Beneficial effects of mesenchymal stem cell delivery via a novel cardiac bioscaffold on right ventricles of pulmonary arterial hypertensive rats.

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms, and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against right ventricle (RV) maladaptation despite PAH progression.

Pulmonary vascular mechanical consequences of ischemic heart failure and implications for right ventricular function.

Left heart failure (LHF) is the most common cause of pulmonary hypertension, which confers an increase in morbidity and mortality in this context. Pulmonary vascular resistance has prognostic value in LHF, but otherwise the mechanical consequences of LHF for the pulmonary vasculature and right ventricle (RV) remain unknown. We sought to investigate mechanical mechanisms of pulmonary vascular and RV dysfunction in a rodent model of LHF to address the knowledge gaps in understanding disease pathophysiology.

Organ-level right ventricular dysfunction with preserved Frank-Starling mechanism in a mouse model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rapidly fatal disease in which mortality is due to right ventricular (RV) failure. It is unclear whether RV dysfunction initiates at the organ level or the subcellular level or both. We hypothesized that chronic pressure overload-induced RV dysfunction begins at the organ level with preserved Frank-Starling mechanism in myocytes.

Characteristic impedance: frequency or time domain approach?

Objective: Characteristic impedance (Zc) is an important component in the theory of hemodynamics. It is a commonly used metric of proximal arterial stiffness and pulse wave velocity. Calculated using simultaneously measured dynamic pressure and flow data, estimates of characteristic impedance can be obtained using methods based on frequency or time domain analysis.

Pulmonary vascular collagen content, not cross-linking, contributes to right ventricular pulsatile afterload and overload in early pulmonary hypertension.

Unlabelled: Hypoxic pulmonary hypertension (HPH) is associated with pulmonary artery (PA) remodeling and right ventricular (RV) overload. We have previously uncovered collagen-mediated mechanisms of proximal PA stiffening in early HPH by manipulating collagen degradation and cross-linking using a transgenic mouse strain and a potent collagen cross-link inhibitor, β-aminopropionitrile (BAPN). However, the roles of collagen in distal PA remodeling, overall RV afterload, and RV hypertrophy in HPH remain unknown.

Increased Red Blood Cell Stiffness Increases Pulmonary Vascular Resistance and Pulmonary Arterial Pressure.

Patients with sickle cell anemia (SCD) and pulmonary hypertension (PH) have a significantly increased risk of sudden death compared to patients with SCD alone. Sickled red blood cells (RBCs) are stiffer, more dense, more frequently undergo hemolysis, and have a sixfold shorter lifespan compared to normal RBCs. Here, we sought to investigate the impact of increased RBC stiffness, independent of other SCD-related biological and mechanical RBC abnormalities, on the hemodynamic changes that ultimately cause PH and increase mortality in SCD.

Impact of increased hematocrit on right ventricular afterload in response to chronic hypoxia.

Chronic hypoxia causes chronic mountain sickness through hypoxia-induced pulmonary hypertension (HPH) and increased hematocrit. Here, we investigated the impact of increased hematocrit and HPH on right ventricular (RV) afterload via pulmonary vascular impedance. Mice were exposed to chronic normobaric hypoxia (10% oxygen) for 10 (10H) or 21 days (21H).

Progressive right ventricular functional and structural changes in a mouse model of pulmonary arterial hypertension.

Right ventricle (RV) dysfunction occurs with progression of pulmonary arterial hypertension (PAH) due to persistently elevated ventricular afterload. A critical knowledge gap is the molecular mechanisms that govern the transition from RV adaptation to RV maladaptation, which leads to failure. Here, we hypothesize that the recently established mouse model of PAH, via hypoxia and SU5416 treatment (HySu), captures that transition from adaptive to maladaptive RV remodeling including impairments in RV function and decreases in the efficiency of RV interactions with the pulmonary vasculature.

Analysis of cardiovascular dynamics in pulmonary hypertensive C57BL6/J mice.

A computer model was used to analyze data on cardiac and vascular mechanics from C57BL6/J mice exposed to 0 (n = 4), 14 (n = 6), 21 (n = 8) and 28 (n = 7) days of chronic hypoxia and treatment with the VEGF receptor inhibitor SUGEN (HySu) to induce pulmonary hypertension. Data on right ventricular pressure and volume, and systemic arterial pressure obtained before, during, and after inferior vena cava occlusion were analyzed using a mathematical model of realistic ventricular mechanics coupled with a simple model of the pulmonary and systemic vascular systems. The model invokes a total of 26 adjustable parameters, which were estimated based on least-squares fitting of the data.