Ischemic preconditioning in unstable coronary syndromes: evidence for time dependence

We hypothesized a time-dependent relation between angina occurring spontaneously before percutaneous transluminal coronary angioplasty (PTCA) and the likelihood of an ischemic response during initial balloon occlusion. We further hypothesized that the ability to elicit the "classic" mode of PTCA-related preconditioning would vary with the interval from clinical angina to PTCA.

Antecedent angina represents a potential for myocardial preconditioning in unstable ischemic coronary syndromes.

We studied 67 patients with Braunwald class III unstable coronary syndromes undergoing PTCA. The interval between the last spontaneous episode of angina preceding PTCA and initial balloon inflation was categorized as follows: 0 to 6 h; 6 to 12 h; 12 to 24 h; and >24 h.

Across the various intervals, there was a significant difference (p = 0.004) in the proportion of patients with an absent ischemic response during the first balloon inflation (0 to 6 h, 50%; 6 to 12 h, 35%; 12 to 24 h, 23%; and >24 h, 4%). There was, however, no difference between the first and second inflations in the proportion of patients with a diminished ischemic response until 6 to 12 h (p = 0.017) had elapsed since the last spontaneous episode of angina. Patients whose angina last occurred >24 h before the first inflation showed the greatest inducibility of PTCA-related preconditioning.

Strong evidence exists for the occurrence of ischemic preconditioning in unstable coronary syndromes. Although the protective effect of spontaneous angina appears to wane beyond 6 h, recovery of preconditioning occurs from 6 to 12 h. Thus, preconditioning can be reinduced during PTCA with a marked potentiation of the effect at 24 h. This suggests an underlying time-dependent mechanism with a physiologic "half-life" of 6 to 12 h.