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Sample records for infarcted rat heart

  1. MLP accumulation and remodelling in the infarcted rat heart.

    PubMed

    Wilding, James R; Lygate, Craig A; Davies, Kay E; Neubauer, Stefan; Clarke, Kieran

    2006-06-01

    Mutation of cytoskeletal protein genes results in abnormal protein function and causes cardiomyopathy. We hypothesised that cardiac levels of cytoskeletal proteins, such as dystrophin, desmin and muscle LIM protein (MLP), would be altered during remodelling caused by myocardial infarction (MI). We measured left-ventricular morphology, function and cytoskeletal protein levels 10 weeks after coronary artery ligation or sham operation in male Wistar rats. Two-dimensional echocardiography revealed significant impairment of systolic function and decreased ejection fraction in infarcted hearts compared with sham (47+/-5% versus 73+/-4%), commensurate with the development of heart failure. Western blotting was used to measure levels of beta-myosin heavy chain (beta-MyHC), a marker of hypertrophy, and levels of dystrophin, desmin, MLP, beta-tubulin, utrophin and syncoilin, using GAPDH for normalization. Relative to shams, beta-MyHC and MLP levels were increased 1.9-fold and 1.7-fold, respectively, in infarcted rat hearts, whereas the levels of other cytoskeletal proteins were unchanged. Both MLP and desmin protein levels correlated negatively with ejection fraction, with the strongest relation between MLP and ejection fraction (r=-0.95, n=13, p<0.0001). This work suggests that MLP may play an important compensatory role in cardiac remodelling following MI.

  2. [Dynamic detection of surface blood flow in rat heart and its application in real time identification of myocardial infarction model].

    PubMed

    Lei, Q; Chen, C; Wu, X L; Chen, W J; Yi, T; Ma, M D; He, Y; Shui, X R; Huang, S A; Chen, C; Lei, W

    2017-04-04

    Objective: To establish a method for monitoring the surface blood flow in the heart of rats, and to clarify the relationship between the degree of myocardial infarction and the blood perfusion on the surface of the heart, so as to provide a new indicator for the identification of rat myocardial infarction model. Methods: The rats were divided into control group (n=23) and model group (n=107), the rat hearts were scanned by the laser doppler perfusion imager before and after operation respectively, and the data was analyzed to acquire the rate of surface blood flow change of the heart. Myocardial infarction size of model group was detected by NBT. Model group were divided into three subgroups of mild myocardial infarction, moderate myocardial infarction and severe myocardial infarction according to the myocardial infarction size, and an analysis was made on the correlativity between rate of surface blood flow change of the heart and myocardial infarction size. Results: Myocardial infarction size was highly correlated to the rate of surface blood flow change of the heart in model group (r=0.849 6, P<0.000 1). There was no significant correlation between infarction size and heart blood flow in the mild myocardial infarction subgroup (r=-0.133 6, P>0.05), while the correlation in moderate myocardial infarction was significant (r=0.721 7, P<0.000 1), and the highest correlation was shown in severe myocardial infarction subgroup (r=0.910 2, P<0.000 1). Conclusion: The heart surface blood flow has a close relationship with the myocardial infarction size in rat, so the change of heart blood perfusion can beused as an effective reference to establish and identify rat myocardial infarction model.

  3. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

    PubMed Central

    Neubauer, S; Horn, M; Naumann, A; Tian, R; Hu, K; Laser, M; Friedrich, J; Gaudron, P; Schnackerz, K; Ingwall, J S

    1995-01-01

    The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress. PMID:7883957

  4. Engineered heart tissue graft derived from somatic cell nuclear transferred embryonic stem cells improve myocardial performance in infarcted rat heart.

    PubMed

    Lü, Shuanghong; Li, Ying; Gao, Shaorong; Liu, Sheng; Wang, Haibin; He, Wenjun; Zhou, Jin; Liu, Zhiqiang; Zhang, Ye; Lin, Qiuxia; Duan, Cumi; Yang, Xiangzhong Jerry; Wang, Changyong

    2010-12-01

    The concept of regenerating diseased myocardium by implanting engineered heart tissue (EHT) is intriguing. Yet it was limited by immune rejection and difficulties to be generated at a size with contractile properties. Somatic cell nuclear transfer is proposed as a practical strategy for generating autologous histocompatible stem (nuclear transferred embryonic stem [NT-ES]) cells to treat diseases. Nevertheless, it is controversial as NT-ES cells may pose risks in their therapeutic application. EHT from NT-ES cell-derived cardiomyocytes was generated through a series of improved techniques in a self-made mould to keep the EHTs from contraction and provide static stretch simultaneously. After 7 days of static and mechanical stretching, respectively, the EHTs were implanted to the infarcted rat heart. Four weeks after transplantation, the suitability of EHT in heart muscle repair after myocardial infarction was evaluated by histological examination, echocardiography and multielectrode array measurement. The results showed that large (thickness/diameter, 2-4 mm/10 mm) spontaneously contracting EHTs was generated successfully. The EHTs, which were derived from NT-ES cells, inte grated and electrically coupled to host myocardium and exerted beneficial effects on the left ventricular function of infarcted rat heart. No teratoma formation was observed in the rat heart implanted with EHTs for 4 weeks. NT-ES cells can be used as a source of seeding cells for cardiac tissue engineering. Large contractile EHT grafts can be constructed in vitro with the ability to survive after implantation and improve myocardial performance of infarcted rat hearts.

  5. Tert-butylhydroquinone promotes angiogenesis and improves heart functions in rats after myocardial infarction.

    PubMed

    Zhou, Nan-Qian; Liu, Ning; Li, Peng; Ping, Song; Peng, Qi-Sheng; Shi, Wei-Dong

    2017-01-01

    Hypertension is an increased risk of heart failure and acute myocardial infarction (MI). Tert-butylhydroquinone (tBHQ), as an antioxidant, shows multiple cardioprotective actions including the reduction in blood pressure. The aim of this study was to investigate whether and how tBHQ improves heart functions in rats. The MI model was established in WKY and spontaneously hypertensive rats (SHRs) by ligation of left anterior descending coronary artery. Akt phosphorylation was examined by western blot in human umbilical vein endothelial cells (HUVECs) or in rats. Angiogenesis was assessed by immunohistochemistry and immunofluorescence. Heart function was determined by echocardiography. tBHQ increased Akt phosphorylation, promoted cell proliferations and migrations in HUVECs, which were abolished by Akt inhibitor wortmannin. In SHRs following MI, administration of tBHQ significantly increased Akt phosphorylation, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of tBHQ were ablated by wortmannin in SHRs. tBHQ via Akt activation promotes ischemia-induced angiogenesis and improves heart functions in hypertensive rats. In perspectives, the application of tBHQ should be considered in patients with ischemic diseases such as MI and stroke.

  6. Reconstitution of myocardial lymphatic vessels after acute infarction of rat heart.

    PubMed

    Sun, Q N; Wang, Y F; Guo, Z K

    2012-06-01

    We investigated the regeneration of cardiac lymphatic vessels and capillaries in the infarcted myocardiac zones after acute myocardial infarction in rats. The anterior descending artery of the heart was ligated for infarction and both immunohistochemistry and immunofluorescence were used to detect pathological changes of lymphatic vessels in infarcted zone (IZ), infarcted margin zone (MZ) and remote margin zone (RMZ) on days 7, 14, 21, and 28 after surgery. Dynamic variation of lymphatic vessels existed in IZ, MZ and RMZ at different stages after surgery. At day 7, lymphatic vessels and capillaries were not seen in the IZ, very thin lymphatic capillaries were obviously increased in the inner layer of the margin zone, and enlarged and increased lymphatic capillaries were found in the outer layer of margin zone. At 14 days, a few sparsely arranged lymphatic capillaries were observed in the IZ without marked changes in the MZ. At 21 days, constricted regenerating lymphatic capillaries in MZ were decreased, and lymphatic vessels exhibited sprouting towards the IZ. At 28 days, more lymphatic capillaries emerged in the IZ, and the morphology and number of lymphatic vessels and capillaries had returned to normal. There were no marked changes of lymphatic vessels and capillaries in RMZ compared to control myocardium at the 4 time points. This study demonstrates varied remodeling of lymphatic vessels and capillaries in the IZ and MZ after acute myocardial infarction, and these changes in lymphatic vessels likely play an important role for recovery of infarcted myocardiac function.

  7. Total and high molecular weight adiponectin levels in the rat model of post-myocardial infarction heart failure.

    PubMed

    Kalisz, M; Baranowska, B; Wolinska-Witort, E; Maczewski, M; Mackiewicz, U; Tulacz, D; Gora, M; Martynska, L; Bik, W

    2015-10-01

    Adiponectin is a protein secreted primarily by adipose tissue. It has been suggested that adiponectin plays a protective role in the early phase following myocardial infarction. Our primary aim was to investigate the effects of post-myocardial infarction heart failure well-characterized by left ventricular hemodynamic parameters on the total and high molecular weight adiponectin concentrations in plasma, fat and cardiac tissue. Eight weeks after myocardial infarction or sham operation, total and high molecular weight adiponectin concentrations in plasma, fat, and cardiac tissues were assayed in rats. In addition, hemodynamic parameters and expression of the genes encoding atrial natriuretic peptide and brain natriuretic peptide in left ventricle were evaluated. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in left ventricle tissue were higher in rats with myocardial infarction-induced heart failure compared with the controls. Similarly, total adiponectin concentration was increased in left ventricle (but not in right ventricle) in rats with post-myocardial infarction heart failure. In contrast, adiponectin levels in plasma and cardiac adipose tissue in rats with post-myocardial infarction heart failure were lower than in sham-operated animals. Furthermore, there were no significant differences in levels of high molecular weight adiponectin in plasma, cardiac tissue or adipose tissue between these two groups. We conclude that in the rat model of post-myocardial infarction heart failure, adiponectin level is increased in left ventricle tissue. This is accompanied by decreased adiponectin levels in plasma and cardiac adipose tissue.

  8. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

    PubMed

    Gerbin, Kaytlyn A; Yang, Xiulan; Murry, Charles E; Coulombe, Kareen L K

    2015-01-01

    Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC)-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of

  9. Stromal cell derived factor-1 (SDF-1) targeting reperfusion reduces myocardial infarction in isolated rat hearts.

    PubMed

    Jang, Young-Ho; Kim, June-Hong; Ban, Changill; Ahn, Kyohan; Cheong, Jae-Hun; Kim, Hyung-Hoi; Kim, Jung-Soo; Park, Yong-Hyun; Kim, Jun; Chun, Kook-Jin; Lee, Gyeong-Ho; Kim, Miju; Kim, Cheolmin; Xu, Zhelong

    2012-10-01

    Recent studies have shown that stromal cell derived factor-1 (SDF-1), first known as a cytokine involved in recruiting stem cells into injured organs, confers myocardial protection in myocardial infarction, which is not dependent on stem cell recruitment but related with modulation of ischemia-reperfusion (I/R) injury. However, the effect of SDF has been studied only in a preischemic exposure model, which is not clinically relevant if SDF is to be used as a therapeutic agent. Our study was aimed at evaluating whether or not SDF-1 confers cardioprotection during the reperfusion period. Hearts from SD rats were isolated and perfused with the Langendorff system. Proximal left coronary artery ligation, reperfusion, and SDF perfusion in KH buffer was done according to study protocol. Area of necrosis (AN) relative to area at risk (AR) was the primary endpoint of the study. Significant reduction of AN/AR by SDF in an almost dose-dependent manner was noted during both the preischemic exposure and reperfusion periods. In particular, infusion of a high concentration of SDF (25 nM/L) resulted in a dramatic reduction of infarct size, which was greater than that achieved with ischemic pre- or postconditioning. SDF perfusion during reperfusion was associated with a similar significant reduction of infarct size as preischemic SDF exposure. Further studies are warranted to assess the potential of SDF as a therapeutic agent for reducing I/R injury in clinical practice.

  10. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts

    PubMed Central

    Gerbin, Kaytlyn A.; Yang, Xiulan; Murry, Charles E.; Coulombe, Kareen L. K.

    2015-01-01

    Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC)-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300–390 beats per minute (5–6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart’s pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of

  11. Changes in ECG and enzyme activity in rat heart after myocardial infarction: effect of TPP and MnCl2.

    PubMed

    Tylicki, A; Czerniecki, J; Godlewska, A; Kieliszek, M; Zebrowski, T; Bielawski, T; Wojcik, B

    2008-06-01

    Heart infarction is one of the main causes of death in the human population. Assurance of a sufficient level of bioenergetic processes is very important for the heart after infarction. Mn2+ as well as thiamine pyrophosphate (TPP) are positive effectors of the pyruvate dehydrogenase complex (PDH) and the 2-oxoglutarate dehydrogenase complex (OGDH), both of which play a very important role in the Krebs cycle. Thus, we have established the effect of MnCl2 (10mg/kg) and TPP (20mg/kg)--4 injections every 12 h--on the activity of PDH, OGDH, lactate dehydrogenase (LDH) and malate dehydrogenase (MDH). Additionally, we perform an analysis of ECG to affirm the changes in the heart electrophysiology of healthy rats after MnCl2 and TPP treatment. We then analyzed changes in the activity of these enzymes after experimental myocardial infarction in rats. We observed a decrease of OGDH and MDH activity in rat hearts after infarction in comparison with sham-operated rats. Treatment of healthy rats with MnCl2 caused an increase of OGDH activity. Moreover both MnCl2 and TPP caused an increase of PDH activity and a decrease of MDH activity (TPP revealed a stronger effect). We found no changes in LDH activity. Electrocardiography data showed a slight shortening of the QT interval and an enhanced heartbeat rate after treatment with MnCl2. TPP caused only elongation of the QT interval. In conclusion, application of MnCl2 enhanced the activity of some very important enzymes in the respiration process (PDH and OGDH). This effect, connected with enhanced heartbeat and a slightly shortened ventricle relaxation, may have potential application during the key period of convalescence following heart infarction.

  12. Heart failure progression is accelerated following myocardial infarction in type II diabetic rats

    USDA-ARS?s Scientific Manuscript database

    Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients and following an infarction, diabetes is associated with an increased risk for the development of left ventricular dysfunction and heart failure. The goal of this study was to determine if the progression o...

  13. Methanolic seed extract of Vitis vinifera ameliorates oxidative stress, inflammation and ATPase dysfunction in infarcted and non-infarcted heart of streptozotocin-nicotinamide induced male diabetic rats.

    PubMed

    Giribabu, Nelli; Roslan, Josef; Rekha, Somesula Swapna; Salleh, Naguib

    2016-11-01

    We hypothesized that consumption of Vitis vinifera seed by diabetics could help to ameliorate myocardial damage. Therefore, in this study, we investigated effects of V. vinifera seed methanolic extract (VVSME) on parameters related to myocardial damage in diabetes with or without myocardial infarction (MI). Streptozotocin-nicotinamide induced diabetic rats received oral VVSME for 28days. MI was induced by intraperitoneal injection of isoproterenol on last two days. Prior to sacrifice, blood was collected and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid profile and insulin levels were measured. Levels of serum cardiac injury marker (troponin-I and CK-MB) were determined and histopathological changes in the heart were observed following harvesting. Levels of oxidative stress (LPO, SOD, CAT, GPx and RAGE), inflammation (NF-κB, TNF-α, IL-1β and IL-6) and cardiac ATPases (Na(+)/K(+)-ATPase and Ca(2+)-ATPase) were determined in heart homogenates. LC-MS was used to identify constituents in the extracts. Consumption of VVSME by diabetic rats with or without MI improved the metabolic profiles while decreased the cardiac injury marker levels with lesser myocardial damage observed. Additionally, VVSME consumption reduced the levels of LPO, RAGE, TNF-α, Iκκβ, NF-κβ, IL-1β and IL-6 while increased the levels of SOD, CAT, GPx, Na(+)/K(+)-ATPase and Ca(2+)-ATPase in the infarcted and non-infarcted heart of diabetic rats (p<0.05). LC-MS analysis revealed 17 major compounds in VVSME which might be responsible for the observed effects. Consumption of VVSME by diabetics helps to ameliorate damage to the infarcted and non-infarcted myocardium by decreasing oxidative stress, inflammation and cardiac ATPases dysfunctions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat

    PubMed Central

    Zhao, Baoyin; Chen, Shang; Liu, Juanjuan; Yuan, Ziqiang; Qi, Xufeng; Qin, Junwen; Zheng, Xin; Shen, Xiaotao; Yu, Yanhong; Qnin, Thomas J; Chan, John Yeuk-Hon; Cai, Dongqing

    2013-01-01

    Recently, cardiac telocytes were found in the myocardium. However, the functional role of cardiac telocytes and possible changes in the cardiac telocyte population during myocardial infarction in the myocardium are not known. In this study, the role of the recently identified cardiac telocytes in myocardial infarction (MI) was investigated. Cardiac telocytes were distributed longitudinally and within the cross network of the myocardium, which was impaired during MI. Cardiac telocytes in the infarction zone were undetectable from approximately 4 days to 4 weeks after an experimental coronary occlusion was used to induce MI. Although cardiac telocytes in the non-ischaemic area of the ischaemic heart experienced cell death, the cell density increased approximately 2 weeks after experimental coronary occlusion. The cell density was then maintained at a level similar to that observed 1–4 days after left anterior descending coronary artery (LAD)-ligation, but was still lower than normal after 2 weeks. We also found that simultaneous transplantation of cardiac telocytes in the infarcted and border zones of the heart decreased the infarction size and improved myocardial function. These data indicate that cardiac telocytes, their secreted factors and microvesicles, and the microenvironment may be structurally and functionally important for maintenance of the physiological integrity of the myocardium. Rebuilding the cardiac telocyte network in the infarcted zone following MI may be beneficial for functional regeneration of the infarcted myocardium. PMID:23205601

  15. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat.

    PubMed

    Zhao, Baoyin; Chen, Shang; Liu, Juanjuan; Yuan, Ziqiang; Qi, Xufeng; Qin, Junwen; Zheng, Xin; Shen, Xiaotao; Yu, Yanhong; Qnin, Thomas J; Chan, John Yeuk-Hon; Cai, Dongqing

    2013-01-01

    Recently, cardiac telocytes were found in the myocardium. However, the functional role of cardiac telocytes and possible changes in the cardiac telocyte population during myocardial infarction in the myocardium are not known. In this study, the role of the recently identified cardiac telocytes in myocardial infarction (MI) was investigated. Cardiac telocytes were distributed longitudinally and within the cross network of the myocardium, which was impaired during MI. Cardiac telocytes in the infarction zone were undetectable from approximately 4 days to 4 weeks after an experimental coronary occlusion was used to induce MI. Although cardiac telocytes in the non-ischaemic area of the ischaemic heart experienced cell death, the cell density increased approximately 2 weeks after experimental coronary occlusion. The cell density was then maintained at a level similar to that observed 1-4 days after left anterior descending coronary artery (LAD)-ligation, but was still lower than normal after 2 weeks. We also found that simultaneous transplantation of cardiac telocytes in the infarcted and border zones of the heart decreased the infarction size and improved myocardial function. These data indicate that cardiac telocytes, their secreted factors and microvesicles, and the microenvironment may be structurally and functionally important for maintenance of the physiological integrity of the myocardium. Rebuilding the cardiac telocyte network in the infarcted zone following MI may be beneficial for functional regeneration of the infarcted myocardium. © 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  16. Functional capacity in a rat model of heart failure: impact of myocardial infarction size.

