In this work the roles of coronary flow (CF) and metabolism in Rb ؉ (K ؉ congener) uptake were studied. In isolated pig hearts the left anterior descending artery (LAD) was cannulated to maintain adequate perfusion of the LAD bed. Rb ؉ loading was initiated and the LAD flow was either completely stopped (no flow (NF)) or reduced to 12% (low flow (LF)), or buffer was deoxygenated without change in flow (hypoxic flow (HYP)) for 2 h. CF through the LAD was then restored to normal, or perfusion was switched to oxygenated buffer. Serial 87 Rb MR images or localized 31 P spectra were acquired to compare the Rb ؉ uptake and energetics in the left ventricular (LV) anterior (ischemic/hypoxic) and posterior (normal) walls. End-ischemic/ hypoxic 87 Rb signal intensities in the anterior wall were higher and the fluxes were greater in the HYP and LF groups than in the NF group. Phosphocreatine and ATP decreased less significantly and recovered better in the HYP and LF groups. Upon reperfusion/reoxygenation, the HYP and LF groups showed higher 87 Rb signal intensities and smaller or no infarctions in the anterior wall compared to those in the NF group. Ischemia reduces Rb ؉ uptake due to both flow limitations and metabolic inhibition of cellular transport. 87 Rubidium ion (Rb ϩ ) is a K ϩ congener that replaces K ϩ in many processes of ion transport (1-8). It contains two natural nonradioactive NMR-sensitive isotopes:87 Rb (28%) and 85 Rb (72%). 87 Rb NMR spectroscopy and imaging have been used successfully to observe K ϩ fluxes in normal and abnormal myocardium (1,3,4 -7). We have shown that Rb ϩ uptake is significantly reduced in the anterior left ventricular (LV) wall of isolated pig hearts exposed to Rb ϩ for 60 min during 120-min occlusion of the left anterior descending artery (LAD) (6). This observation is in agreement with early studies showing K ϩ loss in ischemic rat, dog, and pig hearts (9 -13), and reduced radioactive 82 Rb uptake in the ischemic dog myocardium (14). 82 Rb uptake is typically measured following bolus injection of a short-lived isotope (t 1/2 ϭ 75 s), which does not allow measurements of steady-state Rb ϩ distribution. In contrast, 87 Rb NMR measures both the uptake rate and steady-state Rb ϩ distribution. Two main factors are responsible for inhibition of Rb ϩ uptake in the ischemic myocardium: reduced Rb ϩ delivery by collateral flow to the LAD bed (2-5% of normal in pigs (15-17)) and reduced cellular uptake caused by energy deprivation (6,14). The relative contributions of these two factors could not be determined in our previous work (6). In those experiments, the ischemic damage produced by 120-min ischemia without reperfusion was reversible, as judged by normal staining of the ischemic area with triphenyltetrazolium chloride (TTC).We also found that Rb ϩ uptake in the anterior wall was considerably inhibited (threefold) when Rb ϩ was added during reperfusion, i.e., in the absence of flow limitations (18). In this case, reperfusion resulted in formation of a significant necrotic zone (lack ...