Effects of Pulmonary Hypertension on Microcirculatory Hemodynamics in Rat Skeletal Muscle

Abstract

Introduction Pulmonary hypertension (PH) has previously been characterized as a disease of the pulmonary vasculature resulting subsequently in myocardial dysfunction. However, because heart failure compromises skeletal muscle microvascular function, contributing to exercise intolerance, we tested the hypothesis that such changes might be present in PH. Thus, we investigated skeletal muscle oxygen (O2) transport in the rat model of PH to determine if O2 delivery (Q̇O2) is impaired at the level of the microcirculation as evidenced via reduced red blood cell (RBC) flux, velocity, hematocrit, and percentage of capillaries flowing at rest. Methods Adult male Sprague-Dawley rats were randomized into healthy (n=9) and PH groups (n=4). Progressive PH was induced via a one-time intraperitoneal injection of monocrotaline (MCT; 50 mg/kg) and disease progression was monitored via echocardiography. Intravital microscopy in the resting spinotrapezius muscle was performed when moderate PH (preceding right ventricular (RV) failure) became evident. Results At 23 ± 1 days post-MCT, PH rats displayed RV hypertrophy (RV/Left ventricle+Septum: 0.28 ± 0.01 vs. 0.44 ± 0.04), pulmonary congestion, increased right ventricular systolic pressure (20 ± 3 vs. 48 ± 6 mmHg), and arterial hypoxemia (PaO2: 84 ± 3 vs. 64 ± 4 mmHg) compared to healthy rats (all P ≤ 0.05). Reduced capillary RBC velocity (403 ± 140 vs. 216 ± 88 µm/s; P = 0.03) and% of capillaries supporting RBC flux at rest (87 ± 5 vs. 75 ± 11%; P = 0.017) were evident in PH rats compared to healthy rats. Interestingly, no differences were observed in capillary RBC flux (P > 0.05) which was due, in part, to increased capillary hematocrit (10 ± 3 vs. 16 ± 4%; P < 0.05) in PH. However, when we quantified total Q̇O2 within a given field of view (RBC flux x % of capillaries supporting continuous RBC flux), PH rats demonstrated lower overall Q̇O2 (↓ 43%; P = 0.04). Conclusions These data support that microcirculatory hemodynamic impairments (↓ Q̇O2 and altered Q̇O2-to-V̇O2 matching) may compromise blood-myocyte O2 flux in PH. The mechanistic bases for the decreased capillary RBC velocity, elevated hematocrit, and reduced percentage of capillaries supporting RBC flux remains an important topic for future investigations.