    PubMed

    Hentschke, Vítor Scotta; Capalonga, Lucas; Rossato, Douglas Dalcin; Perini, Júlia Luíza; Alves, Jadson Pereira; Quagliotto, Edson; Stefani, Giuseppe Potrick; Karsten, Marlus; Pontes, Mauro; Dal Lago, Pedro

    2017-08-25

    Oxygen uptake (VO2 ) and exercise tolerance in rats classified by myocardial infarction (MI) size are underexplored. The aim of this study was to evaluate VO2 /carbon dioxide production (VCO2 ) and exercise tolerance in rats that have undergone MI. Fourteen weeks after MI or sham surgery, rats underwent an integrated approach to left ventricular function and VO2 /VCO2 , exercise tolerance and skeletal muscle weight evaluation. Based on MI size determination, rats were assigned to sham operated controls (Sham, n = 12), small myocardial infarction (SMI, n = 8), and large myocardial infarction (LMI, n = 5) groups. LMI rats showed lower systolic (ejection fraction and fractional shortening) and diastolic (E/A ratio) left ventricular function compared with SMI. VO2max (∼24%, P < 0.05), VO2reserve (∼30%, P < 0.05), time to exhaustion (∼36%, P < 0.05) and maximal velocity (∼30%, P < 0.05) was lower in LMI compared with sham operated controls, with no difference between SMI rats and sham operated controls. VCO2max and respiratory exchange ratio (RER) showed no significant difference between MI rats and sham operated control rats. LMI rats demonstrated lower gastrocnemius weight (∼12%, P < 0.05) and soleus weight (∼19%, P = 0.07) compared with sham operated control rats. Significant correlations between MI size, left ventricular end-diastolic pressure, right ventricle hypertrophy, pulmonary congestion, ejection fraction, and fractional shortening with VO2max and run distance were observed. O2 uptake and exercise intolerance are MI size dependent. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts

    PubMed Central

    Song, Heesang; Hwang, Hye Jin; Chang, Woochul; Song, Byeong-Wook; Cha, Min-Ji; Lim, Soyeon; Choi, Eun Ju; Ham, Onju; Lee, Chang Youn; Park, Jun-Hee; Lee, Se-Yeon; Choi, Eunmi; Lee, Chungkeun; Lee, Myoungho; Lee, Moon-Hyoung; Kim, Sung-Hou; Jang, Yangsoo; Hwang, Ki-Chul

    2011-01-01

    Despite the safety and feasibility of mesenchymal stem cell (MSC) therapy, an optimal cell type has not yet emerged in terms of electromechanical integration in infarcted myocardium. We found that poor to moderate survival benefits of MSC-implanted rats were caused by incomplete electromechanical integration induced by tissue heterogeneity between myocytes and engrafted MSCs in the infarcted myocardium. Here, we report the development of cardiogenic cells from rat MSCs activated by phorbol myristate acetate, a PKC activator, that exhibited high expressions of cardiac-specific markers and Ca2+ homeostasis-related proteins and showed adrenergic receptor signaling by norepinephrine. Histological analysis showed high connexin 43 coupling, few inflammatory cells, and low fibrotic markers in myocardium implanted with these phorbol myristate acetate-activated MSCs. Infarct hearts implanted with these cells exhibited restoration of conduction velocity through decreased tissue heterogeneity and improved myocardial contractility. These findings have major implications for the development of better cell types for electromechanical integration of cell-based treatment for infarcted myocardium. PMID:21173226

  18. Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction.

    PubMed

    Paul, Arghya; Nayan, Madhur; Khan, Afshan Afsar; Shum-Tim, Dominique; Prakash, Satya

    2012-01-01

    The objective of this study was to develop angiopoietin-1 (Ang1)-expressing genetically modified human adipose tissue derived stem cells (hASCs) for myocardial therapy. For this, an efficient gene delivery system using recombinant baculovirus complexed with cell penetrating transactivating transcriptional activator TAT peptide/deoxyribonucleic acid nanoparticles (Bac-NP), through ionic interactions, was used. It was hypothesized that the hybrid Bac- NP(Ang1) system can efficiently transduce hASCs and induces favorable therapeutic effects when transplanted in vivo. To evaluate this hypothesis, a rat model with acute myocardial infarction and intramyocardially transplanted Ang1-expressing hASCs (hASC-Ang1), genetically modified by Bac-NP(Ang1), was used. Ang1 is a crucial pro-angiogenic factor for vascular maturation and neovasculogenesis. The released hAng1 from hASC-Ang1 demonstrated profound mitotic and anti-apoptotic activities on endothelial cells and cardiomyocytes. The transplanted hASC-Ang1 group showed higher cell retention compared to hASC and control groups. A significant increase in capillary density and reduction in infarct sizes were noted in the infarcted hearts with hASC-Ang1 treatment compared to infarcted hearts treated with hASC or the untreated group. Furthermore, the hASC-Ang1 group showed significantly higher cardiac performance in echocardiography (ejection fraction 46.28% ± 6.3%, P < 0.001 versus control, n = 8) than the hASC group (36.35% ± 5.7%, P < 0.01, n = 8), 28 days post-infarction. The study identified Bac-NP complex as an advanced gene delivery vehicle for stem cells and demonstrated its potential to treat ischemic heart disease with high therapeutic index for combined stem cell-gene therapy strategy.

  19. Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction

    PubMed Central

    Aires, R.; Pimentel, E.B.; Forechi, L.; Dantas, E.M.; Mill, J.G.

    2017-01-01

    Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance. PMID:28076450

  20. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats.

    PubMed

    Huisamen, Barbara; Genis, Amanda; Marais, Erna; Lochner, Amanda

    2011-02-01

    Cardiovascular risk is closely associated with insulin resistance and type 2 diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel approach to treat this disease. The aims of this study was therefore to use an animal model to determine whether (i) pre-treatment of obese, insulin resistant but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10 mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject hearts to ischaemia/reperfusion to determine infarct size, functional recovery and post-ischaemic activation of proteins associated with cardiac protection. Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity. Other assessments included body weight, intra-peritoneal fat weight, insulin and GLP-1 levels as well as histological evaluation of the pancreata. Results showed that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed animals. They presented with elevated plasma insulin levels and lower GLP-1 levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size development in hearts from DIO rats after ischaemia/reperfusion accompanied by activation of cardioprotective kinases. GLP-1 levels were elevated and plasma insulin levels lower after treatment. In addition, the beta-cell to alpha-cell ratio of the pancreas was improved. We conclude that treatment with PFK275-055 for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

  1. Transmural stretch-dependent regulation of contractile properties in rat heart and its alteration after myocardial infarction.

    PubMed

    Cazorla, Olivier; Szilagyi, Szabolcs; Le Guennec, Jean-Yves; Vassort, Guy; Lacampagne, Alain

    2005-01-01

    The "stretch-sensitization" response is essential to the regulation of heart contractility. An increase in diastolic volume improves systolic contraction. The cellular mechanisms of this modulation, the Frank-Starling law, are still uncertain. Moreover, their alterations in heart failure remains controversial. Here, using left ventricular skinned rat myocytes, we show a nonuniform stretch-sensitization of myofilament activation across the ventricular wall. Stretch-dependent Ca2+ sensitization of myofilaments increases from sub-epicardium to sub-endocardium and is correlated with an increase in passive tension. This passive tension-dependent component of myofibrillar activation is not associated with expression of titin isoforms, changes in troponin I level, and phosphorylation status. Instead, we observe that stretch induces phosphorylation of ventricular myosin light chain 2 isoform (VLC2b) in sub-endocardium specifically. Thus, VLC2b phosphorylation could act as a stretch-dependent modulator of activation tuned within normal heart. Moreover, in postmyocardial infarcted rat, the gradient of stretch-dependent Ca2+ sensitization disappears associated with a lack of VLC2b phosphorylation in sub-endocardium. In conclusion, nonuniformity is a major characteristic of the normal adult left ventricle (LV). The heterogeneous myocardial deformation pattern might be caused not only by the morphological heterogeneity of the tissue in the LV wall, but also by the nonuniform contractile properties of the myocytes across the wall. The loss of a contractile transmural gradient after myocardial infarction should contribute to the impaired LV function.

  2. Aerobic training prior to myocardial infarction increases cardiac GLUT4 and partially preserves heart function in spontaneously hypertensive rats.

    PubMed

    Schaun, Maximiliano Isoppo; Marschner, Rafael Aguiar; Peres, Thiago Rodrigues; Markoski, Melissa Medeiros; Lehnen, Alexandre Machado

    2017-03-01

    We assessed cardiac function (echocardiographic) and glucose transporter 4 (GLUT4) expression (Western blot) in response to 10 weeks of aerobic training (treadmill) prior to acute myocardial infarction (AMI) by ligation of the left coronary artery in spontaneously hypertensive rats. Animals were allocated to sedentary+sham, sedentary+AMI, training+sham, and training+AMI. Aerobic training prior to AMI partially preserves heart function. AMI and/or aerobic training increased GLUT4 expression. However, those animals trained prior to AMI showed a greater increase in GLUT4 in cardiomyocytes.

  3. Expression of the multifunctional Y-box protein, YB-1, in myofibroblasts of the infarcted rat heart

    SciTech Connect

    Kamalov, German; Varma, Balwantkumar R.; Lu Li; Sun Yao; Weber, Karl T.; Guntaka, Ramareddy V. . E-mail: rguntaka@utmem.edu

    2005-08-19

    Intracellular signaling mechanisms regulating the turnover of {alpha}-SMA-positive myofibroblasts (myoFbs) at the site of myocardial infarction (MI) are poorly understood. Y-Box (YB)-1, a multifunctional protein, may be involved in regulation of proliferation, migration and apoptosis of myoFbs. Our objective was to study the expression of YB-1 in the infarcted rat heart and its localization in myoFbs. On days 3-28 following MI, we monitored YB-1 expression and its colocalization with {alpha}-SMA, and proliferation markers PCNA and Ki-67 in infarcted tissue by Western blot, immunohistochemistry, and immunofluorescent double-labeling. YB-1 is barely detectable in normal myocardium. At the infarct site, however, YB-1 is markedly elevated from day 3 post-MI concomitant with the induction of cell proliferation. MyoFbs are the major source of YB-1 and retain it up to day 28 post-MI. We suggest early expression of YB-1 promotes proliferation and migration of myoFbs, whereas prolonged expression may be responsible for scar formation.

  4. The Impact of Different Plasma Glucose Levels on Heart Rate in Experimental Rats With Acute Myocardial Infarction

    PubMed Central

    Pan, Guo-Zhong; Xie, Jing; Tian, Xiao-Fang; Yang, Shi-Wei; Zhou, Yu-Jie

    2016-01-01

    Background The aim of the study was to evaluate the impact of different plasma glucose levels on heart rate (HR) in experimental rats with acute myocardial infarction (AMI). Methods One hundred and twenty-one male Wistar rats were randomly divided into AMI group (n = 70) and sham-operation group (n = 51). Both groups had low, normal and high glucose levels, respectively. In the former group, hypertonic glucose was injected into the rats to make their blood glucose levels above 16 mmol/L and insulin below 3.3 mmol/L; then, the left anterior descending artery was ligated. In the later group, the models of different blood glucose levels were the same as the former ones, but false operations, thread without ligating, were given to the rats. Electrocardiogram and troponin I (TnI) confirmed that the models were prepared successfully. Electrocardiogram expression of AMI was the formation of Q-wave in over three adjacent leads and abnormal elevation of TnI. Results The HR of the rats in the hypoglycemic group is higher than that of the hyperglycemic group and normal blood glucose group before AMI (P < 0.05). The HR of the hyperglycemic rats is higher than that of the hypoglycemic group and normal blood glucose group after AMI (P < 0.05). In the hypoglycemic group, the HR of the rats who suffered from AMI was lower than that of the rats of the sham group (P < 0.05). Conclusion Hypoglycemia allows faster HR and the HR in the rats with hyperglycemia is higher than that in the rats with hypoglycemia among the AMI rats. PMID:28197283

  5. [Expression changes of Notch and nuclear factor-κB signaling pathways in the rat heart with myocardial infarction].

    PubMed

    Jin, J L; Deng, Z T; Lyu, R G; Liu, X H; Wei, J R

    2017-06-24

    Objective: To observe the expression changes of Notch and nuclear factor-κB (NF-κB) signaling pathways in rat myocardium post myocardial infarction. Methods: Myocardial infarction was established by ligation of the left anterior descending coronary artery(MI group), sham rats (similar surgical procedure without coronary artery ligation) served as control, the rats were sacrificed at first week, 4th and 8th week after operation, the non-infarct myocardial tissue in both groups was obtained to detect the mRNA expression of Notch1, Dll4 and Hes1 by RT-PCR, the protein expression of NICD1 was detected by Western blot, the nuclear protein p65 content was detected to reflect the activation degree of NF-κB signaling in the cardiomyocytes. Results: The myocardial mRNA expression of Notch1 in MI group was significantly higher than in control group (1.68±0.35 vs. 0.47±0.12, P<0.05) at first week, and tended to be higher at the 4th week and 8th week (P>0.05). The mRNA expression of Dll4 and Hes1 was similar between the two groups at the three time points. NICD1 protein level was increased at the first week in MI group as compared with control group (1.31±0.33 vs.0.45±0.11, P<0.05), which tended also to be higher at the 4th week and 8th week post operation (P>0.05). For NF-κB activation study, the nuclear protein p65 content was higher at first week, 4th week and 8th week in MI group as compared with respective control groups (0.286±0.052 vs.0.049±0.016 (P<0.01), 0.247±0.056 vs. 0.043±0.018 (P<0.01), 0.120±0.033 vs. 0.044±0.009 (P<0.05)), the most significant increase was found in the first week. Conclusions: Notch and NF-κB signaling pathways are actively involved in the process of ventricular remodeling after myocardial infarction. Notch1 and NF-κB signaling pathways are both activated at the first week after myocardial infarction, NF-κB signaling pathway activation after myocardial infarction continues up to 8 weeks. These two signal transduction pathways

  6. Effect of an Ilex paraguariensis (yerba mate) extract on infarct size in isolated rat hearts: the mechanisms involved.

    PubMed

    González Arbeláez, Luisa F; Fantinelli, Juliana C; Ciocci Pardo, Alejandro; Caldiz, Claudia I; Ríos, José Luis; Schinella, Guillermo R; Mosca, Susana M

    2016-02-01

    Tea made from Ilex paraguariensis (IP) dried and minced leaves is a beverage widely consumed by large populations in South America as a source of caffeine (stimulant action) and for its medicinal properties. However, there is little information about the action of IP on the myocardium in the ischemia-reperfusion condition. Therefore, the objective of this study was to examine the effects of an aqueous extract of IP on infarct size in a model of regional ischemia. Isolated rat hearts were perfused by the Langendorff technique and subjected to 40 min of coronary artery occlusion followed by 60 min of reperfusion (ischemic control hearts). Other hearts received IP 30 μg mL(-1) during the first 10 min of reperfusion in the absence or presence of l(G)-nitro-l-arginine methyl ester [l-NAME, a nitric oxide synthase (NOS) inhibitor]. The infarct size was determined by triphenyltetrazolium chloride (TTC) staining. Post-ischemic myocardial function and coronary perfusion were also assessed. Cardiac oxidative damage was evaluated by using the thiobarbituric acid reactive substance (TBARS) concentration and the reduced glutathione (GSH) content. To analyze the mechanisms involved, the expressions of phosphorylated forms of eNOS and Akt were measured. In isolated mitochondria the Ca(2+)-induced mitochondrial permeability transition pore (mPTP) opening was determined. IP significantly decreased the infarct size and improved post-ischemic myocardial function and coronary perfusion. TBARS decreased, GSH was partially preserved, the levels of P-eNOS and P-Akt increased and mPTP opening diminished after IP addition. These changes were abolished by l-NAME. Therefore, our data demonstrate that acute treatment with IP only during reperfusion was effective in reducing myocardial post-ischemic alterations. These actions would be mediated by a decrease of mitochondrial permeability through IP-activated Akt/eNOS-dependent pathways.

  7. Protective effect of geranylgeranylacetone via enhanced induction of HSPB1 and HSPB8 in mitochondria of the failing heart following myocardial infarction in rats.

    PubMed

    Marunouchi, Tetsuro; Inomata, Satomi; Sanbe, Atsushi; Takagi, Norio; Tanonaka, Kouichi

    2014-05-05

    The mechanisms underlying mitochondrial impairment in the failing heart are not yet clear. In a previous study, we found that the levels of small heat shock proteins (HSP) such as mitochondrial HSPB1 and HSPB8 in the failing heart following myocardial infarction were decreased. In the present study, to verify the hypothesis that mitochondrial dysfunction in the failing heart is associated with alterations in mitochondrial small heat shock proteins, we examined the effects of geranylgeranylacetone, a heat shock protein inducer, on the cardiac mitochondrial function after myocardial infarction. When hemodynamic parameters of rats with myocardial infarction were measured at the 8th (8W) week after coronary artery ligation (CAL), the 8W-CAL showed signs of chronic heart failure concomitant with a reduced mitochondrial oxygen consumption rate. HSPB1 and HSPB8 contents in the mitochondrial fraction prepared from the failing heart were decreased, suggesting that an attenuation of mitochondrial translocation of HSPB1 and HSPB8 had led to an impairment of mitochondrial energy-producing ability. Geranylgeranylacetone treatment from the 2nd to 8th week after myocardial infarction attenuated the reduction in mitochondrial HSPB1 and HSPB8 contents. Furthermore, the mitochondrial energy-producing ability and cardiac pump function were preserved by orally administered geranylgeranylacetone during the development of heart failure. These results suggest that the induction of small heat shock proteins in the infarcted heart by geranylgeranylacetone treatment contributed to the preservation of mitochondrial function, leading to an improvement of cardiac contractile function.

  8. Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.

    PubMed

    Garg, Monika; Khanna, Deepa; Kalra, Sanjeev; Balakumar, Pitchai

    2016-10-01

    Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.

  9. [Protective effect of peptide semax the rat heart in acute myocardial infarction].

    PubMed

    Golubeva, A V; Gavrilova, S A; Lipina, T V; Shornikova, M V; Postnikov, A B; Andreeva, L A; Chentsov, Iu S; Koshelev, V B

    2006-06-01

    Semax, a member of ACTH-derived peptides family, has been employed in the treatment of acute ischemic stroke in patients. It decreased neurological deficit and reduced NO hyperproduction in the rat brain, caused by acute cerebral hypoperfusion. We suggested that semax is also able to protect rat heart from ischemic damage in acute myocardial infaction (AMI). AMI was induced by left coronary artery occlusion, myocardial ischemic area averaged 30 % of left ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 % reduced mean arterial blood pressure and 48 % increased diastolic blood pressure in left ventricle in comparison with sham-operated control group. However, infusion of either dobutamine, which directly stimulates myocardial contractility, or sodium nitroprusside and phenylephrine, that change vascular resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic parameters between groups. These data indicate absense or only moderate cardiac dysfunction in rats with AMI and are consistent wih morphometrical and histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test) changes in left ventricular cardiomyocytes in spite of development of distinct ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after coronary occlusion, caused no effect on cardiac function, but completely prevented ischemia-induced ultrastructural changes of cardiomyocytes. This protective effect was accompanied by the ability of peptide to blunt the increase in plasma concentrations of nitrates, observed in AMI group.

  10. Mesenchymal stem cell therapy associated with endurance exercise training: Effects on the structural and functional remodeling of infarcted rat hearts.

