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Lymph Formation and Transport: Role in Trauma-Hemorrhagic Shock

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Severe Trauma and Sepsis

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Abstract

Microcirculatory disturbance is the key line of multiple organ dysfunction and failure following trauma-hemorrhagic shock (T/HS). The lymphatic circulation is an important component of the circulatory system, which is involved in the pathogenesis of T/HS. In the early stage of T/HS, the enhanced lymphatic constriction and reactivity, paralleling with the increased lymph formation and transport, play an important compensatory role in alleviating tissue edema and organ injury. Afterward, along with the continuation of hypotension, the lymphatic contractility and reactivity are reduced that causes tissue edema and organ injury. Moreover, T/HS-induced ischemia and/or reperfusion result in intestinal barrier injury and lymphatic endothelial barrier dysfunction. Because mesenteric lymph return is a vital contributor to intestinal bacteria-endotoxin translocation, these adverse effects further lead to uncontrolled inflammation, vascular hyperpermeability and hyporeactivity, immunosuppression, and subsequent multiple organ injury. Thus, increasing lymph formation and transport via regulation of lymphatic function may serve as a means of antagonizing the pathogenesis of T/HS.

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References

  1. Chakraborty S, Gurusamy M, Zawieja DC, Muthuchamy M. Lymphatic filariasis: perspectives on lymphatic remodeling and contractile dysfunction in filarial disease pathogenesis. Microcirculation. 2013;20(5):349–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Von Der Weid PY, Rehal S. Lymphatic pump function in the inflamed gut. Ann N Y Acad Sci. 2010;1207(Suppl 1):E69–74.

    Google Scholar 

  3. Zawieja SD, Wang W, Wu X, Nepiyushchikh ZV, Zawieja DC, Muthuchamy M. Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome. Am J Physiol Heart Circ Physiol. 2012;302(3):H643–53.

    Article  CAS  PubMed  Google Scholar 

  4. Jacob M, Kumar P. The challenge in management of hemorrhagic shock in trauma. Med J Armed Forces India. 2014;70(2):163–9.

    Article  PubMed  PubMed Central  Google Scholar 

  5. McGhan LJ, Jaroszewski DE. The role of toll-like receptor-4 in the development of multi-organ failure following traumatic haemorrhagic shock and resuscitation. Injury. 2012;43(2):129–36.

    Article  PubMed  Google Scholar 

  6. Duan C, Yang G, Li T, Liu L. Advances in vascular hyporeactivity after shock: the mechanisms and managements. Shock. 2015;44(6):524–34.

    Article  PubMed  Google Scholar 

  7. Deng X, Cao Y, Huby MP, Duan C, Baer L, Peng Z, et al. Adiponectin in fresh frozen plasma contributes to restoration of vascular barrier function after hemorrhagic shock. Shock. 2016;45(1):50–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Soliman M. Protective effects of estradiol on myocardial contractile function following hemorrhagic shock and resuscitation in rats. Chin Med J. 2015;128(17):2360–4.

    Article  PubMed  PubMed Central  Google Scholar 

  9. D’Alessandro A, Moore HB, Moore EE, Wither M, Nemkov T, Gonzalez E, et al. Early hemorrhage triggers metabolic responses that build up during prolonged shock. Am J Physiol Regul Integr Comp Physiol. 2015;308(12):R1034–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Dekker SE, Sillesen M, Bambakidis T, Jin G, Liu B, Boer C, et al. Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs. Surgery. 2014;156(3):556–63.

    Article  PubMed  Google Scholar 

  11. Ding N, Chen G, Hoffman R, Loughran PA, Sodhi CP, Hackam DJ, et al. Toll-like receptor 4 regulates platelet function and contributes to coagulation abnormality and organ injury in hemorrhagic shock and resuscitation. Circ Cardiovasc Genet. 2014;7(5):615–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang Y, Zhang J, Korff S, Ayoob F, Vodovotz Y, Billiar TR. Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock. Shock. 2014;42(3):218–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pati S, Pilia M, Grimsley JM, Karanikas AT, Oyeniyi B, Holcomb JB, et al. Cellular therapies in trauma and critical care medicine: forging new frontiers. Shock. 2015;44(6):505–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Schadt JC, Ludbrook J. Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Phys. 1991;260(2 Pt 2):H305–18.

    CAS  Google Scholar 

  15. Hubbard W, Keith J, Berman J, Miller M, Scott C, Peck C, et al. 17alpha-Ethynylestradiol-3-sulfate treatment of severe blood loss in rats. J Surg Res. 2015;193(1):355–60.

    Article  CAS  PubMed  Google Scholar 

  16. Zhang J. Changes in lymphatic microcirculation during hemorrhagic shock. Zhonghua Yi Xue Za Zhi. 1991;71(1):24–8.

    CAS  PubMed  Google Scholar 

  17. Johnston MG, Elias RM, Hayashi A, Nelson W. Role of the lymphatic circulatory system in shock. J Burn Care Rehabil. 1987;8(6):469–74.

    Article  CAS  PubMed  Google Scholar 

  18. Higaki A, Kawahara M, Yuge O, Fujii K, Morio M. Mesenteric lymphatic vasomotion following hemorrhage and retransfusion in the rat. Lymphology. 1990;23(4):209–14.

