DIFFERENT EFFECTS OF SPECIFIC PHOSPHODlESTERASE INHIBITORS ON OXIDATIVE STRESS DURING CORONARY AUTORECULATION IN ISOLATED RAT HEART Vladimir Lj. Jakovljevic’, Vujadin M Mujovic’, Slobodan S Novokmct’, Momcilo M. Miloradovic’ and Drazan M. Diuric! ‘Institute of Physiology. Faculty of Medicme. Kragujevac ‘Inst~tufe of Physiology, Faculty of Medicine. Belgrade, F.K.Yugoslavia Only few articles reponed that some spcclfic phosphodtesrc:ate (PDEs) inhibitors modulate the generation of rcacwe oxygen species (ROS). In order IO evaluate possible effect\ of specific PDEr inhibitors on oxidative stress the experiments were performed on isolated rat heartr, perfuxd at constant pressure. The hean were obtained horn Wistar albino, male rats (EM=200 g) and perfused wirh KH buffer. The coronary autoregulatwn (CA) was investigated with follow-up of Perfusion pressure (CPP) changes from 40 to I20 cm H20 (CA between SO and 90 cm H20). The hearts were perfwed with specific PDEs inhibitors: EHNA (PDEZ-specific. 3 u:M) and milrinone (PDE3-specific I PM) Oxidative stress was determined as a level of lipid paroxidation (as TBARS) or a level of superoxide anion radical (0,‘) formation Basic release (60 cm H1O) of TBARS or Ol’were 1.73fo.37 pmoVmin/g wt and 34.7522.56 nmol/min/g wt. respectively. Specific PDEs inhibitors induced oppocite effects on oxidativc stress during coronary autoregulation EHNA induced decrease of TBARS at all values of CPP (61 % at 50 cm H,O), bw increase ofOl’ at all values 0fCPP (20 %-24 %). However, n~tlrtnonc mduced increase of TEARS (3 I% (I 20 cm HIO)-40 o/o50 cm [IlO)), but decrease of 0; (8lo/d40 cm HIO)-33 %(lIO cm II@)) In addition, EHNA and milrinone have a completely opposite effects on different ROS generation during CA, what may be important from clinical point of view.

PIiAHMACoI.OC;lCI. PRECONDITIONIIVC; WITH ANGIOTESSIN CONVERTING ENZYME INHIBITORS: INFARCT SIZE STUD\ Gbbor Jan&, Mohammad T. Jaberansari, Balhzs Borsiwky. %alzin SzBnt6, Katalin Kiss & Elizabeth R&h. Dept of Experimental Surgery, Dept of Biology, IJniversiq of P&s, P&s, Hungary

In our prcwnt srudy WC would ltkc II) dsmonstratc that

pcrindoprllat (I’). an AC‘I.. inhibttor. car potcnttarc

suhthrcshold tschaemtc precondtriontng (IX’) via clcvatinf bradykinln activtt);. leadq to a t‘ull delayed cardioprorectton

responw. In a cloxd chc\I Inodcl on da) I. PIB\ wrc

whlccwd to \ham (group I) or PC protocols (groups II-VII).

III group\ II and III wc performed 4x5 and 2~2 mm (wbIhrcsholtlI PC, In group IV WC adtlcd I’ (O.OhIne kg i.\ I

hetilrc 2x1 min PC’. (jr~jup V \\as prctrcatctl with inrtacoronay lloel40 (hradykintn rcccptor antagontst) prtor

to 1x3-P PC‘ Groups VI and VII (drug control>) \vcrc suhlcctcd tcI P and 2x2-Hocl40. 0n jccond day all animal\

undcrwznt 40-min LAI) li@on and 3 hour3 rcperfusmn.

followed by Infarct \i/c mcasurcmcnt. The infhrct \i/c risk ,onc‘ (l..R) ratio was as follo~vs in Groups I-VII rcspccti\cl>: 42x!h: 19.5”;, (p 0,oj: 33.‘l’J;,; 1x.41:, (p 0.05): 30.8”G

3 I .2’1;, hi ii h”,,. Our rc‘hulth confirm thar although P can nor contcr total pharmacologtcnl dcla~cd protection again.st

intarction. it cnhancch a >ubthrcshold tschacmic insult.

scemmgl~ through augmented bradykintn Ic\ cl,. cxhtbtring a coparable dcgrcc of tolcrancc: a\ with robust tschacmtc PC. Supponed by I;TT 3h‘L01 and OTKA-TMX IO.

