ORIGINAL CONTRIBUTION Basic Res Cardiol 95: 228 – 234 (2000) © Steinkopff Verlag 2000 Jens Munch-Ellingsen Jan Eirik Løkebø Einar Bugge Anne K. Jonassen Tanya Ravingerová Kirsti Ytrehus 5-HD abolishes ischemic preconditioning independently of monophasic action potential duration in the heart Abstract Objective: Blocking of the K ATP channel with either glibenclamide or 5-hydroxydecanoate (5-HD) has been shown to abolish the infarct reducing effect of ischemic preconditioning (IPC) in hearts from several species, but the results in rat and rabbit have been equivocal. In this study we investigated if 5-HD could abolish IPC in rat and rabbit and further if IPC or IPC + 5-HD were affecting action potential duration in the rabbit heart. Methods: The rat hearts were isolated and retrogradely perfused on a Langendorff perfusion apparatus with Krebs-Henseleit buffer. The rabbit experiments were per- formed in an in situ model. Rat and rabbit hearts were subjected to 30 min regional ischemia by ligating a coronary artery followed by 120 min (rat) or 150 min (rab- bit) of reperfusion. The preconditioning protocol was one or three cycles of 5 min ischemia plus 5 min reperfusion in the rat and one cycle of 5 min ischemia plus 10 min reperfusion in the rabbit. In the rat 5-HD was added to the reservoir before ischemic preconditioning in different concentrations, and in the rabbit 5-HD was given as a bolus 5 mg/kg intraventricularly 2 min before the preconditioning ischemia. In the rabbit epicardial monophasic action potential duration at 50 % repo- larization (MAPD 50 ) was measured at 1, 2 and 5 min in each of the ischemic periods using a contact pressure electrode. Infarcts were measured with tetrazolium staining and risk zone volumes with fluorescent microspheres. Results: All data are presented as infarct size in % of risk zone volume (mean ± SEM). In the rat 200 μM of 5-HD abolished the protective effect of one cycle of IPC (28.6 ± 4.7 versus 8.4 ± 0.8) and 500M of 5-HD abolished three cycles of IPC (50.7 ± 7.8 versus 8.4 ± 2.0). Control was 40.9 ± 2.8. In the rabbit 5-HD abolished IPC (41.2 ± 7.2 versus 8.1 ± 3.2). Control was 53.5 ± 12.4. MAPD 50 were significantly more shortened compared to control at 1 and 2 min into the 30 min ischemia for the IPC and IPC+5-HD. Conclusions: We conclude that 5-HD abolishes ischemic preconditioning when given before the preconditioning ischemia in both rat and rabbit but does not abolish the ischemia induced shortening of the action potential duration in the rabbit; thus, a role for the mitochondrial K ATP channel and not the sarcolemmal K ATP channel in the protective mechanism behind IPC is probable. Key words Infarction – ion channels – ischemia – K-ATP channel – preconditioning J. Munch-Ellingsen () · E. Løkebø E. Bugge · A. K. Jonassen · K. Ytrehus Department of Medical Physiology Institute of Medical Biology University of Tromsø N-9037 Tromsø, Norway E-Mail: jensme@fagmed.uit.no R. Ravingerová Institute for Heart Research Slovak Academy of Sciences Bratislava, Slovakia Received: 15 July 1999 Returned for 1. revision: 17 August 1999 1. Revision received: 13 September 1999 Returned for 2. revision: 12 October 1999 2. Revision received: 3 November 1999 Accepted: 17 November 1999 BRC 191