Inhalation of hydrogen improves myocardial function and survival outcomes in a porcine model of prolonged cardiac arrest

doi:10.3877/cma.j.issn.2095-9133.2017.02.006

Abstract

Abstract:

Objective

To investigate the beneficial effect of hydrogen(H₂)on myocardial dysfunction after cardiopulmonary resuscitation (CPR) in a pig model with a prolonged cardiac arrest.

Methods

Healthy domestic pigs were subjected to 10 minutes of ventricular fibrillation cardiac arrest induced electrically and followed by CPR. After achieving the return of spontaneous circulation (ROSC), the post-cardiac arrest pigs were randomized into two groups: mechanically ventilated with room air (control group); mechanically ventilated with 2% H₂(H₂∶O₂∶N₂=2%∶21%∶77%)for 2 hours after ROSC and turned to ventilate with room air (H₂ group). Hemodynamic parameters including HR, MAP, left ventricular pressure derivative (±dp/dt_max) and cardiac index (CI) were recorded for 6 hours continually after successful resuscitation. Arterial blood gas, lactate and serum marker of myocardial injury (cTnT and NT-pro-BNP) were measured at baseline, and at 0.5, 2, 4 and 6 hours after CPR. The survival outcomes of animals were evaluated and recorded until 96 hours after CPR.

Results

Worse post-resuscitation myocardial function was found in both groups compared to the status prior to CA, but the myocardial function of the H₂ group was superior to that of the control group. The indicators of myocardial function in the H₂ group especially at 5 hours and 6 hours after CPR [+ dp/dt_max: (3320.1±433.4)mmHg/s and (3294.5±390.4)mmHg/s; -dp/dt_max: (3756.1±498.8)mmHg/s and (3667.4±406.8)mmHg/s; CI: (6.8±1.0) L/min·m² and(6.7±1.2)L/min·m²] were much better than those of the control group at the same time points [+ dp/dt_max: (2863.5±340.8)mmHg/s and(2925.2±251.3) mmHg/s; -dp/dt_max: (3245.4±259.6)mmHg/s and (3261.9±311)mmHg/s; CI: (5.3±1.5)L/min·m² and(5.1±1.4)L/min·m²](all P<0.05). At 4 hours and 6 hours after CPR, the serum levels of cTnT and NT-pro-BNP in H₂ group [cTnT: (2.7±0.9)ng/mL and (2.7±0.8)ng/mL; NT-pro-BNP: (0.34±0.13)ng/mL and(0.37±0.17)ng/mL] were obviously lower compared to the control group [cTnT: (4.9±1.2)ng/mL and (5.8±1.2)ng/mL; NT-pro-BNP: (0.54±0.12)ng/mL and(0.78±0.21)ng/mL](all P<0.05). In addition, greater survival duration was also observed in H₂ group compared to the control group [96(25, 96)hours vs. 16(12, 22)hours, P<0.05].

Conclusion

Inhalation of H₂ improves post-resuscitation myocardial dysfunction and survival outcomes in a porcine model with prolonged cardiac arrest.

Key words: Cardiac arrest, Cardiopulmonary resuscitation, Myocardial dysfunction, Hydrogen

Cai Wen, Tao Yu, Xiaozhu Zhai, Zhengfei Yang, Longyuan Jiang, Wanchun Tang. Inhalation of hydrogen improves myocardial function and survival outcomes in a porcine model of prolonged cardiac arrest[J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2017, 03(02): 92-97.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhwsyjdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-9133.2017.02.006

