Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

Wang,Guoxing; Zhang,Qian; Yuan,Wei; Wu,Junyuan; Li,Chunsheng

doi:10.3892/ijmm.2016.2737

Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

Authors:
- Guoxing Wang
- Qian Zhang
- Wei Yuan
- Junyuan Wu
- Chunsheng Li
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Affiliations: Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation (NO.BZ0370), Beijing 100020, P.R. China
Published online on: September 15, 2016 https://doi.org/10.3892/ijmm.2016.2737
Pages: 1463-1473
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham‑operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre‑treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang‑(1‑7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang‑(1‑7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre‑treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA.

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1	Lerakis S, Hayek S, Arepalli CD, Thourani V and Babaliaros V: Cardiac magnetic resonance for paravalvular leaks in post-transcatheter aortic valve replacement. Circulation. 129:e430–e431. 2014. View Article : Google Scholar : PubMed/NCBI
2	Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, et al American Heart Association Statistics Committee and Stroke Statistics Subcommittee: Heart disease and stroke statistics - 2014 update: a report from the American Heart Association. Circulation. 129:e28–e292. 2014. View Article : Google Scholar
3	Dumas F, White L, Stubbs BA, Cariou A and Rea TD: Long-term prognosis following resuscitation from out of hospital cardiac arrest: role of percutaneous coronary intervention and therapeutic hypothermia. J Am Coll Cardiol. 60:21–27. 2012. View Article : Google Scholar : PubMed/NCBI
4	Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 346:549–556. 2002. View Article : Google Scholar : PubMed/NCBI
5	Stub D, Bernard S, Duffy SJ and Kaye DM: Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 123:1428–1435. 2011. View Article : Google Scholar : PubMed/NCBI
6	Paul M, Poyan Mehr A and Kreutz R: Physiology of local renin-angiotensin systems. Physiol Rev. 86:747–803. 2006. View Article : Google Scholar : PubMed/NCBI
7	Li K and Chen X: Protective effects of captopril and enalapril on myocardial ischemia and reperfusion damage of rat. J Mol Cell Cardiol. 19:909–915. 1987. View Article : Google Scholar : PubMed/NCBI
8	Sharma JN: The kallikrein-kinin system: from mediator of inflammation to modulator of cardioprotection. Inflammopharmacology. 12:591–596. 2005. View Article : Google Scholar : PubMed/NCBI
9	Kusch A, Hoff U, Bubalo G, Zhu Y, Fechner M, Schmidt-Ullrich R, Marko L, Müller DN, Schmidt-Ott KM, Gürgen D, et al: Novel signalling mechanisms and targets in renal ischaemia and reperfusion injury. Acta Physiol (Oxf). 208:25–40. 2013. View Article : Google Scholar
10	Geng Y, Li E, Mu Q, Zhang Y, Wei X, Li H, Cheng L and Zhang B: Hydrogen sulfide inhalation decreases early blood-brain barrier permeability and brain edema induced by cardiac arrest and resuscitation. J Cereb Blood Flow Metab. 35:494–500. 2015. View Article : Google Scholar
11	Guo ZJ, Li CS, Yin WP, Hou XM, Gu W and Zhang D: Comparison of shock-first strategy and cardiopulmonary resuscitation-first strategy in a porcine model of prolonged cardiac arrest. Resuscitation. 84:233–238. 2013. View Article : Google Scholar
12	Idris AH, Becker LB, Ornato JP, Hedges JR, Bircher NG, Chandra NC, Cummins RO, Dick W, Ebmeyer U, Halperin HR, et al Writing Group: Utstein-style guidelines for uniform reporting of laboratory CPR research A statement for healthcare professionals from a task force of the American Heart Association the American College of Emergency Physicians, the American College of Cardiology, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for Resuscitation Research, and the Society for Academic Emergency Medicine. Circulation. 94:2324–2336. 1996. View Article : Google Scholar : PubMed/NCBI
13	Wang S, Li C, Ji X, Yang L, Su Z and Wu J: Effect of continuous compressions and 30:2 cardiopulmonary resuscitation on global ventilation/perfusion values during resuscitation in a porcine model. Crit Care Med. 38:2024–2030. 2010. View Article : Google Scholar : PubMed/NCBI
