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Reperfusion Interval as a Prevention of Lung Injury Due to Limb Ischemia–Reperfusion After Application of Tourniquet in Murine Experimental Study

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Abstract

Background

Tourniquet use is prevalent in the orthopaedic field to achieve a bloodless operating field, but it poses risks of local and systemic complications, including lung injury. This study aims to examine the effect of tourniquet application on the hindlimb of a rat to its lung.

Materials and Methods

This is an experimental study with 48 male Wistar strain rats as samples. The rats were divided into group A (n = 24), killed directly after fracturization and tourniquet application, and group B (n = 24), killed 14 days post-procedure. Each group was divided into four: group A1/B1 (control group, three hours tourniquet application without reperfusion interval), A2/B2 (5-min reperfusion between 2-h and 1-h tourniquet application), A3/B3 (10-min reperfusion), and A4/B4 (15-min reperfusion). The lung tissue was examined histologically within ten high-power fields (400 × magnification). The severity of lung injury was measured using the Lung Injury Score (LIS). The oxidative damage was measured by determining the malondialdehyde (MDA) level, using the TBARS (thiobarbituric acid reactive substance assay) method.

Results

There was a dose-dependent decrease of LIS and MDA in groups A and B with increasing reperfusion interval. Fifteen-minute reperfusion interval caused a 54.55% and 45.33% LIS reduction in groups A and B, respectively. All pair-wise group comparisons (p < 0.05) showed significant differences. Five-minute interval reduced the MDA level by 16.56% and 30.13% in groups A and B, respectively. All possible pair-wise comparisons in both groups A and B also showed a significant difference (p < 0.05).

Conclusions

Reperfusion interval is a possible clinical approach to mitigate the remote organ damage induced by limb ischemia–reperfusion injury.

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References

  1. Kumar, K., Railton, C., & Tawfic, Q. (2016). Tourniquet application during anesthesia: “What we need to know?”. Journal of Anaesthesiology Clinical Pharmacology, 32(4), 424–430. https://doi.org/10.4103/0970-9185.168174.

    Article  Google Scholar 

  2. Sharma, J. P., & Salhotra, R. (2012). Tourniquets in orthopedic surgery. Indian Journal of Orthopaedics, 46(4), 377–383. https://doi.org/10.4103/0019-5413.98824.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Odinsson, A., & Finsen, V. (2006). Tourniquet use and its complications in Norway. Journal of Bone and Joint Surgery British volume, 88-B(8), 1090–1092. https://doi.org/10.1302/0301-620X.88B8.17668.

    Article  Google Scholar 

  4. Van der Spuy, L. A. (2012). Complications of the arterial tourniquet. Southern African Journal of Anaesthesia and Analgesia, 18(1), 14–18.

    Article  Google Scholar 

  5. Leurcharusmee, P., Sawaddiruk, P., Punjasawadwong, Y., Chattipakorn, N., & Chattipakorn, S. C. (2018). The possible pathophysiological outcomes and mechanisms of tourniquet-induced ischemia-reperfusion injury during total knee arthroplasty. Oxidative Medicine and Cellular Longevity, 2018, 8087598. https://doi.org/10.1155/2018/8087598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen, L., Zhao, H., Alam, A., et al. (2019). Postoperative remote lung injury and its impact on surgical outcome. BMC Anesthesiology, 19(1), 1–10. https://doi.org/10.1186/s12871-019-0698-6.

    Article  Google Scholar 

  7. Lin, L., Wang, L., Bai, Y., et al. (2010). Pulmonary gas exchange impairment following tourniquet deflation: A prospective, single-blind clinical trial. Orthopedics, 33(6), 395. https://doi.org/10.3928/01477447-20100429-15.

    Article  PubMed  Google Scholar 

  8. Jin, Z., Suen, K. C., & Ma, D. (2016). Perioperative, “remote” acute lung injury: Recent update. Journal of Biomedical Research, 2016(31), 197–212. https://doi.org/10.7555/jbr.31.20160053.

