Introduction:Propofol has been suggested as a useful adjunct to cardiopulmonary bypass (CPB) because of its potential protective effect on the heart mediated by a decrease in ischemia-reperfusion injury and inflammation at clinically relevant concentrations. In view of these potentially protective properties, which modulate many of the deleterious mechanism of inflammation attributable to reperfusion injury and CPB, we sought to determine whether starting a low dose of propofol infusion at the beginning of CPB would decrease inflammation as measured by pro-inflammatory markers.Materials and Methods:We enrolled 24 patients undergoing elective coronary artery bypass graft (CABG). The study group received propofol at rate of 120 mcg/kg/min immediately after starting CPB and was maintained throughout the surgery and for the following 6 hours in the intensive care unit (ICU). The control group received propofol dose of 30-50 mcg/kg/min which was started at the time of chest closure with wires and continued for the next 6 hours in the ICU. Interleukins (IL) -6, -8 and -10 and tumor necrosis factor alpha (TNFalpha) were assayed.Result:The most significant difference was in the level of IL-6 which had a P value of less than 0.06. Starting a low dose propofol early during the CPB was not associated with significant hemodynamic instability in comparison with the control group.Conclusion:Our study shows that propofol may be suitable as an anti-inflammatory adjunct for patients undergoing CABG.
BACKGROUND/AIMS
Norepinephrine (NE) pathways may be important in the pathogenesis of several neuropsychiatric disorders. This study was the first administration of LY2124275 ‐ a selective NE reuptake inhibitor ‐ in humans where the safety, tolerability and pharmacokinetics of LY2124275 were investigated in healthy male subjects. In addition, the pharmacodynamic effects were evaluated through pupillary light reflex and vital signs measurements.
METHODS
This was a double blind, randomised, placebo‐controlled study involving 18 subjects. Each subject received 2 single escalating oral doses of LY2124275 and 1 placebo. The constriction and redilatation rates of the pupil after a light stimulation were modelled with a U‐shape function.
RESULTS
Single dose of LY2124275 (20 – 200 mg) was generally well tolerated, although some adverse events, such as nausea and urinary hesitation, appeared to increase with dose.
A dose‐related increase in standing pulse rate was observed from 2 to 8 hours post‐dose starting at 80 mg dose. Pupillary diameter increased by 0.6 mm at concentrations higher than 60 ng/ml. The constriction rate seemed to decrease beyond concentrations of 30 ng/ml.
CONCLUSIONS
LY2124275 doses up to 200 mg were well tolerated when administered as single dose. A dose‐related increase in standing pulse rate was observed following drug administration. Pupillary initial diameter increased and constriction rate decreased when concentrations increased.
Clinical Pharmacology & Therapeutics (2005) 79, P44–P44; doi:
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