In patients of group I, there was a slight dilatation of capillaries, a plethora of arterioles, capillaries and venules. In patients with CLL in stage A, no leucostasis was found in the vessels of the microcirculatory bed of the bronchi. In patients with group II, dilatation and plethora of arterioles, capillaries, and venules were observed with varying degrees of severity. In 6 patients of group II, accumulations of lymphocytes with the formation of leuco- stasis were observed in the vessels of the microcirculatory bed. In patients with group III, dilatation of arterioles, capillaries and venules was also diagnosed with varying degrees of severity. All group III patients were diagnosed with leukostasis in the vessels of the microcirculatory bed.

In order to study microhemocirculation in the proximal parts of the bronchial tree, endobronchial laser Doppler flowmetry (LDF) was performed in 25 patients with CLL. The results were compared with the data of 20 people from the control group, who were conducted PBS and LDF. According to the research data in patients with CLL, in the process of tumor progression, various types and degree of severity of microcirculatory circulation were registered.

The LDF method is based on probing tissue by laser radiation and subsequent processing of radiation reflected from a tissue in accordance with the Doppler effect. The amount of probed tissue in the LDF method is determined by the geometry and optical parameters of the light probe. The amplitude of the reflected signal is formed as a result of the reflection of radiation from erythrocytes, moving at different speeds and differently quantitatively distributed in arterioles, capillaries, venules and arterial venous anastomosis. Thus, PM determines the change in blood flow per unit time in the volume of tissue being probed and is represented by the following expression: PM = K × Ner × Vav; where: PM – microhemocirculation parameter , K – proportionality coefficient, (K = 1), Ner – red blood cell count, Vav – average erythrocyte rate – tov in the probed volume . A decrease in the PM values ​​may be due to a change in the number of blood cells and their speed in the microvessels of the area being examined. In CLL, microhemocirculation in the lungs and bronchi is undoubtedly promoted by accumulations of lymphocytes in small caliber vessels and anemic syndrome. In order to minimize the effect of anemia on the PM, in patients with group III (stage C, according to the J. Binet classification), the anemic syndrome was stopped before the study. The hemoglobin level during LDF was not lower than 100 × 10 9 / l, the content of red blood cells was at least 3 × 10 9 / l. Thus, they tried to establish a decrease in the speed of red blood cells in the microvessels, which in CLL may be primarily due to the presence of vascular accumulations of lymphocytes.

The amplitudes of oscillations in the N-range (due to sympathetic effects on smooth muscle cells of arterioles and arterio-venular anastomoses) and in the M-range (characterizing the state of the muscle tone of the pre-capillaries regulating blood flow to the nutritive channel) did not have significant differences with control .

The amplitudes of oscillations in the D-range in patients of the first subgroup did not have significant differences compared with the control indicators; in the second subgroup, there was a decrease in the amplitudes of oscillations in the D-range (P <0.05). The decrease in the amplitudes of the respiratory waves is due to insufficient blood flow into the venules, which may be due to the presence of leucostasis in CLL patients in the later stages of the tumor progression.

The amplitudes of oscillations in the C-band decreased during the tumor progression, in the first subgroup they did not have significant differences compared with the control, in the second subgroup the cardiac wave indices decreased (P <0.01). A decrease in cardiac wave values ​​indicates a decrease in arterial blood flow into the microvasculature, which may be due to the presence of vascular accumulations of lymphocytes, in some cases completely blocking the gaps of small vessels.

Significant inverse correlations were found between the level of leukocytosis in peripheral blood and a decrease in the fluctuations in the D and C ranges (respectively, r = –0.64, P <0.01 and r = –0.68, P <0.01), between duration of illness and a decrease

It can be concluded that in patients with CLL, in the process of tumor progression, the parameters characterizing the passive factors of LDF grams (causing fluctuations in blood flow outside the microcirculation system) —the amplitudes of fluctuations in the heart and respiratory ranges (pulse wave from the arteries and suction action ” respiratory pump “from the veins). These oscillations propagate with the bloodstream into the probed area, since the microvasculature, which is an integral part of the circulatory system, is topographically located between the arteries and the veins. Thus, in patients with CLL in the late stages of tumor progression, the flow of arterial blood into the microvasculature and its outflow to the venules due to the presence of leukostasis decrease.Indicators of active factors controlling microcirculation (directly affecting the microcirculation system — amplitudes of vibration in the EH and M bands), modulating blood flow from the vessel wall and realized through its muscular component, change to a much lesser extent. One of the reasons for this can be the fact that active mechanisms create transverse oscillations of the blood flow as a result of alternation of contraction and relaxation of vascular muscles (alternating episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workermodulating blood flow from the vascular wall and implemented through its muscular component, change to a much lesser extent. One of the reasons for this can be the fact that active mechanisms create transverse oscillations of the blood flow as a result of alternation of contraction and relaxation of vascular muscles (alternating episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workermodulating blood flow from the vascular wall and implemented through its muscular component, change to a much lesser extent. One of the reasons for this can be the fact that active mechanisms create transverse oscillations of the blood flow as a result of alternation of contraction and relaxation of vascular muscles (alternating episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workerthat active mechanisms create transverse blood flow oscillations as a result of alternation of contraction and relaxation of vascular muscles (successive episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workerthat active mechanisms create transverse blood flow oscillations as a result of alternation of contraction and relaxation of vascular muscles (successive episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the worker rhythm of the respiratory pump . Lecostasis in small vessels of the lungs and bronchi present in a significant number of CLL patients to a greater extent impede longitudinal fluctuations in blood flow.

