| Co-Investigator(Kenkyū-buntansha) |
MORISHITA Yasuo Gunma University, Department of Surgery, Professor, 大学院・医学系研究科, 教授 (40145470)
TAKAHASHI Toru Gunma University, Department of Surgery, Assistant Professor, 医学部, 助手 (20292584)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
(Experiment 1)Purpose : The purpose of this study was to investigate the effects of direct hemoperfusion using polymyxin B-immobilized fiber (PMX) on normothermic cardiac surgery in pigs. Methods : Ten pairs of pigs were divided into two groups. After anesthesia of animals, Normothermic CPB was established in a usual fashion. Control group animals were perfused using a normothermic CPB circuit. PMX group animals were perfused using an endotoxin removal column containing polymyxin B-imrhobilized fiber, which was introduced at a flow rate of 80ml/min from CPB to the end of experiment. Cardiac arrest was obtained by intermittent antegrade warm blood cardioplegia. Aortic cross clamping time was 34 min. Maximal ventricular elastance (Emax), cardiac output(CO), left ventricular pressure(LVP), the maximum rate of increase and decrease of LVP (LV dP/dt), and arterial blood gas were measured at pre-CPB and 2hr after weaning from CPB. Cardiac functional recovery rates were expressed as a percent
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age of pre-CPB values. Results : Emax,LVP,CO,-LV dP/dt and PaO_2 were significantly better in the PMX group than in the control group. Histopathological tissue damage of the myocardium was milder in the PMX group than in the control group. Conclusion : Direct hemoperfusion using polymyxin B-immobilized fiber in the condition of normothermic CPB ameliorates ischemia-reperfusion injury of the heart and lung.
(Experiment 2)Purpose : In a previous study, we reported that suppression of proinflammatory cytokines, such as tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of proinflammatory cytokines, improves donor heart function following transplantation. Methods : Adult mongrel dogs were used. Coronary vascular beds were washed out with University of Wisconsin(UW) solution following cardiac arrest obtained. The heart was then excised and preserved for 12 h with a combination of immersion and coronary perfusion using a preservation apparatus. Adult mongrel dogs were divided into two groups : the coronary perfusion(CP) group and the FR167653 (FR-CP) group. In the CP group, a 4℃ UW solution was used for both immersion and coronary perfusion. In the FR-CP group, a 4℃ UW solution supplemented with 20 mg/L of the anti-inflammatory agent FR167653 was used for both immersion and coronary perfusion. At 2 and 3 h after orthotopic transplantation, hemodynamic parameters were compared with preoperative values of donor animals. Serum levels of TNF-αin blood from the coronary sinus and electron microscopic studies were compared between the two groups. Results : Three hours after transplantation, cardiac output(CO), left ventricular pressure(LVP) and-LV dp/dt were significantly higher in the FR-CP group than in the CP group. Electron microscopic studies showed that glycogen was well preserved in the FR-CP group as compared with the CP group. Serum levels of TNF-α were significantly reduced in the FR-CP group relative to the CP group. Conclusion : Hemodynamics following transplantation was significantly better in the FR-CP group than in the CP group. The combined preservation method of continuous per fusion and immersion using our apparatus in conjunction with suppression of proinflammatory cytokines improves donor heart function following transplantation. Less
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