[Ischemia-reperfusion injury during experimental heart transplantation. Evaluation of trimetazidine's cytoprotective effect].
OBJECTIVE
The objectives of this study were to analyze the ischemia-reperfusion injury due to free radicals that occurs during heart transplantation and to determine the potential cytoprotective effect of trimetazidine.


METHODS
A total of 21 orthotopic heart transplantations were performed in pigs. We divided the experimental animals into 2 groups: in group A (n=11),standard myocardial protection was used; in group B (n=10), trimetazidine was added to the cardioplegic solution used to protect the donor heart and to the solution administered to the recipient prior to release of the aortic clamp (trimetazidine, 10(-5) mol/L), and recipients were pretreated with trimetazidine, 2.5 mg/kg. Blood samples were taken from the recipients coronary sinus at three times: at baseline, during ischemia, and during reperfusion. We measured the levels of malondialdehyde, a marker of lipid peroxidation, and of several antioxidants: glutathione peroxidase, glutathione reductase, superoxide dismutase, alpha-tocopherol, and retinol. The total antioxidant status was also determined.


RESULTS
Malondialdehyde production and enzymatic antioxidant activity rose during ischemia and reperfusion, while the retinol level decreased. The increases in malondialdehyde level and glutathione peroxidase activity that occurred between baseline and reperfusion were significantly higher in group A. CONCLUSIONS. The degree of lipid peroxidation and the level of activity of intracellular antioxidant mechanisms increased progressively throughout transplantation. Trimetazidine had a cytoprotective effect. It ameliorated free radical-induced reperfusion injury and modified the response pattern of several defense mechanisms.
Castedo
Evaristo
E
Servicio de Cirugía Cardiovascular, Clínica Puerta de Hierro, Madrid, Spain. evaristocm@terra.es
Segovia
Javier
J
Escudero
Cristina
C
Olmedilla
Begoña
B
Granado
Fernando
F
Blas
Carmen
C
Guardiola
José M
JM
Millán
Isabel
I
Pulpón
Luis A
LA
Ugartea
Juan
J
D000818:Animals; D000975:Antioxidants; D002314:Cardioplegic Solutions; D019610:Cytoprotection; D005260:Female; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000097:blood; D016027:Heart Transplantation; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000097:blood; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013552:Swine; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000975:Antioxidants; D002314:Cardioplegic Solutions; D005609:Free Radicals; D014665:Vasodilator Agents; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D014292:Trimetazidine