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


CONCLUSIONS
Custodiol-N improves myocardial and endothelial function during the critical phase of reperfusion after heart transplantation.
Loganathan
Sivakkanan
S
Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 326 (2.OG), 69120 Heidelberg, Germany. sivakkanan.loganathan@googlemail.com
Radovits
Tamás
T
Hirschberg
Kristóf
K
Korkmaz
Sevil
S
Koch
Achim
A
Karck
Matthias
M
Szabó
Gábor
G
D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects; D008297:Male; D009206:Myocardium; D019188:Organ Preservation Solutions / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
C549285:Custodiol-N solution; D019188:Organ Preservation Solutions