Delayed attenuation of myocardial ischemia with repeated exercise in subjects with stable angina: a possible model for the second window of protection?

Aims: A delayed myocardial protection extends between 24 and 96 h after ischemic preconditioning in animals. To test for this phenomenon in humans, subjects with stable angina were subjected to exercise test-induced myocardial ischemia and the effect of this preconditioning ischemic insult on the exercise-induced myocardial ischemia with the re-exercise after 24-96 hours was studied. Methods and results: Forty-eight males with a history of infarction and positive exercise test were recruited to the study. After baseline symptom-limited exercise test, the subjects were randomized to four experimental groups (n = 12/group). The groups were allowed to recover for 24 h, 48 h, 72 h or 96 h before performing the second exercise test. Variables analyzed were heart rate-systolic blood pressure product at 1 mm ST segment depression, time to 1 mm ST segment depression, maximum ST segment depression, exercise duration, and the total ischemic time. There were no intergroup differences in baseline values for these variables. All variables were significantly improved at 24 h, the improvement peaked usually at 48 h (maximum increase in the variables by 31-46%), and the variables returned to baseline by 96 h after the first test. Conclusions: The exercise-induced ischemia caused transient attenuation of myocardial ischemia with re-exercise. Although the time-window and the timecourse of this effect shows striking resemblance to those of the delayed preconditioning in animals, its mechanism remains speculative. The most probable mechanisms that may be involved include increased myocardial perfusion and/or some adaptive changes in the myocardium, the delayed preconditioning being one possibility.