Breathing during excercise

Question 1

How do you measure exercise capacity?

Answer 1

1. Cardiopulmonary exercise testing (CPET) is a non-invasive method used to assess the functions of the heart and lungs at rest and during exercise.
2. CPET tests are often needed for patients scheduled for major surgery and patients taking part in a testing for the diagnosis of heart and lung disease.
3. The test will measure several variables as the patient performs incremental exercise including VO2 (l/min) and VCO2 (l/min) which are the rate of oxygen uptake and rate of carbon dioxide produced by the body, respectively.
4. VO2 and VCO2 are calculated on the assumption of the Fick Principle, i.e. the total uptake or release of a substance is equal to the product of the blood flow to the peripheral tissues and the arterial-venous gradient of the substance.

Question 2

How do you measure VO2?

Answer 2

V02 = Cardiac output x difference in O2 content between blood going to the lungs and leaving

Question 3

Describe phases of steady state exercise

Answer 3

1. The onset of steady state exercise is composed of 3 phases.
2. Phase one is characterised by a rapid increase in minute ventilation (VE) with a time constant of a few seconds.
3. Phase 2 consists of a slow exponential increase ventilation. VO2 increases faster than VCO2 due to differences in solubility of these gases in the tissues.
4. By the third minute, phase 3 represents the steady state of exercise; however, during heavy exercise (i.e. above anaerobic threshold) or incremental exercise this steady state is not reached and ventilation and VCO2 and VO2 will continue to rise until volitional exercise cessation.

Question 4

Describe respiration at rest

Answer 4

1. At rest, the respiratory exchange rate, which is the ratio of VCO2/VO2 (l/min) is 0.8, indicating that muscles have oxidative capacity i.e. aerobic respiration is occurring to produce ATP using a mixture of both carbohydrates and oxygen.
2. The metabolic equivalent task (MET), which is ratio of the rate at which a person expends energy, relative to the mass of that person, while performing some specific physical activity compared to baseline VO2.
3. 1 MET is the baseline VO2 consumption at rest which is set at 3.5ml/min/kg.

Question 5

Kakutani et al 2017

Answer 5

Kakutani et al (2017) have shown in a retrospective study that a high respiratory exchange ratio at AT predicts adverse clinical outcomes in patients with heart failure compared to patients with low RER at AT, highlighting yet another possible clinical measurement which could be used in practice.

Question 6

What is the anaerobic threshold?

Answer 6

The anaerobic threshold aka lactate threshold is defined as the highest metabolic rate where blood lactate (La) concentrations are maintained at a steady-state during prolonged exercise. Anaerobic threshold is a key measure of fitness – the higher it is the more aerobic exercise an individual can do before supplementing it with ATP from anaerobic respiration.

Question 7

Gitt et al 2002

Answer 7

Gitt et al (2002) performed CPET on 223 patients with chronic heart failure and concluded that AT better identified patient at high risk for early death from CHF than did VO2max (discussed below), highlighting its importance in the clinic.

Question 8

Barron et al 2016

Answer 8

Barron et al (2016) concluded that AT is not a good discriminant between patients with cardiovascular over chronic obstructive pulmonary disease while the VO2/work rate slope showed poor to moderate discriminant ability.

Question 9

What is the respiratory compensation point?

Answer 9

1. They will then progress towards a respiratory compensation point where there is significantly more minute ventilation as a result of increased respiratory rate, to compensate for the metabolic acidosis occurring as a result of the exhaustion of the HOC3- buffer system and build of H+.
2. Thus, at severe exercise levels, ventilation is increased to subserve CO2 removal rather than O2 provision. It is not until more severe exercise that there is an increase in respiratory rate (which can become as high as 60 breaths per minute).
3. The metabolic acidosis is detected by both the peripheral and central chemoreceptors and the respiratory center is stimulated.

Question 10

VO2 max

Answer 10

1. From the CPET, the VO2max is calculated – which is the measurement of the rate of maximum amount of oxygen a person can utilize during intense exercise.
2. However, if individuals don’t utilise their full ventilatory capacity in the exercise test then VO2max measured may not be the true VO2max.
3. Using the VO2max value, the MET can also be calculated.
4. Women on average have less muscle than men so the average VO2max for women is less than men.

