Effects of Chronic Hypoxia on Hemodynamics, Morphology, and Distensibility of the Piglet Pulmonary Vasculature
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Federation of the American Society of Experimental Biology
We sought to relate hemodynamic changes during the development of pulmonary hypertension to changes in vascular structure as assessed by conventional microscopy and CT measurement of vascular distensibility. Piglets (3 days old) were exposed to 3, 10 or 21 days chronic normoxia (CN) or chronic hypoxia (CH, 10% O2). In vivo pulmonary vascular resistance indexed to body weight (PVRI) was then measured during acute normoxia, acute hypoxia, and acute hypoxia + inhaled NO. Lungs from 3-4 piglets per group were subsequently excised and 1 lower lobe was fixed for morphologic study. The other lobe was infused with perfluorooctyl bromide and pressure-diameter relationships of 90 arteries (undistended diameters= 0.1 - 3.0 mm) were measured at 4 pressures using micro- CT. The slope of the linear pressure diameter data for each artery was plotted as a function of its 0 pressure (undistended) diameter intercept. The resulting slope describes a distensibility parameter (% change in diameter / torr pressure) for that lobe. The microscopy studies showed that peripheral extension of muscularization in arteries < 0.4 mm diameter was significantly greater in CH than CN lungs after 10 or 21 days. In contrast, distensibility was less in CH compared to CN only after 21 days. Hemodynamics were similar in CH and CN piglets after 3 and 10 days, but both normoxic PVRI and hypoxic reactivity were significantly greater in CH than CN after 21 days. In addition, NO significantly reduced hypoxic PVRI in all groups, but reduced PVRI below normoxic values only in the 21 day CH piglets. These data suggest that despite vascular remodeling, both pressor and dilator responses remained intact after 21 days of hypoxia in piglets. Supported by a grant from the AHA Northland Affiliated and HL 19298.