Impact of alcohol intoxication on hemodynamic, metabolit, and cytokine responses to hemorrhagic shock
Impact of alcohol intoxication on hemodynamic, metabolit, and cytokine responses to hemorrhagic shock
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DOI：
10.1097/00005373-200204000-00010
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发表时间：
2002-04-01
影响因子：
--
通讯作者：
Molina, PE
中科院分区：
文献类型：
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作者：
Phelan, H;Stahls, P;Molina, PE
背景：酒精中毒与创伤损伤的高发生率有关，尤其是在年轻的健康人群中。酒精中毒对损伤的直接病理生理反应的影响还没有被仔细研究。我们假设急性酒精中毒会损害失血量的动态平衡反调节，从而加重失血性休克的即刻结局。方法：慢性插管雄性SD大鼠，随机分成两组，分别给予乙醇(1.75g/kg，随后250~300 mg/kg/h)或等热量葡萄糖(3mL静注+0~375mL/h)灌胃15h。在开始定压出血和液体复苏之前，额外给予1.75g/kg的乙醇灌胃。在出血期和复苏完成时评估血流动力学、代谢、细胞因子和酸碱参数。结果：酒精中毒(血液酒精浓度135+/-12 mg/dL)动物的基础平均动脉压在基线期间(20%)和初始液体复苏后(30%)显著低于对照组(20%)。失血使动脉血HCO3和PCO2降低，PO2升高，但对动脉血pH无明显影响。酒精中毒使基线和整个出血期的二氧化碳分压降低、血氧分压升高和血pH降低变得迟钝。在对照组中，失血导致血糖和乳酸水平显著和进行性升高，而酒精中毒抑制了这一过程。失血后血浆肿瘤坏死因子-α(686+/-252pg/m L)和白介素10(178+/-25pg/m L)水平升高，而IL-6和IL-1水平无明显变化。酒精抑制失血性血浆肿瘤坏死因子-α的升高(142+/-48pg/mL)，增强失血性血浆中IL-10的升高(678+/-187pg/mL)。失血使肺组织中的肿瘤坏死因子-α、白介素1-α和白介素6的含量增加两到三倍，而对肺组织的白介素10没有显著影响。酒精可加重失血性休克大鼠肺组织中IL-1α、IL-6和IL-10水平的升高，但不影响肺组织中IL-1α、IL-6和IL-10的水平。结论：酒精中毒可引起失血性休克大鼠血流动力学和代谢反应的明显改变。此外，我们的研究结果表明，酒精调节失血性休克的早期促炎反应。综上所述，这些对出血的代谢和炎症反应的改变可能会损害即刻的结果，并容易导致组织损伤。
Background: Alcohol intoxication is associated with a high incidence of traumatic injury, particularly in the young healthy population. The impact of alcohol intoxication on the immediate pathophysiologic response to injury has not been closely examined. We hypothesized that acute alcohol intoxication would aggravate the immediate outcome from hemorrhagic shock by impairing homeostatic counterregulation to blood loss.Methods: Chronically catheterized male Sprague-Dawley rats were randomized to receive an intragastric infusion of ethyl alcohol (1.75 g/kg followed by 250-300 mg/kg/h) or isocaloric dextrose (3-mL bolus + 0-375 mL/h) for 15 hours. Before initiating fixed-pressure hemorrhage followed by fluid resuscitation, an additional intragastric bolus of ethyl alcohol (1.75 g/kg) was administered. Hemodynamic, metabolic, cytokine, and acid-base parameters were assessed during the hemorrhage period and at completion of resuscitation. Lungs were obtained for cytokine determinations.Results: Basal mean arterial pressure was significantly lower in alcohol-intoxicated (blood-alcohol concentration, 135 +/- 12 mg/dL) animals than in controls during baseline (20%) and after the initial fluid resuscitation period (30%). Hemorrhage decreased arterial HCO3 and PCO2, and increased PO2 without significant alteration in arterial blood pH. Alcohol intoxication blunted the decrease in PCO2 and increase in PO2 and decreased blood pH during baseline and throughout the course of the hemorrhage period. Hemorrhage produced marked and progressive elevations in plasma glucose and lactate levels in controls, and this was inhibited by alcohol intoxication. Hemorrhage elevated plasma tumor necrosis factor-alpha (TNF-alpha) (686 +/- 252 pg/mL) and interleukin (IL)-10 (178 +/- 25 pg/mL), and did not alter IL-6 and IL-1 levels. Alcohol blunted the hemorrhage-induced rise in plasma TNF-alpha (142 +/- 48 pg/mL) and enhanced the hemorrhage-induced increase in IL-10 (678 +/- 187 pg/mL). Hemorrhage produced a two- to threefold increase in lung content of TNF-alpha, IL-1alpha, and IL-6 without significantly altering lung IL-10. Alcohol exacerbated the hemorrhage-induced increase in lung TNF-a, and did not alter the IL-1alpha, IL-6, and IL-10 lung responses.Conclusion: These results indicate marked alterations in the hemodynamic and metabolic responses to hemorrhagic shock by alcohol intoxication. Furthermore, our findings suggest that alcohol modulates the early proinflammatory responses to hemorrhagic shock. Taken together, these alterations in metabolic and inflammatory responses to hemorrhage are likely to impair immediate outcome and predispose to tissue injury.