The thesis deals with the improvement of therapeutic efficacy of gastroesophageal reflux disease (GERD) and stable angina of effort (SAE) by means of elimination of the determined pathogenic links of their compromised anamnesis.
For the first time scientific data are obtained that a comorbid development of GERD and SAE is characterized by a higher occurrence and intensity of GERD subjective symptoms in comparison with isolated GERD, occurrence of erosive GERD, and more pronounced signs of pathologic gastroesophageal reflux (according to the findings of twenty-four-hour multichannel intraluminal impedance-pH-monitoring of the esophagus).
The author considerably supplied a pathogenic conception of mutually compromised GERD and SAE consisting of a reliable activation of oxidative and nitrate stress against the ground of insufficiency of the antioxidant protective system components, intensification of lipid distress-syndrome and activation of plasma proteolysis, endothelial dysfunction with activation of thrombocyte hemostasis, inhibition of the total and enzymatic fibrinolysis, that become more intensified under conditions of hyperprolactinemia. For the first time a pathogenic role of hyperprolactinemia is evidenced as a risk factor of GERD and SAE progressing: interdependency between prolactin content and manifestation of esophageal inflammation, degree and rate of ADP-induced platelet aggregation, amount of myocardial ischemia episodes and the index of the left ventricle myocardial contractility.
For the first time it was found that a comorbid course of GERD and SAE is associated with a higher intensity of oxidative stress and deeper deficiency of antioxidant protection factors, increase of blood plasma proteolytic activity in comparison with isolated GERD and SAE. For the first time dependence of nitrate stress activation on the amount of nitroglycerin tablets taken is determined in patients with SAE and GERD, and its effect on the functional ability of the inferior esophageal sphincter and its kinetic function and esophageal clearance are confirmed; scientific data concerning a negative effect of nitrate stress promoting ulceration of the esophageal mucosa are specified.
For the first time it was found that in case of comorbid GERD and SAE imbalance of plasma fibrinolysis and thrombocyte hemostasis is more pronounced as compared to isolated SAE. It consists of decrease of the total, enzymatic and nonenzymatic fibrinolytic activity of the blood plasma, considerable increase of the degree and rate of ADP-induced platelet aggregation against the ground of reduced time and proportional increase of the degree and rate concerning blood serum prolactin.
For the first time, on the basis of a comprehensive investigation of physical and psychic health components of GERD and SAE patients it was found that the majority of parameters characterizing the quality of life are on reliably lower level as compared to isolated SAE (р<0,05). Occurrence and chance to find clinically manifested anxiety and depression were reliably higher, since their manifestation was associated with the content of prolactin in the blood. A high level of specificity and sensitivity of prolactin content in the blood in prediction of anxiety and depression occurrence in GERD and SAE patients was determined for the first time.
A negative effect of GERD on SAE was first confirmed including a higher chance of SAE progression: increased total amount of angina attacks (p<0,05), amount of nitroglycerine tablets taken for a week; the number of episodes of painful and painless myocardial ischemia, their total duration, reduced contractile ability of the left ventricle in comparison with the parameters in patients with isolated SAE. The interrelations between hyperprolactinemia and the number of episodes of painful myocardial ischemia per day and contractile ability of the myocardium are determined for the first time. The method to reduce the risk of angina occurrence during esophagogastroduodenoscopy (EGDS) in patients with GERD and SAE is developed for the first time, its efficacy is confirmed as compared to the patients who did not receive it.
For the first time, a comprehensive therapy of SAE and comorbid GERD is suggested to be supplied by administration of anti-dopaminergic prokinetics provoking hyperprolactinemia, acetylsalicylic acid is suggested to be changed into clopidogrel, Meldonium intake is proved to be reasonable due to its positive effect on pathogenic mechanisms of mutually compromised GERD and SAE, that enabled to increase the effect of treatment of both comorbid diseases considerably.
