Protective effect of nicorandil on collapse‑induced lung injury in rabbits by inhibiting apoptosis

  • Authors:
    • Chunguang Wang
    • Honggang Ke
    • Xingguo Xu
    • Junjie Chen
    • Dongyun Sun
    • Fuhai Ji
  • View Affiliations

  • Published online on: June 6, 2019     https://doi.org/10.3892/ijmm.2019.4236
  • Pages: 725-736
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The one‑lung ventilation (OLV) technique is vital in thoracic surgery. However, it can result in severe lung injury, which is difficult to manage. The main solution at present is the use of ventilation strategies, including continuous positive oxygen pressure, low tidal volume and high frequency ventilation, and the administering of drugs, including phenylephrine, dexmedetomidine and morphine. However, the protective effect of these methods on the lungs is not sufficient to improve the prognosis of patients. Therefore, how to develop a novel protective drug remains an open question. Nicorandil, a mitochondrial (mito)KATP‑specific opener, serves an important role in cardioprotection, although its effect on lung injury remains unclear. The present study examined the protective role of nicorandil against collapse‑induced lung injury in rabbits undergoing OLV. Changes in arterial oxygen saturation (SaO2), arterial partial pressure for oxygen (PaO2), wet/dry weight ratio, and the microstructure of tissues and cells were observed. Enzyme‑linked immunosorbent assays were used to determine the concentrations of malondialdehyde (MDA) and tumor necrosis factor (TNF)‑α, and the activity of superoxide dismutase (SOD) in rabbits treated with nicorandil. Terminal deoxynucleotidyl transferase transfer‑mediated dUTP nick end‑labeling was used to detect apoptosis and western blotting was used to analyze the relative proteins involved in apoptosis. Western blotting and reverse transcription‑quantitative polymerase chain reaction analysis were used to examine the expression of hypoxia inducible factor 1α (HIF‑1α), phosphatidylinositol‑3‑kinase (PI3K), protein kinase B (Akt) and nuclear factor (NF)‑κB in the lungs of rabbits treated with nicorandil. The SaO2 and PaO2 in the high‑dose group were significantly higher than those in the control group in the process of OLV. The wet/dry weight ratio, and the concentrations of MDA and TNF‑α in the collapsed lung of the high‑dose group were significantly lower than those in the control group. The activity of SOD in the high‑dose group was significantly higher than that in the control group. The lung had improved microstructure and less apoptosis, which was determined by the Bax/Bcl2 ratio in the high‑dose group. The expression levels of PI3K, phosphorylated Akt and HIF‑1α were upregulated, whereas the expression of NF‑κB was downregulated. In conclusion, nicorandil had a protective effect via inhibiting apoptosis in non‑ventilated lung collapsed and re‑expansion during OLV in the rabbit. It acted on mitoKATP through the PI3K/Akt signaling pathway.

References

1 

Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, Wang X, MacArthur PH, Shoja A, Raghavachari N, et al: Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med. 204:2089–2102. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Liu B, Tewari AK, Zhang L, Green-Church KB, Zweier JL, Chen YR and He G: Proteomic analysis of protein tyrosine nitration after ischemia reperfusion injury: Mitochondria as the major target. Biochim Biophys Acta. 1794:476–485. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Pak O, Sydykov A, Kosanovic D, Schermuly RT, Dietrich A, Schröder K, Brandes RP, Gudermann T, Sommer N and Weissmann N: Lung ischaemia-reperfusion injury: The role of reactive oxygen species. Adv Exp Med Biol. 967:195–225. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Bernasconi F and Piccioni FL: One-lung ventilation for thoracic surgery: Current perspectives. Tumori. 103:495–503. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Dolch ME, Choukèr A, Hornuss C, Frey L, Irlbeck M, Praun S, Leidlmair C, Villinger J and Schelling G: Quantification of propionaldehyde in breath of patients after lung transplantation. Free Radic Biol Med. 85:157–164. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Ju NY, Gao H, Huang W, Niu FF, Lan WX, Li F and Gao W: Therapeutic effect of inhaled budesonide (pulmicort® turbuhaler) on the inflammatory response to one-lung ventilation. Anaesthesia. 69:14–23. 2014. View Article : Google Scholar

