A pilot study for inducing chronic heart failure in calves by means of oral monensin.

INTRODUCTION: Heart failure remains a major cause of mortality in the United States, despite advancing technologies, newer methods of treatment, and novel devices. To evaluate such novel devices, a large-animal model of chronic heart failure is critical in carrying out preclinical animal studies. METHODS: We evaluated the efficacy of oral monensin in inducing stable heart failure in five Jersey calves. Various doses of monensin were administered. Hemodynamics, pressure-volume loops, echocardiographic measurements, extent of tissue perfusion, and histopathologic data were recorded before and after induction of heart failure. RESULTS: Responses were variable in the animals. One experiment showed a significant decrease in cardiac output within one week, associated with simultaneous increases in left atrial pressure, central venous pressure, and mean pulmonary artery pressure. Left ventricular pressure-volume loops showed that the slope of the end-systolic pressure-volume relation decreased markedly between the baseline and terminal study, suggesting a decrease in contractility. Echocardiographic studies indicated a decrease in ejection fraction. Histopathologic analysis in cardiac tissue showed extensive fibrosis and necrosis. CONCLUSION: We demonstrated the feasibility of inducing and maintaining severe yet stable heart failure for up to 3 weeks in a calf model by administration of oral monensin.