Conference: 2008 International PHA Conference and Scientific Sessions
Release Date: 06.20.2008
Presentation Type: Abstracts
Allen R.P.1, Milstein J.M.1, Moon-Grady A.J.1,2, Raff G.W.1,2, Black S.M.3, Fineman J.R.2, Bennett S.H.1, Eldridge M.W.4
1University of California, Davis, CA, USA
2University of California, San Francisco, CA, USA
3Medical College of Georgia, Augusta, GA, USA
4Medical College of Wisconsin, Milwaukee, WI, USA
BACKGROUND: The etiology of idiopathic pulmonary hypertension (IPH) is unknown. We evaluated whether the mechanical cause of IPH arises from the recapitulation/exacerbation of a fetal phenoytpe of arterial diameter network organization remodeling under a positive-feedback shear stress paradigm(1).
METHODS: We reviewed available morphometric evidence of the fractal arterial branching characteristics of the pulmonary arterial circulation under condition of IPH versus normal pressures, evidenced by a vessel number-diameter scaling property , where Nn is the number of arteries of diameter d at generation, D0 is the fractal dimension phenotype:(fetal, adult). Hemodynamic evidence of phenotype was evaluated by the analysis of pulmonary vascular resistance via a fractal network to functionally identify D0 under conditions of minimum work where the shear stress load on generation n vessels is predicted by with= MPA shear stress. We evaluated hemodynamic D0 and for diverse forms of PH: Control (Con); High-Altitude pulmonary edema susceptibility (HAPE-S); Chronic Thromboembolism CTEPH; mitral stenonsis MS; and IPH
RESULTS: Figure 1 indicates morphometric and hemodynamic phenotypes for CON and IPH with significant differences to Con (*) with IPH different from all groups (¢). Acute and chronic PH conditions revert to a fetal phenotype, with IPH the most severe. Shear stress evaluated in generation 19 vessels of 0.005 cm with line demarcating t=365 dynecm-5 threshold for acute injury in large diameter arteries.
COMMENTS AND CONCLUSIONS: The fetal phenotype is found in intraacinar arteries free of smooth muscle and vascuopathy in the physiological-hypertensive fetal pulmonary circulation. Its existence in secondary pulmonary hypertension(1) human IPH, and diverse forms of PH indicate a common mechanical cause whose etiology can be traced to a fetal origin under a shear stress paradigm of arterial diameter network remodeling. The fetal/adult phenotypes possess dissimilar, yet identifiable, architectural and hemodynamic signatures. This suggests that the dynamics of the architectural phenotype may help elucidate susceptibility/triggering profiles to PAH that precede endothelial injury and vascular wall changes.