    PubMed

    Lavorato, Victor Neiva; Del Carlo, Ricardo Junqueira; da Cunha, Daise Nunes Queiroz; Okano, Barbara Silva; Belfort, Felipe Gomes; de Freitas, Juliana Silveira; da Mota, Gloria de Fatima Alves; Quintão-Júnior, Judson Fonseca; Silame-Gomes, Luis Henrique Lobo; Drummond, Filipe Rios; Carneiro-Júnior, Miguel Araújo; de Oliveira, Edilamar Menezes; Monteiro, Betania Souza; Prímola-Gomes, Thales Nicolau; Natali, Antônio José

    2016-01-01

    We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40 days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1 × 10(6 )cells). Twenty-four hours later ET groups exercised on a treadmill (5 days/week; 60 min/day; 60% of maximal running velocity) for 12 weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca(2 +)]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p < 0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p < 0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca(2 +)]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca(2 +)]i transient. Early endurance exercise intervention increased (p < 0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca(2 +)]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to

  11. Aerobic interval training partly reverse contractile dysfunction and impaired Ca2+ handling in atrial myocytes from rats with post infarction heart failure.

    PubMed

    Johnsen, Anne Berit; Høydal, Morten; Røsbjørgen, Ragnhild; Stølen, Tomas; Wisløff, Ulrik

    2013-01-01

    There is limited knowledge about atrial myocyte Ca(2+) handling in the failing hearts. The aim of this study was to examine atrial myocyte contractile function and Ca(2+) handling in rats with post-infarction heart failure (HF) and to examine whether aerobic interval training could reverse a potential dysfunction. Post-infarction HF was induced in Sprague Dawley rats by ligation of the left descending coronary artery. Atrial myocyte shortening was depressed (p<0.01) and time to relaxation was prolonged (p<0.01) in sedentary HF-rats compared to healthy controls. This was associated with decreased Ca(2+) amplitude, decreased SR Ca(2+) content, and slower Ca(2+) transient decay. Atrial myocytes from HF-rats had reduced sarcoplasmic reticulum Ca(2+) ATPase activity, increased Na(+)/Ca(2+)-exchanger activity and increased diastolic Ca(2+) leak through ryanodine receptors. High intensity aerobic interval training in HF-rats restored atrial myocyte contractile function and reversed changes in atrial Ca(2+) handling in HF. Post infarction HF in rats causes profound impairment in atrial myocyte contractile function and Ca(2+) handling. The observed dysfunction in atrial myocytes was partly reversed after aerobic interval training.

  12. Aerobic Interval Training Partly Reverse Contractile Dysfunction and Impaired Ca2+ Handling in Atrial Myocytes from Rats with Post Infarction Heart Failure

    PubMed Central

    Johnsen, Anne Berit; Høydal, Morten; Røsbjørgen, Ragnhild; Stølen, Tomas; Wisløff, Ulrik

    2013-01-01

    Background There is limited knowledge about atrial myocyte Ca2+ handling in the failing hearts. The aim of this study was to examine atrial myocyte contractile function and Ca2+ handling in rats with post-infarction heart failure (HF) and to examine whether aerobic interval training could reverse a potential dysfunction. Methods and results Post-infarction HF was induced in Sprague Dawley rats by ligation of the left descending coronary artery. Atrial myocyte shortening was depressed (p<0.01) and time to relaxation was prolonged (p<0.01) in sedentary HF-rats compared to healthy controls. This was associated with decreased Ca2+ amplitude, decreased SR Ca2+ content, and slower Ca2+ transient decay. Atrial myocytes from HF-rats had reduced sarcoplasmic reticulum Ca2+ ATPase activity, increased Na+/Ca2+-exchanger activity and increased diastolic Ca2+ leak through ryanodine receptors. High intensity aerobic interval training in HF-rats restored atrial myocyte contractile function and reversed changes in atrial Ca2+ handling in HF. Conclusion Post infarction HF in rats causes profound impairment in atrial myocyte contractile function and Ca2+ handling. The observed dysfunction in atrial myocytes was partly reversed after aerobic interval training. PMID:23799089

  13. [Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction].

    PubMed

    Gavrilova, S A; Golubeva, A V; Lipina, T V; Fominykh, E S; Shornikova, M V; Postnikov, A B; Andrejeva, L A; Chentsov, Iu S; Koshelev, V B

    2006-11-01

    Semax, a member of ACTH-derived peptides family, was used in treatment of ischemic stroke in patients. It decreased neurological deficiency and reduced NO hyperproduction in the rat brain caused by acute cerebral hypoperfusion. We suggest that semax is also capable of protecting the rat heart from ischemic damage 28 days after myocardial infarction (MI) induced by left descendent coronary artery occlusion. Semax (150 microg/kg) was given i. p. in the operating day twice: 15 min and 2 hours after coronary occlusion, and once a day for the following 6 days. In 28 days after infarction, the MI group developed cardiac hypertrophy, cell growth was caused mainly by the increase of contractile filaments not supported by the appropriate mitochondrial growth that indicated an impaired energy supply of the cells. Moreover, cardiac hypertrophy was accompanied by decreased mean arterial blood pressure and cardiac contractile function and increased left ventricular end-diastolic pressure. Pharmacological change of cardiac afterload revealed that, in 28 days after MI, the rat heart was not able to change its contractile performance in response to either increase or decrease of systemic blood pressure, and as a result could not maintain its diastolic pressure. All these changes obviously reflect development of heart failure. Semax did not affect cardiac work but partially prevented end-diastolic pressure growth in left ventricle as well as ameliorated cardiomyocyte hypertrophy and disproportionate growth of contractile and mitochondrial apparatus, thus exerting beneficial effect on the left ventricular remodeling and heart failure development late after myocardial infarction.

  14. Effects of ranolazine on the exercise capacity of rats with chronic heart failure induced by myocardial infarction.

    PubMed

    Aaker, A; McCormack, J G; Hirai, T; Musch, T I

    1996-09-01

    Ranolazine was previously shown to stimulate cardiac glucose oxidation. Dichloroacetate (DCA) also does and was shown to improve exercise capacity in animals, but it has long-term toxicity problems. To test the hypothesis that ranolazine would increase exercise performance in the chronic heart failure (CHF) condition, we compared the exercise endurance capacities of rats with a surgically induced myocardial infarction (MI) with those of noninfarcted sham-operated (Sham) controls both before and after 14 and 28 days of drug administration. Chronic administration of ranolazine, 50 mg/kg twice daily (b.i.d.) oral, significantly reduced the endurance capacities of both Sham and MI rats (measured after a 12-h fast to reduce liver glycogen stores), as indicated by the reductions in run times to fatigue during a progressive treadmill test. Ranolazine produced reductions in resting plasma lactate and glucose concentrations of animals fasted for 12 h (consistent with stimulating glucose oxidation); however, tissue glycogen concentrations measured in various locomotor muscles located in the animal's hindlimb were unaffected when measured 48 h after the last treadmill test and after 12 h of fasting. Chronic administration of ranolazine did not increase the endurance capacity of rats with CHF induced by MI at the dosage and with the protocol used. To the contrary, the chronic administration of ranolazine appears to reduce the work capacity of all rats, suggesting that this drug may not be useful therapeutically in the treatment of CHF. Whether the decrements in endurance capacity produced by ranolazine are related to the high plasma concentrations of the drug produced in this study as compared with previous studies in humans remains subject to further experimentation.

  15. Chronic administration of an endothelin-A receptor antagonist improves exercise capacity in rats with myocardial infarction-induced congestive heart failure.

    PubMed

    Miyauchi, Takashi; Fujimori, Akira; Maeda, Seiji; Iemitsu, Motoyuki; Sakai, Satoshi; Shikama, Hisataka; Tanabe, Takumi; Matsuda, Mitsuo; Goto, Katsutoshi; Yamaguchi, Iwao

    2004-11-01

    The effects of long-term administration of YM598, a selective endothelin-A antagonist, on improving the exercise tolerance of chronic heart failure model rats were examined using a treadmill exercise loading test. Rats were acclimatized to the treadmill apparatus and the coronary artery was ligated to prepare a myocardial infarction-induced congestive heart failure (CHF) model. Starting 10 days postoperatively, when the acute phase of infarction was over, YM598 was administered orally once daily for approximately 25 weeks at a dose of 1 mg/kg. At weeks 20 and 24 the treadmill test was performed. YM598 prolonged running time, which had been shortened as a result of heart failure. The weights, relative to the body weight, of the left and right ventricles and lungs of surviving rats with CHF were significantly greater than those of sham-operated rats, suggesting hypertrophy of the ventricles and congestion of the lungs. Administration of YM598 markedly reduced ventricular hypertrophy and pulmonary congestion. Examination of cardiac function revealed that, in surviving CHF rats, the peak positive first derivative of left ventricular pressure was significantly lower, and left ventricular end-diastolic pressure, right ventricular systolic pressure and central venous pressure were significantly higher in comparison to sham-operated rats. These data demonstrate that, in rats with CHF, the contractile and diastolic capacity of the left ventricle decreased and pulmonary hypertension and systemic congestion occurred. Long-term administration of YM598 improved left ventricular function of CHF rats to the level of sham-operated rats, and reduced the workload placed on the right side of the heart. Histological examination revealed that long-term treatment with YM598 prevented fibrosis of the surviving left ventricular myocardium. In conclusion, long-term administration of YM598 to rats with CHF improved exercise tolerance and inhibited remodeling of cardiac muscles, leading to

  16. Beta-Adrenoceptor Stimulation Reveals Ca2+ Waves and Sarcoplasmic Reticulum Ca2+ Depletion in Left Ventricular Cardiomyocytes from Post-Infarction Rats with and without Heart Failure.

    PubMed

    Sadredini, Mani; Danielsen, Tore Kristian; Aronsen, Jan Magnus; Manotheepan, Ravinea; Hougen, Karina; Sjaastad, Ivar; Stokke, Mathis Korseberg

    2016-01-01

    Abnormal cellular Ca2+ handling contributes to both contractile dysfunction and arrhythmias in heart failure. Reduced Ca2+ transient amplitude due to decreased sarcoplasmic reticulum Ca2+ content is a common finding in heart failure models. However, heart failure models also show increased propensity for diastolic Ca2+ release events which occur when sarcoplasmic reticulum Ca2+ content exceeds a certain threshold level. Such Ca2+ release events can initiate arrhythmias. In this study we aimed to investigate if both of these aspects of altered Ca2+ homeostasis could be found in left ventricular cardiomyocytes from rats with different states of cardiac function six weeks after myocardial infarction when compared to sham-operated controls. Video edge-detection, whole-cell Ca2+ imaging and confocal line-scan imaging were used to investigate cardiomyocyte contractile properties, Ca2+ transients and Ca2+ waves. In baseline conditions, i.e. without beta-adrenoceptor stimulation, cardiomyocytes from rats with large myocardial infarction, but without heart failure, did not differ from sham-operated animals in any of these aspects of cellular function. However, when exposed to beta-adrenoceptor stimulation, cardiomyocytes from both non-failing and failing rat hearts showed decreased sarcoplasmic reticulum Ca2+ content, decreased Ca2+ transient amplitude, and increased frequency of Ca2+ waves. These results are in line with a decreased threshold for diastolic Ca2+ release established by other studies. In the present study, factors that might contribute to a lower threshold for diastolic Ca2+ release were increased THR286 phosphorylation of Ca2+/calmodulin-dependent protein kinase II and increased protein phosphatase 1 abundance. In conclusion, this study demonstrates both decreased sarcoplasmic reticulum Ca2+ content and increased propensity for diastolic Ca2+ release events in ventricular cardiomyocytes from rats with heart failure after myocardial infarction, and that these

  17. Beta-Adrenoceptor Stimulation Reveals Ca2+ Waves and Sarcoplasmic Reticulum Ca2+ Depletion in Left Ventricular Cardiomyocytes from Post-Infarction Rats with and without Heart Failure

    PubMed Central

    Danielsen, Tore Kristian; Aronsen, Jan Magnus; Manotheepan, Ravinea; Hougen, Karina; Sjaastad, Ivar; Stokke, Mathis Korseberg

    2016-01-01

    Abnormal cellular Ca2+ handling contributes to both contractile dysfunction and arrhythmias in heart failure. Reduced Ca2+ transient amplitude due to decreased sarcoplasmic reticulum Ca2+ content is a common finding in heart failure models. However, heart failure models also show increased propensity for diastolic Ca2+ release events which occur when sarcoplasmic reticulum Ca2+ content exceeds a certain threshold level. Such Ca2+ release events can initiate arrhythmias. In this study we aimed to investigate if both of these aspects of altered Ca2+ homeostasis could be found in left ventricular cardiomyocytes from rats with different states of cardiac function six weeks after myocardial infarction when compared to sham-operated controls. Video edge-detection, whole-cell Ca2+ imaging and confocal line-scan imaging were used to investigate cardiomyocyte contractile properties, Ca2+ transients and Ca2+ waves. In baseline conditions, i.e. without beta-adrenoceptor stimulation, cardiomyocytes from rats with large myocardial infarction, but without heart failure, did not differ from sham-operated animals in any of these aspects of cellular function. However, when exposed to beta-adrenoceptor stimulation, cardiomyocytes from both non-failing and failing rat hearts showed decreased sarcoplasmic reticulum Ca2+ content, decreased Ca2+ transient amplitude, and increased frequency of Ca2+ waves. These results are in line with a decreased threshold for diastolic Ca2+ release established by other studies. In the present study, factors that might contribute to a lower threshold for diastolic Ca2+ release were increased THR286 phosphorylation of Ca2+/calmodulin-dependent protein kinase II and increased protein phosphatase 1 abundance. In conclusion, this study demonstrates both decreased sarcoplasmic reticulum Ca2+ content and increased propensity for diastolic Ca2+ release events in ventricular cardiomyocytes from rats with heart failure after myocardial infarction, and that these

  18. The cardioprotective effect of vanillic acid on hemodynamic parameters, malondialdehyde, and infarct size in ischemia-reperfusion isolated rat heart exposed to PM10

    PubMed Central

    Radmanesh, Esmat; Dianat, Mahin; Badavi, Mohammad; Goudarzi, Gholamreza; Mard, Seyyed Ali

    2017-01-01

    Objective(s): Particulate matter (PM) exposure can promote cardiac ischemia and myocardial damage. The effects of PM10 on hemodynamic parameters, lipid peroxidation, and infarct size induced by ischemia-reperfusion injury and the protective effects of vanillic acid (VA) in isolated rat heart were investigated. Materials and Methods: Eighty male Wistar rats (250–300 g) were divided into 8 groups (n=10): Control, Sham, VAc, VA, PMa (0.5 mg/kg PM, intratracheal instillation), PMb (2.5 mg/kg PM, intratracheal instillation), PMc (5 mg/kg PM, intratracheal instillation), and PMc + VA (5 mg/kg PM, intratracheal instillation; and 10 mg/kg vanillic acid, gavage for 10 days). PM10 was instilled into the trachea in two stages, within 48 hr. After isolating the hearts and transfer to a Langendorff apparatus, hearts were subjected to 30 min ischemia and 60 min reperfusion. Hemodynamic parameters (±dp/dt, LVSP, LVDP, and RPP), production of lipid peroxidation (MDA), and infarct size were assessed. Results: A significant decrease in ±dp/dt, LVSP, LVDP and RPP occurred in PM groups. A significant increase in MDA and myocardial infarct size occurred in PM groups. A significant increase in LVDP, LVSP, ±dp/dt, RPP and decrease in infarct size, MDA, and myocardial dysfunction was observed in groups that received vanillic acid after ischemia–reperfusion. Conclusion: It was demonstrated that PM10 increases MDA, as well as the percentage of cardiac infarct size, and has negative effects on hemodynamic parameters. This study suggests that vanillic acid may serve as an adjunctive treatment in delaying the progression of ischemic heart disease. PMID:28852440

  19. Influence of fastigial nucleus stimulation on heart rate variability of surgically induced myocardial infarction rats: fastigial nucleus stimulation and autonomous nerve activity.

    PubMed

    Abulaiti, Alimujiang; Hu, Dayi; Zhu, Danian; Zhang, Runfeng

    2011-11-01

    Electrical stimulation of the rostal cerebellar fastigial nucleus (FNS) has been proved to have neuroprotective effects, but it is not known whether FNS also has a cardioprotective effect. One hundred Sprague-Dawley rats were randomly allocated into four groups, including a sham-operation group (Sham group), rats whose coronary arteries were ligated but the FNs were sham stimulated (AMI group), rats in which both coronary arteries were ligated and FNs were stimulated (FNS group), and rats whose fastigial nuclei were lesioned 5 days before ligation, then their coronary arteries were ligated and FNs were stimulated (FNL group). Heart rate variability parameters were monitored 6 h, 24 h, 7 days and 21 days after ligation, and mortality rates, hemodynamic parameters and infarction sizes were compared after 21 days. FNS improved the survival of rats, and this may be due to the increased vagal and decreased sympathetic tone. FN stimulation does not affect infarction size and hemodynamic parameters. FN stimulation may have a protective effect on surgically induced myocardial infarction rats.

  20. The effects of allitridi and amiodarone on the conduction system and reverse use-dependence in the isolated hearts of rats with myocardial infarction.

    PubMed

    Xing, Yanwei; Chen, Jianxin; Wang, Jie; Gao, Yonghong; Niu, Weizhen; Zhao, Mingjing; Zhu, Haiyan; Guo, Lili; Lu, Peng; Wang, Shuoren

    2012-06-01

    Allium sativum L. (DaSuan in Mandarin) is a traditional Chinese herb that has been used to prevent and heal cardiovascular diseases. To study the effects of allitridi (an active constituent of Allium sativum L.) and amiodarone on the conduction system and on reverse use-dependence in the isolated hearts of normal rats and rats with myocardial infarction (MI). Male Sprague Dawley rats, with a ligated left anterior descending coronary artery, were used as myocardial infarction models to investigate the biological effects of the traditional Chinese herb. A single-phase electrode assay and isolated heart perfusion administration methods were employed to study and compare the electrophysiological effects of allitridi and amiodarone on normal and MI rats. Monophasic action potential (MAP) in vitro, effective refractory period (ERP) and monophasic action potential duration (MAPD)/ERP were measured to investigate reverse use-dependence (RUD) with allitridi and amiodarone. Moreover, bundle maps and heart rates were analyzed to evaluate the electrophysiological effects of allitridi on the conduction system of the cardiac muscles. Coronary flow was used to study the beneficial effects of the two drugs on the bundle of His in myocardial infraction. (1) Allitridi and amiodarone can reduce the infarction model of the His bundle (A-H, H-V) conduction and cardiac sinus rhythm in normal rats and isolated rat hearts. After washing in physiological solution (AK-H) for 15 min, the allitridi group partially recovered, but the amiodarone group did not recover. (2) Allitridi and amiodarone had no significant effects on the change of MAPD(90) or ERP in normal and MI rat hearts at different pacing frequencies (200, 250 and 300 beats/min), which indicated no RUD. In addition, the effects of allitridi on prolonging MAPD(90) and ERP were weaker than those of amiodarone (P<0.01). The effects of allitridi on myocardial repolarization and its variation rate were also weaker than those of

  1. Lavandula Reduces Heart Injury via Attenuating Tumor Necrosis Factor-Alpha and Oxidative Stress in A Rat Model of Infarct-Like Myocardial Injury

    PubMed Central

    Vakili, Abedin; Sameni, Hamid Reza; Zahedi khorasani, Mahdi; Darabian, Mohsen

    2017-01-01

    Objective Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated. Materials and Methods In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury (MI). The carotid artery and left ventricle were cannulated to record arterial blood pressure (BP) and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha (TNF-α) level were evaluated. Results Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-α and troponin I in heart tissue (P<0.001). Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-α. In addition, it improved cardiac function and antioxidant enzyme activity (P<0.01). Conclusion Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease. PMID:28367419

  2. Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction.

