42 Sunday 22 June 2003 tions at the molecular level, and about the reasons for the variability in clinical symptoms typical for FHC. We therefore attempted (i) to identify functional effects of these muta- tions in the head domain of β-MHC and (ii) to determine the amount of mutated myosin expressed in M. soleus biopsies from several individuals with FHC. In humans the cardiac β-MHC isoform is also expressed in slow soleus muscle which was therefore used for this study. In 6 out of 7 biopsies we found a deviation from the generally assumed 1:1 ratio between mutated and wildtype β-MHC, the deviation being quite large in some cases. For example, in biopsies of two patients (mu- tation Val606Met) where we could not identify any functional changes compared to control fibers, less than 15% of the β-MHC carried the mu- tation. Even in biopsies with other mutations for which we could identify functional differences to control fibers, a deviation from the 1:1 ratio between mutated and wildtype myosin heavy chain was observed. The results imply that the expression level of mutated protein may represent an additional factor that affects the severity of the disease. Comparison of members of two different families with the same mutation (Val606Met) suggest that the expression level of mutated protein may be characteristic for each mutation. 203 Increase in cardiac Na+/H+ exchange activity in type 2 diabetes D. Baetz 1 , F. Prunier 2 , S. Tamareille, A. Darmellah 1 , D. Mesangeau 3 , D. Feuvray 1 1 CNRS U 8078, Hôp. M. Lannelongue, Université Paris XI, Le Plessis Robinson, France; 2 Fac. Médecine d’Angers, IFR02, Fac. Médecine X. Bichat &, Paris, France; 3 Merck-Santé, Chilly-Mazarin, France Most reports of diabetes-induced cardiac dysfunction, especially con- cerning the sarcolemmal Na+/H+ exchanger (NHE), have used insulin- deficient diabetic (IDD; type 1) animals. To our knowledge, no study has been conducted with non-insulin-dependent diabetes (NIDD; type 2) animal models. However, type 2 comprises the largest group of di- abetic patients. The Goto-Kakizaki (GK) rat is a polygenic model of diabetes that shows rather mild fasting hyperglycemia and peripheral insulin resistance. We performed echocardiographic studies of 10 wk di- abetic GK rats. These studies revealed significant left cavitary dilation and increased wall thickness (n=8/10). This was associated with alter- ations of left ventricular relaxation and with a lower systolic function. The heart weight index was higher in GK rats. Single myocytes isolated from left ventricular walls were loaded with the pH-sensitive fluoroprobe seminaphtorhodafluor-1, and acid efflux rates (JH) calculated during re- covery from intracellular acidosis were used to quantify both NHE and NBC (Na+-HCO3- cotransport) activity. NHE activity after acidification was significantly increased compared to that in non-diabetic myocytes (JH increased by approximately 100% at an intracellular pH of 6.9) whereas NBC activity was unchanged. ERK phosphorylation (measured by immunoblot analysis) during intracellular acidification was increased (by approx. 90%) in GK ventricular myocytes and this effect was abol- ished by the ERK kinase inhibitor U0126 (10 μM). The increase in NHE activity in ventricular myocytes obtained from type 2 GK rats is opposite to the decrease in cardiac NHE activity previously described with type 1 diabetes in cardiac myocytes. These results, together with those of recent studies, suggest that the exchanger could play a determinant role in type 2 diabetes associated cardiac remodelling process. 