Condition of microcirculatory and hemostasis systems in rats after moderate hypothermia

Natalia A. Lycheva , Igor I. Shakhmatov , Anton V. Sedov , Daria A. Makushkina , Vyacheslav M. Vdovin

I.P. Pavlov Russian Medical Biological Herald ›› 2019, Vol. 27 ›› Issue (2) : 160 -171.

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I.P. Pavlov Russian Medical Biological Herald ›› 2019, Vol. 27 ›› Issue (2) :160 -171. DOI: 10.23888/PAVLOVJ2019272160-171
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Condition of microcirculatory and hemostasis systems in rats after moderate hypothermia

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Abstract

Hypothermia produces a generalized impact on an organism, with involvement  of all organs and systems into the response. It was shown that hypothermia promotes multi-organ dysfunction syndrome, which makes it important to study the influence of hypothermia on condition of hemostasis and microcirculatory systems.

Aim. To study the condition of the hemostasis system and the microcirculatory bed in different periods of moderate hypothermia in rats.

Materials and Methods. The current study was performed on 50 male Wistar rats. Condition of microcirculatory blood stream in all animals was assessed with laser Doppler flowmetry. Condition of hemostasis system was studied according to routine protocols and an integrated method of examination – thromboelastography. Statistical analysis was performed using Statistica 6.0 software package (StatSoft, USA) with calculation of Mann-Whitney nonparametric test.

Results. Analysis of the experimental data showed that moderate hypothermia produced a pronounced modulating influence on the microcirculatory system. Vasodilatation occurred immediately after reaching the stage of hypothermia, suggesting the beginning of decompensation in the experimental animals. The highest risk for hemodynamic pathologies was observed 5 days after cessation of cooling and was characterized by a massive reduction in the vascular tone, intensification of hemodynamics against the background appearance of thrombinemia markers in the blood stream and pronounced inhibition of fibrinolysis. Enhanced hemodynamics of the nutritional vascular bed with the underlying progressive prothrombotic condition is a potent risk factor for thrombosis and multiple organ dysfunction syndrome. Vasospasm that developed 2 weeks after recovery of the body temperature, indicated a profound modulation of vasculature and preservation of high-level sympathetic input, as well as increasing rigidity of blood vessel walls. Rising fibrinogen concentrations confirm a progressive inflammatory reaction.

Conclusion. A moderate degree of hypothermia produces a pronounced modulating effect on the microcirculation. The established regularities make it possible to form a clear understanding of the course and development of the pathological reaction in the body of victims and to give recommendations on the use of pharmacological medicine for preventive therapy. Thus, a period has been established when thrombotic readiness is maximal, and use of anticoagulant and antiplatelet drugs is required, together with drugs that improve rheological properties of blood.

Keywords

hypothermia / hemostasis / thrombosis / microcirculation / rats

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Natalia A. Lycheva, Igor I. Shakhmatov, Anton V. Sedov, Daria A. Makushkina, Vyacheslav M. Vdovin. Condition of microcirculatory and hemostasis systems in rats after moderate hypothermia. I.P. Pavlov Russian Medical Biological Herald, 2019, 27(2): 160-171 DOI:10.23888/PAVLOVJ2019272160-171

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References

[1]

Potapov AF, Alexeev RZ, Evgrafov SYu. Efferent therapy in treatment of cold injury, complicated by multiple organ dysfunction syndrome. Yakut Medical Journal. 2012;2(38):114-8.

[2]

Потапов А.Ф., Алексеев Р.З., Евграфов С.Ю. Эфферентная терапия в комплексном лечении холодовой травмы, осложненной синдромом полиорганной недостаточности // Якутский медицинский журнал. 2012. №2(38). С. 114-118.

[3]

Bouchama A. Pathogenetic mechanisms of heatstroke and novel therapies. Critical Care. 2012; 16(Suppl 2):17-20. doi:10.1186/cc11265

[4]

Bouchama A. Pathogenetic mechanisms of heatstroke and novel therapies // Critical Care. 2012. Vol. 16, Suppl. 2. Р. 17-20. doi:10.1186/cc11265

[5]

Shah TA, Mauriello CT, Hair PS, et al. Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway. Journal of Translational Medicine. 2014;12: 181-7. doi:10.1186/1479-5876-12-181

[6]

Shah T.A., Mauriello C.T., Hair P.S., et al. Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway // Journal of Translational Medicine. 2014. Vol. 12. P. 181-187. doi:10.1186/1479-5876-12-181

[7]

