Increases in ectosolic 5'-nucleotidase activity and adenosine release are primarily responsible for the infarct size-limiting effect of ischemic preconditioning. Exposures to adenosine during the ischemic preconditioning procedure and enhanced release of adenosine during reperfusion synergistically contribute to the infarct size-limiting effects.

We conclude that activation of ecto-5'-nucleotidase and protein kinase C contributes to the infarct size-limiting effect of ischemic preconditioning.

We have reported that ischemic preconditioning may limit infarct size by increasing 5'-nucleotidase activity. The present study tested whether alpha1-adrenoceptor stimulation in ischemic preconditioning mediates the infarct size-limiting effect through augmentation of 5'-nucleotidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 dogs. Then the coronary artery was occluded for 90 min followed by 6 h of reperfusion. Infarct size normalized by risk area was smaller after ischemic preconditioning than in the control group (40.6±2.3 vs 6.7±2.0%, P < 0.001), even though no difference existed in endomyocardial collateral flow during ischemia (8.7±1.0 vs 8.9±1.0 ml/100 g per min). Ectosolic and cytosolic 5'-nucleotidase activity was increased after ischemic preconditioning. However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning (infarct size: 42.8±3.7%). Intermittent alpha1-adrenoceptor stimulation by methoxamine mimicked the increase in 5 '-nucleotidase activity and the infarct size-limiting effect, which were abolished by alpha, beta,-methyleneadenosine 5'-diphosphate. Identical results were obtained in the conscious model (n = 20). Therefore, we conclude that increases in ectosolic 5'-nucleotidase activity due to alpha,-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic preconditioning. (J.

We have developed a monochromatic synchrotron radiation-excited system for two-dimensional mapping of x-ray fluorescence evoked from heavy element-loaded microspheres, which can evaluate myocardial blood flow in small contiguous regions with a small methodological error: 10.8 +/- 2.4% of the average of difference of the dual flow for 7- to 10-mg myocardial tissue (4 dogs). The fractal D value obtained from the slope of the log relative dispersion-log mass plot was 1.21 +/- 0.08 for a voxel size of 7 to 1260 mg (5 dogs) and that for a voxel size of 2.5 to 40 mg (1.12 +/- 0.06) was smaller than that for a voxel size of 40 to 1280 mg (1.25 +/- 0.14, P < .05, ANOVA, 4 dogs). The distance-correlation coefficient relation for paired myocardial regions was attenuated (correlation analysis), and the correlation coefficients between the original grouping and the two aggregates of the adjacent regions were dissociated (extended correlation analysis) under reduction of coronary perfusion pressure (6 dogs). Suppression of myocardial contraction with lidocaine (3 dogs) and vasodilation with adenosine partly improved the distance-correlation coefficient relation under reduced coronary perfusion pressure. Thus, an x-ray fluorescence system designed for precise flow measurement shows that the fractal nature of local flow distribution can be extended into regions smaller than previously reported, that in these regions the flow becomes more homogeneous, and that the self similarity and continuity of local flow are attenuated by the reduction of coronary perfusion pressure and improved by contractile suppression and coronary vasodilation.

We tested the hypothesis that the opening of ATP-sensitive K+ channels contributes to activation of ectosolic 5'-nucleotidase and the infarct size-limiting effect of ischemic preconditioning. In open-chest dogs, the left anterior descending coronary artery was occluded four times for 5 min each, separated by a 5-min period of reperfusion (ischemic preconditioning, n = 8). After this procedure, the coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Infarct size was smaller in this group than in the group (control, n = 8) with a 45 min interval instead of the ischemic preconditioning procedure (40.1 +/- 3.9 vs. 6.4 +/- 1.9%). Glibenclamide blunted the infarct size-limiting effect of ischemic preconditioning (infarct size, 37.3 +/- 5.8%; n = 7), and transient exposures to cromakalim and nicorandil mimicked it [infarct size, 10.1 +/- 3.1 (n = 7) and 11.1 +/- 2.7% (n = 8), respectively]. Ectosolic and cytosolic 5'-nucleotidase activity increased in the ischemic preconditioning group compared with that in the control group; this preconditioning-induced increase in 5'-nucleotidase activity was blunted by glibenclamide (n = 5) and mimicked by cromakalim (n = 5) and nicorandil (n = 5). The infarct size-limiting effect due to cromakalim and nicorandil was blunted by alpha,beta-methyleneadenosine 5'-diphosphate, an inhibitor of ectosolic 5'-nucleotidase [infarct size, 37.7 +/- 5.6 (n = 9) and 36.8 +/- 4.8% (n = 7), respectively] and 8-sulfophenyltheophylline (infarct size with cromakalim, 44.7 +/- 4.6%; n = 7). We conclude that activation of ectosolic 5'-nucleotidase due to the openers of ATP-sensitive K+ channels contributes to the infarct size- limiting effect of ischemic preconditioning.