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J Appl Physiol 103: 1456, 2007; doi:10.1152/japplphysiol.00716.2007
8750-7587/07 $8.00
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LETTER TO THE EDITOR

Last Word on Point:Counterpoint "Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature"

To the Editor: There are several points that Dr. Rabinovitch and colleagues (6) make in their rebuttal that might be usefully clarified by some final comments. First, our discussion of the topic of vascular loss relates only to chronic hypoxic pulmonary hypertension; the vascular changes that occur in other models of pulmonary hypertension, including the monocrotaline model, are likely to be very different and cannot provide reliable information regarding the effects of chronic hypoxic pulmonary hypertension. Second, Dr. Rabinovitch and colleagues were not able to find the evidence for an absence of vessel loss in two manuscripts that we had cited in our original Counterpoint (Refs. 3, Refs. 1 and 3 therin). Regarding the manuscript of Brusselmans et al. (1) our statement was based on the data presented in Table 1 of that manuscript in which the authors reported that the mean (± SE) total number of vessels per 100 alveoli in wild-type normoxic mice (3.0 ± 0.06) was not significantly different from that in wild-type hypoxic (2.8 ± 0.16) mice. In the paper of Meyrick and Reid (4), Fig. 4 shows that no reduction in the total number of vessels per square millimeter could be found in hypoxic lungs, a finding that they discuss in some detail. While we do not believe the methods of vessel enumeration used were reliable, for the reasons outlined in our original Counterpoint (3), we cited these papers to demonstrate the lack of agreement between investigators using this "traditional" approach. Finally, our opponents in this debate cite previous work (5) to rebut our argument that the problem of changing alveolar number has not been adequately considered. In that study, vessel numbers were expressed per 100 alveoli observed on the tissue sections. The problem is that the number of alveoli seen per section does not reliably indicate the number of alveoli per unit volume of lung. The number seen in each field of view is also affected by the volume of the alveoli and their shape (more specifically their dimension perpendicular to the plane of section), the thickness of the sections and bias due to edge effects (see Ref. 2 for detailed review of this issue). Moreover, this technique cannot take account of increased numbers of alveoli in an enlarging lung. For these reasons the method used does not take account of changes in the total alveolar number.

FOOTNOTES


Address for reprint requests and other correspondence: P. McLoughlin (e-mail: paul.mcloughlin{at}ucd.ie)

REFERENCES

  1. Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D, Carmeliet P. Heterozygous deficiency of hypoxia-inducible factor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Invest 111: 1519–1527, 2003.[CrossRef][Web of Science][Medline]
  2. Howell K, Hopkins N, McLoughlin P. Combined confocal microscopy and stereology: a highly efficient and unbiased approach to quantitative structural measurement in tissues. Exp Physiol 87: 747–756, 2002.[Abstract]
  3. McLoughlin P, McMurtry I. Counterpoint: Chronic hypoxia-induced pulmonary hypertension does not lead to loss of pulmonary vasculature. J Appl Physiol; doi:10.1152/japplphysiol.00274a.2007.
  4. Meyrick B, Reid L. Hypoxia and incorporation of 3H-thymidine by cells of the rat pulmonary arteries and alveolar wall. Am J Pathol 96: 51–70, 1979.[Abstract]
  5. Rabinovitch M, Gamble WJ, Miettinen OS, Reid L. Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery. Am J Physiol Heart Circ Physiol 240: H62–H72, 1981.[Abstract/Free Full Text]
  6. Rabinovitch M, Chessler N. Molthen RC. Point: Chronic hypoxia-induced pulmonary hypertension does lead to loss of pulmonary vasculature. J Appl Physiol; doi:10.1152/japplphysiol.00274.2007.

Paul McLoughlin
Ivan McMurtry


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This Article
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