Parkhomenko V. Clinical and pathogenetic features and treatment of gastropathies induced by nonsteroidal anti-inflammatory drugs in elderly patients with ischemic heart disease.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0421U102112

Applicant for

Specialization

  • 14.01.02 - Внутрішні хвороби

11-05-2021

Specialized Academic Board

Д 44.601.02

Ukrainian medical stomatological Academy

Essay

The study involved 125 patients, who were under observation in the gastroenterology department of Poltava Regional Clinical Hospital for War Veterans, including 9 (7.2%) women and 116 (92.8%) men, the average age of patients was 71.5±6.2 years. The patients underwent general clinical examination, assessment of gastric mucosa (GM) mucus-producing function: concentration of N-acetylneuraminic acid (NANA) and fucoproteins in the blood serum, free radical oxidation, antioxidant protection system state, NO system, instrumental examination, H. pylori antigen test in faeces; mathematical and statistical analysis of the results. H. pylori, NSAIDs duration and doses, peptic ulcer disease history were determining factors in the clinical manifestations of NSAID gastropathy in elderly patients with concomitant ischemic heart disease (IHD). Abdominal pain and dyspeptic syndromes were moderate intensity, but in patients with NSAID gastropathy associated with H. pylori, the corresponding rates were 1.4 times higher (p<0.05) and 1.6 times higher (p<0.05) compared with H. pylori-negative patients. The decrease in mucosal barrier resistance in elderly patients with NSAID gastropathy and concomitant ischemic heart disease in the absence of H. pylori was characterized by 1.4-fold increased NANA concentration (p<0.001) and 1.9-fold decreased serum fucoproteins content, and in patients with H.pylori infection – 1.6-fold and 2.3-fold (p<0.001), respectively. Oxidative stress activation did not depend on H. pylori status and was accompanied by 1.9-fold increased TBA reactive products concentration in the blood serum with simultaneous 1.5-fold decreased catalase activity (p<0.001) compared with the corresponding values of almost healthy individuals. In patients with NSAID gastropathy associated with H. pylori, with concomitant ischemic heart disease, the iNOS activity was 1.3 times higher (p<0.02) compared with H. pylori-negative patients and peroxynitrite concentration in the blood serum was 1.4-fold increased (p<0.01), which proves the important role of H. pylori in the pathogenesis of endothelial dysfunction. The severity of GM erosive-ulcerative lesions according to Lanzascore in elderly patients with NSAID gastropathy and concomitant ischemic heart disease was determined by patients’ age, the number and duration of NSAIDs, the presence of H. pylori, increased NANA concentration and increased serum iNOS activity, the degree of GM infiltration by polymorphonuclear leukocytes against the background of inverse correlation with reduced catalase activity (r=-0.41; p=0.030) and eNOS (r=-0.48; p=0.031). Administration of eupatilin together with antihelicobacter therapy in elderly patients with NSAID gastropathy associated with H.pylori and concomitant ischemic heart disease after 14 and 45 days of combined therapy helped to reduce the intensity of epigastric pain in 1.9 times (р<0.05) and 2.8 times (p <0.01), respectively. After 1.5 months of complex therapy, the sialoproteins degradation was 1.2-fold reduced (p<0.05) while fucoprotein’s content was 1.5-fold increased (p<0.02), TBA reactive products concentration – 1.5-fold decreased, and 1.2-fold increased serum catalase activity (p<0.05); recovery of the NO system by reducing iNOS activity by 1.6-fold (p<0.005), peroxynitrite content in 2.0 times (p<0.001) in the blood serum. Combined treatment with eupatilin and AHBT accelerated the achievement of clinical and endoscopic remission after (4.1±0.3) days versus (5.9±0.6) days and eradication of H.pylori in 90% versus 82.6% of patients who received AHBT alone, respectively. After 1.5 months of treatment in elderly patients with NSAID gastropathy H.pylori-negative with concomitant ischemic heart disease, eupatilin showed the cytoprotective effect, inhibiting the depolymerization of mucus glycoproteins (1.2-fold decreased NANA content on the background of increased concentration of fucoproteins in 3 times (p<0.01) in the blood serum, normalizing the activity of oxidative stress and showing endothelium-protective effect by reducing the iNOS activity in the blood serum in 1.4 times (p<0.02) and reducing the peroxynitrites concentration in 1.3 times (p<0.001). In elderly patients with NSAID gastropathy with concomitant ischemic heart disease the severity of GM erosive-ulcerative lesions according to Lanzascore decreased in 1.5 times (p<0.02) during treatment, regardless of H.pylori status. Thus, the dissertation presents a theoretical generalization and a new solution of the scientific problem, which is to increase the effectiveness of NSAID gastropathy treatment in elderly patients with concomitant ischemic heart disease by studying the pathogenetic mechanisms of syntropy and development of therapeutic complexes for these disorders correction with cytoprotector – eupatilin.

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