ABC | Volume 113, Nº3, September 2019

Original Article Acute Physical Stress Preconditions the Heart Against Ischemia/ Reperfusion Injury Through Activation of Sympathetic Nervous System Alireza Imani, 1, 2 Hoda Parsa, 1* Leila Gholami Chookalaei, 1* Kamran Rakhshan, 3 Masoomeh Golnazari, 4 Mahdieh Faghihi 1 Department of physiology - School of Medicine - Tehran University of Medical Sciences, 1 Tehran – Iran Occupational Sleep Research Center - Baharloo Hospital - Tehran University of Medical Sciences, 2 Tehran – Iran Department of physiology - School of Medicine - Iran University of Medical Sciences, 3 Tehran – Iran Biology Department - Basic Sciences faculty - Hamedan Branch of Islamic Azad University, 4 Hamedan – Iran * Contributed equally to this work. Mailing Address: Alireza Imani • Department of Physiology - School of Medicine - Tehran University of Medical Sciences, Tehran – Iran E-mail :aimani@tums.ac.ir Manuscript received Auust 26, 2018, revised manuscript November 18, 2018, accepted October 16, 2018 DOI: 10.5935/abc.20190189 Abstract Background: Stress is defined as a complicated state that related to homeostasis disturbances, over-activity of the sympathetic nervous system and hypothalamus-pituitary-adrenal axis responses. Cardiac preconditioning reduces myocardial damages. Objective: This study was designed to assess the cardioprotective effects of acute physical stress against ischemia/ reperfusion (I/R) injury through the activation of the sympathetic nervous system. Methods: Thirty-two male Wistar rats were divided into four groups; (1) IR (n = 8): rats underwent I/R, (2) Acute stress (St+IR) (n = 8): physical stress induced 1-hour before I/R, (3) Sympathectomy (Symp+IR) (n = 8): chemical sympathectomy was done 24-hours before I/R and (4) Sympathectomy- physical stress (Symp+St+IR) (n = 8): chemical sympathectomy induced before physical stress and I/R. Chemical sympathectomy was performed using 6-hydroxydopamine (100 mg/kg, sc). Then, the hearts isolated and located in the Langendorff apparatus to induce 30 minutes ischemia followed by 120 minutes reperfusion. The coronary flows, hemodynamic parameters, infarct size, corticosterone level in serum were investigated. P < 0.05 demonstrated significance. Results: Physical stress prior to I/R could improve left ventricular developed pressure (LVDP) and rate product pressure (RPP) of the heart respectively, (63 ± 2 versus 42 ± 1.2, p < 0.05, 70 ± 2 versus 43 ± 2.6, p < 0.05) and reduces infarct size (22.16 ± 1.3 versus 32 ± 1.4, p < 0.05) when compared with the I/R alone. Chemical sympathectomy before physical stress eliminated the protective effect of physical stress on I/R-induced cardiac damages (RPP: 21 ± 6.6 versus 63 ± 2, p < 0.01) (LVDP: 38 ± 4.5 versus 43 ± 2.6, p < 0.01) (infarct size: 35 ± 3.1 versus 22.16 ± 1.3, p < 0.01). Conclusion: Findings indicate that acute physical stress can act as a preconditional stimulator and probably, the presence of sympathetic nervous system is necessary. (Arq Bras Cardiol. 2019; 113(3):401-408) Keywords: Stress, Mechanical; Sympathetic Nervous System; Hypothalamo-Hypophyseal System; Ischemia; Sympathectomy . Introduction Ischemic heart disease is the major health problem in the world. 1 Although reperfusion, which refers to the rapid reestablishment of blood flow, can be one of the most effective methods against lethal injuries, 2 it is associated with additional myocardial damage. 3 Many methods have been proposed to diminish the deleterious effect of ischemia/reperfusion (I/R) injuries and increase cardiac endurance. Based on these advances, induction the short-term episodes of I/R or using the pharmacological agents earlier than prolonged I/R period induces cardiac preconditioning which can successfully attenuate cellular necrosis and conserve high levels of energy. 4,5 Sympathetic nervous system and hypothalamus-pituitary- adrenal (HPA) axis are two coordinated defence systems. They can mediate two-way brain-body communication during stressful situations. 6 Autonomic system activation contributes to behavioral responses in animals and enables them to regulate homeostasis and improve endurance. 7 Stress is characterized as a general HPA axis response against potential and deleterious stimuli. 8 In fact, stress through increasing the activity of HPA axis and corticosterone release plays a critical role in coordinating of neuroendocrine, autonomic and behavioral functions and leads to adaptive responses. 9,10 The activity of the sympathetic nervous system increases and neurotransmitter secretion alters during the occurrence of stress. 11 Several body systems such as nervous, cardiovascular and immune systems are influenced by stress. Moreover, significant changes in hemodynamic parameters such as; heart rate (HR) and blood pressure are observed during stress which ultimatelymay lead to heart diseases. 12 On the other hand, the release of norepinephrine from the sympathetic nervous system is increased during lethal ischemia and it has a role for inducing of I/R injuries through the generation of hydroxyl free radicals. This current study was designed to evaluate the role of the sympathetic nervous system inmediating acute stress-induced cardioprotection against I/R injury in isolated rat heart. 401