METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.

RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).

MATERIALS AND METHODS: Antinociceptive activity of ethanol pomegranate extract was examined using three models of pain: the writhing test, the hot tail flick test and the plantar test. The ethanolic extract of pomegranate was administered by oral gavages in doses of (100,150 and 200mg/kg, p.o (orally)), for all the tests and compared with aspirin (100mg/kg, p.o.) which was considered as the standard drug. Phytochemical screening and HPLC analysis of the plant species was carried out.

RESULTS: In the writhing test, the index of pain inhibition (IPI) was 37% for ethanolic extract of pomegranate (200mg/kg, p.o.), and 59% for aspirin. In the hot tail flick test, the ethanolic extract of pomegranate (200mg/kg, p.o.), has shown significant analgesia reaching its peak at 60 min maximum possible analgesia (MPA), was 24.1% as compared with aspirin 37.5%. Hyperalgesia was successfully induced by the plantar test and the ethanol extract of pomegranate (100,150,200mg/kg, p.o.), reduced the hyperalgesia in a dose dependent manner comparable to aspirin at (100mg/kg, p.o.). HPLC analysis revealed the presence of gallic acid, ellagic acid and Punicalagins A&B.