Abstract
This being clarified, let us examine the four main arguments developed by Anholm that high pulmonary artery pressures (PAP) are irrelevant to exercise.
1. Prediction of mathematical models. This argument is particularly weak. The purpose of mathematical models is to explain, not to contradict experimental observations. For example, after Messner and Habeler reached the summit of Mount Everest without supplemental oxygen (O2), in 1978, previous modelling which predicted that this was impossible had to be re-evaluated (West, 1983). Prediction of models had luckily not prevented the climb. 2. Supplemental O2 does not decrease PVR at high altitudes, but “almost” restores sea level maximal O2 uptake (VO2max). This discussion is about “almost” and the complicated multiple effects of supplemental O2. Here it is agreed with Anholm that there are discrepancies in the literature. This is related to the lack of specific evaluations of the pulmonary circulation and right ventricular afterload. It is interesting that such data have been recently gathered in normoxic exercising athletes at sea level, and the results indicate that steep PAP-flow relationships are associated with a limitation in VO2max (La Gerche and others, 2010). 3. Pulmonary artery pressure does not limit exercise capacity in chronic mountain sickness (CMS). True. But CMS patients also present with huge increases in arterial O2 content and lung diffusing capacity and differently adapted ventilatory responses, which probably compensate for the cardiovascular problem. 4. Pulmonary vasodilator studies. Anholm is right that pharmacological pulmonary vasodilator interventions may or not increase VO2max in hypoxia, and that improved arterial oxygenation by some of these interventions confuses the interpretation. Variations in experimental design may mask an admittedly small gain in VO2max by 2-3 ml/kg/min. But VO2max improved in proportion to decreased PAP with a r2 of 0.33 to 0.53 in subjects treated with endothelin receptor antagonists and in whom arterial oxygenation was not changed. Thus decreased PAP explained 30 to 50 % of the improvement in aerobic exercise capacity. This is not trivial! As for the improved VO2max reported with the intake of dexamethasone and not with the intake of tadalafil in HAPE-susceptible volunteers rapidly brought to high altitude, Anholm might wish to know that this was clearly related mainly to more important decrease in PAP (Fischler and others, 2009).
In conclusion, data are accumulating suggesting that PAP is an important modulator of aerobic exercise capacity in hypoxia, and may be even also in normoxia. Where we agree with Anholm is that the proof of it remains incomplete, and that more experiments are needed. Mathematical modelling will follow.