Basic—Liver, Pancreas, and Biliary TractPulmonary Angiogenesis in a Rat Model of Hepatopulmonary Syndrome
Section snippets
Animals
Male Sprague–Dawley rats (200–250 g; Charles River, Wilmington, MA) were used in all experiments. CBDL was performed as described.22 Normal control animals underwent mobilization of the common bile duct without ligation. Some rats were intraperitoneally injected with TAA (Sigma–Aldrich, St Louis, MO) 200 mg/kg body weight or saline 3 times each week for 2 or 8 weeks as described.7 PTX (Sigma–Aldrich) 50 mg/kg body weight per day was given orally in drinking water for 2 weeks beginning 1 week
Physiologic Assessment for Hepatopulmonary Syndrome After CBDL and TAA Administration
To evaluate the development of HPS in relation to hepatic and pulmonary alterations in models of biliary and nonbiliary cirrhosis, we measured arterial blood gases and microsphere shunting through the pulmonary microcirculation, portal venous pressure, spleen weight, and liver histology at serial time points after CBDL and TAA administration (Table 1). HPS developed only after CBDL, as reflected by the development of a widened alveolar arterial oxygen gradient and increased shunting of
Discussion
The pathogenesis of HPS is poorly understood and has hampered the development of effective treatments. The current study was undertaken to define whether pulmonary angiogenesis is a unique feature that contributes to experimental HPS. We find that HPS induced by CBDL is associated with pulmonary angiogenesis, activation of Akt and eNOS in the pulmonary endothelium, and VEGF-A production in intravascular monocytes. In contrast, angiogenesis was absent; monocyte accumulation was minimal; and Akt,
Acknowledgments
J.H. and B.L. contributed equally to this paper.
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2021, Life SciencesCitation Excerpt :The accumulation of mononuclear cells in the pulmonary vascular endothelium promotes the expression of inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and interleukin 8 (IL−8), that play an important role in HPS development [10]. The effects of different treatment agents for HPS have already been evaluated experimentally; the administration of antibiotics [11–13], methylene blue, [14] and garlic [15,16] showed benefits in terms of vascular alterations and hypoxemia. However, clinically, none of these treatments showed positive results for HPS patients, and the only treatment capable of reversing the hypoxemia present in these patients is liver transplantation [17].
Conflicts of interest The authors disclose no conflicts.
Funding Supported by DK02030 and a VA Merit Review grant (to M.B.F.) and AHA 0735468N (to J.Z.).