Effect of Melatonin and Atenolol on Carbon Monoxide Cardiotoxicity: An Experimental Study in Rats

Abstract

The aim of this study was to define the characteristics of heart rates and myocardial changes in rats exposed to carbon monoxide (CO), and the effects of reoxygenation, atenolol (a b-blocker) and melatonin after sublethal CO intoxication. Widespread use of b-blockers in cardiology practice and growing literature on the positive effect of melatonin in ischaemia reperfusion lead us to question their effects in case of CO intoxication. Rats were exposed to CO. After sublethal intoxication the rats were reoxygenated with ambient air. Subsequently blood values, electrocardiographic recordings and pathological changes were examined for each groups. Five rats died after CO intoxication in the control group: no myocardial changes were seen in light microscopy. However, myocardium of seven reoxygenated rats presented contraction bands. Seven reoxygenated rats pretreated with atenolol had a higher number of contraction bands of myocardial cells. Seven reoxygenated rats pretreated with melatonin had more contraction bands than reoxygenated rats, and heart rate recordings of these animals revealed a profund and sustained bradycardia. Thus, melatonin and atenolol appear to have some adverse effects in CO intoxication on the myocardial cells.It is a well-known fact that carbon monoxide (CO) is cardiotoxic (Gandini et al. 2001). Cardiac failure and myocardial ischaemias have been described in man after acute CO poisoning (Varon et al. 1999). CO poisoning is the most common cause of death in combustion-related inhalation injury. The incidence of non-lethal CO poisoning is not well established nor is that of unrecognized CO poisoning (subacute poisoning). Also, there are some reports on myocardial morphologic changes in acute CO poisoning, especially stressing the importance of contraction bands (Fineschi et al. 2000;Baroldi et al. 2001).Melatonin is a pineal hormone, and also commercially available as over-the-counter for use in hope of rejuvenation. Melatonin affects the heart by direct and indirect ways (Pang et al. 2000;Sewerynek 2002). Melatonin was widely used in experimental animal models to reduce the infarct size in ischaemia reperfusion injury (Kashimoto et al. 1999;Sahna et al. 2002).Atenolol is a b-blocker and antagonizes the b1 adrenergic effects on cardiovascular system; it lowers the blood pressure and decreases the heart rate (Vidrio et al. 1998). It is routinely prescribed by cardiologists to treat hypertension and some cardiac problems.Levels of blood carboxyhaemoglobin have been found to vary in suspected CO victims (Gorman et al. 2003). This variability may depend on metabolic differences of individuals, and various drugs may effect synergistically or antagonistically. Thus physicians involved in forensic medicine Author for correspondence: Bülent Mızrak, Department of Pathology, İnö nü University Medical School, P.K.2 Karakas Malatya 44020, Turkey (fax π90 422 3410174, e-mail bmizrak/inonu.edu. tr).are faced with the interactions between CO and drugs sometimes leading to confusion.In this study we ...

Delayed Neurological Sequelae Successfully Treated with Adjuvant, Prolonged Hyperbaric Oxygen Therapy: Review and Case Report

“…Specifically, the increase in biomarkers of cardiac damage without changes seen on ECGs at the admission and on cardiac ultrasound at the follow-up can be due to cell death without clinically significant ischemic lesions. Such explanation is consistent with previous findings of Fineschi et al on human heart histological samples of fatal CO intoxications [31] and experimental CO intoxication and reoxygenation mouse models by Mizrak et al [32].…”

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy

“…n Author disclosures are available with the text of this article at www.atsjournals.org. (118) Rats Pretreatment associated with increased contraction band necrosis Nimodipine (115) Mice Decreased impairment of memory function and improved mortality rate Verapamil (113) Rats No improvement in survival, blood pressure, blood lactate, or cerebral edema…”

“…Therapies targeting inflammation and oxidative stress induced by CO poisoning may be effective. Nodal blocking agents seem to have a mixed picture despite CO poisoning being proarrhythmic (113,115,118). Ionotropes can be used to support severe cardiac dysfunction with shock or hypotension.…”

The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: An in-depth analysis

“…erythrocytes) injury, as shown in both experimental animal studies and clinical studies. [1][2][3][4] ROS-mediated pathology has also been supported by the amelioration of some pathologies, and by the reduced lipid peroxidation seen following treatment with antioxidants like melatonin, 5 atenolol, 5 some internal molecules like bilirubin 6 and hydrogen, 7 and some others such as hydrogen sulfide (H 2 S) 8 and other free radical blockers. 9 ROS-mediated neuronal injury occurs when oxidative stress exists.…”