Atorvastatin Therapy during the Peri-Infarct Period Attenuates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction

Abstract

Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dtmax, end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism

“…Collagen types I and III (COL I and COL III, respectively) are the most abundant collagen types in cardiac tissue, together accounting for 95% of the total collagen [2, 7, 8]. Ventricular remodeling is unfavorable to the myocardium in part because it is associated with accumulation of collagen and other ECM components [9]. …”

“…Statins stabilize atherosclerotic plaques in cardiovascular disease. Their pleiotropic effects include antioxidant and anti-inflammatory activities, improvement of endothelial function, and reduction of cytokine expression [9, 21, 22]. Atorvastatin has shown beneficial effects in the inhibition of cardiac fibroblasts in vitro , the reduction of fibrosis, and the expressions of COL I and COL III [21, 23, 24].…”

Pathophysiology of Myocardial Infarction

“…Although lipid lowering effects account for a significant part of statin-mediated protection, additional benefit may be afforded by anti-inflammatory effects, by modulation of the coagulation and fibrinolytic systems, by direct protection of ischemic cardiomyocytes, or by actions on endothelial cell behavior (185). In experimental models of myocardial infarction, statins reduced adverse remodeling without affecting the size of the infarct (359); the clinical significance of these observations remains unclear. The protective effects of statins on the remodeling infarcted heart may be mediated through antifibrotic effects (55,359) suppression of MMP expression (154,271), through activation of the angiogenic response (213), or through attenuation of inflammation (229).…”

“…In experimental models of myocardial infarction, statins reduced adverse remodeling without affecting the size of the infarct (359); the clinical significance of these observations remains unclear. The protective effects of statins on the remodeling infarcted heart may be mediated through antifibrotic effects (55,359) suppression of MMP expression (154,271), through activation of the angiogenic response (213), or through attenuation of inflammation (229). Experimental studies showed that statin-mediated protection in the infarcted and remodeling myocardium requires endothelial nitric oxide availability (213,266).…”

Atorvastatin Inhibits Myocardial Apoptosis in a Swine Model of Coronary Microembolization by Regulating PTEN/PI3K/Akt Signaling Pathway

“…In recent years, many studies further validated its anti-apoptotic effect in animal models of myocardial ischemia and reperfusion injury [27], coronary atherosclerosis [28], myocardial infarction [29], and renal ischemia-reperfusion injury [30]. More and more studies show that atorvastatin may regulate PTEN/PI3K/Akt cell signaling pathways, although statins may have different regulatory effects in different pathological conditions.…”