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

Kiana M Schulze; Andrew G Horn; Ramona E Weber; Bradley J Behnke; David C Poole; Timothy I Musch

doi:10.3389/fphys.2023.1281715

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

Front Physiol. 2023 Dec 22:14:1281715. doi: 10.3389/fphys.2023.1281715. eCollection 2023.

Authors

Kiana M Schulze^#¹, Andrew G Horn^#¹, Ramona E Weber¹, Bradley J Behnke¹, David C Poole^{1

2}, Timothy I Musch^{1

2}

Affiliations

¹ Department of Kinesiology, Kansas State University, Manhattan, KS, United States.
² Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, United States.

^# Contributed equally.

Abstract

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 ( $\dot{Q}$ ), 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. Methods: 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. Results: PH rats displayed morphometric and echocardiographic criteria for disease (i.e., acceleration time/ejection time, right ventricular hypertrophy). In all rats, total costal diaphragm $\dot{Q}$ increased during contractions and did not differ between groups. In HC rats, there was a greater increase in medial costal $\dot{Q}$ compared to PH rats (55% ± 3% vs. 44% ± 4%, p < 0.05), who demonstrated a redistribution of $\dot{Q}$ to the ventral costal region. Conclusion: 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.

Keywords: monocrotaline; oxygen transport; perfusion; respiratory muscle; vascular dysfunction.

Abstract

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