Nitrate tolerance-induced deterioration of the ischemic adaptability of the heart

BioMed Central Page 1 of 1 (page number not for citation purposes) BMC Pharmacology Open Access Meeting abstract Nitrate tolerance-induced deterioration of the ischemic adaptability of the heart Zoltán Szilvássy*1, János Szaszkó2, Róbert Döbrönte3, József Németh2, Réka Zs Sári2, Csaba Pankucsi2, Angelika Varga2, József Tőzsér4, László Fésüs4 and Barna Peitl1 Address: 1CERAMED Research Group, University Debrecen, Hungary, 2Department of Pharmacology and Pharmacotherapy, University of Debrecen, Hungary, 3Department of Anesthesiology and ICU, Petz Aladár County Hospital, Győr, Hungary and 4Department of Biochemistry and Molecular Biology, University of Debrecen, Hungary Email: Zoltán Szilvássy* - [email protected] * Corresponding author Introduction We tested whether postconditioning limited infarct size in rabbits with haemodynamic nitrate tolerance. Methods Male rabbits made tolerant to the hypotensive response to 30 μg/kg intravenous nitroglycerin (NG) by a preceding one-week exposure to transdermal NG (0.07 mg/kg/h) were subjected to 35 min coronary occlusion (test ischemia) followed by 3 h of reperfusion with the following additional interventions: no intervention (NI); postconditioning pacing (PPC): five cycles of 5 min periods of rapid ventricular pacing (500 b.p.m.), or postconditioning coronary occlusion (PCO): five cycles of 5 min coronary occlusion with 10 min interpacing/interocclusion intervals, applied after the end of the test ischemia. These protocols were applied in both nitrate-tolerant and nontolerant animals. Infarct size expressed as a percentage of area at risk (I/R) was determined by triphenyltetrazolium chloride staining, left ventricular cyclic nucleotides were determined by radioimmunoassay from samples out of the area at risk, 75 min after the test ischemia. Results In non-tolerant animals both PPC and PCO reduced the I/R compared to the NI group. When animals had been made nitrate-tolerant, the I/R was significantly higher in the NI group compared with non-tolerant animals and the beneficial effect of the PPC or PCO on the I/R disappeared. Conclusion We conclude that (i) nitrate tolerance blocks postconditioning induced by either PPC or PCO, (ii) PPC is more effective post-conditioning challenge than PCO, and (iii) nitrate tolerance per se reduces the capability of the heart to tolerate an ischemic insult. from 13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT) Vienna, Austria. 22–24 November 2007 Published: 14 November 2007 BMC Pharmacology 2007, 7(Suppl 2):A49 doi:10.1186/1471-2210-7-S2-A49 <supplement> <title> <p>13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)</p> </title> <editor>Ernst Singer and Thomas Griesbacher</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="[http://www.biomedcentral.com/content/files/pdf/1471-2210-7-S2-full.pdf]">here</a></note> <url>http://www.biomedcentral.com/content/pdf/1471-2210-7-S2-info.pdf</url> </supplement> This abstract is available from: http://www.biomedcentral.com/1471-2210/7/S2/A49 © 2007 Szilvássy et al; licensee BioMed Central Ltd.