| Project/Area Number |
15591463
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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 |
Thoracic surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
IGUCHI Atsushi Tohoku University, Gradate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90222851)
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| Co-Investigator(Kenkyū-buntansha) |
TABAYASHI Koichi Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90142942)
ODA Katsuhiko Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (60323002)
畑 正樹 東北大学, 医学部附属病院, 助手 (00282070)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | non-heart-beating donor / heart transplantation / conductance catheter / pressure-volume relation / left ventricular function / right ventricular function / ischemia reperfusion injury / sodium / hydrogen exchange / Na(+) / H(+)交換抑制剤 / 右心機能 / 再灌流障害 / 心保存 / 薬剤デリバリー法 / 圧-用量関係 / Na^+ H^+交換抑制剤 |
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| Research Abstract |
The purpose of present study was to elucidate the side effects and optimal timing and delivery method of Na(+)/H(+) exchange inhibitor (NHEI). Effect of NHEI on myocardial functional recovery was investigated and the function of both right ventricle and left ventricle was studied. After long-term myocardial preservation using cold crystalloid cardioplegic solution, NHEI has been demonstrated to reduce reperfusion injury of the heart. However, systemic drug delivery may lead to adverse effect on central nerves system. Selective intracoronary delivery can achieve higher concentrations of the agent and a smaller total dose of agent can be lowering systemic exposure and potential non-target organ toxicity. The function of right ventricle and left ventricle was assessed by pressure-volume relationship as a reliable measure of myocardial performance. Pigs were allocated to one of four study groups. In group 1 (n=6) donor animal received NHEI (1 mg/kg) 10 minutes before exanguination, and hea
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rts were harvested after 30 min of normothermic ischernia following cardiac arrest. Hearts were perfused with cold Celsior solution and transplanted orthotopically. Ten minutes before reperfusion, NHEI (2 mg/kg) was injected to cardiopulmonary bypass circuit. In group 2 (n=6) donor animal received NHEI (1 mg/kg) 10 minutes before exanguination, and hearts were transplanted orthotopically. NHEI (6.7 mg/kg/min) was selectively delivered to coronary artery for 30 minutes after reperfusion. In group 3 (n=6) donor animal received NHEI (1 mg/kg) 10 minutes before exanguination, and hearts were transplanted orthotopically. NHEI (6.7 mg/kg/min) was selectively delivered to coronary artery for 10 minutes after reperfusion. In group 4 (n=6) donor animal received saline 10 minutes before exanguination, and hearts were transplanted orthotopically. Ten minutes before reperfusion, NHEI (2 mg/kg) was injected to cardiopulmonary bypass circuit. After heart transplantation, pulmonary vascular resistance was elevated and afterload was increased, but right ventricular volume remained unchanged in groups 1 and 2. In groups 3 and 4, maintenance of the cardiac output during an increased afterload was obtained by an increased end-diastolic volume (Frank-Starling mechanism). It was demonstrated that in groups 1 and 2, the right ventricle maintains its output by improving its contractile performance. Selective intracoronary delivery can achieve lower systemic exposure and improved myocardial preservation. Less
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