Membranoprotector Therapy in the Correction of Gastrointestinal Disorders in Acute Pancreatitis

The dissertation addresses the issue of membranoprotector therapy in the correction of gastrointestinal disorders in acute edematous pancreatitis. The work combines experimental and clinical investigations aimed at studying morphological, microcirculatory, and metabolic changes in gastric and small intestinal tissues, as well as lipid peroxidation processes. It is established that the use of the membranoprotector reamberine helps reduce gastrointestinal disorders by restoring lipid metabolism in the tissue structures of the organs under study.

The scientific novelty of the work lies in establishing the link between morphofunctional changes in the stomach and small intestine in acute pancreatitis and disruption of lipid metabolism in their tissue structures. It is shown that reamberine exerts a positive pathogenetic effect sufficiently rapidly, which is of great importance for preventing the progression of the edematous form of pancreatitis and its transformation into the necrotic form. The results of the dissertation have been implemented in the clinical hospital of emergency medical care in Saransk and incorporated into the educational program of Mordovian State University.

Relevance of the study

The problem of acute pancreatitis in emergency surgery remains relevant to the present day (Sazhin V.P. et al., 1996; Saveliev V.S. et al., 1999; Fedorov V.D. et al., 1999; Shalimov A.A. et al., 2000; Tarasenko S.V. et al., 2001; Jonson C.N., Imre C.W., 1999). Among various pathologies of the abdominal organs, mortality from acute pancreatitis is the highest (ranging from 2.3 to 86% and 98-100% in the lightning-fast form) (Viskunov V.G., 1996; Tugdumov B.V., 1999; Briskin B.S. et al., 2001; Tolstoy A.D. et al., 2001; Harris et al., 1995). According to recent literature, there is a trend toward an increase in the incidence of acute pancreatitis (Briskin B.S., 2000; Vlasov A.P. et al., 2003; Gening T.P. et al., 2004; Lankisch P.G., 1997). Moreover, in 15-20% of patients, inflammatory changes in the pancreas have a severe destructive character (Filin V.I., Kostyuchenko A.L., 1994; Lishchenko A.N., Laptev V.V., 1995; Shalimov A.A. et al., 1997; Nesterenko Yu.A. et al., 1998; Saveliev V.S. et al., 2000; Beriyashvili Z.A. et al., 2001).

Microcirculatory changes arising at the earliest stages of the disease in acute pancreatitis (Vladimirov P.V., Sergeenko V.I., 1986; Kozlov V.A., 1990; Vinnik Yu.S., Cherdantsev D.V., 1997), as a rule, have a generalized character, have a certain stage specificity, and are determined by the form of pancreatitis and the severity of destructive changes in the gland (Saveliev V.S., Prokubovsky V.I., 1984).

In the pancreas during acute pancreatitis, there is an accumulation of products of incomplete metabolism, acidosis and hypoxia intensify, the concentration of proteolytic and lipolytic enzymes, vasoactive substances and their metabolic products increases (Vashetko R.V. et al., 2000). As a result of these processes, the process of lipid peroxidation is activated, the antioxidant defense system is suppressed, lysosomal membranes are damaged, and enzymes within pancreatic cells are activated, which serves as the cause of destructive processes not only in the pancreas but also in surrounding organs, leading to the syndrome of multiple organ failure (Filin V.I., Kostyuchenko A.L., 1994). One of the main manifestations of multiple organ failure is the development of gastroenteral insufficiency, which reflects the severity of the pathological process (Balashova T.S. et al., 1996). Enteral insufficiency holds a special place in the complex of visceral disorders, also because it serves as one of the triggering mechanisms of endotoxicosis, whereas other visceral disorders are mediated by endotoxicosis and can be regarded as its manifestation (Saveliev V.S., 2004).

In acute pancreatitis, the gastrointestinal tract, becoming involved in the pathological process, initiates a mechanism of systemic damage (Gologorovsky V.A. et al., 1988; Gelfand B.R. et al., 1998; Billing A. et al., 1992). In the formation of intestinal insufficiency, according to I.A. Kozhemyakin et al. (1991), hyperreactivity and unregulated processes of lipid peroxidation play a substantial role, which are the leading pathogenetic factors of organ and system damage. Active oxidants are also generated with a reduction in antioxidant defense (Vasilkov V.G. et al., 2001); neutrophilic chemotaxis and adhesion of neutrophils to endothelial cells; depletion of intracellular energy reserves (Lyzikov A.N., 1993). Antioxidants substantially prevent mucosal damage during intestinal ischemia-reperfusion, however, with regard to increased permeability of mesenteric microvessels, they are less effective: superoxide dismutase and dimethyl sulfoxide correct vascular permeability only in the muscular layer, and the xanthine oxidase inhibitor, allopurinol, has practically no effect on it.

