Effects of inosine on reperfusion injury after heart transplantation

Gábor Szabó, Nicole Stumpf, Tamás Radovits, Karin Sonnenberg, Domokos Gerö, Siegfried Hagl, Csaba Szabo, Susanne Bährle

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)96-102
Number of pages7
JournalEuropean Journal of Cardio-thoracic Surgery
Volume30
Issue number1
DOIs
StatePublished - Jul 2006
Externally publishedYes

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Inosine
Heart Transplantation
Reperfusion Injury
Reperfusion
Poly(ADP-ribose) Polymerases
Nitroprusside
Acetylcholine
Ventricular Pressure
Vasodilation
Endothelium
Heterotopic Transplantation
Blood Pressure
Peroxynitrous Acid
Left Ventricular Function
Adenosine
Anti-Inflammatory Agents
Phosphates
Staining and Labeling
Transplants

Keywords

  • Endothelial function
  • Inosine
  • Rat
  • Reperfusion injury
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Szabó, G., Stumpf, N., Radovits, T., Sonnenberg, K., Gerö, D., Hagl, S., ... Bährle, S. (2006). Effects of inosine on reperfusion injury after heart transplantation. European Journal of Cardio-thoracic Surgery, 30(1), 96-102. https://doi.org/10.1016/j.ejcts.2006.04.003

Effects of inosine on reperfusion injury after heart transplantation. / Szabó, Gábor; Stumpf, Nicole; Radovits, Tamás; Sonnenberg, Karin; Gerö, Domokos; Hagl, Siegfried; Szabo, Csaba; Bährle, Susanne.

In: European Journal of Cardio-thoracic Surgery, Vol. 30, No. 1, 07.2006, p. 96-102.

Research output: Contribution to journalArticle

Szabó, G, Stumpf, N, Radovits, T, Sonnenberg, K, Gerö, D, Hagl, S, Szabo, C & Bährle, S 2006, 'Effects of inosine on reperfusion injury after heart transplantation', European Journal of Cardio-thoracic Surgery, vol. 30, no. 1, pp. 96-102. https://doi.org/10.1016/j.ejcts.2006.04.003
Szabó, Gábor ; Stumpf, Nicole ; Radovits, Tamás ; Sonnenberg, Karin ; Gerö, Domokos ; Hagl, Siegfried ; Szabo, Csaba ; Bährle, Susanne. / Effects of inosine on reperfusion injury after heart transplantation. In: European Journal of Cardio-thoracic Surgery. 2006 ; Vol. 30, No. 1. pp. 96-102.
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abstract = "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.",
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AU - Szabó, Gábor

AU - Stumpf, Nicole

AU - Radovits, Tamás

AU - Sonnenberg, Karin

AU - Gerö, Domokos

AU - Hagl, Siegfried

AU - Szabo, Csaba

AU - Bährle, Susanne

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N2 - 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.

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KW - Endothelial function

KW - Inosine

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