    Article  Google Scholar 

  9. Halladin, N. L., Zahle, F. V., Rosenberg, J., & Gögenur, I. (2014). Interventions to reduce tourniquet-related ischaemic damage in orthopaedic surgery: A qualitative systematic review of randomised trials. Anaesthesia, 69(9), 1033–1050. https://doi.org/10.1111/anae.12664.

    Article  CAS  PubMed  Google Scholar 

  10. Horlocker, T. T., Hebl, J. R., Gali, B., et al. (2006). Anesthetic, patient, and surgical risk factors for neurologic complications after prolonged total tourniquet time during total knee arthroplasty. Anesthesia and Analgesia, 102(3), 950–955. https://doi.org/10.1213/01.ane.0000194875.05587.7e.

    Article  PubMed  Google Scholar 

  11. Drysch, M., Wallner, C., Schmidt, S. V., et al. (2019). An optimized low-pressure tourniquet murine hind limb ischemia reperfusion model: Inducing acute ischemia reperfusion injury in C57BL/6 wild type mice. PLoS ONE, 14(1), e0210961. https://doi.org/10.1371/journal.pone.0210961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tran, T. P., Tu, H., Pipinos, I. I., Muelleman, R. L., Albadawi, H., & Li, Y.-L. (2011). Tourniquet-induced acute ischemia-reperfusion injury in mouse skeletal muscles: Involvement of superoxide. European Journal of Pharmacology, 650(1), 328–334. https://doi.org/10.1016/j.ejphar.2010.10.037.

    Article  CAS  PubMed  Google Scholar 

  13. Prodinger, P. M., Bürklein, D., Foehr, P., et al. (2018). Improving results in rat fracture models: Enhancing the efficacy of biomechanical testing by a modification of the experimental setup. BMC Musculoskeletal Disorders, 19(1), 1–8. https://doi.org/10.1186/s12891-018-2155-y.

    Article  CAS  Google Scholar 

  14. Moreno, L. D., Waldman, S. D., & Grynpas, M. D. (2006). Sex differences in long bone fatigue using a rat model. Journal of Orthopaedic Research, 24(10), 1926–1932. https://doi.org/10.1002/jor.20250.

    Article  PubMed  Google Scholar 

  15. Hiltunen, A., Vuorio, E., & Aro, H. T. (1993). A standardized experimental fracture in the mouse tibia. Journal of Orthopaedic Research, 11(2), 305–312. https://doi.org/10.1002/jor.1100110219.

    Article  CAS  PubMed  Google Scholar 

  16. Otto, T. E., Patka, P., & Haarman, H. J. T. M. (1995). Closed fracture healing: A rat model. European Surgical Research, 27(4), 277–284. https://doi.org/10.1159/000129410.

    Article  CAS  PubMed  Google Scholar 

  17. Handool, K. O., Ibrahim, S. M., Kaka, U., et al. (2018). Optimization of a closed rat tibial fracture model. Journal of Experimental Orthopaedics. https://doi.org/10.1186/s40634-018-0128-6.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Crawford, R. S., Hashmi, F. F., Jones, J. E., et al. (2007). A novel model of acute murine hindlimb ischemia. Am J Physiol - Hear Circ Physiol, 292(2), 830–837. https://doi.org/10.1152/ajpheart.00581.2006.

    Article  CAS  Google Scholar 

  19. Matute-Bello, G., Downey, G., Moore, B. B., et al. (2011). An official American thoracic society workshop report: Features and measurements of experimental acute lung injury in animals. American Journal of Respiratory Cell and Molecular Biology, 44(5), 725–738. https://doi.org/10.1165/rcmb.2009-0210ST.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mansour, Z., Charles, A. L., Kindo, M., et al. (2014). Remote effects of lower limb ischemia-reperfusion: Impaired lung, unchanged liver, and stimulated kidney oxidative capacities. BioMed Research International, 2014, 1–7. https://doi.org/10.1155/2014/392390.

    Article  Google Scholar 

  21. Men, X., Han, S., Gao, J., et al. (2010). Taurine protects against lung damage following limb ischemia reperfusion in the rat by attenuating endoplasmic reticulum stress-induced apoptosis. Acta Orthopaedica, 81(2), 263–267. https://doi.org/10.3109/17453671003587085.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sotoudeh, A., Takhtfooladi, M. A., Jahanshahi, A., Asl, A. H. K., Takhtfooladi, A., & Khansari, M. (2012). Effect of N-acetylcysteine on lung injury induced by skeletal muscle ischemia-reperfusion: Histopathological study in rat model. Estudo Histopatólogi, 27(2), 168–171.

