Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112-1393, USA.
Shock. 2011 Jan;35(1):74-9. doi: 10.1097/SHK.0b013e3181e9aaaf.
Previous studies from our laboratory have identified a role for blunted central sympathetic activation in the acute alcohol intoxication (AAI)-induced impairment of the counterregulatory response to hemorrhagic shock (HS). Immediate fluid resuscitation (FR) with acetylcholinesterase inhibitors restores the neuroendocrine and pressor responses to FR in AAI + HS. We hypothesized this intervention would remain beneficial after delay and that restoration of mean arterial blood pressure (MABP) during FR would attenuate organ damage. Male Sprague-Dawley rats received a primed constant alcohol infusion (2.5 g · kg + 0.3 g · kg · h for 15 h) or isocaloric dextrose (DEX) before HS (40 mmHg for 60 min) and FR with lactated Ringer's (LR) solution ± physostigmine (PHYS; 100 µg · kg) immediately or after a 60-min delay after HS. Immediate LR solution elevated MABP in DEX + HS. Acute alcohol intoxication delayed the initial MABP recovery. Delayed LR solution did not further increase MABP in DEX- or AAI + HS. LR solution + PHYS increased MABP in DEX- and AAI + HS after immediate and delayed FR. No differences were noted in markers of organ dysfunction (alanine aminotransferase [ALT], aspartate aminotransferase, blood urea nitrogen, creatinine) after DEX + HS, and this was unaltered by immediate or delayed LR solution + PHYS. Acute alcohol intoxication + HS increased ALT, which was attenuated by immediate LR solution + PHYS. In contrast, delayed LR solution + PHYS exacerbated tissue injury in AAI + HS, as reflected by increased ALT, aspartate aminotransferase, blood urea nitrogen, creatinine, and liver protein carbonylation over time-matched LR solution. In conclusion, PHYS enhanced blood pressure recovery independent of time of FR and presence of AAI. However, in AAI + HS, delayed LR solution + PHYS accentuated organ damage and dysfunction. These findings suggest that although enhancing the sympathetic response can improve hemodynamic recovery during AAI, it may compromise tissue perfusion and enhance tissue injury.
先前我们实验室的研究已经确定，在急性酒精中毒（AAI）引起的出血性休克（HS）时的代偿性反应受损中，中枢交感神经激活减弱起作用。用乙酰胆碱酯酶抑制剂立即进行液体复苏（FR）可恢复 AAI + HS 时的神经内分泌和升压反应。我们假设这种干预措施在延迟后仍然有益，并且 FR 期间平均动脉血压（MABP）的恢复会减轻器官损伤。雄性 Sprague-Dawley 大鼠在 HS（60 分钟，40mmHg）和 FR 之前接受预给药的持续酒精输注（2.5g·kg + 0.3g·kg·h 共 15 小时）或等热量的右旋糖（DEX），并用乳酸林格氏液（LR）溶液+毒扁豆碱（PHYS；100μg·kg）立即或在 HS 后 60 分钟进行 FR。立即给予 LR 溶液可升高 DEX + HS 中的 MABP。急性酒精中毒延迟了初始 MABP 的恢复。延迟给予 LR 溶液并不能进一步增加 DEX 或 AAI + HS 中的 MABP。LR 溶液+PHYS 可在 DEX 和 AAI + HS 中的立即和延迟 FR 后增加 MABP。DEX + HS 后，器官功能障碍的标志物（丙氨酸氨基转移酶[ALT]，天冬氨酸氨基转移酶，血尿素氮，肌酐）无差异，且立即或延迟给予 LR 溶液+PHYS 后也无差异。急性酒精中毒+HS 增加了 ALT，这可通过立即给予 LR 溶液+PHYS 来减轻。相比之下，延迟给予 LR 溶液+PHYS 加剧了 AAI + HS 中的组织损伤，表现为随着时间的推移，ALT，天冬氨酸氨基转移酶，血尿素氮，肌酐和肝蛋白羰基化增加。总之，PHYS 增强了血压恢复，而与 FR 的时间和 AAI 的存在无关。但是，在 AAI + HS 中，延迟给予 LR 溶液+PHYS 加重了器官损伤和功能障碍。这些发现表明，尽管增强交感神经反应可以改善 AAI 期间的血液动力学恢复，但可能会损害组织灌注并加重组织损伤。
