QUANTITATIVE DOUBLE-TRACER DIGITALRADIOGRAPHY BASED ON DESMETHYLIMIPRAMINE DEPOSITION: APPLICATION TO STUDIES ON MYOCARDIAL PERFUSION HETEROGENEITY

Abstract

Desmethylimipramine (DMI), an α2-adrenergic antagonist, is a nearly ideal deposition tracer for evaluating the myocardial flow distribution with the least artifactual effects on microcirculation. Myocardial retentions of tritium- and iodine-125-labeled DMI (HDMI, IDMI) were confirmed to be satisfactory; the retentions of IDMI and HDMI at 1 min were 95 and 91% respectively in isolated Tyrode-perfused rabbit hearts (n=6) at a perfusion rate of 8.1 ml/min/g, and 98 and 96% respectively, in blood-perfused rat hearts (n=4) at a perfusion rate of 3.1 ml/min/g. Using these tracers combined with subtraction digitalradiography, it allowed the assessing of changes of myocardial flow distribution with 400×400 μ m 2 resolution. In blood-perfused rat hearts (n=4), the validity of this method was verified by the strong cross-correlation between regional densities of two tracers injected simultaneously (r=0.94) and the regression line having a slope close to one. Furthermore, in Tyrode-perfused rabbit hearts, the flow distributions were evaluated before and after decreasing perfusion rate moderately by 34% (n=7) and severely by 70% (n=7). Severe flow reduction increased the coefficient of variation of tracer density (CV) significantly from 19 to 25%, but CV did not change with moderate flow reduction (20 vs. 19%). Regional densities of two tracers were cross-correlated still substantially under severe low-flow perfusion (r=0.84). Accordingly, flow differences between originally high- and low-flow regions were enlarged under severe flow reduction. In conclusion, double-tracer digitalradiography based on the DMI deposition will be a potent method for the analysis of flow heterogeneity at microvascular levels.