Naproxen and Diclofenac Attenuate Atorvastatin-induced Preconditioning of the Myocardium.

Zoltan Varga,Viera Kristova,Martina Nemcekova,Tana Ravingerova,Veronika Slezakova,Marek Majdan,Miriam Petrova,Slavka Carnicka

doi:10.7759/cureus.1201

Abstract

Statins reduce infarct size (IS) in ischemia-reperfusion injury of the myocardium. Inhibition of cyclooxygenase-2 (COX-2) attenuates this benefit. We investigated the effect of two widely used non-selective non-steroidal anti-inflammatory drugs (NSAIDs) with different degree of anti-COX-2 activity on atorvastatin-mediated preconditioning. Wistar rats received oral atorvastatin (10 mg∙kg-1∙day-1), naproxen (10 mg∙kg-1∙day-1), diclofenac (8 mg∙kg-1∙day-1), atorvastatin+naproxen, atorvastatin+diclofenac or water for three days. Hearts were then excised and perfused in the Langendorff system. Area at risk (AR) and IS were determined after 30 min of regional ischemia and 120 min of reperfusion. Atorvastatin reduced IS by 51.3% compared with controls (14.7 ± 3.9% vs. 30.2 ± 4.6% of the AR; P < 0.001). Naproxen and diclofenac alone did not alter IS compared to control. Diclofenac completely abrogated atorvastatin-mediated protection of the myocardium. Naproxen significantly attenuated but did not eliminate the IS reducing the effect of atorvastatin when compared with controls (P = 0.038). The difference in IS between the atorvastatin+naproxen group and the atorvastatin+diclofenac group showed a strong trend in reaching statistical significance (P = 0.058), but was not found to be significant. Our results suggest relatively small, but noticeable differences among non-selective NSAIDs in their potential to attenuate statin-mediated preconditioning.

Highlights

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely used in the treatment of patients at the time or after various forms of acute coronary syndromes (ACS)
There were no significant differences between the groups in the number of excluded isolated hearts, body weight or in the values of heart rate (HR), LV systolic pressure (LVSP), LV diastolic pressure (LVDiP), LV developed pressure (LVDP) and coronary flow (CF) at baseline, i.e., prior to ischemia (Table 1)
We can summarize our findings as follows: 1) Three-day atorvastatin administration led to a significant reduction of infarct size (IS); 2) Three-day administration of both naproxen and diclofenac significantly attenuated the IS limiting effect of atorvastatin; 3) Diclofenac completely abrogated atorvastatin-mediated protection of the myocardium

Summary

Introduction

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) are widely used in the treatment of patients at the time or after various forms of acute coronary syndromes (ACS). Guidelines advocate the early initiation of statin therapy in ACS irrespective of cholesterol levels [1-2]. The benefit of statins is likely achieved partially by cholesterol-independent (pleiotropic) effects [3]. One of these pleiotropic effects is an increase in resistance of myocardium to ischemia-reperfusion (IR) injury. Guidelines for the management of ST-elevation myocardial infarction call for the investigation of new pharmacological strategies to help minimize the consequences of IR injury.

Results

Discussion

Conclusion