Moving beyond the “Allegory of the Cave” in the assessment of pulmonary arterial hypertension

Abstract

PULMONARY ARTERIAL HYPERTENSION (PAH) remains a clinically vexing problem considering the high morbidity and mortality that plagues this entity despite indication of improved survival after the introduction of more targeted therapy. While this syndrome is well described from a pathological standpoint the mechanisms involved in the pulmonary vascular remodeling are less clear but are thought to involve endothelial dysfunction and proliferation of various cell types that comprise the wall of distal pulmonary vessels (3). The specific mechanisms leading to distal vessel obliteration and increased pulmonary vascular resistance have been particularly elusive for several decades (14), and although vasoconstriction as a primary event was the focus of research and targeted therapy in early studies, the PAH research community has witnessed a paradigm shift in recent years with a strong tendency to now view the PAH lesion as a quasi-cancerous process (12). In this issue of the Journal of Applied Physiology, Schwenke et al. (8) bring a new tool for assessment of the distal pulmonary vasculature and shake an old specter, vasoconstriction. The investigators employ synchrotron radiation microangiography (SRA), a fairly novel and powerful technique, to more directly evaluate vascular tone in a classic animal model of PAH, monocrotaline (MCT)-challenged rats, providing new insight into regional specific responses of the pulmonary circulation in PAH. SRA allows for both the measurement and assessment of control of blood flow in vivo and collection of data on small arteries and arterioles in situ over time (10). Thus it can supply superior information on kinetic events relative to ex vivo techniques. Since SRA has no focal plane, it can visualize both surface and penetrating vessels simultaneously unlike intravital microscopy, which is limited to assessment of vessel caliber at a single vascular plan. In dynamic organs such as the lung and heart, which are subject to motion, temporal