Catalytic peroxynitrite decomposition improves reperfusion injury after heart transplantation.

Abstract

OBJECTIVE:

Peroxynitrite, a reactive nitrogen species, has been implicated in the development of ischemia-reperfusion injury. The present study investigated the effects of the potent peroxynitrite decomposition catalyst FP15 on myocardial and endothelial function after hypothermic ischemia-reperfusion in a heterotopic rat heart transplantation model.

METHODS:

After a 1-hour ischemic preservation and implantation of donor hearts, reperfusion was started after application of vehicle (5% glucose solution) or FP15 (0.3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, immunohistochemical markers of nitro-oxidative stress, and myocardial high-energy phosphates was performed at 1 and 24 hours of reperfusion.

RESULTS:

After 1 hour of reperfusion, myocardial contractility (maximal slope of systolic pressure increment at 140 μL left ventricular volume: 5435 ± 508 mm Hg/s vs 2346 ± 263 mm Hg/s), coronary blood flow (3.98 ± 0.33 mL/min/g vs 2.74 ± 0.29 mL/min/g), and endothelial function were significantly improved, nitro-oxidative stress was reduced, and myocardial high-energy phosphate content was preserved in the FP15-treated animals compared with controls.

CONCLUSIONS:

Pharmacologic peroxynitrite decomposition reduces reperfusion injury after heart transplantation as the result of reduction of nitro-oxidative stress and prevention of energy depletion and exerts a beneficial effect against reperfusion-induced graft cardiac and coronary endothelial dysfunction.

• Authors: Gábor Szabó, Sivakkanan Loganathan, Béla Merkely, John T Groves, Matthias Karck, Csaba Szabó, Tamás Radovits
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 143 Issue 6 Pg. 1443-9 (Jun 2012) ISSN: 1097-685X [Electronic] United States
• PMID: 22401641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Chemical References

• Biomarkers
• FeCl tetrakis-2-(triethyleneglycolmonomethylether)pyridylporphyrin
• Metalloporphyrins
• Peroxynitrous Acid
• Poly Adenosine Diphosphate Ribose
• 3-nitrotyrosine
• Adenosine Monophosphate
• Tyrosine
• Adenosine Diphosphate
• Adenosine Triphosphate

Topics

• Adenosine Diphosphate (metabolism)
• Adenosine Monophosphate (metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Biomarkers (metabolism)
• Coronary Circulation (drug effects)
• Disease Models, Animal
• Endothelium, Vascular (drug effects, metabolism, physiopathology)
• Energy Metabolism (drug effects)
• Heart Transplantation (adverse effects)
• Immunohistochemistry
• Male
• Metalloporphyrins (pharmacology)
• Myocardial Reperfusion Injury (etiology, metabolism, physiopathology, prevention & control)
• Myocardium (metabolism)
• Oxidative Stress (drug effects)
• Peroxynitrous Acid (metabolism)
• Poly Adenosine Diphosphate Ribose (metabolism)
• Rats
• Rats, Inbred Lew
• Time Factors
• Tyrosine (analogs & derivatives, metabolism)
• Vasodilation (drug effects)
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)