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      The establishment of rat model in myocardial ischemia with psychological stress

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          Abstract

          Background

          Psychological stress can provoke and aggravate myocardial ischemia, and this stress can even trigger acute coronary syndromes or sudden cardiac death. Therefore, for the first time, this study aimed to investigate the method for establishing a rat model of myocardial ischemia with psychological stress and its evaluation.

          Methods

          Forty male Wistar rats were randomly divided into the sham (S, n=10), myocardial infarct (MI, n=10), psychological stress (MODEL, n=10), and myocardial infarct with psychological stress (MI + MODEL, n=10) groups. The rat model of psychological stress was established by measuring the data from activity restriction for 6 hours and followed by tail clamp stimulation for 5 minutes every day for 14 days. The rat model of the myocardial infarct with psychological stress was established by occluding the left coronary anterior descending artery in the MODEL rats. The body weight of rats was measured daily, the behavior parameters were evaluated via open-field test and elevated plus-maze, tongue color and sublingual vein were observed, rats’ acral blood flow perfusion was detected by PIM II (Perfusion Imager II), mesenteric microcirculation was measured by capillaroscopy, and hemodynamics was measured by a polygraph system. An automatic biochemical analyzer determined the content of serum cTnT (cardiac troponin T), Hcy (homocysteine), and activity of LDH (lactate dehydrogenase). Myocardial infarct size was measured with TTC (triphenyhetrazolium chloride) staining.

          Results

          We found that rats in the psychological stress (MODEL) group were characterized by coarse hair, dark mucosa of the lips and claw, low spirit, decreased body weight, and increased anxiety. Compared with rats in the sham group, rats in the MODEL + MI group showed decreased mesenteric blood flow, narrowed arteriole and venule diameter, reduced acral blood flow perfusion, and LV ±dp/dt max (the maximal rate of the increased and decrease of left ventricular pressure), as well as increased serum content of cTnT, Hcy, and LDH activity. Compared with the MI group, rats in the MODEL + MI group showed deteriorated microcirculation dysfunction manifested as a dark tongue color of deep purple, prominently extended and varicose sublingual vein, and aggravated myocardial damage in the form of increased infarct size and LDH leakage.

          Conclusions

          In conclusion, the rat model of myocardial ischemia with psychological stress was successfully established, and manifested as aggravating behavioral disorder, mesenteric microcirculation and left ventricular dysfunction, and myocardial damage.

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          Most cited references33

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          State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease.

          The notion that psychological states can influence physical health is hardly new, and perhaps nowhere has the mind-body connection been better studied than in cardiovascular disease (CVD). Recently, large prospective epidemiologic studies and smaller basic science studies have firmly established a connection between CVD and several psychological conditions, including depression, chronic psychological stress, posttraumatic stress disorder (PTSD), and anxiety. In addition, numerous clinical trials have been conducted to attempt to prevent or lessen the impact of these conditions on cardiovascular health. In this article, we review studies connecting depression, stress/PTSD, and anxiety to CVD, focusing on findings from the last 5 years. For each mental health condition, we first examine the epidemiologic evidence establishing a link with CVD. We then describe studies of potential underlying mechanisms and finally discuss treatment trials and directions for future research.
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            Psychological Stress, Inflammation, and Coronary Heart Disease.

            In this review, we summarize evidence on the risk factor psychological stress in the context of coronary heart disease (CHD) in humans and explore the role of inflammation as a potential underlying mechanism.
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              Depression and the Link with Cardiovascular Disease

              This review provides an outline of the association between major depressive disorder (MDD) and coronary heart disease (CHD). Much is known about the two individual clinical conditions; however, it is not until recently, biological mechanisms have been uncovered that link both MDD and CHD. The activation of stress pathways have been implicated as a neurochemical mechanism that links MDD and CHD. Depression is known to be associated with poorer outcomes of CHD. Psychological factors, such as major depression and stress, are now known as risk factors for developing CHD, which is as important and is independent of classic risk factors, such as hypertension, diabetes mellitus, and cigarette smoking. Both conditions have great socioeconomic importance given that depression and CHD are likely to be two of the three leading causes of global burden of disease. Better understanding of the common causal pathways will help us delineate more appropriate treatments.
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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                March 2020
                March 2020
                : 8
                : 6
                : 322
                Affiliations
                [1 ]Department of Pathophysiology, Chinese PLA General Hospital , Beijing 100853, China;
                [2 ]Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences , Beijing 100853, China;
                [3 ]Out-patient Department, Chinese PLA General Hospital , Beijing 100853, China
                Author notes

                Contributions: (I) Conception and design: XH Liu, C Wang, XR Wang; (II) Administrative support: XH Liu, XD Wu; (III) Provision of study materials or patients: XH Liu, XR Wang; (IV) Collection and assembly of data: C Wang, TQ Tao, DD Song, M Liu; (V) Data analysis and interpretation: JL Wang, Y Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Xiu-Hua Liu. Department of Pathophysiology, Chinese PLA General Hospital, Beijing 100853, China. Email: xiuhualiu98@ 123456163.com ; Xu-Dong Wu. Out-patient Department, Chinese PLA General Hospital, Beijing 100853, China. Email: wuxudong60@ 123456163.com.cn .
                Article
                atm-08-06-322
                10.21037/atm.2020.02.128
                7186656
                32355766
                6681a6d9-28a2-468a-b9e7-05ecff65ddbf
                2020 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 24 September 2019
                : 07 February 2020
                Categories
                Original Article

                myocardial ischemia,psychological stress,rat model
                myocardial ischemia, psychological stress, rat model

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