It is a combination of biochemical and pulmonary receptor mediated dyspnea.
1. Hypoxia gets accentuated on exertion and it stimulates chemoreceptors located in brainstem as well as aortic arch and its branches.
2. Equally important is the ventilation /perfusion mismatch that occur during exertion as the pulmonary blood flow significantly drops while the lung will continue with normal ventilation .This increases the Vp/Vq (> 1) and worsen the hypoxia and can independently trigger the sensation of dyspnea due to stretching of airway mechanoreceptors..(It is prudent to recall ,the later mechanism (Vp/Vq mismatch ) is explicitly involved in isolated valvular pulmonary stenosis .Here , there is no admixture mediated hypoxia , still the patient experience significant dyspnea due to meager reduction in pulmonary blood flow.)
3. Further , there are some morphological changes that occur in pulmonary vasculature in patients with TOF.This is due to chronic hypoxia as well as “chronic low flow” mediated vascular reactivity. Micro vascular dysfunction in the alveolar capillary bed is possible in TOF. There is some evidence to suggest pulmonary gaseous exchange is impaired when compared to normal lungs.This can also contribute to the dyspnea in TOF.
The following article excellently describes the pulmonary dysfunction that occurs in patients with TOF .It is prudent to note ,the abnormal lung function fails to get corrected even after total surgical correction in many.