    CAS  PubMed  Google Scholar 

  19. Qin LP, Niu CY, Zhao ZG, Zhang J, Zhang YP. Nitric oxide modulates biphasic changes of isolated lymphatic contraction in hemorrhagic shock rats. Sheng Li Xue Bao. 2011;63(4):367–76.

    CAS  PubMed  Google Scholar 

  20. Wang HH, Zhang LM, Zhao ZG, Niu CY. Reduction of contractility and reactivity in isolated lymphatics from hemorrhagic shock rats with resuscitation. Acta Cir Bras. 2015;30(3):216–21.

    Article  PubMed  Google Scholar 

  21. Niu CY, Zhao ZG, Zhang YP, Liu ZQ, Zhang J. Lymphatic hyporeactivity and calcium desensitization following hemorrhagic shock. Shock. 2012;37(4):415–23.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang LM, Niu CY, Zhao ZG, Qin LP, Si YH, Zhang J. Reactivity to substance P of isolated lymphatics in hemorrhagic shock rat. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2012;28(1):57–61.

    PubMed  Google Scholar 

  23. Ruan X, Shi H, Xia G, Xiao Y, Dong J, Ming F, et al. Encapsulated Bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation. Nutrition. 2007;23(10):754–61.

    Article  CAS  PubMed  Google Scholar 

  24. Moore FA, Moore EE, Poggetti RS, Read RA. Postinjury shock and early bacteremia. A lethal combination. Arch Surg. 1992;127(8):893–7. discussion 897–8.

    Article  CAS  PubMed  Google Scholar 

  25. Baker JW, Deitch EA, Li M, Berg RD, Specian RD. Hemorrhagic shock induces bacterial translocation from the gut. J Trauma. 1988;28(7):896–906.

    Article  CAS  PubMed  Google Scholar 

  26. Deitch EA, Xu D, Kaise VL. Role of the gut in the development of injury- and shock induced SIRS and MODS: the gut-lymph hypothesis, a review. Front Biosci. 2006;11:520–8.

    Article  CAS  PubMed  Google Scholar 

  27. Deitch EA. Gut-origin sepsis: evolution of a concept. Surgeon. 2012;10(6):350–6.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Leak LV, Cadet JL, Griffin CP, Richardson K. Nitric oxide production by lymphatic endothelial cells in vitro. Biochem Biophys Res Commun. 1995;217(1):96–105.

    Article  CAS  PubMed  Google Scholar 

  29. Liu ZY, Casley-Smith JR. The fine structure of the amphibian lymph sac. Lymphology. 1989;22(1):31–5.

    CAS  PubMed  Google Scholar 

  30. Moore EE. Mesenteric lymph: the critical bridge between dysfunctional gut and multiple organ failure. Shock. 1998;10(6):415–6.

    Article  CAS  PubMed  Google Scholar 

  31. Magnotti LJ, Xu DZ, Lu Q, Deitch EA. Gut-derived mesenteric lymph: a link between burn and lung injury. Arch Surg. 1999;134(12):1333–40. discussion 1340–1.

    Article  CAS  PubMed  Google Scholar 

  32. Fanous MY, Phillips AJ, Windsor JA. Mesenteric lymph: the bridge to future management of critical illness. JOP. 2007;8(4):374–99.

    PubMed  Google Scholar 

  33. Deitch EA. Gut lymph and lymphatics: a source of factors leading to organ injury and dysfunction. Ann N Y Acad Sci. 2010;1207(Suppl 1):E103–11.

    Article  PubMed  Google Scholar 

  34. Deitch EA. Role of the gut lymphatic system in multiple organ failure. Curr Opin Crit Care. 2001;7(2):92–8.

    Article  CAS  PubMed  Google Scholar 

  35. Magnotti LJ, Upperman JS, Xu DZ, Lu Q, Deitch EA. Gut-derived mesenteric lymph but not portal blood increases endothelial cell permeability and promotes lung injury after hemorrhagic shock. Ann Surg. 1998;228(4):518–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Deitch EA, Adams C, Lu Q, Xu DZ. A time course study of the protective effect of mesenteric lymph duct ligation on hemorrhagic shock-induced pulmonary injury and the toxic effects of lymph from shocked rats on endothelial cell monolayer permeability. Surgery. 2001;129(1):39–47.

    Article  CAS  PubMed  Google Scholar 

  37. Sambol JT, Xu DZ, Adams CA, Magnotti LJ, Deitch EA. Mesenteric lymph duct ligation provides long term protection against hemorrhagic shock-induced lung injury. Shock. 2000;14(3):416–9. discussion 419–20.

    Article  CAS  PubMed  Google Scholar 

  38. Gonzalez RJ, Moore EE, Ciesla DJ, Biffl WL, Johnson JL, Silliman CC. Mesenteric lymph is responsible for post-hemorrhagic shock systemic neutrophil priming. J Trauma. 2001;51(6):1069–72.

    CAS  PubMed  Google Scholar 

  39. Xu DZ, Lu Q, Adams CA, Issekutz AC, Deitch EA. Trauma-hemorrhagic shock-induced up-regulation of endothelial cell adhesion molecules is blunted by mesenteric lymph duct ligation. Crit Care Med. 2004;32(3):760–5.

