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Current methods used in the diagnosis of coronary artery disease vary in sensitivity and specificity and have a number of limitations. The aim of this thesis investigation was to explore a new technique for inducing hypocapnia in resting subjects and investigate whether this technique has any clinical applications in the diagnosis of coronary artery disease. In 18 healthy subjects, the effects of hypocapnia, induced by mechanical hyperventilation (in 21% or 15% inspired O₂), on cardiac electrical activity and heart function were investigated using an electrocardiogram (ECG) and echocardiogram. In addition, a pilot study was conducted to examine the effect of hypocapnia on the ECG of four patients suffering from coronary artery disease with stable angina. Experiments using mechanical hyperventilation showed that the most severe hypocapnia tolerable (PetCO₂ = 20 ± 0mmHg) in normal healthy subjects causes a significant increase in T wave amplitude (increase of up to 0.09 ± 0.02mV, P < 0.01) in the anteroseptal leads (V₁-3) of 18 normal subjects but these changes do not exceed the clinical thresholds for hyperacute T wave amplitudes. Hypocapnia did not cause any other significant ECG or echocardiographic changes during mechanical hyperventilation. Reducing inspired O₂ to 15% during hypocapnia in nine normal subjects did not accentuate any of the T wave changes seen during hypocapnia, nor did it cause any clinically significant changes to appear. In two patients suffering from coronary artery disease with stable angina, no clinically significant ECG changes were seen during hypocapnia. These patients were taking isosorbide mononitrate medication which could have interfered with the vasoconstrictive effects of hypocapnia. In two patients not taking this type of medication, small increases in T wave amplitude (of up to 0.05 ± 0.01mV) and decreases in ST segment height (of up to 0.05 ± 0.01mV) were observed. These results show that hypocapnia, induced by mechanical hyperventilation, of the greatest severity tolerable in normal subjects, does not induce clinically significant ECG changes in normal healthy subjects as has been previously suggested. Preliminary results from four patients suffering from stable angina suggest that hypocapnia does cause small ECG changes but these are not consistent and are unlikely to be of clinical importance. However, conclusions about the clinical applications of this technique cannot be made until more patients are studied.


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