14	Pereira AJ, Jeger V, Fahrner R, Djafarzadeh S, Lensch M, Takala J and Jakob SM: Interference of angiotensin II and enalapril with hepatic blood flow regulation. Am J Physiol Gastrointest Liver Physiol. 307:G655–G663. 2014. View Article : Google Scholar : PubMed/NCBI
15	Gu W, Li CS, Yin WP, Hou XM, Zhang J, Zhang D and Guo Z: Expression imbalance of transcription factors GATA-3 and T-bet in post-resuscitation myocardial immune dysfunction in a porcine model of cardiac arrest. Resuscitation. 84:848–853. 2013. View Article : Google Scholar
16	Zhang Q and Li C: Combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction in journalporcine model of cardiac arrest. PLoS One. 8:e826772013. View Article : Google Scholar
17	Ji XF, Li CS, Wang S, Yang L and Cong LH: Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest. Resuscitation. 81:1031–1036. 2010. View Article : Google Scholar : PubMed/NCBI
18	Valenzuela TD, Roe DJ, Cretin S, Spaite DW and Larsen MP: Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation. 96:3308–3313. 1997. View Article : Google Scholar : PubMed/NCBI
19	Wang P, Xu TY, Wei K, Guan YF, Wang X, Xu H, Su DF, Pei G and Miao CY: ARRB1/β-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia. Autophagy. 10:1535–1548. 2014. View Article : Google Scholar : PubMed/NCBI
20	Wang YG, Li Y, Wang CY, Ai JW, Dong XY, Huang HY, Feng ZY, Pan YM, Lin Y, Wang BX and Yao LL: L-3-n-Butylphthalide protects rats' cardiomyocytes from ischaemia/reperfusion-induced apoptosis by affecting the mitochondrial apoptosis pathway. Acta Physiol (Oxf). 210:524–533. 2014. View Article : Google Scholar
21	Wang P, Du H, Zhou CC, Song J, Liu X, Cao X, Mehta JL, Shi Y, Su DF and Miao CY: Intracellular NAMPT-NAD⁺-SIRT1 cascade improves post-ischaemic vascular repair by modulating Notch signalling in endothelial progenitors. Cardiovasc Res. 104:477–488. 2014. View Article : Google Scholar : PubMed/NCBI
22	Ragone MI, Torres NS and Consolini AE: Energetic study of cardioplegic hearts under ischaemia/reperfusion and [Ca(²⁺)] changes in cardiomyocytes of guinea-pig: mitochondrial role. Acta Physiol (Oxf). 207:369–384. 2013. View Article : Google Scholar
23	Wang P, Xu TY, Guan YF, Zhao Y, Li ZY, Lan XH, Wang X, Yang PY, Kang ZM, Vanhoutte PM and Miao CY: Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis. Cardiovasc Res. 102:448–459. 2014. View Article : Google Scholar : PubMed/NCBI
24	Wang P, Xu TY, Guan YF, Tian WW, Viollet B, Rui YC, Zhai QW, Su DF and Miao CY: Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol. 69:360–374. 2011. View Article : Google Scholar : PubMed/NCBI
25	Wang P, Guan YF, Du H, Zhai QW, Su DF and Miao CY: Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemia. Autophagy. 8:77–87. 2012. View Article : Google Scholar
26	Wang P, Xu TY, Guan YF, Su DF, Fan GR and Miao CY: Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide. Cardiovasc Res. 81:370–380. 2009. View Article : Google Scholar
27	Mapanga RF, Joseph D, Symington B, Garson KL, Kimar C, Kelly-Laubscher R and Essop MF: Detrimental effects of acute hyperglycaemia on the rat heart. Acta Physiol (Oxf). 210:546–564. 2014. View Article : Google Scholar
28	Reynolds JC and Lawner BJ: Management of the post-cardiac arrest syndrome. J Emerg Med. 42:440–449. 2012. View Article : Google Scholar : PubMed/NCBI
29	Gu W, Li CS, Yin WP, Guo ZJ, Hou XM and Zhang D: Apoptosis is involved in the mechanism of postresuscitation myocardial dysfunction in a porcine model of cardiac arrest. Am J Emerg Med. 30:2039–2045. 2012. View Article : Google Scholar : PubMed/NCBI
30	Wang S, Radhakrishnan J, Ayoub IM, Kolarova JD, Taglieri DM and Gazmuri RJ: Limiting sarcolemmal Na⁺ entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca²⁺ accumulation and attenuates myocardial injury. J Appl Physiol (1985). 103:55–65. 2007. View Article : Google Scholar
31	Adams JA: Endothelium and cardiopulmonary resuscitation. Crit Care Med. 34(Suppl): S458–S465. 2006. View Article : Google Scholar : PubMed/NCBI
