Cardioprotective effect of chronic hypoxia is blunted by hypercapnia

THE

CARDIAC

Zoldn

EFFECT

OF CHRONIC

ESDOTOXEMIA

Nbdhazi’,

Attila Tatits”, Katalin Offenmiiller’, L&ant Bert&, P&r And&a** SE 2”d Department of Medicme, Budapest, HLFrtdenc Joliot-Curie OSSKI, Budapest, HIfir’ llmversity of ~Iarm School of Medicine, Miami, USA*

THE EFFECTS OF CATECHOlAMNESlWUCE PRECONDillOmmj AND ACUTE DIA@ElES ON RAT HEART MITOCHONDRIA: THE ROLE OF -NE FLUIDITY Krldina Nagyovi’, hzaf Tbcxd, Junl WavJ’, Jh StyIt’, hta warxul&vy, wllh zIqphm@. rnatliaatRa+sovdtAdsd, Brdalava,Sbvda,?h@dB@hyahChamPhya,FacMdhf’hya~ Inform&a,

Cluucal studies suggest that endotoxm (LPS) conccntrauons are raised m patients with septicemia and this hqh LPS level IS partly responsible for the deterloratlon of cardiac performance. In this study we investigated whether chronic I.PS elevation could also affect the heart performance. Plasma levels of LPS were determmed in 116 healthy blood donors after a comprehenslve cardlo-vascular exammahon. Thirty-two Wistar rats were treated with endotoxin (200 &rat/day) for three months; ten rats were used as controls. Hlstologcal examination was performed to evaluate the effect of chronic LPS treatment on the cardio-vascular system. Since apoptotic cell death is involved m the deteriorauon of heart function in septicerma, DNA laddering and TIJNEL assays were carried out to determine if programmed cell death is Increased m our model of chronic LPS exposure. In addition ten Wlstar rats were treated with LPS for three months and nonInvasive hemodynamic measurements were performed using a Toshiba echocardiography system with 12 MHz transducer. The LPS levels m the human blood donors varied widely 0.01-l ,574 Ell!ml. In rats chronic LPS treatment did not cause any detectable hlstologlcal alterations in the cardio-vascular system and did not ImpaIr any echocardlographc parameters measured. We were also unable to detect any markers of apoptotic cell death. In contrast to other studies we have examined the effect of chrome LPS exposure. Thus whilst LPS has acute effects on heart performance we could not detect any following chrome exposure. Our results demonstrate that a hvmg organism can tolerate chrome LPS exposure without any detrimental effects on cardiac performance.

CARDIOPROTECTIVE EFFECT OF CHROSIC HYPOXIA IS BLUNTED BY HYPERCAPNIA Jan Neck&i”, Ondrej Szlrszoi”, Jan Herget*‘, FrantiZek PapouSeklJ, Bohuslav OSt’bdal’3 & FrantiIek KolPf’-‘. ‘Inst. of Physiology Acad. Sci. CR ‘Dept. of Physiology, Znd Medical Fat.. Charles IJniv.. and ‘Center for Exoerimental Cardiovascular Research, Prague, Czech Hepubic. H!powa IS assoc~atcd v.lth Increased p&u&on ot‘rcacu\c oz?gcn spccl~s (ROS) w+uch conmbutc to the dcvclopmcnnt of ussuc damage It has been shown that the exttnt of hlpo~clc mJu5 can bc reduced by h!percaprua bccausc C& mtctacu ulth r&cal mtcrmcdtatcs (1.2) On the other hand. chroruc h>poxla u1creasLs car&ac tolerance to subsequent acute lschcmlc mJup and ROS slgnahng may bc Imphcated m dus process. Thcr&rc. our rum H* to examine whcthcr hypzrcapma modulti the protccmc cffcct of chronic hyposla on &nua-mduccd mvocarti qu? Adult male Wistar rats were exposed to chrome &obanc hkpoxla ( IO ‘%, 0;) for three v.eeks. In the first cxpenmental group (n I I). C‘O- in the chamber was &lly absorbed. u1 the second group (n-12). 1t.s Ic\cI was mcrcased to 4 I % (mngc i X 4 3) and conunuousl> morutored Notmox~c controls (n= 12) wcrc kept u1 aanosphcnc ar One day after the last exposure. antlithcuzcd opLn-chc!t anunals wcrc subjectfzd to 20-mm LAD coronary artcn’ occlusion and 3-h repctiion for Infarct sm dctcmunauon (-ITc‘ stammg) C‘hroruc

