Pharmacological Research 64 (2011) 218–225 Contents lists available at ScienceDirect Pharmacological Research journa l h o me pa ge: www.elsevier.com/locate/yphr s Beneficial effects of l-leucine and l-valine on arrhythmias, hemodynamics and myocardial morphology in rats Katarzyna Mitr ˛ ega a,∗ , Michał ˙ Zorniak a , Benoy Varghese a , Dariusz Lange b , Jerzy No ˙ zynski c , Maurycy Porc a , Szymon Białka a , Tadeusz F. Krzemi ´ nski a a Chair and Department of Pharmacology, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze, Poland b Department of Tumor Pathology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwce Branch, ul. Wybrze ˙ ze Armii Krajowej 15, 44-101 Gliwice, Poland c Silesian Centre for Heart Diseases, ul. Szpitalna 2, 41-800 Zabrze, Poland a r t i c l e i n f o Article history: Received 17 December 2010 Received in revised form 14 April 2011 Accepted 26 April 2011 Keywords: l-Leucine l-Valine Reperfusion arrhythmias Hemodynamic Rat a b s t r a c t Branched chain amino acids (BCAA) have been shown to have a general protective effect on the heart in different animal models as well as in humans. However, so far no attempt has been made to specifi- cally elucidate their influence on arrhythmias. Our study was performed to evaluate whether an infusion of either l-leucine or l-valine in a dose of 1 mg kg -1 h -1 10 min before a 7-min period of left anterior descending artery occlusion followed by 15 min of reperfusion, had an effect on arrhythmias measured during the reperfusion phase in the ischemia- and reperfusion-induced arrhythmias model in rats in vivo. The effect of the infusion of these substances on mean arterial blood pressure was monitored throughout the experiment. Both of the tested amino acids exhibited significant antiarrhythmic properties. l-Leucine reduced the duration of ventricular fibrillation (P < 0.05) and l-valine decreased the duration of ventric- ular fibrillation (P < 0.001) and ventricular tachycardia (P < 0.05). The two amino acids were generally hypotensive. l-Valine lowered blood pressure in all phases of the experiment (P < 0.05) while l-leucine lowered this parameter mainly towards the end of occlusion and reperfusion (P < 0.05). In addition, 30 min infusion of the amino acids in the used dose did not produce any apparent adverse histological changes that were remarkably different from control. In summary, the results of our study suggest that l-leucine and l-valine in the dose that was used attenuates arrhythmias and are hypotensive in their influence. Our findings lend support to the many ongoing investigations into the benefit of the application of l-leucine and l-valine in cardiology like their addition to cardioplegic solutions. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Branched chained amino acids (BCAA) are widely studied mainly for the role they play in regulating and enhancing skeletal muscle protein anabolism [1–3]. Numerous studies have shown that BCAA have various diverse actions such as protection against ischemia and reperfusion induced injuries in isolated rat liver [4] and rat kidney [5], modulation of seizure activity [6,7] and stimulation of respiration [8]. This class of amino acids is unique in that they are metabolized mainly in peripheral tissues such as skeletal and cardiac muscle [9–12] unlike the rest of the amino acids which are metabolized mainly in the liver. After absorption in the gut all BCAA undergo transamination by branched-chain aminotrans- ∗ Corresponding author at: Chair and Department of Pharmacology, Cardiovascu- lar Research Division, Medical University of Silesia, ul. Jordana 38, 41-808 Zabrze, Poland. Tel.: +48 32 2724657; fax: +48 32 2724657. E-mail address: kas-k2@o2.pl (K. Mitr ˛ ega). ferase (BCAT) followed by decarboxylation. The activity of BCAT is low in the liver and is highest in the kidney and muscle tissue [13,14]. BCAA are known to protect skeletal muscle against damage after extensive exercise. In one study, long term (14 days) dietary supplementation with BCAA was shown to reduce serum creatine kinase (CK) and lactose dehydrogenase concentrations after pro- longed exercise in human subjects [15]. In another study ingestion of BCAA immediately before and during endurance exercise was shown to lower serum CK concentrations [16]. Interestingly, there is also evidence which attributes a potential cardioprotective role to the BCAA. Li and Gao [17] reported that dietary supplementation with BCAA protected cardiomyocytes against acute ischemic injury induced by isoproterenol. In isolated rat hearts BCAA was shown to enhance postischemic pressure recovery, improve postischemic systolic and diastolic myocardial function and delay the time to ischemic contracture [18]. Similar protection of the myocardium against adverse effects of ischemia has been noted by others [19]. Finally, in human subjects with coronary artery disease [20], 1043-6618/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.phrs.2011.04.011