The Effects of Prolonged Mechanical Ventilation on Diaphragm Arteriolar Response to Alpha‐Adrenergic Agonists

Abstract

IntroductionMechanical ventilation (MV) is a life‐saving intervention and is employed in Intensive Care Units across the world. Previous work has shown a substantial time‐dependent reduction in diaphragmatic blood flow and O2 delivery with MV that may contribute to ventilator‐induced diaphragm dysfunction. However, the precise mechanism responsible for these alterations in blood flow are unknown. Given the reduction in diaphragm blood flow with prolonged MV, we tested the hypothesis that prolonged MV (e.g. 6 hours) enhances diaphragm arteriole contractile responses to alpha‐adrenergic agonists.MethodsFemale Sprague Dawley rats (5–8 mo) were divided into spontaneous breathing (SPB; n= 10) and MV (n= 3). Following SPB and 6 hours of MV, diaphragm arterioles (~200mm diameter, ~2mm in length) were isolated, cannulated, and pressurized to develop spontaneous tone. Thereafter, contractile responses to cumulative doses of norepinephrine (NE) and phenylephrine (PE) (10−9 to 10−4M) were determined.Results and ConclusionFrom this preliminary data, vasoconstrictor responses to NE, and PE in diaphragm arterioles were not different after prolonged MV (% max constriction, NE=23.3± 20.47, PE=16.8± 16.41 compared to SPB (% max constriction, NE= 37.5± 16.71 (P = 0.27); PE= 38.03± 21.76 (P =0.098). Between SPB and MV % max constriction with NE, there was mean difference of 14.2%, and 21.2% with PE. Additional studies are under way to increase the sample size herein. These investigations will seek to resolve the impact of prolonged MV on the diaphragm resistance vasculature and responsiveness to these (i.e. NE, PE) and other vasoactive mediators such as Angiotensin‐II and Endothelin‐1 that may be upregulated with MV as well as potential structural alterations.Support or Funding InformationNIH (1 R15 HL137156‐01A1)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.