Author + information
We thank Dr. Krohn for his thoughtful comments. The mechanism for the desaturation seen in some elite athletes is likely to be related to the high cardiac output leaving insufficient time for equilibration of oxygen tensions between the alveolus and alveolar capillaries. Oxyhemoglobin desaturation in response to maximal exercise is a very unusual finding in normal adults performing exercise near sea level (1). Cardiac output at peak exercise is low in patients with primary pulmonary hypertension (PPH). Desaturation is unlikely to be due to the same mechanism as that occurring in elite athletes. Arterial oxyhemoglobin desaturation is not a feature of circulatory diseases or deconditioning.
We found that nitric oxide (NO) reduced right ventricular systolic pressure (RVSP) at rest in our patients with PPH, but failed to alter exercise responses. Several factors may have been responsible: 1) Nitric oxide may not have improved cardiac output, despite causing a fall in pulmonary vascular resistance; NO may adversely affect the positive inotropic response to beta-adrenergic stimulation in left ventricular dysfunction (2)resulting in reduced cardiac contractility. 2) Hemodynamic improvement present at rest may not have been sustained during exercise; our study was noninvasive and we could not be sure that NO improved either RVSP or cardiac output during exercise. 3) As proposed by Dr. Krohn, peripheral factors may have limited the benefit of any rise in cardiac output with NO. In patients with chronic left ventricular failure, Wilson et al. (3,4)found an increase in cardiac output with the acute administration of hydralazine or isosorbide dinitrate during submaximal exercise or dobutamine during maximal exercise. However, none of these drugs improved total oxygen consumption, oxygen uptake across the exercising leg or venous lactate. This paradox was attributed to a failure of “nutritive” flow to increase in the exercising muscle. Even though peripheral oxygen extraction is high in patients with PPH (5), it is possible that the peripheral circulation may not have been able to distribute appropriately any additional acute increase in cardiac output caused by NO inhalation.
We agree that the study of neurohumoral mechanisms in PPH may prove fruitful. Endothelin is known to be elevated in patients with PPH (6)and may be important in promoting vascular remodeling. At present it is unclear whether abnormalities of other vasoactive hormones also occur. However, even if neurohumoral abnormalities occur under conditions of circulatory stress, the matter of discerning cause and effect will remain.
- American College of Cardiology
- Hare J.M.,
- Loh E.,
- Creager M.A.,
- Colucci W.S.
- Wilson J.R.,
- Ferraro N.