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Protection of cardiomyocytes by anesthetic preconditioning involves endothelial cell derived nitric oxide
Author(s) -
Leucker Thorsten Martin,
Bienengraeber Martin,
Brzezinska Anna K,
Pratt Phillip F,
Warltier David C
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.601.7
Subject(s) - isoflurane , cardioprotection , anesthetic , ischemic preconditioning , hypoxia (environmental) , nitric oxide , endothelial stem cell , reperfusion injury , pharmacology , nitric oxide synthase , ischemia , chemistry , medicine , anesthesia , cardiology , biochemistry , in vitro , oxygen , organic chemistry
NO is involved in the anesthetic preconditioning‐induced protection against cardiac ischemic injury. The goal of this investigation was to test the hypothesis that endothelial cell derived NO enhaces cellular protection against hypoxia and reoxygenation‐induced cardiomyocyte injury. We studied anesthetic preconditioning in a coculture model of human endothelial cells and HL‐1 cardiomyocytes. Cells were exposed to 0.5 mM isoflurane for 30 min followed by 15 min wash out. Then cells were exposed to 3 h of hypoxia followed by 4 h of reperfusion. To determine cell survival we assessed LDH release and tryptan blue staining. Our results demonstrate that co‐culturing endothelial cells and HL‐1 cardiomyocytes protects from ischemia‐reperfusion injury. Isoflurane exerts protective effects on HL‐1 cardiomyocytes. However, metabolic interactions between endothelial cells and cardiomyocytes exceed the protective effect of isoflurane alone, adding additional layer of cardioprotection. The protective effect of isoflurane is reversed by the NO synthase inhibitor L‐NMMA given prior to reperfusion, but not when given only during isoflurane treatment. In conclusion, during reperfusion, anesthetic induced cardioprotection, in part, depends upon the activity of endothelial NO synthase.