Physiological Basis of CPX (CPET)

Cardiopulmonary exercise testing is arguably now the 'gold standard' for evaluation of cardiopulmonary function. It supersedes ECG treadmill studies which are focused on detection of ischaemia. The focus of CPET is measurement of ventricular function, respiratory function and cellular function via measurement of gas exchange, as well as detection of myocardial ischaemia. CPET is the most cost effective method of evaluating the pathophysiology of both the cardiovascular and respiratory systems; in addition it is totally non-invasive. For these reasons it should be the first test performed to evaluate exertional dyspnoea. It is one of the best ways of evaluating fitness of athletes and CPET is commonplace in our Sports Institutes. CPET is also used to evaluate patients for cardiac transplantation in many centres.

Why is CPET such a good determinant of cardiorespiratory dysfunction? Exercise requires immediate breakdown of intracellular adenosine triphosphate (ATP) as a source of high energy phosphate (~P). The source of this ATP is aerobic oxidation of mainly glycogen (via carbohydrate) and fatty acids; and in addition by anaerobic hydrolysis of phosphocreatine (Cr~P). The Cr~P becomes the immediate source of ~P to regenerate ATP. If aerobic metabolism is unable to support the requirement of ATP, anaerobic metabolism of glucose via pyruvate and lactic acid will provide some ATP but in much smaller amounts. Aerobic metabolism supplies the majority of ATP up to the anaerobic threshold and after that there is an increasing need for anaerobic supplementation. It is essential to realize that when anaerobic production of ATP commences (at the anaerobic threshold), aerobic production does not cease; anaerobic metabolism merely supplements aerobic production of ATP as the work rate increases. Because different metabolic pathways have different signatures on gas exchange it is possible for a CPET study to identify aerobic metabolism, anaerobic metabolism and indeed the intracellular response to exercise; it looks therefore at the 'total metabolic picture'.

This entire system is finally limited by, and must be supported by, substrate and oxygen availability which is a direct function of the cardiopulmonary system. The change from predominant aerobic to partial anaerobic metabolism is not only detectable by CPX it is actually the basis for determination of the anaerobic threshold and therefore of cardiopulmonary function.

Cellular respiration is coupled to external respiration via the cardiovascular and pulmonary systems. This may be best understood by using the schematic devised by Professor Karlman Wasserman and his group, and described in detail in their book 'Principles of Exercise Testing and Interpretation". This book is referenced in the Resources page of this site. A simplified version is used here.

From this schematic one can see that any increase in QO2 will result in an increase in QCO2; the carbon dioxide will be transported to the lungs via the systemic circulation and the pulmonary circulation. At the same time the increase in oxygen requirement will be met by the same pathway. Similarly substrate will need to be transported. The limiting factors in this chain become the cardiac function (i.e. is cardiac output adequate?), the effectiveness of ventilation ( i.e. are Ve and V/Q matching adequate?), the state of the vascular system (i.e. is there widespread vascular disease?), the pulmonary vascular system (i.e. is there significant pulmonary artery hypertension?) and finally the actual intracellular metabolic pathways (i.e. is the oxygen and substrate being utilized?). All these questions can be answered by CPX testing.

CPET will measure the increase in both Vt and Ve, the changes in VO2 and VCO2 at the mouth, and as the work rate is progressively increased, the rate of change of these variables will also be measured. By using bivariate graphical analysis it is possible to relate the rate of change in one variable to the rate of change in another. For example, is the rate of increase in VO2 appropriate to the increase in work rate? The normal range for this parameter is accurately known. The rate of change in VO2 during exercise, is 10.2 ml/min/watt. Sedentary patients may have a value nearer to 8 ml/min/watt. If this value is not achieved then there is an inadequate increase in cardiac output for the exercise being performed. The heart rate/VO2 relationship is also well documented and if it is above normal then the stroke index is below normal. These are just examples of the depth to which physiology that may be explored by CPET.

CPET may be used in all age groups to evaluate cardiac function objectively. It may be used to evaluate the treatment of cardiac disease, whether this be for myocardial ischaemia or cardiac failure. Respiratory function may be evaluated dynamically by exercise spirometry thus detecting exercise induced asthma as well as restrictive and obstructive lung disease. More subtle measurements are possible which allow the presence of pulmonary artery hypertension to be diagnosed or suspected.

CPET may be performed with invasive monitoring, in which a pulmonary artery catheter and arterial catheter are inserted prior to exercise. Such a test will allow for very accurate measurement of pulmonary artery pressures, stroke volume and oxygen extraction ratios during exercise as well as determining the adequacy of oxygen extraction from exercising muscles themselves. The latter giving an insight into failure of substrate utilization in the cell itself.

At the Western Hospital in Melbourne Australia, we pioneered the concept of using CPET to determine the cardiopulmonary status of elderly patients prior to major surgery. Some of the results of this work can be found under 'Resources'.