The Impact of Aging and Biological Sex on Diaphragm Hyperemia and Blood Flow Distribution
Authors: Horn Andrew , Schulze Kiana , Weber Ramona , Kunkel Olivia , C Poole David , Behnke Bradley 
Published: May 2024

INTRODUCTION: Age-related respiratory muscle dysfunction (i.e., the diaphragm) diminishes physical capacity and increases the susceptibility to respiratory failure. The diaphragm dysfunction associated with old age is characterized by decreased diaphragm muscle mass and strength, and increased fatiguability. While inadequate perfusion and diminished microvascular function are well recognized to play a central role in age-related peripheral skeletal muscle dysfunction, the impact of aging on diaphragm hyperemia and blood flow distribution, and whether sex differences exist, has not been investigated. METHODS: Young (Y; 4-6 months) and Old (O; 22-24 months) Fischer 344 rats (n=34) were divided into four groups: 1) Young female (YF; n=8), 2) Young male (YM; n=8), 3) Old female (OF; n=9), and 4) Old male (OM; n=9). Fluorescent microspheres were used to assess bulk and regional diaphragm blood flow at rest and during electrically-induced 1Hz contractions. RESULTS: There were no age-related or sex differences in quiescent diaphragm blood flow (BF) or vascular conductance (VC) ( P>0.05). Age-related differences during 1Hz contractions: The increase in total diaphragm BF was significantly lower in OM (98 ± 11 ml/min/100g) compared to YM (141 ± 7 ml/min/100g; p<0.05). Total and regional diaphragm BF was not different in F rats ( P>0.05); however, medial costal diaphragm VC was decreased in OF (1.2 ± 0.1 ml/mmHg/min/100g) compared to YF (1.8 ± 0.2 ml/mmHg/min/100g; p<0.05). Sex differences during 1Hz contractions: Total diaphragm BF and VC were similar in YF and YM ( P > 0.05). While both ventral and medial costal diaphragm BF responses were not different between YF and YM, dorsal costal diaphragm BF was higher in YF (144 ± 27 ml/min/100g) versus YM (84 ± 11 ml/min/100g; p<0.05). Total and regional (ventral, medial, and dorsal costal) diaphragm BF was significantly higher in OF compared to OM ( p<0.05). CONCLUSION: These data demonstrate that aging impaired the ability of the diaphragm to augment BF in response to contractile activity in M rats and decreased medial costal diaphragm VC during contractions in F rats with no significant effect on diaphragmatic hyperemia. In regards to sex differences, these data suggest that both YF and OF may have a greater regional recruitment of the diaphragm compared to YM and OM. The data herein provide a putative mechanism for age-related diaphragm contractile dysfunction and future studies are needed to investigate the impact of aging and biological sex on diaphragm vascular function. National Institute of Aging 1R15AG078060, Ruth L. Kirschstein National Research Service Awards from the National Heart, Lung, and Blood Institute 1F31HL167618-01 and 1F31HL170643-01, and Sustained Momentum for Investigators with Laboratories Established (SMILE) Grants at Kansas State University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.