Adaptation to myocardial ischemia during repeated dynamic exercise in relation to findings at cardiac catheterization

It has been suggested that the myocardium is able to recruit endogenous protective mechanisms in response to repeated ischemia and reperfusion. We set out to study whether this is manifested in patients with coronary artery disease in the form of fewer signs of myocardial ischemia during the second of two successive exercise tests and whether any relations exist between ischemia adaptation and findings at cardiac catheterization. Twenty-one patients with typical angina pectoris symptoms underwent two repeated bicycle exercise tests with identical protocols, followed by cardiac catheterization and coronary angiography the next day. The first exercise test was discontinued whenever a 2 mm ST depression in the electrocardiogram (ECG) was achieved or further exercise was limited by symptoms. The second exercise test was performed after disappearance of the symptoms or ST depression or both. Kaplan-Meier survival analysis for the appearance of a 1 mm ST depression demonstrated improved ischemia tolerance during the second test, when the required time for its appearance was significantly longer (6.5 +/- 0.8 min vs 4.5 +/- 0.5 min; p = 0.005). The maximal intensity of anginal pain was lower during the second exercise (2.2 +/- 1.0 min vs 0.7 +/- 0.3 min in Borg's scale; p < 0.001), and the time required for disappearance of the ST depression was shorter after this exercise (3.0 +/- 0.8 min vs 6.2 +/- 0.9 min; p = 0.003), with a similar tendency in the disappearance of angina. The rate-pressure product on the appearance of a 1 mm ST depression was significantly higher during the second test (17,990 +/- 1210 mm Hg x min-1 vs 15,960 +/- 869 mm Hg x min-1; p = 0.009). Eighteen of the patients had three-vessel disease, as evidenced by coronary angiography, and the change in the time required for the appearance of a 1 mm ST depression in the repeated exercise tests was inversely correlated with the severity of the left anterior descending (LAD) coronary artery obstruction (r = -0.61; p = 0.006) and left ventricular end-diastolic pressure (r = -0.50; p = 0.03). No significant correlation with the degree of collateral vessels was found. We conclude that most patients with extensive coronary artery disease are able to increase their tolerance of ischemia during repeated dynamic exercise and that increased vasodilation and oxygen delivery are the major mechanisms for this warm-up phenomenon. On the other hand, collaterals visible in routine resting anglography do not predict the degree of adaptation to ischemia during repeated dynamic exercise.