2003 Fiscal Year Final Research Report Summary
Role of oxidative stress in pathogenesis of failing heart.
| Project/Area Number |
14570662
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
KAWAI Hiroya Kobe University, Graduate School of Medical Science, Assistant Professor, 医学部附属病院, 助手 (20346266)
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| Co-Investigator(Kenkyū-buntansha) |
SHITE Junya Kobe University, Graduate School of Medical Science, Assistant Professor, 医学部附属病院, 助手 (40362793)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Oxidative stress / Cardiac function / Antioxidant / Myocardial oxygen consumption / Myocardial efficiency / Heart failure / 心不全 |
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| Research Abstract |
Recent studies reported that heart failure (HF) is characterized by hyporesponsiveness to β-adrenergic stimulation accompanied by disproportionately high myocardial energy expenditure, partly due to the increased myocardial oxidative stress. We hypothesized that antioxidants reverses myocardial mechanoenergetic uncoupling in patients with HF. Methods : 24 patients with HF due to previous myocardial infarction (left ventricular (LV) ejection fraction ; 42±1%) were instrumented with conductance and coronary sinus thermodilution catheters. LV contractility (E_<max>; the slope of end-systolic pressure-volume relation) and mechanical efficiency (the ratio of LV external work to myocardial oxygen consumption (EW/MVO_2)) were measured in response to the intravenous infusion of dobutamine (4μg/kg/min) before (Dob) and during the intravenous infusion of ascorbic acid (Vit C ; n=10, 2.0g bolus injection and subsequent 50mg/min infusion for 10minutes), or reduced glutathion (GSH ; n=9,600mg/min i
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nfusion for 10minutes), or 0.9% saline (vehicle ; 2ml/min for 10minutes). Results : Dob increased E_<max> (65±12%), EW (45±8%) and MVO_2 (29±7%), resulting in unchanged mechanical efficiency (9±7%). Vit C enhanced the response of E_<max> (22±7%) and EW (20±4%), without changes in MVO_2 (0±3%), resulting in improved mechanical efficiency (21±5%) over Dob alone (p<0.01 vs Dob). GSH also enhanced the response of E_<max> (49±12%) and EW (36±7%), without increases in MVO_2 (8±9%), resulting in increased mechanical efficiency (31±7%) (p<0.01 vs Dob). Vehicle did not change these variables. Conclusion : Administratipn of antioxidants improves myocardial efficiency during β-adrenergic stimulation in human HF. These findings have biological implications for the role of oxidative stress in myocardial energetics in HF. Furthermore, they provide clinical implications for the use of antioxidants as a novel therapeutic strategy to restore the imbalance between cardiac performance and myocardial energy expenditure in patients avith HF. Less
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Research Products
(12 results)
