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The Role of Systemic Inflammatory Process in Pathogenesis of Hemorrhagic Shock

Author: Rotaru Victoria
Degree:doctor of medicine
Speciality: 14.00.16 - Normal and Pathological Physiology
Scientific adviser: Vasile Lutan
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Institution: Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Scientific council: DH 50-14.00.16-27.03.08
Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova


The thesis was presented on the 31 March, 2011
Approved by NCAA on the 8 July, 2011


Adobe PDF document0.51 Mb / in romanian


hemorrhagic shock, hyaluronic acid, systemic inflammation, oxidative stress, post-infusion syndrome, proinflammatory cytokines, pro-oxidant indexes, anti-oxidant indexes, acute phase proteins, couples Fe-transferrin and Cu-ceruloplasmine


The thesis contains 147 pages and consists of an introduction, 6 chapters, conclusion, practical recommendations, bibliography of 353 sources, the results obtained have been published in 7 scientific works.

Field of study: medicine – pathophysiology.

Topic timeliness: The hemorrhagic shock is a polyetiliogical syndrome characterized by a severe hemodynamic disturbance with tisular hyperperfusion caused by reduction of blood volume, reduction of cardiac debit, which leads to efficiently inadequate circulatory blood volume. As a result of deficitary perfusion there is no oxygen and nutriments afflux sufficient for tissues and deficitary elimination of metabolites takes place.

Nowadays hemorrhages and especially hemorrhagic shock is one of the most frequent and serious complications of many pathologies. Thus, for about 25% of patients of surgery department have hemorrhages, which are further complicated with hemorrhagic shock and lead to death in 40% of cases.

The growing incidence of hemorrhages and complications, high level of lethality of patients suffering from hemorrhages stimulates the researches in the sphere of pathogenesis study, diagnostics improvement and increase of efficiency of pathogenic resuscitation by stabilizing evolution of systemic inflammation, oxidative stress in hemorrhagic shock and post-infusion syndrome. The survival of patients with hemorrhages is directly influenced by success of resuscitation and anti-shock therapy. Their efficiency at present is far from being satisfactory.

Nowadays there are no efficient methods of treatment during the resuscitation with therapeutic action upon the whole pathogenic spectrum of shock: restoration of circulating blood volume, arterial and venous tension, improvement of blood afflux to the heart and as a consequence restoration of cardiac debit, hypoxia elimination, determination of systemic inflammation and oxidative stress. The aforesaid confirms the topic timeliness and necessity of studying pathogenesis of systemic inflammatory process in hemorrhagic shock.

Work aim: Studying the impact of systemic inflammation, oxidative stress in pathogenesis of hemorrhagic shock and post-infusion syndrome and improving the experimental methods of pathogenic treatment of hemorrhagic shock.

Research methodology: The material studied has been researched as a result of experiment and by estimation of biochemical indexes. The hemorrhagic shock was reproduced at masculine rabbits with body weight of 2.3-2.5 kg. The blood effusion from femoral vein in 3 stages (per 15-20 ml each time) within a 15-20 min interval; the total volume taken – 45-55 ml (40% of circulating blood volume); the final blood pressure maintained at the severe shock level 45-50 mmHg – by repeated blood effusions and re-infusions for a 24-hour period.

Scientific novelty and originality:

During the work execution the following scientific results have been achieved:

• The dynamics peculiarities of circulatory levels of IL-1-alfa, IL-6, and TNF-alfa and their correlation with the serum content of acute phase proteins, ferrum, and cuprum during a period of HS and post-infusion syndrome duration have been revealed;
• The impact of couples of ferrum-transferrin, cuprum- ceruloplasmine during the period of HS and post-infusion syndrome duration has been determined;
• The therapeutic effect of hyaluronic acid upon the cytokinic and oxidative impact in case of systemic inflammation and post-infusion syndrome in hemorrhagic shock.

Scientific significance and practical value of data obtained

There has been revealed the role of cytokines IL-1, IL-6, and TNF-alfa in launching the systemic inflammatory reaction in HS, and namely the premature growth of circulatory level of IL-1, followed by further growth of IL-6, and TNF-alfa with superior value of increment at the end of a 24-hour period of shock.

The reactive C protein in blood correlates with cytokines dynamics until the end of a 5-hour period, after which it declines, it would mean the affection of hepatic function.

The cytokinic impact is amplified by oxidative stress activated in the conditions of progressive growth during the whoel period of serum content of ferrum, cuprum and ceruloplasmine, factors with pro-oxidative action. Their blood value also grows in the first 5 hours of post-infusion syndrome and is surely associated with the degree of cytokines growth during this period, which confirms the causal connection between the inflammatory response and oxidative stress.

As concerns the field of application the positive diagnostic correlation of dynamics of circulatory levels IL-1, IL-6, and TNF-alfa in relation to severeity of systemic inflammatory response in HS as well as its duration has been imposed.

The monitoring of reactive C protein dynamics can furnish indexes concerning the evolution of hepatic dysfunction.

In case the serum dosing of cytokines is impossible, the estimation of ferrum and cuprum dynamics may be useful as similar cytokine diagnostics.

The application of hyaluronic acid in infusion therapy lessens the inflammatory and oxidative impact in the hemorrhagic shock and post-infusion syndrome, manifested by significant reduction of cytokine, ferrum, cuprum and ceruloplasmine content in blood and may offer clinical benefits in prevention and treatment of polyorganic dysfunction syndrome.

Implementation of scientific results:

1. Evaluation of dynamics of ferrum and cuprum content may offer indexes predicting severity of systemic inflammatory response and polyorganic dysfunction both during the period of hemorrhagic shock and post-infusion syndrome evolution.

2. The hyaluronic acid can be applied aiming at lessening the cytokinic impact and impact of oxidative stress in post-infusion syndrome and may strengthen the therapeutic management of emergency states worsened by hemorrhage or hemorrhagic shock.