7 

Tojo K, Goto T and Kurahashi K: Protective effects of continuous positive airway pressure on a nonventilated lung during one-lung ventilation: A prospective laboratory study in rats. Eur J Anaesthesiol. 33:776–783. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Jung DM, Ahn HJ, Jung SH, Yang M, Kim JA, Shin SM and Jeon S: Apneic oxygen insufflation decreases the incidence of hypoxemia during one-lung ventilation in open and thoraco-scopic pulmonary lobectomy: A randomized controlled trial. J Thorac Cardiovasc Surg. 154:360–366. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Xia R, Xu J, Yin H, Wu H, Xia Z, Zhou D, Xia ZY, Zhang L, Li H and Xiao X: Intravenous infusion of dexmedetomidine combined isoflurane inhalation reduces oxidative stress and potentiates hypoxia pulmonary vasoconstriction during one-lung ventilation in patients. Mediators Inflamm. 2015:2380412015. View Article : Google Scholar : PubMed/NCBI

10 

Huang SQ, Zhang J, Zhang XX, Liu L, Yu Y, Kang XH, Wu XM and Zhu SM: Can dexmedetomidine improve arterial oxygenation and intrapulmonary shunt during one-lung ventilation in adults undergoing thoracic surgery? A meta-analysis of randomized, placebo-controlled trials. Chin Med J (Engl). 130:1707–1714. 2017. View Article : Google Scholar

11 

Schloss B, Martin D, Beebe A, Klamar J and Tobias JD: Phenylephrine to treat hypoxemia during one-lung ventilation in a pediatric patient. Thorac Cardiovasc Surg Rep. 2:16–18. 2013. View Article : Google Scholar

12 

Yang J, Zhang J, Cui W, Liu F, Xie R, Yang X, Gu G, Zheng H, Lu J, Yang X, et al: Cardioprotective effects of single oral dose of nicorandil before selective percutaneous coronary intervention. Anatol J Cardiol. 15:125–131. 2015. View Article : Google Scholar

13 

Saha KK, Kumar A, Deval MM, Saha KK, Jacob RV, Jagdale L and Kaul SK: Nicorandil infusion during off-pump coronary artery bypass grafting reduces incidence of intra-aortic balloon pump insertion. Innovations (Phila). 11:123–127. 2016. View Article : Google Scholar

14 

Su Q, Li L, Zhao J, Sun Y and Yang H: Effects of nicorandil on PI3K/Akt signaling pathway and its anti-apoptotic mechanisms in coronary microembolization in rats. Oncotarget. 8:99347–99358. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Ahmed LA, El-Maraghy SA and Rizk SM: Role of the KATP channel in the protective effect of nicorandil on cyclophosphamide-induced lung and testicular toxicity in rats. Sci Rep. 5:140432015. View Article : Google Scholar : PubMed/NCBI

16 

Asarian L and Geary N: Sex differences in the physiology of eating. Am J Physiol Regul Integr Comp Physiol. 305:R1215–R1267. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Xu ZP, Gu LB, Bian QM, Li PY, Wang LJ, Chen XX and Zhang JY: A novel method for right one-lung ventilation modeling in rabbits. Exp Ther Med. 12:1213–1219. 2016. View Article : Google Scholar : PubMed/NCBI

18 

You Z, Feng D, Xu H, Cheng M, Li Z, Kan M and Yao S: Nuclear factor-kappa B mediates one-lung ventilation-induced acute lung injury in rabbits. J Invest Surg. 25:78–85. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, Hori M, Higashino Y, Fujii K and Minamino T: Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol. 33:654–660. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Olson ME, McCabe K and Walker RL: Guaifenesin alone or in combination with ketamine or sodium pentobarbital as an anesthetic in rabbits. Can J Vet Res. 51:383–386. 1987.PubMed/NCBI

21 

Pérez-Martínez A, Gonzálvez-Piñera J, Marco-Macián A, Carpintero-Moreno F and Moya-Marchante M: Propofol in continuous perfusion as anesthetic in experimental surgery in the rabbit. Rev Esp Anestesiol Reanim. 42:253–256. 1995.In Spanish.

