Abnormalities in oxygen metabolism during sepsis

当全身氧供给量(DO_2)降低时，氧耗量(VO_2)将维持到一个临界值(DO_2crit)。脓毒症被认为使DO_2crit向右移动，并延长了依赖供应的部分。我们检测了与脓毒症相关的关键细胞因子之一的白介素1β对VO2/DO2关系的影响。将自制球囊置入心包囊内，逐步充气心脏充盈以降低DO2。7只兔在分级心包填塞前静脉注射10μg/kg的IL-1β。其余8例仅给予生理盐水(对照组)。用双线法分析VO2/DO2的关系。IL-1β显著降低平均动脉压(从基线的85±7毫米汞降至65±11毫米汞柱)，但不改变心输出量。IL-1β组的非供应依赖性直线斜率显著高于对照组(分别为0.19±0.02vs.0.11±0.02)。IL-1β组也显示GREA…门静脉血氧分压和血浆乳酸水平明显高于对照组。这些结果表明，IL-1β甚至在VO2变得供应依赖之前就已经损害了全身的氧摄取，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引起的VO2/DO2异常的变力作用。12只大白兔随机分为两组，每组6只，分别静脉注射10μg/kg IL-1β或生理盐水(对照组)。在基线测量后，两组在整个研究过程中以20μg/kg/分钟的速度持续注入多巴胺。多巴胺不能使IL-1β引起的平均动脉压(72±9)mm Hg恢复到基线水平(91±5 mm Hg)。在DO2递减的过程中，IL-1β组的非供给线斜率明显大于对照组(IL-1β：Y=0.14 x 6.3，对照组：Y=0.06 x 8.6)。结果表明，持续滴注20μg/kg/β的多巴胺能增加DO_2，但既不能改善血管舒缩障碍，也不能恢复IL-1 MAP所致的VO_2/DO_2异常。较少

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