    PubMed

    Liepinsh, Edgars; Vilskersts, Reinis; Loca, Dagnija; Kirjanova, Olga; Pugovichs, Osvalds; Kalvinsh, Ivars; Dambrova, Maija

    2006-12-01

    The inhibition of gamma-butyrobetaine (GBB) hydroxylase, a key enzyme in the biosynthesis of carnitine, contributes to lay ground for the cardioprotective mechanism of action of mildronate. By inhibiting the biosynthesis of carnitine, mildronate is supposed to induce the accumulation of GBB, a substrate of GBB hydroxylase. This study describes the changes in content of carnitine and GBB in rat plasma and heart tissues during long-term (28 days) treatment of mildronate [i.p. (intraperitoneal) 100 mg/kg/daily]. Obtained data show that in concert with a decrease in carnitine concentration, the administration of mildronate caused a significant increase in GBB concentration. We detected about a 5-fold increase in GBB contents in the plasma and brain and a 7-fold increase in the heart. In addition, we tested the cardioprotective effect of mildronate in isolated rat heart infarction model after 3, 7, and 14 days of administration. We found a statistically significant decrease in necrotic area of infarcted rat hearts after 14 days of treatment with mildronate. The cardioprotective effect of mildronate correlated with an increase in GBB contents. In conclusion, our study, for the first time, provides experimental evidence that the long-term administration of mildronate not only decreases free carnitine concentration, but also causes a significant increase in GBB concentration, which correlates with the cardioprotection of mildronate.

  3. Purinergic signalling in the rostral ventro-lateral medulla controls sympathetic drive and contributes to the progression of heart failure following myocardial infarction in rats.

    PubMed

    Marina, Nephtali; Tang, Feige; Figueiredo, Melina; Mastitskaya, Svetlana; Kasimov, Vitaliy; Mohamed-Ali, Vidya; Roloff, Eva; Teschemacher, Anja G; Gourine, Alexander V; Kasparov, Sergey

    2013-01-01

    Heart failure may lead to hypoperfusion and hypooxygenation of tissues and this is often exacerbated by central and obstructive sleep apnoeas associated with recurrent episodes of systemic hypoxia which triggers release of ATP within the CNS circuits controlling sympathetic outflow. Using in vitro and in vivo models we tested two hypotheses: (1) activated brainstem astroglia release ATP and via release of ATP activate sympathoexcitatory neurones of the rostral ventrolateral medulla (RVLM); and (2) ATP actions in the RVLM contribute to sympathoexcitation, progression of left ventricular (LV) remodelling and development heart failure secondary to myocardial infarction. In vitro, optogenetic activation of RVLM astrocytes transduced to express light-sensitive channelrhodopsin-2 activated sympathoexcitatory RVLM neurones in ATP-dependent manner. In anaesthetised rats in vivo, similar optogenetic activation of RVLM astrocytes increased sympathetic renal nerve activity, arterial blood pressure and heart rate. To interfere with ATP-mediated signalling by promoting its extracellular breakdown, we developed a lentiviral vector to express an ectonucleotidase--transmembrane prostatic acid phosphatase (TMPAP) on the cellular membranes. In rats with myocardial infarction-induced heart failure, expression of TMPAP bilaterally in the RVLM led to lower plasma noradrenaline concentration, maintained left ventricular end diastolic pressure, attenuated decline in dP/dT (max) and shifted the LV pressure-volume relationship curve to the left. These results show that activated RVLM astrocytes are capable of increasing sympathetic activity via release of ATP while facilitated breakdown of ATP in the RVLM attenuates the progression of LV remodelling and heart failure secondary to myocardial infarction.

  4. MET-88, a gamma-butyrobetaine hydroxylase inhibitor, improves cardiac SR Ca2+ uptake activity in rats with congestive heart failure following myocardial infarction.

    PubMed

    Hayashi, Y; Ishida, H; Hoshiai, M; Hoshiai, K; Kirimoto, T; Kanno, T; Nakano, M; Tajima, K; Miyake, H; Matsuura, N; Nakazawa, H

    2000-06-01

    We previously reported that MET-88, 3-(2,2,2-trimethylhydrazinium) propionate, improved left ventricular diastolic dysfunction induced by congestive heart failure (CHF) in rats. The present study was designed to investigate the mechanism by which MET-88 improved the cardiac relaxation impaired in CHF rats. The left coronary artery of the animals was ligated, and the rats were then orally administered vehicle (control), MET-88 at 50 or 100 mg/kg or captopril at 20 mg/kg for 20 days. Myocytes were isolated from the non-infarcted region in the left ventricle, and cell shortening and [Ca2+]i transients were measured with a video-edge detector and by fluorescence analysis, respectively. In CHF control rats, the diastolic phase of cell shortening was prolonged compared with that of the sham-operated (sham) rats. This prolongation was prevented by treatment with MET-88 at 100 mg/kg or captopril at 20 mg/kg. CHF control rats also showed an increase in the decay time of [Ca2+]i transients compared with sham rats. MET-88 at 100 mg/kg and captopril at 20 mg/kg attenuated the increase in decay time of [Ca2+]i transients. Ca2+ uptake activity of the sarcoplasmic reticulum (SR) isolated from the non-infarcted region in the left ventricle was measured, and Lineweaver-Burk plot analysis of the activity was performed. CHF control rats revealed a decrease in the Vmax for SR Ca2+ uptake activity without alteration in Kd. MET-88 at 100 mg/kg significantly prevented the decrease in Vmax, but had no effect on Kd. Also, treatment with MET-88 at 100 mg/kg improved myocardial high-energy phosphate levels impaired in CHF rats. These results suggest that one of the mechanisms by which MET-88 improved cardiac relaxation in CHF rats is based on the amelioration of [Ca2+]i transients through increase of SR Ca2+ uptake activity.

  5. Possible involvement of HSP90-HSF1 multichaperone complex in impairment of HSP72 induction in the failing heart following myocardial infarction in rats.

    PubMed

    Marunouchi, Tetsuro; Araki, Masato; Murata, Mao; Takagi, Norio; Tanonaka, Kouichi

    2013-01-01

    It is generally accepted that an increase in the myocardial level of heat-shock protein 72 (HSP72) protects viable cardiac tissue against myocardial infarction (MI)-induced stress. However, the induction of HSP72 after exposure to heat shock (HS) is blunted in the failing rat heart following MI. The mechanisms underlying this impairment in the HSP72 induction ability of the failing heart are not yet clearly defined. In the present study, we examined the involvement in heat-shock factor 1 (HSF1), a transcription factor of HSPs, in decreased ability for HSP72 induction in the failing rat heart following MI. In the failing heart, nuclear translocation of the HSF1 after exposure to hyperthermia was markedly reduced, whereas HSF1 in the cytosolic fraction and the HSP90 chaperone complex containing HSF1, a repressor of HSF1, were increased. Treatment with an HSP90 inhibitor, 17-allylamino-17-demethoxygel-danamycin, appeared to dissociate the interaction of HSF1 with HSP90, and then induced HSP72 in the failing heart after exposure to hyperthermia. These results suggest that an increase in the multichaperone complex, especially the HSF1-HSP90 interaction, associated with attenuation of HSF1 translocation into the nucleus, was involved in the impairment of HS-induced HSP72 induction in the failing heart following MI.

  6. Role of myocardial neuronal nitric oxide synthase-derived nitric oxide in beta-adrenergic hyporesponsiveness after myocardial infarction-induced heart failure in rat.

    PubMed

    Bendall, Jennifer K; Damy, Thibaud; Ratajczak, Philippe; Loyer, Xavier; Monceau, Virginie; Marty, Isabelle; Milliez, Paul; Robidel, Estelle; Marotte, Françoise; Samuel, Jane-Lise; Heymes, Christophe

    2004-10-19

    An emerging concept is that a neuronal isoform of nitric oxide synthase (NOS1) may regulate myocardial contractility. However, a role for NOS1-derived nitric oxide (NO) in heart failure (HF) has not been defined. Using a model of myocardial infarction-induced HF, we demonstrated that cardiac NOS1 expression and activity increased in HF rats (P<0.05 and P<0.001 versus shams, respectively). This was associated with translocation of NOS1 from the ryanodine receptor to the sarcolemma through interactions with caveolin-3 in HF hearts. With ex vivo and in vivo pressure-volume analysis, cardiac NOS1-derived NO was found to be negatively inotropic in shams but not HF hearts. Ventricular elastance (E(es)) was significantly reduced in HF rats (P<0.05), and tau, the time constant of left ventricular relaxation, was prolonged (both P<0.05). Acute NOS1 inhibition significantly increased E(es) by 33+/-3% and tau by 17+/-2% (P<0.05) in shams, although these effects were significantly attenuated in HF hearts. beta-Adrenergic stimulation induced a marked increase in systolic performance in sham hearts, with the responses being significantly blunted in HF hearts. E(es) increased by 163+/-42% (P<0.01) in sham hearts and 56+/-9% in HF hearts, and LV +dP/dt increased by 97+/-9% (P<0.01) in shams and 37+/-7% (P<0.05) in the HF group. Interestingly, preferential NOS1 inhibition enhanced the blunted responses of LV +dP/dt and E(es) to beta-adrenergic stimulation in HF rats but had no effect in shams. These results provide the first evidence that increased NOS1-derived NO production may play a role in the autocrine regulation of myocardial contractility in HF.

  7. ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction.

    PubMed

    Yu, Yang; Wei, Shun-Guang; Zhang, Zhi-Hua; Weiss, Robert M; Felder, Robert B

    2016-03-15

    Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5-7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediators. HF rats treated with ERK1/2 siRNAs also had reduced PVN neuronal excitation (fewer Fos-related antigen-like-immunoreactive neurons), lower plasma norepinephrine levels, and improved peripheral manifestations of HF compared with HF rats treated with control siRNAs. These results demonstrate that ERK1/2 signaling in the PVN plays a pivotal role in mediating sympathetic drive in HF induced by myocardial infarction and may be a novel target for therapeutic intervention. Copyright © 2016 the American Physiological Society.

  8. ERK1/2 MAPK signaling in hypothalamic paraventricular nucleus contributes to sympathetic excitation in rats with heart failure after myocardial infarction

    PubMed Central

    Yu, Yang; Wei, Shun-Guang; Zhang, Zhi-Hua; Weiss, Robert M.

    2016-01-01

    Brain MAPK signaling pathways are activated in heart failure (HF) induced by myocardial infarction and contribute to augmented sympathetic nerve activity. We tested whether decreasing ERK1/2 (also known as p44/42 MAPK) signaling in the hypothalamic paraventricular nucleus (PVN), a forebrain source of presympathetic neurons, would reduce the upregulation of sympathoexcitatory mediators in the PVN and augmented sympathetic nerve activity in rats with HF. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce HF, with left ventricular dysfunction confirmed by echocardiography. One week after coronary artery ligation or sham operation, small interfering (si)RNAs targeting ERK1/2 or a nontargeting control siRNA was microinjected bilaterally into the PVN. Experiments were conducted 5–7 days later. Confocal images revealed reduced phosphorylated ERK1/2 immunofluorescence in the PVN of HF rats treated with ERK1/2 siRNAs compared with HF rats treated with control siRNA. Western blot analysis confirmed significant reductions in both total and phosphorylated ERK1/2 in the PVN of HF rats treated with ERK1/2 siRNAs along with reduced expression of renin-angiotensin system components and inflammatory mediators. HF rats treated with ERK1/2 siRNAs also had reduced PVN neuronal excitation (fewer Fos-related antigen-like-immunoreactive neurons), lower plasma norepinephrine levels, and improved peripheral manifestations of HF compared with HF rats treated with control siRNAs. These results demonstrate that ERK1/2 signaling in the PVN plays a pivotal role in mediating sympathetic drive in HF induced by myocardial infarction and may be a novel target for therapeutic intervention. PMID:26801309

  9. Nanog expression in heart tissues induced by acute myocardial infarction.

    PubMed

    Luo, Huanhuan; Li, Qiong; Pramanik, Jogen; Luo, Jiankai; Guo, Zhikun

    2014-10-01

    Nanog is a potential stem cell marker and is considered a regeneration factor during tissue repair. In the present study, we investigated expression patterns of nanog in the rat heart after acute myocardial infarction by semi-quantitative RT-PCR, immunohistochemistry and Western blot analyses. Our results show that nanog at both mRNA and protein levels is positively expressed in myocardial cells, fibroblasts and small round cells in different myocardial zones at different stages after myocardial infarction, showing a spatio-temporal and dynamic change. After myocardial infarction, the nanog expression in fibroblasts and small round cells in the infarcted zone (IZ) is much stronger than that in the margin zone (MZ) and remote infarcted zone (RIZ). From day 7 after myocardial infarction, the fibroblasts and small cells strongly expressed nanog protein in the IZ, and a few myocardial cells in the MZ and the RIZ and the numbers of nanog-positive fibroblasts and small cells reached the highest peak at 21 days after myocardial infarction, but in this period the number of nanog-positive myocardial cells decreased gradually. At 28 days after myocardial infarction, the numbers of all nanog-positive cells decreased into a low level. Therefore, our data suggest that all myocardial cells, fibroblasts and small round cells are involved in myocardial reconstruction after cardiac infarction. The nanog-positive myocardial cells may respond to early myocardial repair, and the nanog-positive fibroblasts and small round cells are the main source for myocardial reconstruction after cardiac infarction.

  10. 5-Methoxyleoligin, a Lignan from Edelweiss, Stimulates CYP26B1-Dependent Angiogenesis In Vitro and Induces Arteriogenesis in Infarcted Rat Hearts In Vivo

    PubMed Central

    Messner, Barbara; Kern, Johann; Wiedemann, Dominik; Schwaiger, Stefan; Türkcan, Adrian; Ploner, Christian; Trockenbacher, Alexander; Aumayr, Klaus; Bonaros, Nikolaos; Laufer, Günther; Stuppner, Hermann; Untergasser, Gerold; Bernhard, David

    2013-01-01

    Background Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail. Methods and Results 5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI). Conclusion The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI. PMID:23554885

  11. Adipose-derived mesenchymal stem cells embedded in platelet-rich fibrin scaffolds promote angiogenesis, preserve heart function, and reduce left ventricular remodeling in rat acute myocardial infarction

    PubMed Central

    Chen, Yung-Lung; Sun, Cheuk-Kwan; Tsai, Tzu-Hsien; Chang, Li-Teh; Leu, Steve; Zhen, Yen-Yi; Sheu, Jiunn-Jye; Chua, Sarah; Yeh, Kuo-Ho; Lu, Hung-I; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

    2015-01-01

    Objective: This study tested the hypothesis that autologous adipose-derived mesenchymal stem cells (ADMSCs) embedded in platelet-rich fibrin (PRF) can significant promote myocardial regeneration and repair after acute myocardial infarction (AMI). Summary background: With avoiding the needle-related complications, PRF-embedded autologous ADMSCs graft provides a new effective stem cell-based therapeutic strategy for myocardial repair. Methods: Adult male Sprague-Dawley rats were equally divided (n = 8 per group) into group 1 (sham-operated), group 2 (AMI by ligating left coronary artery), group 3 (AMI+ PRF), and group 4 (AMI+PRF-embedded autologous ADMSCs). RPF with or without ADMSCs was patched on infarct area 1h after AMI induction. All animals were sacrificed on day 42 after echocardiography. Results: Left ventricular (LV) dimension and infarct/fibrotic areas were lowest in group 1, highest in group 2, in group 3 higher than in group 4, whereas LV performance and wall thickness exhibited a reversed pattern in all groups (all p < 0.001). Protein expressions of inflammatory (MMP-9, IL-1β), oxidative, apoptotic (Bax, cleaved PARP), fibrotic (Smad 3, TFG-β), hypertrophic (β-MHC), and heart failure (BNP) biomarkers displayed an identical pattern in infarct/fibrotic areas, whereas the protein expressions of anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), anti-fibrotic (Smad1/5, BMP-2) biomarkers and α-MHC showed an opposite pattern (all p < 0.01). Angiogenic activities (c-Kit+, Sca-1+, CD31+, SDF-1α+, CXCR4+ cells; protein expressions of SDF-1α, CXCR4, VEGF) were highest in group 4 and lowest in group 1 (all p < 0.001). Conclusion: ADMSCs embedded in PRF offered significant benefit in preserving LV function and limiting LV remodeling after AMI. PMID:26175843

  12. Post-infarct treatment with [Pyr1]apelin-13 exerts anti-remodelling and anti-apoptotic effects in rats' hearts.

    PubMed

    Azizi, Yaser; Imani, Alireza; Fanaei, Hamed; Khamse, Safoura; Parvizi, Mohammad Reza; Faghihi, Mahdieh

    2017-01-01

    Ischaemic heart disease is the main cause of mortality in the world. After myocardial infarction (MI) cardiomyocytes apoptosis and ventricular remodelling have occurred. Apelin is a peptide that has been shown to exert cardioprotective effects. The aim of this study was to investigate the anti-apoptotic and anti-remodelling effects of [Pyr¹]apelin-13 in the rat model of post-MI. Thirty-six male Wistar rats were randomly divided into three groups: (1) sham, (2) MI, and (3) MI treated with [Pyr¹] apelin-13 (MI+Apel). MI animals were subjected to 30-min ligation of the left anterior descending coronary artery (LAD) and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr¹]apelin-13 (10 nmol/kg/day, i.p.) was administered for five consecutive days. Hypertrophic parameters, left ventricular (LV) remodelling, and gene expression of Apel, apelin receptor (Apelr), Bax, caspase-3 (Casp-3), and Bcl-2 by real-time polymerase chain reaction and cardiomyocytes apoptosis by TUNEL immunostaining were assessed on day 14 post-MI. Post-infarct treatment with [Pyr¹]apelin-13 improved myocardial hypertrophic and LV remodelling parameters and led to a significant increase in the expression of Apel, Apelr, and Bcl-2, and a decrease in the expression of Bax and Casp-3. Furthermore, treatment with [Pyr¹]apelin-13 decreased cardiomyocyte apoptosis. [Pyr¹]apelin-13 has anti-hypertrophic, anti-remodelling, and anti-apoptotic effects via overexpression of Apel, Apelr, and Bcl-2 and reduces gene expression of Bax and Casp-3 in the infarcted myocardium, which can in turn lead to repair myocardium.

  13. Noradrenaline-induced increases in calcium and tension in skeletal muscle conductance and resistance arteries from rats with post-infarction heart failure.

