The myocardial transmicrovascular transport of thallium-201 (201Tl) and technetium-99m hexakis(2-methoxyisobutylisonitrile) (MIBI) were compared during variable blood flow levels in nine blood-perfused, isolated rabbit hearts. Seventeen injections of radiolabeled albumin and EDTA as well as 201Tl and MIBI were performed by indicator-dilution techniques. When coronary flow was varied from 0.52 to 3.19 ml/g/min, myocardial extraction for MIBI averaged 0.38 +/- 0.09 (SD) whereas 201Tl myocardial extraction averaged 0.73 +/- 0.10 (p less than 0.001). Net extraction, which was calculated using end points of 1.8-4.9 minutes, averaged 0.41 +/- 0.15 for MIBI and was less than the 201Tl net extraction of 0.57 +/- 0.13 (p less than 0.001). The mean capillary permeability-surface area product for MIBI (0.44 +/- 0.13 ml/g/min) was one third of 201Tl (1.30 +/- 0.45 ml/g/min; p less than 0.001). However, parenchymal cell permeability-surface area product for MIBI (47.58 +/- 25.85 ml/g/min) was much higher than 201Tl (6.52 +/- 6.51 ml/g/min; p less than 0.0001), and apparent cellular volume of distribution for MIBI (15.15 +/- 3.31 ml/g) was also higher than 201Tl (10.19 +/- 4.00 ml/g; p less than 0.01). These data suggest that capillary permeability for 201Tl is greater than MIBI, but the reverse is true at the parenchymal cell wall. In addition, a new blood-perfused preparation is used for indicator-dilution techniques, and previously developed modeling analyses are also extended to these experiments.

Patel RA, Glover DK, Broisat A, Kabul HK, Ruiz M, Goodman NC, Kramer CM, Meerdink DJ, Linden J, Beller GA. Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A2A receptor agonist.

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Effects of no-flow ischemia (NFI) and reperfusion (RPF) on myocardial extraction and retention of technetium-99m hexakis(2-methoxyisobutylisonitrile) (sestamibi) and thallium-201 were investigated in 12 isolated, blood-perfused rabbit hearts with isotope dilution studies at constant coronary perfusion. After a control injection of tracers, NFI was induced for 30-60 minutes. After coronary reflow, repeat tracer injections were given at early RPF (5-15 minutes of RPF) and late RPF (40-60 minutes of RPF). After NFI-RPF, maximal fractional extraction and capillary permeability-surface area product increased for sestamibi (from +39%o to 69o) and decreased for thallium (from -14% to -68%). Net extraction was 33% lower for sestamibi than for thallium at control, 13% lower at early RPF, and 90% higher than thallium at late RPF. Interstitial-myocyte exchange estimates were always higher for sestamibi than for thallium and increased for both with NFI-RPF (sestamibi, from 57.4 to 122.4 ml/min/g; thallium, from 3.1 to 22.3 ml/min/g). Intramyocyte volumes of distribution were higher for sestamibi than for thallium (>200% at control, 800-1,000% with RPF), and NFI-RPF had opposite effects on the two tracers (late RPF vs. control: +28% for sestamibi, -50%o for thallium). Our Accurate interpretation of myocardial perfusion images would benefit from a thorough understanding of the capillary-tissue exchange process of the imaging tracer and the factors that affect this exchange. Our previous studies7 demonstrated that sestamibi, like thallium, was taken up by the myocardium in proportion to flow but that peak sestamibi extraction and capillary permeability were significantly less than for thallium. However, myocyte permeability and volume of distribution was higher for sestamibi than for thallium.7 Little is known about the effects of altered cell metabolism on sestamibi uptake in the heart. Cell culture studies8 have revealed that myocyte uptake of sestamibi and thallium are inhibited during hypoxia and that thallium is more affected than sestamibi. In other reports,9 thallium uptake by the myocardium was independent of tissue viability, which seems to contradict cell culture evidence that a ouabain-sensitive mechanism (i.e., Na+, K+-ATPase) contributes about 60% of thallium uptake.'0"11To critically evaluate effects of myocardial metabolic function on the transport of sestamibi and thallium, an isolated heart model was used to deterby guest on

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