Question 11

Shah et al (2017)?

Answer 11

1. The measurement of VO2, like AT, has significant clinical benefits as indicated by Shah et al (2017) who showed that VO2max is robustly predictive of worse prognosis in heart failure with preserved ejection fraction, heart failure with midrange ejection fraction, and heart failure with reduced ejection fraction.
2. Further, CPETs variables provided greater risk discrimination in heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction.

Question 12

What are the cardiovascular changes which accompany respiration?

Answer 12

1. As a result of more heat, 2,3DPG and acidosis there is a rightward shift in the oxygen-Hb dissociation curve meaning oxygen transfer from the blood the muscles is more efficient and faster
2. Cardiac output also increases and in athletes this can reduce the pulmonary transit time significantly as they increase their stroke volume up to 30L during exercise which may even reduce oxygen transfer into the blood.

Question 13

Tedjasaputra et al (2016)?

Answer 13

1. Tedjasaputra et al (2016) demonstrate that the pulmonary diffusion capacity at near-maximal exercise is greater in endurance male athletes that this is primarily a result of enhanced diffusing membrane capacity, independent of mean pulmonary flow or alveolar volume.

2. This adaptation permits the transfer of oxygen from the alveoli to the blood without limitation during the performance of high intensity exercise suggesting that despite reduced transit time, our body will adapt to this change as to prevent any compromise on the respiratory system.

Question 14

Describe the mechanism behind the ventilatory changes behind exercise?

Answer 14

i) neural feed-forward ii) neural feedback iii) humoral (blood-born) feedback.
1. The rationale for the neural hypotheses is that initial VE response is too rapid to be mediated by an exercise metabolite transported in the blood to a receptor in the central circulation. The term neural feed forward is used to simply refer to a signal generated in the brain that initiates the hyperpnea simultaneous with or in advance of locomotion.
2. Neural feedback refers to a signal generated in the locomotor limbs that reaches the brainstem respiratory neurons via spinal afferents.
3. The major rationale for the humoral hypothesis is that there is a loose relationship between hyperpnea and metabolic rate, during exercise.

Question 15

Band et al 1980

Answer 15

During exercise there is increased rate of change of breath-to-breath oscillations in PaCO2, in the absence of any change in mean PaCO2.

The chemoreceptors are sensitive to the rate of change of PaCO2, so this may provide a signal for altered ventilation during exercise. Indeed, other studies have demonstrated that manipulating the rate of change of PaCO2 during exercise can alter respiration. However, the greatest increases in ventilation occur in strenuous exercise, but these oscillations are much attenuated in severe exercise. Thus, this rate of change of PaCO2 signal is unlikely to mediate ventilatory changes in severe exercise but may play a role in moderate exercise.

Question 16

Shea et al (1993)

Answer 16

1. Shea et al (1993) assess exercise hyperpnoea in individuals with congenital central hypoventilation syndrome (CCHS).

2. CCHS is caused a mutation in the PHOX2B homeobox gene which leads to dysfunctional chemoreception, most likely at the level of the retrotrapezoid nucleus (Dubreuil et al, 2008).
3. These individuals have no ventilatory response to hypercapnia and experience hypoventilation/apnoea during sleep.
4. However, subjects with CCHS had the same profile of ventilation at the onset of exercise, during steady state exercise, and in incremental exercise up to AT.
5. Thus, the central chemoreceptors appear to play no role in hyperpnoea at mild-moderate exercise levels.
6. The only difference is that CCHS individuals did not demonstrate respiratory compensation at exercise above AT.

Answer 17

1. Thus, it would appear that chemoreceptors play a very limited role in submaximal (normal) exercise hyperpnoea. As such the signals described above involving changes in PaCO2 may not play a significant role.

2. However, a case may be made for the involvement of carotid bodies detecting changes in H+ during heavy exercise as a result of the production of lactate.
3. Asthmatic patients with deverbative carotid bodies did not display hyperventilatory response to heavy exercise even though they a show normal isocapnic hypercapnia.
4. Again, there is contrasting evidence for this theory too; when dietary-induced glycogen depletion was used to prevent exercise induced lactic acid production a normal hyperventilatory response persisted in heavy exercise.
5. This data suggests that although the carotid bodies may play a part it is not only lactate levels but also potassium, adenosine levels which could contribute to the hyperpnea observed in heavy exercise.

