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Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia.
Interact Cardiovasc Thorac Surg. 2009 Jun; 8(6):629-34.IC

Abstract

Sivelestat, a neutrophil elastase inhibitor, has been shown to attenuate pulmonary injury during ischemia and reperfusion by improving microcirculation and may be effective as a cardioprotective agent. Isolated rat hearts were Langendorff-perfused (constant pressure, 75 mmHg) with oxygenated Krebs-Henseleit bicarbonate buffer (KHB). The optimal sivelestat concentration at 19 micromol/l was revealed because left ventricular developed pressure (LVDP) recovery in 19 micromol/l sivelestat was highest among 0.19, 1.9, 19, 190, and 1900 micromol/l sivelestat (26+/-10, 33+/-7, 56+/-5*, 35+/-2, and 15+/-5%, respectively; *P<0.01). In order to examine the optimal administration timing, sivelestat was administered at pre- and post-ischemic phases. LVDP recovery and troponin-T were observed in pre-, post-ischemic sivelestat groups and control. After 60 min-reperfusion, LVDP recoveries were 42+/-10*, 45+/-19*, and 14+/-5%, respectively (*P<0.01 compared to control), and troponin-T values were 4+/-1, 2+/-1**, and 8+/-2, respectively (**P<0.05 compared to control). Acetylcholine-induced increase in coronary flow was also investigated to examine the sivelestat's cardioprotective mechanism. Ischemia-reperfusion (I/R) impaired the acetylcholine-induced increase in coronary flow (maximal changes: sham, 125+/-11%; I/R, 98+/-3; P<0.01) and this impairment was attenuated by sivelestat-perfusion at reperfusion (maximal change: 112+/-7%; P<0.05 vs. I/R). Sivelestat attenuates coronary endothelial ischemia-reperfusion injury and improves myocardial protection even when administered at the reperfusion period. This suggests a role for sivelestat in the preservation of coronary endothelial function enhancing myocardial protection.

Authors+Show Affiliations

Department of Biological Regulation and Regenerative Surgery, Nippon Medical School Graduate School of Medicine, Tokyo, Japan. shaw@nms.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19279053

Citation

Kambe, Masaru, et al. "Sivelestat Reduces Myocardial Ischemia and Reperfusion Injury in Rat Hearts Even when Administered After Onset of Myocardial Ischemia." Interactive Cardiovascular and Thoracic Surgery, vol. 8, no. 6, 2009, pp. 629-34.
Kambe M, Bessho R, Fujii M, et al. Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia. Interact Cardiovasc Thorac Surg. 2009;8(6):629-34.
Kambe, M., Bessho, R., Fujii, M., Ochi, M., & Shimizu, K. (2009). Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia. Interactive Cardiovascular and Thoracic Surgery, 8(6), 629-34. https://doi.org/10.1510/icvts.2008.195933
Kambe M, et al. Sivelestat Reduces Myocardial Ischemia and Reperfusion Injury in Rat Hearts Even when Administered After Onset of Myocardial Ischemia. Interact Cardiovasc Thorac Surg. 2009;8(6):629-34. PubMed PMID: 19279053.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia. AU - Kambe,Masaru, AU - Bessho,Ryuzo, AU - Fujii,Masahiro, AU - Ochi,Masami, AU - Shimizu,Kazuo, Y1 - 2009/03/11/ PY - 2009/3/13/entrez PY - 2009/3/13/pubmed PY - 2009/7/29/medline SP - 629 EP - 34 JF - Interactive cardiovascular and thoracic surgery JO - Interact Cardiovasc Thorac Surg VL - 8 IS - 6 N2 - Sivelestat, a neutrophil elastase inhibitor, has been shown to attenuate pulmonary injury during ischemia and reperfusion by improving microcirculation and may be effective as a cardioprotective agent. Isolated rat hearts were Langendorff-perfused (constant pressure, 75 mmHg) with oxygenated Krebs-Henseleit bicarbonate buffer (KHB). The optimal sivelestat concentration at 19 micromol/l was revealed because left ventricular developed pressure (LVDP) recovery in 19 micromol/l sivelestat was highest among 0.19, 1.9, 19, 190, and 1900 micromol/l sivelestat (26+/-10, 33+/-7, 56+/-5*, 35+/-2, and 15+/-5%, respectively; *P<0.01). In order to examine the optimal administration timing, sivelestat was administered at pre- and post-ischemic phases. LVDP recovery and troponin-T were observed in pre-, post-ischemic sivelestat groups and control. After 60 min-reperfusion, LVDP recoveries were 42+/-10*, 45+/-19*, and 14+/-5%, respectively (*P<0.01 compared to control), and troponin-T values were 4+/-1, 2+/-1**, and 8+/-2, respectively (**P<0.05 compared to control). Acetylcholine-induced increase in coronary flow was also investigated to examine the sivelestat's cardioprotective mechanism. Ischemia-reperfusion (I/R) impaired the acetylcholine-induced increase in coronary flow (maximal changes: sham, 125+/-11%; I/R, 98+/-3; P<0.01) and this impairment was attenuated by sivelestat-perfusion at reperfusion (maximal change: 112+/-7%; P<0.05 vs. I/R). Sivelestat attenuates coronary endothelial ischemia-reperfusion injury and improves myocardial protection even when administered at the reperfusion period. This suggests a role for sivelestat in the preservation of coronary endothelial function enhancing myocardial protection. SN - 1569-9285 UR - https://www.unboundmedicine.com/medline/citation/19279053/Sivelestat_reduces_myocardial_ischemia_and_reperfusion_injury_in_rat_hearts_even_when_administered_after_onset_of_myocardial_ischemia_ L2 - https://academic.oup.com/icvts/article-lookup/doi/10.1510/icvts.2008.195933 DB - PRIME DP - Unbound Medicine ER -