Dipyridamole with low-dose aspirin augments the infarct size-limiting effects of simvastatin.

Cardiovascular Drugs and Therapy
Yumei YeYochai Birnbaum

Abstract

Statins protect against ischemia-reperfusion injury and limit myocardial infarct size (IS). This effect is dependent on increased generation of adenosine by ecto-5' nucleotidase and downstream activation of cyclooxygenase-2 (COX2). Dipyridamole (DIP) augments the IS-limiting effects of statins by blocking the cellular reuptake of adenosine; whereas aspirin (ASA) attenuates the effect by inhibiting COX2. We studied the effect of acute administration of DIP, ASA and their combination on the IS-limiting effect of simvastatin (SIM). Rats received oral SIM (10 mg/kg/d) or vehicle for 3 days. Rats underwent 30 min of coronary artery occlusion and 4 h reperfusion. After 5 min of ischemia rats received i.v. DIP (5 mg/kg), ASA (20 mg/kg or 2 mg/kg) or DIP+ASA (2 mg/kg) or vehicle alone. Ischemia area at risk (AR) was assessed by blue dye and IS by TTC. Myocardial samples were analyzed for the activation of Akt, ERK 1/2, endothelial nitric oxide synthase (eNOS), and cyclic-AMP-response-element-binding-protein (CREB). SIM limited IS. High- or low-dose ASA alone had no effect on IS. DIP alone or with low-dose ASA significantly reduced IS. Low-dose ASA did not attenuate the SIM effect, whereas high-dose ASA completely blocked the effect. Th...Continue Reading

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Citations

Dec 27, 2011·Cellular and Molecular Neurobiology·Kirtiman SrivastavaUlvi Bayraktutan
May 28, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Pitchai BalakumarSokkalingam A Dhanaraj
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Nov 11, 2016·Cardiovascular Drugs and Therapy·Yochai BirnbaumYumei Ye
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Jun 6, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Yumei YeYochai Birnbaum
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Jul 11, 2021·Cardiovascular Drugs and Therapy·Mahmoud AllahhamY Birnbaum
Jul 20, 2021·Journal of Oral Biosciences·Keita KagawaTakuro Sanuki

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Methods Mentioned

BETA
percutaneous transluminal coronary angioplasty
electrophoresis

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