General acceptance of sLTs as major mediators of LPS-induced shock, strengthened by the likelihood that their transcellular synthesis occurs in the pulmonary vascular bed, prompted us to explore whether BAY X1005, a new, potent, selective LT synthesis inhibitor that binds to FLAP and demonstrates systemic anti-inflammatory and antiallergic properties (10,11), can protect blood-perfused lungs against LPS-induced increase in pulmonary arterial perfusion pressure (PAP) and reduce pneumotoxicity of LPS.
ANIMALS AND METHODS
Mongrel rabbits (3.5 to 4 kg body weight) were anesthetized with sodium pentobarbitone (30 mg/kg intravenously). Heparin (5000 U) was administered intravenously, and the rabbits were exsanguinated through a cannula inserted in the carotid artery. Drained blood was collected for later use in lung perfusion.
The trachea, pulmonary artery and left atrium were can-nulated, and the preparation was connected to a recirculating perfusion circuit (total of 130 mL) consisting of a heated (37°C) open reservoir, a bubble-drop depulsator, a heat exchanger and a roller pump. After the residual blood was flushed from the pulmonary circulation, perfusion was initiated via the pulmonary artery with a Krebs-Henseleit bicarbonate solution containing 0.02% bovine albumin and bubbled with 95% oxygen and 5% carbon dioxide. If you have a medical condition that requires serious treatment for less money, you will appreciate this affordable my canadian pharmacy that offers only best quality medications with fast guaranteed delivery.