[Animal modeling] - Improvement and evaluation of conditions of rat model of myocardial hypertrophy induced by isoproterenol based on implantable osmotic pump

  Objective Myocardial hypertrophy is a slowly developing and effective compensatory function, an adaptive response to hemodynamics or myocardial injury, and an independent risk factor leading to heart failure. It has been reported that the administration route and induction dose of isoproterenol induced cardiac hypertrophy rat models vary greatly, and the development process of pathological phenotype of model animals is uneven.

  Methods Integrating the progressiveness of previous methods, the uniformity of model phenotype, the stability of the method and the difficulty of replication, this paper used the method of subcutaneous implantation of osmotic pump to induce the construction of rat model of myocardial hypertrophy by low-dose long-term administration of ISO (4 mg/kg for 28 days), and evaluated the model phenotype by using ultrasound imaging, pathological staining, immunofluorescence staining and Real time PCR.

  Results The pathological phenotype of model rats was typical. Overall phenotype, including increased cardiac volume, ventricular wall thickness and cardiac weight index; Cell phenotype, including enlarged myocardial cells, severe myocardial fibrosis, rupture and dissolution of myocardial fibers, disappearance and vacuolization of mitochondrial ridges, distortion and blurring of myocardial Z lines, M lines and intercalated discs; Molecular phenotypes, including cardiac natriuretic peptide (ANP), a marker of cardiac hypertrophy, and brain natriuretic peptide (BNP), were significantly increased.

  Conclusion The rat model of myocardial hypertrophy established in this paper is stable and reproducible, with typical phenotypic characteristics, and is more suitable for scientific research such as gene function analysis and related drug screening.