    Article  CAS  PubMed  Google Scholar 

  40. Zallen G, Moore EE, Johnson JL, Tamura DY, Ciesla DJ, Silliman CC. Posthemorrhagic shock mesenteric lymph primes circulating neutrophils and provokes lung injury. J Surg Res. 1999;83(2):83–8.

    Article  CAS  PubMed  Google Scholar 

  41. Gonzalez RJ, Moore EE, Ciesla DJ, Nieto JR, Johnson JL, Silliman CC. Post-hemorrhagic shock mesenteric lymph activates human pulmonary microvascular endothelium for in vitro neutrophil-mediated injury: the role of intercellular adhesion molecule-1. J Trauma. 2003;54(2):219–23.

    Article  CAS  PubMed  Google Scholar 

  42. Deitch EA, Adams CA, Lu Q, Xu DZ. Mesenteric lymph from rats subjected to trauma-hemorrhagic shock are injurious to rat pulmonary microvascular endothelial cells as well as human umbilical vein endothelial cells. Shock. 2001;16(4):290–3.

    Article  CAS  PubMed  Google Scholar 

  43. Davidson MT, Deitch EA, Lu Q, Hasko G, Abungu B, Nemeth ZH, et al. Trauma-hemorrhagic shock mesenteric lymph induces endothelial apoptosis that involves both caspase-dependent and caspase-independent mechanisms. Ann Surg. 2004;240(1):123–31.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Niu CY, Zhao ZG, Li JC, Chen RH, Zhang J, Zhang YP, et al. Damage effects of shock lymph on the pulmonary micro-vascular endothelial cells of rats. Fen Zi Xi Bao Sheng Wu Xue Bao. 2007;40(2):145–52.

    CAS  PubMed  Google Scholar 

  45. Barlos D, Deitch EA, Watkins AC, Caputo FJ, Lu Q, Abungu B, et al. Trauma-hemorrhagic shock-induced pulmonary epithelial and endothelial cell injury utilizes different programmed cell death signaling pathways. Am J Physiol Lung Cell Mol Physiol. 2009;296(3):L404–17.

    Article  CAS  PubMed  Google Scholar 

  46. Senthil M, Watkins A, Barlos D, Xu DZ, Lu Q, Abungu B, et al. Intravenous injection of trauma-hemorrhagic shock mesenteric lymph causes lung injury that is dependent upon activation of the inducible nitric oxide synthase pathway. Ann Surg. 2007;246(5):822–30.

    Article  PubMed  Google Scholar 

  47. Wohlauer MV, Moore EE, Harr J, Eun J, Fragoso M, Banerjee A, et al. Cross-transfusion of postshock mesenteric lymph provokes acute lung injury. J Surg Res. 2011;170(2):314–8.

    PubMed  PubMed Central  Google Scholar 

  48. Tsan MF, Gao B. Endogenous ligands of toll-like receptors. J Leukoc Biol. 2004;76(3):514–9.

    Article  CAS  PubMed  Google Scholar 

  49. Reino DC, Pisarenko V, Palange D, Doucet D, Bonitz RP, Lu Q, et al. Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice. PLoS One. 2011;6(8):e14829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chatpun S, Cabrales P. Cardiac systolic function recovery after hemorrhage determines survivability during shock. J Trauma. 2011;70(4):787–93.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Piquereau J, Godin R, Deschenes S, Bessi VL, Mofarrahi M, Hussain SN, et al. Protective role of PARK2/Parkin in sepsis-induced cardiac contractile and mitochondrial dysfunction. Autophagy. 2013;9(11):1837–51.

    Article  CAS  PubMed  Google Scholar 

  52. Zaky A, Deem S, Bendjelid K, Treggiari MM. Characterization of cardiac dysfunction in sepsis: an ongoing challenge. Shock. 2014;41(1):12–24.

    Article  PubMed  Google Scholar 

  53. Zhao ZG, Niu CY, Chen RH, Zhang YP, Zhang J, Liu YK, et al. Effect of intestinal lymphatic pathway on free radical and inflammatory mediator of myocardium in shock rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007;23(4):385–9.

    CAS  PubMed  Google Scholar 

  54. Sambol JT, Lee MA, Caputo FJ, Kawai K, Badami C, Kawai T, et al. Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction. J Appl Physiol (1985). 2009;106(1):57–65.

    Article  Google Scholar 

  55. Du HB, Wang SH, Zhao ZG, Niu CY. Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock. Acta Cir Bras. 2015;30(6):439–44.

    Article  PubMed  Google Scholar 

  56. Sambol JT, Lee MA, Jiang M, Dosi G, Dong W, Deitch EA, et al. Mesenteric lymph from rats with trauma-hemorrhagic shock causes abnormal cardiac myocyte function and induces myocardial contractile dysfunction. J Appl Physiol (1985). 2011;111(3):799–807.

    Article  Google Scholar 

  57. Wohlauer MV, Sauaia A, Moore EE, Burlew CC, Banerjee A, Johnson J. Acute kidney injury and posttrauma multiple organ failure: the canary in the coal mine. J Trauma Acute Care Surg. 2012;72(2):373–8. discussion 379–80.

