Forced vital capacity maneuvers in safety pharmacology studies of the respiratory system

Abstract

The pharmacologic and toxicologic effects of drugs on the respiratory system are best studied with combinations of different pulmonary function tests. The different tests probe the behavior of specific regions of the lung, or measure products of related pulmonary and systemic processes. Effects on integrated neurorespiratory function, pulmonary gas exchange, and bronchial or large airway mechanics may all be assessed with pulmonary function tests in spontaneously breathing animals. Effects on the parenchyma and small airways are tested for by measuring lung dynamics during externally controlled forced vital capacity breathing maneuvers (FVCMs) in anesthetized, intubated animals. Effective use of FVCMs in safety pharmacology studies depends on repeatedly producing controlled lung volume changes, and accurately measuring the dynamic physiologic signals occurring during those events. The physiological basis for FVCM testing and the technical aspects of accurate and repeatable experimental methodology are discussed in context of safety pharmacology applications. © 1996 Wiley-Liss, Inc.