https://zhwsyjdzzz.cma-cmc.com.cn/EN/Y2017/V03/I02/92

Figures/Tables 10

References 16

1	Meyer L, Stubbs B, Fahrenbruch C, et al.Incidence, causes, and survival trends from cardiovascular-related sudden cardiac arrest in children and young adults 0 to 35 years of age a 30-year review[J]. Circulation, 2012, 126(126): 1363-1372.
2	Kazaure HS, Roman SA, Sosa JA.Epidemiology and outcomes of in-hospital cardiopulmonary resuscitation in the United States, 2000-2009[J]. Resuscitation, 2013, 84(9): 1255-1260.
3	Laver S, Farrow C, Turner D, et al.Mode of death after admission to an intensive care unit following cardiac arrest[J]. Intensive Care Med, 2004, 30(11): 2126-2128.
4	Nolan JP, Neumar RW, Adrie C, et al.Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication: A scientific statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care；the Council on Clinical Cardiology; the Council on Stroke[J]. Resuscitation, 2008, 79(3): 350-379.
5	Zheng XF, Sun XJ, Xia ZF.Hydrogen resuscitation, a new cytoprotective approach[J]. Clin Exp Pharmacol Physiol, 2011, 38(3): 155-163.
6	Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine[J]. Pharmacol Ther, 2014, 144(1): 1-11.
7	Hayashida K, Sano M, Kamimura N, et al.H(2) gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model[J]. J Am Heart Assoc, 2012, 1(5): e003459.
8	Wang P, Jia L, Chen B, et al.Hydrogen inhalation is superior to mild hypothermia in improving cardiac function and neurological outcome in an asphyxial cardiac arrest model of rats[J]. Shock, 2016, 46(3): 312-318.
9	Konietzke D, Gervais H, Dick W, et al.Models and methods in animal experiments in resuscitation[J]. Der Anaesthesist, 1988, 37(3): 140-149.
10	Von PI, Weil MH, Von PM, et al.Cardiopulmonary resuscitation in the rat[J]. J App Physiol, 1988, 65(6): 2641-2647.
11	van Alem AP, Vrenken RH, de Vos R, et al.Use of automated external defibrillator by first responders in out of hospital cardiac arrest: prospective controlled trial[J]. BMJ, 2003, 327(7427): 1312.
12	Kern KB, Hilwig RW, Berg RA, et al.Postresuscitation left ventricular systolic and diastolic dysfunction.Treatment with dobutamine[J]. Circulation, 1997, 95(12): 2610-2613.
13	Kern KB, Hilwig RW, Rhee KH, et al.Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning[J]. J Am Coll Cardiol, 1996, 28(1): 232-240.
14	Laurent I, Monchi M, Chiche JD, et al.Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest[J]. J Am Coll Cardiol, 2002, 40(12): 2110-2116.
15	Ruiz-Bailén M, Aguayo de Hoyos E, Ruiz-Navarro S, et al.Reversible myocardial dysfunction after cardiopulmonary resuscitation[J]. Resuscitation, 2005, 66(2): 175-181.
16	Ohsawa I, Ishikawa M, Takahashi K, et al.Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals[J]. Nat Med, 2007, 13(6): 688-694.

组别	动物数(只)	体重(kg)	心率(次/min)	MAP(mmHg)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)	CPR时长(min)	总除颤次数(次)	肾上腺素总用量(μg)
氢气组	9	38.3±1.5	122±18	115.7±13.0	7.47±0.07	79.3±8.9	35.6±3.8	0.9±0.4	6.4±0.9	1.8±0.7	960±352
对照组	9	37.3±2.5	128±18	112.1±14.3	7.45±0.05	81.2±13.5	34.5±5.0	1.2±0.6	6.7±1.0	2.0±1.1	1040±400
t值	－	－1.01	0.74	1.04	－0.88	－0.35	－0.49	0.81	0.50	1.02	0.50
P值	－	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05

组别	动物数(只)	体重(kg)	心率(次/min)	MAP(mmHg)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)	CPR时长(min)	总除颤次数(次)	肾上腺素总用量(μg)
氢气组	9	38.3±1.5	122±18	115.7±13.0	7.47±0.07	79.3±8.9	35.6±3.8	0.9±0.4	6.4±0.9	1.8±0.7	960±352
对照组	9	37.3±2.5	128±18	112.1±14.3	7.45±0.05	81.2±13.5	34.5±5.0	1.2±0.6	6.7±1.0	2.0±1.1	1040±400
t值	－	－1.01	0.74	1.04	－0.88	－0.35	－0.49	0.81	0.50	1.02	0.50
P值	－	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05	>0.05

组别	PR 0.5 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.33 ± 0.08	80 ± 13	39 ± 6	9.5 ± 3.8
对照组	9	7.35 ± 0.15	77 ± 8	42 ± 4	8.6 ± 2.9
统计值	－	0.32	－0.56	1.08	－0.57
P值	－	>0.05	>0.05	>0.05	>0.05
组别	PR 2 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.38 ± 0.09	79 ± 9	36 ± 3	2.9 ± 1.5
对照组	9	7.43 ± 0.06	80 ± 10	37 ± 4	3.0 ± 1.7
统计值	－	1.49	0.17	0.58	0.17
P值	－	>0.05	>0.05	>0.05	>0.05
组别	PR 4 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.47 ± 0.11	83±12	41 ± 5	1.9 ± 0.8
对照组	9	7.42 ± 0.07	77 ± 12	38 ± 4	2.4 ± 0.9
统计值	－	－0.69	－0.98	－1.43	1.06
P值	－	>0.05	>0.05	>0.05	>0.05
组别	PR 6 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.46 ± 0.07	84 ± 6	38 ± 3	1.6 ±1.3
对照组	9	7.44 ± 0.09	83 ± 11	37 ± 5	1.9 ± 1.0
统计值	－	－0.38	－0.23	－0.32	0.54
P值	－	>0.05	>0.05	>0.05	>0.05

