Background. Actuality is determined by understudied fibrinolytic reactions in case of diabetes mellitus (DM) with acute peritonitis (AP) which is to be found in practice more frequent. The purpose of the study was to investigate the features of fibrinolytic activity in AP developed on the background of DM. Materials and methods. 100 albino outbred rats. AP was simulated through the esophageal perforation of the stomach. DM was modeled by the 1.6% alloxan solution injection. During the study, total (TFA), non-enzymatic (NFA) and enzymatic fibrinolytic activity (EFA) of the blood plasma was studied. The animals were divided into such groups: 1 — intact animals with AP models; 2 — animals with models of AP and underlying DM. Results. The activity of fibrinolysis in animals with DM models was higher than that of intact animals. Six hours after the AP have been induced, the fibrinolytic activity increased. There was a less augmentation in group 1. TFA, NFA and EFA in group 2 sharply increased and prevailed significantly in 12 hours. EFA significantly increased in group 1. NFA/EFA ratio was decreasing in both groups. TFA in group 1 slightly increased in 24 hours. All of the indicators in group 2 increased significantly. While the ratio of NFA/EFA in group 1 was increasing, in group 2 it was decreasing. TFA and NFA/EFA ratio in group 1 remained more or less constant in 48 hours. The parameters of TFA, NFA and EFA statistically significantly predominated in group 2, and EFA continued to grow. Conclusions. The increase in the fibrinolytic activity of the blood plasma with the fermentation mechanisms predomination have been found in experimental diabetes mellitus. The activation of fibrinolysis with balance maintenance between its links within 24 hours has been observed in case of experimental acute peritonitis. In 6 hours, the development of acute peritonitis in animals with simulated diabetes mellitus differs substantially in terms of its quantitative characteristics of the fibrinolytic activity of the blood plasma, which is shown by its excessive increase, development of imbalance between the links of fibrinolysis, uncontrolled increase in the activity of fermentation mechanisms with disseminated intravascular coagulation syndrome in 24 hours. The basis for the differences that have been detected are the changes in the functional activity of the fibrinolytic system caused by diabetes mellitus influence that, in addition to changes in the hemostasis system, provide the grounds for disorders of mechanisms of activation, migration and interaction of effector cells, processes of proliferation, etc
diabetes mellitus; peritonitis; comorbidity; fibrinolytic system
Zak KP, Tron'ko MD, Popova VV, Butenko AK. Sakharnyi diabet. Immunitet. Tsitokiny [Diabetes. Immunity. Cytokines]. Kyiv: Kniga-plius; 2015. 488 p. (in Russian).
Tancredi М, Rosengren А, Svensson АМ, et al. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med. 2015 Oct 29;373(18):1720-32. doi: 10.1056/NEJMoa1504347.
Polianskyi IYu, Hrynchuk FV, Bilookyi VV, et al. Acute peritonitis on the modern stage-problems, achievements and prospects. Clinical anatomy and operative surgery. 2014;13(1):83-87. (in Ukrainian).
Akahoshi T, Sugimori H, Kaku N, et al. Comparison of recombinant human thrombomodulin and gabexate mesylate for treatment of disseminated intravascular coagulation (DIC) with sepsis following emergent gastrointestinal surgery: a retrospective study. Eur J Trauma Emerg Surg. 2015 Oct;41(5):531-8. doi: 10.1007/s00068-014-0478-4.
Derive M, Boufenzer A, Bouazza Y, et al. Effects of a TREM-like transcript 1-derived peptide during hypodynamic septic shock in pigs. Shock. 2013 Feb;39(2):176-82. doi: 10.1097/SHK.0b013e31827bcdfb.
Bocharov AV. Tissue fibrinolytic activity in the organs of the peritoneal cavity in the experimental bile peritonitis. Buk Med Herald. 2002;1-2:46-49. (in Ukrainian).
Wu R, Peng LG, Zhao HM. Diverse coagulopathies in a rabbit model with different abdominal injuries. World J Emerg Med. 2017;8(2):141-147. doi: 10.5847/wjem.j.1920-8642.2017.02.011.
Behl T, Velpandian T, Kotwani A. Role of altered coagulation-fibrinolytic system in the pathophysiology of diabetic retinopathy. Vascul Pharmacol. 2017 May;92:1-5. doi: 10.1016/j.vph.2017.03.005.
Grynchuk FV, Poljanskyj IJu. Sposib modeljuvannja gostrogo perytonitu [Method of simulation of acute peritonitis]. Patent UA № 4766 A, 2005. (in Ukrainian).
Shaw Dunn J, Mcletchie NGB. Experimental alloxan diabetes in the rat. The Lancet. 1943 Sept;242(6265):384-387. doi: 10.1016/S0140-6736(00)87397-3.