    PubMed

    Trautner, Simon; Amtorp, Ole; Boesgaard, Soren; Andersen, Claus B; Galbo, Henrik; Haunsoe, Stig; Sheykhzade, Majid

    2006-05-10

    We tested the hypothesis that arterial reactivity to noradrenaline is augmented in congestive heart failure (CHF), which could contribute to the deleterious changes in peripheral vascular resistance and compliance in this condition. From male Wistar rats with post-infarction CHF and sham-operated rats, skeletal muscle conductance and resistance arteries (mean lumen diameters: 514 and 186 microm) were isolated and mounted on wire myographs, and wall tension was recorded in response to cumulative application of acetylcholine and noradrenaline to the vessel segments. In a subset of experiments, wall tension and cytosolic free calcium ion concentration [Ca(2+)](i) were recorded simultaneously during noradrenaline application, using wire myography and the FURA-2 technique. No significant differences were found in the arterial baseline levels of [Ca(2+)](i) or tension between CHF and sham rats. In the resistance arteries of CHF rats, the noradrenaline-induced increases in [Ca(2+)](i) were significantly enhanced (P=0.003). Despite the augmented [Ca(2+)](i) levels, the tension responses to noradrenaline were unaltered in these arteries. In the conductance arteries, there were no significant differences in noradrenaline-induced [Ca(2+)](i) or tension responses between CHF and control rats. CHF did not alter vascular morphology or change vascular relaxations to acetylcholine in either type of artery. In conclusion, these results do not support the contention that arterial reactivity to noradrenaline is augmented in the skeletal muscle vascular bed in CHF. On the contrary, the unchanged contractile responsiveness in the resistance arteries despite the enhanced levels of [Ca(2+)](i) during noradrenaline application suggests that the contractile function of these vessels is compromised in CHF. Neither vascular remodeling, endothelial dysfunction nor changes in baseline vascular tone could be demonstrated in the skeletal muscle vascular bed of this animal model of heart failure.

  14. [Streptokinase in impending heart infarct].

    PubMed

    Kiemeneij, F; Schuilenburg, R M

    1989-02-18

    A patient is described with an impending myocardial infarction due to presence of an intracoronary thrombus in an otherwise normal left anterior descending artery. This case illustrates that intracoronary and intravenous administration of streptokinase can be of value in the treatment of impending myocardial infarction.

  15. Acute inhibition of monoamine oxidase and ischemic preconditioning in isolated rat hearts: interference with postischemic functional recovery but no effect on infarct size reduction.

    PubMed

    Dănilă, Maria D; Privistirescu, Andreea I; Mirica, Silvia N; Sturza, Adrian; Ordodi, Valentin; Noveanu, Lavinia; Duicu, Oana M; Muntean, Danina M

    2015-09-01

    Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts. Animals subjected to 30 min global ischemia and 120 min reperfusion were assigned to the following groups: (i) Control, no additional intervention; (ii) IPC, 3 cycles of 5 min ischemia and 5 min reperfusion before the index ischemia; (iii) IPC-clorgyline, IPC protocol bracketed for 5 min with clorgyline (50 μmol/L); (iv) IPC-pargyline, IPC protocol bracketed for 5 min with pargyline (0.5 mmol/L). The postischemic functional recovery was assessed by the left ventricular developed pressure (LVDP) and the indices of contractility (+dLVP/dt max) and relaxation (-dLVP/dt max). Infarct size (IS) was quantified by TTC staining. In both genders, IPC significantly improved functional recovery that was further enhanced in the presence of either clorgyline or pargyline. IS reduction was comparable among all the preconditioned groups, regardless of the presence of MAO inhibitors. In isolated rat hearts, acute inhibition of MAOs potentiates the IPC-induced postischemic functional recovery without interfering with the anti-necrotic protection.

  16. Effects of Postconditioning, Preconditioning and Perfusion of L-carnitine During Whole Period of Ischemia/ Reperfusion on Cardiac Hemodynamic Functions and Myocardial Infarction Size in Isolated Rat Heart

    PubMed Central

    Najafi, Moslem

    2013-01-01

    Objective(s): In the present work, the effects of L-carnitine (LC) on postischemic cardiac hemodynamic functions and infarction size were studied in isolated rat heart. Materials and Methods: The hearts were subjected to 30 min regional ischemia followed by 120 min reperfusion. Then they were perfused by a drug-free or LC-enriched Krebs–Henseleit (K/H) solution during ischemia/ reperfusion (I/R) (Protocol 1), 10 min before ischemia induction (Protocol 2; preconditioning group) or the first 10 min of reperfusion (Protocol 3; postconditioning group). Results: The perfusion of LC in protocol 1 significantly reduced left ventricular end diastolic pressure (LVEDP) (P<0.05), and increased left ventricular developed pressure (LVDP) (P<0.05), rate pressure product (RPP) (P<0.01) and coronary flow rate (CFR) (P<0.05). The short-term preischemic administration of LC in protocol 2 improved RPP, CFR and decreased the extent of LVEDP elevation. However, protective effects of LC in this protocol were low compared to the whole period perfusion. In protocol 3, LC preserved postischemic cardiac functions not as much as the other protocols. In addition, infarct size significantly decreased by LC in all protocols as opposed to the control group (P<0.001). Conclusion: The results of the present work showed that LC produced protective effects against I/R injury. These protective actions were reversed by concomitant use of etomoxir (a CPT-I inhibitor), suggesting that the efficacy of LC could be due to its mitochondrial action, probably related to the raise in glucose oxidation of the reperfused hearts. PMID:24250945

  17. Effects of Postconditioning, Preconditioning and Perfusion of L-carnitine During Whole Period of Ischemia/ Reperfusion on Cardiac Hemodynamic Functions and Myocardial Infarction Size in Isolated Rat Heart

    PubMed Central

    Najafi, Moslem

    2013-01-01

    Objective(s): In the present work, the effects of L-carnitine (LC) on postischemic cardiac hemodynamic functions and infarction size were studied in isolated rat heart. Materials and Methods: The hearts were subjected to 30 min regional ischemia followed by 120 min reperfusion. Then they were perfused by a drug-free or LC-enriched Krebs–Henseleit (K/H) solution during ischemia/ reperfusion (I/R) (Protocol 1), 10 min before ischemia induction (Protocol 2; preconditioning group) or the first 10 min of reperfusion (Protocol 3; postconditioning group). Results: The perfusion of LC in protocol 1 significantly reduced left ventricular end diastolic pressure (LVEDP) (P<0.05), and increased left ventricular developed pressure (LVDP) (P<0.05), rate pressure product (RPP) (P<0.01) and coronary flow rate (CFR) (P<0.05). The short-term preischemic administration of LC in protocol 2 improved RPP, CFR and decreased the extent of LVEDP elevation. However, protective effects of LC in this protocol were low compared to the whole period perfusion. In protocol 3, LC preserved postischemic cardiac functions not as much as the other protocols. In addition, infarct size significantly decreased by LC in all protocols as opposed to the control group (P<0.001). Conclusion: The results of the present work showed that LC produced protective effects against I/R injury. These protective actions were reversed by concomitant use of etomoxir (a CPT-I inhibitor), suggesting that the efficacy of LC could be due to its mitochondrial action, probably related to the raise in glucose oxidation of the reperfused hearts. PMID:24250943

  18. Receptor-interacting protein 140 overexpression impairs cardiac mitochondrial function and accelerates the transition to heart failure in chronically infarcted rats.

    PubMed

    Chen, YanFang; Chen, ShaoRui; Yue, ZhongBao; Zhang, YiQiang; Zhou, ChangHua; Cao, WeiWei; Chen, Xi; Zhang, LuanKun; Liu, PeiQing

    2017-02-01

    Heart failure (HF) is associated with myocardial energy metabolic abnormality. Receptor-interacting protein 140 (RIP140) is an important transcriptional cofactor for maintaining energy balance in high-oxygen consumption tissues. However, the role of RIP140 in the pathologic processes of HF remains to be elucidated. In this study, we investigated the role of RIP140 in mitochondrial and cardiac functions in rodent hearts under myocardial infarction (MI) stress. MI was created by a permanent ligation of left anterior descending coronary artery and exogenous expression of RIP140 by adenovirus (Ad) vector delivery. Four weeks after MI or Ad-RIP140 treatment, cardiac function was assessed by echocardiographic and hemodynamics analyses, and the mitochondrial function was determined by mitochondrial genes expression, biogenesis, and respiration rates. In Ad-RIP140 or MI group, a subset of metabolic genes changed, accompanied with slight reductions in mitochondrial biogenesis and respiration rates but no change in adenosine triphosphate (ATP) content. Cardiac malfunction was compensated. However, under MI stress, rats overexpressing RIP140 exhibited greater repressions in mitochondrial genes, state 3 respiration rates, respiration control ratio, and ATP content and had further deteriorated cardiac malfunction. In conclusion, RIP140 overexpression leads to comparable cardiac function as resulted from MI, but RIP140 aggravates metabolic repression, mitochondrial malfunction, and further accelerates the transition to HF in response to MI stress.

  19. Cholinergic stimulation with pyridostigmine improves autonomic function in infarcted rats.

    PubMed

    de La Fuente, Raquel N; Rodrigues, Bruno; Moraes-Silva, Ivana C; Souza, Leandro E; Sirvente, Raquel; Mostarda, Cristiano; De Angelis, Kátia; Soares, Pedro P; Lacchini, Silvia; Consolim-Colombo, Fernanda; Irigoyen, Maria-Cláudia

    2013-09-01

    In the present study we evaluated the effects of short-term pyridostigmine bromide (0.14 mg/mL) treatment started early after myocardial infarction (MI) on left ventricular (LV) and autonomic functions in rats. Male Wistar rats were divided into control, pyridostigmine, infarcted and infarcted + pyridostigmine-treated groups. Pyridostigmine was administered in the drinking water, starting immediately after MI or sham operation, for 11 days. Left ventricular function was evaluated indirectly by echocardiography and directly by LV catheterization. Cardiovascular autonomic control was evaluated by baroreflex sensitivity (BRS), heart rate variability (HRV) and pharmacological blockade. All evaluations started after 7 days pyridostigmine treatment and were finalized after 11 days treatment. Pyridostigmine prevented the impairment of +dP/dT and reduced the MI area in infarcted + pyridostigmine compared with infarcted rats (7 ± 3% vs 17 ± 4%, respectively). Mean blood pressure was restored in infarcted + pyridostigmine compared with infarcted rats (103 ± 3 vs 94 ± 3 mmHg, respectively). In addition, compared with the infarcted group, pyridostigmine improved BRS, as evaluated by tachycardic (1.6 ± 0.2 vs 2.5 ± 0.2 b.p.m./mmHg, respectively) and bradycardic (-0.42 ± 0.01 vs -1.9 ± 0.1 b.p.m./mmHg) responses, and reduced the low frequency/high frequency ratio of HRV (0.81 ± 0.11 vs 0.24 ± 0.14, respectively). These improvements are probably associated with increased vagal tone and reduced sympathetic tone in infarcted + pyridostigmine compared with infarcted rats. In conclusion, the data suggest that short-term pyridostigmine treatment started early after MI can improve BRS, HRV and parasympathetic and sympathetic tone in experimental rats. These data may have potential clinical implications because autonomic markers have prognostic significance after MI. © 2013 Wiley Publishing Asia Pty Ltd.

  20. The role of apelin in central cardiovascular regulation in rats with post-infarct heart failure maintained on a normal fat or high fat diet.

    PubMed

    Czarzasta, Katarzyna; Cudnoch-Jedrzejewska, Agnieszka; Szczepanska-Sadowska, Ewa; Fus, Lukasz; Puchalska, Liana; Gondek, Agata; Dobruch, Jakub; Gomolka, Ryszard; Wrzesien, Robert; Zera, Tymoteusz; Gornicka, Barbara; Kuch, Marek

    2016-10-01

    Based on the available literature, it can be assumed that in cases of post-infarct heart failure (HF) and obesity, a significant change in the central regulation of the cardiovascular system takes place with, among others, the involvement of the apelinergic system. The main objective of the present study was to clarify the role of apelin-13 in the central regulation of the cardiovascular system in Sprague Dawley rats with HF or sham operated (SO) and fed on a normal fat (NFD) or a high fat diet (HFD). The study was divided into two parts: Part I, hemodynamic studies; and Part II, biochemical and molecular studies. The animals were subjected to the following research procedures. Part I and II: feeding NFD or HFD; experimental induction of HF or SO; Part I: intracerebroventricular (ICV) infusion of the examined substances, monitoring of mean arterial blood pressure (MABP) and heart rate (HR); Part II: venous blood and tissue samples collected. ICV infusion of apelin-13 caused significantly higher changes in ΔMABP in the SO NFD group. No changes were noted in ΔHR in any of the studied groups. Apelin and apelin receptor (APJ) mRNA expression in the brain and adipose tissues was higher in the HF rats. HFD causes significant increase in expression of apelin and APJ mRNA in the left ventricle. In conclusion, HF and HFD appear to play an important role in modifying the activity of the central apelinergic system and significant changes in mRNA expression of apelin and APJ receptor. © 2016 John Wiley & Sons Australia, Ltd.

  1. Insulin and GSK3β-inhibition abrogates the infarct sparing-effect of ischemic postconditioning in ex vivo rat hearts.

    PubMed

    Helgeland, Erik; Wergeland, Anita; Sandøy, Rune M; Askeland, Maren; Aspevik, Anne; Breivik, Lars; Jonassen, Anne K

    2017-06-01

    Pharmacological treatment of reperfusion injury using insulin and GSK3β inhibition has been shown to be cardioprotective, however, their interaction with the endogenous cardioprotective strategy, ischemic postconditioning, is not known. Langendorff perfused ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. For the first 15 min of reperfusion hearts received either vehicle (Ctr), insulin (Ins) or a GSK3β inhibitor (SB415286; SB41), with or without interruption of ischemic postconditioning (IPost; 3 × 30 s of global ischemia). In addition, the combination of insulin and SB41 for 15 min was assessed. Insulin, SB41 or IPost significantly reduced infarct size versus vehicle treated controls (IPost 33.5 ± 3.3%, Ins 33.5 ± 3.4%, SB41 30.5 ± 3.0% vs. Ctr 54.7 ± 6.8%, p < 0.01). Combining insulin and SB415286 did not confer additional cardioprotection compared to the treatments given alone (SB41 + Ins 26.7 ± 3.5%, ns). Conversely, combining either of the pharmacological reperfusion treatments with IPost completely abrogated the cardioprotection afforded by the treatments separately (Ins + IPost 59.5 ± 3.4% vs. Ins 33.5 ± 3.4% and SB41 + IPost 50.2 ± 6.6% vs. SB41 30.5 ± 3.0%, both p < 0.01), and was associated with blunted Akt, GSK3β and STAT3 phosphorylation. Pharmacological reperfusion treatment with insulin and SB41 interferes with the cardioprotection afforded by ischemic postconditioning.

  2. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts.

    PubMed

    Lee, Tsung-Ming; Chang, Nen-Chung; Lin, Shinn-Zong

    2017-03-01

    During myocardial infarction, infiltrated macrophages have pivotal roles in cardiac remodeling and delayed M1 toward M2 macrophage phenotype transition is considered one of the major factors for adverse ventricular remodeling. We investigated whether dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, attenuates cardiac fibrosis via regulating macrophage phenotype by a reactive oxygen and nitrogen species (RONS)/STAT3-dependent pathway in postinfarcted rats. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline, dapagliflozin (a specific SGLT2 inhibitor), phlorizin (a nonspecific SGLT1/2 inhibitor), dapagliflozin + S3I-201 (a STAT3 inhibitor), or phlorizin + S3I-201 for 4 weeks. There were similar infarct sizes among the infarcted groups at the acute and chronic stages of infarction. At day 3 after infarction, post-infarction was associated with increased levels of superoxide and nitrotyrosine, which can be inhibited by administering either dapagliflozin or phlorizin. SGLT2 inhibitors significantly increased STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels and the percentage of M2 macrophage infiltration. At day 28 after infarction, SGLT2 inhibitors were associated with attenuated myofibroblast infiltration and cardiac fibrosis. Although phlorizin decreased myofibroblast infiltration, the effect of dapagliflozin on attenuated myofibroblast infiltration was significantly higher than phlorizin. The effects of SGLT2 inhibitors on cardiac fibrosis were nullified by adding S3I-201. Furthermore, the effects of dapagliflozin on STAT3 activity and myocardial IL-10 levels can be reversed by 3-morpholinosydnonimine, a peroxynitrite generator. Taken together, these observations provide a novel mechanism of SGLT2 inhibitors-mediated M2 polarization through a RONS-dependent STAT3-mediated pathway and selective SGLT2 inhibitors are more effective in attenuating myofibroblast infiltration during

  3. Nitrendipine binding in congestive heart failure due to myocardial infarction

    SciTech Connect

    Dixon, I.M.; Lee, S.L.; Dhalla, N.S. )

    1990-03-01

    Depressed cardiac pump function is the hallmark of congestive heart failure, and it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Since Ca2+ channels in the sarcolemmal membrane are considered to be an important route for the entry of Ca2+, we examined the status of Ca2+ receptors/channels in failing rat hearts after myocardial infarction of the left ventricular free wall. For this purpose, the left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. Hemodynamic assessment revealed decreased total mechanical energy (left ventricular systolic pressure x heart rate), increased left ventricular diastolic pressure, and decreased positive and negative dP/dt in experimental animals at 4, 8, and 16 weeks. Although accumulation of ascites in the abdominal cavity was evident at 4 weeks, other clinical signs of congestive heart failure in experimental rats were evident from the presence of lung congestion and cardiac dilatation at 8 and 16 weeks after induction of myocardial infarction. The density of Ca2+ receptors/channels in crude membranes, as assessed by (3H)nitrendipine binding assay, was found to be decreased in the uninfarcted experimental left ventricle at 8 and 16 weeks; however, no change in the affinity of nitrendipine was evident. A similar depression in the specific binding of another dihydropyridine compound, (3H)PN200-110, was also evident in failing hearts. Brain and skeletal muscle crude membrane preparations, unlike those of the right ventricle and liver, revealed a decrease in Ca2+ receptors/channels density in experimental animals at 16 weeks.

  4. Endogenous C1-inhibitor production and expression in the heart after acute myocardial infarction.

    PubMed

    Emmens, Reindert W; Baylan, Umit; Juffermans, Lynda J M; Karia, Rashmi V; Ylstra, Bauke; Wouters, Diana; Zeerleder, Sacha; Simsek, Suat; van Ham, Marieke; Niessen, Hans W M; Krijnen, Paul A J

    2016-01-01

    Complement activation contributes significantly to inflammation-related damage in the heart after acute myocardial infarction. Knowledge on factors that regulate postinfraction complement activation is incomplete however. In this study, we investigated whether endogenous C1-inhibitor, a well-known inhibitor of complement activation, is expressed in the heart after acute myocardial infarction. C1-inhibitor and complement activation products C3d and C4d were analyzed immunohistochemically in the hearts of patients who died at different time intervals after acute myocardial infarction (n=28) and of control patients (n=8). To determine putative local C1-inhibitor production, cardiac transcript levels of the C1-inhibitor-encoding gene serping1 were determined in rats after induction of acute myocardial infarction (microarray). Additionally, C1-inhibitor expression was analyzed (fluorescence microscopy) in human endothelial cells and rat cardiomyoblasts in vitro. C1-inhibitor was found predominantly in and on jeopardized cardiomyocytes in necrotic infarct cores between 12h and 5days old. C1-inhibitor protein expression coincided in time and colocalized with C3d and C4d. In the rat heart, serping1 transcript levels were increased from 2h up until 7days after acute myocardial infarction. Both endothelial cells and cardiomyoblasts showed increased intracellular expression of C1-inhibitor in response to ischemia in vitro (n=4). These observations suggest that endogenous C1-inhibitor is likely involved in the regulation of complement activity in the myocardium following acute myocardial infarction. Observations in rat and in vitro suggest that C1-inhibitor is produced locally in the heart after acute myocardial infarction. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Protective effects of sinapic acid on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats.

