Caffeinated coffee blunts the myocardial protective effects of statins against ischemia-reperfusion injury in the rat

Cardiovasc Drugs Ther. 2008 Aug;22(4):275-82. doi: 10.1007/s10557-008-6105-z. Epub 2008 Mar 11.

Abstract

Purpose: We asked whether caffeinated coffee (CC) blunts the infarct size (IS)-limiting effects of atorvastatin (ATV).

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Administration, Oral
  • Animals
  • Atorvastatin
  • Blood Pressure / drug effects
  • Caffeine / administration & dosage
  • Caffeine / pharmacology*
  • Coffee*
  • Disease Models, Animal
  • Food-Drug Interactions*
  • Heart Rate / drug effects
  • Heptanoic Acids / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P1 / drug effects
  • Receptors, Purinergic P1 / metabolism

Substances

  • Coffee
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Receptors, Purinergic P1
  • Caffeine
  • Atorvastatin
  • Proto-Oncogene Proteins c-akt