EVALUATION OF THE PROTECTIVE EFFECT OF A NOVEL PROSTACYCLIN ANALOG ONMESENTERIC CIRCULATION FOLLOWING WARM ISCHEMIA

The protective effect of a novel prostacyclin (PGI(2)) analog, OP-2507 , on mesenteric circulation was investigated in a canine warm ischemia model. In 20 mongrel dogs, the entire portion of the intestine suppli ed by the superior mesenteric artery (SMA) and drained by the superior mesenteric vein (SMV) was completely isolated, maintaining the blood and lymph vessels intact. Sixty or 120 min of complete warm ischemia ( WI) of the intestine was induced by clamping SMA and SMV, followed by reperfusion for 120 min. Animals were divided into five groups (each n = 4): group 1, sham operation; group 2, 60 min WI; group 3, 120 min W I; group 4, 60 min WI with PGI(2) analog administration; group 5, 120 min WI with PGI(2) analog administration. The analog was administered at a rate of 6 mu g . kg(-1). h(-1) immediately after laparotomy until the end of the observation period. Mean arterial pressure, SMA blood flow (SMABF), SMV pressure were monitored and total mesenteric vascula r resistance (TMVR) was calculated. To evaluate the endothelial activa tion, endothelin, which is secreted from the endothelium under hypoxic stress, was assayed from blood samples of SMV. None of the animals sh owed significant changes in mean arterial pressure. In groups 2 and 3, SMABF decreased significantly to les than 60% of preoperative value ( 15 ml . kg(-1). min(-1)) and TMVR significantly increased from 8.1 and 7.3 mm Hg . ml(-1). kg . min before WI to 14.0 and 16.4 mm Hg . ml(-1 ). kg . min after 120 min reperfusion, respectively, resulting in dela yed hypoperfusion. In contrast, in groups 4 and 5, SMABF increased to over 110% of preoperative level, while TMVR declined from 7.8 and 8.4 mm Hg ml(-1) kg min before WI to 6.2 and 6.3 mm Hg ml(-1) kg min after 120 min reperfusion. After 60 min reperfusion, SMABF and TMVR showed a significant difference between the treated and nontreated groups. On ly in group 3, high endothelin concentrations (over 20 pg/ml) were obs erved even after 120 min reperfusion. It was concluded that the PGI(2) analog was able to suppress the endothelial activation and the distur bance of mesenteric circulation caused by WI and reperfusion.