OBJECTIVETo investigate the role of anti- interleukin-2 receptor (CD25) monoclonal antibody in the regulation of cytokine mRNA expression of IL-1beta, IL-2, CD25, IL-4, IL-5, IL-6, IL-10, tumour necrosis factor-alpha (TNFalpha), and interferon-gamma (IFNgamma) in cardiac allografts to elucidate its immunological mechanism and role in rats that have undergone cardiac transplantation.

METHODSThese in vivo studies were conducted using a rat MHC mismatch SD to Wistar heterotopic cardiac transplant model. Simulect, an anti-CD25 antibody, was used to prevent allograft rejection. An increase in the rate of allograft survival was observed. Rats were sacrificed on day 1, 3, 5, 7, 9, 11, 14 post-transplantation and hearts were harvested for further study. Cytokine mRNA expression was determined by semiquantitative RT-PCR.

RESULTSIn the control group, cardiac allografts were rejected at 8.3 +/- 1.7 days after transplantation (x +/- s). The rats who received CsA rejected the cardiac allograft at 26.4 +/- 5.7 days post-transplant. Allograft survival of Simulect-treated rats was 29.2 +/- 7.1 days (P < 0.05 vs controls). Rats treated with simulect and CsA had the longest survival of 55.0 +/- 11.6 days (P < 0.001 vs controls). CD25 mRNA expression in the heart tissue samples of treated rats was undetectable or very weak. However, the untreated group, CD25 expression increased, although anti-CD25 decreased this CD25 expression in the heart graft. Furthermore, in untreated allografts, IL-2, TNFalpha and IFN-gamma were strongly expressed, an effect that markedly decreased after simulect treatment. Finally, IL-4, IL-5, IL-6 and IL-10 expression was strong in anti-CD25-treated allografts.

CONCLUSIONSThese results suggest that anti-CD25 antibody treatment may not only neutralize CD25 activity but also play a role in altering cytokine mRNA expression and prolong the survival of allografts.

Animals ; Antibodies, Monoclonal ; therapeutic use ; Cytokines ; genetics ; Graft Survival ; Heart Transplantation ; immunology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, Interleukin-2 ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Homologous

The cardioprotective effects of melatonin on recovery of rat donor hearts after 12 h of preservation were investigated. Wistar rats weighing 200 to 250 g (n=24) were randomly divided into 3 groups. In the non-storage group (n=8), donor hearts were not stored. In the melatonin group (n=8), donor hearts were stored in 4 degrees C St. Thomas solution with melatonin (0.1 mmol/L). In the control group (n=8), donor hearts were stored in 4 degrees C St. Thomas solution only. The coronary flow (CF), cardiac function, coronary vasodilatory response, creatine kinase (CK) and high energy phosphate levels were measured after the hearts had been preserved for 12 h. Transmission electron microscopy was used to examine the microstructural changes after 12 h of preservation. The recovery of cardiac function and coronary vasodilatory response were significantly improved in the melatonin group (P<0.01). CK release decreased greatly in the melatonin group (P<0.01). High energy phosphate levels were significantly better preserved in the melatonin group (P<0.01). Histological findings were much better in the melatonin group than in the control group. These results suggest that melatonin has cardioprotective effects on the recovery of rat donor hearts after 12 h of preservation.
Animals ; Cardiotonic Agents ; pharmacology ; Creatine Kinase ; metabolism ; Free Radical Scavengers ; pharmacology ; Heart Transplantation ; Humans ; Hydroxyl Radical ; Male ; Melatonin ; pharmacology ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; metabolism ; ultrastructure ; Organ Preservation ; methods ; Random Allocation ; Rats ; Rats, Wistar ; Time Factors

To study the effects of different pH HEPES-KH reperfusate solution on immature myocardial protection, isolated perfused Langendorff model from immature rabbit hearts were developed formed. Control group (C) was perfused only with pH 7.4 HEPES-KH solution for 90 min. Ischemia/reperfusion group (group I/R) was perfused with pH 7.4 HEPES-KH solution before ischemia or after ischemia. Experimental group (group E), after ischemia, was perfused with pH 6.8, pH 7.1 and pH 7.4 HEPES-KH solutions for 5 min, 5 min, and 20 min, respectively. The left ventricular function recovery, MWC, LDH and CK leakage, MDA, ATP content, and SOD activity were determined. Our results showed that the left ventricular function recovery, ATP content and SOD activity in group E were higher than those of group I/R (P < 0.05). MWC, MDA content, LDH and CK leakage in group E were lower than those of group I/R (P < 0.05). These findings suggested that pH paradox might be one of important mechanisms for immature myocardial ischemia-reperfusion injury, and acidic perfusate, at the beginning of reperfusion, might attenuate pH paradox and ameliorate functional recovery in isolated perfused immature rabbit hearts.
Animals ; Cardioplegic Solutions ; pharmacology ; Female ; Heart ; physiopathology ; Heart Arrest, Induced ; Hydrogen-Ion Concentration ; Male ; Myocardial Ischemia ; metabolism ; physiopathology ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; prevention & control ; Myocardium ; metabolism ; Rabbits ; Random Allocation ; Superoxide Dismutase ; metabolism