1 Milwaukee, USA 2 Ankara, Turkey
EditorThe recent article by Sayin and colleagues1 well demonstrates decreased peroxidation in patients undergoing cardiac surgery receiving an infusion of propofol rather than fentanyl. Despite the well known injurious effects of free radicals when formed in large quantities during ischaemia/reperfusion, I think that their recommendation for the use of propofol in an anaesthetic drug regimen during CABG if ischaemia and reperfusion injury is of concern should carry an important caveat based on recent findings. Indeed, a contrary conclusion could be drawn. Free radicals are certainly injurious in large quantities. However, there is now considerable evidence that they are essential mediators in clinically important endogenous pathways of cardioprotection.25 Scavenging of free radicals before ischaemia may impede the hearts innate ability to protect itself from the effects of ischaemia/reperfusion; this has been demonstrated in terms of myocardial stunning, arrhythmias and infarction. It may account for the failure of several clinical trials to demonstrate a benefit of scavengers given before ischaemia. Laboratory reports describe abrogation of cardioprotection when radicals are scavenged; this applies to protection effected by ischaemic preconditioning,2 by endogenous substances,3 and by volatile anaesthetic agents.4 In humans, even transient exposure to isoflurane has been shown to induce a state of cardioprotection;6 this occurs by a mechanism that is believed to be free radical mediated.4 5 A recent clinical trial compared propofol with sevoflurane in cardiac surgery patients;7 using left ventricular function and troponin as markers of cardiac injury, sevoflurane, but not propofol, was found to be cardioprotective. Generation of free radicals by volatile anaesthetics,4 and scavenging of free radicals by propofol, may account for this difference. Unfortunately, the study by Sayin and colleagues1 does not report these or other indices of cardiac injury. Finally, it is important to note that opioids have been shown to generate free radicals in the heart.3 8
L. G. Kevin
Milwaukee, USA
EditorWe appreciate Dr Kevins comments on our article on propofol decreasing lipid peroxidation during cardiopulmonary bypass.1 In his letter he claimed that our recommendation about the use of propofol during CABG where ischaemia and reperfusion is of concern, could be rebutted by the recent view that free radicals are important mediators for ischaemic preconditioning, leading to better ventricular function after bypass. Free radicals may have contrasting opposite effects when produced during beneficial ischaemic preconditioning or during prolonged and deleterious ischaemia and reperfusion,9 but they are not considered to be the only trigger for ischaemic preconditioning.10 Activation of the kinase cascade is thought to be a key feature of preconditioning signals.11 Although better postoperative ventricular function was found in patients with ischaemic preconditioning, the reason was found to be multifactorial and not only attributable to free radicals.9 10 Free radicals are still thought to be deleterious during reperfusion after cross-clamping.
Our study was a biochemical one, which aimed to show whether the use of propofol during CABG decreased free radicals in the myocardial tissue. Previous studies were carried out on coronary sinus blood. Free radicals in blood disappear very rapidly, so we planned to investigate them in myocardial tissue. Indices of cardiac injury such as CK-MB or troponin could produce misleading results, as tissue damage from surgery potentiates the effects of the ischaemic injury on these enzymes. We did not aim to investigate if propofol was cardioprotective, but whether it was a scavenger of free radicals.
It has recently been claimed that volatile anaesthetics have a cardioprotective effect through ischaemic preconditioning.6 7 Pouzet and colleagues,12 in contrast, showed cardiopulmonary bypass triggered activation of the kinase cascade that is mechanically linked to opening of potassium channels. Opening of these channels by sevoflurane did not increase kinase activation, however, nor did it improve markers of cell necrosis.
Some recent studies have shown that opioids may generate free radicals8 13 and many other i.v. anaesthetics have been shown to have antioxidant properties.14 15 We chose fentanyl as a control group drug because many anaesthetists use opioid-based anaesthesia for cardiac surgery, and fentanyl does not interfere with the antioxidant properties of propofol.
We think that our recommendation of the use of propofol during CABG is still valid, as free radicals have deleterious effects during reperfusion after cross-clamp removal. In the light of these results, further studies are needed on when to use opioids and propofol during CABG, to achieve better myocardial performance.
M. M. Sayin
O. Özatamer
N. Ünal
Ankara, Turkey
References
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