Bulk and regional diaphragm blood flow during chemical hyperpnea in pulmonary hypertensive rats

Abstract

Pulmonary hypertension (PH) is a disease characterized by increased pulmonary arterial pressures, impaired gas exchange, dyspnea, and diaphragmatic dysfunction. Specifically, in PH, the diaphragm displays impaired contractility, vascular dysfunction, and blood flow redistribution toward less mechanically advantageous regions such as the ventral costal and crural diaphragm at rest and during submaximal exercise. While diaphragm blood flow is not a limitation to maximal exercise in health, whether it limits diaphragm function in PH is unknown. We hypothesized that, during chemically induced hyperpnea: 1) diaphragm blood flow will be lower in rats with PH compared with healthy controls due to vasodilatory impairments in the diaphragm vasculature, and 2) in PH, blood flow will be redistributed toward less mechanically advantageous regions of the diaphragm. Female Sprague-Dawley rats were randomized into healthy (n = 12) or monocrotaline-induced PH (n = 12) groups. Fluorescent microspheres were used to determine bulk and regional diaphragm blood flow at rest and during hypoxic-hypercapnic gas inhalation (10 % O₂-8 % CO₂). During chemically induced hyperpnea, diaphragm blood flow was higher in PH compared with healthy controls (483 ± 102 vs. 298 ± 119 ml/min/100 g; P < 0.001), and the ventral costal and crural regions of the diaphragm supported greater perfusion in PH. These results are consistent with previous findings at rest and during submaximal exercise in PH, which may help explain diaphragmatic weakness and dyspnea across a range of ventilatory demands in PH.