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CLINICAL STUDY

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

^* Department of Cardiology, King’s College London, The Rayne Institute, St. Thomas’ Hospital, London, United Kingdom

Manuscript received April 29, 2002; revised manuscript received October 15, 2002, accepted November 19, 2002.

^* Reprint requests and correspondence: Prof. Michael S. Marber, Department of Cardiology, King’s College London, The Rayne Institute, St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK.
mike.marber{at}kcl.ac.uk

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.

Abbreviations and Acronyms   ANCOVA = analysis of covariance   ANOVA = analysis of variance   ATP = adenosine triphosphate   CFI = collateral flow index   ECG = electrocardiogram   ETT = exercise tolerance test   HR = heart rate   IEP = isolated early preconditioning   iNOS = inducible nitric oxide synthase   LAD = left anterior descending coronary artery   PCI = percutaneous coronary intervention   RPP = rate pressure product   SWOP = second window of protection

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