Use of isolated perfused lung in determining pulmonary disposition and potential toxicological significance of inhaled environmental pollutants

摘要

AbstractRecent interest in the investigation of the effect of environmental pollutants on the nonrespiratory and respiratory functions of the lung has stimulated the refinement and application of the technique of perfusing isolated intact lung preparations from suitable experimental animals in toxicological and biochemical studies. Available techniques include perfusion with whole blood or constituted perfusion media via pulmonary artery while maintaining ventilation with alternating negative or positive pressure. Viable, ventilating lung preparations can be maintained for 3 h. Such preparations have been employed for studies of uptake, metabolism and disposition of intratracheally or vascularly administered endogenous or exogenous chemicals. Recent development in unilateral or split‐lung perfusion preparations will undoubtedly further enhance the application of these techniques in the study of the interactions of endogenous and exogenous substances in the lung tissue. Isolated, perfused split‐lung preparations are particularly suited to investigate early toxic effects of inhaled pollutants in an attempt to gain insight into underlying mechanisms that lead to lung injury. Areas in which intact perfused lungs have been employed extensively with notable success include uptake, metabolism and disposition of toxic chemicals. These preparations have been used to study the effects of gases such as SO2, NO2, O3and CO on lung metabolism. Perfused lung preparations have been particularly useful in demonstrating pulmonary activation of toxic chemicals and in the demonstration of specific effects on the lung after chronic administration of chemicals. Areas which have not been actively investigated include the uptake and disposition of gases or vapors, effects of toxic chemicals on respiratory and nonrespiratory functions of the lung and alteration in the hemodynamics of the pulmonary circulation in the presence of interacting chemical or physical agents. It should be technically feasible to adapt the perfused lung preparations for such investigations, and interest in this area will conti