    Article  PubMed  Google Scholar 

  58. Rohrig R, Ronn T, Lendemans S, Feldkamp T, de Groot H, Petrat F. Adverse effects of resuscitation with lactated ringer compared with ringer solution after severe hemorrhagic shock in rats. Shock. 2012;38(2):137–45.

    Article  CAS  PubMed  Google Scholar 

  59. Yang HY, Yen TH, Lin CY, Chen YC, Pan MJ, Lee CH, et al. Early identification of leptospirosis as an ignored cause of multiple organ dysfunction syndrome. Shock. 2012;38(1):24–9.

    Article  PubMed  Google Scholar 

  60. Niu CY, Zhao ZG, Ye YL, Hou YL, Zhang YP. Mesenteric lymph duct ligation against renal injury in rats after hemorrhagic shock. Ren Fail. 2010;32(5):584–91.

    Article  CAS  PubMed  Google Scholar 

  61. Stringham JR, Moore EE, Gamboni F, Harr JN, Fragoso M, Chin TL, et al. Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock. J Trauma Acute Care Surg. 2014;76(5):1214–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhao ZG, Zhu HX, Zhang LM, Zhang YP, Niu CY. Mesenteric lymph drainage alleviates acute kidney injury induced by hemorrhagic shock without resuscitation. ScientificWorldJournal. 2014;2014:720836.

    PubMed  PubMed Central  Google Scholar 

  63. Han B, Zhao ZG, Zhang LM, Li SG, Niu CY. Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats. Braz J Med Biol Res. 2015;48(7):622–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhao ZG, Niu CY, Qiu JF, Chen XD, Li JC. Effect of mesenteric lymph duct ligation on gene expression profiles of renal tissue in hemorrhagic shock rats with fluid resuscitation. Ren Fail. 2014;36(2):271–7.

    Article  PubMed  CAS  Google Scholar 

  65. Zhao ZG, Zhang LM, Lv YZ, Si YH, Niu CY, Li JC. Changes in renal tissue proteome induced by mesenteric lymph drainage in rats after hemorrhagic shock with resuscitation. Shock. 2014;42(4):350–5.

    Article  CAS  PubMed  Google Scholar 

  66. Douzinas EE. Hemorrhagic shock resuscitation: a critical issue on the development of posttraumatic multiple organ failure. Crit Care Med. 2012;40(4):1348–9.

    Article  PubMed  Google Scholar 

  67. Zhou R, Ding XL, Liu LM. Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats. Acta Pharmacol Sin. 2014;35(11):1375–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lei Y, Peng X, Liu L, Dong Z, Li T. Beneficial effect of cyclosporine A on traumatic hemorrhagic shock. J Surg Res. 2015;195(2):529–40.

    Article  CAS  PubMed  Google Scholar 

  69. Liu S, Li T, Yang G, Hu Y, Xiao X, Xu J, et al. Protein markers related to vascular responsiveness after hemorrhagic shock in rats. J Surg Res. 2015;196(1):149–58.

    Article  CAS  PubMed  Google Scholar 

  70. Zhao KS, Liu J, Yang GY, Jin C, Huang Q, Huang X. Peroxynitrite leads to arteriolar smooth muscle cell membrane hyperpolarization and low vasoreactivity in severe shock. Clin Hemorheol Microcirc. 2000;23(2–4):259–67.

    CAS  PubMed  Google Scholar 

  71. Zhao KS, Huang X, Liu J, Huang Q, Jin C, Jiang Y, et al. New approach to treatment of shock--restitution of vasoreactivity. Shock. 2002;18(2):189–92.

    Article  PubMed  Google Scholar 

  72. Pan BX, Zhao GL, Huang XL, Jin JQ, Zhao KS. Peroxynitrite induces arteriolar smooth muscle cells membrane hyperpolarization with arteriolar hyporeactivity in rats. Life Sci. 2004;74(10):1199–210.

    Article  CAS  PubMed  Google Scholar 

  73. Pan BX, Zhao GL, Huang XL, Zhao KS. Mobilization of intracellular calcium by peroxynitrite in arteriolar smooth muscle cells from rats. Redox Rep. 2004;9(1):49–55.

    Article  CAS  PubMed  Google Scholar 

  74. Zhao KS. Hemorheologic events in severe shock. Biorheology. 2005;42(6):463–77.

    PubMed  Google Scholar 

  75. Zhao ZG, Niu CY, Wei YL, Zhang YP, Si YH, Zhang J. Mesenteric lymph return is an important contributor to vascular hyporeactivity and calcium desensitization after hemorrhagic shock. Shock. 2012;38(2):186–95.

    Article  CAS  PubMed  Google Scholar 

  76. Li T, Fang Y, Yang G, Zhu Y, Xu J, Liu L. The mechanism by which RhoA regulates vascular reactivity after hemorrhagic shock in rats. Am J Physiol Heart Circ Physiol. 2010;299(2):H292–9.

    Article  CAS  PubMed  Google Scholar 

  77. Li T, Yang G, Xu J, Zhu Y, Liu L. Regulatory effect of Rac1 on vascular reactivity after hemorrhagic shock in rats. J Cardiovasc Pharmacol. 2011;57(6):656–65.

