Heart and Trauma Research Laboratory, College of Medicine and Dentistry, James Cook University, Queensland, Australia.
Shock. 2022 Feb 1;57(2):264-273. doi: 10.1097/SHK.0000000000001886.
Excessive sympathetic outflow following trauma can lead to cardiac dysfunction, inflammation, coagulopathy, and poor outcomes. We previously reported that buprenorphine analgesia decreased survival after hemorrhagic trauma. Our aim is to examine the underlying mechanisms of mortality in a non-compressible hemorrhage rat model resuscitated with saline or adenosine, lidocaine, magnesium (ALM). Anesthetized adult male Sprague-Dawley rats were randomly assigned to Saline control group or ALM therapy group (both n = 10). Hemorrhage was induced by 50% liver resection. After 15 min, 0.7 mL/kg 3% NaCl ± ALM intravenous bolus was administered, and after 60 min, 0.9% NaCl ± ALM was infused for 4 h (0.5 mL/kg/h) with 72 h monitoring. Animals received 6-12-hourly buprenorphine for analgesia. Hemodynamics, heart rate variability, echocardiography, and adiponectin were measured. Cardiac tissue was analyzed for adrenergic/cholinergic receptor expression, inflammation, and histopathology. Four ALM animals and one Saline control survived to 72 h. Mortality was associated with up to 97% decreases in adrenergic (β-1, α-1A) and cholinergic (M2) receptor expression, cardiac inflammation, myocyte Ca2+ loading, and histopathology, indicating heart ischemia/failure. ALM survivors had higher cardiac output and stroke volume, a 30-fold increase in parasympathetic/sympathetic receptor expression ratio, and higher circulating adiponectin compared to Saline controls. Paradoxically, Saline cardiac adiponectin hormone levels were higher than ALM, with no change in receptor expression, indicating intra-cardiac synthesis. Mortality appears to be a "systems failure" associated with CNS dysregulation of cardiac function. Survival involves an increased parasympathetic dominance to support cardiac pump function with reduced myocardial inflammation. Increased cardiac α-1A adrenergic receptor in ALM survivors may be significant, as this receptor is highly protective during heart dysfunction/failure.
创伤后过度的交感神经输出可导致心功能障碍、炎症、凝血异常和预后不良。我们之前的研究报告表明，丁丙诺啡镇痛会降低失血性创伤后的存活率。我们的目的是在使用生理盐水或腺苷、利多卡因、镁（ALM）复苏的非可压缩性出血大鼠模型中研究死亡率的潜在机制。成年雄性 Sprague-Dawley 大鼠被随机分为生理盐水对照组或 ALM 治疗组（每组 n=10）。通过 50%肝切除术诱导出血。15 分钟后，给予 0.7mL/kg 的 3%生理盐水±ALM 静脉推注，60 分钟后，输注 0.9%生理盐水±ALM 4 小时（0.5mL/kg/h），并进行 72 小时监测。动物接受 6-12 小时的丁丙诺啡镇痛。测量血流动力学、心率变异性、超声心动图和脂联素。分析心脏组织中的肾上腺素能/胆碱能受体表达、炎症和组织病理学。4 只 ALM 动物和 1 只生理盐水对照组动物存活至 72 小时。死亡率与肾上腺素能（β-1、α-1A）和胆碱能（M2）受体表达、心脏炎症、心肌 Ca2+负荷和组织病理学的减少高达 97%相关，表明心肌缺血/衰竭。与生理盐水对照组相比，ALM 幸存者的心脏输出量和每搏量更高，副交感神经/交感神经受体表达比值增加了 30 倍，循环脂联素水平更高。矛盾的是，生理盐水心脏脂联素激素水平高于 ALM，但受体表达没有变化，表明心脏内合成。死亡率似乎是一种与中枢神经系统对心脏功能失调相关的“系统故障”。存活涉及增加副交感神经优势，以支持心脏泵功能，同时减少心肌炎症。ALM 幸存者的心脏α-1A 肾上腺素能受体增加可能具有重要意义，因为这种受体在心脏功能障碍/衰竭期间具有高度保护作用。
