On behalf of: European Society of Cardiology European Association for Cardiovascular Prevention and Rehabilitation

During exercise, ventilation for a given work rate is increased in pulmonary hypertension. In the present editorial a new look at the ventilatory behaviour, which may change the common approach to VE/VCO2 relationship analysis, is presented. The behaviour of ventilation (VE) in a ramp protocol exercise test is peculiar, and it implies relevant physiological information. In a healthy individual, VE increase during exercise is characterized by four linear phases, during which the steepness of the VE vs. workload relationship progressively increases (Figure 1). The first phase is delimited by the beginning of loaded pedalling (provided that an appropriate unloaded exercise period has been performed) and the anaerobic threshold; the second phase is between anaerobic threshold and the respiratory compensation point; the third between the respiratory compensation point and peak exercise; and the fourth phase, usually very brief, is sometimes observed in fit individuals close to peak exercise and is characterized by an extremely elevated slope of the VE vs. workload relationship. Why does the VE relationship have this peculiar behaviour? The classical physiological interpretation is a switch in VE driver during exercise, being VO2 at the beginning of exercise, VCO2 during the isocapnic buffering period (between anaerobic threshold and the respiratory compensation point), unbuffered acidosis above the respiratory compensation point, and heat exchange at peak exercise in some fit individual. The last one is most evident in fur-coated animals, in which heat cannot or can minimally be eliminated by sweating, and ventilation becomes the main heat exchanger during exercise through the mechanism of panting. Indeed, at the beginning of exercise, below the anaerobic threshold, energy production is aerobic, so that VO2 drives VE, and above the anaerobic threshold energy production is both aerobic and anaerobic. Anaerobic energy production implies an extra CO2 production to buffer acidosis, which is compensated up to the respiratory compensation point and not compensated above it. Accordingly, VCO2 and unbuffered acidosis drive VE in the isocapnic buffering period and above the respiratory compensation point, respectively. The behaviour of the VCO2 vs. workload relationship is different, being linear but characterized by two instead of four linear phases, with a steeper slope in the second phase (Figure 2). The first phase is from the beginning of exercise to the anaerobic threshold; the second is from anaerobic threshold to peak exercise. Indeed, above the anaerobic threshold, more CO2 is needed to buffer lactic acid. The VE vs. VCO2 relationship also has two phases; the first from the beginning of exercise to the respiratory compensation point; and the second above the respiratory compensation point (Figure 3). Indeed, up to the respiratory compensation Centro Cardiologico Monzino, IRCCS, Milan, Italy Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milano, Milan, Italy Division of Pulmonary and Critical Care and Medicine, Department of Medicine, University of Washington, Seattle, WA, USA Department of Cardiovascular and Respiratory Sciences, ‘‘La Sapienza’’ University, Rome, Italy Corresponding author: Piergiuseppe Agostoni, Centro Cardiologico Monzino, IRCCS, Dipartimento di Scienze Cliniche e Medicina di Comunità, Università degli Studi di Milano, via Parea 4, 20138, Milano, USA. Email: [email protected] European Journal of Preventive Cardiology 2014, Vol. 21(3) 268–271 ! The European Society of