Effects of a phosphodiesterase 3 inhibitor, olprinone, on rhythmical change in tension of human gastroepiploic artery

The gastroepiploic artery, used widely as a conduit in coronary artery bypass grafting, has high vasospasticity. The aims of this study were to examine the vasorelaxant effects of three phosphodiesterase 3 (PDE3) inhibitors, olprinone, milrinone and amrinone, on isolated gastroepiploic arterial preparations in comparison with a calcium channel blocker diltiazem, and to confirm the mRNA expression of PDE3A isoenzyme using reverse transcription-polymerase chain reaction (RT-PCR) in the human gastroepiploic artery isolated from stomach removed in cancer surgery. In endothelium-denuded gastroepiploic arterial preparations, phenylephrine (100 μM) produced spontaneous, rhythmical changes in tension consisting of repeated contraction and relaxation. Olprinone at a concentration of 10 μM (n = 6) significantly inhibited the frequency (2.7 ± 1.1 times/30 min vs. 6.2 ± 0.7 times/30 min in the vehicle group), maximum tension (1.7 ± 0.6 g vs. 3.6 ± 0.6 g in the vehicle group) and minimum tension (0.6 ± 0.2 g vs. 1.7 ± 0.3 g in the vehicle group) of rhythmical changes. Such potency is comparable to that of diltiazem, but is stronger than milrinone and amrinone. RT-PCR using PDE3A- or PDE3B-specific oligonucleotide primer demonstrated the existence of PDE3A sequence in the gastroepiploic artery. These results suggest that olprinone, a potent PDE3A inhibitor, would be suitable for protecting against perioperative spasm during coronary artery bypass graft surgery.