    Article  CAS  PubMed  Google Scholar 

  78. Li T, Fang Y, Yang G, Xu J, Zhu Y, Liu L. Effects of the balance in activity of RhoA and Rac1 on the shock-induced biphasic change of vascular reactivity in rats. Ann Surg. 2011;253(1):185–93.

    Article  PubMed  Google Scholar 

  79. Liu L, Zang J, Chen X, Yang G, Zhu Y, Wu Y, et al. Role of miR-124 and miR-141 in the regulation of vascular reactivity and the relationship to RhoA and Rac1 after hemorrhage and hypoxia. Am J Physiol Heart Circ Physiol. 2016;310(2):H206–16.

    Article  PubMed  Google Scholar 

  80. Li T, Liu L, Xu J, Yang G, Ming J. Changes of Rho kinase activity after hemorrhagic shock and its role in shock-induced biphasic response of vascular reactivity and calcium sensitivity. Shock. 2006;26(5):504–9.

    Article  PubMed  CAS  Google Scholar 

  81. Li T, Liu L, Liu J, Ming J, Xu J, Yang G, et al. Mechanisms of Rho kinase regulation of vascular reactivity following hemorrhagic shock in rats. Shock. 2008;29(1):65–70.

    PubMed  Google Scholar 

  82. Yang G, Liu L, Xu J, Li T. Effect of arginine vasopressin on vascular reactivity and calcium sensitivity after hemorrhagic shock in rats and its relationship to Rho-kinase. J Trauma. 2006;61(6):1336–42.

    Article  CAS  PubMed  Google Scholar 

  83. Xu J, Yang GM, Li T, Ming J, Chen W, Zhang Y, et al. The regulatory effect of protein kinase C epsilon on vascular reactivity and calcium sensitivity during hemorrhagic shock in rats. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008;20(3):144–7.

    CAS  PubMed  Google Scholar 

  84. Fang Y, Li T, Fan X, Zhu Y, Liu L. Beneficial effects of activation of PKC on hemorrhagic shock in rats. J Trauma. 2010;68(4):865–73.

    CAS  PubMed  Google Scholar 

  85. Yang G, Li T, Xu J, Liu L. PKC plays an important mediated effect in arginine vasopressin induced restoration of vascular responsiveness and calcium sensitization following hemorrhagic shock in rats. Eur J Pharmacol. 2010;628(1–3):148–54.

    Article  CAS  PubMed  Google Scholar 

  86. Yang GM, Li T, Xu J, Ming J, Liu LM. Effect of arginine vasopressin on vascular reactivity and calcium sensitivity of vascular smooth muscle and its relationship to protein kinase C following hemorrhagic shock in rats. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008;20(3):139–43.

    CAS  PubMed  Google Scholar 

  87. Xu J, Li T, Yang G, Liu L. Pinacidil pretreatment improves vascular reactivity after shock through PKCalpha and PKCepsilon in rats. J Cardiovasc Pharmacol. 2012;59(6):514–22.

    Article  CAS  PubMed  Google Scholar 

  88. Xu J, Lan D, Yang G, Li T, Liu L. Hemorrhagic preconditioning improves vascular reactivity after hemorrhagic shock by activation of PKCalpha and PKCepsilon via the adenosine A1 receptor in rats. J Trauma Acute Care Surg. 2013;74(5):1266–74.

    CAS  PubMed  Google Scholar 

  89. Li T, Liu LM, Liu JC. Regulatory effect of protein kinase C and protein kinase G on calcium sensitivity of vascular smooth muscle cells following hemorrhagic shock. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007;19(5):257–60.

    PubMed  Google Scholar 

  90. Yang G, Li T, Xu J, Peng X, Liu L. Mitogen-activated protein kinases regulate vascular reactivity after hemorrhagic shock through myosin light chain phosphorylation pathway. J Trauma Acute Care Surg. 2013;74(4):1033–43.

    Article  CAS  PubMed  Google Scholar 

  91. Yang G, Xu J, Li T, Ming J, Chen W, Liu L. Role of V1a receptor in AVP-induced restoration of vascular hyporeactivity and its relationship to MLCP-MLC20 phosphorylation pathway. J Surg Res. 2010;161(2):312–20.

    Article  CAS  PubMed  Google Scholar 

  92. Zhao Z, Si Y, Zhang Y, Du S, Zhang L, Niu C. Postshock mesenteric lymph drainage ameliorates vascular reactivity and calcium sensitivity through RhoA. J Surg Res. 2014;186(1):304–9.

    Article  CAS  PubMed  Google Scholar 

  93. Zhang YP, Niu CY, Zhao ZG, Zhang LM, Si YH. Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats. Braz J Med Biol Res. 2013;46(7):574–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Niu CY, Zhao ZG, Wei YL, Zhang YP, Zhang J. Involvement of protein kinase C in enhancement of vascular calcium sensitivity by blocking mesenteric lymph return in hemorrhagic shock rats. Sheng Li Xue Bao. 2012;64(2):213–9.

