Background: The “warm up” effect in angina may represent ischaemic preconditioning, which is mediated by adenosine A1 receptors in most models. Objective: To investigate the effect of a selective A1 agonist, GR79236 (GlaxoSmithKline), on exercise induced angina and ischaemic left ventricular dysfunction in patients with coronary artery disease. Design: A double blind crossover study. Patients: 25 patients with multivessel coronary artery disease. Interventions: On mornings one week apart, patients received intravenous GR79236 10 μg/kg or placebo, and then carried out two supine bicycle exercise tests separated by 30 minutes. Equilibrium radionuclide angiography was done before and during exercise. Results: The onset of chest pain or 1 mm ST depression was delayed and occurred at a higher rate–pressure product during the second exercise test following either placebo or GR79236. Compared with placebo, GR79236 did not affect these indices during equivalent tests. GR79236 reduced resting global ejection fraction from (mean (SD)) 63 (7)% to 61 (5)% (p < 0.05) by a selective reduction in the regional ejection fraction of “ischaemic” left ventricular sectors (those where the ejection fraction fell during the first exercise test following placebo). Ischaemic sectors showed increased function during the second test following placebo (72 (21)% v 66 (20)%; p = 0.0001), or during the first test following GR79236 (69 (21)% v 66 (20)%; p = 0.0001). Sequential exercise further increased the function of ischaemic sectors even after drug administration. Conclusions: GR79236 failed to mimic the warm up effect, and warm up occurred even in the presence of this agent. This suggests that ischaemic preconditioning is not an important component of this type of protection. The complex actions of the drug on regional left ventricular function at rest and during exercise suggest several competing A1 mediated actions.

OBJECTIVES The goal of this study was to investigate whether the "warm-up" effect in angina protects against ischemic left ventricular (LV) dysfunction.BACKGROUND After exercise, patients with coronary disease demonstrate persistent myocardial dysfunction, which may represent stunning, as well as warm-up protection against further angina, which may represent ischemic preconditioning. The effect of warm-up exercise on LV function during subsequent exercise has not been investigated.METHODS Thirty-two patients with multivessel coronary disease and preserved LV function performed two supine bicycle exercise tests 30 min apart. Equilibrium radionuclide angiography was performed before, during and up to 60 min after each test. Global LV ejection fraction and volume changes and regional ejection fraction for nine LV sectors were calculated for each acquisition.RESULTS Onset of chest pain or 1 mm ST depression was delayed and occurred at a higher rate-pressure product during the second exercise test. Sectors whose regional ejection fraction fell during the first test showed persistent reduction at 15 min (68 +/- 20 vs. 73 +/- 20%, p < 0.0001). These sectors demonstrated increased function during the second test (71 +/- 20 vs. 63 +/- 20%, p = 0.0005). The reduction at 15 min and the increase during the second test were both in proportion to the reduction during the first test. Effects on global function were only apparent when the initial response to exercise was considered.CONCLUSIONS The warm-up effect is accompanied by protection against ischemic regional LV dysfunction. The degree of stunning and protection after exercise is related to the severity of dysfunction during exercise, consistent with results from experimental models. (J Am Coil Cardiol 2001; 37:705-10) (C) 2001 by the American College of Cardiology.