Simvastatin alleviates myocardial contractile dysfunction and lethal ischemic injury in rat heart independent of cholesterol-lowering effects

Title:

Simvastatin alleviates myocardial contractile dysfunction and lethal ischemic injury in rat heart independent of cholesterol-lowering effects

Creator:

Adriana Adameová, Anna Harčárová, Jana Matejíková, Dezider Pancza, Magdaléna Kuželová, Slávka Čarnická, Peter Švec, Monika Barteková, Ján Styk, and Ravingerová, T.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:bf847955-0a57-4d63-a317-e9b80a661b26
uuid:bf847955-0a57-4d63-a317-e9b80a661b26
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, cholesterol, statiny, srdce, ischemie, statins, heart, ischemia, pleiotropic effects, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

a1_Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol- lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection ag ainst myocardial ischemia- reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff- perfused hearts of healthy control (C) and diabetic- hypercholesterolemic (D-H; strept ozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium stai ning). Postischemic recovery of left ventricular developed pressu re (LVDP) in animals with D-H was improved by simvastatin therapy (62.7±18.2 % of preischemic values vs. 30.3±5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperf usion. Likewise, simvastatin shortened the duration of ventri cular tachycardia (10.2±8.1 s and 57.8±29.3 s in C and D-H vs. 143.6±28.6 s and 159.3±44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C., a2_The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the improvement of contractile recovery and attenuation of lethal I/R injury in both, healthy and diseased individuals., A. Adameová, A. Harčárová, J. Matejíková, D. Pancza, M. Kuželová, S. Čarnická, P. Švec, M. Barteková, J. Styk, T. Ravingerová., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2009 Volume:58 | Number:3

Harvested from:

CDK

Metadata only:

false