Why the study?
Does ezetimibe prevent myocardial dysfunction evaluated by tissue Doppler imaging in rabbits fed a high cholesterol diet?
Does ezetimibe prevent myocardial dysfunction evaluated by tissue Doppler imaging in rabbits fed a high cholesterol diet?
In a rabbit model, hypercholesterolemia was associated with decreased systolic and diastolic function on tissue Doppler imaging, which was prevented by lipid-lowering therapy with ezetimibe.
Ezetimibe may preserve myocardial function in hypercholesterolemic rabbits; leaves open translation to human therapy.
OBJECTIVE: To establish a link between hypercholesterolemia and myocardial dysfunction. BACKGROUND: Heart failure is a complex disease involving changes in systolic and diastolic function. Newer echocardiographic imaging modalities may be able to detect discreet changes in myocardial function associated with hypercholesterolemia. Therefore we sought to establish a link between hypercholesterolemia and myocardial dysfunction with tissue Doppler imaging (TDI). METHODS: Twenty-seven rabbits were studied: 7 were fed normal chow (group 1) and 20 a high cholesterol diet (10 with ezetimibe, 1 mg/kg/day; group 2 and 10 without, group 3). Echocardiographic images were obtained under general anesthesia. Serum cholesterol levels were obtained at baseline, 3 and 6 months and myocardial cholesterol levels measured following euthanasia. RESULTS: Doppler measurements, including E/A, E'/A' and S' were significantly lower in group 3 compared to both groups 1 and 2 but no significant differences were noted in chamber sizes or ejection fraction among the groups. Average serum cholesterol was higher in group 3 compared to groups 1 and 2 respectively (495 +/- 305 mg/dl vs. 114 +/- 95 mg/dl and 87 +/- 37 mg/dl; p < 0.01). Myocardial cholesterol content was also higher in group 3 compared to group 2 (0.10 +/- 0.04 vs. 0.06 mg/dl +/- 0.02; p = 0.05). There was significant correlation between S', E'/A', E/E' and serum cholesterol (r2 = 0.17 p = 0.04, r2 = 0.37 p = 0.001 and r2 = 0.24 p = 0.01). CONCLUSION: Cholesterol load in the serum and myocardium was significantly associated with decreased systolic and diastolic function by TDI. Moreover, lipid lowering was protective.
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Rubinstein et al. (2009) studied this question.
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