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      Naproxen and Diclofenac Attenuate Atorvastatin-induced Preconditioning of the Myocardium

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          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.

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          ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents.

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            Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial.

            This study sought to investigate potential protective effects of atorvastatin in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Randomized studies have shown that pretreatment with atorvastatin may reduce periprocedural myocardial infarction in patients with stable angina during elective PCI; however, this therapy has not been tested in patients with ACS. A total of 171 patients with non-ST-segment elevation ACS were randomized to pretreatment with atorvastatin (80 mg 12 h before PCI, with a further 40-mg preprocedure dose [n = 86]) or placebo (n = 85). All patients were given a clopidogrel 600-mg loading dose. All patients received long-term atorvastatin treatment thereafter (40 mg/day). The main end point of the trial was a 30-day incidence of major adverse cardiac events (death, myocardial infarction, or unplanned revascularization). The primary end point occurred in 5% of patients in the atorvastatin arm and in 17% of those in the placebo arm (p = 0.01); this difference was mostly driven by reduction of myocardial infarction incidence (5% vs. 15%; p = 0.04). Postprocedural elevation of creatine kinase-MB and troponin-I was also significantly lower in the atorvastatin group (7% vs. 27%, p = 0.001 and 41% vs. 58%, p = 0.039, respectively). At multivariable analysis, pretreatment with atorvastatin conferred an 88% risk reduction of 30-day major adverse cardiac events (odds ratio 0.12, 95% confidence interval 0.05 to 0.50; p = 0.004). The ARMYDA-ACS trial indicates that even short-term pretreatment with atorvastatin may improve outcomes in patients with ACS undergoing early invasive strategy. These findings may support routine use of high-dose statins before intervention in patients with ACS.
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              The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion.

              The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                29 April 2017
                April 2017
                : 9
                : 4
                : e1201
                Affiliations
                [1 ] Internal Medicine Residency, Florida Hospital Orlando
                [2 ] Institute for Heart Research, Slovak Academy of Sciences
                [3 ] Department of Pharmacology and Clinical Pharmacology, Comenius University in Bratislava
                [4 ] Department of Public Health, Trnava University
                Author notes
                Article
                10.7759/cureus.1201
                5446225
                ed210697-77dc-446d-a913-7725af3acee3
                Copyright © 2017, Varga et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 April 2017
                : 28 April 2017
                Funding
                This work was supported by the Scientific Grant Agency of Ministry of Education, Science, Research and Sports of Slovak Republic (Vedecka Grantova Agentura Ministerstva Skolstva, Vedy, Vyskumu a Sportu Slovenskej Republiky) [grant VEGA 1/0501/11]; Comenius University (Univerzita Komenskeho) [grant GUK 408/2011]; and the Slovak Research and Development Agency (Agentura na Podporu Vyskumu a Vyvoja) [grant APVV-0102-11]. The grant providers played no role in the design, methods, data collection, analysis and interpretation of the data, preparation of the paper or in the decision to submit the manuscript.
                Categories
                Pain Management
                Cardiology
                Internal Medicine

                preconditioning,cyclooxygenase-2,atorvastatin,naproxen,diclofenac,myocardial infarction

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