All patients who underwent diffuse endobronchitis during PBS underwent therapeutic measures: active aspiration of the bronchial contents, selective / partial lavage with dioxidine solution, local administration of antibiotics, etc. Two to three weeks after the start of treatment, endobronchial LDF was re-performed in these patients. Changes in the microcirculatory blood flow in the mucous membrane of the proximal bronchi in CLL patients, after normalization of the bronchoscopic picture, were preserved, which is explained by the morphological changes in the microvasculature vessels in CLL patients.

Disruption of microhemocirculation leads to the development of tissue hypoxia, metabolic disturbances in the mucous membrane cells of the bronchi and, along with marked secondary immunodeficiency, contribute to the occurrence of the inflammatory process in the bronchi. Violation of microhemocirculation supports the inflammatory reaction in the bronchi, contributes to its recurrent course, the development of disturbances in gas exchange and the ineffectiveness of antibacterial therapy. In 60% of patients with a progressive course of CLL (40% of the total number of patients with CLL), with PBS, an inflammatory process in the bronchi has been diagnosed with no pronounced clinical manifestations. However, the presence of a chronic focus of infection may contribute to the development of pneumonia in patients with a progressive course of CLL. Considering the above, patients with a progressive course of CLL,in the absence of contraindications, diagnostic bronchoscopy is recommended, and in the presence of an inflammatory process in the bronchi, the appointment of therapeutic measures.

The presence of the inflammatory process in the bronchi, along with their leukemic infiltration, contributes to an increase in bronchial resistance in patients with CLL group III.

Violation of microhemocirculation indices is registered earlier than the clinical manifestations of the bronchopulmonary system lesions appear. Thus, the study of endobronchial microcirculation can help predict the occurrence of inflammatory diseases of the bronchopulmonary system in patients with CLL.

In the study of the functional ability of the right from the heart of the business in patients of group I, a decrease in the ratio E / A TC was observed . In group II, a further decrease in the E / A TC ratio was diagnosed . In group III, a significant increase in KDR, KDO and RV CSR was diagnosed. In patients with group III, the cardiac index (SI) of the pancreas was increased, which is associated with an increase in heart rate in the later stages of hemoblastosis, due to anemia and intoxication. A decrease in the maximum blood flow velocity in the early diastole (E TC ), an increase in the maximum blood flow velocity in the late filling phase of the pancreas (A TC ) and a decrease in the E / A ratio were detected. Increase A TC in the process of tumor progression in CLL can be explained by an increase in heart rate in these patients. E TC depends on the difference in pressure gradient in the cavities of the right heart and is not related to the heart rate, therefore, this indicator does not change in groups I and II. A decrease in E TC was diagnosed only in patients of group III, where dilatation of the pancreatic cavity takes place. Thus, early signs of diastolic dysfunction of the pancreas were detected in patients with CLL I group; in the II and III groups, disturbance of the diastolic function of the pancreas progressed. A significant decrease in the fraction of the prostate ejection was diagnosed only in patients of group III. The index of TMPS PZHDincreased in patients in groups II and III .

In group I patients with CLL, there was an increase in TMZS LC , in groups II and III, it continues to increase. In patients with groups II and III, the thickness of the interventricular septum increases. An increase in the A MC and reduction ratio E / A is diagnosed at the early stages of tumor progression (I group), which is evidenced by the presence of left ventricular diastolic dysfunction. In the process of tumor development, disorders of LV diastolic function are progressing: A MKincreases, reaching maximum values ​​in group III, and, accordingly, the ratio E / A MK significantly decreases . Due to an increase in heart rate, an increase in the LV LV and LV LV . Only in group III there was a significant increase in KDR, KSR, KDO, KS O and a decrease in LV EF .

The revealed changes can be explained by tumor intoxication, cardiotoxic effects of cytostatics, rheological disorders in the coronary vessels in patients with high leukocytosis, anemia, and in some cases lymphoid infiltration of the myocardium. Dilatation of the cavities of both ventricles, an increase in their size and corresponding volumes, a decrease in the ejection fraction were diagnosed only in CLL patients in stage C (with the presence of anemic syndrome). Patients with CLL are people, in the overwhelming majority of cases, elderly, many of them had coronary heart disease, which also contributed to the violation of the LV myocardium and the development of circulatory failure.

