Chest
Volume 97, Issue 2, February 1990, Pages 268-275
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Hypoxic Pulmonary Vasoconstriction and Gas Exchange During Exercise in Chronic Obstructive Pulmonary Disease

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In patients with chronic obstructive pulmonary disease (COPD) studied at rest, nifedipine releases hypoxic pulmonary vasoconstriction (HPV) and worsens gas exchange. During exercise, this drug lowers pulmonary hypertension, but the effects of this lower pulmonary vascular tone on ventilation-perfusion ( V˙A/ Q˙) relationships are still poorly understood. To analyze them, we determined the V˙A/ Q˙ distributions in eight patients with stable COPD (FEV1, 36 percent of predicted) at rest and during exercise (60 percent V˙O2max), before and after nifedipine (20 mg sublingually). Nifedipine shifted to the right the pulmonary pressure-flow relationship (p<0.01) and increased the dispersion of the blood flow distribution at rest and during exercise (p<0.005). These observations strongly suggest that nifedipine released HPV under both conditions. However, even after releasing HPV by nifidipine, exercise distributed blood flow more homogeneously than at rest (p<0.05). Besides, exercise greatly decreased the overall degree of V˙A/ Q˙ mismatching (p<0.001) not only before but also after nifedipine. Thus, we postulate that most of the V˙A/ Q˙ improvement that exercise may induce in patients with COPD, as it is shown here, is due to improvement in the ventilation distribution. Interestingly, this V˙A/ Q˙ improvement was not paralleled by a significant decrease of P(A-a)O2. This apparent paradox could be explained by 20 percent of the actual P(A-a)O2 during exercise due to diffusion limitation, as assessed through the inert gas approach. Taken all together, these results help to better understand the mechanisms that govern pulmonary gas exchange during exercise in COPD.

(Chest 1990: 97:268–75)

Section snippets

Patients

Eight male patients ( x¯± SEM, 62 ±1 year) with the standard clinical criteria of COPD and with previous functional confirmation of nonreversible chronic airflow limitation (FEV1, 1.15 ±0.12 L [36 ±3 percent predicted]) were selected from the outpatient clinic of our institution. None of them had clinical evidence of overt right heart failure. Type B COPD was present in five patients whereas the three remaining patients had predominantly type A COPD. Consent was obtained after the

RESULTS

Airflow obstruction was severe in all but patient 8, and all but one subject (patient 2) showed marked air trapping (Table 1). Hyperinflation was noticed only in patient 5. The Dco was reduced in four subjects (patients 2, 3, 5, and 6) (Table 1). Table 2 provides the metabolic, hemodynamic, and gas exchange data at rest and during exercise, before and after nifedipine. Nifedipine was well tolerated by all the patients and did not produce any symptomatic adverse side effect.

DISCUSSION

Our study documents that exercise can improve V˙A/ Q˙ mismatching in COPD. In addition, it confirms that nifedipine releases HPV in these patients1 and lowers right ventricular afterload during exercise.2, 3, 4 To our knowledge, however, no previous information regarding the role of HPV in modulating gas exchange during exercise in COPD has yet been raised. Our results show that the release of HPV induced by nifedipine clearly interferes with the ability of the pulmonary circulation

ACKNOWLEDGMENTS

The authors thank C. Gistau for her chromatographic work; F.A. Lopez, F. Burgos, T. Lecha, M. Simo, and C. Argaña for their skillful technical assistance; A. Cobos (Department of Statistics, University of Barcelona) for his statistical advice; and the Medical Staff of our Service for their cooperation and care of the patients.

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  • Cited by (0)

    Supported in part by Grant CCA 8309185 from the Joint US-Spain Committee, and CICYT PA 82–1787 and PA 86–0345.

    Presented in part at the American Thoracic Society Meeting, Las Vegas, May 8–11, 1988.

    Recipient of a Postdoctoral Research Fellowship Award of the Fondo de Investigaciones de la Seguridad Social (FISss IIE/88), Spain

    Former Research Fellow, Universitat de Barcelona (FPI/85)

    Manuscript received March 20; revision accepted July 13.

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