Effect of ischemia-related metabolic factors on thallium exchange in cultured rat myocardial cells

Failure of the myocardium to take up Thallium-201 is widely used as a diagnostic marker for ischemia or infarction. Although this is commonly related to a reduction in coronary flow or myocardial perfusion, other possible metabolic factors are poorly understood. The present studies investigated the influence of various interventions, designed to simulate the metabolic consequences of ischemia, on thallium-204 uptake and release in cultured myocardial cells. In these cells, where thallium exchanged rapidly (t 1/2 = 5 min), and 60% of thallium uptake occurred via the sodium pump, thallium uptake was markedly influence by changes in extracellular potassium. Increasing extracellular potassium from a physiologic level of 5 mM to those levels reported to occur in ischemic myocardium (7.5 mM to 18mM) effected a 25% to 60% reduction in thallium influx. The decrease in thallium influx produced by increasing extracellular potassium was rapid (30 sec.) in onset and readily reversible by restoring extracellular potassium towards normal. Changes in extracellular pH in the range 6.4 to 8.0 had no demonstrable effect on thallium uptake despite the fact that this was accompanied by similar, although less marked, changes in intracellular pH. Addition of adenine nucleosides, adenosine, inosine and hypoxanthine, to the incubating solution in concentrations from 1 nM to 0.1 mM had no effect on thallium influx or efflux in the cells. This observation held true even when 10 μM dipyridamole was used to inhibit nucleoside uptake by the cells. Addition of 1 mM 2,4-dinitrophenol or 4 mM potassium cyanide to the cultures maximally inhibited 42% of the thallium influx within 30 min. Similarly, treatment with 0.1 mM iodoacetic acid decreased thallium influx by 38%. The combination of dinitrophenol and iodoacetic acid almost completely abolished active thallium influx, although the effect developed slowly over a 30 min. period. This suggests that in these cells the membrane sodium pump derives energy from both oxidative phosphorylation and glycolysis. Overall, the results indicate that failure or reduction of thallium uptake can result from local increases in extracellular potassium or inhibition of oxidative phosphorylation and/or glycolytic pathways, all of which may be present in the ischemic myocardium.