Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats

Ali Sepehrinezhad,Farzaneh Ketabchi,Ali Rafati,Amirreza Dehghanian

doi:10.1186/s12872-019-01297-z

Ali Sepehrinezhad, Farzaneh Ketabchi + Show 2 more

Open Access

https://doi.org/10.1186/s12872-019-01297-z

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Abstract

BackgroundLiver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases.MethodsFemale Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology.ResultsLiver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group.ConclusionSevere liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.

Highlights

Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH)
Alanine aminotransferase (ALT) in the common bile duct ligation (CBDL)+partial portal vein ligation (PPVL) group was higher than the ones in the Sham and PPVL groups (P < 0.01), and in the CBDL group was higher than that in the Sham group (P < 0.05)
There was no alteration in Arterial carbon dioxide pressure (PaCO2) values among the CBDL+PPVL, PPVL, and Sham groups

Summary

Introduction

Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). Endothelin-1 has a vasoconstrictive effect through endothelin A and B receptors in the smooth muscle cells of pulmonary vessels [13]. We previously indicated that ET-B receptors on the pulmonary smooth muscle cells play roles in the regulation of pulmonary vascular tone in animal model of liver cirrhosis [14]. High level of ROS may decrease the bioavailability of NO and lead to the constriction of pulmonary vessels [19] Taken together, all these suggested mechanisms cannot be linked directly to POPH because of lacking an accepted animal model for POPH, and some limitations in human studies [20,21,22]

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