ABC | Volume 113, Nº3, September 2019

Original Article Imani et al. Sympathetic nervous system and cardioprotection Arq Bras Cardiol. 2019; 113(3):401-408 160 140 120 100 80 60 Systolic blood pressure (mmHg) 40 20 0 pre Sympathectomy * post Figure 6 – Systolic blood pressure before and after chemical sympathectomy. *p < 0.05 compared to before sympathectomy. the hemodynamic parameters are improved in St+IR group in compare to the IR group. Diminished infarct size led to reducing in cardiac arrhythmia occurrence 31,32 and also improved cardiac contractility. 33 It seems the beneficial effects of acute stress induction may relate to the improvement of immune system function due to elevated corticosterone level encounter inflammatory factors, which trigger I/R injuries. The effects of sympathectomy It has been established that exposure to stressful conditions increase autonomic nervous system activity. 30 The cardioprotection of sympathetic activity has been investigated 34 and we used chemical sympathectomy after acute stress induction to confirm the protective effects of the sympathetic nervous system. Animals in Symp+IR group were subjected to chemical sympathectomy before induction of I/R and there was no significant change in infarct size in comparison to IR group, indicating that chemical sympathetic denervation has no effect on IR injury. In addition, chemical sympathectomy prior to physical acute stress removed the cardioprotection effect of acute stress on infarct size in Symp+St+IR group that emphasizes the presence of sympathetic system is necessary for cardioprotective effects of acute stress. We found that acute stress induction after chemical sympathectomy could overcome harm effects of deleted sympathetic system on hemodynamic parameters in Symp+St+IR groupwhen compared to Symp+IR group that indicates the essential role of sympathetic system physiological activity in regulating HR, pressure and flow. 35 Hara and Abiko declared norepinephrine has two opposite effects on ischemia damages according to the duration of ischemia, means that it could protect the heart with short ischemia and increase the injuries with prolonged ischemia. 28 Positive and negative properties of the sympathetic nervous system are associated with the duration of stimulus exposure. At the long term ischemia, large quantities of norepinephrine are released from the sympathetic nervous system, acting as a source of the free radical and subsequent generation of OH free radical. 36 Protective effect of norepinephrine can be emerged by producing energy for cardiac muscle in short term ischemia episode. 37 Moreover, Yohimbine (as an alpha2 receptor antagonist) administration reduced the incidence of arrhythmia through increasing sympathetic norepinephrine release. 37,38 According to our previous studies, pretreatment with alpha receptor agonist such as phenylephrine could protect the cardiomyocytes against I/R damages in isolatedHR. 39 Activation of protein kinase-C (PKC) signalling pathway 40 and NO release 41 by norepinephrine, are involved in the opening of mitochondrial KATP channels, which in turn can reduce mitochondrial calcium load 42 and will lead to attenuation of norepinephrine beneficial effects. Also, we showed that systolic blood pressure declined after chemical sympathectomy that is compatible with this fact that muscle sympathetic outflow is responsible for the regulation of blood pressure. 43 The limitations of this study were the method of induction physical stress does not commonly occur in daily life. Unfortunately, the data of corticosterone level in Symp+IR group were missed so we can’t discuss the effect of sympathectomy on corticosterone level and comparison between St+IR group and Symp+St+IR group is not significant. In consistence with our results, Lowrance et al. showed that stress-induced corticosterone level didn’t change following pharmacological sympathectomy. 44 Conclusion Thepresent study showed that inductionof physical acute stress before I/R led to cardioprotection and chemical sympathectomy removed this beneficial effect of physical acute stress. Acknowledgements This study was supported by Tehran University of medical sciences. Author contributions Conception and design of the research: Imani A, Faghihi M; Acquisition of data: Rakhshan K, Golnazari M; Analysis and interpretation of the data: Imani A, Parsa H, Chookalaei LG, Faghihi M; Statistical analysis and Writing of the manuscript: 406