DOES YITKIC OXYDE SYNTHASE INHIBITOR INFLUENCE OX CORONARY FLOW AND NITRITE OUTFLOW CHANGES INDUCED RY DIFFEREST PHOSPHODIESTERASE (PDEs) INHIBITORS IN ISOLATED RAT HEART? Vladtmlr LI. Jakovltevlc’. VuJadm M Mujovlc’. Slohodan S Sovokmer’. Momcllo M M!loradovlc’ and Dragan M Djwc’ ‘InsIltu~e of Physwlogy. Faculty of Medtclne, KraguJevac. ‘lns:~tuie IIt Ph~~wlog~. Faculty of Medtcmc. Belgrade. FK Yugosiavla

11s urde~ IO s\aluate powhle ~nterdction be~uccn I:arglr,,ne \.r I \>51cm and I’IJLc our expertmenrs acre performed on ~srjlatcd in: !lear~c perfused at constant pres,l;tc The hean\ were ohtamed frown \Vlsta: albino. male rats (BM- ZOO g) and perfused wtth KtI buffer The coronary autoregularton (CA) was mvesttgated wtth Iollo\r-up of perfuslon pressure (C‘PP) changes from 40 IO 120 cln II:0 (CA was observed between 50 and 90 cm H#J U(J (deIerm:ned a\ nltrlte) showed ba\lc release fat 60 cm I( 01 I 7h-t0 27 nnwl’mt~~:g u’i and waz \IIIcII> parallel w nil pre~wrc 110~

CIII~~ I’Dt:s lnhthttors Induced opposlie etfcctc on corr::lar) .i,llo,e~“larlcll theophylltne Induced \l~_cht vasodllatwn. F’IIUA (PDF.2 mhtbltor. 3 LIM) abollshed autoregulatory range and II~IIIIIIUIIC ~PI)r? Inhibnor I i&M) didn‘t Induce ctgntficantl> change :n corouarb flow However. nttrite outflow was strongly affected I-)INA Induced Increase ar all values of C‘PP (from 74 % a~ If) clll tl.0 IO 12 “/a a~ I20 cm H!O). 1nIl1 inone Induced decrease 21 411 L~IUC\ ofCPl’(fror:~ 83 % at 40 cm Ii;0 IO 68 % ar I?0 cm H-0) and t,lcq?h) ll~nc mduced decrease bellow and durmg autoregulawr! range (from 65 “‘0 al 40 cm lI:C) IO 2.: “‘0 ar 90 cm H-0). huI rll\(. ~?i~eased above auroregulatorq raqe (57 “b at I?0 cm ti,O) The rewl:< with applied I,-NAME and dtfferenr PDt: inhtbltorc suygo: that h’OS Inhibition In tsolaied rat heart i? <Irongly dependent 011 cer!,l~n l’l)E\ isoform lnhlbttor

ACUTE PHASE REAClANl IHTERLEUIUN-6 IS AXOCIATED WITH QT DISPERSION DURlN6 KllTE MYXAXiiAL IN-N lmrc lanuty’. Amon bbtid#, Staffan AJwe?# ’ Preventiva Hcdkine, InstMution of Public Health Sciences, krolinska Instilutet. stodrhdm. Sweden # Dep. 01 Cardcbgy, Had% University Hospital, Slockholm. Sweden

Background: Recent research suggeslc that inflammatory markers play a role not only in atheroxlermb but ako in acute coronary events The increased cylokme activity fobwing &se eve&s may predkt mwtafity independently of the well- ertabfkhed clhlii tisk factors. Hehrqaridty of venbicalar repolarization increases lhe incidmtx of ticulu urhl(hnia and mortality after acute myoardial hfarcticm (AM). The relationship belwaen inflammation and repoluiuth atmmulitfes, &mated Lry QT dlspepnion. hu not been irwstigakd. thus we hera studii (hh during AM. Methods: l’hirly-ma c-Uva p&k& [age 69+13 years, 19 males] wth AMI me studied pmsp&My during Uta Ant fm days. Blood for interkukin 6 (IL-6) w*u saqkd on hx#bf aWnon aad far tima the first day, twice day hm, and once ddy &y 3-5. QTc dkpusicm (mahal imkrlcad diffaence belween QT hteds correekl for hart rate) was measured once pr day during this period. Hun and peak values of IL-C and mean and maximum values of Ql dkpersion rae ealeulated. ftewlts: IL-6 tevek reuhed a peak plateau on day one. hating absolute maximum (68.48+152.89 q/L) the second day and d-eased rapidly thereafter (21.4t30.86 t-q/l., day liw). The QTcdbpnaion had lb maximum value the Rrsl day (725+228.5) and deoeased grad* to day 5 (640+269.2). Mean vale of IL-6 was Ggnllkanlly condated with mean Qlc dispersion (r=O.521, p<O.Ol) and tk ~aak kwk d H-6 with maximum of QTc dispersion (~0.46, p<O.OS). These resulls did not change consideraMy alter contmllingforTroponinToruaatfimkinuaHekvds. Conhubn: Mcpendbltly of the my0cAM daaaga the pro-inflammatory cyiobna in- k uaociatrd d tha Qlc ilrlcml dipdon daring AMI. whetha thfs flndiq earl “pm predk8on of Wkmna needs lurtfw CVdUatiar.