组别	PR 0.5 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.33 ± 0.08	80 ± 13	39 ± 6	9.5 ± 3.8
对照组	9	7.35 ± 0.15	77 ± 8	42 ± 4	8.6 ± 2.9
统计值	－	0.32	－0.56	1.08	－0.57
P值	－	>0.05	>0.05	>0.05	>0.05
组别	PR 2 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.38 ± 0.09	79 ± 9	36 ± 3	2.9 ± 1.5
对照组	9	7.43 ± 0.06	80 ± 10	37 ± 4	3.0 ± 1.7
统计值	－	1.49	0.17	0.58	0.17
P值	－	>0.05	>0.05	>0.05	>0.05
组别	PR 4 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.47 ± 0.11	83±12	41 ± 5	1.9 ± 0.8
对照组	9	7.42 ± 0.07	77 ± 12	38 ± 4	2.4 ± 0.9
统计值	－	－0.69	－0.98	－1.43	1.06
P值	－	>0.05	>0.05	>0.05	>0.05
组别	PR 6 h
组别	动物数(只)	pH值	PaO₂(mmHg)	PaCO₂(mmHg)	乳酸(mmol/L)
氢气组	9	7.46 ± 0.07	84 ± 6	38 ± 3	1.6 ±1.3
对照组	9	7.44 ± 0.09	83 ± 11	37 ± 5	1.9 ± 1.0
统计值	－	－0.38	－0.23	－0.32	0.54
P值	－	>0.05	>0.05	>0.05	>0.05

[1]	Yingying Kong, Lutao Xie, Xiaochi Lu, Jiefeng Xu, Guangju Zhou, Mao Zhang. Protective effect and mechanism of sodium butyrate on cardio-brain injury after cardiac arrest resuscitation in pigs [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(05): 355-362.
[2]	Jianbiao Meng, Geng Zhang, Yanna Jiao. Exploratory study on early intestinal microecological changes in patients with sepsis-induced myocardial dysfunction [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(04): 279-285.
[3]	Hengtong Lou, Yuanqiang Lu. Risk factors of prognosis in patients with non-traumatic out-of-hospital cardiac arrest and development of a nomogram prediction model [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(03): 177-186.
[4]	Mei Yang, Chun Zhou, Aihong Zhao, Qin Wang. Construction of a risk nomograph model for plastic bronchitis caused by refractory mycoplasma pneumoniae pneumonia in children [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2023, 17(04): 274-281.
[5]	Bingtong Lu, Yingrong Hou, Yongqiang Hu, Yaxin Qi. Clinical analysis of serum lactate dehydrogenase, interleukin-6, procalcitonin and high-sensitivity C-reactive protein levels in evaluating the prognosis of multiple myeloma patients with bacterial infection [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2023, 17(03): 187-193.
[6]	Guohua Ren, Xiaoxiao Du, Shanling Hong, Shuai Shao. Change and significance of serum interleukin-22, hydrogen sulfide, and osteoprotegerin levels of patients with hypertensive acute kidney injury in pregnancy [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(03): 150-155.
[7]	Haiyan Xiao, Yeying Duan, Yuelin Wu, Lichan Wu, Haoke Tang. Neurologic music therapy for a maternal women with hypoxia-ischemias encephalopathy after cardiac arrest: a case report [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(02): 217-224.
[8]	Min Sun. Value of blood amylase, C-reactive protein, procalcitonin, and lactate dehydrogenase in the evaluation and prognosis prediction of acute pancreatitis patients [J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(05): 331-336.
[9]	Minjie Zhang, Xiaoshan Zhang, Shasha Duan, Yilu Shi, Jie Zhao, Tianhao Bai, Yaxi Wang. Hydrogen for treatment of myocardial ischemia-reperfusion injury: mechanism and prospect [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 744-748.
[10]	Yang Yu, Xiaojie Liu, LiJuan Wang, Yuchen Gao, Yao Ding, Hushan Ao. Training model for cardiopulmonary resuscitation under the background of regular control of COVID-19 [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(04): 483-486.
[11]	Xue Wang, Jiayin Xu, Lijuan Liao, Ganrong Huang, Yongyi Huang, Xian Wei, Yanqiang Huang, Liang Huang. Emodin enhances succinate dehydrogenase activity and oxidation in Cryptococcus neoformans [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(03): 314-319.
[12]	Yalin Han, Ding Luo, Pengfei Cheng, Ming Zhou, Hua Zhang. Quality of life of caregivers of cardiac arrest survivors [J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(09): 847-850.
[13]	Zheng Ni, Yinghua Zhu. Progress in research of video-assisted dispatcher-guided extramural cardiopulmonary resuscitation [J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(09): 842-846.
[14]	Yixin Wang, Pingjing Zheng, Xianxiong Huang, Yang Bai, Guoguo Du, Hua Zhang. Intention of bystanders to perform cardiopulmonary resuscitation: a review [J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(09): 828-832.
[15]	Donglan Mei, Shouyi Ling, Bing Mei, Guangliang Shao, Zhihui Sun. Application value of sequential pre-hospital automatic cardiopulmonary resuscitation machine and marrow infusion in rescuing patients with cardiac arrest [J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2023, 09(03): 159-162.

Please choose a citation manager

Content to export