Differential Effects Of Flow Stasis On Flow-mediated Dilation In Diaphragm And Soleus Skeletal Muscle Arterioles

Abstract

Unlike limb muscle, the diaphragm is active during the entire lifespan of an individual. However, with inactivity from mechanical ventilation (MV), there is a time-dependent reduction in diaphragm blood flow and inability to augment flow with contractions which is not evident in hindlimb locomotory muscle. One potential mechanism for the reduced hyperemia after MV is a diminished vasodilatory capacity due to the prolonged reduction in blood flow in the diaphragm. PURPOSE: The purpose of the present investigation was to test the hypothesis that prolonged flow stasis (i.e., absence of flow through vascular lumen) will elicit a rapid reduction in flow-mediated dilation (FMD) in diaphragm resistance vessels, whereas those from locomotory muscle (soleus) muscle will exhibit a preserved vasodilation. METHODS: Using the isolated microvessel technique, resistance arterioles were harvested from the diaphragm and soleus muscles of female Sprague-Dawley rats (n=8, 4 mo., ∼275 g). After the vessels were cannulated, FMD was measured after 1, 3, and 6 hours of flow stasis in the vessels. RESULTS: Despite no difference in initial diameter after cannulation between muscles, the maximal arteriolar diameter (at the end of the experiment) of the arterioles in the diaphragm was smaller than those of the soleus (165 ± 16 vs. 195 ± 22 μm, respectively; p≤0.05). After 1 hour of stasis, maximal FMD was not different between groups (diaphragm, 49 ± 4, Sol, 44 ± 7%, p>0.1). However, in the diaphragm at 3 and 6 hours of flow stasis, there was a 46 ± 6% and 83 ± 4% reduction in maximal FMD, respectively (both p<0.05 vs. 1 hour). There was no difference in maximal FMD over time in the soleus muscle arterioles. After 6 hours of flow stasis maximal FMD was lower in the diaphragm (8 ± 2%) compared to the soleus (42 ± 9%; p<0.05) muscle arterioles. CONCLUSION: There are several unique vascular properties of the diaphragm in relation to other skeletal muscle which, when coupled with its chronic activation, may expedite the time-course of vasomotor dysfunction with disuse in this muscle. The severely blunted FMD observed herein may predispose patients subjected to MV to weaning difficulties due, in part, to a diminished capacity to increase oxygen delivery to the diaphragm during contractions. Supported by NIH AG-31317 (BJB) and R21 AG044858 (JMD).