204 Effects of the hypertrophy-inducing agent etomoxir on fatty acid utilization and fatty acid transporters in rat heart and liver S.L.M. Coort 1 , H.E.C. Niessen 1 , D.P.Y. Koonen 1 , W.A. Coumans 1 , A. Bonen 2 , G.J. Van der Vusse 1 , J.F.C. Glatz 1 , J.J.F.P. Luiken 1 1 University of Maastricht, CARIM, Physiology, Maastricht, Netherlands; 2 University of Waterloo, Kinesiology, Waterloo, Ontario, Canada Etomoxir is a specific inhibitor of carnitine palmitoyltransferase I (CPT- I), which enzyme catalyses the rate-limiting step in the uptake of activated fatty acids (FA) by mitochondria. Inherited defects of mitochondrial beta- oxidation are increasingly recognized as a cause of cardiac hypertrophy and hepatic failure. In rats it has been demonstrated that cardiac hypertrophy develops after treatment with etomoxir. However, the effect of an arrest in mitochon- drial beta-oxidation on FA utilization and on plasma membrane FA trans- porters is largely unknown. In heart and liver from rats daily treated via intraperitoneal injection with 20 mg etomoxir per kg body weight for 8 days and in saline-injected control rats we investigated (i) FA uptake rates using giant membrane vesicles, (ii) the plasmalemmal amounts of the transporters FA-translocase (FAT)/CD36 and plasmalemmal FA-binding protein (FABPpm), and (iii) the tissue amounts of triacylglycerols (TAG). To verify the inhibitory action of etomoxir on CPT-I we determined CPT-I activities in heart and liver total homogenates. Etomoxir treatment resulted in a significant enlargement (p<0.05) of both heart and liver, and inhibited CPT-I activity by 42% and 50%, re- spectively. In the heart of etomoxir-treated rats the vesicular FA uptake rate as well as the total amount of TAG were not altered. In contrast, in the liver of etomoxir-treated rats there was a marked reduction (-50%) of vesicular FA uptake rate, while the total amount ofTAG was markedly elevated (2-fold). The plasmalemmal amount of FAT/CD36 and that of FABPpm in both heart and liver of etomoxir-treated rats were unaffected by etomoxir treatment. It is concluded that etomoxir exerts tissue-specific effects on FA utiliza- tion. In the liver a partly blockade of mitochondrial beta-oxidation is likely to lead to both a reduced FA uptake rate and targetting of FA to- wards esterification, causing accumulation of TAG. In contrast, in heart a 50% reduction of CPT-I activity apparently remains without an effect on FA uptake and TAG content. We speculate that CPT-I activity is rate- governing for cellular FA utilization in liver but not in heart. Supported by the Netherlands Heart Foundation (2000.156). 205 Septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: an analysis of the patients with persisting NYHA class III symptoms during long-term follow-up L. Faber 1 , D. Welge 1 , H. Seggewiss 2 , D. Fassbender 1 , D. Horstkotte 1 1 Heart Center North Rhine-Westphalia, Cardiology Dept., Bad Oeynhausen, Germany; 2 Leopoldina Hospital, Department of Internal Medicine, Schweinfurt, Germany Background and Introduction: In about 90% of the patients (pts). with symptomatic hypertrophic obstructive cardiomyopathy (HOCM), symp- toms and outflow gradient (LVOTG) can significantly be reduced by septal ablation (PTSMA). Pts. with a dissatisfactory long-term course af- ter PTSMA are not yet characterized sufficiently. We therefore analyzed our long-term cohort of pts. treated between 1996 and 1998 with respect to persisting or recurrent NYHA functional class >= III symptoms after PTSMA. Results: Hospital mortality of PTSMA was 1.7% (VF, pulmonary em- bolism, and pericardial tamponade in 1 pt. each). Mean CK rise was 599±300 U/l. A DDD-pacemaker (DDD-PM) had to be implanted in 13 pts. (7%). Mean follow-up time was 45±12 months, 8 pts. (5%) were lost to follow- up. Out of the 167 cases analyzed, 12 pts. (7%) underwent a re-PTSMA and 4 (2%) a myectomy. Including these cases, 156 pts. (88%) had com- plete elimination of obstruction, and 151 pts. (85%) reported sustained symptomatic improvement at their last follow-up. Persisting or recurrent class >= III symptoms, however, were reported by 16 pts. (10%). LVOTG recurrence or persistence was the suspected reason in only 2 of these cases, 8 pts. were free from LVOT obstruction, and 6 had provocable gradients <60 mm Hg considered hemodynami- cally irrelevant. The assumed leading reason for persisting class >= III symptoms despite satisfactory LVOTG reduction were marked obesity (BMI > 30/m 2 ) in 5, severe diastolic LV dysfunction in 5, and coex- istent pulmonary disease in 4 pts. There were 2 further DDD-PM and