In this regard, it becomes obvious that preventing the progression of gastrointestinal disorders in acute pancreatitis is possible by influencing the cascade of pathogenetic reactions involved in tissue trophism of the organ.

Goal of the study

To study the effects of the membranoprotector reamberine in the correction of gastrointestinal disorders in acute edematous pancreatitis in experiments and clinical practice.

Main tasks

1. In the dynamics of acute experimental biliary pancreatitis, based on the macro-microscopic picture, microcirculation indicators, trophism, and tissue metabolism, to study morphofunctional changes of the stomach and small intestine.

2. In experiments, to determine the relationship between morphofunctional disorders of the stomach and small intestine and membrane-destabilizing phenomena assessed by disruption of the lipid composition of cellular structures, intensity of lipid peroxidation processes, and phospholipase activity.

3. In acute experimental pancreatitis, to investigate the effect of the membranoprotector reamberine on morphofunctional changes of the stomach and small intestine.

4. In complex therapy with reamberine of patients with acute edematous pancreatitis, based on the features of the clinical picture and changes in laboratory indicators, to identify the effectiveness of the drug in the correction of gastrointestinal disorders.

Scientific novelty

It has been established that in acute biliary pancreatitis, the occurrence of morphofunctional changes in the stomach and small intestine is associated with a disruption of lipid metabolism in their tissue structures.

It has been shown that in the tissue structures of the stomach compared to the small intestine, lipid metabolism disorders are less pronounced, which accounts for a significant reduction in the development of morphofunctional changes in them.

It has been found that the use of the membranoprotector reamberine in the therapy of acute experimental pancreatitis contributes to a reduction of gastrointestinal disorders.

It has been established that the basis of the positive pathogenetic effect of the drug in acute pancreatitis lies in its ability to restore lipid metabolism in the tissue structures of the studied organs of the digestive tract.

It has been shown that reamberine sufficiently rapidly leads to correction of clinico-laboratory indicators in acute pancreatitis: a significant positive effect of the drug is evident in the early stages of therapy.

Clinical studies have confirmed the effectiveness of the membranoprotector reamberine in correcting gastrointestinal disorders in patients with acute edematous pancreatitis. Against the background of the drug use compared with the control group, a significant reduction in morphological changes of the gastric and duodenal mucosa, rapid restoration of intestinal peristalsis, and a decrease in the severity of toxic and oxidative syndromes have been noted.

Practical significance of the work

A sufficiently high effectiveness of the complex therapy scheme for acute edematous pancreatitis using reamberine has been demonstrated. It has been found that one of the components of the positive action of the drug is its ability to correct phenomena of one of the leading pathogenetic factors of the studied pathology — gastrointestinal disorders. The established fact provides grounds for the widespread use of reamberine in abdominal surgery.

Clinico-experimental studies have shown that forecasting the course and evaluating the effectiveness of therapy for acute pancreatitis is possible through the assessment of lipid metabolism indicators.

Positions to be defended

Morphofunctional changes in the stomach and small intestine in acute pancreatitis are associated with lipid metabolism disorders in their tissue structures. In the stomach, these changes are less pronounced, which accounts for a significant reduction in the development of pathomorphofunctional phenomena in it.

The use of the membranoprotector reamberine in the therapy of acute edematous pancreatitis contributes to a reduction of gastrointestinal disorders both in experiments and in clinical practice.

The positive effect of the drug in acute pancreatitis is due to its ability to restore lipid metabolism, microcirculation, and trophism of the tissue structures of the studied organs of the digestive tract.

The effectiveness of reamberine is demonstrated sufficiently rapidly, which is an extremely important circumstance in the prevention of pathology progression and transformation of the edematous form of pancreatitis into the necrotic form.

Implementation into practice

The developed dissertation positions have been implemented in the practical activities of the clinical hospital of emergency medical care in Saransk, and included in the student training program at the department of surgical surgery of the medical faculty of Mordovian State University named after N.P. Ogarov.

Dissertation defense

The main results of the work have been reported and discussed at the Ogarov Readings — a scientific-practical conference of Mordovian State University (Saransk, 2003-2006), the VII International Conference "Bioantioxidant" (Moscow, 2006), the Scientific Conference of Young Scientists of Mordovian State University (Saransk, 2005-2006), and the II International Scientific-Practical Conference "Health and Education in the 21st Century" (Moscow, 2006).

The dissertation was carried out in accordance with the research plan on the topic of Mordovian State University named after N.P. Ogarov "New methods of intensive therapy and resuscitation in surgery and experiments" (state registration number 019900117470).