Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment

Objectives This study was designed to examine if exercise-induced ischemia initiated late preconditioning in humans that becomes manifest during subsequent exercise and serial balloon occlusion of the left anterior descending coronary artery (LAD). Background The existence of late preconditioning in humans is controversial. We therefore compared myocardial responses to exercise-induced and intracoronary balloon inflation–induced ischemia in two groups of patients subjected to different temporal patterns of ischemia. Methods Thirty patients with stable angina secondary to single-vessel LAD disease underwent percutaneous coronary intervention (PCI) after two separate exercise tolerance test (ETT) protocols designed to investigate isolated early preconditioning (IEP) alone or the second window of protection (SWOP). The IEP subjects underwent three sequential ETTs at least two weeks before PCI. The SWOP subjects underwent five sequential ETTs commencing 24 h before PCI. Results During PCI there was no significant difference in intracoronary pressure–derived collateral flow index (CFI) between groups (IEP = 0.15 ± 0.13, SWOP = 0.19 ± 0.15). In SWOP patients, compared with the initial ETT, the ETT performed 24 h later had a 40% (p < 0.001) increase in time to 0.1-mV ST depression and a 60% (p < 0.05) decrease in ventricular ectopic frequency. During the first balloon inflation, peak ST elevation was reduced by 49% (p < 0.05) in the SWOP versus the IEP group, and the dependence on CFI observed in the IEP group was abolished (analysis of covariance, p < 0.05). The significant attenuation of ST elevation (47%, p < 0.005) seen at the time of the second inflation in the IEP patients was not seen in the SWOP patients. Conclusions Exercise-induced ischemia triggers late preconditioning in humans, which becomes manifest during exercise and PCI. This is the first evidence that ischemia induced by coronary occlusion is attenuated in humans by a late preconditioning effect induced by exercise.