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Simvastatin improves left ventricular function after myocardial infarction in hypercholesterolemic rabbits by
Johann Bauersachs1, Katrin Hiss, Daniela Fraccarollo
1Medizinische Klinik und Poliklinik I, Universitätsklinikum, Universität Würzburg, Germany. bauersachs_J@medizin.uni-wuerzburg.de
Insights
Hypercholesterolemia worsens heart function after myocardial infarction (MI). Simvastatin treatment improved cardiac function in hypercholesterolemic MI rabbits, suggesting anti-inflammatory and anti-oxidative benefits.
Area of Science:
- Cardiovascular Science
- Pharmacology
Background:
- Hypercholesterolemia is a risk factor for coronary artery disease.
- The impact of hypercholesterolemia on left ventricular (LV) function post-myocardial infarction (MI) is not fully understood.
Purpose of the Study:
- To investigate the effects of hypercholesterolemia on LV function in a rabbit model of MI.
- To evaluate the impact of simvastatin treatment on LV function in hypercholesterolemic rabbits with MI.
Main Methods:
- New Zealand White rabbits were fed either a normal or cholesterol-rich diet.
- Experimental myocardial infarction was induced via coronary artery ligation.
- Rabbits received placebo or simvastatin treatment post-MI for 9 weeks.
Main Results:
- Hypercholesterolemia impaired LV systolic and diastolic function in MI rabbits.
- Simvastatin treatment improved LV function in hypercholesterolemic MI rabbits and also benefited normocholesterolemic MI rabbits.
- Simvastatin normalized inflammatory markers (C-reactive protein) and oxidative stress markers (Rac1-GTPase activity) in hypercholesterolemic MI rabbits.
Conclusions:
- Hypercholesterolemia exacerbates LV dysfunction following MI.
- Simvastatin confers significant cardioprotection post-MI, likely through its anti-inflammatory and anti-oxidative properties.
- Statin therapy offers benefits beyond cholesterol reduction in managing cardiac function after MI.
Objectives:
Hypercholesterolemia contributes to coronary artery disease progression but little is known about its effect on left ventricular (LV) function after myocardial infarction (MI). The aim of this study was to investigate the effects of hypercholesterolemia and statin treatment in rabbits with experimental MI.
Methods And Results:
New Zealand White rabbits on a normal or cholesterol-rich diet for 4 weeks, underwent permanent coronary artery ligation. Starting on the first day post-MI rabbits were treated with either placebo or simvastatin (5 mg/kg/day) for 9 weeks. Hypercholesterolemia itself did not affect LV function in sham-operated animals but further impaired LV systolic (dP/dtmax -42%) and diastolic (dP/dtmin -47%) function in MI rabbits on placebo. Simvastatin treatment not only prevented deterioration of LV function associated with hypercholesterolemia but improved LV function (dP/dtmax +130%; dP/dtmin +144%, P < 0.05). Simvastatin also attenuated the depression of LV function in normocholesterolemic MI rabbits (dP/dtmax +46%; dP/dtmin +53%, P < 0.05). Hypercholesterolemia in MI rabbits coincided with a significant increase in C-reactive protein levels (marker of inflammation) and Rac1-GTPase activity (marker of oxidative stress), and a reduction in cardiac sarcoplasmic-reticulum calcium ATPase-2 expression and endothelial nitric oxide synthase protein phosphorylation, all of which were normalised by simvastatin treatment. Elevated serum cholesterol levels were only partially reduced by simvastatin.
Conclusions:
Hypercholesterolemia further impaired the depressed LV function in rabbits post-MI. Statin treatment reversed this effect, and conferred additional protection, as in normocholesterolemic animals. Our study suggests that anti-inflammatory and anti-oxidative effects of simvastatin substantially contribute to its beneficial effects on cardiac function after MI.
