Functional effects of adrenomedullin in human cardiac muscle

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FREE RADICAL INHIBFIIMtS (Fltl) CAN PREVENT CELGMCDIATED LDL OXfDATloN m lBCllEMlA (I) AND R C?ERKlSKN (R) OF VASCULAR WALL in dry

Mariaana Biomedical

V. Biknko Chemistry,

and Akksei V. Kbikhenko, RAMS, Moscow, Russia.

Institute

of

As we showed previously, end&&al cells (EC) and macrophages (MP) can oxidatively modifj~ LDL in situ under aezobic (A) conditions and, especially, upon I and R, thus enhancing the a&erogenic properties of LDI.. However, the fi-eeradicai mecbaaimn of this process has not been proved The aim of this work was to compare the ability of several FRI to prevent LDL oxidation by EC and MP and the cytotoxic effect (CTE) on the vascular wall. Methods. EC from the human umbilical vein, MP from the blood of healthy donors and patients with lscheanic heart disease, and LDI, from the blood of donors with normal and high cholesterol levels were incubated under A and I conditions (I-24h)andtmder R(I-6h).Pmbucol.K-Phmosane,and Desfd (10-9-10-5 M); succiaic acid (2.5-40 @ml); Hypoxen (0.3-10 &ml); and Dehoraa (0,00&60 @ml) were used as FRI. l%c d showed that Probucol and Desferal (IO-‘-- 10.’ M). K-Phenosane ( 10.’ M), and Deltoran (0.06-60 rig/ml) inbibited I.DL modification, as estimated from the decrease of LDL eloctropboretic mobility, lipid peroxide accumulation, CTE on MP and EC, and LDL. accelerated uptake by MP. Succinic acid at all doses protected the ceils f?om CTE of LDL and I, but a dose of 2.5 p&ml enhan& LDL oxidation. Hypoxen was ineffbUive. Thus, FRI proved to inhibit LDL oxi&ion by MP, EC, and MP t EC and, hence, to reduce the risk of atharosckrosis development in the heart. brain and other vessels that are mostoftcnexposodtoIaadR.7benewproposcdtestsystan may be used for idcatifying antioxidants capable of preventing atherosclerosis. 7‘hls work was .suppried by the ltussian

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FL’NCTIONAL EFFECI’S OF HUMAN CARDIAC MUSCLE tgbegen &ping, I’ieske

ADRENOMEDULLIN

Paul Rarckhausen.

Abr. Kardiologie u. Pncumologie. %lycr AG. Irverk”sen

Research.

(iilnther

lkmhouski”.

(;eorg-August-IJnivcrsitl

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INTERACTION OF DIFFERENT POTASSIUM [email protected]: ROLE OF THE REP0 LARIZATIONRESERVE P&r Bltkzki’, Lhz16 Virig’, Norbert Iod, Jdhs Gy. Papplf & Aadrh Varr6’. ‘Department of Pharmacology, University of Szeged; 2Academic Division of Cardiovascular Pharmacology, Szeged, Hungary lhe aim of this sndy was to mnvcshgatethe possible role of andtheintl!ra&xofd&ultpo&sium thcrepo~resavc c~lsindrdogventriculin~le~~byapplyingthe c4ln~alalrr6aDe~andwlx)kd Lrnpwa 37”C.CompleteblockofK,by1 /.LMQ tiztlz ‘. @oF)leq&xd action pcmial dundon (APD) by 45x93.6 %, 1~13 (at c#e length CL=Moo m). bl2!23B (CRO) at 10 pM (cancentration which selecM.ly blocks 4c, cumnt) applied akmc SKI not m&zdly lcngthm APD (< 7 %), but wlul repolari&m was all&y prolongedbycomplete~block(l pMDOQ,inhiMicmof~~?th10 ph4 CR0 sulada@ delayedrep~(38.5*82 %,I+ at CL=5Mx) n-s). BaC12(BA) applied alone in tk ccnamrmticm of 10 pM (which dtivcly blocks 4, cumnt) IAPD by

33.0+3.l%

Rurkert

Cldningen

Admnomedullin (ADM) is a recentI) discovered endogenous peptidc with pcsent vasodilamry effects. In hearf failure. plasma levels of ADM arc elevated. but it is unknown whether ADM directly afr‘ccrs cardiac amlraailc limaions. We 1csted funaional responses 1o ADM in human atrial and ventricular myocerdium. Methods: Isolated atrial (n=l I), ventricular non-failing (n=IO) and v~mtricular failing (11~18) trabeculac were electrically driven a~ I 11~ 37°C. Application of ADM 0. I pmol/l or I bmol/l and simultaneous registraticm of mntractile force and calcium IranGnU (Aeqtin Ii P signal (AI.)). APPlication of lsopmterenol (0.003 pmol/l) or (Ca 1” 3.2 mmolll for CcHnparison. Results: ADM signiticantly increased cnmractile force in atrial myocardium (by maximally 33 * 6 % at I @mol/l: p
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(1 pM DOF)

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FLECAINIDE CONTRACTILE

BUT NOT AMIODARONE FUNCTION

L&en Dicrcr

Christian Pagel, Rurken Pieskc

ljisping Zenker”.

I)irk

fT 032558

und

IMPAIRS

V. Lewinski.

lhomas

Abt. Kardiologie u. l’neumologie. Gwrg-August-Universiti ‘Ab1. 1HGChimrgie, Gzorg-Augwt-Univcrsitat (i(lttingen

Busch”.

Cidrringen

f3oth 1he anriarrhythmic class I agent f+zainidc (Flee) and the class 111 agent Amicdamnc (AM) are widely applied in patients in cardiac arrhythmias. However, their effects on oontraaile behaviour and calcium handling in the human heart are not charaaerizd. We compared the funaional effects of these two annpounds in isolated human cardiac muscle. MetCods: Isolated vcntriLular muscle strips (n==61) !iwm failing human hearts (n=31). Eltxtrieal stimulation, 3’l”C, I Hz Interventions: a) Cumula1ivc concentration-rap curves (0.1 - 100 pmol/l) for Flecainide. b) Flecainidc in a concentration cl= IO its F.Cw (3 pmol/l) compared IO Amiodarone 100 gmol/l (similar IO in viva tissue conczntratians,dissolved in Twan 80 (10%) and ethanol (10%): ~.tT..s on cmfractile fonx, calcium transians (Aeqtin light signal) or forcefrequetgwelationship (FFR); stepwise i-qe of stimulation ticquency from 0.5 IO 3.0 Hz RanIts: I+x exerted a mnantration dependent negative inotropic eflwr (by maximally 61 i 6% a IO0 pm&I). ‘Ihis effect was associated with a parallel decline in acquorin Ii&t signal. AM did not affect contractile funaion cnfnpared lo solvent amtml. Ret impaircd the FFR significantly with inversion of a pusitive lo a negative FFR (fom inaeased maximally by 38 * I I% at 2.0 HI w&out Flee but continouslq declined in the presenti of Flc~). This WBS partly r&ted to an increase in diastolic tension (at 3.0 II? maximally by 36 * IO % without Ret and by 87 f 26 % with Flee. p