The release of systemic inflammatory mediators is independent of cardiopulmonary bypass temperature

OBJECTIVE: The aim of this study was to investigate the effect of systemic CPB temperature on the production of the key mediators of the systemic inflammatory response to coronary artery bypass graft (CABG) surgery. DESIGN: Randomized clinical study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing first-time CABG surgery. INTERVENTIONS: The patients were randomized to hypothermic (32 degrees C, n = 15) or normothermic (36 degrees C, n = 15) CPB. MEASUREMENTS AND MAIN RESULTS: Plasma interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), cortisol, and neutrophils were measured the day before operation, at closure of the sternum, and 4, 16, and 44 hours later. The cytokine, CRP, cortisol, and neutrophil responses were independent of temperature during CPB with peak concentrations of IL-10 at closure of the sternum followed by IL-6, IL-8, cortisol, neutrophils, and finally CRP. A correlation between maximal plasma concentrations of IL-10 and cortisol was seen in both groups after surgery (p = 0.02). Drainage after surgery was lower after normothermic CPB (p=0.02), with no difference in the requirement for blood transfusion. All patients were discharged from the intensive care unit within 24 hours after surgery. CONCLUSIONS: The release of systemic inflammatory mediators after cardiac surgery was independent of mild hypothermia (32 degrees C) versus normothermia (36 degrees C) during CPB.     

The "inverted cup" -- a novel in vitro release technique for drugs in lipid formulations.

The aim of this study was to develop a membrane-free in vitro release method for drugs in lipid formulations. It was intended to be applicable to as wide a range as possible of preparations, independently of their polarity and viscosity. The principle of the novel technique is to keep the sample suspended in the release medium in an inverted glass cup, allowing a possible phase transition or swelling. Thirteen formulations containing bupivacaine, lidocaine and/or prilocaine in lipid vehicles with different physical properties were prepared and examined. When possible, in vitro release profiles obtained by the new method were compared to profiles obtained by earlier techniques. For three formulations of either bupivacaine or lidocaine in polar lipid formulations, in vitro release profiles were evaluated in relation to in vivo data, from nerve block and pharmacokinetic studies in rats. Preparations that could be investigated both by the "inverted cup" and by the earlier published "single drop" technique generally showed good agreement between the two release profiles. In the case of the polar lipid formulations, arterial blood concentration curves in rats could reasonably be predicted from the in vitro release profiles. In conclusion, the "inverted cup" technique should potentially be applicable to a wide range of lipid formulations of drugs, both for physico-chemical characterisation and for obtaining in vitro -- in vivo correlations.