Comparative efficacy of ace inhibitors in diabetes-induced cardiovascular disorders: From experimental evidences to clinical data

LIPID INTERACTIONS WITH THE CARDIAC SARCOLEMMAL NA+-H’ EXCHANGER Danny P. Coel, Thnne G. Maddaford and Grant S. Pierce. Div. of Stroke & Vast. Dis., St. Boniface Hosp. Res. Ctr, and the Dept of Physiology, Unlversie of Manitoba, Winnipeg, Canada Ischemia-reperfusion (I/R) in the heart induces arrhythmias and cell damage through an activation of Na’-H’ exchange (NaHX). Inhibition of NaHX during I/R reduces cell damage and lowers the incidence of arrhythmias.

Omega-3

polyunsaturated

fatty

acids

(PUFAs) are cardioprotective and anti-arrhythmic during I/R but., conversely, lysolipids augment damage. It is possible that these different lipid species may influence the

heart’s

response

to I/R

through

an effect

on NaHX.

NaHX in cardiac sarcolemmal vesicles was inhibited by 30-50% after exposure to 1O-l OOpM eicosapentanoic acid or docosahexanoic

acid.

Other

PUFAs

(linoleic

acid

and

linolenic acid) had no significant effect. A variety of lysolipids also had no direct effect on NaHX We conclude that long chain fatty acids selectively inhibit cardiac sarcolemmal NaHX. This action would inhibit I/R arrhythmogenesis and explain their may cardioprotective and anti-arrhythmic actions. Supported by Heart & Stroke Fdn of Manitoba.

COMPAJ?ATfVE EFFtCACY OF ACE tNHMORS IN DMETEWWCED CARMOVMWLAR DISORDERS: FROM M-Al EVQEMES TO CLINICAL DATA Rmmh K. Goyd, Ibshmg V. hjapd, Anil Jaln, S. MRlkyqYC.!3&&amLshukbLM.~of Phmcy, a !ItefMg tiospual AJwmdabad, ImA Our earlier &rims have indcated that tile most anfhypattensives prevented Jheprasolocin (STz)induced hypeRena in rats, arg&an& converting enqnw (ACE) Inhibitors, prevented SlZ-indoed carbamyopalhy. hyperlipidaemia and #JOZM Mrance.AmongACEinMikxs,usedinourstudypwindo@, spita@, w fwnd to fnudwe an iwxeese in insulin sensitivity. EdensionoftheresMa~deq&mentstothadiniolpr~ subs&ntiaedmanyoftherwitatiagoodcwMonb6twm theresultsabtainedfrume~Ush&sanddinicddataACE inhbitors,mrefarndbreduceelleclivelythe~yc&eand dldesterdlevst.3hdi~~whenmparedtheelle&sof variousACEinhibibrsandlo&anind&eticandn-dabetic palients nho had undergone coronary artery bypass graft (CABG) surgery and had bad xmitide (LVEF ( 40%) prior to the a&nir&atbnoflhewagenbThaimprovementinLMFaRsrone maIlhdw3GYPBndsylkaefdllermtbervmend~and lltxKaabe6cgag.-,afIerlhreeronthscfsurgecy,~diat&p&&shc+wd~increaeeintheLWasmnpared to dii patie&. The l8sults i&o IBded that ptwldqril pr&wdma&nim&?easeiilejf&ollfraclionaite0Jlreemonthsof CABG in &&tic p&en& aticdy, olre(ul selection of s.fmdf~c ACE inhititarisrequimdaspeMyina~whencardiowiar crmplicatis a~ a.smd&d wilh dMus. Al ACE inhii may ti produce similar affects with resped to improvement in cardiac fun&s or insulin sensitivity

SERUM CONCENTRATIONS OF NARTIUMURETIC PEPTIDES CORRELATE WITH HEMODYNAMICS IN CONGESTIVE HEART FAILURE Eva Goncalvesova, Vllam Bernat, Ivan Pech&i Jura) Fabian Slovak Institute of Cardiovascular Diseases, Bratlslava. Slovakia Aim of the study was to evaluate the relatIonshIps of ANP, BNP to hemodynamlc parameters in pts with advanced heart failure (HF) Patients and methods. 39 patients (8 females) median age 42 (79 - 64) years were evaluated Mean left ventricular ejectIon fraction (EF) was 21 2 (+I-5 2 ) %. 22 suffered from dilated cardiomyopathy, 10 from CAD and 7 from other diseases For statIstIcal analysis pts were divided to the two groups according serum levels of the ANP and BNP Parameters of central hemodynamrc were measured cslng themodllutlon method Results In pts with serum concentration of BNP 5 200 pg/ml (n= 19) In comparison with pts where BNP was > 200 pg/ml there were slgnlflcant (pi 0.01) ddferences of right atria1 pressure (RAP) and pulmonary capillary wedge pressure (PCWP) 6.9 (+I-2,6) vs 12,0(+/5.3) mmHg and 14,5 (+I-5.4) vs 22.5 (+/-5.1) resp In the group with ANP i 300 pgiml (n=19) the values of RAP and PCWP were lower than In group with ANP i 300 pglml 7 4 (+/-3 2) vs 11 1 (+/-5 7) mmHg and 16,4 +I- 5.5) vs 20.5(+1-7,l) resp (p402j Conclusion Serum levels of ANP and BNP reflect values cf right and left ventricular flllmg pressures. All but 3 pts wtth BNP ; 200 pglml had elevated RAP and PCWP at rest It seem reasonable to xe leveis of BNP to qutde therapy of HF BRADYCARDIA SEEN IN MABETIC MAY RESULT FROM DECREASED mRNA EXPRESSIONS IN HUMAN

PATIENTS j3,- AND &-(AR)S DIABETIC ATWA

Sahlka Gunor, Salt Aslamacl

At+glu, Ablay Taukbm’, , U.Dentz Mncer

Aydin Toy, EON , Kaho~~ RBldaaee

Unlverstty of Ankara, Faculty of.Phumacy, Do~arbnont of Pharmacology, Ankara, Turkey; Baakent Unlvemty School of Mediche, DoPubunt of Cwdbvwcular Surgoq, Ankara, Turkey; “Unlvamfty of lndluu ScJbool of Modkh~e, Depwbnent of Phrnnacobogy & Toxkology, Indknafbofla, IN, USA Clinical diabetic cardiomyopathy independent of the coronary atherosclerosis and together v&h depressed cardiac function as vvell as slwmr sinus rate, inhomogeneity of atrial conduction and longer sinus node reuxery time The prindpal goal of the present study was to investigate PI- and j3r arJrenoce@or (AR) mRNA expressions in diabetic and nondiabetic human atrial tissues. Human right atrial appendages were obtained from five diabetic (mean age 6-4.5; 4F, 1M) and five nondiabetic patients (mean age !56.2+2.8; 4M, 1F) undergoing cor~ra~ artery by-pass grafting. Diabetic patients received insulin treatment for at least two years and were diabetic for at least five years. No patient suffered from acut myocardial infarctiOn and/or failure in nondiabetic group. We used reverse transcriptaseqdymerase chain reacbm (RT-PCR) techniques to compare mRNA expression. Beta actin gene used for P,-AR mRNA expression found internal contra. The excessively (to 69.2k7.6 % of control) and the BrAR mRNA expression moderately decrease (to 32.2ti.5 % of control) In diabetic atria (p