Can a selective adenosine A1-agonist protect against exercise-induced ischaemic left ventricular dysfunction?

Introduction. The "warm-up" effect in angina may represent ischaemic preconditioning, which is mediated by adenosine A1-receptors in most models. Protection may also occur against ischaemic left ventricular (LV) dysfunction. We investigated whether warm-up can be reproduced by a selective adenosine A1-agonist, GR79236 (Glaxo-Wellcome). Methods. 25 patients with three vessel coronary disease and normal resting LV function entered a double-blind crossover study, receiving IV GR79236 10μg/kg or placebo on mornings one week apart. Two symptom-limited supine bicycle exercise (ex) tests were performed 30 minutes apart on each day. Equilibrium radionuclide angiography (ERNA) was used to derive regional ejection fractions (REFs) for 9 LV sectors. Sectors were defined as ischaemic or nonischaemic based on whether REF fell or not during the first test following placebo. Results. During the second of two ex tests following either placebo or drug, the onset of chest pain or 1mm ST depression was delayed and occurred at a higher rate-pressure product, whilst the mean REF of ischaemic sectors increased (P<0.05). GR79236 did not affect resting or ex haemodynamic and ECG indices compared with placebo. For ischaemic sectors, the drug reduced the mean REF at rest, but increased it during the first ex test compared with placebo. Exercise test Ischaemic sectors (n=55) Noinschaemic sectors (n=89) Rest REF Exercise REF Rest REF Exercise REF Placebo 1 0.74±0.20 0.66±0.20 0.62±0.21 0.70±0.22 Placebo 2 0.74±0.19* 0.72±0.21* 0.63±0.24 0.69±0.22 Drug 1st 0.69±0.20* 0.69±0.21* 0.63±0.23 0.64±0.23* Drug 2nd 0.70±0.21 0.74±0.19*# 0.62±0.23 0.66±0.22# Data expressed as mean±SD * P<0.05 versus Placebo 1st # P<0.05 versus Drug 1st Conclusion. A selective adenosine A1-receptor agonist reduces ischaemic LV dysfunction during exercise. Warm-up protection still occurs suggesting that additional mechanisms may be involved.