| Project/Area Number |
10671114
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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 |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
KUWAGATA Yasuyuki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50273678)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Hiroshi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90252676)
SUGIMOTO Hisashi Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (90127241)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Circulatory shock / Cytokine / Oxygen delivery / Oxygen consumption / Sepsis / サイトカイン / Interleukin-1β / 低体温 |
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| Research Abstract |
When systemic oxygen delivery (DO_2)is reduced, oxygen consumption(VO_2)is maintained until a critical level is reached (DO_2crit). Sepsis is thought to shift DO_2crit to the right and lengthen the supply-dependent portion. We tested the effect of interleukin(IL)-1β, which is one of the key cytokines related to sepsis, on the VO_2/DO_2 relationship. Rabbits were subjected to stepwise cardiac tamponade to reduce DO_2 by inflating a handmade balloon placed into the pericardial sac. Seven rabbits were given 10 μg/kg of IL-1β intravenously prior to the graded cardiac tamponade. The remainder(n = 8)received saline alone(control group). The VO_2/DO_2 relationship was analyzed by the dual-line method. IL-1β significantly decreased mean arterial pressure(65±11 mmHg from baseline 85±7 mmHg)without altering cardiac output. The IL-1β group showed significantly steeper supply-independent line slopes than did the control group(0.19±0.02 vs.0.11 ±0.02, respectively). The IL-1β group also showed grea
… More
ter PO_2 and plasma lactate levels in the portal vein than did the control group. These results indicate that IL-1β impairs systemic oxygen uptake even before VO_2 becomes supply-dependent, presumably due to maldistribution of the blood flow including the splanchnic circulation. Subsequently, we investigated the inotropic effect of dopamine on the VO_2/DO_2 abnormality induced by IL-1β. Twelve rabbits were divided into two groups(n = 6, each)and given 10 μg/kg of IL-1β or saline(control group)intravenously. After baseline measurements, dopamine was continuously infused at a rate of 20 μg/kg/min throughout the study in both groups. Dopamine failed to restore IL-1β-induced decrease in mean arterial pressure(72±9 mmHg)to baseline level(91±5 mmHg). Dopamine increased cardiac output ant DO_2, but did not affect VO_2. The IL-1β group showed significant greater slopes of the supply-independent line than the control group (IL-1β : y = 0.14 x + 6.3, control : y = 0.06 x + 8.6)during the stepwise decrease in DO_2. These results indicate that the continuous infusion of dopamine at 20 μg/kg/min increased DO_2, but failed either to improve the vasomotor disturbance or to restore the VO_2/DO_2 abnormality induced by IL-1β. Less
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