Basic Science and Experimental Studies
Hypercholesterolemia Exacerbates Ventricular Remodeling in the Rat Model of Myocardial Infarction

https://doi.org/10.1016/j.cardfail.2006.03.005Get rights and content

Abstract

Background

Detrimental left ventricular (LV) remodeling is exacerbated in hypercholesterolemic patients with myocardial infarction; however, this could result from either larger infarcts or more extensive remodeling itself in this population. Therefore, we sought to investigate whether high cholesterol feeding exacerbates LV remodeling and heart failure in rats with myocardial infarction independently from its influence on infarct size.

Methods and Results

Myocardial infarction was induced by permanent ligation of left coronary artery in rats fed normal and high-cholesterol diet and the animals were followed for 8 weeks. Hypercholesterolemic rats were matched with normocholesterolemic animals for infarct size 24 hours after infarction and exhibited more pronounced LV dilation at 8 weeks after infarction (LV systolic/diastolic diameter 8.1 ± 0.2/10.2 ± 0.3 versus 6.7 ± 0.2/8.9 ± 0.2, respectively, measured by echocardiography, P < .05 each). Pressure-volume curves obtained in isolated Langendorff-perfused hearts revealed higher diastolic LV volumes (1677 ± 102 versus 1385 ± 46 μL/kg body weight, P < .05) and hemodynamic examination demonstrated higher LV end-diastolic pressure (21.8 ± 0.7 versus 18.7 ± 1.0 mm Hg, P < .05) in hypercholesterolemic rats compared with normocholesterolemic animals.

Conclusion

In a rat model of myocardial infarction, LV remodeling and heart failure are more pronounced in rats fed high-cholesterol diet in comparison to animals fed normal chow. This effect is independent from effect of hypercholesterolemia on infarct size.

Section snippets

Study Design and Induction of MI

The study was conducted in accordance with the Guide for the Care and Use of Laboratory Animals (US National Institutes of Health Publication No. 85-23, revised 1985) and was approved by the Ethics Committee of our institution.

Male 6-week-old Sprague-Dawley rats were randomly assigned to normal chow (normocholesterolemic) or high-cholesterol chow (hypercholesterolemic) (n = 31 per group) and were maintained on such diets for 8 weeks before induction of MI and until the end of the experiment.

Results

Table 1 shows baseline data for both hypercholesterolemic and normocholesterolemic rats. Baseline echocardiography (Fig. 2) revealed no differences between these 2 groups.

Of 31 normocholesterolemic rats subjected to left coronary ligation, 2 animals died within first 3 hours and additional 4 between 3 hours and 24 hours after the procedure. In high-cholesterol group, these figures were 3 and 5, respectively. All 14 animals that died within first 24 hours after the procedure had WMI ≤15

Discussion

In the present study, we show that diet-induced hypercholesterolemia exacerbates LV remodeling and heart failure in the rat model of nonreperfused myocardial infarction and that mechanism of this phenomenon is unrelated to effect of hypercholesterolemia on MI size. This observation adds new dimension to the recognized risk factor of coronary artery disease—hypercholesterolemia. Our results suggest that apart from its well known effects on coronary plaque progression and stability it can worsen

References (28)

  • G. Nickenig et al.

    Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression

    Am J Physiol Heart Circ Physiol

    (1997)
  • O. Feron et al.

    Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase

    J Clin Invest

    (1999)
  • A. Ito et al.

    Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase

    Circulation

    (1999)
  • Y. Huang et al.

    Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet

    Circulation

    (2004)
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    Supported by a grant of Medical Center of Postgraduate Education 501-2-1-27-97/03 and a grant of Polish Ministry of Science 2 P05A02827.

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