Suppression of Aseptic Inflammation Reduces the Severity of Pulmonary Artery Remodeling and Improves the Clinical Course of Experimental Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is acomplication of pulmonary embolism, characterized by high bloodpressure in the pulmonary artery combined with impaired lysis of fibrinclots. Previously, the presence of aseptic inflammation in CTEPHwas found in the wall of the pulmonary artery branches, as wellas perivascularly. However, the role of this inflammation in shaping CTEPHis unknown. The aim of the work was to study the effect of asepticinflammation on CTEPH formation and progression. The experimentswere carried out on male Wistar rats (n =54). The CTEPH model was reproduced by repeated intravenous administrationof partially biodegradable microspheres (MS). Immediately afterthe last MS administration, all animals were randomly allocatedinto four groups: (1) control (c.CTEPH) group—physiological salinewas administered intramuscularly (i.m.) for 6 weeks; (2) low-doseprednisolone (LDP) group—prednisolone was administered i.m. at adose of 1.5 mg/kg; (3) high-dose prednisolone (HDP) group—prednisolonewas administered i.m. at a dose of 6 mg/kg; (4) healthy or intact(INT) group. After 6 weeks, there were performed the treadmill test, transthoracicechocardiography, cardiac catheterization with blood pressure manometry,and lung tissue histological examination. In a separate series ofexperiments, the degree of vascular wall and perivascular spaceinflammatory infiltration was assessed immunohistochemically. InLDP group, the vascular wall hypertrophy index (HI) and the percentageof collagen fibers in the vascular wall were reduced compared tothe control group, with the HI being reduced significantly greaterthan in HDP group. In the latter, there was revealed a positiveeffect of high-dose prednisolone on the percentage of collagen fibersin the vascular wall, with this parameter being non-significantlydifferent from that in intact animals. By immunohistochemical data,low-dose prednisolone effectively suppressed inflammatory infiltrationof the vascular wall and perivascular space. Thus, we revealed theability of low-dose prednisolone to reduce the degree of remodelingof the pulmonary artery branches by suppressing aseptic inflammation.