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POINT-COUNTERPOINT
Regarding the limitations of the barium-gelatin infusion technique, our opponents argue that studies in which small pulmonary arteries were identified using anti-PECAM immunostaining also report vascular loss. However, others who have used anti-von Willebrand Factor or elastin staining to identify vessels did not detect reduced vascular density in hypoxic hypertensive lungs (2, 4, 5).
Dr. Rabinovitch and her coauthors next discuss studies of the pulmonary vasculature undertaken using contrast (PFOB)-based microCT imaging. While this elegant approach holds much promise for the future, we do not believe it can at present address the issue of angiogenesis or rarefaction in the lung. First, the resolution of the technique means that the smallest vessel that can be visualized is at best 70 µm in diameter (6). Second, the principal pathway analysis that this technique uses does not examine parallel distal pathways. Finally, as we have all agreed, full relaxation of vascular tone is essential for angiographic techniques to accurately detect structural changes. It seems unlikely that brief exposure to papaverine, which was used to prepare the lungs for the PFOB-microCT studies (6), could have achieved this. Rho kinase inhibitors appear to be uniquely potent in reducing vascular tone in the chronically hypoxic pulmonary circulation (3, 7), and to our knowledge transient exposure to papaverine has not been shown to be similarly effective. Thus the PFOB-microCT technique cannot provide unambiguous information regarding distal vessel number.
We agree with Dr. Rabinovitch and her colleagues that Rho kinase inhibitors have only been shown to abolish chronic hypoxic pulmonary hypertension at low flow rates and their effects should be examined over a larger range of flows. They suggest that angiogenesis and precapillary arteriolar loss may occur simultaneously. Such a mechanism could reconcile seemingly disparate views on this issue and warrants further investigation. Finally, we agree that there can be major discrepancies between hemodynamic changes and structural changes in the vascular bed following chronic hypoxia. Factors such as reduced vascular compliance may contribute importantly to right ventricular overloading, although it should be recognized that, in addition to changes in structure, smooth muscle contraction can also alter compliance (1).
REFERENCES
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