Effects of hypothermia on the liver in a swine model of cardiopulmonary resuscitation

doi:10.5847/wjem.j.issn.1920-8642.2013.04.011

Abstract

Abstract:

BACKGROUND: The study aimed to explore the effects of hypothermia state induced by 4 ºC normal saline (NS) on liver biochemistry, enzymology and morphology after restoration of spontaneous circulation (ROSC) by cardiopulmonary resuscitation (CPR) in swine.
METHODS: After 4 minutes of ventricular fibrillation (VF), standard CPR was carried out. Then the survivors were divided into two groups: low temperature group and normal temperature group. The low temperature (LT) group (n=5) received continuously 4 ºC NS at the speed of 1.33 mL/kg per minute for 22 minutes, then at the speed lowering to 10 mL/kg per hour. The normal temperature (NT) group (n=5) received NS with normal room temperature at the same speed of the LT group. Hemodynamic status and oxygen metabolism were monitored and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured in blood samples obtained at baseline and at 10 minutes, 2 hours and 4 hours after ROSC. At 24 hours after ROSC, the animals were killed and the liver was removed to determine the Na⁺-K⁺-ATPase and Ca²⁺-ATPase enzyme activities and histological changes under a light or electron microscope.
RESULTS: Core temperature was decreased in the LT group (P<0.05), while HR, MAP and CPP were not significantly decreased (P>0.05) compared with the NT group (P>0.05). The oxygen extraction ratio was lower in the LT group than in the NT group (P<0.05). The serum levels of ALT, AST and LDH increased in both groups but not significantly in the LT group. The enzyme activity of liver ATP was much higher in the LT group (Na⁺-K⁺-ATP enzyme: 8.64±3.32 U vs. 3.28±0.71 U; Ca²⁺-ATP enzyme: 10.92±2.12 U vs. 2.75±0.78 U, P<0.05). The LT group showed less cellular edema, inflammation and few damaged mitochondria as compared with the NT group.
CONCLUSION: These data suggested that infusing 4 ºC NS continuously after ROSC could quickly lower the core body temperature, while maintaining a stable hemodynamic state and balancing oxygen metabolism, which protect the liver in terms of biochemistry, enzymology and histology after CPR.

Key words: Therapeutic hypothermia, Cardiac arrest, Liver, Hemodynamics

Yi Han, Zhen-ju Song, Chao-yang Tong, Chun-sheng Li. Effects of hypothermia on the liver in a swine model of cardiopulmonary resuscitation[J]. World Journal of Emergency Medicine, 2013, 4(4): 298-303.

Figures/Tables 5

Figure 1.

Table 1

Table 2

Figure 2.

Figure 3.

