Effects of flow and energy metabolism on injury and Rb uptake in pig hearts: An 87Rb and 31P NMR study

Abstract

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 ...

Imaging of ischemia and infarction in blood‐perfused pig hearts using 87Rb MRI

“…87 Rb MR spectroscopy (1–6) and imaging (7–10) were used to monitor K + transport and distribution in isolated hearts under normal and pathological conditions. Two important properties of rubidium ion were utilized in these studies.…”

The effects of drugs modulating K+ transport on Rb+ uptake and distribution in pig hearts following regional ischemia: 87Rb MRI study

“…Indeed, we have recently shown that low flow ischemia and regional hypoxia result in a decrease in Rb image intensity in the affected area to 75-80%, which corresponds to reversibly damaged tissue. 10 …”

“…At the same time the infarction size was less than half of the area at risk ($40% of the maximum). [8][9][10] Note that in the in vivo pig model of cardiac infarction, periods of 120 min occlusion [20][21][22] or longer 23 resulted in formation of infarct areas of 50-95% of the area at risk upon reperfusion.…”

“…This duration of the LAD occlusion used in our previous studies [8][9][10] was chosen for the following reasons. Upon reperfusion it provides large, clearly cut transmural infarctions easily detectable by low-resolution 87 Rb imaging.…”

“…[2][3][4][5] In particular, we have developed a 87 Rb MR imaging method that allows spatial kinetics of Rb uptake and distribution to be determined in the isolated pig hearts. [8][9][10] The method was applied to visualize areas of ischemic damage, [8][9][10] which are known to lose K . [11][12][13] Ischemia-reperfusion damage produced by 120 min occlusion of the left anterior descending artery (LAD) in pig hearts and subsequent reperfusion results in severe inhibition of Rb uptake, over a 60-120 min period, in the area at risk.…”