BOUNDARY-LAYER INFUSION OF NITRIC-OXIDE REDUCES EARLY SMOOTH-MUSCLE CELL-PROLIFERATION IN THE ENDARTERECTOMIZED CANINE ARTERY

To evaluate the direct effect of nitric oxide (NO) on vascular smooth muscle cell (SMC) proliferation in vivo, we used an expanded polytetra fluoroethylene (ePTFE)-based local infusion device to deliver an NO do nor, proline/NO (PROLI/NO), to the luminal boundary layer of endartere ctomized artery and the distal anastomosis of the graft in a canine mo del. Once delivered to the blood, PROLI/NO releases NO by a mechanism involving pH-dependent decomposition. Six dogs underwent bilateral fem oral artery endarterectomies. ePTFE infusion devices, blindly primed w ith PROLI/NO to one artery or proline to the contralateral vessel, wer e anastomosed proximal to the injured segments so that each animal ser ved as its own control. PROLI/NO or proline was continuously delivered for 7 days from an osmotic reservoir, through the wall of the graft i nfusion device. Euthanasia was carried out at 7 days, and the processe d specimens were blindly analyzed for SMC proliferation at both graft anastomoses and endarterectomized segments by a bromodeoxyuridine inde x assay. All dogs survived with no clinical side effects. In comparing the treated and control vessels, NO released from PROLI/NO significan tly reduced SMC proliferation by 43% (13.24 +/- 1.24% versus 23.24 +/- 1.01%, P = 0.004) at the distal anastomoses and by 68% (10.58 +/- 1.6 3% versus 25.17 +/- 3.39%, P = 0.007) at endarterectomized segments. H owever, there was no significant difference in blood flow measurements between treated and control arteries (56.25 +/- 6.50 ml/min versus 46 .50 +/- 3.20 ml/min, P = 0.094). These data demonstrate that local bou ndary layer infusion of NO released from PROLI/NO significantly reduce s SMC proliferation in injured arteries with no effect on regional blo od flow. This study suggests a new strategy to inhibit early SMC proli feration in injured arteries and probably to control intimal hyperplas tic lesion formation in the manipulated vessels. (C) 1997 Academic Pre ss.