Angina is characterized by brief periods of ischemia followed by reperfusion; the cumulative effect of these episodes on energetics of the myocardium has not been fully elucidated. This study used an in vivo feline model for the assessment of high-energy phosphate compounds during brief sequential periods of ischemia and reperfusion. Nine adult, open-chest, anesthetized cats were prepared with a reversible occluder around the proximal left anterior descending artery and a 1.2-cm-inside diameter coil sutured on the myocardial surface in the distribution of the left anterior descending coronary artery. Levels of PCr, Pi, and ATP (beta-phosphate signal) were measured by 31P MRS in a GE CSI 2-T NMR spectrometer/imager. Measurements were obtained during a control period and during three successive occlusion-deocclusion periods of roughly 12 and 20 min' duration, respectively. The last deocclusion period was observed for 60 min. Electron microscopy was performed in two animals. PCr declined (P less than 0.01) rapidly following each occlusion to 51 +/- 5.2% (occlusion 1), 53 +/- 5.8% (occlusion 2), and 48 +/- 5.7% (occlusion 3) of the control value by 6 min. Pi rose (P less than 0.01) with the three sequential occlusions to 253 +/- 46, 288 +/- 57, and 277 +/- 46%, respectively. PCr and Pi returned to baseline promptly with reperfusion, while ATP showed a gradual decline throughout the experiment, decreasing to 77 +/- 7.2% of control at the end of the last reperfusion (P less than 0.05). Although PCr returned to baseline during reperfusion, ATP did not, suggesting a reduction in the nucleotide pool. These findings indicate that the repeated episodes of ischemia, which are insufficient to produce necrosis, can have an effect on myocardial high-energy phosphate metabolism as evidenced by mild depletion of ATP.