Myocardial Fibrosis Caused by Angiotensin II Implant in Rabbit Atherosclerosis Model Induced by High Cholesterol Diet

在由高胆固醇饮食诱导的兔动脉粥样硬化模型中,血管紧张素II植入可引起心肌纤维化。

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Abstract

Rabbits are widely used in biomedical research as models for atherosclerosis with disease induction achieved through a high-cholesterol diet, transgenic approaches, or spontaneous development with aging. At our institution, New Zealand White rabbits were induced to develop atherosclerosis via a high-cholesterol diet followed by arterial balloon injury. This model was established to support intravascular molecular imaging studies aimed at tracking atheromatous plaque progression in vivo. To accelerate plaque development, a subcutaneous osmotic pump delivering angiotensin II at 50 ng/kg/min was implanted. While this method enhanced disease progression, unexpected clinical complications were observed. In this retrospective case report, we reviewed clinical records from 54 rabbits over a 2-year period. Clinically, most study animals showed different levels of inappetence. Three presented respiratory symptoms including cyanosis, dyspnea, or tachypnea, while another 3 exhibited neurologic signs such as altered mentation and paralysis. Eight rabbits (14.8%) were euthanized due to severe clinical signs. Necropsy findings in the affected animals commonly revealed pleural and/or peritoneal effusion; one case included chyloabdomen, a condition not previously reported in rabbits. Of these, 7 had myocardial degeneration and fibrosis. These findings suggest that angiotensin II infusion in this rabbit model of atherosclerosis may induce myocardial fibrosis as a significant adverse effect. This report highlights potential complications associated with the model and provides guidance for clinical monitoring, diagnosis, and management in future studies.

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