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Preconditioning with Bay 60–2770, An Activator of Soluble Guanylate Cyclase, Attenuates Myocardial Infarction in eNOS Knockout Mice
Author(s) -
Wang Meifang,
Wang Derek Z,
Jones Allan W,
Zuidema Mozow Y,
Wang Walter Z,
Korthuis Ronald J
Publication year - 2013
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.27.1_supplement.682.4
Subject(s) - enos , medicine , troponin i , ischemia , cardiology , reperfusion injury , evans blue , endocrinology , myocardial infarction , nitric oxide , nitric oxide synthase
Our previous studies showed that soluble Guanylate Cyclase (sGC) activation protects against postischemic intestinal injury when used as a preconditioning stimulus in wild type, heme‐oxygenase‐1 KO and eNOS KO (eNOS −/− )mice. The aim of this study was to determine whether a similar protective effect of sGC activation by Bay60–2770 (Bay 60) would occur in postischemic cardiac injury. Infarct size (% LV), assessed by 2,3,5‐triphenyltetrazolium chloride (TTC) staining, was significantly increased in eNOS −/− mice after 30 min left anterior descending coronary artery (LAD) ischemia and 24 hr reperfusion as compared with eNOS −/− sham mice (p < 0.001). Bay 60 treatment (300ug/kg, ip bolus, 24hr prior to LAD ischemia) significantly attenuated I/R‐induced increase in infarct size (p < 0.05) in eNOS −/− mice. Serum Troponin‐I (cTnI), a marker of myocardial injury, after 30 min LAD ischemia and at 4 hr reperfusion, was markedly elevated in eNOS −/− mice, compared with eNOS −/− sham mice (p < 0.01). Preconditioning with Bay 60 24hr prior to cardiac I/R did not prevent the increase in cTnI levels. These findings indicate that Bay 60 preconditioning 24hr prior to cardiac I/R limits the size of the evolving infarct area at 24 hr of perfusion independently of eNOS and factors leading to early release of cTnI. Supported by a grant from the NIH (AA‐014945). BAY 60–2770 was a gift from Bayer Schering Pharma AG.