Melatonin beeinträchtigt die Mikrozirkulation und verstärkt die Nekrose kritisch perfundierten Gewebes in 'random pattern flaps'

Background: Melatonin is predominantly produced in the pineal gland, the retina and the enterochromaphine cells during the dark period. As receptors for melatonin are spread in diverse tissues, multiple physiological roles of melatonin in a variety of organs may be assumed. Recent investigations showed a vasoconstricting effect not only in the cerebrum but also in the intestine and the skin with downregulation of metabolism and thus a higher tolerance towards ischemia. Additionally, melatonin acts as a radical scavenger and thus may improve tissue survival during oxidative stress. Because flap necrosis still represents a challenge in plastic and reconstructive surgery, the present study was performed to investigate the effects of melatonin on survival of ischemic myocutaneuos tissue in random pattern flaps. Material and Methods: Dorsal random pattern flaps were prepared in C57BL/6 mice. By means of intravital fluorescence microscopy, we analyzed the area of necrotic tissue, functional capillary density (FCD) in the proximal, central and distal part of the flaps as well as arteriolar diameter and blood flow. Animals were either treated with melatonin (10 mg/kg twice daily, ip, n = 9) or vehicle (controls, 1 % ethanol, 0.1 ml/kg twice daily, ip, n = 7). Microscopic analyses were performed at day 1, 3, 5, 7 and 10 after surgery. Results: In vehicle-treated animals, tissue necrosis of about 30 % of the total flap surface developed within 10 days. The application of melatonin significantly increased the amount of necrotic tissue to about 60 % (p < 0.05). In parallel, FCD was significantly reduced in treated mice as compared to controls, especially in the proximal and the most critical central part (controls: 200 ± 29 cm/cm2; melatonin: 24 ± 14 cm/cm2; day 10). In the distal part, differences between groups were not significant. In addition, we found a distinct arteriolar constriction (36 ± 1 µm vs 54 ± 3 µm in controls) and reduction of blood flow (121 ± 121 pl/s vs 1136 ± 577 pl/s in controls) after melatonin treatment. Conclusion: In our model of chronic ischemia, we could not demonstrate a protective effect of melatonin that has been observed in other experimental models. In contrast, there was a significant impairment of perfusion an thus an increase of tissue necrosis. This discrepancy may be explained by the fact that in studies showing protection models were used exhibiting predominantly ischemia/reperfusion-injury rather than chronic ischemia, but also by the melatonin- induced reduction of NOS-expression, which may be the cause of the observed arteriolar hypoperfusion.