A pressure overload model to track the molecular biology of heart failure

• Published in: European journal of cardio-thoracic surgery 2003-12, Vol.24 (6), p.920-925
• Main Authors: Moorjani, Narain, Catarino, Pedro, El-Sayed, Raafat, Al-Ahmed, Samaher, Meyer, Brian, Al-Mohanna, Futwan, Westaby, Stephen
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Biological and medical sciences; Cardiology. Vascular system; Disease Models, Animal; Disease Progression; Echocardiography, Doppler; Gene Expression Regulation; Heart; Heart failure; Heart Failure - etiology; Heart Failure - genetics; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hypertrophy, Left Ventricular - diagnostic imaging; Hypertrophy, Left Ventricular - etiology; Hypertrophy, Left Ventricular - physiopathology; Left ventricular biopsy; Male; Medical sciences; Models, Cardiovascular; Myocardial Contraction; Ovine model; Pressure overload; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sheep; Ventricular Function, Left; Ventricular Remodeling
• ISSN: 1010-7940; 1873-734X
• DOI: 10.1016/S1010-7940(03)00514-1

Objectives: Pressure overload plays an important role in left ventricular remodelling and the development of heart failure. The underlying molecular mechanisms behind these processes are poorly understood at the myocyte level. To investigate this, we developed an ovine model of pressure overload-induced heart failure, in which serial left ventricular biopsies were obtained. Methods: Adult male sheep were chronically banded with a novel variable aortic constriction device. This was progressively inflated via a subcutaneous port to increase left ventricular afterload. The animals were monitored clinically and echocardiographically. Serial left ventricular endomyocardial biopsies were obtained via the right external carotid artery under fluoroscopic guidance. They were used to measure mRNA expression of the genetic regulators of apoptosis by reverse transcription polymerase chain reaction. In a subset of the animals, once left ventricular failure had been established, the constriction device was deflated to produce unloading of the left ventricle. Results: Ten of the 17 sheep banded developed left ventricular failure. Over the first 3–4 weeks, left ventricular mass index increased acutely (88±18 vs. 44±10 g/m2, P