Decreased nocturnal melatonin levels during acute myocardial infarction Introduction Melatonin (N-acetyl-5-methoxytryptamine) is synthesized by the pineal gland of vertebrates, including humans, and released following a circadian rhythm that regulates several physiological and neuroendocrine functions [1]. Synthesis and release of melatonin is stimulated at night by norepi- nephrine via b 1 -adrenoceptors, and this process is further potentiated by stimulation of a 1 -adrenoceptors [2]. Serum melatonin is hydroxylated in the liver to 6-hydroxymelato- nin, which, in turn, is conjugated to either sulphate (70– 80%) or glucuronide (5%) derivatives. These conjugates are then excreted in the urine [3]. Furthermore, it is also non- enzymatically metabolized to cyclic 3-hydroxymelatonin when it scavenges the hydroxyl radical (OH . ) [4]. Myocardial ischemia occurs when oxygen delivery to the myocardium is insufficient to satisfy mitochondrial oxida- tion. During ischemia, there is insufficient oxygen availab- ility but oxygen free radicals are still formed from the residual molecular oxygen [5]. Also, the activities of the mitochondrial electron-transport chain are reduced increas- ing electron leakage from the respiratory chain, which reacts with residual molecular oxygen and forms, among other free radicals, the superoxide anion (O 2 . ) ). In acute myocardial infarction, excess production of active oxygen species such as O 2 . ) and hydrogen peroxide (H 2 O 2 ) [6] can lead to the generation of more toxic oxidants such as the OH . [7]. If biomembranes are near the site of these reactive radicals, the membrane fatty acids are peroxidized and several different aldehyde products are generated. These aldehydes, malondialdehyde (MDA) + 4-hydroxyalkenals (4-HDA), appear to be intimately in- volved in cell degeneration induced by oxidative stress [8]. Glutathione peroxidase (GSH-Px) activity appears to account for all the hydroperoxide-reducing activity in human plasma. Considering the potentially deleterious effects of fatty acid hydroperoxides, this peroxidase may play an important protective role against hydroperoxide pathology [9]. Therefore, levels of these aldehydes and of GSH-Px in serum, are a good index of oxidative cellular stress. Melatonin protects against certain pathological condi- tions by scavenging reactive oxygen species [10] and reduces ischemic injury in several organs, the brain [11], the liver [12] and the heart [13]. There has been little published research, in humans, concerning the possible relevance of melatonin and free radical production in acute myocardial infarction. In the Abstract: Acute myocardial infarction is accompanied by an increase in cellular oxidative stress in the pericardial coverings of the heart. Melatonin is a highly potent and efficient radical scavenger. Little research has been carried out concerning the relationship between this antioxidant and acute myocardial infarction in humans. In this work, serum levels of melatonin and parameters of oxidative stress, such as glutathione peroxidase and lipid peroxidation levels were examined in light/dark periods in patients with acute myocardial infarction. Twenty-five patients diagnosed with acute myocardial infarction were studied and 25 patients with no evidence of coronary artery disease served as controls. Venous blood samples were obtained from the patients and control subjects to determine melatonin, glutathione peroxidase and lipid peroxidation; the samples were collected at 10:00 hr (light period) and 03:00 hr (dark period) in the first 24 hr after admission to the coronary care unit. Our results demonstrate the existence of differences between changes in melatonin levels in control subjects and acute myocardial infarction patients, revealing a reduced nocturnal elevation in the acute myocardial infarction group. Glutathione peroxidase levels were lower after acute myocardial infarction and did not show diurnal variations. In the control group, lipid peroxidation levels presented a light/dark pattern but in the acute myocardial infarction group diurnal variations of this parameter were lost. Our data show that acute myocardial infarction is associated with a nocturnal serum melatonin deficit as well as increased oxidative stress, suggesting that melatonin is, at least in part, depleted during the dark phase to reduce the free radicals formed in acute myocardial infarction. Alberto Domı ´nguez-Rodrı ´guez 1 , Pedro Abreu-Gonza ´lez 2 , Martı ´n J. Garcı ´a 1 , Juan Sanchez 2 , Francisco Marrero 1 and Diego de Armas-Trujillo 1 1 Department of Cardiology, Hospital Universitario de Canarias; 2 Department of Physiology, University of La Laguna, School of Medicine, Tenerife, Spain Key words: antioxidants, free radicals, ischemia, light/dark, melatonin, myocardial infarction Address reprint requests to: Pedro Abreu-Gonza ´ lez, Departamento de Enfermerı ´a, E.U. de Enfermerı ´a y Fisioterapia, Universidad de La Laguna, Campus de Cien- cias de La Salud, La Cuesta, La Laguna 38200, Tenerife, Spain. E-mail: pabreu@ull.es Received June 3, 2002; accepted July 22, 2002. J. Pineal Res. 2002; 33:248–252 Copyright Ó Blackwell Munksgaard, 2002 Journal of Pineal Research ISSN 0742-3098 248