Diaphragmatic Blood Flow Is Increased In A Rat Model Of Pulmonary Arterial Hypertension

PURPOSE: Skeletal muscle dysfunction including atrophy, decreased force production and a shift toward anaerobic metabolism have been suggested as contributing to exercise limitations in pulmonary arterial hypertension (PAH). We recently reported a reduction in skeletal muscle blood flow at rest and during exercise in a rat model of PAH; however, evidence suggests that increased energy requirements of the respiratory muscles may lead to increased flow to sustain ventilatory function in this condition. We therefore performed novel characterization of blood flow to the diaphragm at rest and during exercise in a rat model of PAH. METHODS: Treadmill running at 50% VO2max was performed by male Sprague-Dawley rats (368 ± 13 g) injected with monocrotaline (MCT, 60 mg/kg) to elicit a severe PAH phenotype (MCT, n = 12), or vehicle control (saline) (CON, n = 13). Fluorescent microspheres injected during run and rest bouts were utilized to determine blood flow via photo spectroscopy of harvested diaphragm muscles. VO2max was measured prior to terminal blood flow studies to characterize exercise capacity of each rat and determine relative exercise intensity for flow analysis. RESULTS: MCT exhibited elevated right ventricular (RV) relative mass (p = <0.0001) and wall thickness (p = 0.01), higher RV systolic pressure (p = <0.0001) and lower VO2max (p = 0.0002) vs. CON, consistent with severe PAH. Opposite to previous findings in skeletal muscle, diaphragmatic blood flow (in mL.min-1.kg-1) was significantly elevated in PAH vs. CON at rest (2.09 ± 0.22 vs. 1.11 ± 0.06, p = <0.0001) and tended to be higher during exercise in PAH (2.25 ± 0.26 vs. 1.60 ± 0.20, p = 0.07). Further, exercising blood flow to the diaphragm in PAH was significantly correlated with whole body lactate measured during exercise (r = 0.49, p = 0.01). CONCLUSIONS: Blood flow to the diaphragm is elevated at rest and during exercise in a rat model of PAH. Additionally, increased blood to the diaphragm during exercise is related to whole body lactate in PAH rats. These findings imply a greater energy demand of respiratory muscles in the disease, potentially contributing to exercise intolerance. Funding: NIH-NHLBI R-15 (MB Brown).