经食道降温对猪复苏后肺损伤及全身性炎症反应的影响

The effects of esophageal cooling on lung injury and systemic inflammatory response after cardiopulmonary resuscitation in swine

目的探讨经食道降温对猪心肺复苏后肺损伤及全身性炎症反应的影响。方法采用随机数字表法将32头国产雄性白猪分为假手术组(S组,n=5)、正常温度组(NT组,n=9)、体表降温组(SC组,n=9)与食道降温组(EC组,n=9)。S组仅进行动物准备,其余3组通过8 min心室颤动与5 min心肺复苏的方法制备心肺复苏模型。S组和NT组使用控温毯全程维持(38.0±0.5)℃。复苏后5 min时,SC组和EC组分别经体表控温毯与食道降温导管降温和维持在33℃持续24 h,再以1℃/h复温5 h。复苏后1、6、12、24、30 h时检测血管外肺水指数(extra-vascular lung water index,ELWI)、肺血管通透性指数(pulmonary vascular permeability index,PVPI),采集动脉血检测氧合指数(oxygenation index,OI),采集静脉血检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)与白细胞介素-6(inerleukin-6,IL-6)的血清水平。复苏后30 h时处死动物,检测肺组织TNF-α、IL-6、丙二醛含量及超氧化物歧化酶(superoxide dismutase,SOD)活性。结果复苏后,EC组较SC组诱导低温的速率加快(2.8 vs.1.5℃/h,P<0.05),同等效率地维持低温及复温。与NT组相比,EC组在复苏6 h后、SC组在复苏12 h后的ELWI与PVPI降低,OI升高(均P<0.05)。与SC组相比,EC组在复苏12 h后的ELWI与PVPI下降、OI增加[ELWI:12 h为(13.4±3.1)vs.(16.8±2.7)mL/kg,24 h为(12.4±3.0)vs.(16.0±3.6)mL/kg,30 h为(11.1±2.4)vs.(13.9±1.9)mL/kg;PVPI:12 h为3.7±0.9 vs. 5.0±1.1,24 h为3.4±0.8 vs. 4.6±1.0,30 h为3.1±0.7 vs. 4.2±0.7;OI:12 h为(470±41)vs.(417±42)mm Hg(1 mm Hg=0.133 kPa),24 h为(462±39)vs.(407±36)mm Hg,30 h为(438±60)vs.(380±33)mm Hg;均P<0.05]。与NT组相比,SC组与EC组在复苏6 h后TNF-α与IL-6的血清水平降低(P<0.05)。与SC组相比,EC组在复苏6 h后IL-6与复苏12 h后TNF-α的血清水平下降[IL-6:6 h为(299±23)vs.(329±30)pg/mL,12 h为(336±35)vs.(375±30)pg/mL,24 h为(297±29)vs.(339±36)pg/mL,30 h为(255±20)vs.(297±33)pg/mL;TNF-α:12 h为(519±46)vs.(572±49)pg/mL,24 h为(477±77)vs.(570±64)pg/mL,30 h为(436±49)vs.(509±51)pg/mL;均P<0.05]。与NT组相比,SC组与EC组肺组织TNF-α、IL-6、丙二醛含量减少及SOD活性升高(P<0.05)。与SC组相比,EC组肺组织炎症反应与氧化应激损伤进一步减轻[TNF-α:(557±155)vs.(782±154)pg/mg prot;IL-6:(616±134)vs.(868±143)pg/mg prot;丙二醛:(4.95±1.53)vs.(7.53±1.77)nmol/mg prot;SOD:(3.18±0.74)vs.(2.14±1.00)U/mg prot;均P<0.05]。结论复苏后经食道降温较传统体表降温法能快速地诱导治疗性亚低温,减轻复苏后肺损伤与全身性炎症反应。

Objective To investigate the effects of esophageal cooling(EC) on lung injury and systemic inflammatory response after cardiopulmonary resuscitation in swine. Methods Thirty-two domestic male white pigs were randomly divided into sham group(S group, n=5), normothermia group(NT group, n=9), surface cooling group(SC group, n=9), and EC group(n=9). The animals in the S group only experienced the animal preparation. The animal model was established by 8 min of ventricular fibrillation and then 5 min of cardiopulmonary resuscitation in the other three groups. A normal temperature of(38.0±0.5)℃ was maintained by surface blanket throughout the experiment in the S and NT groups. At 5 min after resuscitation, therapeutic hypothermia was implemented via surface blanket or EC catheter to reach a target temperature of 33℃, and then maintained until 24 h post resuscitation, and followed by a rewarming rate of1℃/h for 5 h in the SC and EC groups. At 1, 6, 12, 24 and 30 h after resuscitation, the values of extra-vascular lung water index(ELWI) and pulmonary vascular permeability index(PVPI) were measured, and meanwhile arterial blood samples were collected to measure the values of oxygenation index(OI) and venous blood samples were collected to measure the serum levels of tumor necrosis factor-α(TNF-α) and inerleukin-6(IL-6). At 30 h after resuscitation, the animals were euthanized, and then the lung tissue contents of TNF-α, IL-6 and malondialdehyde, and the activities of superoxide dismutase(SOD) were detected. Results After resuscitation, the induction of hypothermia was significantly faster in the EC group than that in the SC group(2.8 vs. 1.5℃/h, P<0.05), and then its maintenance and rewarming were equally achieved in the two groups. The values of ELWI and PVPI significantly decreased and the values of OI significantly increased from 6 h after resuscitation in the EC group and from 12 h after resuscitation in the SC group compared with the NT group(all P<0.05). Additionally, the values of ELWI and PVPI were significantly lower and the values of OI were significantly higher from 12 h after resuscitation in the EC group than those in the SC group [ELWI:(13.4±3.1) vs.(16.8±2.7) mL/kg at 12 h,(12.4±3.0) vs.(16.0±3.6) mL/kg at 24 h,(11.1±2.4) vs.(13.9±1.9) mL/kg at 30 h;PVPI: 3.7±0.9 vs. 5.0±1.1 at 12 h, 3.4±0.8 vs. 4.6±1.0 at 24 h, 3.1±0.7 vs. 4.2±0.7 at 30 h;OI:(470±41) vs.(417±42) mm Hg(1 mm Hg=0.133 kPa) at 12 h,(462±39) vs.(407±36) mm Hg at 24 h,(438±60) vs.(380±33) mm Hg at 30 h;all P<0.05]. The serum levels of TNF-α and IL-6 significantly decreased from 6 h after resuscitation in the SC and EC groups compared with the NT group(all P<0.05). Additionally, the serum levels of IL-6 from 6 h after resuscitation and the serum levels of TNF-αfrom 12 h after resuscitation were significantly lower in the EC group than those in the SC group [IL-6:(299±23) vs.(329±30) pg/mL at 6 h,(336±35) vs.(375±30) pg/mL at 12 h,(297±29) vs.(339±36) pg/mL at 24 h,(255±20) vs.(297±33)pg/mL at 30 h;TNF-α:(519±46) vs.(572±49) pg/mL at 12 h,(477±77) vs.(570±64) pg/mL at 24 h,(436±49) vs.(509±51)pg/mL at 30 h;all P<0.05]. The contents of TNF-α, IL-6, and malondialdehyde significantly decreased and the activities of SOD significantly increased in the SC and EC groups compared with the NT group(all P<0.05). Additionally, lung inflammation and oxidative stress were further significantly alleviated in the EC group compared with the SC group[TNF-α:(557±155) vs.(782±154) pg/mg prot;IL-6:(616±134) vs.(868±143) pg/mg prot;malondialdehyde:(4.95±1.53) vs.(7.53±1.77) nmol/mg prot;SOD:(3.18±0.74) vs.(2.14±1.00) U/mg prot;all P<0.05]. Conclusion Therapeutic hypothermia could be rapidly induced by EC after resuscitation, and further significantly alleviated post-resuscitation lung injury and systemic inflammatory response compared with conventional surface cooling.