22 

Bellis DJ, Day S and Barnes PK: The chronotropic effect of acetylcholine in the presence of vecuronium and atracurium. A study in the isolated perfused rabbit heart Anaesthesia. 45:118–119. 1990.

23 

Shinozawa E and Kawamura M: Anti-thrombotic effect of a factor Xa inhibitor TAK-442 in a rabbit model of arteriove-nous shunt thrombosis stimulated with tissue factor. BMC Res Notes. 11:7762018. View Article : Google Scholar

24 

Lin L, Zhang L, Yu L, Han L, Ji W, Shen H and Hu Z: Time-dependent changes of autophagy and apoptosis in lipopolysaccharide-induced rat acute lung injury. Iran J Basic Med Sci. 19:632–637. 2016.PubMed/NCBI

25 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

26 

Kostic J, Djordjevic-Dikic A, Dobric M, Milasinovic D, Nedeljkovic M, Stojkovic S, Stepanovic J, Tesic M, Trifunovic Z, Zamaklar-Tifunovic D, et al: The effects of nicorandil on microvascular function in patients with ST segment elevation myocardial infarction undergoing primary PCI. Cardiovasc Ultrasound. 13:262015. View Article : Google Scholar : PubMed/NCBI

27 

Wang YP, Zhang Y, Sun YR, Sun ZG, Zuo ZK, Feng ZR, Chang FY, Xu YC, Chen BZ and Ye YY: Effect of nicorandil on ventricular arrhythmia in patients with acute ST-segment elevation myocardial infarction underwent emergent percutaneous coronary intervention treatment. Zhonghua Xin Xue Guan Bing Za Zhi. 45:701–705. 2017.In Chinese. PubMed/NCBI

28 

Suleimani HF, Eshraghi A, Daloee MH, Hoseini S and Nakhaee N: Effect of nicorandil on QT dispersion in patients with stable angina pectoris undergoing elective angioplasty: A triple-blind, randomized, placebo-controlled study. Electron Physician. 9:4934–4941. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Tanaka K, Kato K, Takano T, Katagiri T, Asanoi H, Nejima J, Nakashima M, Kamijo T and Sakanashi M: Acute effects of intravenous nicorandil on hemodynamics in patients hospitalized with acute decompensated heart failure. J Cardiol. 56:291–299. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Minami Y, Nagashima M, Kajimoto K, Shiga T and Hagiwara N: Acute efficacy and safety of intravenous administration of nicorandil in patients with acute heart failure syndromes: Usefulness of noninvasive echocardiographic hemodynamic evaluation. J Cardiovasc Pharmacol. 54:335–340. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Kong J, Ren G, Jia N, Wang Y, Zhang H, Zhang W, Chen B and Cao Y: Effects of nicorandil in neuroprotective activation of PI3K/AKT pathways in a cellular model of Alzheimer's disease. Eur Neurol. 70:233–241. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Yamazaki H, Oshima K, Sato H, Kobayashi K, Suto Y, Hirai K, Odawara H, Matsumoto K and Takeyoshi I: The effect of nicorandil on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model. J Surg Res. 167:49–55. 2011. View Article : Google Scholar

33 

Shimizu S, Saito M, Kinoshita Y, Ohmasa F, Dimitriadis F, Shomori K, Hayashi A and Satoh K: Nicorandil ameliorates ischaemia-reperfusion injury in the rat kidney. Br J Pharmacol. 163:272–282. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Szegedi LL, Bardoczky GI, Engelman EE and d'Hollander AA: Airway pressure changes during one-lung ventilation. Anesth Analg. 84:1034–1037. 1997. View Article : Google Scholar : PubMed/NCBI

