Vascular Changes During Resolution Of Pulmonary Arterial Hypertension

Abstract

Pulmonary hypertension associated with myointimal proliferation is produced by low grade, sustained damage to the arterial surfaces by Dirofilaria immitis (DI) infection in dogs. This study correlated changes during and after infection in pulmonary vascular hemodynamics, arteriograms, and morphology {scanning electron microscopy (SEM) and light microscopy (LM)}. Seven beagles were infected with 50 infective DI larvae. Twelve months after infection, mild pulmonary hypertension {mean pulmonary arterial pressure (MPAP) during normoxia was 26.4 mmHg versus 16.0 pre-infection, during isoproterenol infusion was 37.6 vs. 14.3 pre-infection and reduction of pulmonary vascular resistance was 31.1% versus 47.2% pre-infection} was present. Angiograms at this time revealed dilation and tortuosities of the main and intralobar pulmonary arteries. SEM revealed large villus proliferations, disoriented cell axis, and pore formation. The villi projected (LM) into the vessel lumen and consisted of intimai thickening with multiplying smooth muscle cells and collagen.Seven months after treatment to eliminate the DI as a cause of the arterial trauma, pulmonary hypertension was resolved (MPAP of 19.8 during normoxia, 17.7 during isoproterenol infusion, and reduction of pulmonary vascular resistance of 45.2%). The arteriographie changes of dilation, aneurysms, and tortuosities were decreased, especially in the main and lobar arteries. LM revealed that larger arteries, which had greater arteriographie resolution, had relatively more elastic tissue and that the intralobar arteries had more collagen. SEM revealed that the villus proliferations were markedly reduced in numbers and sizes. This study characterized a reduction of hypertension as related to resolution of the muscular hypertrophy of arteries and related arteriographie changes to the type of connective tissue being produced by smooth muscle cells in the arterial wal.