32	Lant AF, McNabb RW and Noormohamed FH: Kinetic and metabolic aspects of enalapril action. J Hypertens Suppl. 2:S37–S42. 1984.PubMed/NCBI
33	Doğan R, Farsak B, Tuncer M and Demirpençe E: Attenuation of ischemia-reperfusion injury by enalapril maleat. Gen Pharmacol. 31:203–208. 1998. View Article : Google Scholar
34	Montalescot G, Drexler H, Gallo R, Pearson T, Thoenes M and Bhatt DL: Effect of irbesartan and enalapril in non-ST elevation acute coronary syndrome: Results of the randomized, double-blind ARCHIPELAGO study. Eur Heart J. 30:2733–2741. 2009. View Article : Google Scholar : PubMed/NCBI
35	Miclescu A, Sharma HS, Martijn C and Wiklund L: Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions. Crit Care Med. 38:2199–2206. 2010. View Article : Google Scholar : PubMed/NCBI
36	Hoyer A, Kempfert J, Pritzwald-Stegmann P, Mohr FW and Dhein S: Acute hemodynamic effects of angiotensin-converting enzyme inhibition after prolonged cardiac arrest with Bretschneider's solution. Naunyn Schmiedebergs Arch Pharmacol. 387:1221–1229. 2014. View Article : Google Scholar : PubMed/NCBI
37	Wu B, Lin R, Dai R, Chen C, Wu H and Hong M: Valsartan attenuates oxidative stress and NF-κB activation and reduces myocardial apoptosis after ischemia and reperfusion. Eur J Pharmacol. 705:140–147. 2013. View Article : Google Scholar : PubMed/NCBI
38	Kobara M, Tatsumi T, Kambayashi D, Mano A, Yamanaka S, Shiraishi J, Keira N, Matoba S, Asayama J, Fushiki S and Nakagawa M: Effects of ACE inhibition on myocardial apoptosis in an ischemia-reperfusion rat heart model. J Cardiovasc Pharmacol. 41:880–889. 2003. View Article : Google Scholar : PubMed/NCBI
39	Bjerregaard J and Jaffe RA: Intraoperative cardiac arrest: was it the ACE inhibitor? J Clin Anesth. 26:62–64. 2014. View Article : Google Scholar : PubMed/NCBI
40	Chua HR, Glassford N and Bellomo R: Acute kidney injury after cardiac arrest. Resuscitation. 83:721–727. 2012. View Article : Google Scholar
41	Zhang Y, Boddicker KA, Rhee BJ, Davies LR and Kerber RE: Effect of nitric oxide synthase modulation on resuscitation success in a swine ventricular fibrillation cardiac arrest model. Resuscitation. 67:127–134. 2005. View Article : Google Scholar : PubMed/NCBI
42	Marques Neto SR, da H Silva A, dos Santos MC, Ferraz EF and Nascimento JH: The blockade of angiotensin AT1 and aldosterone receptors protects rats from synthetic androgen-induced cardiac autonomic dysfunction. Acta Physiol (Oxf). 208:166–171. 2013. View Article : Google Scholar
43	Biwer LA, Broderick TL, Xu H, Carroll C and Hale TM: Protection against L-NAME-induced reduction in cardiac output persists even after cessation of angiotensin-converting enzyme inhibitor treatment. Acta Physiol (Oxf). 207:156–165. 2013. View Article : Google Scholar
44	Paradis NA, Rose MI and Garg U: The effect of global ischemia and reperfusion on the plasma levels of vasoactive peptides. The neuroendocrine response to cardiac arrest and resuscitation Resuscitation. 26:261–269. 1993.
45	Soler MJ, Wysocki J and Batlle D: ACE2 alterations in kidney disease. Nephrol Dial Transplant. 28:2687–2697. 2013. View Article : Google Scholar : PubMed/NCBI
46	Varagic J, Ahmad S, Nagata S and Ferrario CM: ACE2: Angiotensin II/angiotensin-(1–7) balance in cardiac and renal injury. Curr Hypertens Rep. 16:4202014. View Article : Google Scholar
47	Bernardi S, Toffoli B, Zennaro C, Tikellis C, Monticone S, Losurdo P, Bellini G, Thomas MC, Fallo F, Veglio F, et al: High-salt diet increases glomerular ACE/ACE2 ratio leading to oxidative stress and kidney damage. Nephrol Dial Transplant. 27:1793–1800. 2012. View Article : Google Scholar
48	Liu R, Qi H, Wang J, Wang Y, Cui L, Wen Y and Yin C: Angiotensin-converting enzyme (ACE and ACE2) imbalance correlates with the severity of cerulein-induced acute pancreatitis in mice. Exp Physiol. 99:651–663. 2014. View Article : Google Scholar : PubMed/NCBI
49	Hsieh WY, Kuan TC, Cheng KS, Liao YC, Chen MY, Lin PH, Hsu YC, Huang CY, Hsu WH, Yu SY and Lin CS: ACE/ACE2 ratio and MMP-9 activity as potential biomarkers in tuberculous pleural effusions. Int J Biol Sci. 8:1197–1205. 2012. View Article : Google Scholar : PubMed/NCBI