Activated protein C has been demonstrated to play an important role in the regulation of inflammation in addition to coagulation. We investigated the anti-inflammatory effects of activated protein C in a rat model of cardiopulmonary bypass.
Methods: Rats were randomized to receive an intravenous bolus of vehicle (control), 0.1 mg/kg diisopropyl
fluorophosphate-activated protein C, or 0.1 mg/kg activated protein C 10 minutes before the initiation of cardiopulmonary bypass. Rats underwent cardiopulmonary bypass for 60 minutes followed by another 60-minute observation.
Results: The activated protein C group showed significantly higher mean arterial oxygen pressure and lower mean lung wet-to-dry weight ratio after cardiopulmonary bypass than the control and diisopropyl fluorophosphate-activated protein C groups. Furthermore, lung pathology revealed minimal inflammatory Ralimetinib research buy change in the activated protein C group. A marked increase in CD11b expression Blasticidin S datasheet and a decrease in CD62L expression after cardiopulmonary bypass were observed in the control and diisopropyl fluorophosphate-activated
protein C groups. However, administration of activated protein C significantly attenuated these changes. Lung content of tumor necrosis factor-alpha and interleukin-1 beta in the activated protein C group tended to be lower than in the other groups. Lung content of macrophage inflammatory protein-2 in the activated protein C group was significantly lower than in the diisopropyl fluorophosphate-activated protein C group.
Conclusions: Administration of activated protein C before cardiopulmonary bypass attenuates acute lung injury induced by cardiopulmonary bypass at least in part through the inhibition of neutrophil activation and possibly via the attenuation of proinflammatory cytokine production in this rat model of cardiopulmonary bypass. (J Thorac Cardiovasc Surg 2011;141:1246-52)”
“Class I antiarrhythmic drugs are commonly used to treat cardiac
rhythm disorders. Some of those drugs were recently reported to have both a cutaneous analgesic and a neural blocking effect. We evaluated whether these drugs have a spinal anesthetic effect. Three Class I antiarrhythmic drugs (class IA: quinidine, selleck inhibitor IB: mexiletine, and IC: flecainide) were tested. After they had been intrathecally injected in rats, the potencies and durations of these drugs on spinal anesthesia were recorded. Bupivacaine, a commonly used local anesthetic, and 5% dextrose solution were used as controls. Bupivacaine, flecainide, quinidine, and mexiletine produced a dose-related spinal blockade of motor function, proprioception, and nociception, but dextrose solution produced no spinal anesthetic effect. The descending order of potency was bupivacaine > flecainide > quinidine > mexiletine (p<0.05 for all differences). On an equipotent basis, flecainide, quinidine, and bupivacaine produced similar durations of action, all of which were significantly longer than that of mexiletine (p<0.