Bovine model of chronic ischemic cardiomyopathy: implications for ventricular assist device research.

Academic Article

Abstract

  • Ventricular assist devices (VADs) have emerged as a successful treatment option for advanced heart failure. The objective of this study was to develop a clinically relevant model of chronic ischemic cardiomyopathy to investigate functional, histological, and molecular changes during mechanical circulatory support. In calves (n = 17, 94 ± 7 kg), 90 μm microspheres were injected percutaneously into the left coronary artery. Serial echocardiography was performed weekly to evaluate cardiac function. Sixty days after coronary microembolization, a terminal study was performed via thoracotomy to measure hemodynamics. Regional myocardial and end-organ blood flows were quantified with 15-μm fluorescent-labeled microspheres. Myocardial fibrosis, myocyte size, and myocardial apoptosis were quantified with histological stains. Eleven animals survived coronary microembolization and exhibited clinical and statistically significant echocardiographic and hemodynamic signs of severe systolic dysfunction. Statistically significant decreases in regional myocardial blood flow and increases in myocardial fibrosis, myocyte size, total myocardial apoptosis, and cardiac myocyte-specific apoptosis were observed. End-organ hypoperfusion was observed. Coronary microembolization induced stable and reproducible chronic left ventricular failure in calves. The anatomical size and physiology of the bovine heart and thorax are appropriate to study novel interventions for the clinical management of heart failure. This model is an appropriate physiological substrate in which to test VAD and adjunctive biological therapies.
  • Authors

    Published In

  • Artificial Organs  Journal
  • Keywords

  • Apoptosis, Bovine, Fibrosis, Heart failure, Hypertrophy, Ischemic cardiomyopathy, Microembolization, Microspheres, Ventricular assist device, Animals, Apoptosis, Cardiomyopathies, Cattle, Chronic Disease, Coronary Circulation, Disease Models, Animal, Fibrosis, Heart-Assist Devices, Hemodynamics, Humans, Myocardial Ischemia, Myocardium, Prosthesis Design, Species Specificity, Time Factors, Ventricular Dysfunction, Left, Ventricular Function, Left
  • Digital Object Identifier (doi)

    Author List

  • Bartoli CR; Sherwood LC; Giridharan GA; Slaughter MS; Wead WB; Prabhu SD; Koenig SC
  • Start Page

  • E202
  • End Page

  • E214
  • Volume

  • 37
  • Issue

  • 12