HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Gábor Szabó Siegfried Hagl Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Szabó, G. Articles by Bährle, S. Search for Related Content PubMed PubMed Citation Articles by Szabó, G. Articles by Bährle, S. Related Collections Cardiac - pharmacology Extracorporeal circulation Myocardial protection Transplantation - heart

Eur J Cardiothorac Surg 2006;30:96-102
© 2006 Elsevier Science NL

Effects of inosine on reperfusion injury after heart transplantation

^a Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany
^b Department of Physiology and Experimental Clinical Research, Semmelweis University, Budapest, Hungary
^c Department of Cardiology, University of Heidelberg, Heidelberg, Germany

Received 4 October 2005; received in revised form 12 March 2006; accepted 4 April 2006.

^_* Corresponding author. Tel.: +49 6221 566246; fax: +49 6221 565585. (Email: dzsi{at}hotmail.com).

Objective: Inosine, a break-down product of adenosine, has been recently shown to exert inodilatory and anti-inflammatory properties. We investigated the effects of inosine on ischemia/reperfusion injury in a rat heart transplantation model. Methods: Intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of ischemic preservation, reperfusion was started after application of either saline vehicle (control, n = 12) or inosine (100 mg/kg, n = 12). Coronary blood flow, left ventricular function, endothelium-dependent vasodilatation to acetylcholine and endothelium-independent vasodilatation to sodium nitroprusside, and high energy phosphate content were measured after 1 and 24 h of reperfusion. In addition, the activation of the poly(ADP-ribose) polymerase was detected by immunhistology. Results: After 1 h, coronary blood flow (4.1 ± 0.3 ml/(min g) vs 2.9 ± 0.3 ml/(min g), p < 0.05), left ventricular systolic pressure (102 ± 9 mmHg vs 83 ± 4 mmHg, p < 0.05) and dP/dt (2765 ± 609 mmHg/s vs 1740 ± 116 mmHg/s, p < 0.05) were significantly higher in the inosine group in comparison to control. Vasodilatatory response to sodium nitroprusside was similar in both groups. Acetylcholine resulted in a significantly higher increase in coronary blood flow in the inosine group (76 ± 5% vs 48 ± 9%, p < 0.05). Energy charge potential was significantly higher in the inosine group (1.69 ± 0.10 µmol/g vs 0.74 ± 0.27 µmol/g, p < 0.05). After 24 h, there was no difference between the groups in basal coronary blood flow, left ventricular systolic pressure, dP/dt, and the response to sodium nitroprusside. However, acetylcholine led to a still significantly higher response in the inosine group (112 ± 13% vs 88 ± 7%, p < 0.05). Immunhistologic stainings revealed activation of poly(ADP-ribose) polymerase in control animals which was abolished by inosine. Conclusions: Thus, inosine improves myocardial and endothelial function during early reperfusion after heart transplantation with a persisting beneficial effect against reperfusion induced graft coronary endothelial dysfunction. The effects of inosine are mediated at least partly by modulation of the peroxynitrite-poly(ADP-ribose) polymerase pathway.

Key Words: Transplantation • Reperfusion injury • Inosine • Endothelial function • Rat

This article has been cited by other articles:

				S. Aharinejad, O. Andrukhova, M. Gmeiner, A. Thomas, A. Aliabadi, A. Zuckermann, K. Krenn, and M. Grimm Donor Serum SMARCAL1 Concentrations Predict Primary Graft Dysfunction in Cardiac Transplantation Circulation, September 15, 2009; 120(11_suppl_1): S198 - S205. [Abstract] [Full Text] [PDF]

				J. B. Rose and I. R. Coe Physiology of Nucleoside Transporters: Back to the Future. . . . Physiology, February 1, 2008; 23(1): 41 - 48. [Abstract] [Full Text] [PDF]