Maladaptive right ventricular (RV) hypertrophic responses lead to RV dysfunction and failure in patients with pulmonary arterial hypertension, but the mechanisms responsible for these changes are not well understood. The objective of this study was to evaluate the effect of treatment with bosentan on RV hypertrophy (RVH), fibrosis and expression of protein kinase C (PKC) isoforms in the RV of rats exposed to chronic hypoxia. Methods Adult Sprague Dawley rats were housed in normoxia or hypoxia (FiO2: 10%) and administered vehicle or 100mg/kg/day of bosentan. After 3 weeks, echocardiographic, hemodynamic assessment was performed. PKC, procollagen-1, and collagen expression was assessed using immunoblot or colorimetric assay. Results RV systolic pressure (RVSP) and RVH were higher in hypoxic compared to normoxic animals (RVSP: 72 ± 4 vs. 25 ± 2 mmHg, p<0.05; RVH: 1.2 ± 0.06 vs. 0.5 ± 0.03 mg/g body wt., p<0.05). Bosentan had no effect on RVSP or mass in normoxic animals, but did attenuate RVH in hypoxic animals (Hypoxic/vehicle: 1.2 ± 0.06; Hypoxic/bosentan: 1.0 ± 0.05 mg/g body wt., p<0.05). Hypoxia increased RV procollagen-I, and total collagen expression, effects that were attenuated by bosentan treatment. Hypoxia increased RV total and cytosolic PKC-δ protein expression, but had no effect on PKC-α or -ε isoforms. Administration of bosentan did not affect total PKC-δ protein expression. However, animals treated with bosentan had an increase in membranous PKC-δ when exposed to hypoxia. Conclusion Bosentan inhibits RVH and RV collagen expression in rats exposed to chronic hypoxia possibly via alteration of PKCδ activity.

Glottic insufficiency has been successfully managed by Teflon augmentation of paretic vocal cords over the past two decades. Collagen fulfills the criteria for a suitable bioimplant and is an attractive alternative as it is a normal constituent of the extracellular protein matrix. This study explores the use of modified bovine collagen injected into the canine larynx. Clinical situations are simulated by creating lesions and injecting collagen at different sites. The technique permits precise placement and quantification. Histologic study of the collagen implant fails to show evidence of significant foreign body reaction. The injected collagen appears similar to viable connective tissue and is colonized by host fibroblasts and nourishing capillaries.

Pulmonary arterial hypertension is a rare disease, which requires a high index of suspicion to diagnose when patients initially present. Initial symptoms can be nonspecific and include complaints such as fatigue and mild dyspnea. Once the disease is suspected, echocardiography is used to estimate the pulmonary arterial (PA) pressure and to exclude secondary causes of elevated PA pressures such as left heart disease. Right heart catheterization with vasodilator challenge is critical to the proper assessment of pulmonary hemodynamics and to determine whether patients are likely to benefit from vasodilator therapy. Pathologically, the disease is characterized by deleterious remodeling of the distal pulmonary arterial and arteriolar circulation, which results in increased pulmonary vascular resistance. In the last fifteen years, medications from three different classes have been approved for the treatment of pulmonary arterial hypertension. These include the prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors.