Inhibition of smooth muscle proliferation by cyclic nucleotides in an organ culture of human saphenous vein

J Mol Cell Cardiol 23 (Supplement V) (1991)

Hatty Vrolix, Ivan De Scheerder,JohanVanLierde, Philip Hoersan, An Cornelis, Bilaire DaGee&, UE Gasthuisberq, Leuven,Belqius Vesselinjury dueto Microporous balloon inflations(B1) (PiccolinoR,Schneider)wascompared with conventionalBI in normalperipheral(P)and coronary(C) arteries in 10 mongreldogs.Axterioqraphywasperformed via the right carotid approachusing a 8.3PStertser quiding catheter. For P BI, a 5.0 m balloon wasused; for C BI, balloon size was 2.51f0.16~~. Vessellumenandinflated balloondiameterwereassessed usinqquantitative analysis. Hicroporous BI were performed as to obtain a 1.5 ml and1.0 ml infusion in P andC vesselsrespectively. Thereforeinflation pressureand durationin P arteries(lI=20)was4.1tO.5atm; 63.5t46.6set and4.9f1.6 atm; lllltl01.7sec in C arteries (N=29). (*%EID: lelastica interna disruption) iBm w I! PERIPBERAL : Conventional 8 0.86 t 0.08 37.5 1.06 f 0.36 p=NS Kicroporous 20 40.0 CORONARY : Conventional 11 0.85 f 0.15 18.0 66.0 p
P173 INHIBITION OF SMOOTH MUSCLE PROLIFERATION

BY CYCLIC NUCLEOTIDES IN AN ORGAN CULTURE OF HUMAN SAPHENOUS VEIN Abigail Soyombo, Andrew Newby. Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff GF4 4XN, UK Vascular smooth muscle proliferation toads to reoccluslon of saphenous vein grafts and restenosis after angioplasty. There are no clinically useful inhibitors of proliferation although endotheliumderfved pmstaglandins that elevate CAMP concentration and nitric oxide that elevates cGMP concentration probably exert physiological control. We used an established organ culture model of human saphenous vein to test the effect of analogues of cyclic nucleotides and isobutylmethylxanthine, a nonselective cyclic nucleotide phosphodiesterase inhibitor, all at 0.1 mM. Cultures were labelled with 1 @ml of [63H] thytidine for the last 24 hours of a 14 day culture period at 37%. Smooth muscle proliferation was quantifled by total thymidine incorporation, and by measurements of intimal thickness and the number of labelled nuclei in autoradlographs of 5 urn transverse paraffin-embedded sections. Condition Thymidine incorkltimal Thymidine- labelled poration (dpmAng) thickness (urn) nuclei/mm of section 1540f270 Control (n=13) 31f6 10.6ct3.1 6Br-CAMP (n=13) 720flO5’ 11f3’ 3.0i0.6' 6-Br-cGMP (n=lO) 1030f220 12f4* 6.0il.6 isobutylmethyl770f200' llf4' 4.6fl.7' xanthine (n-9) ‘p < 0.05 vs control (palred t test) All the agents tested significantly reduced intimal thickening and either reduced or tended to reduce the number of thymidine labelled nuclei and the total thymidine incorporation. The data suggest that anabgues of cyclic nucleotides or agents that increase cyclic nucleotide concentrations might be clinically useful inhibitors.

PI74 IS THE CORONARY ATHERONATOSIS OF CHOLESTEROL-FED NEW ZEALAND RABBITS A SUITABLE HHPHRIMHNTALMODEL FOR HUMANCORONARYARTRRY PLAQUES?Fleckenstein-Griin G. Thinmn F. Frey M, a.Fleckenstein A. Study Group for Calcium Antagonism, Physiol.Inst;, Hermann-Herder-Str. 7; W-7800 Freiburg. The present study examines the widespread hypothesis that the coronary atheromatosis of cholesterol-fed New Zealand rabbits is comparable to human spontaneous coronary arteriosclerosis. Therefore, we analyzed the calcium content (by atomic absorption spectrometry) and the cholesterol content (by gas chromatographic methods for free and total cholesterol) in human coronary plaques of different types (types I,II,III according to WHOclassification) and in stenosing plaques of New Zealand rabbits (fed with 2% cholesterol diet for 14 weeks). In human coronary plaques of type III (severe stenosing plaques with fatal consequences), the calcium content was found to be increased up to 80 times above normal, whereas the cholesterol content was only doubled. On the other hand, in severe stenosing plaques of cholesterol-fed rabbits,the calcium content was unchanged, whereas the cholesterol content was increased by 13-15 times above normal, indicative for a cholesterol type of atherosclerosis. We conclude that the model of coronary atheromatous lesions of cholesterol-fed New Zealand rabbits does not represent the calcium type of human arteriosclerotic coronary plaques. s.114