Sunday 22 June 2003 17 septal hypertrophy. Therefore, the Arg1053Gln mutation may result in two different phenotypes presenting with either DCM or HCM. The other mutation, Arg1500Trp, was found in patient with typical DCM. The Arg1500Trp mutation carrier has only one family member alive and, therefore the mode of inheritance of the mutation in the family could not be reliably verified. Conclusions: We detected two novel mutations in the beta-myosin heavy chain gene in two patients with DCM. No other disease causing mutations were found in screened sarcomere protein genes. The DCM-causing mu- tations in the beta-myosin heavy chain gene seem to be quite uncommon in Finnish DCM subjects, but should be taken into consideration when genetic screening is performed in familial cases. 117 Use of drosophila to approach the in vivo function of human cardiac myosin binding protein C L. Röder 1 , M. Piovant 1 , M. Sémériva 1 , L. Carrier 2 , J. Flavigny 2 , M. Mokrane 1 , T.P. Vu Manh 1 1 LGPD, Marseille Cedex 09, France; 2 INSERM UR523, Institut de Myologie, Paris, France Missense and C-terminal truncated mutations in the MYBPC3 gene, cod- ing the human cardiac myosin binding protein C (cMyBPC), are associ- ated with Familial Hypertrophic Cardiomyopathy (FHC) but the molecu- lar mechanism by which such mutated proteins may lead to the FHC are still poorly understood. We are using Drosophila as a model organism to approach the in vivo function of human cMyBPC proteins. The aim of this study is not to mimic a cardiomyopathy phenotype in the fly but rather to use this simple system (∼14000 genes, 67% homology with the hu- man genome) to evaluate the molecular functions and the genes networks common to fly and human. No homologue of cMyBPC has been found in the Drosophila genome however a portion of the Drosophila Projectin protein, a I-band muscle protein involved in strech activation, shows 30% homology with human cMyBPC. We have first produced transgenic flies that can express wild type or C-terminal truncated forms of cMyBPC in the Indirect Flight Muscles (IFMs) of the fly, a tissue whose the physiol- ogy resembles that of cardiac muscle (secondly we will express wild type or mutant forms of human cMyBPC in the fly heart). Our results shows that the proteins are correctly expressed and incorporated in the I Band of the IFMs sarcomeres. The expression of truncated human cMyBPC in the IFM results in flightless flies with abnormal wing position. Elec- tronic microscopy analysis of the IFMs of the flies expressing cMyBPC showed that the muscle fibers had their Z-line/I-band torn. Moreover, the sarcomere length was reduced of 10% compared to the wild type. These data suggest that human c-MyBPC may interact with yet unidentified sarcomeric proteins to produce hypercontraction of the muscle fibers. In order to gain insight in the molecular consequence of the transgene ex- pression and to characterize the genetic network involved in the flightless phenotype, we have performed a transcriptome analysis using the nylon microarray technology with the help of Marseille Genopole. Preliminary result on 3700 genes shows that the expression of human cMyBPC in Drosophila sarcomeres modifies the transcription of 115 specific genes that will be described. Work is in progress to performed genetic tests on putative modifier genes identified by microarray analysis. 118 Increased susceptibility to ischaemia-reperfusion of hearts from diabetic (db/db) mice: a functional and 23Na-NMR spectroscopy study R. Anzawa 1 , M. Bernard 2 , D. Baetz 1 , S. Confort-Gouny 2 , J.P. Gascard 1 , D. Feuvray 1 1 CNRS U 8078, Hôp. M. Lannelongue, Université Paris XI, Le Plessis Robinson; 2 Fac. Médecine, CNRS U 6612-CRMBM, Marseille, France Experimental studies with animal models of diabetes allow assessment of the direct deleterious effects of a diabetic cardiomyopathy. The db/db mouse is a genetic model of type 2 diabetes mellitus that mimics several pathologies commonly associated with human diabetes. We examined the susceptibility to ischaemia-reperfusion of isovolumic perfused hearts of db/db and non-diabetic control db/+ (fasted dietary status; 12-15 wk of age) mice. The hearts were perfused with crystalloid buffer (37°C; 80 mmHg) and subjected to 30 min of global no-flow ischaemia and 1 h of reperfusion. 