    PubMed

    Roy, Subhro Jyoti; Stanely Mainzen Prince, Ponnian

    2012-11-01

    In the pathology of myocardial infarction, lysosomal lipid peroxidation and resulting enzyme release play an important role. We evaluated the protective effects of sinapic acid on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats. Male Wistar rats were treated with sinapic acid (12 mg/kg body weight) orally daily for 10 days and isoproterenol (100 mg/kg body weight) was injected twice at an interval of 24 h (9th and 10th day). Then, lysosomal lipid peroxidation, lysosomal enzymes in serum, heart homogenate, lysosomal fraction and myocardial infarct size were measured. Isoproterenol induced myocardial infarcted rats showed a significant increase in serum creatine kinase-MB and lysosomal lipid peroxidation. The activities of β-glucuronidase, β-galactosidase, cathepsin-B and D were significantly increased in serum, heart and the activities of β-glucuronidase and cathepsin-D were significantly decreased in lysosomal fraction of myocardial infarcted rats. Pre-and-co-treatment with sinapic acid normalized all the biochemical parameters and reduced myocardial infarct size in myocardial infarcted rats. In vitro studies confirmed the free radical scavenging effects of sinapic acid. The possible mechanisms for the observed effects are attributed to sinapic acid's free radical scavenging and membrane stabilizing properties. Thus, sinapic acid has protective effects on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats.

  6. Reduction of experimental myocardial infarct size by pre-treatment with magnesium sulfate in rats.

    PubMed

    Lal, A; Rana, G C

    1991-01-01

    Experimental myocardial infarction was induced in albino rats by administration of isoprenaline hydrochloride, 85 mg/kg, sc, daily for two consecutive days. Such rats were pretreated with either saline or magnesium sulfate (60 mg/kg) po, daily for three weeks, to serve as control or treated groups respectively. Heart specimens were taken for gross and histological examination at 24 hr, on 5th day, 12th day and 21st day. Infarct size was significantly reduced in the magnesium-treated group (P less than 0.05). We conclude that magnesium sulfate exerted a potent prophylactic effect in limiting infarct size in rats.

  7. Intestinal microbiota determine severity of myocardial infarction in rats

    PubMed Central

    Lam, Vy; Su, Jidong; Koprowski, Stacy; Hsu, Anna; Tweddell, James S.; Rafiee, Parvaneh; Gross, Garrett J.; Salzman, Nita H.; Baker, John E.

    2012-01-01

    Signals from the intestinal microbiota are important for normal host physiology; alteration of the microbiota (dysbiosis) is associated with multiple disease states. We determined the effect of antibiotic-induced intestinal dysbiosis on circulating cytokine levels and severity of ischemia/reperfusion injury in the heart. Treatment of Dahl S rats with a minimally absorbed antibiotic vancomycin, in the drinking water, decreased circulating leptin levels by 38%, resulted in smaller myocardial infarcts (27% reduction), and improved recovery of postischemic mechanical function (35%) as compared with untreated controls. Vancomycin altered the abundance of intestinal bacteria and fungi, measured by 16S and 18S ribosomal DNA quantity. Pretreatment with leptin (0.12 μg/kg i.v.) 24 h before ischemia/reperfusion abolished cardioprotection produced by vancomycin treatment. Dahl S rats fed the commercially available probiotic product Goodbelly, which contains the leptin-suppressing bacteria Lactobacillus plantarum 299v, also resulted in decreased circulating leptin levels by 41%, smaller myocardial infarcts (29% reduction), and greater recovery of postischemic mechanical function (23%). Pretreatment with leptin (0.12 μg/kg i.v.) abolished cardioprotection produced by Goodbelly. This proof-of-concept study is the first to identify a mechanistic link between changes in intestinal microbiota and myocardial infarction and demonstrates that a probiotic supplement can reduce myocardial infarct size.—Lam, V., Su, J., Koprowski, S., Hsu, A., Tweddell, J. S., Rafiee, P., Gross, G. J., Salzman, N. H., Baker, J. E. Intestinal microbiota determine severity of myocardial infarction in rats. PMID:22247331

  8. Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts

    PubMed Central

    Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

    2015-01-01

    Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization. PMID:26251592

  9. Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

    PubMed

    Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

    2015-01-01

    Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

  10. A segmentation method for myocardial ischemia/infarction applicable in heart photos.

    PubMed

    Baracho, Salety Ferreira; Pinheiro, Daniel José Lins Leal; Godoy, Carlos Marcelo Gurjão de; Coelho, Regina Célia

    2017-08-01

    The myocardial infarction, known as heart attack, is the ultimate result of a prolonged/untreated cardiac ischemia. The accurate segmentation of the myocardial infarction or ischemia in images obtained from diversified sources, such as Magnetic Resonance Images or Echocardiograph, is worthwhile for the medical area or the animal experimentation. An alternative image source for ischemia/infarction segmentation is the photo, which can depict the actual heart image. This work presents a method for ischemia segmentation in rat heart photos. The method applicability was tested in pictures of human hearts available in public databases from the Internet. At first, heart images were separated from the background using GrabCut method. Secondly, the segmentation of the cardiac ischemia region was performed by using Fuzzy Clustering method. Finally, a sequence of image processing (including morphological operations to remove small components and to fill the holes) was performed to obtain the final segmentation image. All resulting images were compared with the corresponding images containing contours of cardiac ischemia drawn manually by specialists. The mean accuracy was 83.24% ± 04.16%. As for the intrinsically human errors (tracing error between two specialists: 18.94% ± 05.30%), the average accuracy is within the inter-operator variability. As for the human heart pictures obtained from public libraries, the algorithm segmented the infarction areas correctly. The results show that the algorithm effectively helps the visualization of the cardiac ischemia/infarction region and has the potential to be applied to heart images of animals or humans, representing a versatile tool to assist advances in cardiomyopathology studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats.

    PubMed

    Jumabay, Medet; Matsumoto, Taro; Yokoyama, Shin-ichiro; Kano, Koichiro; Kusumi, Yoshiaki; Masuko, Takayuki; Mitsumata, Masako; Saito, Satoshi; Hirayama, Atsushi; Mugishima, Hideo; Fukuda, Noboru

    2009-11-01

    Adipose tissue-derived stem cells have been demonstrated to differentiate into cardiomyocytes and vascular endothelial cells. Here we investigate whether mature adipocyte-derived dedifferentiated fat (DFAT) cells can differentiate to cardiomyocytes in vitro and in vivo by establishing DFAT cell lines via ceiling culture of mature adipocytes. DFAT cells were obtained by dedifferentiation of mature adipocytes from GFP-transgenic rats. We evaluated the differentiating ability of DFAT cells into cardiomyocytes by detection of the cardiac phenotype markers in immunocytochemical and RT-PCR analyses in vitro. We also examined effects of the transplantation of DFAT cells into the infarcted heart of rats on cardiomyocytes regeneration and angiogenesis. DFAT cells expressed cardiac phenotype markers when cocultured with cardiomyocytes and also when grown in MethoCult medium in the absence of cardiomyocytes, indicating that DFAT cells have the potential to differentiate to cardiomyocyte lineage. In a rat acute myocardial infarction model, transplanted DFAT cells were efficiently accumulated in infarcted myocardium and expressed cardiac sarcomeric actin at 8 weeks after the cell transplantation. The transplantation of DFAT cells significantly (p<0.05) increased capillary density in the infarcted area when compared with hearts from saline-injected control rats. We demonstrated that DFAT cells have the ability to differentiate to cardiomyocyte-like cells in vitro and in vivo. In addition, transplantation of DFAT cells led to neovascuralization in rats with myocardial infarction. We propose that DFAT cells represent a promising candidate cell source for cardiomyocyte regeneration in severe ischemic heart disease.

  12. Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

    PubMed

    Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

    2014-01-01

    Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

  13. Cardiac Motion Analysis Using High-Speed Video Images in a Rat Model for Myocardial Infarction

    NASA Astrophysics Data System (ADS)

    Ishii, Idaku; Okuda, Toshikazu; Nie, Yuman; Takaki, Takeshi; Orito, Kensuke; Tanaka, Akane; Matsuda, Hiroshi

    In this study, we performed a cardiac motion analysis by using 1000-frames per second (fps) stereo images to capture the three-dimensional motion of small color markers in a rat heart. This method of recording cardiac motion could quantify the rate of change in the myocardial area, which indicated localized myocardial activity of rhythmic expansion and contraction. We analyzed the three-dimensional motion distributions in a rat model for myocardial infarction, in which the heart rate was 4 times/s or more. In the analysis, we spatiotemporally quantified the characteristic cardiac motion in ischemic heart diseases and found that infarction due to ischemia in the rat heart was spread around the left ventricle.

  14. Anti-inflammatory and anti-thrombotic effects of zingerone in a rat model of myocardial infarction.

    PubMed

    Hemalatha, K L; Stanely Mainzen Prince, P

    2016-11-15

    Myocardial infarction continues to be a major public health problem. Reduction in mortality rate and prevention of myocardial infarction are of utmost importance. Inflammation and thrombosis play an important role in the pathogenesis of myocardial infarction. The anti-inflammatory and anti-thrombotic effects of zingerone were evaluated in isoproterenol induced myocardial infarcted rats. Rats were pretreated with zingerone (6mg/kg body weight) daily for 14 days and were then induced myocardial infarction with isoproterenol (100mg/kg body weight) on 15th and 16th day. Isoproterenol induced myocardial infarcted rats showed significant (P<0.05) increase in the levels/ activities of cardiac troponin-I (cTnI), high sensitive C-reactive protein (Hs CRP), lysosomal hydrolases in the serum and concentration of heart lysosomal lipid peroxidation (LPO) products. RT-PCR study revealed over expression of myocardial tumour necrosis factor - alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) genes in the myocardial infarcted rats. Histopathology of heart and coronary artery revealed marked inflammation and coronary thrombosis. Zingerone pretreatment significantly (P<0.05) decreased serum cTnI, Hs CRP, lysosomal hydrolases and heart lysosomal LPO and down regulated myocardial TNF-α, IL-1β and IL-6 genes and prevented coronary thrombosis in isoproterenol induced myocardial infarcted rats. The observed effects of zingerone could be attributed to its anti-inflammatory and anti-thrombotic properties.

  15. Low-Level Vagus Nerve Stimulation Reverses Cardiac Dysfunction and Subcellular Calcium Handling in Rats With Post-Myocardial Infarction Heart Failure.

    PubMed

    Zhang, Yunhe; Chen, Ao; Song, Lei; Li, Min; Luo, Zhangyuan; Zhang, Wenzan; Chen, Yingmin; He, Ben

    2016-05-25

    Vagus nerve stimulation (VNS), targeting the imbalanced autonomic nervous system, is a promising therapeutic approach for chronic heart failure (HF). Moreover, calcium cycling is an important part of cardiac excitation-contraction coupling (ECC), which also participates in the antiarrhythmic effects of VNS. We hypothesized that low-level VNS (LL-VNS) could improve cardiac function by regulation of intracellular calcium handling properties. The experimental HF model was established by ligation of the left anterior descending coronary artery (LAD). Thirty-two male Sprague-Dawley rats were divided into 3 groups as follows; control group (sham operated without coronary ligation, n = 10), HF-VNS group (HF rats with VNS, n = 12), and HF-SS group (HF rats with sham nerve stimulation, n = 10). After 8 weeks of treatment, LL-VNS significantly improved left ventricular ejection fraction (LVEF) and attenuated myocardial interstitial fibrosis in the HF-VNS group compared with the HF-SS group. Elevated plasma norepinephrine and dopamine, but not epinephrine, were partially reduced by LL-VNS. Additionally, LL-VNS restored the protein and mRNA levels of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), Na(+)-Ca(2+) exchanger 1 (NCX1), and phospholamban (PLB) whereas the expression of ryanodine receptor 2 (RyR2) as well as mRNA level was unaffected. Thus, our study results suggest that the improvement of cardiac performance by LL-VNS is accompanied by the reversal of dysfunctional calcium handling properties including SERCA2a, NCX1, and PLB which may be a potential molecular mechanism of VNS for HF.

  16. Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats

    PubMed Central

    Annapurna, Akula; Challa, Siva Reddy; Prakash, Gomedhikam J; Viswanath, Routhu Kasi

    2008-01-01

    BACKGROUND Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. OBJECTIVES To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. METHODS Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. RESULTS Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. CONCLUSIONS The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac. PMID:19343118

  17. Therapeutic potential of sulindac against ischemia-reperfusion-induced myocardial infarction in diabetic and nondiabetic rats.

    PubMed

    Annapurna, Akula; Challa, Siva Reddy; Prakash, Gomedhikam J; Viswanath, Routhu Kasi

    2008-01-01

    Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state. To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats. Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically. Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats. The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.

  18. High rate of right ventricular infarction after ligation of mid left anterior descending artery in rats.

    PubMed

    Samsamshariat, Seyed Ahmad; Movahed, Mohammad-Reza

    2005-01-01

    The left anterior descending artery (LAD) supplies the left ventricle in humans. LAD ligation has been commonly used in rats to induce left ventricular (LV) infarction for research purposes. However, the myocardial supply territories of LAD are not well established in rats. We measured the infarction zone in rats after ligation of the mid-LAD. Twenty-four male Sprague-Dawley rats weighing 300-350 g were selected for LAD ligation for the induction of ischemic cardiomyopathy. The surgery was performed under full anesthesia. Left-sided thoracotomy was performed through cuts in the fifth and sixth ribs. Ligation of the LAD was performed 1 to 2 mm distal to a line between the left border of the pulmonary conus and the right border of the left atrial appendage. LAD was ligated after the first diagonal and septal branches. After 24 h, the hearts were removed and stained with Tetrazolium Tetrachloride (TTC) for the detection of infracted areas. Ligation of LAD induces 85% infarction of the right anterior free wall and anterior right ventricular septum and induces 100% infarction of the anterior free wall of the left ventricle and anterior septum. Infarction after LAD ligation extends all the way to the distal of the ligation site down to the apex of the heart. Mid-LAD ligation after the first septal and diagonal branches causes substantial right ventricular infarction in addition to LV infarct in rats. Therefore, the hemodynamic effect of right ventricle infarct should be considered in research involving LAD ligation in rats.

  19. Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats.

    PubMed

    Vallée, Jean-Paul; Hauwel, Mathieu; Lepetit-Coiffé, Matthieu; Bei, Wang; Montet-Abou, Karin; Meda, Paolo; Gardier, Stephany; Zammaretti, Prisca; Kraehenbuehl, Thomas P; Herrmann, Francois; Hubbell, Jeffrey A; Jaconi, Marisa E

    2012-03-01

    Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.

  20. Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart

    PubMed Central

    Hansen, Katrina J.; Favreau, John T.; Guyette, Jacques P.; Tao, Ze-Wei; Coffin, Spencer T.; Cunha-Gavidia, Anny; D'Amore, Brian; Perreault, Luke R.; Fitzpatrick, John P.; DeMartino, Angelica; Gaudette, Glenn R.

    2016-01-01

    Abstract Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW) and systolic area of contraction (SAC) and global parameters derived from the pressure waveform. MI (n = 6) significantly decreased RSW (0.026 ± 0.011) and SAC (0.022 ± 0.015) when compared with sham operation (RSW: 0.141 ± 0.009; SAC: 0.166 ± 0.005, n = 6) (p < 0.05). The delivery of unseeded biological sutures to the infarcted hearts did not change regional mechanical function compared with the infarcted hearts (RSW: 0.032 ± 0.004, SAC: 0.037 ± 0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend toward increase of regional mechanical function compared with the infarcted heart (RSW: 0.057 ± 0.011; SAC: 0.051 ± 0.014, n = 6). Global function showed no significant differences between any group (p > 0.05); however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0% ± 2.2%), where unseeded (3.8% ± 0.6%) and hMSC-seeded (3.7% ± 0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining suture area

  1. Adipose-Derived Cell Construct Stabilizes Heart Function and Increases Microvascular Perfusion in an Established Infarct

    PubMed Central

    Nguyen, Quang T.; Touroo, Jeremy S.; Aird, Allison L.; Chang, Raymond C.; Ng, Chin K.; Hoying, James B.; Williams, Stuart K.

    2013-01-01

    We have previously shown that myocardial infarction (MI) immediately treated with an epicardial construct containing stromal vascular fraction (SVF) from adipose tissue preserved microvascular function and left ventricle contractile mechanisms. In order to evaluate a more clinically relevant condition, we investigated the cardiac recovery potential of an SVF construct implanted onto an established infarct. SVF cells were isolated from rat adipose tissue, plated on Vicryl, and cultured for 14 days. Fischer-344 rats were separated into MI groups: (a) 6-week MI (MI), (b) 6-week MI treated with an SVF construct at 2 weeks (MI SVF), (c) 6-week MI with Vicryl construct at 2 weeks (MI Vicryl), and (d) MI 2wk (time point of intervention). Emax, an indicator of systolic performance and contractile function, was lower in the MI and MI Vicryl versus MI SVF. Positron emission tomography imaging (18F-fluorodeoxyglucose) revealed a decreased percentage of relative infarct volume in the MI SVF versus MI and MI Vicryl. Total vessel count and percentage of perfusion assessed via immunohistochemistry were both increased in the infarct region of MI SVF versus MI and MI Vicryl. Overall cardiac function, percentage of relative infarct, and percentage of perfusion were similar between MI SVF and MI 2wk; however, total vessel count increased after SVF treatment. These data suggest that SVF treatment of an established infarct stabilizes the heart at the time point of intervention by preventing a worsening of cardiac performance and infarcted volume, and is associated with increased microvessel perfusion in the area of established infarct. PMID:24106337

  2. The therapeutic potential of hepatocyte growth factor for myocardial infarction and heart failure.

    PubMed

    Jin, Hongkui; Wyss, J Michael; Yang, Renhui; Schwall, Ralph

    2004-01-01

    Hepatocyte growth factor (HGF) is a cytokine whose multipotent actions are mediated by c-Met receptor. This review focuses on effects of HGF on myocardial infarction (MI) and heart failure. Circulating concentrations of HGF and myocardial concentrations of HGF and c-Met mRNA and protein are substantially increased following acute MI. HGF has been shown to be cardioprotective towards acute cardiac ischemia-reperfusion injury. Gene transfection of HGF into rat hearts attenuates acute ischemia injury. Administration of HGF protein reduces infarct size and increases cardiac performance in a rat model of acute ischemia/reperfusion. In contrast, acute blockade of endogenous HGF increases infarct size and mortality. These acute effects of HGF appear to be related to angiogenic and anti-apoptotic mechanisms. Recent studies demonstrate that post-MI treatment with HGF gene or protein attenuates chronic cardiac remodeling and dysfunction. In rats, HGF gene transfer following large MI results in preserved cardiac function and geometry in association with angiogenesis and reduced apoptosis, and treatment with recombinant HGF also significantly improves cardiac performance measured 8 weeks after MI. In mice, post-MI HGF gene therapy improves cardiac remodeling and dysfunction through hypertrophy of cardiomyocytes, infarct wall thickening, preservation of vessels, and antifibrosis. In addition, gene transfer of HGF improves cardiac remodeling, angiogenesis and regional myocardial function in the chronic ischemic myocardium of dogs. Together, these preclinical data highlight the significant acute and chronic cardioprotective effects of HGF following ischemic heart failure. Clinical trials are needed to investigate the therapeutic potential of HGF for postinfarction heart failure in humans.