    CAS  PubMed  Google Scholar 

  95. Zhao ZG, Wei YL, Niu CY, Zhang YP, Zhang LM, Jiang LN. Role of protein kinase G on the post-shock mesenteric lymph blockage ameliorating vascular calcium sensitivity. Acta Cir Bras. 2013;28(7):537–42.

    Article  PubMed  Google Scholar 

  96. Zhao ZG, Niu CY, Wei YL, Zhang YP, Si YH, Zhang J. Role of rho kinase in blocking the return of mesenteric lymph to improve vascular calcium sensitivity in hemorrhagic shock rats. Chin J Pathophysiol. 2012;1:11–5.

    Google Scholar 

  97. Song R, Bian H, Wang X, Huang X, Zhao KS. Mitochondrial injury underlies hyporeactivity of arterial smooth muscle in severe shock. Am J Hypertens. 2011;24(1):45–51.

    Article  CAS  PubMed  Google Scholar 

  98. Wang X, Song R, Chen Y, Zhao M, Zhao KS. Polydatin--a new mitochondria protector for acute severe hemorrhagic shock treatment. Expert Opin Investig Drugs. 2013;22(2):169–79.

    Article  CAS  PubMed  Google Scholar 

  99. Sun GX, Guo YX, Du HB, Zhang LM, Zhao ZG, Liu SJ, et al. Role of post-hemorrhagic shock mesenteric lymph in enhancement of vascular permeability. Chin J Pathophysiol. 2014;30(8):1506–36.

    Google Scholar 

  100. Lu Q, Xu DZ, Davidson MT, Hasko G, Deitch EA. Hemorrhagic shock induces endothelial cell apoptosis, which is mediated by factors contained in mesenteric lymph. Crit Care Med. 2004;32(12):2464–70.

    Article  PubMed  Google Scholar 

  101. Komarova Y, Malik AB. Regulation of endothelial permeability via paracellular and transcellular transport pathways. Annu Rev Physiol. 2010;72:463–93.

    Article  CAS  PubMed  Google Scholar 

  102. Dejana E, Tournier-Lasserve E, Weinstein BM. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell. 2009;16(2):209–21.

    Article  CAS  PubMed  Google Scholar 

  103. Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev. 2006;86(1):279–367.

    Article  CAS  PubMed  Google Scholar 

  104. Komarova YA, Kruse K, Mehta D, Malik AB. Protein interactions at endothelial junctions and signaling mechanisms regulating endothelial permeability. Circ Res. 2017;120(1):179–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wallez Y, Huber P. Endothelial adherens and tight junctions in vascular homeostasis, inflammation and angiogenesis. Biochim Biophys Acta. 2008;1778(3):794–809.

    Article  CAS  PubMed  Google Scholar 

  106. Sun GX, Guo YX, Zhang YP, Zhang LM, Zhao ZG, Niu CY. Posthemorrhagic shock mesenteric lymph enhances monolayer permeability via F-actin and VE-cadherin. J Surg Res. 2016;203(1):47–55.

    Article  CAS  PubMed  Google Scholar 

  107. Angele MK, Chaudry IH. Surgical trauma and immunosuppression: pathophysiology and potential immunomodulatory approaches. Langenbeck’s Arch Surg. 2005;390(4):333–41.

    Article  Google Scholar 

  108. Hostmann A, Jasse K, Schulze-Tanzil G, Robinson Y, Oberholzer A, Ertel W, et al. Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins. Crit Care. 2008;12(1):R8.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Barkhausen T, Frerker C, Putz C, Pape HC, Krettek C, van Griensven M. Depletion of NK cells in a murine polytrauma model is associated with improved outcome and a modulation of the inflammatory response. Shock. 2008;30(4):401–10.

    Article  CAS  PubMed  Google Scholar 

  110. Kawasaki T, Suzuki T, Choudhry MA, Bland KI, Chaudry IH. Salutary effects of 17beta-estradiol on Peyer’s patch T cell functions following trauma-hemorrhage. Cytokine. 2010;51(2):166–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Grootjans J, Hodin CM, de Haan JJ, Derikx JP, Rouschop KM, Verheyen FK, et al. Level of activation of the unfolded protein response correlates with Paneth cell apoptosis in human small intestine exposed to ischemia/reperfusion. Gastroenterology. 2011;140(2):529–539.e3.

    Article  CAS  PubMed  Google Scholar 

  112. Kim JY, Hong YS, Choi SH, Yoon YH, Moon SW, Lee SW. Effect of hypertonic saline on apoptosis of polymorphonuclear cells. J Surg Res. 2012;178(1):401–8.

    Article  CAS  PubMed  Google Scholar 

  113. Tiesi G, Reino D, Mason L, Palange D, Tomaio JN, Deitch EA. Early trauma-hemorrhage-induced splenic and thymic apoptosis is gut-mediated and toll-like receptor 4-dependent. Shock. 2013;39(6):507–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Liu H, Zhao ZG, Xing LQ, Zhang LM, Niu CY. Post-shock mesenteric lymph drainage ameliorates cellular immune function in rats following hemorrhagic shock. Inflammation. 2015;38(2):584–94.