Corry JJ. Use of hypothermia in the intensive care unit. World Journal of Critical Care Medicine. 2012; 1(4):106-22. doi:10.5492/wjccm.v1.i4.106

[8]

Corry J.J. Use of hypothermia in the intensive care unit // World Journal of Critical Care Medicine. 2012. Vol. 1(4). P. 106-122. doi:10.5492/wjccm.v1.i4.106

[9]

Buijsa EAB, Verboom EM, Topb APC, et al. Early microcirculatory impairment during therapeutic hypothermia is associated with poor outcome in post-cardiac arrest children: A prospective observational cohort study. Resuscitation. 2014;85:397-404. doi:10. 1016/j.resuscitation.2013.10.024

[10]

Buijsa E.A.B., Verboom E.M., Topb A.P.C., et al. Early microcirculatory impairment during therapeutic hypothermia is associated with poor outcome in post-cardiac arrest children: A prospective observational cohort study // Resuscitation. 2014. Vol. 85. P. 397-404. doi:10.1016/j.resuscitation.2013.10.024

[11]

Brändström H, Eriksson A, Giesbrecht G, et al. Fatal hypothermia: an analysis from a sub-arctic region. International Journal of Circumpolar Health. 2012;71(1):18502. doi:10.3402/ ijch.v71i0.18502

[12]

Brändström H., Eriksson A., Giesbrecht G., et al. Fatal hypothermia: an analysis from a sub-arctic region // International Journal of Circumpolar Health. 2012. Vol. 71, №1. P. 18502. doi:10.3402/ ijch.v71i0.18502

[13]

Fujita M, Wei EP, Povlishock JT. Intensity- and Interval-Specific Repetitive Traumatic Brain Injury Can Evoke Both Axonal and Microvascular Damage. Journal of Neurotrauma. 2012;29:2172-80. doi:10. 1089/neu.2012.2357

[14]

Fujita M., Wei E.P., Povlishock J.T. Intensity- and Interval-Specific Repetitive Traumatic Brain Injury Can Evoke Both Axonal and Microvascular Damage // Journal of Neurotrauma. 2012. Vol. 29. P. 2172-2180. doi:10.1089/neu.2012.2357

[15]

Council Directive of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes (86/609/EEC). Official Journal of the European Communities. № L 358. Р. 1-28.

[16]

Council Directive of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes (86/609/EEC) // Official Journal of the European Communities. № L 358. Р. 1-28.

[17]

Coyan G, Moncure M, Thomas J, et al. Induced Hypothermia During Resuscitation From Hemorrhagic Shock Attenuates Microvascular Inflammation in the Rat Mesenteric Microcirculation. Shock. 2014;42(6): 518-24. doi:10.1097/shk.0000000000000241

[18]

Coyan G., Moncure M., Thomas J., et al. Induced Hypothermia During Resuscitation From Hemorrhagic Shock Attenuates Microvascular Inflammation in the Rat Mesenteric Microcirculation // Shock. 2014. Vol. 42(6). P. 518-524. doi:10.1097/ shk.0000000000000241

[19]

Koopmans M., Kuiper M.A., Endeman H., et al. Microcirculatory perfusion and vascular reactivity are altered in post cardiac arrest patients, irrespective of target temperature management to 33°C vs 36°C. Resuscitation. 2015;86:14-8. doi:10.1016/ j.resuscitation.2014.09.025

[20]

Koopmans M., Kuiper M.A., Endeman H., et al. Microcirculatory perfusion and vascular reactivity are altered in post cardiac arrest patients, irrespective of target temperature management to 33°C vs 36°C // Resuscitation. 2015. Vol. 86. P. 14-18. doi:10.1016/j.resuscitation.2014.09.025

[21]

Horosz B, Malec-Milewska M. Inadvertent intra-operative hypothermia. Anaesthesiology Intensive Therapy. 2013;45(1):38-43. doi:10.5603/ait.2013.0009

[22]

Horosz B., Malec-Milewska M. Inadvertent intraoperative hypothermia // Anaesthesiology Intensive Therapy. 2013. Vol. 45(1). P. 38-43. doi:10. 5603/ait.2013.0009

[23]

Morley D, Yamane K, O'Malley R, et al. Rewarming for accidental hypothermia in an urban medical center using extracorporeal membrane oxygenation. American Journal of Case Reports. 2013;14:6-9. doi:10.12659/AJCR.883728

[24]

Morley D., Yamane K., O'Malley R., et al. Rewarming for accidental hypothermia in an urban medical center using extracorporeal membrane oxygenation // American Journal of Case Reports. 2013. Vol. 14. P. 6-9. doi:10.12659/AJCR.883728

