The Effects of Prolonged Mechanical Ventilation on Structural and Material Properties of Diaphragm Arterioles

Abstract

IntroductionIn skeletal muscle arterioles, cellular and vasoactive responses are influenced by the physiochemical milieu of the surrounding tissue. Understanding the mechanical properties of the blood vessel wall yields insight into vascular function in health and disease. In blood vessels, the endothelium mediates flow‐dependent vasodilation and contributes to the regulation of arterial mechanics. Prolonged mechanical ventilation (MV)(>6 h) results in large, time‐dependent reductions in diaphragmatic blood flow and impaired endothelium‐dependent (and ‐independent) vasodilation of first‐order (1A) medial costal diaphragm arterioles. The purpose of this investigation was to determine if the severe reductions in diaphragmatic blood flow (and shear‐stress) with MV impair the structural and material properties (i.e. increased stress/stretch relation and/or circumferential stretch) of 1A arterioles from the medial costal diaphragm.MethodsFemale Sprague‐Dawley rats (~5 mo) were randomly divided into two groups, spontaneous breathing (SB, n = 6) and prolonged MV (6 h MV, n =5). Following SB and 6 h MV, 1A medial costal diaphragm arterioles (~200 μm diameter, ~2 mm in length) were isolated and cannulated. After cannulation, vessels were adjusted to a fixed length (L, 1.5 mm) and pressurized. Vessels that exhibited no leaks were subjected to a step‐wise passive‐pressure diameter test (0–140 cmH2O) in calcium‐free Ringer’s solution, at a single fixed axial length (L). Inner diameter (μm) and wall thickness (μm) were measured at each pressure step and used to calculate wall: lumen ratio, incremental distensibility (%/mmHg), Cauchy‐stress (μ), and circumferential stretch (λθ).ResultsFollowing 6 h MV, in the undeformed condition (0 mmHg) the wall: lumen ratio was significantly smaller compared to SB (1.04 ±0.21vs. 2.60 ±0.40; p<0.05). There were no differences in incremental distensibility (%/mmHg) and the stress/stretch (μvs λθ) relation between groups (p>0.05). At every pressure step, circumferential stretch (λθ; undeformed radius (r)/current deformed radius (R)) was significantly increased with 6 h MV versus SB (p<0.05).ConclusionDespite no change in the distensibility and structural behavior (stress/stretch) of resistance vessels from the medial costal diaphragm, prolonged MV resulted in altered material properties (i.e. elevated circumferential stretch (λθ)) of medial costal diaphragm arterioles. Increased circumferential stretch can enhance superoxide generation in the endothelium and vascular smooth muscle cells. Therefore, elevated circumferential stretch of 1A diaphragm arterioles in combination with the severe reductions in blood flow may, in part, explain the previously demonstrated vascular dysfunction in the diaphragm following MV.Support or Funding InformationSupported by: NIH HL137156‐01A1