    Article  CAS  PubMed  Google Scholar 

  115. Liu H, Xing LQ, Zhao ZG, Niu CY. Mesenteric lymph drainage alleviates spleen injury in hemorrhagic shock rats. Chin J Pathophysiol. 2013;29(8):1496–501.

    CAS  Google Scholar 

  116. Adams CA Jr, Xu DZ, Lu Q, Deitch EA. Factors larger than 100 kd in post-hemorrhagic shock mesenteric lymph are toxic for endothelial cells. Surgery. 2001;129(3):351–63.

    Article  PubMed  Google Scholar 

  117. Kaiser VL, Sifri ZC, Dikdan GS, Berezina T, Zaets S, Lu Q, et al. Trauma-hemorrhagic shock mesenteric lymph from rat contains a modified form of albumin that is implicated in endothelial cell toxicity. Shock. 2005;23(5):417–25.

    Article  CAS  PubMed  Google Scholar 

  118. Kaiser VL, Sifri ZC, Senthil M, Dikdan GS, Lu Q, Xu DZ, et al. Albumin peptide: a molecular marker for trauma/hemorrhagic-shock in rat mesenteric lymph. Peptides. 2005;26(12):2491–9.

    Article  CAS  PubMed  Google Scholar 

  119. Jordan JR, Moore EE, Damle SS, Eckels P, Johnson JL, Roach JP, et al. Gelsolin is depleted in post-shock mesenteric lymph. J Surg Res. 2007;143(1):130–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Peltz ED, Moore EE, Zurawel AA, Jordan JR, Damle SS, Redzic JS, et al. Proteome and system ontology of hemorrhagic shock: exploring early constitutive changes in postshock mesenteric lymph. Surgery. 2009;146(2):347–57.

    Article  PubMed  Google Scholar 

  121. Fang JF, Shih LY, Yuan KC, Fang KY, Hwang TL, Hsieh SY. Proteomic analysis of post-hemorrhagic shock mesenteric lymph. Shock. 2010;34(3):291–8.

    Article  CAS  PubMed  Google Scholar 

  122. Mittal A, Middleditch M, Ruggiero K, Loveday B, Delahunt B, Jullig M, et al. Changes in the mesenteric lymph proteome induced by hemorrhagic shock. Shock. 2010;34(2):140–9.

    Article  CAS  PubMed  Google Scholar 

  123. D’Alessandro A, Dzieciatkowska M, Peltz ED, Moore EE, Jordan JR, Silliman CC, et al. Dynamic changes in rat mesenteric lymph proteins following trauma using label-free mass spectrometry. Shock. 2014;42(6):509–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Dzieciatkowska M, D’Alessandro A, Moore EE, Wohlauer M, Banerjee A, Silliman CC, et al. Lymph is not a plasma ultrafiltrate: a proteomic analysis of injured patients. Shock. 2014;42(6):485–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Gonzalez RJ, Moore EE, Biffl WL, Ciesla DJ, Silliman CC. The lipid fraction of post-hemorrhagic shock mesenteric lymph (PHSML) inhibits neutrophil apoptosis and enhances cytotoxic potential. Shock. 2000;14(3):404–8.

    Article  CAS  PubMed  Google Scholar 

  126. Gonzalez RJ, Moore EE, Ciesla DJ, Biffl WL, Offner PJ, Silliman CC. Phospholipase A(2)--derived neutral lipids from posthemorrhagic shock mesenteric lymph prime the neutrophil oxidative burst. Surgery. 2001;130(2):198–203.

    Article  CAS  PubMed  Google Scholar 

  127. Gonzalez RJ, Moore EE, Ciesla DJ, Meng X, Biffl WL, Silliman CC. Post-hemorrhagic shock mesenteric lymph lipids prime neutrophils for enhanced cytotoxicity via phospholipase A2. Shock. 2001;16(3):218–22.

    Article  CAS  PubMed  Google Scholar 

  128. Morishita K, Aiboshi J, Kobayashi T, Mikami S, Yokoyama Y, Ogawa K, et al. Lipidomics analysis of mesenteric lymph after trauma and hemorrhagic shock. J Trauma Acute Care Surg. 2012;72(6):1541–7.

    Article  CAS  PubMed  Google Scholar 

  129. Qin X, Dong W, Sharpe SM, Sheth SU, Palange DC, Rider T, et al. Role of lipase-generated free fatty acids in converting mesenteric lymph from a noncytotoxic to a cytotoxic fluid. Am J Physiol Gastrointest Liver Physiol. 2012;303(8):G969–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Davis MJ, Lane MM, Davis AM, Durtschi D, Zawieja DC, Muthuchamy M, et al. Modulation of lymphatic muscle contractility by the neuropeptide substance P. Am J Physiol Heart Circ Physiol. 2008;295(2):H587–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Nepiyushchikh ZV, Chakraborty S, Wang W, Davis MJ, Zawieja DC, Muthuchamy M. Differential effects of myosin light chain kinase inhibition on contractility, force development and myosin light chain 20 phosphorylation of rat cervical and thoracic duct lymphatics. J Physiol. 2011;589(Pt 22):5415–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Qin LP, Niu CY, Zhao ZG, Zhang J, Zhang YP. Substance P enhances pump function of isolated lymphatics from hemorrhagic shock rats. Chin J Pathophysiol. 2011;27(7):1323–8.

