AUTHOR=Schulze Kiana M. , Horn Andrew G. , Weber Ramona E. , Behnke Bradley J. , Poole David C. , Musch Timothy I. 

TITLE=Pulmonary hypertension alters blood flow distribution and impairs the hyperemic response in the rat diaphragm

JOURNAL=Frontiers in Physiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1281715

DOI=10.3389/fphys.2023.1281715

ISSN=1664-042X

ABSTRACT=<p>Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, respiratory muscle and cardiac impairments, and exercise intolerance. Specifically, impaired gas exchange increases work of the diaphragm; however, compromised contractile function precludes the diaphragm from meeting the increased metabolic demand of chronic hyperventilation in PH. Given that muscle contractile function is in part, dependent upon adequate blood flow (<inline-formula id="equ52"><mml:math id="m52" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">Q</mml:mi><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula>), diaphragmatic dysfunction may be predicated by an inability to match oxygen delivery with oxygen demand. We hypothesized that PH rats would demonstrate a decreased hyperemic response to contractions compared to healthy controls.</p><p><bold>Methods:</bold> Sprague-Dawley rats were randomized into healthy (HC, n = 7) or PH (n = 7) groups. PH rats were administered monocrotaline (MCT) while HC rats received vehicle. Disease progression was monitored via echocardiography. Regional and total diaphragm blood flow and vascular conductance at baseline and during 3 min of electrically-stimulated contractions were determined using fluorescent microspheres.</p><p><bold>Results:</bold> PH rats displayed morphometric and echocardiographic criteria for disease (i.e., acceleration time/ejection time, right ventricular hypertrophy). In all rats, total costal diaphragm <inline-formula id="equ53"><mml:math id="m53" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">Q</mml:mi><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula> increased during contractions and did not differ between groups. In HC rats, there was a greater increase in medial costal <inline-formula id="equ54"><mml:math id="m54" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">Q</mml:mi><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula> compared to PH rats (55% ± 3% vs. 44% ± 4%, <italic>p</italic> &lt; 0.05), who demonstrated a redistribution of <inline-formula id="equ55"><mml:math id="m55" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">Q</mml:mi><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula> to the ventral costal region.</p><p><bold>Conclusion:</bold> These findings support a redistribution of regional diaphragm perfusion and an impaired medial costal hyperemic response in PH, suggesting that PH alters diaphragm vascular function and oxygen delivery, providing a potential mechanism for PH-induced diaphragm contractile dysfunction.</p>