Acetaminophen in the post-ischemia reperfused myocardium.
Acetaminophen was administered acutely at the onset of reperfusion after 20 min of low-flow, global myocardial ischemia in isolated, perfused guinea pig hearts (Langendorff) to evaluate its influence in the postischemia, reperfused myocardium. Similarly prepared hearts were treated with vehicle or with uric acid (another phenol for comparison). Functionally, acetaminophen-treated hearts (0.35 mM) achieved significantly greater recovery during reperfusion. For example, left ventricular developed pressures at 40 min reperfusion were 38 +/- 3, 27 +/- 3, and 20 +/- 2 in the presence of acetaminophen (P < 0.05, relative to the other two groups), vehicle, and uric acid, respectively. Coronary perfusion pressures and calculated coronary vascular resistances, in the acetaminophen-treated hearts, were significantly lower at the same time (e.g., coronary perfusion pressures in the three groups, respectively, were 40 +/- 2 [P < 0.05], 51 +/- 3, and 65 +/- 12 mm Hg). Under baseline, control conditions, creatine kinase ranged from 12-15 units/liter in the three groups. It increased to 35-40 units/liter (P < 0.05) during ischemia but was significantly reduced by acetaminophen during reperfusion (e.g., 5.3 +/- 0.8 units/liter at 40 min). Oxidant-mediated chemiluminescence in all three treatment groups during baseline conditions and ischemia was similar (i.e., approximately 1.5-2.0 min for peak luminescence to reach its half maximal value). It took significantly more time during reperfusion for the oxidation of luminol in the presence of acetaminophen (>20 min, P < 0.05) than in its absence (3-8 min in uric acid- and vehicle-treated hearts). These results suggest that administration of acetaminophen (0.35 mM), at the onset of reperfusion, provides anti-oxidant-mediated cardioprotection in the postischemia, reperfused myocardium.
Golfetti
Roseli
R
Division of Life Sciences, Department of Cell Biology & Neurosciences, Rutgers University, New Brunswick/Piscataway, New Jersey 08854, USA.
VanDyke
Knox
K
Rork
Tyler
T
Spiler
Norell
N
Merrill
Gary
G
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D015425:Myocardial Reperfusion; D030421:Peroxynitrous Acid / Q000378:metabolism; D014527:Uric Acid / Q000494:pharmacology
D030421:Peroxynitrous Acid; D014527:Uric Acid; D000082:Acetaminophen; D003402:Creatine Kinase