35 

Kilpatrick B and Slinger P: Lung protective strategies in anaesthesia. Br J Anaesth. 105(Suppl 1): i108–i116. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Szegedi LL, D'Hollander AA, Vermassen FE, Deryck F and Wouters PF: Gravity is an important determinant of oxygenation during one-lung ventilation. Acta Anaesthesiol Scand. 54:744–750. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Misthos P, Katsaragakis S, Milingos N, Kakaris S, Sepsas E, Athanassiadi K, Theodorou D and Skottis I: Postresectional pulmonary oxidative stress in lung cancer patients. The role of one-lung ventilation. Eur J Cardiothorac Surg. 27:379–382; discussion 382-383. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Licker M, Fauconnet P, Villiger Y and Tschopp JM: Acute lung injury and outcomes after thoracic surgery. Curr Opin Anaesthesiol. 22:61–67. 2009. View Article : Google Scholar : PubMed/NCBI

39 

Jeon K, Yoon JW, Suh GY, Kim J, Kim K, Yang M, Kim H, Kwon OJ and Shim YM: Risk factors for post-pneumonectomy acute lung injury/acute respiratory distress syndrome in primary lung cancer patients. Anaesth Intensive Care. 37:14–19. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Tusman G, Böhm SH, Warner DO and Sprung J: Atelectasis and perioperative pulmonary complications in high-risk patients. Curr Opin Anaesthesiol. 25:1–10. 2012. View Article : Google Scholar

41 

Gajic O, Dara SI, Mendez JL, Adesanya AO, Festic E, Caples SM, Rana R, St Sauver JL, Lymp JF, Afessa B and Hubmayr RD: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med. 32:1817–1824. 2004. View Article : Google Scholar : PubMed/NCBI

42 

Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Espósito DC, Pasqualucci Mde O, Damasceno MC and Schultz MJ: Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: A meta-analysis. JAMA. 308:1651–1659. 2012. View Article : Google Scholar : PubMed/NCBI

43 

Slutsky AS and Ranieri VM: Ventilator-induced lung injury. N Engl J Med. 370:9802014.PubMed/NCBI

44 

Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT, Rothenberg P, Zhu J, Sachdeva R, Sonnad S, Kaiser LR, et al: Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 358:1327–1335. 2008. View Article : Google Scholar : PubMed/NCBI

45 

Karzai W and Schwarzkopf K: Hypoxemia during one-lung ventilation: Prediction, prevention, and treatment. Anesthesiology. 110:1402–1411. 2009. View Article : Google Scholar : PubMed/NCBI

46 

Ishikawa S and Lohser J: One-lung ventilation and arterial oxygenation. Curr Opin Anaesthesiol. 24:24–31. 2011. View Article : Google Scholar

47 

Kozian A, Schilling T, Schütze H, Heres F, Hachenberg T and Hedenstierna G: Lung computed tomography density distribution in a porcine model of one-lung ventilation. Br J Anaesth. 102:551–560. 2009. View Article : Google Scholar : PubMed/NCBI

48 

Benumof JL: One-lung ventilation and hypoxic pulmonary vasoconstriction: Implications for anesthetic management. Anesth Analg. 64:821–833. 1985. View Article : Google Scholar : PubMed/NCBI

49 

Rozé H, Lafargue M and Ouattara A: Case scenario: Management of intraoperative hypoxemia during one-lung ventilation. Anesthesiology. 114:167–174. 2011. View Article : Google Scholar

50 

Lee SM, Kim WH, Ahn HJ, Kim JA, Yang MK, Lee CH, Lee JH, Kim YR and Choi JW: The effects of prolonged inspiratory time during one-lung ventilation: A randomised controlled trial. Anaesthesia. 68:908–916. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Nieman GF, Satalin J, Andrews P, Aiash H, Habashi NM and Gatto LA: Personalizing mechanical ventilation according to physiologic parameters to stabilize alveoli and minimize ventilator induced lung injury (VILI). Intensive Care Med Exp. 5:82017. View Article : Google Scholar : PubMed/NCBI

