Transmural distribution of calcium accumulation and glucose uptake in the calcium paradox in the rat left ventricle

Abstract

The calcium paradox was induced in the isolated perfused rat heart and the transmural distributions of glucose uptake and calcium accumulations were determined using 2-deoxy-D-[ 3H]glucose and 45Ca 2+ as tracers. The regional distribution of coronary flow was measured using radiolabelled microspheres. A significant transmural gradient was observed in left ventricular glucose uptake both in the control and the calcium paradox hearts: subendocardial and subepicardial glucose uptake rates were 5.70 ± 0.65 μmol/min/g protein (mean ± s.e.m.) and 4.29 ± 0.35 μmol/min/g protein ( P < 0.05) in the control hearts, and 8.64 ± 0.79 μmol/min/g protein and 4.09 ± 0.71 μmol/min/g protein ( P < 0.01) in the paradox hearts. This increase in subendocardial glucose uptake in the calcium paradox was also significant ( P < 0.05), while the average left ventricular calcium accumulation was about 10-fold in the paradox hearts compared to the controls ( P < 0.001). A steep transmural gradient was observed in the paradox hearts, calcium influx being 4.72 ± 0.57 μmol × 10 −1/min/g protein in the subendocardium and 14.02 ± 0.93 μmol × 10 −1/min/g protein in the subepicardium ( P < 0.001). The subendocardium received initially 30% more perfusion than subepicardium ( P < 0.01), but the subendocardial flow during the calcium depletion and replenishment periods was only 40% of that in the subepicardium ( P < 0.001) and the average myocardial flow was reduced by c. 60% ( P < 0.001). The data show clear transmural differences in the alterations associated with the calcium paradox. This suggests that the calcium paradox induced myocardial injury is unevenly distributed across the left ventricular wall, this uneven distribution possibly being due to regional differences in the damage of mitochondrial energy production.