Effects of Custodiol-N, a novel organ preservation solution, on ischemia/reperfusion injury.

Abstract

OBJECTIVE:

Custodiol (histidine-tryptophan-ketoglutarate solution) is a leading organ preservation solution. On the basis of this solution, the novel Custodiol-N was developed. The present study investigated the effects of Custodiol-N in a rat model of heart transplantation.

METHODS:

Heterotopic heart transplantation was performed in Lewis rats. Four groups were assigned: 2 Custodiol-N-treated groups and 2 Custodiol-treated control groups with a reperfusion time of 1 hour and 24 hours, respectively. Coronary blood flow, left ventricular pressure, its first derivative, left ventricular end-diastolic pressure, endothelium-dependent vasodilatation to bradykinin and endothelium-independent vasodilatation to sodium nitroprusside, and adenosine triphosphate content were measured. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was performed to detect apoptotic cardiomyocytes.

RESULTS:

After 1 hour, coronary blood flow (3.99 +/- 0.24 mL/min/g vs 2.86 +/- 0.35 mL/min/g; P < .05), left ventricular pressure (117 +/- 18 mm Hg vs 82 +/- 4 mm Hg; P < .05), and first derivative of left ventricular pressure (3453 +/- 577 mm Hg/s vs 1740 +/- 116 mm Hg/s; P < .05) were significantly higher in the Custodiol-N group compared with the corresponding control. The left ventricular systolic pressure-volume relationship was significantly steeper, indicating improved contractility. Vasodilatatory response to sodium nitroprusside did not show any major differences between the groups. Response to bradykinin resulted in a significantly higher increase in coronary blood flow in the Custodiol-N group (92% +/- 4% vs 60% +/- 5%; P < .05). Myocardial adenosine triphosphate content was significantly higher in the Custodiol-N group (9.84 +/- 0.68 mumol/g vs 1.86 +/- 0.41 mumol/g; P < .05). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining showed a significantly reduced apoptosis level (21.58% +/- 1.59% vs 27.23% +/- 1.54%; P < .05) in the Custodiol-N group.

CONCLUSION:

Custodiol-N improves myocardial and endothelial function during the critical phase of reperfusion after heart transplantation.

• Authors: Sivakkanan Loganathan, Tamás Radovits, Kristóf Hirschberg, Sevil Korkmaz, Achim Koch, Matthias Karck, Gábor Szabó
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 139 Issue 4 Pg. 1048-56 (Apr 2010) ISSN: 1097-685X [Electronic] United States
• PMID: 19945120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Chemical References

• Custodiol-N solution
• Organ Preservation Solutions

Topics

• Animals
• Disease Models, Animal
• Endothelium, Vascular (drug effects)
• Heart (drug effects)
• Heart Transplantation (adverse effects)
• Male
• Myocardium
• Organ Preservation Solutions (pharmacology, therapeutic use)
• Rats
• Rats, Inbred Lew
• Reperfusion Injury (etiology, prevention & control)