23Na nuclear magnetic resonance (NMR) spectroscopy was used to monitor intracellular Na+ (Na+i). There were no signifi- cant differences in heart rate or developed pressure preischaemia. Time to onset of contracture during ischaemia was not significantly different between both groups. Ventricular arrhythmias developed on reperfusion. The incidence of ventricular tachycardia (VT) and fibrillation (VF) was markedly higher in hearts from db/db mice. VF incidence was reduced in the presence of the Na+/H+ exchanger cariporide (1 μM). 23Na NMR spectra analysis showed an earlier increase in Na+i during ischaemia and a higher Na+i increase at end ischaemia in the diabetic (185% increase) than in the non-diabetic control (150% increase) hearts. These findings suggest that a greater increase in Na+i during ischaemia in db/db diabetic hearts may contribute to exacerbation of myocardial injury and play a role in the development of reperfusion-induced ventricular arrhythmias. 119 Vasoactive peptide and interleukin-6 levels in relation to indices of left ventricular remodeling and performance in patients with idiopathic dilated cardiomyopathy E. Saastamoinen 1 , J. Magga 1 , P. Sipola 1 , K. Punnonen 1 , E. Vanninen 1 , O. Vuolteenaho 2 , H. Ruskoaho 2 , P. Uusimaa 2 , J. Kuusisto 1 , K. Peuhkurinen 1 1 Kuopio, Finland; 2 Oulu, Finland Aim: Plasma levels of vasoactive peptides and cytokines have been shown to be increased in heart failure. We investigated the interrela- tionships of plasma vasoactive peptides, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) with indices of left ventricular size and performance in 49 patients with idiopathic dilated cardiomyopathy (DCM). Methods: Left ventricular end-diastolic and -systolic volumes (LVEDV, LVESV) and ejection fraction (EF) were determined by scintigraphy, and plasma levels of vasoactive peptides (NT-ANP, NT-BNP) and cytokines (IL-6, TNF-alpha) were measured by specific RIA/ELISA methods. In addition, the patients underwent ergospirometry and both-sided cardiac catheterization. Data was presented in means ± SD or means (range). Results: NT-ANP (756 pmol/l, 135-2750) and NT-BNP (183 pmol/l, 40-1430) levels were elevated. Increased NT-BNP correlated with in- creased LVEDV (203±94 ml) and LVESV (155±95 ml) and decreased EF (28±14%) (p<0.05, p<0.001, p<0.001), with increased pulmonary wedge pressure (PCWP, 9 mmHg, 1.0-32) (p<0.001), and also with decreased Wlast4’ (110±52 W) and maximal O2 consumption (17 ml/min/kg, 3.5-47) (p<0.05, p<0.05). Increased IL-6 (2.2 pg/ml, 0.79- 10) correlated with increased PCWP (p<0.001) and decreased Wlast4’ (p<0.05) and maximal O2 consumption (p<0.05). TNF-alpha (0.96 pg/ml, 0.50-3.36) levels did not correlate with any of the measured vari- ables. Conclusions: Circulating IL-6 concentrations correlated positively with NT-BNP levels and negatively with exercise capacity in DCM patients. The prognostic significance of increased IL-6 remains to be studied. 121 Neuregulin-1 attenuates doxorubicin-induced degradation of myofilament structure and excitation-contraction coupling in adult cardiomyocytes C. Zuppinger 1 , M.P. Trucillo 2 , R.A. Cohen 2 , B. Meier 3 , D.B. Sawyer 2 , T.M. Suter 3 1 University Hospital Bern, Cardiology, L612, Bern, Switzerland; 2 Myocardial Biology Unit, Boston University Medical Center, Boston, USA; 3 University Hospital, Cardiology Dept., Berne, Switzerland There is increasing evidence that neuregulin is a newly discovered cardiac