Document Type

Article

Publication Date

3-9-2023

Comments

This article is the author's final published version in Frontiers in Psychology, Volume 14, 2023, Article number 1102393.

The published version is available at https://doi.org/10.3389/fphys.2023.1102393. Copyright © 2023 Barnhart, Kan, Srivastava, Wessner, Waters, Ambelil, Eisenbrey, Hoek and Vadigepalli.

Abstract

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow rates were seen in most animals, with ethanol-fed males showing higher peak portal flow than any other experimental group. A computational model of liver regeneration was used to evaluate the contribution of physiological stimuli and estimate the animal-specific parameter intervals. The results implicate lower metabolic load, over a wide range of cell death sensitivity, in matching the model simulations to experimental data of ethanol-fed male rats. However, in the ethanol-fed female rats and controls of both sexes, metabolic load was higher and in combination with cell death sensitivity matched the observed volume recovery dynamics. We conclude that adaptation to chronic ethanol intake has a sex-dependent impact on liver volume recovery following liver resection, likely mediated by differences in the physiological stimuli or cell death responses that govern the regeneration process. Immunohistochemical analysis of pre- and post-resection liver tissue validated the results of computational modeling by associating lack of sensitivity to cell death with lower rates of cell death in ethanol-fed male rats. Our results illustrate the potential for non-invasive ultrasound imaging to assess liver volume recovery towards supporting development of clinically relevant computational models of liver regeneration.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Table 1.docx (16 kB)
Table 2.docx (23 kB)
Video 1.MP4 (3810 kB)
Video 2.MP4 (3667 kB)
Video 3.MP4 (4023 kB)
Video 4.MP4 (3720 kB)
Data Sheet 1.docx (17 kB)
Data Sheet 2.docx (23 kB)
Data Sheet 4.zip (40 kB)
Data Sheet 5.zip (28 kB)
Data Sheet 6.zip (122 kB)
Image 1.JPEG (735 kB)
Image 2.JPEG (252 kB)
Image 3.JPEG (638 kB)
Image 4.JPEG (528 kB)
Image 5.JPEG (953 kB)
Image 6.JPEG (5375 kB)
Image 7.JPEG (963 kB)

Language

English

Share

COinS