Ultrasonic examination of the diaphragm in patients of group I showed no significant changes compared to controls. The thickness of the diaphragm (TD) did not differ from that in the control group. The position, shape, echogenicity of the diaphragm also did not change. Excursion of the diaphragm with calm (EDS) and forced (EDF) breathing did not differ from control. In patients with group II, the thickness of the diaphragm did not change. But the echo structure of the diaphragm became non-uniform, flattening of its dome was noted. The excursion of the diaphragm during calm and forced breathing decreased significantly. In group III, the largest morphological changes in the diaphragm were revealed. The dome was not clear. Its echostructure became non-uniform. Significantly decreased excursion of the diaphragm with calm and forced breathing.Violation of the excursion of the diaphragm and its morphological reorganization, in case of CLL, contributes to severe hepato- and splenomegaly, which occur in the majority of patients of groups II and III. Compression of the diaphragmatic muscle with enlarged liver and spleen significantly reduces its mobility and is one of the causes of the onset of severe and prolonged bronchopulmonary pathology in CLL. Another cause of dysfunction of the diaphragm in CLL is its specific leukemic lesion.Another cause of dysfunction of the diaphragm in CLL is its specific leukemic lesion.Another cause of dysfunction of the diaphragm in CLL is its specific leukemic lesion.

A correlation analysis was performed between indicators of pulmonary and intracardiac hemodynamics, the functional state of the diaphragm, respiratory function and blood gas composition in CLL patients at different stages of tumor progression. Patients of groups II and III showed a significant correlation between a decrease in the excursion of the diaphragm with a quiet and forced breathing and a decrease in the MOR of the lower and middle zones of the lungs. In the second group, the correlation coefficient between the decrease in the EDF and the decrease in the MOR of the lower zones was 0.87 (P <0.001); between a decrease in EDF and a decrease in the MOB of the middle zones of 0.68 (P <0.01). The correlation coefficient between the decrease in the EDS and the decrease in the MOR of the lower zones was 0.72 (P <0.01); between a decrease in the EDS and a decrease in the MOB of the middle zones of 0.64 (P <0.05). In group III, a clear correlation was also diagnosed between a decrease in EDF and a decrease in the MOBR of the lower (0.66; P <0.05) and medium (0.65; P <0.05) zones of the lungs. The correlation coefficient between the decrease in the value of the EDS and the decrease in the MOR of the lower zones was 0.64 (P <0.05), the middle zones 0.62 (P <0.05). No significant correlation was found between the EDF, EDS and MOBP indices of the upper zones of the lungs in patients with CLL. Correlation analysis confirms the assumption of the important role of a violation of the excursion of the diaphragm in CLL patients in reducing the ventilation capacity of the lower and middle zones of the lungs and the redistribution of ventilation in the upper zones.

A reliable average inverse correlation was established between a decrease in the excursion of the diaphragm during forced and quiet breathing and an increase in AHDLA in patients II (r = –0.59; P <0.05 and -0.51; P <0.05) and III (r = – 0.66; P <0.01 and – 0.61; P <0.05) groups. A strong positive correlation was found between a decrease in the MOVP of the sum and a decrease in the pO 2 of blood in patients of the II (0.86; P <0.001) and III (0.9; P <0.001) groups. The inverse correlation relationship between the decrease in blood pO 2 and the increase in SrDLA in patients of the II (r = –0.65; P <0.01) and III (r = –0.9; P <0.001) groups was diagnosed. Smaller correlation coefficient and reliability in group II is explained by insignificant changes in pO 2 indices in these patients. and SrDLA. It can be concluded that a violation of the functional capacity of the diaphragm leads to impaired ventilation of the middle and lower zones of the lungs, as a result of which hypoxemia and PH develop.

A significant increase in the liver and spleen, which occurs in many patients with a progressive course of CLL and in the terminal stage of the disease, contributes to a high standing of the diaphragm case and disruption of its excursion. The diaphragm is the main respiratory muscle, which, under physiological conditions, provides 2/3 of the vital capacity of the lungs, and 70–80% of inspiration with forced respiration [208]. So, according to J.L. Shika and V.I. Sobolev, as a result of the movement of the diaphragm, the lower and 40-50% of the ventilation volume of the upper lobes of the lungs is fully ventilated. Violation of the excursion of the diaphragm, the main respiratory muscle, is an important factor in the violation of respiratory function in the late stages of tumor progression in patients with CLL. Compression of the lower parts of the lungs with enlarged liver and spleen is an important factorreducing respiratory volume lower zones and redistribution of ventilation in the upper zones of the lungs. It can be argued that mechanical compression of the diaphragm with enlarged liver and spleen and its specific leukemic lesion contribute to impaired contractility of the diaphragm, which is one of the reasons for the development of hypoxemia and PH in patients with CLL II group without an associated broncho-obstructive process. This group included a greater number of patients with the splenic CLL.

Other causes of hypoxemia and PH in patients with CLL in stage B are a decrease in microhemocirculation and a severe, prolonged course of infections of the bronchopulmonary system, accompanied by impaired ventilation and hemodynamics of the pulmonary circulation.