Abnormal myocardial repolarisation in response to hypoxaemia and fenoterol.
BACKGROUND
Prolongation of the QTc interval has been associated with cardiac dysrhythmias and sudden death. QTc dispersion (interlead variability in QTc interval) has recently been proposed as being a more sensitive marker of repolarisation abnormalities and shown to be a more specific index of arrhythmia risk. Although hypoxaemia and fenoterol have previously been shown to prolong the QTc interval, this does not reflect regional myocardial repolarisation abnormalities.


METHODS
Electrophysiological effects were measured at baseline and after 30 minutes steady state hypoxaemia at an arterial oxygen saturation (SaO2) of 75-80% (study 1) and at baseline then 30 minutes after inhaled fenoterol 2.4 mg (study 2). From the ECG, lead II corrected QT interval (QTc) and overall corrected QT dispersion were measured using a computer linked digitising tablet according to standard criteria.


RESULTS
QTc dispersion was increased during hypoxia compared with baseline values (mean (SE) 69 (6) ms v 50 (5) ms) and after fenoterol compared with baseline (79 (13) v 46 (4) ms), respectively. There was also an increase in QTc interval and heart rate after fenoterol (493 (23) v 420 (6) ms and 98 (3) v 71 (6) bpm, respectively). The heart rate was increased during hypoxaemia compared with baseline (78 (3) v 64 (2) bpm), but no change occurred in the QTc interval.


CONCLUSIONS
Both hypoxaemia and fenoterol cause myocardial repolarisation abnormalities in man in terms of increased QTc dispersion, but only fenoterol increased the QTc interval. This may be relevant in the aetiology of arrhythmias in patients with acute severe asthma where beta agonist therapy and hypoxaemia coexist.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D004562:Electrocardiography / Q000187:drug effects*; D004837:Epinephrine / Q000097:blood; D005280:Fenoterol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood*; D011188:Potassium / Q000097:blood
D000318:Adrenergic beta-Agonists; D005280:Fenoterol; D011188:Potassium; D010100:Oxygen; D009638:Norepinephrine; D004837:Epinephrine