Kuharchuk OL. Patogenetychna rol' ta metody korekcii' integratyvnyh porushen' gormonal'no-mesendzhernyh system reguljacii' gomeostazu natriju pry patologii' nyrok Diss. dokt. med. nauk [Pathogenetic role and correction methods of integrative sodium hormonal-messenger regulation systems disorders in kidney pathology. Dr. med. sci. diss.]. Odesa, Odesa medical institute, 1996. 36 p. (in Ukrainian).
Aboonabi A, Singh I. The effectiveness of antioxidant therapy in aspirin resistance, diabetes population for prevention of thrombosis. Biomed Pharmacother. 2016 Oct;83:277-282. doi: 10.1016/j.biopha.2016.06.044.
Kearney K, Tomlinson D, Smith K, Ajjan R. Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk. Cardiovasc Diabetol. 2017 Mar 9;16(1):34. doi: 10.1186/s12933-017-0515-9.
Pomero F, Di Minno MN, Fenoglio L, Gianni M, Ageno W, Dentali F. Is diabetes a hypercoagulable state? A critical appraisal. Acta Diabetol. 2015 Dec;52(6):1007-16. doi: 10.1007/s00592-015-0746-8.
Gritsiuk AI, Amosova EN, Gritsiuk IA. Prakticheskaia gemostaziologiia [Practical hemostasiology]. Kyiv: Zdorov’ia; 1994. 256 p. (in Russian).
Monastyrs'kyj VA. Trombin-plazminova systema - odna z osnovnyh reguljatornyh system organizmu. Fiziologichna, patogenetychna, sanogenetychna rol' : monografija [Trombin-plasmin system is one of the basic regulatory systems of the body. Physiological, pathogenetic, sanogenetic role: monograph]. L'viv: Liga-Pres; 2007. 228 p. (in Ukrainian).
Cole E, Davenport R, De’Ath H, Manson J, Brockamp T, Brohi K. Coagulation system changes associated with susceptibility to infection in trauma patients. J Trauma Acute Care Surg. 2013 Jan;74(1):51-7; discussion 57-8. doi: 10.1097/TA.0b013e3182788b0f.
Ferluga J, Kouser L, Murugaiah V, Sim RB, Kishore U. Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders. Mol Immunol. 2017 Apr;84:84-106. doi: 10.1016/j.molimm.2017.01.015.
Biltoft D, Sidelmann JJ, Olsen LF, Palarasah Y, Gram J. Calibrated kallikrein generation in human plasma. Clin Biochem. 2016 Oct;49(15):1188-1194. doi: 10.1016/j.clinbiochem.2016.06.011. Epub 2016 Jun 29.
Weiler H. Inflammation-associated activation of coagulation and immune regulation by the protein C pathway. Thromb Res. 2014 May;133(0 1):S32-S34. doi: 10.1016/j.thromres.2014.03.015.
Rajendran P, Rengarajan Th, Thangavel J, et al. The Vascular Endothelium and Human Diseases. Int J Biol Sci. 2013 Nov 9;9(10):1057-69. doi: 10.7150/ijbs.7502.
Erginel B, Oksuz L, Erginel T, et al. Effects of tissue plasminogen activator in experimentally induced peritonitis. Ulus Travma Acil Cerrahi Derg. 2014 Jan;20(1):7-11. doi: 10.5505/tjtes.2014.70594.
McDonald B, Davis RP, Kim SJ, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017 Mar 9;129(10):1357-1367. doi: 10.1182/blood-2016-09-741298.
Bhattacharya S, Ploplis VA, Castellino FJ. Bacterial plasminogen receptors utilize host plasminogen system for effective invasion and dissemination. J Biomed Biotechnol. 2012;2012:482096. doi: 10.1155/2012/482096.
Gebbink MF. Tissue-type plasminogen activator-mediated plasminogen activation and contact activation, implications in and beyond haemostasis. J Thromb Haemost. 2011 Jul;9 Suppl 1:174-81. doi: 10.1111/j.1538-7836.2011.04278.x.
Longstaff C, Kolev K. Basic mechanisms and regulation of fibrinolysis. J Thromb Haemost. 2015 Jun;13 Suppl 1:S98-105. doi: 10.1111/jth.12935.
Li X, Ma X. The role of heparin in sepsis: much more than just an anticoagulant. Br J Haematol. 2017 Nov;179(3):389-398. doi: 10.1111/bjh.14885.
Venugopal A. Disseminated intravascular coagulation. Indian J Anaesth. 2014 Sep-Oct; 58(5):603-608. doi: 10.4103/0019-5049.144666.