Pulmonary hypertension

Abstract

a b s t r a c tA 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.Ó 2009 Elsevier Inc. All rights reserved.Monocrotaline (MCT) 2 is an 11-membered macrocyclic diester member of the pyrrolizidine alkaloid family of plant toxins that produces a delayed onset yet progressive pulmonary vascular disease resulting in pulmonary hypertension (PH) in Sprague-Dawley rats [1][2][3]. Therefore, MCT-induced PH has been used as a model for the study of chronic pulmonary vascular diseases in humans since 1961 [4]. Nevertheless, the exact mechanism by which MCT causes pulmonary toxicity is still not completely understood [3]. Considerable efforts have been made by many research groups to elucidate the mechanism [5][6][7][8]. Some studies have shown monocrotaline pyrroles to react with DNA and other cell macromolecules [9][10][11][12]. Unfortunately, to date, only limited success has been made. This is probably due to the lack of a technique that can noninvasively detect and identify MCT and all of its intermediates and products during its biochemical transformation processes. Near-infrared (NIR) multispectral imaging technique may be the solution to this problem. We have succeeded in developing a novel NIR multispectral imaging (NIR-MSI) instrument that can provide, for the first time, the means to noninvasively, sensitively (single pixel resolution), and rapidly (ms) record not at a single wavelength as in NIR bioimaging instruments but rather on an entire NIR absorption spectrum (as with a Fourier transform [FT]-IR spectrophotometer) and not just one spectrum but rather tens of thousands of spectra at tens of thousands of different locations within a sample during a period as short as a few millise...

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