Sex‐dependent Liver Volume Recovery and Hemodynamics Measured by Non‐Invasive Ultrasound Imaging after Partial Hepatectomy in Rats

Abstract

Initiation of liver regrowth after partial hepatectomy (PHx) is often linked to increased flow per unit tissue through the hepatic portal vein. Previous studies of liver hemodynamics have used surgical implants, however ultrasound‐based methods can non‐invasively measure blood flow, organ volume, and other physiological parameters.Male and female Sprague‐Dawley rats were pair‐fed liquid diet containing ethanol or carbohydrate per Lieber DeCarli protocol for 5–6 weeks prior to a 70% PHx in which left lateral and medial lobes were surgically removed. A VEVO 2100 (VisualSonics, Toronto, Canada) high‐frequency ultrasound system with a motorized‐step ultrasound transducer was utilized to calculate liver volume using a 3D mapping software. Shear‐wave elastography measured liver stiffness with an Aplio i800 ultrasound system (Canon Medical Systems, Tustin, CA, USA). Color and Spectral Doppler evaluated blood flow velocity in the portal vein (PV) and the main hepatic artery (HA) at their entry into the right lobe. Laser coupled photoacoustic imaging aided in quantification of oxygen saturation in the liver tissue.Liver regrowth as measured by liver volume was impaired in ethanol‐fed male rats as early as 48 hours after PHx, only recovering ~70% of initial volume by one week. In contrast, all other animals, including ethanol‐fed females, had recovered to ~100% of liver volume by one week post‐PHx. All animals showed increased PV and HA blood flow per liver volume immediately after PHx. Relative PV flow continued to increase by the 12‐hour time point, while relative HA flow had variable changes. Ethanol‐fed males had decreased ratio of PV/HA flow compared to all other animals prior to PHx. In the first 24 hours after PHx, relative HA flow decreased or remained stable for most groups, but increased for ethanol‐fed females. Liver stiffness increased immediately after PHx and again by 10 hours after PHx for all groups, though never reaching values that would suggest fibrosis. Stiffness remained elevated for at least 96 hours for all groups, and resolved by one week post‐PHx. Photoacoustic imaging showed liver tissue oxygen saturation fluctuating between 50–60% for all animals, with no discernable patterns.Ethanol‐fed male rats had an impaired liver volume recovery response after PHx, however this ethanol‐mediated impairment was not seen in females. Interestingly, ethanol‐fed males were the only group to have a decreased PV/HA flow ratio prior to PHx, while ethanol‐fed females were unique in their prolonged increase in HA flow at 10 hours post‐PHx. Taken together, these results implicate increased HA flow as a compensatory mechanism in chronic ethanol‐fed rats.Support or Funding InformationSupported by NIH NIAAA R01 AA018873, T32 AA007463 and NIBIB U01 EB023224.