Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery
BACKGROUND The warm-up phenomenon has been considered to trigger preconditioning. We investigated whether repeated exercise treadmill tests in humans are capable of inducing adaptation to ischemia by triggering both the early and late phase of preconditioning. METHODS In 25 consecutive patients with stable coronary artery disease, four repeated treadmill tests were performed. Thirty minutes following the first test (T1) a second one was performed (T2), followed 6 h later by a third test (T3). Twenty-four hours later all patients were subjected to a fourth exercise test (T4). In every fifth patient, simultaneous echocardiographic examination was performed at the time of the exercise tests in an attempt to reveal ischemic abnormalities. RESULTS At baseline there was no difference between the variables. At ST segment depression >1.5 mm, the rate-pressure product (RPP) was higher in T2 and T4 (231.3+/-17.9 and 232.6+/-15.8 mm Hg s 10(2)) than in T1 and T3 (210+/-17 and 210.2+/-16.7 mm Hg s 10(2)), p<0.001. Additionally, time to the onset of chest pain was longer in T2 and T4 (430.8+/-60.5 and 438+/-47 s) than in T1 and T3 (345.6+/-69 and 345.6+/-58 s), p<0.001. At peak exercise, the RPP was higher in T2 and T4 (278.6+/-21.6 and 278.3+/-19.6 mm Hg s 10(2)) than in T1 and T3 (255.6+/-23.1 and 256.6+/-23 mm Hg s 10(2)), p<0.001. The wall motion score index was higher in T1 and T3 (1.65+/-0.17 and 1.53+/-0.16) than in T2 and T4 (1.3+/-0.07 and 1.37+/-0.1), p<0.001. CONCLUSION By using repeated exercise treadmill tests both the early and late phase of protection can be obtained.