Dysregulation of hepatic microcirculatory function and tissue oxygenation in a rodent model of sleep apnea

Abstract

Sleep apnea (SA) is highly prevalent in patients with non-alcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD is incompletely understood however hemodynamic dysregulation and tissue hypoxia are hypothesized to play important roles. SA is associated with vascular and autonomic dysfunction however its effects on hepatic hemodynamic control have not been explored. We hypothesized that exposure to an experimental model of SA (CIH) would result in exaggerated reductions in hepatic perfusion (HP) and tissue PO2 (HPO2) during intermittent asphyxia (IA) and that these changes would be exacerbated by ovariectomy (OVX). Female Sprague Dawley rats (n=4-6 per group) were exposed to CIH or sham for 8h/d for 14 days. At the conclusion of CIH or sham, HP and HPO2 responses to IA (ten episodes FiO2 10%, FiCO2 3%, 30s each) were measured under anesthesia. Data was analyzed using ANOVA or unpaired t-tests. IA normoxic HP and PO2 was significantly decreased relative to pre-AIH in all groups, but HP was markedly lower in OVX-CIH vs sham or CIH (p<0.05). Reduction in HP during the hypoxic portion of IA was greater in CIH and OVX-CIH than sham (p<0.05) but was not different between the two CIH groups. HPO2 decreased to a greater extent in CIH v. sham during the hypoxic portion of IA (p<0.05). In conclusion, 14 days of CIH causes dysregulation of hepatic hemodynamics and tissue PO2 and loss of female sex steroid hormones may exacerbate these changes. Our findings identify a potential role of SA in the pathophysiology of NAFLD. DMU Mentored Student Research Program This is the full abstract presented at the American Physiology Summit 2023 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.