52 

de Perrot M, Liu M, Waddell TK and Keshavjee S: Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med. 167:490–511. 2003. View Article : Google Scholar : PubMed/NCBI

53 

Cheng YJ, Chan KC, Chien CT, Sun WZ and Lin CJ: Oxidative stress during 1-lung ventilation. J Thorac Cardiovasc Surg. 132:513–518. 2006. View Article : Google Scholar : PubMed/NCBI

54 

Riva DR, Contador RS, Baez-Garcia CS, Xisto DG, Cagido VR, Martini SV, Morales MM, Rocco PR, Faffe DS and Zin WA: Recruitment maneuver: RAMP versus CPAP pressure profile in a model of acute lung injury. Respir Physiol Neurobiol. 169:62–68. 2009. View Article : Google Scholar : PubMed/NCBI

55 

Rzezinski AF, Oliveira GP, Santiago VR, Santos RS, Ornellas DS, Morales MM, Capelozzi VL, Amato MB, Conde MB, Pelosi P and Rocco PR: Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury. Respir Physiol Neurobiol. 169:271–281. 2009. View Article : Google Scholar : PubMed/NCBI

56 

Silva PL, Moraes L, Santos RS, Samary C, Ornellas DS, Maron-Gutierrez T, Morales MM, Saddy F, Capelozzi VL, Pelosi P, et al: Impact of pressure profile and duration of recruitment maneuvers on morphofunctional and biochemical variables in experimental lung injury. Crit Care Med. 39:1074–1081. 2011. View Article : Google Scholar : PubMed/NCBI

57 

Arnal JM, Paquet J, Wysocki M, Demory D, Donati S, Granier I, Corno G and Durand-Gasselin J: Optimal duration of a sustained inflation recruitment maneuver in ARDS patients. Intensive Care Med. 37:1588–1594. 2011. View Article : Google Scholar : PubMed/NCBI

58 

Chen C, Lu W, Wu G, Lv L, Chen W, Huang L, Wu X, Xu N and Wu Y: Cardioprotective effects of combined therapy with diltiazem and superoxide dismutase on myocardial ischemia-reperfusion injury in rats. Life Sci. 183:50–59. 2017. View Article : Google Scholar : PubMed/NCBI

59 

Liu G, Zhang J, Chen H, Wang C, Qiu Y, Liu Y, Wan J and Guo H: Effects and mechanisms of alveolar type II epithelial cell apoptosis in severe pancreatitis-induced acute lung injury. Exp Ther Med. 7:565–572. 2014. View Article : Google Scholar : PubMed/NCBI

60 

Wu Z, Dai F, Ren W, Liu H, Li B and Chang J: Angiotensin II induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1. Am J Transl Res. 8:28–36. 2016.PubMed/NCBI

61 

Yu D, Fan C, Zhang W, Wen Z, Hu L, Yang L, Feng Y, Yin KJ and Mo X: Neuroprotective effect of nicorandil through inhibition of apoptosis by the PI3K/Akt1 pathway in a mouse model of deep hypothermic low flow. J Neurol Sci. 357:119–125. 2015. View Article : Google Scholar : PubMed/NCBI

62 

Broucek JR, Francescatti AB, Swanson GR, Keshavarzian A, Brand MI and Saclarides TJ: Unusual thrombotic complications. Am Surg. 78:728–729. 2012.PubMed/NCBI

63 

Xia Z, Peng W, Cheng S, Zhong B, Sheng C, Zhang C, Gong W, Cheng S, Li J and Wang Z: Naoling decoction restores cognitive function by inhibiting the neuroinflammatory network in a rat model of Alzheimer's disease. Oncotarget. 8:42648–42663. 2017. View Article : Google Scholar : PubMed/NCBI

