Improved myocardial function with supplement of levosimendan to Celsior solution.
Levosimendan is a calcium-sensitizing agent shown to prevent myocardical contractile depression in various heart diseases. In this study, we investigated the effect of levosimendan on cardiac dysfunction and apoptosis in hypothermic preservation rat hearts. Isolated rat hearts were preserved in Celsior solution with or without levosimendan. The left ventricular developed pressure (LVDP) recovery rate of isolated rat heart significantly decreased, and the apoptosis index increased after 9 hours of hypothermic preservation. Supplement Celsior solution with levosimendan (10 and 10 mole/L) enhanced the LVDP recovery rate and reduced apoptosis. Levosimendan inhibited the hypothermic preservation-induced calpain activation and cleavage of Bid. Levosimendam induced increased myocardial inducible nitric oxide synthase but not endothelial nitric oxide synthase expression. A selective inducible nitric oxide synthase inhibitor 1400W, and a mitochondrial ATP-sensitive potassium (KATP) channel blocker 5-hydroxydecanoate but not a sarcolemmal KATP channel blocker HMR-1098 prevented improvement effect of levosimendam on LVDP recovery rate, abolished the inhibitory effect of levosimendan on hypothermic preservation-induced activation of calpain, cleavage of Bid, and apoptosis. These data suggested that Celsior solution supplement with levosimendan improved cardiac function recovery and reduced myocyte apoptosis in hypothermic preservation rat hearts.
*Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; †Department of Pharmacology, Zhejiang Medical College, Hangzhou, China; and ‡Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
Hai-yan
HY
Zhou
Li-na
LN
Zhang
Ming-zhi
MZ
Zheng
Lin-lin
LL
Wang
Ying-ying
YY
Chen
Yue-Liang
YL
Shen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D004187:Disaccharides / Q000008:administration & dosage / Q000494:pharmacology; D004573:Electrolytes / Q000008:administration & dosage / Q000494:pharmacology; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology; D005978:Glutathione / Q000008:administration & dosage / Q000494:pharmacology; D006639:Histidine / Q000008:administration & dosage / Q000494:pharmacology; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D006880:Hydroxy Acids / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077464:Simendan; D016277:Ventricular Function, Left / Q000187:drug effects*
D001549:Benzamides; D002316:Cardiotonic Agents; C088453:Celsior; D003652:Decanoic Acids; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D006835:Hydrazones; D006880:Hydroxy Acids; D011724:Pyridazines; D000077464:Simendan; D008353:Mannitol; D006639:Histidine; C052853:5-hydroxydecanoic acid; C410297:HMR 1098; D052247:Nitric Oxide Synthase Type II; D005978:Glutathione