(201)Tl and (99m)Tc-MIBI retention in an isolated heart model of low-flow ischemia and stunning: evidence of negligible impact of myocyte metabolism on tracer kinetics

Abstract

It is not known whether cellular metabolic disorders play a role in the decreased tracer uptake that is documented by conventional SPECT during low-flow ischemia or stunning. This study sought to determine the impact of low-flow ischemia and stunning on the kinetics of (201)Tl and MIBI across the plasma membrane of myocytes.

Methods: The global myocardial retention (Rf) of (201)Tl and MIBI was determined in isolated working hearts from rabbits, perfused with red blood cell-enhanced solution. Experiments were performed in normoxia, with physiological values of coronary flow (N; n = 16); in low-flow ischemia, with a >50% reduction of coronary flow and a > or =20-mm Hg fall in systolic left ventricle pressure (L; n = 15); and in stunning, with 15 min of acute ischemia followed by reperfusion (S; n = 15). Concentration ratios across the plasma membrane of myocytes were also determined for both tracers and expressed as Ci/Cc, where Ci is interstitial activity determined with microdialysis, and Cc is activity from cellular space determined from Rf and Ci values.

Results: There was a slight increase in average values of Ci/Cc in ischemia, but not in stunning, for (201)Tl (L, 0.011 +/- 0.006 vs. N, 0.006 +/- 0.004 [P < 0.05]; S, 0.007 +/- 0.004 vs. N [not significant]) and for MIBI (L, 0.011 +/- 0.008 vs. N, 0.005 +/- 0.004 [P < 0.05]; S, 0.005 +/- 0.003 vs. N [not significant]). Moreover, ischemia and stunning had no deleterious effects on the average values of global myocardial retention for (201)Tl (L, 0.63 +/- 0.09 vs. N, 0.50 +/- 0.14 [P < 0.05]; S, 0.59 +/- 0.10 vs. N [P < 0.05]) or for MIBI (L, 0.45 +/- 0.10 vs. N, 0.31 +/- 0.09 [P < 0.05]; S, 0.41 +/- 0.12 vs. N [P < 0.05]). In fact, these values were significantly enhanced in the 2 situations.

Conclusion: The kinetics of (201)Tl and MIBI across the plasma membrane of myocytes were affected only poorly by low-flow ischemia and not at all by stunning, without any deleterious effects on myocardial retention of both tracers. During low-flow ischemia or stunning, therefore, the information provided by (201)Tl or MIBI SPECT is expected to depend on myocardial perfusion but not on cellular metabolic disorders.