Pfib Inhalation Acute Lung Injury Prevention Research

As a colorless gas, Perfluoroisobutylene (PFIB) is a kind of fluoroolefm with high respiratory toxicity as ten times as that of phosgene. It is produced by the pyrolysis, and as a by-product during the manufacture, of polyterafluoroethylene(PTEE) which is widely used as' its trade name Teflon. Up to now, there is little known about the mechanism of acute lung injury (ALI) induced by PFIB, and furthermore no effective prophylactic or therapeutic measure against this potent lung oedemagen. Based on publicly available literature and data from our laboratory, some questions need to be answered: whether partial liquid ventilation (PLV) can do more benefits than conventional mechanic ventilation (CMV) for rat model of PFIB intoxication? What is the insidious nature of PFIB toxicology? What is the structure-effect relationship of some cholinolytics as antidote to PFIB? What kind of role dose BZ play to attenuate pulmonary edema?1. Study on PLV therapeutic effects against ALI induced by PFIBBenefits of PLV appear less adverse effects on many models of ALI than CMV.Although PLV can improve gas exchange and lung compliance, it was not proved to bemore useful in ALI induced by PFIB than CMV. ALI induced by PFIB has its ownetiologic, pathophysiologic and biochemical mechanism different from other ALImodels, thus it has specific disease process- the fulminating pulmonary edema after latent period. Appropriate therapy may arise from particularity of subgroup of ALL2. Study on the prophylactic and therapeutic effects of cholinolytics gainst ALI induced by PFIB inhalationEffects of cholinolytics to attenuate pulmonary edema were observed in BZ, 8018 and higher dosage of 654-2. Detoxication of PFIB inhalation induced pulmonary edema by BZ is in a dose-dependent manner, BZ(5mg/kg) can significantly decrease mortality rate induced by PFIB, and the role of BZ on decreasing protein concentration in BALF 24h after PFIB exposure was also observed.3. Study on role of BZ as antidote to PFIBFirstly, Malondialdehyde(MDA) levels in serum and lung tissue were increased after PFIB exposure, and administration of BZ significantly decreased MDA levels in serum but not in lung tissue. Secondly, Pulmonary edema was indexed by the increased leucosequestration of lung tissue as expressed by the lung myeloperoxidase (MPO) activity. BZ may not act via direct alleviate leucosequestration. The third study showed that the loss of protein sulphydryl levels in lung tissue paralleled with pulmonary edema. It is proposed that BZ increased protein sulphydryl levels in lung tissue, and may contribute to protection by reacting with inhaled electrophiles to prevent or to reduce damage to tissue . We finally investigated The role of blood rheology in ALI induced by PFIB. Hematocrit, plasma viscosity and erythrocyte deformability remained unaffected, while whole blood viscosity, and erythrocyte aggregation significantly increased after PFIB exposure. BZ administration can attenuate this change and show ameliorating pulmonary microcirculation effect.We deduced that (1)The toxicity of PFIB may be correlated with its susceptibility to nucleophilic attack and the generation of reactive intermediates. (2)PFIB reacts readily with NH2-, OH-, SH-groups which are found in living tissues as protein. (3) Direct protein lesion by PFIB might be related to cell's morphology and function changes. (4) Then the lesion activated polymorphonuclear leukocyte (PMN) and alveolar macrophage (AM) that mediate fulminating pulmonary edema. (5)Mechanism of BZ as antidote to PFIB maybe protein protection and ameliorating pulmonary microcirculation effect. Further investigations are needed to prove the above deduction.