Mechanics of the proximal pulmonary artery in pulmonary hypertension.

摘要

Pulmonary hypertension (PH) is an incurable, progressive disease with poor survival. PH is defined as an increase in mean pulmonary arterial pressure above 25mmHg at rest. Despite the rapid advances in PH therapies, the progressive nature of the disease eventually results in right heart failure and death. PH is characterized by vasoconstriction, remodeling, and thickening of the small to medium arteries and arterioles, resulting in increased pulmonary vascular resistance. Pulmonary vascular resistance is often the single parameter used to assess disease severity and response to treatment. However, other markers of vascular function, for example pulmonary vascular stiffness, area strain and vascular capacitance have been shown as predictive of mortality in PH.;This thesis includes three studies that focus on the intersection of clinical and scientific investigations to evaluate mechanical changes in the proximal pulmonary artery during PH and their impact on patient outcomes. The first is a clinical study utilizing a range of clinical measures in combination to accurately predict future patient health status to facilitate proactive clinical therapies. The second and third studies involved animal models. The second study focused on the mechanical impacts of preconditioning tissue. The third study looked at the mechanical changes in the proximal pulmonary artery upon PH onset and recovery. All of these studies centered on defining the mechanical function of the proximal pulmonary arteries through time in order to assess health status. We aim to quantify changes in the proximal pulmonary arteries in the setting of PH to help guide therapeutic targets and clinical interventions.;The findings of these three studies support that the the proximal pulmonary artery mechanics are important for prediction of future patient health status. In animal studies of soft tissue using pressure-inflation testing, sample preparation may significantly affect the resulting mechanics measurements. Care must be taken in tissue preparation and testing in order to preserve the mechanical characteristics as closely as possible to in-vivo settings. Finally, proximal PA segments from rats that have chronic hypoxia-induced PH and are allowed to recover for six weeks in normoxia have impaired mechanics: decreased vessel diameters, decreased vessel compliance and decreased wall tension as compared with age matched controls which may cause longer term right heart dysfunction. We also found, with hypoxic exposure, the PA segments have decreased VSM contraction and that VSM contraction returns to normal levels upon recovery. We speculate that therapies aimed at reducing or preventing collagen deposition may improve proximal PA mechanics upon recovery from PH or upon normalization of the hemodynamics.