64 Abstracts The Journal of Heart and Lung Transplantation January 1999 118 THE IMPACT OF EARLY MYCCARDIAL -IN EXPRESSION ONFUNCTIONALANDM ORpHaoGIcAL CORONARY ALTERATIONS DURING FOLLOW-UP IN CARDIAC TRANSPLANT BEcIPIENTs. M. Weis, S.M. Wildbirt, C. S&&e, W.P. Wolf G. Rieder, U. Wilkt-Lampen, RM Amndt, G. En&s, B.M. Meiser, W. van Scheidt Klinkan Gm&ak& uoive&yofMlmich,Germany Endothelin (ET) opposes the effects of NO and plays a signiiicant role as a modulator of coronary vascular reactivity in the early stages of arteriosclemsis. We have previously detected that coronary endothelial dysbction at&r HTx is associated with imxeased myocardial ET mRNA expression. However, the impact of early ET and eNO.S-activation on development of fimctional and morphological coronary alterations during follow-up is onknown. M&&F: We investigated the imp& of myccudkl ET and e.NOS-gene (RT- FcR)aqaersioasweuasETandniaioitritc/llitrateplasmaleveJs(aortaand conMalysinus;RIA,Gliess)ondevelopneatofmotplmlogicalandtional comllary chaoges in 42 canlbc trlmjht recipients (cm) early (Immth) and 12 months atW ITTx. Epkmdial (QCA) and tlliawascular (ic Dqpler) endothelimu~ (acetylchdine ad eJl&ddimll-w (adenosine) %atlmc&-fmction was studied stxpendauy. MJS uas perbmled to&tennimintimal~. Resuk Signi&am ET uptake by the heart (ao&-na~~ sinus plasma level ~1~vml)wasaoticedearlyand~followupinthemaprityof~r grO.001). Endotb&mn+eakt flow hlCXWSdU?iUgfdlowupWariacrsely correlated to earh amlic m-led.5 (l=xl).38:D<o.o5). cm with newhf det&med aninuwsedETkRNAkqxes&nswreatb&ineaqaredu,patie&with no tbKtional and lllo@loiogical chauges over time (2.8il.O versus 1.7kO 8; 6.03). Inprtdy, eNOS-mRNA expressian and Ilitrawtite levels at basdinewRcompoableincltwithandwithoutdeve~ofintimal thi&dtgmM%readotbelial~ndmingibuow-up. Concltion: coronary erl&wid %?3Eomc&r dy+hmdm as well as nlo~calcomnaryaJtemfio~&iugfollowupafterHrxareatleastiu pttill&cedbyeady~uocardialacbivatiollof. 119 CORONARY VASGMOTOR RESPGNSE TO THE. SELECTIVE Bl KININ RECEPTOR AGONIST DES-ARGg-BRADYKININ LN TRANSPLANT PATIENTS. E. Aptacar, P. Gamt, P. Dupouy, E. Teiger, C. Beaver& J.M. Pemea, A. Castaigoe, D. Loiice. L. Hittingax, J.L. Dubois-Rand& Heari Mondor University Hospital, Cr&eU, Prance. Comnmy Bl receptors to kinins seem to be constitutive and to mediite. endotheliumdepmdmt mhuation when upregulated under inuammatory or traumatic condhkms. In humans, the effects of selective Bl stimulation on conmary arteries vasomotion (CAV) am unknown. The purpose of this study was to amem the in viva e&ts on human native and tmosplantul CAV induced by Bl Belective agonist des-kgg-Bmdykinm (DBK). Ten cuntml subjects and 12 transplant patients (HTX) (3k2 mo after surgery) were inch&d, all with aneiooraphicslly normal coronary artaim. None of the control subjects had any clii or biological ma&x of infe&m or inflammatory disease, and 5 HTX wae in mjectioa @tada 2 or 3) the day of the study. Qmu#itative angiosrsphy of 3 sagmeats of the left comnaty artery, and ammary blood flow velocitv fCBPVl (Tkmoler wire) wee assessed at basal&. afk intmcommw acetyl&oiine (Akij (@jig bolusj) and increasing doses of Di3k.04. .4, .4.9.