Benefits of Aggressive Medical Management in a Bovine Model of Chronic Ischemic Heart Failure

Abstract

A major limitation in the development of mechanical circulatory support (MCS) devices has been the lack of a clinically relevant, stable, and reproducible large animal chronic heart failure (HF) model. High mortality rates have been reported with large animal chronic HF models. In this study, methods of medical management to improve survival rate (SR) were investigated. Chronic ischemic HF (IHF) was induced in Jersey calves using a microembolization technique via fluoroscopy-guided injection of 90 μm microspheres into the coronary vasculature. Animals were divided into 1) Control--multiple embolization procedures with conservative therapy (n = 9); 2) treatment group 1 (TG1)--single embolization procedure with moderately aggressive therapy (n = 8); and 3) TG2--single embolization procedure with aggressive medical management (n = 20). The groups were not randomized with data analyzed retrospectively. Mean SR, body condition score, body weight, hemodynamic, echocardiography, and histopathology indices were recorded up to 60 days postembolization. SR improved from 56% (Control) to 75% (TG1) and 90% (TG2) using an aggressive medical management regimen of analgesia, diuretics, beta-blockade, antiarrhythmics, vasodilators, and inotropes. These findings support the hypothesis that a single coronary microembolization procedure and aggressive medical therapy produces a clinically relevant chronic IHF model with a significantly higher SR than conservative medical therapy.