  3. Spinal cord infarction mimicking ischemic heart disease.

    PubMed

    Lee, Dae Won; Choi, Yoon Hee

    2017-06-01

    Spinal cord infarction is a rare condition and is easily misdiagnosed owing to its initial non-specific manifestation. We report a case of a 77-year-old man who presented with chest pain and upper back pain initially, and was misdiagnosed with a myocardial infarction. Four hours after admission, he complained of numbness in his entire left leg below the knee, with rapid deterioration of neurological symptoms. After 9 hours, loss of sensation progressed up to the T4 dermatome, strength of both lower extremities deteriorated to grade 0, and decrease in anal tone and deep tendon reflex was observed. Initial magnetic resonance imaging findings were normal; however, a signal change occurred 3 days after symptom onset. When patients present with acute chest pain and neurologic symptoms, the possibility of ischemic cardiac disease as well as any neurological manifestations must be investigated. Emergency physicians must remember the value of serial physical examinations.

  4. Cardioprotective activity of chalcones in ischemia/reperfusion-induced myocardial infarction in albino rats

    PubMed Central

    Annapurna, Akula; Mudagal, Manjunatha P; Ansari, Asif; Rao A, Srinivasa

    2012-01-01

    BACKGROUND: There is a comprehensive body of experimental and clinical evidence suggesting that exogenous supplementation of natural antioxidants or augmentation of endogenous antioxidants attenuates the damage caused by myocardial infarction. OBJECTIVE: To evaluate the cardioprotective effects of Cl-chalcone and F-chalcone against ischemia/reperfusion (I/R)-induced myocardial infarction in rats. METHODS: Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. Malondialdehyde was measured in serum and heart tissue, and superoxide dismutase and catalase in heart tissue were measured spectrophotometrically. RESULTS: I/R resulted in significant cardiac necrosis, indicated by a rise in the end products of myocardial lipid peroxidation (malondialdehydes). A loss of antioxidative enzymes (superoxide dismutase and catalase) in heart tissue was also observed in animals subjected to in vivo myocardial I/R injury. DISCUSSION: The present study demonstrated that treatment with Cl-chalcone and F-chalcone significantly limited infarct size, partially but significantly attenuated the level of lipid peroxidation and moderated the loss of antioxidant reserves in rats subjected to 30 min coronary artery occlusion followed by a 4 h reperfusion in comparison with I/R groups. CONCLUSIONS: The results of the present study suggest that chalcones have cardioprotective activity against I/R-induced myocardial infarction in rats. PMID:23620697

  5. Cardioprotective activity of chalcones in ischemia/reperfusion-induced myocardial infarction in albino rats.

    PubMed

    Annapurna, Akula; Mudagal, Manjunatha P; Ansari, Asif; Rao A, Srinivasa

    2012-09-01

    There is a comprehensive body of experimental and clinical evidence suggesting that exogenous supplementation of natural antioxidants or augmentation of endogenous antioxidants attenuates the damage caused by myocardial infarction. To evaluate the cardioprotective effects of Cl-chalcone and F-chalcone against ischemia/reperfusion (I/R)-induced myocardial infarction in rats. Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. Malondialdehyde was measured in serum and heart tissue, and superoxide dismutase and catalase in heart tissue were measured spectrophotometrically. I/R resulted in significant cardiac necrosis, indicated by a rise in the end products of myocardial lipid peroxidation (malondialdehydes). A loss of antioxidative enzymes (superoxide dismutase and catalase) in heart tissue was also observed in animals subjected to in vivo myocardial I/R injury. The present study demonstrated that treatment with Cl-chalcone and F-chalcone significantly limited infarct size, partially but significantly attenuated the level of lipid peroxidation and moderated the loss of antioxidant reserves in rats subjected to 30 min coronary artery occlusion followed by a 4 h reperfusion in comparison with I/R groups. The results of the present study suggest that chalcones have cardioprotective activity against I/R-induced myocardial infarction in rats.

  6. Exercise training prior to myocardial infarction attenuates cardiac deterioration and cardiomyocyte dysfunction in rats

    PubMed Central

    Bozi, Luiz Henrique Marchesi; dos Santos Costa Maldonado, Izabel Regina; Baldo, Marcelo Perim; da Silva, Márcia Ferreira; Moreira, José Bianco Nascimento; Novaes, Rômulo Dias; Ramos, Regiane Maria Soares; Mill, José Geraldo; Brum, Patricia Chakur; Felix, Leonardo Bonato; Gomes, Thales Nicolau Prímola; Natali, Antônio José

    2013-01-01

    OBJECTIVES: The present study was performed to investigate 1) whether aerobic exercise training prior to myocardial infarction would prevent cardiac dysfunction and structural deterioration and 2) whether the potential cardiac benefits of aerobic exercise training would be associated with preserved morphological and contractile properties of cardiomyocytes in post-infarct remodeled myocardium. METHODS: Male Wistar rats underwent an aerobic exercise training protocol for eight weeks. The rats were then assigned to sham surgery (SHAM), sedentary lifestyle and myocardial infarction or exercise training and myocardial infarction groups and were evaluated 15 days after the surgery. Left ventricular tissue was analyzed histologically, and the contractile function of isolated myocytes was measured. Student's t-test was used to analyze infarct size and ventricular wall thickness, and the other parameters were analyzed by the Kruskal-Wallis test followed by Dunn's test or a one-way analysis of variance followed by Tukey's test (p<0.05). RESULTS: Myocardial infarctions in exercise-trained animals resulted in a smaller myocardial infarction extension, a thicker infarcted wall and less collagen accumulation as compared to myocardial infarctions in sedentary animals. Myocardial infarction-induced left ventricular dilation and cardiac dysfunction, as evaluated by +dP/dt and -dP/dt, were both prevented by previous aerobic exercise training. Moreover, aerobic exercise training preserved cardiac myocyte shortening, improved the maximum shortening and relengthening velocities in infarcted hearts and enhanced responsiveness to calcium. CONCLUSION: Previous aerobic exercise training attenuated the cardiac dysfunction and structural deterioration promoted by myocardial infarction, and such benefits were associated with preserved cardiomyocyte morphological and contractile properties. PMID:23778353

  7. Exercise training prior to myocardial infarction attenuates cardiac deterioration and cardiomyocyte dysfunction in rats.

    PubMed

    Bozi, Luiz Henrique Marchesi; Maldonado, Izabel Regina dos Santos Costa; Baldo, Marcelo Perim; Silva, Márcia Ferreira da; Moreira, José Bianco Nascimento; Novaes, Rômulo Dias; Ramos, Regiane Maria Soares; Mill, José Geraldo; Brum, Patricia Chakur; Felix, Leonardo Bonato; Gomes, Thales Nicolau Prímola; Natali, Antônio José

    2013-04-01

    The present study was performed to investigate 1) whether aerobic exercise training prior to myocardial infarction would prevent cardiac dysfunction and structural deterioration and 2) whether the potential cardiac benefits of aerobic exercise training would be associated with preserved morphological and contractile properties of cardiomyocytes in post-infarct remodeled myocardium. Male Wistar rats underwent an aerobic exercise training protocol for eight weeks. The rats were then assigned to sham surgery (SHAM), sedentary lifestyle and myocardial infarction or exercise training and myocardial infarction groups and were evaluated 15 days after the surgery. Left ventricular tissue was analyzed histologically, and the contractile function of isolated myocytes was measured. Student's t-test was used to analyze infarct size and ventricular wall thickness, and the other parameters were analyzed by the Kruskal-Wallis test followed by Dunn's test or a one-way analysis of variance followed by Tukey's test (p<0.05). Myocardial infarctions in exercise-trained animals resulted in a smaller myocardial infarction extension, a thicker infarcted wall and less collagen accumulation as compared to myocardial infarctions in sedentary animals. Myocardial infarction-induced left ventricular dilation and cardiac dysfunction, as evaluated by +dP/dt and -dP/dt, were both prevented by previous aerobic exercise training. Moreover, aerobic exercise training preserved cardiac myocyte shortening, improved the maximum shortening and relengthening velocities in infarcted hearts and enhanced responsiveness to calcium. Previous aerobic exercise training attenuated the cardiac dysfunction and structural deterioration promoted by myocardial infarction, and such benefits were associated with preserved cardiomyocyte morphological and contractile properties.

  8. Chitosan hydrogel improves mesenchymal stem cell transplant survival and cardiac function following myocardial infarction in rats

    PubMed Central

    Xu, Bin; Li, Yang; Deng, Bo; Liu, Xiaojing; Wang, Lin; Zhu, Qing-Lei

    2017-01-01

    Myocardial infarction (MI) remains the leading cause of cardiovascular-associated mortality and morbidity. Improving the retention rate, survival and cardiomyocyte differentiation of mesenchymal stem cells (MSCs) is important in improving the treatment of patients with MI. In the present study, temperature-responsive chitosan hydrogel, an injectable scaffold, was used to deliver MSCs directly into the infarcted myocardium of rats following MI. Histopathology and immunohistochemical staining were used to evaluate cardiac cell survival and regeneration, and cardiac function was assessed using an echocardiograph. It was demonstrated that chitosan hydrogel increased graft size and cell retention in the ischemic heart, promoted MSCs to differentiate into cardiomyocytes and increased the effects of MSCs on neovasculature formation. Furthermore, chitosan hydrogel enhanced the effect of MSCs on the improvement of cardiac function and hemodynamics in the infarcted area of rats following MI. These findings suggest that chitosan hydrogel is an appropriate material to deliver MSCs into infarcted myocardium. PMID:28352335

  9. Parkin Regulates Mitochondrial Autophagy After Myocardial Infarction in Rats.

    PubMed

    Wu, Li; Maimaitirexiati, Xiemuziya; Jiang, Yun; Liu, Liang

    2016-05-08

    BACKGROUND To study the role of Parkin in the regulation of mitochondrial autophagy in the heart by assessing mitochondrial autophagy and changes in Parkin protein expression in rat myocardium after myocardial infarction (MI). MATERIAL AND METHODS Rats were randomly assigned to three groups: control, sham, and MI. Four weeks after induction of MI, ultrasonic examination of the rats was performed to measure left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and left ventricular diastolic/systolic volume. Rat myocardium was collected from each group and examined for changes in morphology, size, and amount of mitochondria and autophagosomes by transmission electronic microscopy. A Western blot was performed to analyze the levels of Parkin and the autophagy-related protein LC3. RESULTS Four weeks after MI, cardiac function of the MI rats was impaired compared with the control rats. Both LVESD and LVEDD were elevated in the MI rats (p<0.05) while EF was decreased, indicating that the MI model was constructed successfully. After MI, increased numbers of mitochondria and autophagosomes were observed in the myocardium (p<0.05), and the mitochondrial morphology was destroyed. Chloroquine (CQ) treatment increased the number of autophagosomes in the myocardium of the control rats (p<0.05) but not in MI rats (p>0.05). In addition, the levels of the autophagy-related proteins LC3II/LC3I were elevated in the myocardium after MI (p<0.05) and the activity of Parkin was significantly reduced (p<0.05). CONCLUSIONS Under conditions of chronic MI, mitochondrial dysfunction and disruption of autophagosomal clearance are associated with Parkin expression.

  10. Discharge heart rate and mortality after acute myocardial infarction.

    PubMed

    Seronde, Marie France; Geha, Raghed; Puymirat, Etienne; Chaib, Aurès; Simon, Tabassome; Berard, Laurence; Drouet, Elodie; Bataille, Vincent; Danchin, Nicolas; Schiele, François

    2014-10-01

    We aimed to describe the determinants of discharge heart rate in acute coronary syndrome patients and assess the impact of discharge heart rate on 5-year mortality in hospital survivors. French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) 2005 is a nationwide French registry that included all consecutive patients with acute myocardial infarction over 1 month in 223 institutions in 2005. Discharge heart rate was recorded in 3079 patients discharged alive; all had 5-year follow-up. Logistic regression was used to detect predictors of high heart rate at discharge. Cox's proportional hazards model was used to assess the hazard ratio for mortality at 5 years. Heart rate was categorized into 4 groups by quartiles (<60, 61-67, 68-75, >75 beats per minute). High heart rate was defined as ≥75 beats per minute. Landmark analysis was performed at 1 year. Independent predictors of heart rate ≥75 beats per minute at discharge were female sex, ST-segment elevation myocardial infarction, diabetes, chronic obstructive pulmonary disease, bleeding/transfusion during hospitalization, left ventricular dysfunction, renal dysfunction, and prescription (type, but not dose category) of beta-blockers at discharge. Discharge heart rate was significantly related to mortality at 1 year (hazard ratio 1.13; 95% confidence interval, 1.03-1.24 per 10 beats per minute, P = .02); this was confirmed by landmark analysis, with a 39% increase (hazard ratio 1.39; 95% confidence interval 1.05-1.84) in the risk of 1-year death for discharge heart rate ≥75 beats per minute vs <75 beats per minute. This relationship was no longer significant between 2 and 5 years. After acute myocardial infarction, patients discharged with high heart rate (≥75 beats per minute) are at higher risk of death during the first year, but not later, irrespective of beta-blocker use. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats.

    PubMed

    Kiss, Krisztina; Csonka, Csaba; Pálóczi, János; Pipis, Judit; Görbe, Anikó; Kocsis, Gabriella F; Murlasits, Zsolt; Sárközy, Márta; Szűcs, Gergő; Holmes, Christopher P; Pan, Yijun; Bhandari, Ashok; Csont, Tamás; Shamloo, Mehrdad; Woodburn, Kathryn W; Ferdinandy, Péter; Bencsik, Péter

    2016-11-01

    Erythropoietin (EPO) has been shown to protect the heart against acute myocardial infarction in pre-clinical studies, however, EPO failed to reduce infarct size in clinical trials and showed significant safety problems. Here, we investigated cardioprotective effects of two selective non-erythropoietic EPO receptor ligand dimeric peptides (AF41676 and AF43136) lacking erythropoietic activity, EPO, and the prolonged half-life EPO analogue, darbepoetin in acute myocardial infarction (AMI) in rats. In a pilot study, EPO at 100U/mL significantly decreased cell death compared to vehicle (33.8±2.3% vs. 40.3±1.5%, p<0.05) in rat neonatal cardiomyocytes subjected to simulated ischemia/reperfusion. In further studies (studies 1-4), in vivo AMI was induced by 30min coronary occlusion and 120min reperfusion in male Wistar rats. Test compounds and positive controls for model validation (B-type natriuretic peptide, BNP or cyclosporine A, CsA) were administered iv. before the onset of reperfusion. Infarct size (IS) was measured by standard TTC staining. In study 1, 5000U/kg EPO reduced infarct size significantly compared to vehicle (45.3±4.8% vs. 59.8±4.5%, p<0.05). In study 2, darbepoetin showed a U-shaped dose-response curve with maximal infarct size-reducing effect at 5μg/kg compared to the vehicle (44.4±5.7% vs. 65.9±2.7%, p<0.01). In study 3, AF41676 showed a U-shaped dose-response curve, where 3mg/kg was the most effective dose compared to the vehicle (24.1±3.9% vs. 44.3±2.5%, p<0.001). The positive control BNP significantly decreased infarct size in studies 1-3 by approximately 35%. In study 4, AF43136 at 10mg/kg decreased infarct size, similarly to the positive control CsA compared to the appropriate vehicle (39.4±5.9% vs. 58.1±5.4% and 45.9±2.4% vs. 63.8±4.1%, p<0.05, respectively). This is the first demonstration that selective, non-erythropoietic EPO receptor ligand dimeric peptides AF41676 and AF43136 administered before reperfusion are able to reduce

  12. EXPERIMENTAL ATHEROSCLEROSIS AND CARDIAC INFARCTS IN RATS

    PubMed Central

    Wilgram, George F.

    1959-01-01

    Marked obesity was induced in rats by feeding a high fat, egg yolk-rich diet. The obese rats were hyperlipemic and showed an increased incidence of lipomatous coronary lesions, but did not develop severe atheromatous lesions. Spontaneous vascular lesions of several kinds have been observed in aging rats. Among them, plaques containing a fibrin-like material seem to be conspicuous. However, these lesions differ from the experimentally induced changes, which were more fatty. Atherosclerosis, as it is defined in human pathology, has not been observed to develop spontaneously in rats. Experimental induction of marked hyperlipemia and hypercholesterolemia by feeding a high fat egg yolk-rich diet (supplemented with cholesterol, choleate, and thiouracil), and use of viosterol to cause vascular injury, led to severe atherosclerosis, coronary occlusion, and myocardial infarction. A consideration of all the findings reported here leads to renewed support of the concept that atherosclerosis has a combination of causes (Aschoff, Anitschkow, Page). Of all the etiological factors considered here, elevation of blood lipides and vascular injury are thought to be the most important ones. PMID:13620855

  13. Thrombospondins in the transition from myocardial infarction to heart failure.

    PubMed

    Kirk, Jonathan A; Cingolani, Oscar H

    2016-01-01

    The heart's reaction to ischemic injury from a myocardial infarction involves complex cross-talk between the extra-cellular matrix (ECM) and different cell types within the myocardium. The ECM functions not only as a scaffold where myocytes beat synchronously, but an active signaling environment that regulates the important post-MI responses. The thrombospondins are matricellular proteins that modulate cell--ECM interactions, functioning as "sensors" that mediate outside-in and inside-out signaling. Thrombospondins are highly expressed during embryonic stages, and although their levels decrease during adult life, can be re-expressed in high quantities in response to cardiac stress including myocardial infarction and heart failure. Like a Swiss-army knife, the thrombospondins possess many tools: numerous binding domains that allow them to interact with other elements of the ECM, cell surface receptors, and signaling molecules. It is through these that the thrombospondins function. In the present review, we provide basic as well as clinical evidence linking the thrombospondin proteins with the post myocardial infarction response, including inflammation, fibrotic matrix remodeling, angiogenesis, as well as myocyte hypertrophy, apoptosis, and contractile dysfunction in heart failure. We will describe what is known regarding the intracellular signaling pathways that are involved with these responses, paving the road for future studies identifying these proteins as therapeutic targets for cardiac disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Stem cells cardiac patch from decellularized umbilical artery improved heart function after myocardium infarction.

    PubMed

    Li, Na; Huang, RanRan; Zhang, XiaoXia; Xin, Yi; Li, Jia; Huang, YiMin; Cui, Wei; Stoltz, Jean-Francois; Zhou, YuJie; Kong, QingYu

    2017-01-01

    The construction of the high biocompatible biomaterials pretreated with MSC offers a promising strategy to improve the effects of stem cell therapy for the myocardial infarction (MI). However, assembling vascularized three-dimensional (3-D) myocardial tissues remains an enormous challenge. In this study, we optimized the decellularization protocol with the umbilical artery to construct microporous 3-D scaffold which is suitable for the stem cells (SC) proliferation. The SD rats underwent proximal left coronary ligation and a 5-mm diameter microporous SC patch was implanted directly on the infarct area (SC patch group). The LV contractile function, regional myocardial wall compliance, and tissue histology were assessed 4 weeks after patch implantation. The MSC patch integrated to the local heart tissue and the neo-vessels have been observed in the MSC patch. The vessels in the MSC patch were positive for the CD31 (marker for the mature endothelial cells). The left ventricle wall was thicker in the MSC patch group than the control group (p<0.05 vs. empty patch group). And the LVEF has been improved in the MSC patch group than empty patch group (59±6.7% vs. 31±4.5%, p<0.05). Our results showed that the implantation of the MSC patch improved cardiac contractile function in heart infarction rat model. The construction of artificial tissue from the decellularized umbilical artery and the MSC may open a promising perspective for the tissue therapy for MI.

