Association of ischemia-modified albumin and melatonin in patients with ST-elevation myocardial infarction
Introduction
In patients with acute coronary syndromes myocardial necrosis is time-dependent and occurs when the action of protective endogenous mechanisms is finally overwhelmed by the ischemic process [1]. During acute ischemic conditions, the metal binding capacity of albumin for transition metals such as copper, nickel and cobalt is reduced, generating a metabolic variant of the protein, known as ischemia-modified albumin (IMA) [2]. The precise mechanism for IMA generation is yet unknown, though it appears that reactive oxygen species (ROS), produced during ischemia and ischemia–reperfusion, generate highly reactive hydroxyl-free radicals resulting in site-specific modification of the N-terminus of the albumin moiety, especially of the N-Asp–Ala–His–Lys sequence [3], [4]. Recently, in vitro studies have shown that ROS, and specifically the hydroxyl radical, may chemically modify human serum albumin, resulting in IMA formation [5].
Several recent publications showed that melatonin, a circadian endogenously indolamine product, is a direct scavenger of ROS. The fact that melatonin directly detoxifies O2-based free radicals and related reactants is well documented [6], [7]. For example, melatonin is a highly effective scavenger of the hydroxyl radical as shown in different studies [8]. Furthermore, some products of melatonin's interaction with O2-based reactants have been identified, and three of them, i.e. cyclic 3-hydroxymelatonin, N-acetyl-N-formyl-5-methoxykynuramine and N-acetyl-5-methoxykynuramine, are also known to be effective free radical scavengers [7]. This cascade of reactions greatly increases the effective concentrations of melatonin and may account, in part, for the high efficacy of this antioxidant in protecting against ischemia–reperfusion injury on the heart.
On the basis of the evidence provided by the reports summarized above, we compared blood levels of IMA and melatonin in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and evaluated the association of these molecules in this model.
Section snippets
Study population
We assessed 27 patients who were admitted to the Coronary Care Unit of the University Hospital of Canarias with a diagnosis of STEMI [9]. Patients who had infectious or autoimmune diseases or malignancies were not included in this study. Similarly, the use of illicit drugs, immunosuppressants, sedatives, antiepileptic drugs, tricyclic antidepressants, and any medications that influence melatonin metabolism was considered an exclusion criterion. Subjects with diabetes mellitus, psychiatric
Results
Baseline characteristics of all subjects in the study are listed in Table 1. Established risk factors for coronary artery disease were similar in both groups. As expected, peak troponin I levels were significantly higher in STEMI-patients than in control subjects. The baseline renal function was defined according to the modification of diet in renal disease (MDRD) equation [12]. There were no differences in the baseline renal function between STEMI-patients and control subjects (ClCr 85
Discussion
In the present study, we showed, for the first time, an association between serum levels of IMA and melatonin in STEMI-patients. IMA has been reported to increase after PCI [13], [14], [15], [16] and in acute coronary syndromes [17], [18]. Our study showed a significant increase in IMA after myocardial ischemia–reperfusion in STEMI-patients treated with primary PCI, during both the day and at night. Detectable changes in IMA have been documented to occur minutes after transient occlusion and
Acknowledgements
The authors thank specially the nursing staff of the Coronary Care Unit of the University Hospital of Canarias for their assistance in blood sample collection. We also thank Professor Armando Torres for assistance with statistical analysis.
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