Ventricular hypertrophy blocked delayed anesthetic cardioprotection in rats by alteration of iNOS/COX-2 signaling.
The aim of the current study was to determine whether ventricular hypertrophy affects the delayed isoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury. Transverse aortic constriction (TAC) was performed on male Sprague-Dawley rats to induce left ventricular (LV) hypertrophy, then sham-operated or hypertrophied rat hearts were subjected to isoflurane preconditioning (2.1% v/v, 1 h). 24 h after exposure, the hearts were isolated and perfused retrogradely by the Langendorff for 30 min (equilibration) followed by 40 min of ischemia and then 120 min of reperfusion. The hemodynamics, infarct size, apoptosis, nitric oxide synthase (NOS), cyclooxygenase-2 (COX-2), Cleaved Caspase-3 and production of NO were determined. We found that the hemodynamic parameters were all markedly improved during the reperfusion period and the myocardial infarct size and apoptosis was significantly reduced by delayed isoflurane preconditioning in sham-operated rats. However, such cardiac improvement induced by delayed isoflurane preconditioning was not observed in hypertrophied hearts. The expression of iNOS, COX-2 and NO was markedly enhanced, whereas Cleaved Caspase-3 activity was inhibited by delayed isoflurane preconditioning in sham-operated rats, a phenomenon was not found in TAC-control groups pretreated with isoflurane. Our results demonstrated that ventricular hypertrophy abrogated isoflurane-induced delayed cardioprotection by alteration of iNOS/COX-2 pathway.
1] Department of Critical Care Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China [2] Department of Anesthesiology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China [3] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Leilei
L
Ma
1] Department of Anesthesiology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China [2] Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Feijuan
F
Kong
Department of Urology, Peking University Shougang Hospital, Beijing, China.
Hongwei
H
Ge
Department of Critical Care Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.
Jingquan
J
Liu
Department of Critical Care Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.
Fangxiao
F
Gong
Department of Critical Care Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.
Liang
L
Xu
Department of Critical Care Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.
Bangchuan
B
Hu
Department of Critical Care Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.
Renhua
R
Sun
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D006439:Hemodynamics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007530:Isoflurane / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D015398:Signal Transduction
D009569:Nitric Oxide; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D053148:Caspase 3