artery bypass graft surgery as compared to patients anesthetized with propofol.