To the Editor:—
We read with great interest the article by Hirata et al.
showing in rats a protective effect against arrhythmias induced by 30 min of left anterior descending coronary artery ligation.
The authors suggest that propofol preserves connexin 43 (Cx43) phosphorylation during acute myocardial ischemia, and that this might better protect the heart, as compared with sevoflurane. This effect would be mediated through vagal nerve stimulation. We would suggest another factor that could play a role in the results obtained in this very interesting study.
As Hirata et al.
state, chronic heart failure, myocardial infarction, and acute myocardial ischemia reduce the phosphorylation of the most important protein of the cardiac gap junctions, Cx43, causing cellular uncoupling and arrhythmias. In a model of myocardial infarction by coronary ligation carried out in both wild-type and inducible nitric oxide synthase (iNOS) −/−
knockout mice, Jackson et al.2
showed that increased nitric oxide production by iNOS has a role in reducing the myocardial content in phosphorylated Cx43 and the ratio of phosphorylated to total Cx43. The mice with iNOS deletion were, as compared with the wild-type mice, relatively protected against reduced Cx43 expression and the consequent depression in cardiac performance.
Propofol has also been shown to down-regulate iNOS expression in macrophages activated by lipopolysaccharide3
and in a model of testicular ischemia–reperfusion injury in rats.4
Furthermore, propofol, as compared with sevoflurane, provides major protection against ischemia reperfusion injury induced by aortic clamping in a piglet model,5
reducing more the systemic inflammatory response and the expression of nuclear factor-kappa B and iNOS.
It is therefore possible that the stronger depressive effect of propofol on iNOS, as compared with sevoflurane, causes a minor down-regulation of total and phosphorylated Cx43, contributing to the antiarrhythmic effects observed in Hirata et al.'s study.
Luca Siracusano, M.D.*
Viviana Girasole, M.D.
*University of Messina School of Medicine, Policlinico Universitario G. Martino, Messina, Italy. firstname.lastname@example.org
1. Hirata N, Kanaya N, Kamada N, Kimura S, Namiki A: Differential effects of propofol and sevoflurane on ischemia-induced ventricular arrhythmias and phosphorylated connexin 43 protein in rats. Anesthesiology 2009; 110:50–7
2. Jackson PE, Feng QP, Jones DL: Nitric oxide depresses connexin 43 after myocardial infarction in mice. Acta Physiol (Oxf) 2008; 194:23–33
3. Chen RM, Wu GJ, Tai YT, Sun WZ, Lin YL, Jean WC, Chen TL: Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase. Arch Toxicol 2003; 77:418–23
4. Yagmurdur H, Ayyildiz A, Karaguzel E, Akgul T, Ustun H, Germiyanoglu C: Propofol reduces nitric oxide-induced apoptosis in testicular ischemia-reperfusion injury by downregulating the expression of inducible nitric oxide synthase. Acta Anaesthesiol Scand 2008; 52:350–7
5. Sánchez-Conde P, Rodríguez-López JM, Nicolás JL, Lozano FS, García-Criado FJ, Cascajo C, González-Sarmiento R, Muriel C: The comparative abilities of propofol and sevoflurane to modulate inflammation and oxidative stress in the kidney after aortic cross-clamping. Anesth Analg 2008; 106:371–8
© 2009 American Society of Anesthesiologists, Inc.