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  • Title: Effects of acetaminophen on myocardial infarct size in rats.
    Author: Dai W, Kloner RA.
    Journal: J Cardiovasc Pharmacol Ther; 2003 Dec; 8(4):277-84. PubMed ID: 14740077.
    Abstract:
    OBJECTIVE: Acetaminophen is widely prescribed as an analgesic agent in hospitals and clinics. However, acetaminophen theoretically could influence myocardial infarct size by reducing prostaglandin synthesis in vivo. To date, the effect of acetaminophen on myocardial infarct size is unknown. The present study investigated (1) whether acetaminophen has any effect on myocardial infarct size when given in an analgesic dose and (2) whether acetaminophen can affect the cardioprotective effect of the early phase of ischemic preconditioning in rats. 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.
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