    Google Scholar 

  23. Wang, L., Chen, B., Lin, B., et al. (2018). Methylene blue attenuates lung injury induced by hindlimb ischemia reperfusion in rats. Mediators of Inflammation. https://doi.org/10.1155/2018/2508620.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Takhtfooladi, M. A., Jahanshahi, A., Sotoudeh, A., Jahanshahi, G., Takhtfooladi, H. A., & Aslani, K. (2013). Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: An experimental study. Jornal Brasileiro de Pneumologia, 39(4), 434–439. https://doi.org/10.1590/S1806-37132013000400006.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Takhtfooladi, H., Takhtfooladi, M., Moayer, F., & Mobarakeh, S. (2015). Melatonin attenuates lung injury in a hind limb ischemia–reperfusion rat model. Revista Portuguesa de Pneumologia (English Edition), 21(1), 30–35. https://doi.org/10.1016/j.rppnen.2014.01.010.

    Article  Google Scholar 

  26. Takhtfooladi, H. A., & Takhtfooladi, M. A. (2019). Effect of curcumin on lung injury induced by skeletal muscle ischemia/reperfusion in rats. Ulusal Travma ve Acil Cerrahi Dergisi, 25(1), 7–11. https://doi.org/10.5505/tjtes.2018.83616.

    Article  PubMed  Google Scholar 

  27. Hausenloy, D. J., & Yellon, D. M. (2009). Preconditioning and postconditioning: Underlying mechanisms and clinical application. Atherosclerosis, 204(2), 334–341. https://doi.org/10.1016/j.atherosclerosis.2008.10.029.

    Article  CAS  PubMed  Google Scholar 

  28. Harkin, D. W., Barros D’Sa, A. A. B., McCallion, K., Hoper, M., & Campbell, F. C. (2002). Ischemic preconditioning before lower limb ischemia–reperfusion protects against acute lung injury. Journal of Vascular Surgery, 35(6), 1264–1273.

    Article  Google Scholar 

  29. Jamshidi, F., Entezari, S., Alimian, M., Siamdoust, A., & Koleini, Z. S. (2016). Remote ischemic preconditioning in lower limb surgery; The hemodynamic and respiratory effects. Journl of Cellular and Molecular Anesthesia, 1(3), 97–102.

    Google Scholar 

  30. Song, S. Q., Gan, H. L., Zhang, J. Q., Feng, L., Sun, J. C., & Wang, S. X. (2015). Post-conditioning through lower limb ischemia-reperfusion can alleviate lung ischemia-reperfusion injury. International Journal of Clinical and Experimental Medicine, 8(9), 14953–14961.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Ferrari, R. S., & Andrade, C. F. (2015). Oxidative stress and lung ischemia-reperfusion injury. Oxidative Medicine and Cellular Longevity, 2015, 590987. https://doi.org/10.1155/2015/590987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li, C., Xu, M., Wu, Y., Li, Y.-S., Huang, W.-Q., & Liu, K.-X. (2014). Limb remote ischemic preconditioning attenuates lung injury after pulmonary resection under propofol-remifentanil anesthesia: A randomized controlled study. Anesthesiology, 121(2), 249–259. https://doi.org/10.1097/ALN.0000000000000266.

    Article  CAS  PubMed  Google Scholar 

  33. Kalogeris, T., Baines, C. P., Krenz, M., & Korthuis, R. J. (2017). Ischemia/reperfusion. Comprehensive Physiology, 7(1), 113–170. https://doi.org/10.1002/cphy.c160006.

    Article  Google Scholar 

  34. Peng, T. C., Jan, W. C., Tsai, P. S., & Huang, C. J. (2011). Heme oxygenase-1 mediates the protective effects of ischemic preconditioning on mitigating lung injury induced by lower limb ischemia-reperfusion in rats. Journal of Surgical Research, 167(2), e245–e253. https://doi.org/10.1016/j.jss.2010.06.010.

