Search

The present study was designed to assess whether acute rejection affects myocardial energy content of the human orthotopically transplanted heart. Adenosine triphosphate content was measured in one tissue sample obtained during 46 routine right ventricular endomyocardial biopsies 6 to 455 days (98 +/- 110) after transplantation in 19 cyclosporine-treated transplant recipients. Tissue samples were immediately frozen in liquid nitrogen within 10 seconds after excision. Adenosine triphosphate analysis was performed with high performance liquid chromatography. Three groups of biopsy specimens were classified according to the standardized cardiac biopsy grading system. Group 1: Eight biopsy specimens without rejection; group 2: 24 biopsy specimens with mild rejection; group 3: 14 biopsy specimens with moderate or severe rejection. Graft systolic function evaluated by echocardiographic fractional shortening was in the normal range the day of biopsy. All patients had normal coronary angiograms within 1 month of the study. In the presence of mild rejection (grade 1A or 1B), adenosine triphosphate content was not significantly different from that of nonrejecting hearts (26.15 +/- 7.1 and 28.57 +/- 8.23 nmol/mg protein, respectively). By contrast, a significant decrease in adenosine triphosphate content was observed when moderate or severe rejection with focal or diffuse aggressive infiltrates were present (10.46 +/- 4.11 nmol/mg protein; p < 0.01 versus two other groups). In seven cases, sequential analysis showed a significant increase in adenosine triphosphate content after rejection therapy concomittant with histologic improvement: 10.19 +/- 2.9 before and 30.13 +/- 7.0 nmol/mg protein after treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The production of free radicals during the reperfusion of hearts after prolonged ischemia might be responsible for the deleterious effects observed. Several strategies have attempted to limit this production or trap the radicals produced. This study aimed to evaluate the efficacy of a sodium lactobionate-based solution supplemented with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, a stable nitroxide free radical, in scavenging hydroxyl radicals produced during the reperfusion of the isolated rabbit heart. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl was administered just before the end of the storage period (6 hours) in a cardioplegic solution, either crystalloid solution or sodium lactobionate-based solution. The production of hydroxyl radicals was assessed through the production of dihydroxybenzoic acid, a reaction compound of hydroxyl radicals with salicylate. Two main isomers of dihydroxybenzoic acid were found in the coronary effluents: 2,3 and 2,5 dihydroxybenzoic acid. The production was 40-fold lower when the hearts received sodium lactobionate-based solution than when they received crystalloid solution (p < 0.001). The presence of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl had no influence on the production of hydroxyl radicals. The production of hydroxyl radicals was maximal during the first minute of the reperfusion. Iron ions, directly involved in the production of hydroxyl radicals, were shown to be complexed by sodium lactobionate in vitro. These results underlie the important role of lactobionate in the prevention of the reperfusion injury and the inefficacy of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to decrease the production of hydroxyl radicals.