Caffeinated Coffee Blunts the Myocardial Protective Effects of Statins against Ischemia–Reperfusion Injury in the Rat
We asked whether caffeinated coffee (CC) blunts the infarct size (IS)-limiting effects of atorvastatin (ATV).
Adenosine receptor activation is essential for mediating the IS-limiting effects of statins. Caffeine is a nonspecific adenosine receptor blocker, and thus drinking CC may block the myocardial protective effects of statins.
Rat received 3-day ATV (10 mg/kg/day) or water by oral gavage once daily. Drinking water was replaced by water + sugar (7.5 g/100 ml), CC with sugar, or decaffeinated coffee (DC) with sugar. On the 4th day, rats were anesthetized and underwent 30 min of coronary artery occlusion and 4 h reperfusion. Area at risk was assessed by blue dye and infarct size by TTC.
Body weight and area at risk was comparable among groups. IS was 25.1 ± 3.9% of the area at risk in the control group. In rats not receiving ATV, CC (25.5 ± 3.1%) and DC (34.0 ± 2.8%) did not affect IS. IS was significantly reduced by ATV in the water + sugar (11.7 ± 0.7%, p = 0.015) and DC (11.5 ± 1.0%; p < 0.001) groups, but not in the CC group (32.3 ± 3.0%; p = 0.719). ATV increased myocardial levels of Ser-473 phosphorylated Akt in the water + sugar and DC groups, but not in the CC group.
CC, but not DC, abrogated the IS-limiting effects of ATV by blocking the adenosine receptors and preventing the phosphorylation of Akt. CC did not affect IS in rats not receiving ATV.
Key wordsinfarct size atorvastatin adenosine coffee caffeine
- 4.Silletta MG, Marfisi R, Levantesi G, Boccanelli A, Chieffo C, Franzosi M, et al. Coffee consumption and risk of cardiovascular events after acute myocardial infarction: results from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)—Prevenzione trial. Circulation. 2007;116:2944–51.PubMedCrossRefGoogle Scholar
- 30.Birnbaum Y, Ye Y, Atar S, Rosanio S, Huang M-H, Lin Y, et al. Atorvastatin-induced myocardial protection against ischemia: iNOS mediates the increase in COX2 activity [Abstract]. Circulation Research. 2005;97:38.Google Scholar
- 44.Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol. 2003;42:1318–33.PubMedCrossRefGoogle Scholar
- 51.Kumai T, Matsumoto N, Koitabashi Y, Takeba Y, Oonuma S, Sekine S, et al. Pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors: candidate mechanisms for anti-lipid deposition in blood vessels. Curr Med Chem Cardiovasc Hematol Agents. 2005;3:195–201.PubMedCrossRefGoogle Scholar
- 53.Landmesser U, Engberding N, Bahlmann FH, Schaefer A, Wiencke A, Heineke A, et al. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation. 2004;110:1933–9.PubMedCrossRefGoogle Scholar
- 58.Chen Z, Li T, Zhang B. Morphine postconditioning protects against reperfusion injury in the isolated rat hearts. J Surg Res. 2007 (in press).Google Scholar