Effects of pulmonary hypertension on microcirculatory hemodynamics in rat skeletal muscle.

Abstract

Pulmonary hypertension (PH) has previously been characterized as a disease of the pulmonary vasculature that subsequently results in myocardial dysfunction. Heart failure compromises skeletal muscle microvascular function, which contributes to exercise intolerance. Therefore, 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 in quiescent muscle. Adult male Sprague-Dawley rats were randomized into healthy (n=9) and PH groups (n=9). Progressive PH was induced via a one-time intraperitoneal injection of monocrotaline (MCT; 50mg/kg) and rats were monitored weekly via echocardiography. Intravital microscopy in the spinotrapezius muscle was performed when echocardiograms confirmed moderate PH (preceding right ventricular (RV) failure). At 25±9days post-MCT, PH rats displayed RV hypertrophy (RV/(Left ventricle+Septum): 0.28±0.05 vs. 0.44±0.11), pulmonary congestion, and increased right ventricular systolic pressure (21±8 vs. 55±14mmHg) compared to healthy rats (all P<0.05). Reduced capillary RBC velocity (403±140 vs. 227±84μm/s; P=0.01), RBC flux (33±12 vs. 23±5 RBCs/s; P=0.04) and % of capillaries supporting continuous RBC flux at rest (79±8 vs. 56±13%; P=0.01) were evident in PH rats compared to healthy rats. When Q̇O2 within a given field of view was quantified (RBC flux x % of capillaries supporting continuous RBC flux), PH rats demonstrated lower overall Q̇O2 (↓ 50%; P=0.002). These data support that microcirculatory hemodynamic impairments (↓ Q̇O2 and therefore altered Q̇O2-to-V̇O2 matching) may compromise blood-myocyte O2 transport in PH. The mechanistic bases for decreased capillary RBC flux, velocity, and percentage of capillaries supporting RBC flow remains an important topic.