OBJECTIVE: METHODS: Female Sprague-Dawley rats were randomly assigned to four groups (n=12 each). Group 1 (no preconditioning): Vehicle (intravenous ethanol, 0.9 mL/kg) was given 39 minutes prior to ischemia. Group 2 ( acetaminophen plus no preconditioning): intravenous acetaminophen (125 mg/kg) was given 39 minutes prior to ischemia. Group 3 (preconditioning): The heart was preconditioned before ischemia, and the vehicle (intravenous ethanol, 0.9 mL/kg) was given 39 minutes prior to the ischemia. Group 4 ( acetaminophen plus preconditioning): The heart was preconditioned before ischemia, and intravenous acetaminophen (125 mg/kg) was given 39 minutes prior to the ischemia. The preconditioning protocol consisted of three cycles of 3 minutes of coronary occlusion and 5 minutes of reperfusion. The left coronary artery was then occluded for 60 minutes, followed by 3 hours of reperfusion. The end points were hemodynamics, body temperature, and risk area and area of necrosis of the left ventricle. RESULTS: The area of risk was similar among the four groups. The area of necrosis, expressed as a percentage of the area at risk, was 55.7% +/- 6.1% in the no-preconditioning group, 62.8% +/- 2.4% in the acetaminophen plus no-preconditioning group, 24.7% +/- 7.3% in the preconditioning group, and 17.2% +/- 6.4% in the acetaminophen plus preconditioning group. The area of necrosis/area at risk was decreased significantly in the preconditioning group and in the acetaminophen plus preconditioning group compared with the no-preconditioning group (P<.05); but there were no significant differences between the no-preconditioning group and the acetaminophen plus no-preconditioning group (P=.29), or between the preconditioning group and acetaminophen plus preconditioning group (P=.45). Among the four groups, heart rate and body temperature were similar. The infusion of the vehicle or acetaminophen increased blood pressure in the four groups, but to a lesser extent in the acetaminophen group. However, during coronary artery occlusion and reperfusion, the four groups had comparable blood pressures. CONCLUSION:
Acetaminophen had no beneficial or adverse effects on infarct size in nonpreconditioned rats, and the beneficial effects of preconditioning were not blocked or prevented by acetaminophen at this analgesic dose.
|