Mechanism of long-term high-dose prednisolone administration producing myocardial fibrosis in beagle dogs

Abstract

Background: We previously reported that myocardial fibrosis may be one of the causes of left ventricular hypertrophy and cardiac dysfunction in dogs with hyperglucocorticism (HGC). The detailed mechanism by which myocardial fibrosis of the left ventricle occurs in dogs with hyperglucocorticism (HGC) remains unclear. Aim: This study investigated the mechanism by which HGC causes fibrosis of the left ventricle. Methods: The impacts of HGC on the heart by comparing samples obtained from high-dose glucocorticoid-treated (P) and untreated (C) dogs. The P group included healthy Beagle dogs (n=6) treated with prednisolone (2 mg/kg, bid, po) for 84 days, and the C group included healthy Beagle dogs (n=6) euthanized for unrelated reasons. In three of the P group dogs, serum was collected before the start of administration (Day 0) and on Day 84 to measure angiotensin II concentrations and oxidative stress markers (8-hydroxy-2'-deoxyguanosine (8OHdG), NADPH oxidase, and superoxide levels). Samples of the left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), and aortic root were harvested from both groups (n = 6 for each group). Using these tissue samples, angiotensin II type 1 receptor (AT1R), 8OHdG, and transforming growth factor β1 (TGFβ1) immunohistochemical stains were performed. Results: The blood NADPH oxidase concentration was significantly higher (P=0.027) in the P group 84 days after initiation of the medication compared to that before prednisolone treatment. By contrast, there was no significant difference in serum angiotensin II (P=0.450), 8OHdG (P=0.068), and superoxide (P=0.057) concentrations. The positive staining rates of AT1R, 8OHdG, and TGFβ1 in the heart (LVFW, RVFW, IVS, and aortic root) were significantly higher in the P group than those in the C group. Conclusion: Angiotensin II and oxidative stress in HGC may cause left ventricular fibrosis in dogs. [Open Vet J 2023; 13(12.000): 1708-1717]

Keywords

• canine
• cushing syndrome
• hyperglucocorticism
• left ventricular
• fibrosis