Hu Quan, Du Ming-Hua, Hu Sen, Chai Jia-ke, Luo Hong-Min, Hu Xiao-Han, Zhang Lin, Lin Zhi-Long, Ma Li, Wang Huan, Sheng Zhi-Yong
From the *Burns Institute and †Department of Obstetrics and Gynecology, First Hospital Affiliated to the PLA General Hospital, Beijing, China; and ‡Medical School of Chinese PLA, Beijing, China.
J Burn Care Res. 2014 Jul-Aug;35(4):e197-204. doi: 10.1097/BCR.0b013e31829afe46.
Excessive inflammation and high vasopermeability can lead to blood volume loss and tissue edema, which can affect the resuscitation and prognosis for serious burn patients. In this experiment, we investigated the effect of PNU-282987, an α7 nicotine cholinergic receptor agonist on the hemodynamic parameters and survival rate by inhibiting vasopermeability and tissue edema during the fluid resuscitation for lethal burn shock. Forty Beagle dogs with intubation of the carotid artery and jugular vein 24 hours before the injury were subjected to 50% TBSA full-thickness burns, and were randomly divided into following four groups: no resuscitation group (group NR), venous fluid resuscitation group (group R), PNU-282987 treatment group (group P), and fluid resuscitation group plus PNU-282987 group (group RP), with 10 dogs in each group. Hemodynamic variables and biochemical parameters were determined with animals in a conscious and cooperative state. The plasma volume and the vasopermeability were determined by indocyanine green and fluorescein isothiocyanate-dextran, respectively. The level of tumor necrosis factor-α and interleukin-1β in plasma, and the water content of different organs were also determined. The mean arterial pressure, cardiac output, and plasma volume of all dogs decreased significantly, and the lung extravascular water index and pulmonary vascular permeability index increased remarkably after burn. The hemodynamic parameters deteriorated continually in group N dogs, and then anuria, hyperlactacidemia, and multiple organ dysfunctions developed. The mean arterial pressure and cardiac output of dogs in group R and group RP returned to preinjury levels at 48 hours postburn. The lung extravascular water index and pulmonary vascular permeability in group R were higher than those before preinjury. The dogs in group RP were found to have a significant increase in plasma volume and urine output, and a remarkable decrease in the levels of tumor necrosis factor-α, interleukin-1α, lactic acid, and organ functions compared with those of group R (P <.05). The survival rate of RP group (100%; 10/10) was significantly higher than that of group N (0; 0/10), group P (20%; 2/10), and group R (60%; 6/10). PNU-282987 combined with intravenous fluid resuscitation significantly improved hemodynamics and the survival rate in the early period after this lethal burn shock. The mechanism may be attributable to the lowering of the level of proinflammatory mediators, amelioration of vasopermeability-induced visceral edema, less of blood volume loss, and protection of vital organs through activation of cholinergic anti-inflammatory pathway.
过度炎症反应和高血管通透性可导致血容量丢失和组织水肿，这会影响严重烧伤患者的复苏及预后。在本实验中，我们研究了α7烟碱型胆碱能受体激动剂PNU-282987在致死性烧伤休克液体复苏过程中，通过抑制血管通透性和组织水肿对血流动力学参数及存活率的影响。40只在受伤前24小时已行颈动脉和颈静脉插管的比格犬，接受50%体表面积的全层烧伤，并随机分为以下四组：未复苏组（NR组）、静脉液体复苏组（R组）、PNU-282987治疗组（P组）和液体复苏加PNU-282987组（RP组），每组10只犬。在动物清醒且合作状态下测定血流动力学变量和生化参数。分别采用吲哚菁绿和异硫氰酸荧光素-葡聚糖测定血浆容量和血管通透性。还测定了血浆中肿瘤坏死因子-α和白细胞介素-1β水平以及不同器官的含水量。所有犬烧伤后平均动脉压、心输出量和血浆容量均显著下降，肺血管外水指数和肺血管通透性指数显著升高。NR组犬的血流动力学参数持续恶化，随后出现无尿、高乳酸血症和多器官功能障碍。R组和RP组犬的平均动脉压和心输出量在烧伤后48小时恢复至伤前水平。R组的肺血管外水指数和肺血管通透性高于伤前。与R组相比，发现RP组犬的血浆容量和尿量显著增加，肿瘤坏死因子-α、白细胞介素-1α、乳酸水平及器官功能显著降低（P<0.05）。RP组的存活率（100%；10/10）显著高于NR组（0；0/10）、P组（20%；2/10）和R组（60%；6/10）。PNU-282987联合静脉液体复苏可显著改善致死性烧伤休克后早期的血流动力学和存活率。其机制可能归因于促炎介质水平降低、血管通透性所致内脏水肿减轻、血容量丢失减少以及通过激活胆碱能抗炎途径对重要器官的保护。
