REDUCED SYSTEMIC OXYGEN EXTRACTION DOES NOT PROVE MUSCLE DYSFUNCTION IN PAH

Abstract

Dear Editor-in-Chief: With interest, we have read the article of Tolle et al. (7)reporting on the systemic oxygen extraction using the Fick principle in patients with either pulmonary arterial hypertension (PAH) or left ventricular systolic (LVSD) and diastolic dysfunction (LVDD). The authors found in PAH patients an impaired systemic oxygen extraction ratio (SER) and concluded that it was pathologic, and they sought explanation in dysfunctioning skeletal muscles in these patients because cardiac output (Q˙t) was found to be normal; this is in contrast to the LVSD patients who are known to have a reduced V˙O2peak but have an increased SER in response to an abnormal Q˙t. We disagree with the authors' conclusion for the following reason: In their Figure 2, Tolle et al. (7) used a Q˙t percentage, normalized to the maximal predicted cardiac output that is calculated from a predicted V˙O2peak, which was derived from a population of healthy men (3). The figure showed that Q˙t in the PAH patients was higher than in theLVSD patients and eventually exceeds 100% of predicted values. Ahyperdynamic circulation is an abnormal phenomenon in PAH patients only encountered in portopulmonary hypertension or PAH secondary to a right-to-left shunt phenomenon. By inserting the PAH patients with a hyperdynamic circulation (Q˙t more than 100% predicted), Tolle et al. (7) concluded that the PAH population has a different linear correlation compared with the LVSD group, and thus another pathophysiological cause, in the skeletal muscles, resulting in a reduced SER. However, many studies performed in different patient groups-including those of Jain et al. (4) in chronic heart failure patients, Ruokonen et al. (6) in ICU patients, and Buheitel et al. (1) in children with congenital heart disease-have shown that the relation between cardiac output and SER is nonlinear (2). Moreover, it is a physiological response of the body that SER is reduced at increased Q˙t because muscle mitochondria operate close to the maximum rate at the predicted V˙O2peak (5). Fitting linear lines for different patient groups with different ranges of cardiac output will automatically lead to different slopes. It is additionally clear from their Figure 2 that if the PAH patients with the hyperdynamic flow are excluded, slopes between the different patient groups will not differ. We conclude that the difference in slopes between the PAH patients and LVSD patients cannot be interpreted as the consequence of dysfunctioning skeletal muscles in the PAH patients, rather it reflects the curvilinear relation between SER and Q˙t. Yeun Ying Wong, MD Willem J. van der Laarse, PhD Anton Vonk-Noordegraaf, MD, PhD Departments of Pulmonology and Physiology Institute of Cardiovascular Disease VU University Medical Center Amsterdam, The Netherlands