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. 2010 Mar;6(1):1-7.

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

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

Roula Zahr et al. Int J Biomed Sci. 2010 Mar.

Abstract

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.

Keywords: animal models; bovine; heart failure; hemodynamics; ionophores.

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Figures

Figure 1
Figure 1
Changes in cardiac output (CO) and left atrial pressure (LAP) after four doses of oral monensin administration in animal 1.
Figure 2
Figure 2
Changes in cardiac output (CO) and left atrial pressure (LAP) after two doses of oral monensin administration in animal 3.
Figure 3
Figure 3
Changes in LV volumes and ejection fraction (EF) from echocardiography in animal 3.
Figure 4
Figure 4
Tissue perfusions in the heart and kidney determined by BioPal™ microspheres in animal 3.

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