    CAS  Google Scholar 

  133. Zhang YP, Niu CY, Zhao ZG, Qin LP, Si YH, Zhang LM, et al. Role of myosin-light-chain kinase in biphasic contractile activity of lymphatics isolated from hemorrhagic shock rats. Chin J Pathophysiol. 2012;28(4):589–94.

    Google Scholar 

  134. Kawai Y, Yokoyama Y, Kaidoh M, Ohhashi T. Shear stress-induced ATP-mediated endothelial constitutive nitric oxide synthase expression in human lymphatic endothelial cells. Am J Physiol Cell Physiol. 2009;298(3):C647–55.

    Article  PubMed  CAS  Google Scholar 

  135. Bohlen HG, Wang W, Gashev A, Gasheva O, Zawieja D. Phasic contractions of rat mesenteric lymphatics increase basal and phasic nitric oxide generation in vivo. Am J Physiol Heart Circ Physiol. 2009;297(4):H1319–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Gasheva OY, Zawieja DC, Gashev AA. Contraction-initiated NO-dependent lymphatic relaxation: a self-regulatory mechanism in rat thoracic duct. J Physiol. 2006;575(Pt 3):821–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. von der Weid PY, Zhao J, Van Helden DF. Nitric oxide decreases pacemaker activity in lymphatic vessels of guinea pig mesentery. Am J Physiol Heart Circ Physiol. 2001;280(6):H2707–16.

    Article  PubMed  Google Scholar 

  138. Bridenbaugh EA, Gashev AA, Zawieja DC. Lymphatic muscle: a review of contractile function. Lymphat Res Biol. 2003;1(2):147–58.

    Article  PubMed  Google Scholar 

  139. von der Weid PY. ATP-sensitive K+ channels in smooth muscle cells of guinea-pig mesenteric lymphatics: role in nitric oxide and beta-adrenoceptor agonist-induced hyperpolarizations. Br J Pharmacol. 1998;125(1):17–22.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Wang W, Nepiyushchikh Z, Zawieja DC, Chakraborty S, Zawieja SD, Gashev AA, et al. Inhibition of myosin light chain phosphorylation decreases rat mesenteric lymphatic contractile activity. Am J Physiol Heart Circ Physiol. 2009;297(2):H726–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Zhang LM, Qin LP, Zhang YP, Zhao ZG, Niu CY. Nitric oxide regulates the lymphatic reactivity following hemorrhagic shock through Atp-sensitive potassium Channel. Shock. 2016;45(6):668–76.

    Article  CAS  PubMed  Google Scholar 

  142. Zhang LM, Niu CY, Zhao ZG, Si YH, Zhang YP. ATP-sensitive potassium channel involved in modulation of nitride oxide regulating contractile activity of isolated lymphatics from hemorrhagic shock rats. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2012;24(8):457–60.

    PubMed  Google Scholar 

  143. Liao MH, Shih CC, Tsao CM, Chen SJ, Wu CC. RhoA/Rho-kinase and nitric oxide in vascular reactivity in rats with endotoxaemia. PLoS One. 2013;8(2):e56331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Hosaka K, Mizuno R, Ohhashi T. Rho-Rho kinase pathway is involved in the regulation of myogenic tone and pump activity in isolated lymph vessels. Am J Physiol Heart Circ Physiol. 2003;284(6):H2015–25.

    Article  CAS  PubMed  Google Scholar 

  145. Souza-Smith FM, Molina PE, Breslin JW. Reduced RhoA activity mediates acute alcohol intoxication-induced inhibition of lymphatic myogenic constriction despite increased cytosolic [Ca(2+)]. Microcirculation. 2013;20(5):377–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Si YH, Niu CY, Zhao ZG, Zhang LM, Zhang YP. Role of RhoA in regulating the pump function of isolated lymphatics from hemorrhagic shock rats. Shock. 2013;40(1):49–58.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

Research reported in this review from the authors’ laboratories was supported by grants from the National Natural Science Foundation of China (39070388, 30370561, 30770845, and 30971203) and the Natural Science Foundation of Hebei Province (C2004000649, C2008000503, C2010001433, and H2012405020). The authors appreciate Prof. Niu Chun-yu and Prof. Zhang Jing for the extraordinary contributions to our researches in shock and lymphatic microcirculation. Also, the authors thank Dr. Xue Bao-jian and Prof. Liu Liang-ming for reviewing the manuscript.

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  1. Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China

    Zi-Gang Zhao, Yu-Ping Zhang, Li-Min Zhang & Ya-Xiong Guo

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  1. Zi-Gang Zhao
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  1. Wound Healing and Cell Biology Lab, First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China

    Xiaobing Fu

  2. State Key Laboratory of Trauma, Burns, and Combined Injury, Daping Hospital, Third Military Medical University, Chong Qing, China

    Liangming Liu

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Zhao, ZG., Zhang, YP., Zhang, LM., Guo, YX. (2019). Lymph Formation and Transport: Role in Trauma-Hemorrhagic Shock. In: Fu, X., Liu, L. (eds) Severe Trauma and Sepsis. Springer, Singapore. https://doi.org/10.1007/978-981-13-3353-8_5

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