[Ischemia-reperfusion injury during experimental heart transplantation. Evaluation of trimetazidine's cytoprotective effect]. / Daño por isquemia-reperfusión durante el trasplante cardíaco experimental. Evaluación del papel citoprotector de la trimetazidina.

INTRODUCTION AND OBJECTIVES: 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. MATERIAL AND METHOD: 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.

Daño por isquemia-reperfusión durante el trasplante cardíaco experimental. Evaluación del papel citoprotector de la trimetazidina / Ischemia-reperfusion injury during experimental heart transplantation. Evaluation of trimetazidine’s cytoprotective effect

Introducción y objetivos. El objetivo de este trabajo fueanalizar el daño por isquemia-reperfusión mediado por radicales libres que se produce durante el trasplante cardíaco y eva-luar el posible efecto citoprotector de la trimetazidina (TMZ). Material y método. Se realizaron 21 trasplantes cardíacos ortotópicos en cerdos. Dividimos los experimentos en 2 grupos: A (n = 11), en el que se realizó una protección miocárdica estándar, y B (n = 10), en el que se administró TMZ en la cardioplejía empleada para parar el corazón donante (TMZ, 10–5 mol/l), como pretratamiento intravenosodel receptor (TMZ, 2,5 mg/kg) y como parte de la cardio-plejía infundida en el receptor antes de despinzar la aorta(TMZ, 10–5 mol/l). Se tomaron muestras de sangre del senocoronario del receptor en 3 momentos: basal, isquemia y reperfusión. Se determinó la concentración de malonildial-dehído como marcador de peroxidación lipídica y de variosantioxidantes: glutatión peroxidasa, glutatión reductasa,superóxido dismutasa, α-tocoferol, retinol y estado de antioxidantes totales. Resultados. Durante la isquemia-reperfusión aumentóla producción de malonildialdehído y la actividad de losantioxidantes enzimáticos, mientras que el retinol disminuyó. El incremento de malonildialdehído y de la actividad de la glutatión peroxidasa entre el momento basal y la reperfusión fue significativamente mayor en el grupo A. Conclusiones. Durante el trasplante se incrementó progresivamente el nivel de peroxidación lipídica y se activaronlos sistemas antioxidantes intracelulares. La TMZ ejerció un efecto citoprotector y limitó el daño por isquemia-reperfusión generado por los radicales libres, además de modificar el patrón de reacción de parte de los sistemas de defensa

Introduction and objectives. The objectives of thisstudy were to analyze the ischemia-reperfusion injury dueto free radicals that occurs during heart transplantationand to determine the potential cytoprotective effect of trimetazidine. Material and method. 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, 10–5mol/L), and recipients were pretreated with trimetazidine, 2.5 mg/kg. Blood samples weretaken from the recipient’s 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, α-tocopherol, and retinol. The total antioxidant status wasalso determined. Results. Malondialdehyde production and enzymaticanti oxidant 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