References 15

1	Geocadin RG, Ritzl EK. Seizures and status epilepticus in post cardiac arrest syndrome: therapeutic opportunities to improve outcome or basis to withhold life sustaining therapies? Resuscitation 2012; 83:791-792. pmid: 22513351
2	Zeiner A, Holzer M, Sterz F, Behringer W, Schörkhuber W, Müllner M, et al. Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group. Stroke 2000; 31:86-94. doi: 10.1161/01.str.31.1.86 pmid: 10625721
3	Choi S, Noh J, Hirose R, Ferell L, Bedolli M, Roberts JP, et al. Mild hypothermia provides significant protection against ischemia/reperfusion injury in livers of obese and lean rats. Ann Surg 2005; 241:470-476. doi: 10.1097/01.sla.0000154259.73060.f1 pmid: 15729070
4	Kulstad EB, Courtney MD, Waller D. Induction of therapeutic hypothermia via the esophagus: a proof of concept study. World J Emerg Med 2012; 3:118-122. pmid: 25215049
5	Stadlbauer KH, Rheinberger K, Wenzel V, Raedler C, Krismer AC, Strohmenger HU, et al. The effects of nifedipine on ventricular fibrillation mean frequency in a porcine model of prolonged cardiopulmonary resuscitation. Anesth Analg 2003; 97:226-230. pmid: 12818971
6	Nordmark J, Rubertsson S. Induction of mild hypothermia with infusion of cold (4 degrees C) fluid during ongoing experimental CPR. Resuscitation 2005; 66:357-365. doi: 10.1016/j.resuscitation.2005.04.002 pmid: 16081199
7	Kulstad EB, Courtney DM, Waller D. Induction of therapeutic hypothermia via the esophagus: a proof of concept study. World J Emerg Med 2012; 3:118-122. doi: 10.5847/wjem.j.issn.1920-8642.2012.02.007 pmid: 25215049
8	Post H, Schmitto JD, Steendijk P, Christoph J, Holland R, Wachter R, et al. Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction. Acta Physiol (Oxf) 2010; 199:43-52. doi: 10.1111/aps.2010.199.issue-1
9	Vijlbrief DC, Benders MJ, Kemperman H, van Bel F, de Vries WB. Cardiac biomarkers as indicators of hemodynamic adaptation during postasphyxial hypothermia treatment. Neonatology 2012; 102:243-248. doi: 10.1159/000339117 pmid: 22907615
10	Gundersen Y, Vaagenes P, Pharo A, Valø ET, Opstad PK. Moderate hypothermia blunts the inflammatory response and reduces organ injury after acute haemorrhage. Acta Anaesthesiol Scand 2001; 45:994-1001. doi: 10.1034/j.1399-6576.2001.450812.x pmid: 11576051
11	Westermann S, Vollmar B, Thorlacius H, Menger MD. Surface cooling inhibits tumor necrosis factor-alpha-induced microvascular perfusion failure, leukocyte adhesion, and apoptosis in the striated muscle. Surgery 1999; 126:881-889. pmid: 10568188
12	Zhang C, Gao GR, Jiang HY, Lv CG, Zhang BL, Xie MS, et al. Effects of environmental hypothermia on hemodynamics and oxygen dynamics in a conscious swine model of hemorrhagic shock. World J Emerg Med 2012; 3:128-134. doi: 10.5847/wjem.j.issn.1920-8642.2012.02.009 pmid: 25215051
13	Hildebrand F, Giannoudis PV, van Griensven M, Chawda M, Pape HC. Pathophysiologic changes and effects of hypothermia on outcome in elective surgery and trauma patients. Am J Surg 2004; 187:363-371. doi: 10.1016/j.amjsurg.2003.12.016 pmid: 15006564
14	Peliowski-Davidovich A; Canadian Paediatric Society, Fetus and Newborn Committee. Hypothermia for newborns with hypoxic ischemic encephalopathy. Paediatr Child Health 2012; 17:41-46. pmid: 23277757
15	Lauriat S, Linas SL. The role of neutrophils in acute renal failure. Semin Nephrol 1998; 18:498-504. pmid: 9754602

Parameters	n	Baseline	ROSC
Parameters	n	Baseline	10 min	2 h	4 h
AST (U/L)
NT	5	66.00±8.60	116.25±15.65^*	141.75±8.14^#	175.00±14.31^#
LT	5	69.50±12.04	114.75±3.82^#	119.75±6.95^#	126.25±11.15^#?
ALT (U/L)
NT	5	44.25±7.37	49.75±3.10	50.25±4.99	52.00±5.89
LT	5	40.00±6.68	42.50±10.38	42.75±9.54	46.00±8.76^?
LDH (U/L)
NT	5	672.25±90.60	829.25±74.20	1010.75±143.87^*	1240.00±116.62^#
LT	5	640.75±52.81	699.00±82.00	705.75±51.33^?	984.00±68.72^?

Parameters	n	ROSC 24 h
Na⁺-K⁺-ATP enzyme (U)
NT	5	3.274±0.710
LT	5	8.614±3.317^*
Ca²⁺-ATP enzyme (U)
NT	5	2.746±0.778
LT	5	10.918±2.122^#

