Prolonged mechanical ventilation increases diaphragm arteriole circumferential stretch without changes in stress/stretch: Implications for the pathogenesis of ventilator‐induced diaphragm dysfunction

Abstract

Prolonged mechanical ventilation (MV) (≥6 h) results in large, time-dependent reductions in diaphragmatic blood flow and shear stress. We tested the hypothesis that MV would impair the structural and material properties (i.e. increased stress/stretch relation and/or circumferential stretch) of first-order arterioles (1A) from the medial costal diaphragm. Methods Shear stress was estimated from isolated arterioles and prior blood flow data from the diaphragm during spontaneous breathing (SB) and prolonged MV (6 h MV). Thereafter, female Sprague-Dawley rats (~5 mo) were randomly divided into two groups, SB (n = 6) and 6 h MV (n = 6). Following SB and 6 h MV, 1A medial costal diaphragm arterioles were isolated, cannulated, and subjected to step-wise (0-140 cmH₂O) increases in intraluminal pressure in calcium-free Ringer’s solution. Inner diameter and wall thickness were measured at each pressure step and used to calculate wall: lumen ratio, Cauchy-stress, and circumferential stretch. Results Compared to SB, there was a ~90% reduction in arteriolar shear-stress with prolonged MV (9 ± 2 versus 78 ± 20 dynes cm^-2; p≤0.05). In the unloaded condition (0 cmH₂O), the arteriolar intraluminal diameter was reduced (37 ± 8 versus 79 ± 13 μm) and wall: lumen ratio was increased (120 ± 18 versus 46 ± 10 %) compared to SB (p≤0.05). There were no differences in the passive diameter responses or the circumferential stress/stretch relationship between groups (p>0.05), but at each pressure step, circumferential stretch was increased with 6 h MV versus SB (p≤0.05). Conclusion During prolonged MV, medial costal diaphragm arteriolar shear stress is severely diminished. Despite no change in the material behavior (stress/stretch), prolonged MV resulted in altered structural and mechanical properties (i.e. elevated circumferential stretch) of medial costal diaphragm arterioles. This provides important novel mechanistic insights into the impaired diaphragm blood flow capacity and vascular dysfunction following prolonged MV.