Question 18

What are the effects of motor activity on exercise hypernoea?

Answer 18

There are two schools of thought regarding the role of motor activity in exercise hyperpnoea:

1. ‘Central command’ or ‘feed-forward’; suggests that direct links exist between the areas of the brain involved in motor activity, and the areas involved in respiration.
2. ‘Feed-back’; suggests that motor activity and metabolic changes at the level of the muscles initiates mechanisms which feed-back to the respiratory centres of the brain.

Question 19

Central command?

Answer 19

1. Groups who advocate the role of central command suggest that correlating ventilation with motor activity provides an appropriate level of control of ventilation during exercise, which can then be fine-tuned by minimal feedback concerning muscle metabolism.
2. There are two main centres of motor control in the brain – the motor cortex and the hypothalamic locomotor area.

Question 20

Eldridge et al (1985)

Answer 20

1. In 1985 Eldridge et al. used a model of decorticate, paralysed cats.

2. They used electrical stimulation of the hypothalamic locomotor area (HLA) or injected GABA-R antagonists, to induce fictive motor activity (as evidence by biceps nerve discharge).
3. However, since the cats were paralysed, there was no muscle contraction and thus no change in metabolism (i.e. no increase in VCO2).
4. However, there was an increase in ventilation, as evidenced by increased phrenic nerve activity.
5. Thus, authors thus argue that there must be central communication between the HLA and the respiratory centres of the brainstem.
6. In support of this theory, Iwamoto et al. utilised c-fosexpressionas anindex of neural activation. They found that after 45 mins of treadmill exercise in rats, there was anincreasedc-fos expression in the hypothalamic/subthalamic locomotor regions.

Question 21

Counter argument against neural feedforward?

Answer 21

1. However, a number of studies have demonstrated that lesioning of the HLA does not disrupt ventilation during exercise, which lends evidence against this hypothesis.
2. Direct electrical stimulation of muscles, which obviates any need for central motor activity, still produces increases in ventilation.
3. Furthermore, the same level of exercise (and thus the same level of activity in the cerebral motor areas) can result in different levels of ventilation in different physiological situations.
4. Thus, there must be other factors involved in exercise hyperpnoea.
5. Overall, a plethora of animal studies suggest that a central command must exist but human studies are more limited and somewhat indirect, therefore it remains questionable whether this hypothesis is definitely true in humans.

Question 22

Evidence for feed-back control?

Answer 22

1. Proprioceptive input from muscle is also likely to feed-back to the brainstem to increase ventilation.
2. Indeed, some studies have demonstrated attenuated hyperpnoea in exercise after section of the spinal cord dorsal root afferents.
3. Haouzi et al (2005) electrically-induced rhythmic muscle contractions (ERCs) in sheep that had a separate cephalic and systemic circulation.
4. Thus, the central chemoreceptors and carotid bodies were perfused separately and not exposed to metabolic changes induced by exercising muscle.
5. ERC induced increases in ventilation which were augmented by blocking venous return – suggesting that signals are induced peripherally.
6. Blocking venous return from the muscle would increase distension of the pre-venous capillaries, and it was thus suggested that this distension of vessels could act via afferent neurones to provide a signal for hyperpnoea. Indeed, vessel vasodilation correlate well with the level of muscle metabolic activity.
7. However, many studies have demonstrated normal ventilatory response in individuals with spinal cord section or anaesthesia. Cross et al (1982) reported that normal steady-state ventilation was achieved in dogs after spinal cord section and electrical stimulation of muscles.

Question 23

Conclusions?

Answer 23

1. The mechanisms which account for exercise hyperpnoea are very uncertain. The chemoreceptors don’t seem to play an essential role.

2. Some groups hold that central command plays a predominant role, with feed-back concerning the level of muscle metabolism acting to adjust ventilation so as to closely match VE to VCO2.

3. Whilst this is a neat hypothesis, there is substantial evidence against the role of both central command and feedback in ventilatory control. Importantly, a great deal of our understanding comes from animal models in situations much departed from normal physiology. Thus, extrapolation of findings from animal models to intact human physiology should be done with caution.