Statins are powerful lipid-lowering drugs, widely used in patients
with hyperlipidemia and coronary artery disease. It was found,
however, that statins appear to have a pleiotropic effect beyond
their lipid-lowering ability. They exert anti-inflammatory,
antithrombotic and antioxidant effects, increase nitric oxide
production and improve endothelial dysfunction. The aim of our
study was to examine the effect of chronic and acute treatment
with simvastatin on the contractile function of the isolated
perfused rat heart after ischemia/reperfusion injury. Contractile
function was measured on isolated rat hearts, perfused according
to Langendorff under constant pressure. The hearts were
subjected to 20 min of global ischemia, followed by 40 min of
reperfusion. To investigate the acute effect, simvastatin at a
concentration of 10 µmol/l was added to the perfusion solution
during reperfusion. In chronic experiments the rats were fed
simvastatin at a concentration of 10 mg/kg for two weeks before
the measurement of the contractile function. Acute simvastatin
administration significantly increased reparation of the peak of
pressure development [(+dP/dt)max] (52.9±8.2 %) after global
ischemia, as compared with the control group (28.8±5.2 %).
Similar differences were also observed in the time course of the
recovery of [(+dP/dt)max]. Chronic simvastatin was without any
protective effect. Our results reveal that the acute administration
of simvastatin during reperfusion, unlike the chronic treatment,
significantly reduced contractile dysfunction induced by
ischemia/reperfusion injury. This supports the idea of possible
cardioprotective effect of statin administration in the first-line
therapy of the acute coronary syndrome.
ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice