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Beneficial effects of Q9 and Q10 in isolated guinea pig hearts
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ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S190–S218
Methods: Male Wistar rats were used to make the model of myocardial ischemia and reperfusion by ligation of the left descending coronary artery in the anaesthetized state. The rats were treated with SHEN-FU injection (i.v.1 mg/kg, 2 mg/kg) after the ischemia/reperfusion. Spectrophotometrical method was used to measure activities of Lactate dehydrogenase(LDH) and creatine kinase (CK) in serum, activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and endothelial nitric oxide synthease (eNOS) as well as malondialdehyde (MDA) and NO levels in heart. cGMP and PKG contents were detected by radioimmunoassay (RIA) method and western blot, respectively. Result: SHEN-FU injection at dose of 2 mg/kg significantly decreased the activities of LDH and CK in serum as well as MDA levels in heart. At the same time SHEN-FU injection markedly increased antioxidant enzymes and eNOS activities and cGMP and PKC contents in heart. Furthermore S-methylisothiourea sulfate (SMT) can significantly enhance the protective effect of SHEN-FU injection, through reducing MDA levels and increasing eNOS activity and cGMP content. On the contrary NG-nitro-L-arginine methyl ester (L-NAME) alleviated the role of SHEN-FU injection. Conclusion: These suggest that SHEN-FU injection is able to provide a protective effect against the heart ischemic injury through antioxidant mechanism and NO-cGMP signal path. Keywords: Ischemia/reperfusion; Myocardial doi:10.1016/j.yjmcc.2007.03.634
Myocardial protection and neutrophil elastase inhibitor: Additive effect of the sivelestat on reperfusion injury M. Fujii, R. Bessho, M. Kambe, M. Ochi, K. Shimizu. Nippon Medical School, Tokyo, Japan Objective: We have previously shown that sivelestat sodium hydrate (sivelestat), a novel synthesized neutrophil elastase inhibitor, affords a cardioprotective effect against 30 min global ischemia. In this study, we examined whether myocardial protection by sivelestat may be additive to that provided by cardioplegic arrest (St. Thomas' Hospital cardioplegia; STH2) in crystalloid perfused rat hearts. Methods: Isolated rat hearts were aerobically Langendorffperfused with bicarbonate buffer and function (left ventricular developed pressure; LVDP) was measured. Hearts were randomly allocated to each of 3 groups before being subjected to 2 min of STH2 infusion and 30 min of normothermic global ischemia. All protocols were followed by 60 min of reperfusion: (i) additional 10 min perfusion and no treatment throughout the protocol (control), (ii) additional 10 min perfusion but 10 min after reperfusion with 19 μmol/L sivelestat in perfusate, (iii) both 10 min before ischemia and 10 min after reperfusion with 19 μmol/L sivelestat in perfusate. The recovery of function was measured at the end of 60 min of
reperfusion. And then endothelial function also was assessed with 1 μmol/L acetylcholine. Results: The final recovery of LVDP (expressed as percentage of preischemic value) was 50 ± 15%, 69 ± 15%* and 69 ± 14%*, respectively (*p < 0.05 v (i)). The response to acetylcholine (expressed as percentage of pretreatment value) was 5 ± 5%, 18 ± 16%* and 20 ± 9%*, respectively (*p < 0.05 v (i)). Conclusion: Addition of an elastase inhibitor, sivelestat during early reperfusion enhances the myocardial protection afforded by St Thomas' Hospital cardioplegia, and it attenuates the endothelial dysfunction evoked by reperfusion injury. Keywords: Cardioprotection; Ischemia/reperfusion; Endothelium doi:10.1016/j.yjmcc.2007.03.635
Beneficial effects of Q9 and Q10 in isolated guinea pig hearts Gergo Szabo1, Istvan Lekli1, Samarjit Das2, Dipak K. Das2, Rudolf Gesztelyi1, Arpad Tosaki1. 1Univ. Debrecen, Hungary, 2 Univ. Connecticut, CT, USA The goal of our study was to investigate the effect of Q9 and Q10 on the recovery of postischemic cardiac function in isolated perfused guinea pig hearts, subjected to 30 of min ischemia followed by 120 of min reperfusion. Guinea pigs were divided into three groups (n = 12 in each group), the first was the control, the second group was treated orally with 1 mg/kg/day of Q9 for a month, and the third group received Q10 orally in a dose of 1 mg/kg/day for a month. Then, hearts were isolated, subjected to ischemia/reperfusion and ECG was recorded to determine the incidence of reperfusioninduced ventricular fibrillation (VF). We measured cardiac function (HR: heart rate; CF: coronary flow, AF: aortic flow; LVDP: left ventricle developed pressure), and at the end of experiments infarct size was determined. The results show that both molecules significantly reduced the incidence of reperfusion-induced VF in comparison with the control values (92% in control, 8% in Q9, and 25% in Q10 treated groups). In both treated groups, a significant improvement in postischemic cardiac function was recorded (e.g., AF and LVDP were 8 ± 1 ml/min and 45 ± 3 kPa in the ischemic/ reperfused control group vs. 18 ± 2 ml/min and 64 ± 3 kPa in the Q9, and 26 ± 1 ml/min and 75 ± 2 kPa in the Q10 treated groups, respectively). HR and CF followed the same pattern. Both antioxidant compounds significantly reduced the infracted area (38 ± 4% in control vs. 21 ± 5% in Q10 and 16 ± 3% in Q9 treated groups). Our results suggest that Q9 is a more potent cardioprotective agent than Q10. Keywords: Ischemia/reperfusion; Cardioprotection; Antioxidants doi:10.1016/j.yjmcc.2007.03.636
ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S190–S218
Methods: Male Wistar rats were used to make the model of myocardial ischemia and reperfusion by ligation of the left descending coronary artery in the anaesthetized state. The rats were treated with SHEN-FU injection (i.v.1 mg/kg, 2 mg/kg) after the ischemia/reperfusion. Spectrophotometrical method was used to measure activities of Lactate dehydrogenase(LDH) and creatine kinase (CK) in serum, activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and endothelial nitric oxide synthease (eNOS) as well as malondialdehyde (MDA) and NO levels in heart. cGMP and PKG contents were detected by radioimmunoassay (RIA) method and western blot, respectively. Result: SHEN-FU injection at dose of 2 mg/kg significantly decreased the activities of LDH and CK in serum as well as MDA levels in heart. At the same time SHEN-FU injection markedly increased antioxidant enzymes and eNOS activities and cGMP and PKC contents in heart. Furthermore S-methylisothiourea sulfate (SMT) can significantly enhance the protective effect of SHEN-FU injection, through reducing MDA levels and increasing eNOS activity and cGMP content. On the contrary NG-nitro-L-arginine methyl ester (L-NAME) alleviated the role of SHEN-FU injection. Conclusion: These suggest that SHEN-FU injection is able to provide a protective effect against the heart ischemic injury through antioxidant mechanism and NO-cGMP signal path. Keywords: Ischemia/reperfusion; Myocardial doi:10.1016/j.yjmcc.2007.03.634
Myocardial protection and neutrophil elastase inhibitor: Additive effect of the sivelestat on reperfusion injury M. Fujii, R. Bessho, M. Kambe, M. Ochi, K. Shimizu. Nippon Medical School, Tokyo, Japan Objective: We have previously shown that sivelestat sodium hydrate (sivelestat), a novel synthesized neutrophil elastase inhibitor, affords a cardioprotective effect against 30 min global ischemia. In this study, we examined whether myocardial protection by sivelestat may be additive to that provided by cardioplegic arrest (St. Thomas' Hospital cardioplegia; STH2) in crystalloid perfused rat hearts. Methods: Isolated rat hearts were aerobically Langendorffperfused with bicarbonate buffer and function (left ventricular developed pressure; LVDP) was measured. Hearts were randomly allocated to each of 3 groups before being subjected to 2 min of STH2 infusion and 30 min of normothermic global ischemia. All protocols were followed by 60 min of reperfusion: (i) additional 10 min perfusion and no treatment throughout the protocol (control), (ii) additional 10 min perfusion but 10 min after reperfusion with 19 μmol/L sivelestat in perfusate, (iii) both 10 min before ischemia and 10 min after reperfusion with 19 μmol/L sivelestat in perfusate. The recovery of function was measured at the end of 60 min of
reperfusion. And then endothelial function also was assessed with 1 μmol/L acetylcholine. Results: The final recovery of LVDP (expressed as percentage of preischemic value) was 50 ± 15%, 69 ± 15%* and 69 ± 14%*, respectively (*p < 0.05 v (i)). The response to acetylcholine (expressed as percentage of pretreatment value) was 5 ± 5%, 18 ± 16%* and 20 ± 9%*, respectively (*p < 0.05 v (i)). Conclusion: Addition of an elastase inhibitor, sivelestat during early reperfusion enhances the myocardial protection afforded by St Thomas' Hospital cardioplegia, and it attenuates the endothelial dysfunction evoked by reperfusion injury. Keywords: Cardioprotection; Ischemia/reperfusion; Endothelium doi:10.1016/j.yjmcc.2007.03.635
Beneficial effects of Q9 and Q10 in isolated guinea pig hearts Gergo Szabo1, Istvan Lekli1, Samarjit Das2, Dipak K. Das2, Rudolf Gesztelyi1, Arpad Tosaki1. 1Univ. Debrecen, Hungary, 2 Univ. Connecticut, CT, USA The goal of our study was to investigate the effect of Q9 and Q10 on the recovery of postischemic cardiac function in isolated perfused guinea pig hearts, subjected to 30 of min ischemia followed by 120 of min reperfusion. Guinea pigs were divided into three groups (n = 12 in each group), the first was the control, the second group was treated orally with 1 mg/kg/day of Q9 for a month, and the third group received Q10 orally in a dose of 1 mg/kg/day for a month. Then, hearts were isolated, subjected to ischemia/reperfusion and ECG was recorded to determine the incidence of reperfusioninduced ventricular fibrillation (VF). We measured cardiac function (HR: heart rate; CF: coronary flow, AF: aortic flow; LVDP: left ventricle developed pressure), and at the end of experiments infarct size was determined. The results show that both molecules significantly reduced the incidence of reperfusion-induced VF in comparison with the control values (92% in control, 8% in Q9, and 25% in Q10 treated groups). In both treated groups, a significant improvement in postischemic cardiac function was recorded (e.g., AF and LVDP were 8 ± 1 ml/min and 45 ± 3 kPa in the ischemic/ reperfused control group vs. 18 ± 2 ml/min and 64 ± 3 kPa in the Q9, and 26 ± 1 ml/min and 75 ± 2 kPa in the Q10 treated groups, respectively). HR and CF followed the same pattern. Both antioxidant compounds significantly reduced the infracted area (38 ± 4% in control vs. 21 ± 5% in Q10 and 16 ± 3% in Q9 treated groups). Our results suggest that Q9 is a more potent cardioprotective agent than Q10. Keywords: Ischemia/reperfusion; Cardioprotection; Antioxidants doi:10.1016/j.yjmcc.2007.03.636