To the best of our knowledge, the present study is the first to comprehensively compare strain parameters-derived STI with the levels of serum and myocardial cholesterol in diet-induced expeimental hypercholesterolemia. Although previous experimental studies have shown that diet-induced hypercholesterolemia resulted in contractile reduction of single ventricular myocyte without any change in pressure or LV morphology , few data are available from in vivo investigations. The present study displayed the application of STE as a noninvasive imaging technique to elucidate the direct effect of hypercholesterolemia on LV myocardial deformation in a rabbit model.
In our study, there were no significant differences in LV morphology, EF and blood pressure among groups, whereas LV strain was found to be reduced in the hypercholesterolemic rabbits. Previous studies failed to show abnormalities using EF, which may be due to EF reflects the whole LV systolic function, under the influence of pre and afterload . With the application of advanced techniques, such as strain, strain rate, incipient systolic dysfunction has been detected in subclinical diseases . Moreover, our analysis indicates that longitudinal dysfunction are the first appeared, followed by circumferential, which suggest the importance of longitudinal strain in the assessment of LV systolic dysfunction in subclinical stage.
Whether similar changes occur in humans with hypercholesterolemia can not confirm from our study. However, a recent human study demontrated longitudinal and circumferential deformations were both impaired in the children with heterozygous familiar hypercholesterolemia . Thus, we believe that the abnormalities we found in rabbit models with hypercholesterolemia indicate an early sign of hypercholesterolemia-induced myocardial dysfunction, in agreement with the in vitro expriments .
Interestingly, our study demonstrates that the increased radial deformation make up for impaired longitudinal and circumferential strain in rabbit hypercholesterolemic models to maintain LVEF. This finding is consistent with prior reports in children with heterozygous familial hypercholesterolemia and other preclinical diseases [14, 20, 21]. The potential mechanism by which hypercholesterolemia causes the increase in radial deformation remains unclear. A possible explanation could be the realignments of myocardial fiber orientation in the outer half of the myocardium may contribute to “transmural compensation” by less impaired epicardial fibers .
In the present study, a significant negative correlation were found between global longitudinal strain and serum cholesterol level as well as myocardial cholesterol levels. These results indicate that the cholesterol accumulated in the myocardium may be responsible for a reduction in myocardial strain. Similar to our study, Wang et al.  reported a positive correlation between serum HDL levels and LVEF in human subjects with serum hypercholesterolemia even in the absence of angiographic evidence of CAD.
The precise mechanism responsible for the association between cholesterol level and impaired myocardial deformation cannot be determined from our study. However, several mechanisms have been proposed to explain LV dysfunction induced by hypercholesterolemia: (1) increased cardiac oxidative stress , (2) alteration of the myocardial energy metabolism , (3) changes in myosin heavy-chain isoform expression patterns , (4) down-regulation and redistribution of connexin-43 expression in myocardium , and (5) impaired activation of myocardial adenosine triphosphate-sensitive potassium channels . These mechanisms may represent the basis for a “hypercholesterolemic cardiomyopathy .
As a limitations of our study, administration of ketamine- Diazepam - Atropine combinations induces mild bradycardia, which slightly alters cardiac function. In addition, LV diastolic function, rotation and torsion mechanics are potentially very important features for the comprehensive understanding of myocardial tissue damage; therefore, lack of measurement of diastolic function, rotation and torsion was another limitation of the present study.