[1]	Young Min Kim, Hyun Seok Chai, Gwan Jin Park, Sang Chul Kim, Hoon Kim, Seok Woo Lee, Hyeon Jeong Park, Han Bit Kim, Hyo Been Lee, Ji Han Lee. Effect of bag valve ventilation versus mechanical ventilation after endotracheal intubation during cardiopulmonary resuscitation on outcomes following out-of-hospital cardiac arrest: a propensity score analysis [J]. World Journal of Emergency Medicine, 2025, 16(4): 313-320.
[2]	Rui Shao, Chenchen Hang, Xingsheng Wang, Luying Zhang, Fei Shao, Ziren Tang. The “SOOTEST-ICU” bundle for optimizing cerebral hypoxia and reperfusion to minimize brain injury after resuscitation from cardiac arrest [J]. World Journal of Emergency Medicine, 2025, 16(3): 206-211.
[3]	Jie Chen, Zhonghao Li, Xiaoyu Liu, Tianpeng Hu, Nan Gao, Weijian Zhang, Guoqiang Zhang. Potential common key genes associated with myocardial dysfunction and brain injury following cardiac arrest resuscitation in a rat model [J]. World Journal of Emergency Medicine, 2025, 16(3): 231-238.
[4]	Tingting Xu, Shaokun Wang, Liqiang Zhao, Jiawen Wang, Jihong Xing. A two-sample Mendelian randomization study on the relationship of body weight, body mass index, and waist circumference with cardiac arrest [J]. World Journal of Emergency Medicine, 2025, 16(2): 129-135.
[5]	Wachira Wongtanasarasin, Daniel K. Nishijima, Wanrudee Isaranuwatchai, Jeffrey S. Hoch. Real-world cost-effectiveness of targeted temperature management in out-of-hospital cardiac arrest survivors: results from an academic medical center [J]. World Journal of Emergency Medicine, 2025, 16(1): 28-34.
[6]	Qiang Sun, Haoze Cao, Xuesong Bai, Xin Han, Wanlu You, Zhongquan Sun, Yixin Zhang, Xiaochang Wu, Feng Fang, Fan Wu, Lianyue Yang, Sheng Yan, Yuan Ding, Weilin Wang. Adult split liver transplantation to treat liver cancer: a single-center retrospective study [J]. World Journal of Emergency Medicine, 2025, 16(1): 57-62.
[7]	Subi Abudurexiti, Shihai Xu, Zhangping Sun, Yi Jiang, Ping Gong. Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest: a prospective single-center observational study [J]. World Journal of Emergency Medicine, 2024, 15(3): 197-203.
[8]	Fengxia Du, Jun Zha, Yan Li, Lichao Fang, Shuyu Xia, Youjia Yu. Risk factors for postpartum posttraumatic stress disorder after emergency admission [J]. World Journal of Emergency Medicine, 2024, 15(2): 121-125.
[9]	Wei Zhou, Maiying Fan, Xiang Li, Fang Yu, En Zhou, Xiaotong Han. Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis [J]. World Journal of Emergency Medicine, 2024, 15(1): 35-40.
[10]	Jing Yang, Hanqi Tang, Shihuan Shao, Feng Xu, Yangyang Fu, Shengyong Xu, Chen Li, Yan Li, Yang Liu, Joseph Harold Walline, Huadong Zhu, Yuguo Chen, Xuezhong Yu, Jun Xu. A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study [J]. World Journal of Emergency Medicine, 2024, 15(1): 16-22.
[11]	Yi Shan, Yang Zhao, Chengcheng Li, Jianxin Gao, Guogeng Song, Tanshi Li. Efficacy of partial and complete resuscitative endovascular balloon occlusion of the aorta in the hemorrhagic shock model of liver injury [J]. World Journal of Emergency Medicine, 2024, 15(1): 10-15.
[12]	Rashed Alremeithi, Quincy K. Tran, Megan T. Quintana, Soroush Shahamatdar, Ali Pourmand. Approach to traumatic cardiac arrest in the emergency department: a narrative literature review for emergency providers [J]. World Journal of Emergency Medicine, 2024, 15(1): 3-9.
[13]	Gannan Wang, Zhe Wang, Yi Zhu, Zhongman Zhang, Wei Li, Xufeng Chen, Yong Mei. The neuro-prognostic value of the ion shift index in cardiac arrest patients following extracorporeal cardiopulmonary resuscitation [J]. World Journal of Emergency Medicine, 2023, 14(5): 354-359.
[14]	Guang-qi Guo, Yan-nan Ma, Shuang Xu, Hong-rong Zhang, Peng Sun. Effect of post-rewarming fever after targeted temperature management in cardiac arrest patients: a systematic review and meta-analysis [J]. World Journal of Emergency Medicine, 2023, 14(3): 217-223.
[15]	Gan-nan Wang, Zhong-man Zhang, Wen Chen, Xiao-quan Xu, Jin-song Zhang. Timing of brain computed tomography for predicting neurological prognosis in comatose cardiac arrest survivors: a retrospective observational study [J]. World Journal of Emergency Medicine, 2022, 13(5): 349-354.