Abnormalities in oxygen metabolism during sepsis

脓毒症期间氧代谢异常

• 批准号: 10671114
• 负责人: KUWAGATA Yasuyuki
• 金额: $ 2.05万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671114/
• 关键词: Circulatory shock; Cytokine; Oxygen delivery; Oxygen consumption; Sepsis; サイトカイン; Interleukin-1β; 低体温

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

当全身供氧量 (DO_2) 减少时，耗氧量 (VO_2) 将保持不变，直到达到临界水平 (DO_2crit)。脓毒症被认为会使 DO_2crit 向右移动并延长依赖供应的部分。我们测试了白细胞介素 (IL)-1β（与脓毒症相关的关键细胞因子之一）对 VO_2/DO_2 关系的影响。通过对置于心包囊中的手工气球进行充气，对兔子进行逐步心脏压塞以减少DO_2。在分级心脏压塞之前，对 7 只兔子静脉注射 10 μg/kg IL-1β。其余人（n = 8）仅接受生理盐水（对照组）。采用双线法分析VO_2/DO_2关系。 IL-1β显着降低平均动脉压（从基线85±7毫米汞柱为65±11毫米汞柱），而不改变心输出量。 IL-1β组显示出比对照组更陡的供应独立线斜率（分别为0.19±0.02和0.11±0.02）。 IL-1β 组的门静脉 PO_2 和血浆乳酸水平也高于对照组。这些结果表明，即使在 VO_2 变得依赖供应之前，IL-1β 也会损害全身摄氧量，这可能是由于包括内脏循环在内的血流分布不均所致。随后，我们研究了多巴胺对IL-1β诱导的VO_2/DO_2异常的正性肌力作用。将12只家兔分为两组（每组6只），静脉注射IL-1β或生理盐水（对照组）10 μg/kg。基线测量后，在整个研究过程中，两组均以 20 μg/kg/min 的速率持续输注多巴胺。多巴胺未能将IL-1β诱导的平均动脉压(72±9 mmHg)降低恢复至基线水平(91±5 mmHg)。多巴胺增加心输出量DO_2，但不影响VO_2。在 DO_2 逐步减少期间，IL-1β 组的供应独立线斜率显着大于对照组（IL-1β：y = 0.14 x + 6.3，对照：y = 0.06 x + 8.6）。这些结果表明，持续输注20μg/kg/min多巴胺可增加DO_2，但既不能改善血管舒缩障碍，也不能恢复IL-1β引起的VO_2/DO_2异常。较少的

项目成果

Kuwagata Y: "Interleukin-1β alters the oxygen delivery-oxygen consumption relationship in rabbits by increasing the slope of the supply-independent line"Shock. 14. 193-9 (2000)

Kuwagata Y：“Interleukin-1β 通过增加供应独立线的斜率来改变兔子的氧气输送-氧气消耗关系”Shock 14. 193-9 (2000)。

Oda J: "Mild hypothermia alters the O_2 consumption/delivery relationship by decreasing the slope of the supply-dependent line."Crit Care Med. (in press.).

Oda J：“轻度低温通过降低供应依赖线的斜率来改变 O_2 消耗/输送关系。”Crit Care Med。

Yasuyuki Kuwagata et al.: "Interleukin-1β alters the oxygen delivery-oxygen consumption relationship in rabbits by increasing the slope of the supply-independent line"Shock. (in press).

Yasuyuki Kuwagata 等人：“Interleukin-1β 通过增加供应独立线的斜率来改变兔子的氧气输送-氧气消耗关系”休克（正在出版）。

Kuwagata Y: "Interluekin-1β alters the oxygen delivery-oxygen consumption relationship in rabbits by increasing the slope of the supply-independent line."Shock. 14. 193-9 (2000)

Kuwagata Y：“Interluekin-1β 通过增加供应独立线的斜率来改变兔子的氧气输送-氧气消耗关系。”Shock 14. 193-9 (2000)

Oda J: "Mild hypothermia alters the O_2 consumption/delivery relationship by decreasing the slope of the supply-dependent line."Crit Care Med. (in press).

Oda J：“轻度低温通过降低供应依赖线的斜率来改变 O_2 消耗/输送关系。”Crit Care Med。