64 

Ambros JT, Herrero-Fresneda I, Borau OG and Boira JM: Ischemic preconditioning in solid organ transplantation: From experimental to clinics. Transpl Int. 20:219–229. 2007. View Article : Google Scholar : PubMed/NCBI

65 

Suzuki T, Yamashita K, Jomen W, Ueki S, Aoyagi T, Fukai M, Furukawa H, Umezawa K, Ozaki M and Todo S: The novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin, prevents local and remote organ injury following intestinal ischemia/reperfusion in rats. J Surg Res. 149:69–75. 2008. View Article : Google Scholar : PubMed/NCBI

66 

Wang H, Zuo X, Wang Q, Yu Y, Xie L, Wang H, Wu H and Xie W: Nicorandil inhibits hypoxia-induced apoptosis in human pulmonary artery endothelial cells through activation of mito-KATP and regulation of eNOS and the NF-κB pathway. Int J Mol Med. 32:187–194. 2013. View Article : Google Scholar : PubMed/NCBI

67 

Xu CQ, Liu BJ, Wu JF, Xu YC, Duan XH, Cao YX and Dong JC: Icariin attenuates LPS-induced acute inflammatory responses: Involvement of PI3K/Akt and NF-kappaB signaling pathway. Eur J Pharmacol. 642:146–153. 2010. View Article : Google Scholar : PubMed/NCBI

68 

Sakamoto N, Ishibashi T, Sugimoto K, Sawamura T, Sakamoto T, Inoue N, Saitoh S, Kamioka M, Uekita H, Ohkawara H, et al: Role of LOX-1 in monocyte adhesion-triggered redox, Akt/eNOS and Ca2+ signaling pathways in endothelial cells. J Cell Physiol. 220:706–715. 2009. View Article : Google Scholar : PubMed/NCBI

69 

Zhao X, Jin Y, Li H, Wang Z, Zhang W and Feng C: Hypoxia-inducible factor 1 alpha contributes to pulmonary vascular dysfunction in lung ischemia-reperfusion injury. Int J Clin Exp Pathol. 7:3081–3088. 2014.PubMed/NCBI

70 

Wan J, Wu W, Chen Y, Kang N and Zhang R: Insufficient radio-frequency ablation promotes the growth of non-small cell lung cancer cells through PI3K/Akt/HIF-1α signals. Acta Biochim Biophys Sin (Shanghai). 48:371–377. 2016. View Article : Google Scholar

71 

Gomez L, Li B, Mewton N, Sanchez I, Piot C, Elbaz M and Ovize M: Inhibition of mitochondrial permeability transition pore opening: Translation to patients. Cardiovasc Res. 83:226–233. 2009. View Article : Google Scholar : PubMed/NCBI

72 

Forgiarini LA Jr, Grun G, Kretzmann NA, de Muñoz GA, de Almeida A, Forgiarini LF and Andrade CF: When is injury potentially reversible in a lung ischemia-reperfusion model? J Surg Res. 179:168–174. 2013. View Article : Google Scholar

Related Articles

Journal Cover

August 2019
Volume 44 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wang, C., Ke, H., Xu, X., Chen, J., Sun, D., & Ji, F. (2019). Protective effect of nicorandil on collapse‑induced lung injury in rabbits by inhibiting apoptosis. International Journal of Molecular Medicine, 44, 725-736. https://doi.org/10.3892/ijmm.2019.4236
MLA
Wang, C., Ke, H., Xu, X., Chen, J., Sun, D., Ji, F."Protective effect of nicorandil on collapse‑induced lung injury in rabbits by inhibiting apoptosis". International Journal of Molecular Medicine 44.2 (2019): 725-736.
Chicago
Wang, C., Ke, H., Xu, X., Chen, J., Sun, D., Ji, F."Protective effect of nicorandil on collapse‑induced lung injury in rabbits by inhibiting apoptosis". International Journal of Molecular Medicine 44, no. 2 (2019): 725-736. https://doi.org/10.3892/ijmm.2019.4236