Discriminating pulmonary hypertension caused by monocrotaline toxicity from chronic hypoxia by near-infrared spectroscopy and multivariate methods of analysis

A new method has been developed for the determination of tissue pathology caused by chronic hypoxia and monocrotaline toxicity. The method is based on the use of near-infrared (NIR) spectrophotometry to measure spectra of lung tissue from normal chronic hypoxia (CH) and monocrotaline (MCT) models of pulmonary hypertension (PH), followed by analysis using multivariate methods, that is, principal component analysis (PCA) and partial least squares (PLS). Synergistic use of NIR with the PCA/PLS method makes it possible, for the first time, not only to divide different lung tissue samples into their respective groups (normal, CH, and MCT) but also to gain insight into mechanisms of PH caused by CH and MCT toxicity. Specifically, MCT metabolites and other hypertensive conditions are known to produce subtle and minor chemical changes in the compositions of tissue (e.g., proteins, carbohydrates, lipids). Although these changes were detected by the NIR technique, they were too small to be discerned through visual inspection of the spectra. However, they can be accurately classified and properly assigned by the PCA/PLS method. The fact that different tissue types can be accurately divided into their corresponding groups by the NIR and PCA/PLS methods suggests that chemical alterations and mechanisms of pulmonary vascular remodeling and PH induced by MCT are different from those induced by CH.