Development of a Novel Large Animal Model of Ischemic Heart Failure Using Autologous Platelet Aggregates

Abstract

Background Current animal models of heart failure lack the biomass of thrombus that occurs in patients undergoing myocardial infarction. We propose a novel animal model of ischemic cardiomyopathy developed by sequential direct injections of autologous platelet aggregates into the coronary circulation resulting in development of ischemic cardiac insufficiency. Methods Autologous platelets from adult sheep were isolated and aggregated. Aggregated platelets were then injected into the coronary circulation of anesthetized animals under fluoroscopic guidance. Troponin I levels were monitored for first three days after embolization to validate cardiac tissue injury. Progression of heart failure was corroborated by monitoring changes in echo-based assessment of ejection fraction and left ventricular end-systolic and end-diastolic dimensions. Thrombus-based obstruction of coronary artery was confirmed with histopathology review by mepacrine labeling of pre-aggregated platelets. Results All experimental animals developed heart failure-like cardiac insufficiency confirmed by elevated levels of troponin I and associated with significant drop in the ejection fraction. Conclusions Sequential injections of aggregated platelets into coronary circulation lead to progressive development of ischemic cardiac insufficiency. This phenomenon seems to mimic development of ischemic heart failure seen in human patients and opens multiple research opportunities to fill the existing gap between basic research and clinical practice.