RESUMO
AIM: To determine the role of enhanced blood coagulation in pathogenesis of pulmonary hypertension (PH) at an early stage of fibrosing alveolitis (FA). MATERIAL AND METHODS: Clinical, functional, roentgenological, coagulation and immunological examinations were performed in 17 patients with idiopathic FA (IFA), in 6 patients with exogenic allergic alveolitis (EAA), in 15 FA patients with diffuse diseases of the connective tissue (FA-DDCT). The diagnosis was verified with high resolution computed tomography (HRCT). Lesser circulation was assessed by Doppler echocardiography. Morphological impairment of the lungs was specified in all the patients using analysis of the bronchoalveolar lavage. In 9 FA patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy volunteers. Thrombin-antithrombin complex (TAT) and thrombocytic factor 4 (TF-4) were estimated with ELISA as stable, highly sensitive markers of thrombophilia. RESULTS: The TF-4 level was elevated in all IPD patients (p < 0.05), the elevation being highest in FA-DDCT (p < 0.007). With FA progression, TF-4 concentration went down. A weak negative correlation (p < 0.047, r = -0.38) was found with average pressure in the pulmonary artery (PAAP). TAT was higher than control in all the groups (p < 0.05). Maximal TAT values were registered in EAA. If HRCT detected active inflammation and in development of irreversible fibrous changes TAT was higher vs control. A direct correlation between TAT level and PAAP was not found. CONCLUSION: Disorders in thrombocytic and plasmic links of hemostasis are detectable early in IPD. Stable markers of thrombophilia (TAT and TF-4) reflect activity of inflammation in FA. They can be also used as sensitive diagnostic tests for diagnosis of PH and diagnosis of patients with activated coagulation system in IPD.
Assuntos
Fatores de Coagulação Sanguínea/análise , Hipertensão Pulmonar/sangue , Fibrose Pulmonar/sangue , Trombofilia/sangue , Adulto , Idoso , Biomarcadores/sangue , Circulação Sanguínea/fisiologia , Coagulação Sanguínea/fisiologia , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/complicações , Fibrose Pulmonar/fisiopatologia , Trombofilia/etiologia , Trombofilia/fisiopatologiaRESUMO
AIM: To study clinical efficacy of vasaprostan in patients with fibrosing alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on functional activity of platelets and endothelium, intensity of free radical processes. MATERIAL AND METHODS: Seven FA patients were examined. They had either idiopathic FA or FA with diffuse diseases of the connective tissues. The following methods were used to assess the effect: standard clinical tests, high resolution computer tomography, Doppler echocardiography, definition of the complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation of oxygen active forms by leukocytes was measured by luminol-dependent chemiluminescence. Morphological verification of the diagnosis was made by the results of open pulmonary biopsies. RESULTS: Vasaprostan reduced pressure in the pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25 +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4 (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced the ability of platelets to inhibit generation of active oxygen forms (from 0.9 +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid peroxidation. CONCLUSION: Good effect of vasaprostan on platelet activity, free radical processes validates its use in combined treatment of various FA forms for correction of PH, its complications and as an antifibrogenic agent.
Assuntos
Alprostadil/uso terapêutico , Fibrinolíticos/uso terapêutico , Hipertensão Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , Adulto , Idoso , Alprostadil/farmacologia , Antitrombina III , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Ecocardiografia Doppler , Feminino , Radicais Livres/análise , Radicais Livres/metabolismo , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Peptídeo Hidrolases/sangue , Fator Plaquetário 4/análise , Fibrose Pulmonar/complicações , Tomografia Computadorizada por Raios XRESUMO
AIM: To ascertain the role of some neurohumoral factors--nitric oxide (NO), ACE, histamine--in development of pulmonary hypertension (PH) in patients with interstitial lung diseases (ILD). MATERIAL AND METHODS: A total of 32 ILD patients were examined. Of them 14 had idiopathic fibrosing alveolitis (IFA), 6 had exogenous allergic alveolitis (EAA) and 12 patients had ILD in diffuse disease of the connective tissue (ILD-DDCT). In addition to routine tests, those for NO, ACE, histamine, serotonin in plasma were performed; Doppler echocardiography and high-resolution computed tomography were conducted. In 9 patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy subjects. RESULTS: The highest mean pressure in the pulmonary artery (PmPA) was registered in IFA vs EAA and ILD-DDCT patients (p < 0.001). NO concentration in plasma was higher in ILD-DDCT than in control patients. In IFA and EAA the level of NO was like in controls. Concentration of NO in plasma of IDL patients correlated with high activity of the process. No correlation was found between ACE in plasma and PmPA, ACE levels were much higher in controls than in the ILD patients (p < 0.05). Histamine levels were higher in ILD patients than in controls being the highest in ILD-DDCT. Serotonin was insignificantly higher in ILD patients than in controls. CONCLUSION: Damage to the endothelium of the pulmonary arteries and imbalance of neurohumoral factors may be considered as a mechanism of development and stabilization of PH in ILD patients.
Assuntos
Histamina/fisiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Óxido Nítrico/fisiologia , Peptidil Dipeptidase A/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Humanos , Pessoa de Meia-IdadeRESUMO
Thirty-two patients with different forms of interstitial lung diseases (ILD), such as idiopathic fibrosing alveolitis (IFA) (n = 17) and fibrosing alveolitis concurrent with diffuse connective tissue diseases (FA-DCTD), were examined. Clinical, echocardiographic, computed tomographic, coagulative, and immunological studies were performed. Enzyme immunoassay was used to determine the levels of a complex of thrombin and antithrombin III (TAT) and platelet factor IV (PF-IV). There were significant increases in the levels of PF-IV (4.36 +/- 0.25 mg/l) and TAT (10.87 +/- 3.8 mg/l) in patients with ILD as compared to the control (2.75 +/- 0.47 and 1.8 +/- 0.2 mg/l, respectively; p < 0.05). In patients with early FA-DCTD with the predominance of the milk glass syndrome during high-resolution CT (HRCT), the level of PF-IV was greater than the normal levels (p < 0.05) and decreased with the progression of the disease and with the formation of the honeycomb lung. If there were HRCT signs of active inflammation, the level of TAT was higher than that in the control; this was also in the development of irreversible fibrous changes.
Assuntos
Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pulmão/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/fisiopatologia , Endotélio/patologia , Endotélio/fisiopatologia , Feminino , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Clinical, functional, immunological and x-ray examinations were performed in 32 patients with interstitial pulmonary diseases (14 with idiopathic fibrosing alveolitis, 6 with exogenic allergic alveolitis and 12 with diffuse affection of the connective tissue). The diagnosis was verified using high resolution computed tomography. Lesser circulation was studied with doppler-echocardiography. In 9 patients the diagnosis was verified by thoracoscopic biopsy of the lung. Control group consisted of 16 healthy subjects. The highest pressure in the trunk of the pulmonary artery (31 +/- 4.3 mmHg) was registered in patients with idiopathic fibrosing alveolitis. The severity of pulmonary arterial hypertension correlated with that of respiratory disorders, clinical symptoms and changes in the lungs. Blood pressure in the pulmonary artery trunk tended to elevation with progression of alterations in the lungs registered by computed tomography.