Hypoxic Pulmonary Vasoconstriction and Gas Exchange During Exercise: DISCUSSION
Our study documents that exercise can improve Va/Q mismatching in COPD. In addition, it confirms that nifedipine releases HPV in these patients and lowers right ventricular afterload during exercise. 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 to distribute blood flow more efficiently both at rest and during exercise (Fig 3). However, the latter has a small functional effect since, even after nifedipine, exercise reduced the overall amount of Va/Q mismatch. This observation suggests that the role of HPV in modulating gas exchange during exercise in COPD is probably minor, and that most of the Va/Q improvement seen under these conditions is due to improvement in the ventilation distribution. To clarify the more relevant aspects of this investigation, the effects of exercise on gas exchange at baseline (before nifedipine) and the role of HPV in modulating gas exchange during exercise will be discussed separately.
Effects of Exercise on Gas Exchange at Baseline (Before Nifedipine)
It has been well established that in patients with COPD Pa02 might increase, decrease, or remain unchanged during exercise. However, there is still a question regarding the effects of exercise on Va/Q maldistribution in COPD. Wagner et al and Dantzker and D’Alonzo used the multiple inert gas elimination technique to study patients with COPD during exercise. Even though Va/Q inequality did not change with exercise, Pa02 fell. This apparent discrepancy was explained by (1) a rise in PaC02 and (2) the effect of a lower Pv02 on the end-capillary Po2 of low VaQ units and shunt. A subsequent study by Minh et al disputed these conclusions. By comparing patients with COPD who improved Pa02 with those who showed a fall in arterial oxygenation with exercise, these authors concluded that the role of Pv02 in modulating such response was minimal, and that the increase in Pa02 with exercise was highly dependent on the reduction of Qs/Qt. However, since the latter investigation used conventional gas exchange measurements, the authors could not separate the precise role of Va/Q mismatching, shunt, and 02 diffusion limitation as potential causes of hypoxemia. To our knowledge, our study is the first one to specifically demonstrate that Va/Q mismatching can improve during exercise in COPD. This is shown by the lower LogsD Q (Fig 1 and 3), Log*» V, and DISP R-E* (Table 2). eriacta tablets
Figure 3. Mean (±SEM) values of oxygen uptake plotted against the dispersion of the blood flow distribution (LogSI, Q) (left jxinel) and the dead space/tidal volume ratio (VD/VT) (right fxinel) at rest and during exercise, before (continuous line) and after nifedipine (dashed line). Stars denote significance (for exact p value, see Table 2). The shaded area corresponds to the expected limits of normality, Iwft panel: Note that, after nifedipine, the dispersion of the blood flow distribution increased, both at rest and during exercise. However, irrespective of nifedipine, exercise (higher 02 uptake) distributed blood flow more homogeneously (lower Logs). Right panel: Before nifedipine, the VD/VT ratio decreased with exercise as expected. However, after nifedipine, this ratio did not change with exercise. As a result, VD/VT was higher during exercise, after than before nifedipine. For further explanations, see text.
It is tempting to speculate that differences from previous studies are related to the severity of COPD. For instance, both Minh et al and Raffestin et al reported that those patients with COPD who developed exertional hypoxemia have a lower FEVi than those who did not. Further, the recent report by Dantzker and D’Alonzo showing no change in the Va/Q distributions with exercise included patients with much more severe airway obstruction than ours (FEV„ 0.56 [in Dantzker and D'Alonzo] vs 1.5 L [in our patients]) together with more C02 retention at rest (56 vs 39 mm Hg, respectively). Thus, we suggest that the less advanced disease of our patients enabled them to hyperventilate during exercise more than those whose cases were reported by Dantzker and D’Alonzo, reducing but not preventing the increase in PaC02 and shifting Q toward higher values. This higher Q would then minimize the impact of a lowered Pv02 on the end-capillary blood of those units with very low Va/Q ratio which, on the other hand, would have been reduced by exercise itself (Table 2). In summary, we postulate that the less severe lung structural derangement of our patients may have facilitated a more homogeneous distribution during exercise of both the alveolar ventilation (lower Logso V) and the pulmonary blood flow (lower LogsD Q)- During exercise, P(A-a)02 did not change (Table 2). levitra plus
At first glance, this suggests that exercise did not modify the efficiency of the lung as a gas exchanger. However, as it has been already pointed out, the inert gas elimination technique showed that the Va/Q distributions definitely improved during exercise. The apparent paradox of a better Va/Q matching without any noticeable change in P(A-a)02 is explained by 20 percent of the P(A-a)02 due to diffusion limitation, as suggested by the higher predicted than measured Pa02 during exercise (p<0.002). This would then limit the expected increase in Pa02 due to the improvement in Va/Q mismatching. This unexpected finding is at variance with previous reports. In our laboratory, the accuracy of Po2 and Pco2 electrodes is checked daily with tonometered blood, and reported Po2 values are systematically corrected for body temperature6 which, in the present study, was obtained through the thermistor of the Swan-Ganz catheter. Using the same methodology, this difference was not seen at rest. Moreover, during exercise after nifedipine (1 h after the first exercise measurements were taken), we observed a similar trend (p = 0.09). Thus, under these circumstances, a technical error seems most unlikely. We lack a precise explanation for this finding, but we would suggest that the higher exercise Vo2 of our patients, compared with former reports, may well clarify it. Clearly, further studies are needed to confirm and explain this observation.