hypoxia alone reduced b& these effects were significantly infarct SIX was reduced from the normoxlc controls (y-0 (15) Hkpcrcaptua

we&t and dunuushed

mcrcased hematint. by hypercapma The

61 Y + 2 Ig % of the arca at nsk in to 44 5 t 3 33 ‘% m the h>poslc group blunted the ~nfkra slzz-llmltmg effect of

hyposla (54 8 I 2 37 %. ~(0.0.5) It IS concluded that Incrcascxl CC& level tn the msp~red ur suppresses the development of chronic hypowa-Induced card~opmtmtwc mechanism. possibly b! mtcrxmg \v~th ROS signahng pathwqs iI) Hcrgct ct al Physlol Rcs 50 P7.200 I. (2) Vcsclh ct aI Ph>slol Rcs 50 P:2,200 1 .Srrppf~rircl h, <;A (‘N 3//.5 l/I I,?"/

Coma&ta

Backqound:

diabetes

Unlv, Bralblava

Norepinephrine

(NE) and carte

(DIA), both have been shorm

of the

heart

arrhythmias, characterized aggravated

against

the

Slav&la

damage

(8 days)

streplozotoan(PC) life threatening venbiatlar

to induce preconditioning and

inaeased

induced by carte ischemia. NE and DIA were also with augmented inlracelblar Ca?‘-transients and with transport of energy from heart mitcchondria, mainly via formation @<0.05) of contact sites in the rnitochondfal

membranes properties

are

(MM). However, the accompanying changes in MM still little understood. Expeninentat Adult male rals, (23090 g b.wt) were treated either with NE (single dose, 1 rng.kg-’ SC.) or with Qeptozotocin (45 tng.kg-’ i.v.). The diabetic status of animals was checked by estimation of blood glucose, triacykjycarols

and cholesterol.

Mitochondria were isdated according to Lehninger (MF) was as@%ed using lhe fluorescence probe 1 ,&diphenyl-1,3,5hexatriene (DPH). Mitochondrial Mg2*-ATPasa

(1973).

MM fluidity

activity

in presence

and absence

of 2,4dinitophend

was measured

by the amount of P, liberated during ATP splitting. Results: NE and DIA induced an increase in the MF crounting 10 and 7 56 (pO.O5). Con&dons: Results indicate that an increase in MF of MM may represent a characteristic effect of PC, parlicularly B its mechanism lnvdves the augmentation of intracellular Cd’- transients. mfs; VEGA No 2/7157LV and The Slwek

h#n&ry

of Educatkm

Grant No l/614999.

THE EFFECTS OF INDOMETHACINE CONTRACTILITY OF THE ISOLATED VENTRICLE OF RAT HEART IN THE L-EPINEPHTUNE AND PRAZOSINE Momir T. Nesic, Darko M. Stevanovic Pavlovic, Institute of Physiology, School Belgrade, Serbia, FR Yugoslavia

ON THE RIGHT PRESENCE

Indomethacme

the

is

very

well

known

as

& of

OF

Mlrjana R. Medicine,

InhIbItor

of

prostaglandm’s blosynthesls. The aim of our study was to mvestlgatc the effects of indomethacme on the contractlllty of Isolated right ventricle of Wlstar rat heart, m the presence of I-cpmephrine. Each ventricle was put on a boot electrode and than placed in a bath with Tyrode’s solution bubbled with 95% 0215% CO> The volume of the bath was 25 ml, pH=7.4 and It’s temperature was kept on 37 “C. ContractIons were induced with square wave Impulses of twice the diastolic threshold and a duration of 5 ms at a frequency on 1 Hz. The contrachons were recorded via an lsometrlc transducer IsensitivIty of 0.05 into a g/cm) microdynamometer (7050 Ugo Raslle). After the statnhzatlon period of 60 mm., indomethacine (Sigma, I!SA. I PM/I). I-epmephrine (Sigma, USA, 1 PM/I) and prazosme (Sigma. USA, IO PM/I) were added m the bath and contractions were recorded contmuously for another 60 min. There IS sigmficant increase (52%) of the amplitude of contractions (p