J Thorac Cardiovasc Surg 2006;131:253
© 2006 The American Association for Thoracic Surgery
Reply to the Editor
Geoffrey P. Dobson, MSc, PhD
Department of Physiology and Pharmacology, James Cook University, Townsville, Queensland, Australia
My colleagues and I thank Lange and colleagues for pointing out that we omitted mentioning the importance of volatile anesthetics and ischemic preconditioning (IPC) in a number of animal models and possibly human beings. For example, Kersten and coworkers
showed that halothane preconditioning in barbiturate-anesthetized dogs led to a profound infarct size reduction (25.3% ± 2.9% to 11.8% ± 2.7%) and that this reduction was as effective as IPC (9.6% ± 2.0%). We were remiss in not discussing these results and their importance to IPC. Lange and colleagues also stated, "Anesthetic preconditioning significantly reduces arrhythmias after ischemic periods." The antiarrhythmic effect of volatile anesthetics is more problematic. Recently Owczuk and associates
discussed how desflurane can prolong the QTc interval and may result in lethal cardiac arrhythmias. Huneke and coworkers
also reported that halothane, and to a lesser extent isoflurane and sevoflurane, may lead to ventricular arrhythmias by shortening the refractory period. In addition, volatile anesthetics are known to inhibit a number of voltage-gated potassium ion channels, which could further increase the risk of ventricular tachycardia in predisposed patients.
It is unfortunate that most animal studies investigating volatile anesthetics and IPC rarely report the incidence and duration of arrhythmias during ischemia-reperfusion. On the other hand, we reported that pretreating the heart with an intravenous solution of the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine and sodium ion fast-channel modulator lidocaine (A1L) administered 5 minutes before and during 30 minutes of acute regional ischemia in the rat in vivo resulted in no deaths, virtually no severe ventricular arrhythmias and an infarct size equivalent to that seen with IPC.
Finally, Lange and colleagues believe it is unlikely that the administration of a selective A1 agonist plus a volatile anesthetic could further enhance cardioprotection. However, we believe the combination may reduce the amount of each agent needed to exert cardioprotection; that is, the A1 receptor agonist may reduce the effective therapeutic threshold of the volatile anesthetic agent. This concept was recently reported by Chiari and colleagues,
in whose study postconditioning during early reperfusion reduced the concentration of isoflurane necessary to exert cardioprotection. Because the underlying mechanisms of volatile anesthetics and the A1L combination are not fully understood, the synergistic effects of volatile anesthetics and A1 analogs (or A1L) remain to be determined. Moreover, modulating cardiac voltage-gated sodium ion fast channels with local anesthetics has received surprisingly little attention in IPC strategies, despite the resetting of the resting membrane potential toward a more depolarized state during ischemic injury.
To quote nineteenth century essayist and politician Benjamin Disraeli, "What we anticipate seldom occurs; what we least expected generally happens."
Importantly, our work has shown that it is the combination of A1 agonist (or adenosine) and lidocaine administration that confers functional, electrical, and metabolic protection during myocardial ischemia-reperfusion.
It would be of interest to study the effects of volatile anesthetics in the presence of the combination of A1 agonist (or adenosine) and lidocaine during and after acute myocardial ischemia in clinically relevant experimental models.
- Kersten JR, Schmeling TJ, Pagel PS, Gross GJ, Warltier DC. Isoflurane mimics ischemic preconditioning via activation of K(ATP) channels. reduction of myocardial infarct size with an acute memory phase. Anesthesiology 1997;87:361-370.[Medline]
- Owczuk R, Wujtewicz MA, Sawicka W, Lasek J, Wujtewicz M. The influence of desflurane on QTc interval. Anesth Analg 2005;101:419-422.[Abstract/Free Full Text]
- Huneke R, Fassl J, Rossaint R, Luckhoff A. Effects of volatile anesthetics on cardiac ion channels. Acta Anaesthesiol Scand 2004;48:547-561.[Medline]
- Canyon SJ, Dobson GP. Pretreatment with an adenosine A1 receptor agonist and lidocaine. a possible alternative to myocardial ischemic preconditioning. J Thorac Cardiovasc Surg 2005;130:371-377.[Abstract/Free Full Text]
- Chiari PC, Bienengraeber MW, Weihrauch D, Krolikowski JG, Kersten JR, Warltier DC, et al. Role of endothelial nitric oxide synthase as a trigger and mediator of isoflurane-induced delayed preconditioning in rabbit myocardium. Anesthesiology 2005;103:74-83.[Medline]
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