This also leads to a high A-a gradient which is not responsive to oxygen In conditions with right to left shunts, there is again a ventilation perfusion defect with high A-a gradient. However, the A-a gradient is responsive to oxygen therapy. In cases of right to left shunts more of deoxygenated blood mixes with oxygenated blood from the lungs and thus to a small extent the condition might neutralize the high A-a gradient with pure oxygen therapy.