-b and 145 pg/min, 5 min each. DBK doe&s wem chosen on the basis of previous in viva animaI studies. The response to ACh was used as the marker of eodothelii function. AC% induced epicardial vasodikion in contml subjects (8f12%, p<.Ol) and cousktion in HTX (-7&9%, p~.O5) whereas CBFV increased similarly in both groups (64k30 and 72kZ91, both pe.001). DBK at the doses of 49 and 145 @nin inducedsignificpntand .simUar epiaudial vasoam&&oa in both groups (-6&9 and -7f12% in conlml subjects (both p<.Oi) and -&g and -9ztll% in HTX (both p<.OOOl)., whexeas CBFV did not &age. Moreovm, the vasoconstricting response was similar in HTX with and without rejection. With lower doses of DBK, no effact on CAV was obscsved. Them remIts show that Bl receptors to kinins exist in human coronary arteries. Theii Active stimulation inducea epicardial -stridion whatever the endothelial %nction is, and evex~ in the pmaence of itdlammatioo (rejection). suggesting that their predominant effect is on smooth muscle cells. 120 RmucIIoN OF CARDIAC WOGRAFT END(31HELIAL DYSFUNCTION BY-INHUMANS MWejsS.P&liva&S.MW~C.Sdmlze,P.Fraunbager,B.M.Meisez,W. “on S&id. Klinhm Gmsddem, University ofMmdch, Germany Upon exposure to cytokines endothelial cells can undergo profound alterations of vasomotor-function. We have recently detected the association between cytokine patterns and c~romuy endothelial dystimction after homan heart transplantation (HTx). In the present stmly we tested the hypothesis that coronary vasomotor dysftmction in the micmcirculation @curing during follow-up) is related to early inhxardiac immune- mediated cytokine activation. Methods: At 1,6 and 12 months tier HTx plasma levels of sohible Interleukin-2-and TNFa-receptors (sIL-2R, sTNF- R55 and -R75), IL4 and TNFu were determined in the cumnary sinus (CS) and arterial blood (AB) using enzyme-inmmooassay in 35 aawxtively cardiac transplant recipients (CTr) without acute rejection of infection episode and normal renal fonction. Coronary flow measmem ent was performed endothelimn&pendent with acetykhokne and endotheliom independent with adenosiae by tippler-Flowire at 1 and 12 months aftex HTx. Cardiac cytokine release (CCR) was identified in up to 61 % of CTr. Highest amounts of CCR were observed for IL-6 (3&14 % increase) and sTNP-R55 (29i14 % increase). Cornnay flow-increase in response to acetylcholine during follow-up was sigoikandy inversly correlated to early sJL-2R levels in the coronary sinus (~-0.47, p<O.Ol). Moreover, micmvascular endothelial function (described as the rat10 of acetylcholine- mediated to adenosine-me&ted-flow response) at 12 months aRet HTx was significantly imersly correlated to TNFa and IL-6 levels in the coronary stnus at baseline @<0.05). Conclusion: These longitadinal investigation in CTr confirms the inqxxtant impact of early cardiac cytoldne activation on development of microvascular endothelial vammotor dysfunction during follow-up after HTx. These data support the hypothesis that coronary endothelial dysrimction ~3% HTx is at least in part an immonologic phenomenon. 121 PROSTACYCLIN- AND THROMBOXANE-S~ IN HUMAN HFAR’IS. RELATlON TO 122 Alterations of the Gnunary Miamimulation by Sduble Adhesim Molecuics P- Sektin and ICAM- after Cmdiac TRnsptatlriaa in Humans S.M. WILDHIRT’, M. W&. C. SCHlJLZE’, N. CONRADI. S. PEHLNANL12. H. RFKHENSPURNEFC1. W.V. SCHEiUYTz, B. REiICHARTl. D$JtsJts&M--y sulgery’wld c3lrdidogy~, Ludwig-m ullivtity.