[25]

Carnevali L, Mastorci F, Audero E, et al. Stress-Induced Susceptibility to Sudden Cardiac Death in Mice with Altered Serotonin Homeostasis. PLoS ONE. 2012;7(7):e41184. doi:10.1371/journal.pone. 0041184

[26]

Carnevali L., Mastorci F., Audero E., et al. Stress-Induced Susceptibility to Sudden Cardiac Death in Mice with Altered Serotonin Homeostasis // PLoS ONE. 2012. Vol. 7, №7. P. e41184. doi:10.1371/ journal.pone.0041184

[27]

Scaravilli V, Bonacina D, Citerio G. Rewarming: facts and myths from the systemic perspective. Critical Care. 2012;16(Suppl 2):25-31. doi:10.1186/cc11283

[28]

Scaravilli V., Bonacina D., Citerio G. Rewarming: facts and myths from the systemic perspective // Critical Care. 2012. Vol. 16 (Suppl 2). P. 25-31. doi:10.1186/cc11283

[29]

Beyer AM, Freed JK, Durand MJ, et al. Critical Role for Telomerase in the Mechanism of Flow-Mediated Dilation in the Human Microcirculation. Circulation Research. 2016;18:856-66. doi:10.1161/ CIRCRESAHA.115.307918

[30]

Beyer A.M., Freed J.K., Durand M.J., et al. Critical Role for Telomerase in the Mechanism of Flow-Mediated Dilation in the Human Microcirculation // Circulation Research. 2016. Vol. 18. P. 856-866. doi:10.1161/CIRCRESAHA.115.307918

[31]

Lindenblatt N, Menger MD, Klar E, et al. Systemic hypothermia increases PAI-1 expression and ac-celerates microvascular thrombus formation in endotoxemic mice. Critical Care. 2014;10:1-9. doi:10.1186/cc5074

[32]

Lindenblatt N., Menger M.D., Klar E., et al. Systemic hypothermia increases PAI-1 expression and accelerates microvascular thrombus formation in endotoxemic mice // Critical Care. 2014. Vol. 10. Р. 1-9. doi:10.1186/cc5074

[33]

Forman KR, Wong E, Gallagher M, et al. Effect of temperature on thromboelastography (TEG) and implications for clinical use in neonates undergoing therapeutic hypothermia. Pediatric Research. 2014; 75(5):663-9. doi:10.1038/pr.2014.19

[34]

Forman K.R., Wong E., Gallagher M., et al. Effect of temperature on thromboelastography (TEG) and implications for clinical use in neonates undergoing therapeutic hypothermia // Pediatric Research. 2014. Vol. 75, №5. P. 663-669. doi:10.1038/pr.2014.19

[35]

Bisschops LA, van der Hoeven JG, Mollnes TE, et al. Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study. Critical Care. 2014;18(5):1-8. doi:10.1186/preaccept-1923890821130266

[36]

Bisschops L.A., van der Hoeven J.G., Mollnes T.E., et al. Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study // Critical Care. 2014. Vol. 18, №5. P. 1-8. doi:10.1186/preaccept-19238 90821130266

[37]

Shapkin YuG, Stekol’nikov NYu, Kapralov SV. Ranneye prognozirovaniye zhiznesposobnosti tkaney pri glubokom otmorozhenii. Estestvennyye i tekhnicheskiye nauki. 2011;6(56):213-7.

[38]

Шапкин Ю.Г., Стекольников Н.Ю., Капралов С.В. Раннее прогнозирование жизнеспособности тканей при глубоком отморожении // Естественные и технические науки. 2011. №6(56). С. 213-217.

[39]

Kander Th, Dankiewicz J, Friberg H, et al. Platelet aggregation and clot formation in comatose survivors of cardiac arrest treated with induced hypothermia and dual platelet inhibition with aspirin and ticagrelor; a prospective observational study. Critical Care. 2014;30(18):1-9. doi:10.1186/ s13054-014-0495-z

[40]

Kander Th., Dankiewicz J., Friberg H., et al. Platelet aggregation and clot formation in comatose survivors of cardiac arrest treated with induced hypothermia and dual platelet inhibition with aspirin and ticagrelor; a prospective observational study // Critical Care. 2014. Vol. 30, №18. P. 1-9. doi:10.1186/ s13054-014-0495-z

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Lycheva N.A., Shakhmatov I.I., Sedov A.V., Makushkina D.A., Vdovin V.M.

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