Apply an integrative interpretation of pulmonary vascular resistance (PVR) change during pulmonary hypertension progression that is theoretically independent of mechanism and timing, as translated from a simple non-equilibrium thermodynamic feedback model of adaptation.
Analyze the flow-independent component of pulmonary arterial vascular resistance in terms of a dissipative fractal tree as a maximum-entropy/minimum-work state function, whose morphology is subject to adaptive remodeling via feedback coupled to signaling from metabolism and hemodynamic forces. Feedback conditionally performs work on tree morphology in an effort to maintain constant the total steady-state entropy production per unit organism body weight, a generalized form of energy dissipation that couples the steady-state pulmonary hydraulic power as the product of pressure and flow to the resting metabolic rate.
The treelike, otherwise known as, “fractal”, phenotype was evaluated from mean pressure-flow data obtained in patients from previous studies diagnosed with PAH. Phenotype evaluation utilized a maximum-entropy/minimum-work state function applied to pulmonary vascular resistance. Compared with available morphometric data, our results indicate that diverse forms of PAH-including mitral stenosis (MS), congenital (CG), chronic obstructive pulmonary lung disease (COPD), chronic thromboembolism (CTE), idiopathic (IPH) and familial (FPH), share the same arterial network design and causal positive-feedback remodeling trajectory, defined by fetal the phenotype, area ratio to precapillary arterioles less than one.
Diverse forms of pulmonary arterial hypertension remodel tree morphology along a positive-feedback trajectory signaled via shear stress amplification towards a common fractal tree phenotype and its exacerbation, characterized topologically as a distribution of cross-sectional area with an area ratio less than one, and a fractal dimension of design that recapitulates the fetal state of physiological hypertension.
The positive-feedback trajectory of area ratio change predicts identifiable morphometric and hemodynamic tree signatures masked in PVR over time well before pulmonary hypertension emerges, evident during vasoconstriction, endothelial dysfunction/injury, and before proliferative changes take place in the arterial wall.
Roblee Allen, No Financial Disclosure Information; No Product/Research Disclosure Information