S-nitroso Human Serum Albumin Attenuates Ischemia/Reperfusion Injury After Cardioplegic Arrest in Isolated Rabbit Hearts
By Semsroth, Severin; Fellner, Barbara; Trescher, Karola; Bernecker, Oliver Y.; Kalinowski, Leszek; Gasser, Harald; Hallström, Seth; Malinski, Tadeusz & Podesser, Bruno K.
Published in The Journal of Heart and Lung Transplantation
2005
Abstract
Background Depletion of nitric oxide (NO) is associated with ischemia/reperfusion injury. The novel NO donor, S-nitroso human serum albumin (S-NO-HSA), could bridge NO depletion during reperfusion in cardiac transplantation and minimize ischemia/reperfusion injury. Methods In an isolated erythrocyte-perfused working heart model, rabbit hearts were randomly assigned after assessment of hemodynamic baseline values to receive S-NO-HSA (0.2 μmol/100 ml, n = 8), L-arginine (10 mmol/100 ml, n = 8) or albumin (control) (0.2 μmol/100 ml, n = 8). After 20 minutes of infusion, the hearts were arrested and stored in Celsior (4°C) enriched with respective drugs for 6 hours, followed by 75 minutes of reperfusion. Hemodynamic values were assessed and biopsy specimens were taken to determine calcium-ionophore stimulated release of NO and superoxide. Results During early reperfusion, recovery of cardiac output (75% ± 6% vs 49% ± 5%, p < 0.05) and coronary flow (99% ± 8% vs 70% ± 5%, p < 0.05) were higher, and myocardial oxygen consumption was reduced in the S-NO-HSA Group compared with Control (4.08 ± 0.46 ml/min/0.1 kg vs 6.78 ± 0.38 ml/min/0.1 kg, p < 0.01). At the end of the experiment cardiac output (53% ± 5% vs 27% ± 5%, p < 0.01) was higher and left atrial pressure (115% ± 9% vs 150% ± 8%, p < 0.05) was lower in the S-NO-HSA Group compared with Control. NO release was increased (1,040 ± 50 nmol/liter and 1,070 ± 60 nmol/liter vs 860 ± 10 nmol/liter, p < 0.01) and superoxide release diminished (31 ± 5 nmol/liter and 38 ± 5 nmol/liter vs 64 ± 5 nmol/liter, p < .01) in the S-NO-HSA and L-arginine Groups compared with Control. Conclusion S-NO-HSA improved hemodynamic functions after prolonged hypothermic cardiac arrest by supplementing NO and thereby decreasing ischemia/reperfusion injury.