istered could affect the myocardial injury in rat cardiac ischemic model. Methods: Sixty SD rats, weighing 210 T 20 g, were divided randomly into 4 groups, with 15 animals in each. One group model was given saline and the other 3 groups were administered huperzine A for 7 days at doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg, respectively. Thirty minutes after last oral administra- tion, the cardiac ischemia was made by ligating left anterior descending coronary artery for 24 h. Then the rats were euthanatized with an overdose of anesthesia, the blood samples were collected, and the hearts were obtained. The myocardial infarct size (MIS, %) was observed in the slices stained with 0.1% nitroblue tetrazolium. The serum creatine hosphokinase (CK) and lactate dehydrogenase (LDH) were assayed. Results: The MIS in animals administered huperzine A was not different from that of animals given saline. The activities of CK and LDH in animals given huperzine were similar with ones in the model group as well. Conclusions: Huperzine A might have no affect on cardiac damage induced by ischemia when it was administered previously. This finding suggests that myocardial injury will not be deteriorated in patients having been administered huperzine A when they suffer from acute myocardial infarction. doi:10.1016/j.yjmcc.2006.03.149 135. Postconditioning fails to reduce the infarct sizes in hearts from rats with metabolic syndrome: role of glycogen synthase kinase 3beta Claudia Reuhner a , Ingrid Klo ¨ ting b , Ruth H. Strasser a , Christof Weinbrenner a . a Department of Cardiology, Medical Clinic, University of Technology, Dresden, Germany. b Department of Laboratory Animal Science, University of Greifswald, Karlsburg, Germany Background: Postconditioning by repetitive ischemia/ reperfusion cycles subsequently to an infarction also reduce the infarct size. The following study tested, whether post- conditioning is still protective in hearts of the Wistar-Ottawa- Karlsburg-W-rats (WOKW), a rat strain with a metabolic syndrome. Methods and Results: WOKW-rats develop a metabolic syndrome with obesity, dyslipidemia, hyperinsulinemia after an age of 10 weeks. The experiments were performed at the age of 28 weeks. The body weights of WOKW-rats were higher (473 T 10 g) compared to Dark-Agouti (DA)-rats, the control strain (286 T 4 g). The hearts were infarcted by 30 min of regional ischemia followed by 30 min of reperfusion. Postconditioning was performed by adding 3 cycles of ischemia/reperfusion 30sec each immediately after the infarction. Infarct size was compa- rable in control hearts between DA- and WOKW-rats (58 T 2%; 49 T 2%). Postconditioning significantly reduced infarct size by 34% in DA-rats. In WOKW-rats, however, the infarct sparing effect of postconditioning was lost (43 T 4%). Western blot experiments revealed that after 30 min of ischemia and 5 min of reperfusion phosphorylation of GSK-3h was increased by 175% in postconditioned hearts of DA-rats (P < 0.05). In contrast, in postconditioned WOKW-rats the phosphorylation of GSK-3h was almost lost (118%). Conclusion: Postconditioning is a powerful mechanism to protect the heart after an infarction, thus making it interesting for clinical applications. Unfortunately the metabolic syn- drome, which is often found in patients with coronary artery disease, blocks the protection and the signal transduction of postconditioning at least in the animal model used. Thus it has to be elucidated further whether post-c is still operative in humans with metabolic syndrome. doi:10.1016/j.yjmcc.2006.03.150 136. Myocardial protection during reperfusion by administration of caspase-3 inhibitor is mediated via PI3 kinase survival pathway H. Al-Rajaibi, A. Hussain, P. Karjian, H.L. Maddock. Faculty of Health and Life Sciences, Coventry University, CV1 5FB, UK Apoptosis contributes significantly to cardiomyocyte death during ischaemia reperfusion injury. Caspase family proteases play an essential role in the execution of apoptosis. Caspase inhibitors have been found to be cardioprotective, although there is a question as to the specificity of these class of compounds. Adult cardiac myocytes were subjected to 6 h simulated ischaemia and 18 h reoxygenation (SIR). The broad spectrum caspase inhibitor (z-VAD.fmk, 0.1 AM) was administered at reox- ygenation in the absence or presence of Wortmannin (Wort, 5 nM, PI3-kinase inhibitor). Cell viability (using flow cytometry) was determined by annexin-V and sytox green as a measure of apoptosis and necrosis, respectively, caspase 3 activity was also assessed. Results are summarised in the table below. z-VAD.fmk significantly reduced apoptosis and necrosis after 18 h reoxygenation compared to the SIR control. To examine whether the anti-apoptotic effects of the caspase-3 inhibitor involved activation of PI3-kinase, z- VAD.fmk was simultaneously administered with the PI3- kinase inhibitor Wort to the adult rat myocytes during reoxygenation. Wort completely abolished the anti-apoptotic effects of z-VAD.fmk and also reversed the reduction in caspase-3 activity induced by z-VAD.fmk back to control SIR levels. These studies are the first to show that the caspase inhibitor z-VAD.fmk reduces apoptosis through a PI3-kinase-dependent cell survival pathway. Table: Effect of administering Ac-DEVD.cmk in the absence and presence of Wortmannin at reoxygenation on cardiomyocyte apoptosis and caspase 3 activity following SIR % caspase-3 activity % apoptosis Ac-DEVD.cmk , 55.4 T 6.7 , 34.5 T 4.8% Ac-DEVD.cmk + Wortmannin j 1.7 T 0.07 j 4.5 T 3.6% ABSTRACTS / Journal of Molecular and Cellular Cardiology 40 (2006) 920 – 1015 970