Effect of a cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, on myocardial reperfusion injury.

ABSTRACT

A new cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, was examined to see whether myocardial reperfusion injury could be reduced in a setting of cardioplegic arrest through its antiaggregation effect on leukocytes. Isolated rabbit heart models with whole blood perfusion were used, and 18 hearts were divided into three groups according to the reperfusion method: control (G-1, n = 5), DN-9693 (G-2, n = 7), and leukocyte depletion (G-3, n = 6). The hearts were subjected to 120 minutes of cold global ischemia under crystalloid cardioplegia followed by 30 minutes of reperfusion. A dose of 20 micrograms.kg-1.min-1 of DN-9693 was administered in G-2, and a leukocyte removal filter was used in G-3 during reperfusion. Ultrastructural changes in mitochondrial injuries, intracellular edema, and capillary injuries of the myocardium showed worse changes in G-1 than in G-2 and G-3. Under microscopic study, the intracapillary leukocyte count was significantly higher in G-1 than in G-2 and G-3. Recovery of rate-pressure product, left ventricular developed pressure, and coronary flow were significantly better in G-2 and G-3 than in G-1. There were no significant differences between G-2 and G-3 for all these indices. These results indicate that reperfusion with leukocyte-depleted blood attenuates reperfusion myocardial injury and DN-9693 has a comparable myocardial protective effect with possible inhibition of leukocyte aggregation.