Pravastatin Decreases Infarct Size Induced by Coronary Artery Ischemia/Reperfusion with Elevated eNOS Expression in Rats

Abstract

Our previous study showed that pravastatin prevents ischemia and reperfusion-induced lethal ventricular fibrillation in rats. This study explored whether pravastatin decreases myocardial infarct size and this effect is associated with endothelial nitric oxide synthase (eNOS) expression in myocardium. Rats were treated with ischemia (30 minutes) and reperfusion (60 minutes) after chronic oral administration of pravastatin, fluvastatin, or vehicle once daily for 22 days. Electrocardiograms and blood pressure were continuously recorded, myocardial infarct size was measured by TTC-staining, and eNOS expression was measured by western blot. The results showed that pravastatin and fluvastatin significantly reduced myocardial infarct size. No statistical differences were found in the areas at risk among all groups. However, a significant reduction in infarct size was observed in three pravastatin groups and one fluvastatin group compared to control. Both pravastatin and fluvastatin significantly increased eNOS protein expression in ischemic and non-ischemic tissues compared to control. Our results suggest that pravastatin decreases cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in reducing infarct size. These effects may be associated with elevation of eNOS expression.

<p>Protective Effect of Pravastatin on Myocardial Ischemia Reperfusion Injury by Regulation of the miR-93/Nrf2/ARE Signal Pathway</p>

“…Previous studies have shown that pravastatin can effectively prevent fatal ventricular fibrillation caused by ischemia reperfusion and reduce the mortality rate of cardiovascular diseases. 10,11 The report showed that pravastatin pretreatment can play a protective role in fatal ventricular arrhythmia caused by reperfusion by inhibiting [Ca 2+] (i) overload and preventing δ Ψ (M) loss caused by H 2 O 2. 11 Moreover, pravastatin may reduce the death rate of cardiovascular diseases by affecting eNOS expression, and is superior to fluvastatin in reducing infarct size.…”

“…11 Moreover, pravastatin may reduce the death rate of cardiovascular diseases by affecting eNOS expression, and is superior to fluvastatin in reducing infarct size. 10 Related studies have suggested that cardiac damage caused by myocardial ischemia is related to the imbalance of various signal pathways, especially the imbalance of intracellular signal pathways. 12 miRNA, as a small noncoding RNA, can participate in gene regulation and cell activities, such as development, metabolism, proliferation and differentiation.…”

“… 6 Moreover, more and more reports showed that statins can effectively resist myocardial infarction and improve survival rate, inhibit inflammation and apoptosis of cells, stabilize artery plaque, maintain endothelial function and eliminate free radicals. 7 – 10 Pravastatin belongs to statins. Previous studies have shown that pravastatin can effectively prevent fatal ventricular fibrillation caused by ischemia reperfusion and reduce the mortality rate of cardiovascular diseases.…”

“… 11 Moreover, pravastatin may reduce the death rate of cardiovascular diseases by affecting eNOS expression, and is superior to fluvastatin in reducing infarct size. 10 …”

Electrophysiological Measurement of Rat Atrial Epicardium Using a Novel Stereotaxic Apparatus

“…After testing, rats were intracardially perfused with 300 mL PBS, then hearts were excised and stained with 2, 3, 5triphenyltetrazolium (TTC) to delineate the detection sites in the outside surface of both the atrium and the ventricle. 24,25) Hearts were post-fixed in paraformaldehyde overnight and dehydrated in a 30% sucrose solution. Then, hearts were sectioned (40 μm), images were taken using a Leica microscope, and the detection sites were visualized by light microscopy (AHBT3; Olympus, Tokyo, Japan).…”