Deferoxamine, the newly developed iron chelator LK-614 and N-alpha-acetyl-histidine in myocardial protection.
During cold storage of donor hearts, reactive oxygen species produced by intracellular redox-active chelatable iron potentially alter myocardial function. To reduce this cold-induced injury we investigated the efficacy of two new modifications of the well established histidine-tryptophan-ketogluterate (HTK) solution (Custodiol) with the addition of N-alpha-acetyl-l-histidine and iron-chelators in a heterotopic rat heart transplantation model. The donor hearts were cardioplegically arrested with 20 ml cardioplegia and stored for 1 h. Then the hearts were anastomosed to the abdominal aorta and vena cava of the recipient (n=30). After 1 h reperfusion, myocardial function and energy charge potential were measured in three groups: HTK-1: addition of l-arginine and N-alpha-acetyl-l-histidine; HTK-2: addition of iron-chelators deferoxamine and LK-614; traditional HTK - control. After 1 h reperfusion, left ventricular systolic pressure (106+/-33 vs. 60+/-39, vs. 67+/-8 mmHg, P<0.05) and dP/dt minimal (-1388+/-627 vs. -660+/-446, vs. 871+/-188 mmHg/s, P<0.05) were significantly higher in the HTK-1 group. Energy charge potentials were not significantly different. This study showed that the novel modified HTK-1 solution improves myocardial contractility and relaxation after heart transplantation. Nevertheless, addition of the iron-chelators deferoxamine and LK-614 diminished these beneficial effects.
Koch
Achim
A
Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. achim_koch@med.uni-heidelberg.de
Loganathan
Sivakkanan
S
Radovits
Tamas
T
Sack
Falk-Udo
FU
Karck
Matthias
M
Szabó
Gabor B
GB
D000818:Animals; D050377:Cold Ischemia / Q000009:adverse effects*; D003676:Deferoxamine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D016027:Heart Transplantation; D006639:Histidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009926:Organ Preservation; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
C039984:Bretschneider cardioplegic solution; D006877:Hydroxamic Acids; D007502:Iron Chelating Agents; D019188:Organ Preservation Solutions; D008353:Mannitol; D006639:Histidine; D011343:Procaine; D011189:Potassium Chloride; D005947:Glucose; D003676:Deferoxamine; C023495:N-acetylhistidine