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May 14, 2026Physiology0 citations

Effects of heart failure on the diaphragm hyperemic response in old rats

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ADAddison DePlataKansas State UniversityAHAndrew HornUniversity of UtahNKNathan KenneyKansas State University

Key Points

  • This study aims to assess the impact of heart failure on diaphragm blood flow and vascular conductance in aged rats.
  • Fischer-344 rats aged 22–24 months were divided into old sham and heart failure groups.
  • Heart failure was induced through coronary artery ligation, with recovery for 7-8 weeks before measurements.
  • Diaphragm blood flow was assessed using fluorescent microspheres during rest and contraction.
  • O-HF rats showed significantly lower total diaphragm blood flow (219 ± 44 ml/min/100g vs. 367 ± 60 ml/min/100g, P=0.024).
  • O-HF rats had reduced vascular conductance (1.6 ± 0.4 ml/mmHg/100g/min vs. 3.4 ± 1.3 ml/mmHg/100g/min, P=0.049).
  • The medial costal diaphragm blood flow was also significantly lower in O-HF rats (171 ± 61 ml/min/100g vs. 435 ± 29 ml/min/100g, P=0.005).

Abstract

Introduction: The diaphragm is the primary ventilatory muscle and continually contracts throughout life. Sufficient perfusion and vascular function are major determinants of diaphragm contractile function. Importantly, the medial costal region of the diaphragm is critical to overall diaphragm function, performing the largest proportion of contractile work and receiving the highest relative perfusion among diaphragm regions. In old age and with heart failure (HF), diaphragm contractile function is compromised despite elevated diaphragm metabolic demands, suggesting that diaphragm hyperemia and/or blood flow (BF) regulation is compromised. Aging impairs diaphragm regional BF distribution; however, direct measurements of diaphragm hyperemic responsiveness and regional diaphragm perfusion (primarily the medial costal region) in HF and advanced age have not been interrogated. Methods: Fischer-344 (22–24-mo-old) rats were divided into old sham (O-SHAM; n=2) and myocardial infarction (MI)-induced heart failure (O-HF; n=4) groups. For this preliminary study, HF was induced by surgically ligating the coronary artery. For sham surgeries, the left main coronary artery was not ligated. Rats were allowed to recover for 7–8 weeks to develop HF and were confirmed via echocardiography. To assess bulk and regional diaphragm BF, the right carotid and caudal artery was cannulated, and a laparotomy was performed. Stainless-steel electrodes were sutured to the abdominal surface of the diaphragm at the ventral-medial (anode) and dorsal-medial borders (cathode). Thereafter, fluorescent microspheres (15 μM diameter) were infused into the aortic arch via the carotid artery catheter at rest and during electrically induced 1 Hz contractions. Results were compared via t-tests. Results: Body mass (O-SHAM: 324 ± 60 g; O-HF: 316 ± 33 g) and diaphragm mass (O-SHAM: 660 ± 47 mg; O-HF: 647 ± 62 mg) did not differ between groups. During 1 Hz contractions, O-SHAM rats displayed a greater total diaphragm BF (367 ± 60 ml/min/100g vs. 219 ± 44 ml/min/100g, P= 0.024) and vascular conductance (VC: 3.4 ± 1.3 ml/mmHg/100g/min vs. 1.6 ± 0.4 ml/mmHg/100g/min, P= 0.049) compared to O-HF. O-HF rats additionally had significantly lower medial costal BF (171 ± 61 ml/min/100g vs. 435 ± 29 ml/min/100g, P= 0.005) and VC (1.57 ± 0.5 ml/mmHg/100g/min vs. 3.99 ± 1.13 ml/mmHg/100g/min, P= 0.019) responses compared to O-SHAM. Conclusion: These findings suggest that the ability to augment diaphragm BF and VC is blunted in O-HF rats and that this results in poor matching of oxygen delivery to metabolic demand. HF in advanced age, where diaphragm BF regulation is already compromised, may further exacerbate the inability to regulate regional diaphragm perfusion. The lower BF and VC in the medial costal diaphragm of O-HF rats suggest that vascular dysfunction may be a key contributor to inspiratory muscle fatigue and dysfunction prevalent in the older heart failure population. Future studies are warranted to fully elucidate the combined effects of HF and old age on diaphragm hemodynamics. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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DePlata et al. (2026) studied this question.

synapsesocial.com/papers/6a05684ea550a87e60a20b5ahttps://doi.org/10.1152/physiol.2026.41.s1.2301123
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