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Correspondence  |   August 2009
Propofol and Cardioprotection against Arrhythmias
Author Affiliations & Notes
  • Naoyuki Hirata, M.D.
    *
  • *Sapporo Medical University School of Medicine, Sapporo, Japan.
Article Information
Correspondence
Correspondence   |   August 2009
Propofol and Cardioprotection against Arrhythmias
Anesthesiology 8 2009, Vol.111, 448. doi:10.1097/ALN.0b013e3181acfda3
Anesthesiology 8 2009, Vol.111, 448. doi:10.1097/ALN.0b013e3181acfda3
In Reply:—  We are grateful to Dr. Siracusano for the helpful comments regarding our article.1 As Dr. Siracusano suggests, the effects of propofol on inducible nitric oxide synthase (iNOS) might be another factor of preservation of phosphorylated-connexin 43 contributing to the antiarrhythmic effect.
While we have suggested that propofol reduced ischemia-induced arrhythmias through vagal nerve stimulation, the effect of propofol on nitric oxide production or iNOS have not been mentioned in our manuscript.
It has been reported that propofol has a number of nonanesthetic effects. Regarding nitric oxide, not only does propofol inhibit iNOS, but it also stimulates constitutive nitric oxide production as previously shown by Yamamoto et al.  2 They showed that propofol caused the enhancement of nitric oxide production in cultured rat ventricular myocytes mediated by muscarinic acetylcholine receptors activation. This cholinergic nitric oxide–cyclic guanine monophosphate signaling pathway might be associated with our suggestion that propofol would stimulate the cardiac vagal nerve system.
Regarding the relation between antiarrhythmic effects via  vagal nerve stimulation and nitric oxide production, there have been several studies showing that nitric oxide plays an important role. Black et al.  3 demonstrated that nitric oxide mediates the vagal protective effect on ventricular fibrillation, and that those effects were blocked using the NOS inhibiter N  G-nitro-arginine and reversed by replenishing the substrate for nitric oxide production with L-arginine in an isolated rabbit heart. Moreover, Zhang et al.  4 showed that a nitric oxide donor, S-nitroso-N-acetyl-1, 1-penicilamine, partially inhibits the hypoxiainduced reduction of connexin 43 in H9c2 cells, immortalized ventricular myoblasts from rat embryos. This cholinergic nitric oxide-cGMP signaling pathway could be associated with not iNOS, but neural NOS.5 
Based on these results, further investigation of the effects of propofol on nitric oxide production, iNOS, and neural NOS, which is associated with ischemia-induced arrhythmias, is required.
*Sapporo Medical University School of Medicine, Sapporo, Japan.
References
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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; 110:50–7Hirata, N Kanaya, N Kamada, N Kimura, S Namiki, A ×
2. Yamamoto S, Kawana S, Miyamoto A, Ohshika H, Namiki A: Propofol-induced depression of cultured rat ventricular myocytes is related to the M2-acetylcholine receptor-NO-cGMP signaling pathway. Anesthesiology 1999; 91:1712–9Yamamoto, S Kawana, S Miyamoto, A Ohshika, H Namiki, A
2. Yamamoto S, Kawana S, Miyamoto A, Ohshika H, Namiki A: Propofol-induced depression of cultured rat ventricular myocytes is related to the M2-acetylcholine receptor-NO-cGMP signaling pathway. Anesthesiology 1999; 91:1712–9Yamamoto, S Kawana, S Miyamoto, A Ohshika, H Namiki, A ×
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