    Article  CAS  PubMed  Google Scholar 

  35. Kao, M. C., Jan, W. C., Tsai, P. S., Wang, T. Y., & Huang, C. J. (2011). Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats. Journal of Surgical Research, 171(1), e97–e106. https://doi.org/10.1016/j.jss.2011.03.028.

    Article  CAS  PubMed  Google Scholar 

  36. Hsu, K. Y., Tsai, P. S., Lee, J. J., Wang, T. Y., & Huang, C. J. (2011). Platonin mitigates acute lung injury induced by bilateral lower limb ischemia-reperfusion in rats. Journal of Surgical Research, 167(2), e255–e262. https://doi.org/10.1016/j.jss.2010.03.075.

    Article  CAS  PubMed  Google Scholar 

  37. Schofield, Z. V., Woodruff, T. M., Halai, R., Wu, M. C.-L., & Cooper, M. A. (2013). Neutrophils—a key component of ischemia-reperfusion injury. Shock, 40(6), 463–470. https://doi.org/10.1097/SHK.0000000000000044.

    Article  CAS  PubMed  Google Scholar 

  38. Moldoveanu, B., Otmishi, P., Jani, P., Walker, J., Sarmiento, X., Guardiola, J., et al. (2009). Inflammatory mechanisms in the lung. Journal of Inflammation Research, 2, 1–11.

    CAS  PubMed  Google Scholar 

  39. Wu, Q., Zhong, Z.-M., Pan, Y., et al. (2015). Advanced oxidation protein products as a novel marker of oxidative stress in postmenopausal osteoporosis. Medical Science Monitor, 21, 2428–2432. https://doi.org/10.12659/MSM.894347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ibrahim, M. A. A., Elwan, W. M., & Elgendy, H. A. (2019). Role of scutellarin in ameliorating lung injury in a rat model of bilateral hind limb ischemia-reperfusion. Anatomical Record (Hoboken). https://doi.org/10.1002/ar.24175.

    Article  Google Scholar 

  41. Demling, R., & LaLonde, C. (1989). Relationship between lung injury and lung lipid peroxidation caused by recurrent endotoxemia. The American Review of Respiratory Disease, 139(5), 1118–1124. https://doi.org/10.1164/ajrccm/139.5.1118.

    Article  CAS  PubMed  Google Scholar 

  42. Bajpai, J., Prakash, V., Kant, S., et al. (2017). Study of oxidative stress biomarkers in chronic obstructive pulmonary disease and their correlation with disease severity in north Indian population cohort. Lung India, 34(4), 324. https://doi.org/10.4103/lungindia.lungindia_205_16.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Budic, I., Pavlovic, D., Kitic, D., et al. (2013). Tourniquet-induced ischemia-reperfusion injuries during extremity surgery at children’s age: Impact of anesthetic chemical structure. Redox Report, 18(1), 20–26. https://doi.org/10.1179/1351000212y.0000000037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was solely funded by the authors.

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Authors and Affiliations

  1. Faculty of Medicine, Universitas Brawijaya, Jl. Veteran, Malang, 65145, Indonesia

    Thomas Erwin Christian Junus Huwae

  2. Department of Orthopaedics and Traumatology, Saiful Anwar General Hospital, Malang, Indonesia

    Thomas Erwin Christian Junus Huwae, Agung Riyanto Budi Santoso, Wongso Kesuma, William Putera Sukmajaya & Mohammad Hidayat

  3. Department of Ophthalmology, Saiful Anwar General Hospital, Malang, Indonesia

    Hidayat Sujuti

  4. Department of Physiology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia

    Retty Ratnawati

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  1. Thomas Erwin Christian Junus Huwae
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Correspondence to Thomas Erwin Christian Junus Huwae.

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Huwae, T.E.C.J., Santoso, A.R.B., Kesuma, W. et al. Reperfusion Interval as a Prevention of Lung Injury Due to Limb Ischemia–Reperfusion After Application of Tourniquet in Murine Experimental Study. JOIO 54, 704–710 (2020). https://doi.org/10.1007/s43465-020-00100-y

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