Ann Thorac Surg 2002;73:225
© 2002 The Society of Thoracic Surgeons
Invited commentary
Karl S. Ulicny, Jr, MDa
a Northern Kentucky Cardiac Surgery, Inc, 20 Medical Village Dr, Suite 204, Edgewood, KY 41017, USA
e-mail: nkycardiac{at}yahoo.com
Early acute graft dysfunction continues to plague successful lung transplantation. Reperfusion injury is characterized by an increase in pulmonary vascular resistance, poor oxygenation, decreased pulmonary compliance, and increased pulmonary capillary permeability leading to pulmonary edema. The literature consistently shows that Melatonin is one of the most potent oxygen free radical scavengers with the ability to neutralize the hydroxyl radical, singlet oxygen, the peroxyl radical and the superoxide anion. It is believed to directly detoxify the free radical by electron donation and to alter enzyme activity, ie, superoxide dismutase, to augment the antioxidative defense. Its antioxidant effect has been shown to protect nuclear DNA, membrane lipids and cystosolic proteins. It is readily absorbed and it crosses all physiologic barriers.
The University of Zurich group examined the effects of donor and recipient treatment with Melatonin in the rat single lung transplantation model after 18 hours of cold ischemia and 2 hours of reperfusion. The study demonstrated that the Melatonin treated group showed significantly improved oxygenation and reduced peak airway pressures. There was a decrease in lipid peroxidation, myeloperoxidase activity and thiobarbituric acid reactive substances in the treated group when compared to non-treated controls. The high BAL nitrite levels in non-treated controls were found to be nearly normal in the Melatonin treated group. However, plasma nitrite levels were close to normal in both groups implicating localized production of nitrous oxide in the injured lung. Neutrophil infiltration in the treatment group was also significantly less than control.
While the effects demonstrated are most likely related to Melatonin, it is not clear from this study whether ethanol had an impact on attenuating reperfusion injury. The control group received intraperitoneal saline only, despite the fact that the Melatonin solvent was 10% ethanol. Intraperitoneal ethanol injection would have served as a superior control for this experimental design, since ethanol itself may have some free radical scavenging capabilities. This study also does not delineate whether treatment only at the time of reperfusion is adequate, or whether the drug is required to be present in the lung at the time of initial ischemia (harvest). Since the authors administered Melatonin to both the donors prior to retrieval as well as to the recipients prior to reperfusion, it remains unclear whether or not Melatonin acts primarily during the ischemic period or during reperfusion.
Nevertheless, this elegant and simple study makes an interesting contribution to the transplant literature. The details of solvent and dosing strategy should be elucidated in subsequent trials.
Related Article
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Melatonin attenuates posttransplant lung ischemia-reperfusion injury
- Ilhan Inci, Demet Inci, André Dutly, Annette Boehler, and Walter Weder
Ann. Thorac. Surg. 2002 73: 220-225.
[Abstract]
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