  15. Borage oil attenuates progression of cardiac remodeling in rats after myocardial infarction.

    PubMed

    Maldonado-Menetti, Julianne dos Santos; Vitor, Taise; Edelmuth, Rodrigo Camargo Leão; Ferrante, Fernanda Amá; Souza, Pamella Ramona de Moraes; Koike, Marcia Kiyomi

    2016-03-01

    To investigate the effects of Borage oil on cardiac remodeling after myocardial infarction (MI). Male Wistar rats underwent ligation of the left coronary artery and divided into three groups: MI (control), BO-18 (18 mg/kg of borage oil) and BO-180 (180 mg/kg of borage oil). After seven days, heart was arrested in diastole and processed for histological evaluation of: MI size, LV dilation, myocyte hypertrophy, inflammatory infiltration and fibrosis in MI region and in remote region. The relative weight of the lung was used as a marker of heart failure. The MI size was comparable among groups. Compared to control, BO treated groups showed lower weight of heart and lungs, reduced LV dilation and myocyte hypertrophy. Hemodynamic measurements were comparable. The treatment attenuated the inflammatory infiltration and fibrosis in remote myocardium. Borage oil attenuates progression of cardiac remodeling after myocardial infarction and congestive heart failure.

  16. Cardioprotective Effect of the Compound Yangshen Granule in Rat Models with Acute Myocardial Infarction

    PubMed Central

    Ming, Xie; Tongshen, Wang; Delin, Wu; Ronghua, Zhao

    2012-01-01

    The protective effect of Compound Yangshen Granules was observed in myocardial infarction rat model. Rats were randomly divided into 6 groups: the model group, the control group (sham operated), the positive drug group, and small, medium, and large dosage of the Yangshen granule groups, respectively. The rats in the 3 Yangshen granule groups were orally administrated with 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg for 7 consecutive days, whereas the rats of the positive drug group treated with 0.14 g/kg of Danshen Dropping Pills, and rats in the control and model groups orally administrated with saline. The rat model of acute myocardial infarction was established with ligation of coronary artery. Electrocardiograms at different time points, the blood rheology, myocardial enzymes, infarct size, and myocardial morphologic changes were measured. The results demonstrated that the granules could improve blood rheology, decrease st-segment of electrocardiograms and the activities of LDH and CK in serum, reduce myocardial infarction size, and alleviate myocardial histopathologic changes. In addition, the effect of the granules depended on the dose administrated orally. The results suggest that the Yangshen granules could produce cardioprotection effect and have potential benefits in the prevention of ischemic heart disease. PMID:22474518

  17. Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression.

    PubMed

    Sirry, Mazin S; Butler, J Ryan; Patnaik, Sourav S; Brazile, Bryn; Bertucci, Robbin; Claude, Andrew; McLaughlin, Ron; Davies, Neil H; Liao, Jun; Franz, Thomas

    2016-10-01

    Understanding the passive mechanical properties of infarcted tissue at different healing stages is essential to explore the emerging biomaterial injection-based therapy for myocardial infarction (MI). Although rats have been widely used as animal models in such investigations, the data in literature that quantify the passive mechanical properties of rat heart infarcts is very limited. MI was induced in rats and hearts were harvested immediately (0 day), 7, 14 and 28 days after infarction onset. Left ventricle anterioapical samples were cut and underwent equibiaxial and non equibiaxial tension followed by uniaxial compression mechanical tests. Histological analysis was conducted to confirm MI and to quantify the size of the induced infarcts. Infarcts maintained anisotropy and the nonlinear biaxial and compressive mechanical behaviour throughout the healing phases with the circumferential direction being stiffer than the longitudinal direction. Mechanical coupling was observed between the two axes in all infarct groups. The 0, 7, 14 and 28 days infarcts showed 438, 693, 1048 and 1218kPa circumferential tensile moduli. The 28 day infarct group showed a significantly higher compressive modulus compared to the other infarct groups (p=0.0060, 0.0293, and 0.0268 for 0, 7 and 14 days groups). Collagen fibres were found to align in a preferred direction for all infarct groups supporting the observed mechanical anisotropy. The presented data are useful for developing material models for healing infarcts and for setting a baseline for future assessment of emerging mechanical-based MI therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure

    PubMed Central

    de Morais, Sharon Del Bem Velloso; da Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Silva, Carlos Alberto Aguiar; de Oliveira, Luciano Fonseca Lemos; de Carvalho, Eduardo Elias Vieira; Simões, Marcus Vinicius; da Silva Meirelles, Lindolfo; Fazan, Rubens

    2015-01-01

    Heart failure induced by myocardial infarct (MI) attenuates the heart rate variability (HRV) and baroreflex sensitivity, which are important risk factors for life-threatening cardiovascular events. Therapies with mesenchymal stem cells (MSCs) have shown promising results after MI. However, the effects of MSCs on hemodynamic (heart rate and arterial pressure) variability and baroreflex sensitivity in chronic heart failure (CHF) following MI have not been evaluated thus far. Male Wistar rats received MSCs or saline solution intravenously 1 week after ligation of the left coronary artery. Control (noninfarcted) rats were also evaluated. MI size was assessed using single-photon emission computed tomography (SPECT). The left ventricular ejection fraction (LVEF) was evaluated using radionuclide ventriculography. Four weeks after MSC injection, the animals were anesthetized and instrumented for chronic ECG recording and catheters were implanted in the femoral artery to record arterial pressure. Arterial pressure and HRVs were determined in time and frequency domain (spectral analysis) while HRV was also examined using nonlinear methods: DFA (detrended fluctuation analysis) and sample entropy. The initial MI size was the same among all infarcted rats but was reduced by MSCs. CHF rats exhibited increased myocardial interstitial collagen and sample entropy combined with the attenuation of the following cardiocirculatory parameters: DFA indices, LVEF, baroreflex sensitivity, and HRV. Nevertheless, MSCs hampered all these alterations, except the LVEF reduction. Therefore, 4 weeks after MSC therapy was applied to CHF rats, MI size and myocardial interstitial fibrosis decreased, while baroreflex sensitivity and HRV improved. PMID:26059001

  19. Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts

    PubMed Central

    Liu, Yu; Chen, Li; Diaz, Andrea Diaz; Benham, Ashley; Xu, Xueping; Wijaya, Cori S.; Fa’ak, Faisal; Luo, Weijia; Soibam, Benjamin; Azares, Alon; Yu, Wei; Lyu, Qiongying; Stewart, M. David; Gunaratne, Preethi; Cooney, Austin; McConnell, Bradley K.; Schwartz, Robert J.

    2016-01-01

    Mesp1 directs multipotential cardiovascular cell fates, even though it’s transiently induced prior to the appearance of the cardiac progenitor program. Tracing Mesp1-expressing cells and their progeny allows isolation and characterization of the earliest cardiovascular progenitor cells. Studying the biology of Mesp1-CPCs in cell culture and ischemic disease models is an important initial step toward using them for heart disease treatment. Because of Mesp1’s transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1Cre/+; Rosa26EYFP/+ ES cells. We captured EYFP+ cells that strongly expressed cardiac mesoderm markers and cardiac transcription factors, but not pluripotent or nascent mesoderm markers. BMP2/4 treatment led to the expansion of EYFP+ cells, while Wnt3a and Activin were marginally effective. BMP2/4 exposure readily led EYFP+ cells to endothelial and smooth muscle cells, but inhibition of the canonical Wnt signaling was required to enter the cardiomyocyte fate. Injected mouse pre-contractile Mesp1-EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells. PMID:27538477

  20. PET/MRI assessment of the infarcted mouse heart

    NASA Astrophysics Data System (ADS)

    Buonincontri, Guido; Methner, Carmen; Krieg, Thomas; Hawkes, Robert C.; Adrian Carpenter, T.; Sawiak, Stephen J.

    2014-01-01

    Heart failure originating from myocardial infarction (MI) is a leading cause of death worldwide. Mouse models of ischaemia and reperfusion injury (I/R) are used to study the effects of novel treatment strategies targeting MI, however staging disease and treatment efficacy is a challenge. Damage and recovery can be assessed on the cellular, tissue or whole-organ scale but these are rarely measured in concert. Here, for the first time, we present data showing measures of injury in infarcted mice using complementary techniques for multi-modal characterisation of the heart. We use in vivo magnetic resonance imaging (MRI) to assess heart function with cine-MRI, hindered perfusion with late gadolinium enhancement imaging and muscular function with displacement encoded with stimulated echoes (DENSE) MRI. These measures are followed by positron emission tomography (PET) with 18-F-fluorodeoxyglucose to assess cellular metabolism. We demonstrate a protocol combining each of these measures for the same animal in the same imaging session and compare how the different markers can be used to quantify cardiac recovery on different scales following injury.

  1. Analyzing the Release of Copeptin from the Heart in Acute Myocardial Infarction Using a Transcoronary Gradient Model

    PubMed Central

    Boeckel, Jes-Niels; Oppermann, Jana; Anadol, Remzi; Fichtlscherer, Stephan; Zeiher, Andreas M.; Keller, Till

    2016-01-01

    Copeptin is the C-terminal end of pre-provasopressin released equimolar to vasopressin into circulation and recently discussed as promising cardiovascular biomarker amendatory to established markers such as troponins. Vasopressin is a cytokine synthesized in the hypothalamus. A direct release of copeptin from the heart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of a potential release of copeptin from the human heart in acute myocardial infarction (AMI) has been done. PMID:26864512

  2. Analyzing the Release of Copeptin from the Heart in Acute Myocardial Infarction Using a Transcoronary Gradient Model.

    PubMed

    Boeckel, Jes-Niels; Oppermann, Jana; Anadol, Remzi; Fichtlscherer, Stephan; Zeiher, Andreas M; Keller, Till

    2016-02-11

    Copeptin is the C-terminal end of pre-provasopressin released equimolar to vasopressin into circulation and recently discussed as promising cardiovascular biomarker amendatory to established markers such as troponins. Vasopressin is a cytokine synthesized in the hypothalamus. A direct release of copeptin from the heart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of a potential release of copeptin from the human heart in acute myocardial infarction (AMI) has been done.

  3. CARDIOPROTECTIVE ROLES OF THE CHINESE MEDICINAL FORMULA BAO-XIN-TANG ON ACUTE MYOCARDIAL INFARCTION IN RATS.

    PubMed

    Wang, Yang; Wang, Weihao; Peng, Weijun; Liu, Weiping; Cai, Weijun; Xia, Zian; Zhang, Honggeng; Xing, And Zhihua

    2017-01-01

    Bao-Xin-Tang (BXT) is a traditional Chinese medicinal formula used for the treatment of coronary heart disease and known to have favorable therapeutic benefits. The current study was designed to determine whether BXT has a cardioprotective role for acute myocardial infarction. The underlying mechanisms were also explored. The Sprague-Dawley rat model of acute myocardial infarction was established by occluding the left anterior descending branch of the coronary artery. After a 3-h ischemic period, we determined the myocardial infarction size, inflammatory components, and antioxidant activities. The data showed that BXT could reduce the infarction size and lower the levels of C-reactive protein, interleukin-6, and myeloperoxidase, and increase the activities of superoxide dismutase and the anti-inflammatory cytokine, interleukin-10. These results indicate that administration of BXT, following acute myocardial infarction, could reduce infarct size. The effects of BXT may be related to its anti-inflammatory and anti-oxidative properties.

  4. Bioengineering the infarcted heart by applying bio-inspired materials.

    PubMed

    Ruvinov, Emil; Harel-Adar, Tamar; Cohen, Smadar

    2011-10-01

    Induction of cardiac muscle regeneration following myocardial infarction (MI) represents a major challenge in cardiovascular therapy, as the current clinical approaches are limited in their ability to regenerate a new muscle tissue and to replace infarcted myocardium. Here, we describe the conception of two strategies based on bio-inspired materials, aimed at myocardial repair after MI. In the first strategy, alginate biomaterial was designed with affinity-binding moieties, enabling the binding of heparin-binding proteins and their controlled presentation and release. The combined features of this unique alginate hydrogel, as a temporary extracellular matrix replacement and a depot for bio-molecules such as insulin-like growth factor-1 and hepatocyte growth factor, led to improvements in cardiac structure and function, as demonstrated by the biomaterial's abilities to thicken the scar and prevent left-ventricular remodeling and dilatation. Endogenous regeneration occurring at the infarct as manifested by the enhanced angiogenesis, cardiomyocyte proliferation, and appearance of cardiac-related stem cells is likely to have contributed to this. In the second strategy, phosphatidylserine (PS)-presenting liposomes were developed to mimic apoptotic cells bodies, specifically their capability of immunomodulating activated macrophages into anti-inflammatory state. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging. The treatment promoted angiogenesis, the preservation of small scars, and prevention of ventricular dilatation and remodeling. Collectively, the two bio-inspired material-based strategies presented herein represent unique and clinical accessible approaches for myocardial infarct repair.

  5. Metabolomic Analysis of Pressure-overloaded and Infarcted Mouse Hearts

    PubMed Central

    Sansbury, Brian E.; De Martino, Angelica M.; Xie, Zhengzhi; Brooks, Alan C.; Brainard, Robert E.; Watson, Lewis J.; DeFilippis, Andrew P.; Cummins, Timothy D.; Harbeson, Matthew A.; Brittian, Kenneth R.; Prabhu, Sumanth D.; Bhatnagar, Aruni; Jones, Steven P.; Hill, Bradford G.

    2014-01-01

    Background Cardiac hypertrophy and heart failure are associated with metabolic dysregulation and a state of chronic energy deficiency. Although several disparate changes in individual metabolic pathways have been described, there has been no global assessment of metabolomic changes in hypertrophic and failing hearts in vivo. Here, we investigated the impact of pressure overload and infarction on myocardial metabolism. Methods and Results Male C57BL/6J mice were subjected to transverse aortic constriction (TAC) or permanent coronary occlusion (myocardial infarction; MI). A combination of LC/MS/MS and GC/MS techniques was used to measure 288 metabolites in these hearts. Both TAC and MI were associated with profound changes in myocardial metabolism affecting up to 40% of all metabolites measured. Prominent changes in branched amino acids acids (BCAAs) were observed after 1 week of TAC and 5 days after MI. Changes in BCAAs after MI were associated with myocardial insulin resistance. Longer duration of TAC and MI led to a decrease in purines, acylcarnitines, fatty acids and several lysolipid and sphingolipid species, but a marked increase in pyrimidines as well as ascorbate, heme and other indices of oxidative stress. Cardiac remodeling and contractile dysfunction in hypertrophied hearts were associated also with large increases in myocardial, but not plasma, levels of the polyamines putrescine and spermidine as well as the collagen breakdown product prolylhydroxyproline. Conclusions These findings reveal extensive metabolic remodeling common to both hypertrophic and failing hearts that are indicative of extensive extracellular matrix remodeling, insulin resistance and perturbations in amino acid, lipid and nucleotide metabolism. PMID:24762972

  6. Effect of Calotropis procera latex on isoproterenol induced myocardial infarction in albino rats.

    PubMed

    Ahmed, K K Mueen; Rana, A C; Dixit, V K

    2004-01-01

    The alcoholic extract of the latex obtained from Calotropis procera (Asclepidaceae) was evaluated for protection against isoproterenol (20 mg/100 g body wt., s.c.)-induced myocardial infarction in albino rats. The heart damage induced by isoproterenol was indicated by elevated levels of the marker enzymes such as Creatine Kinase-isoenzyme (CK-MB), Lactate dehydrogenase (LDH), Serum Glutamate Oxaloacetic Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT) in serum with increased lipid peroxide and reduced glutathione content in heart homogenates. Microscopical examination (histopathology) was also performed on the myocardial tissue. Pretreatment with an ethanolic latex extract of Calotropis procera at a dose of 300 mg/kg body wt., administered orally thrice a day for 30 days, reduced significantly (p < 0.01) the elevated marker enzyme levels in serum and heart homogenates in isoproterenol-induced myocardial infarction. Histopathological observation revealed a marked protection by the extract in myocardial necrotic damage.

  7. Estimation of infarct size by determination of myocardial 3H-tetracycline accumulation in the coronary ligated rat

    SciTech Connect

    Modrak, J.B.; Rovang, K.S.

    1981-10-01

    Myocardial infarction was produced in rats by ligation of the left coronary artery. Rats were injected with 3H-tetracycline (50 muCi/kg) i.p., 10 minutes prior to ligation. The rats were killed at various time periods after ligation and the myocardial accumulation of 3H-tetracycline determined in the left ventricle or in whole heart homogenates. CPK was also determined in the myocardium or serum. Myocardial 3H-tetracycline was not significantly elevated in the whole heart homogenates. However, there was a significant increase in 3H-tetracycline in the digests of the left ventricle 6 h post-infarct. This increase correlated very well with serum CPK activity. This suggest that this method could be a useful tool in the estimation of infarct size.

  8. YM598, an orally active ET(A) receptor antagonist, ameliorates the progression of cardiopulmonary changes and both-side heart failure in rats with cor pulmonale and myocardial infarction.

    PubMed

    Fujimori, Akira; Miyauchi, Takashi; Sakai, Satoshi; Yuyama, Hironori; Iemitsu, Motoyuki; Sanagi, Masanao; Sudoh, Katsumi; Goto, Katsutoshi; Shikama, Hisataka; Yamaguchi, Iwao

    2004-11-01

    The effects of the novel, selective endothelin-A (ETA) receptor antagonist YM598 on both-side heart failure were investigated. Right-side heart failure secondary to pulmonary hypertension was produced by a single subcutaneous injection of 60 mg/kg monocrotaline, and post-ischemic congestive left-side heart failure (CHF) produced by surgical left coronary artery ligation. In right-side heart failure rats, oral YM598 (0.1 and 1 mg/kg for 4 weeks), but not bosentan (30 mg/kg), significantly inhibited the progression of pulmonary hypertension and the development of right ventricular hypertrophy. YM598 also improved hypoxemia and morphological pulmonary lesions in these rats. In CHF rats, moreover, long-term oral administration of YM598 (1 mg/kg/day for approximately 30 weeks) significantly ameliorated their poor survival rate (P < 0.05). In the measurement of cardio-hemodynamic parameters, YM598 improved the contractile/diastolic capacity of the left ventricle and the preload in the right ventricle to the levels seen in sham-operated rats. YM598 also markedly inhibited both ventricular hypertrophy and pulmonary congestion, as well as lowering high plasma brain natriuretic peptide levels in CHF rats. These findings suggest that YM598 may have a clinical benefit with regards to ameliorating the cardiopulmonary changes of right-side heart failure, and the cardiac dysfunction and mortality/morbidity of CHF.

  9. Acute Myocardial Infarction Quality of Care: The Strong Heart Study

    PubMed Central

    Best, Lyle G.; Butt, Amir; Conroy, Britt; Devereux, Richard B.; Galloway, James M.; Jolly, Stacey; Lee, Elisa T.; Silverman, Angela; Yeh, Jeun-Liang; Welty, Thomas K.; Kedan, Ilan

    2014-01-01

    Objectives Evaluate the quality of care provided patients with acute myocardial infarction and compare with similar national and regional data. Design Case series. Setting The Strong Heart Study has extensive population-based data related to cardiovascular events among American Indians living in three rural regions of the United States. Participants Acute myocardial infarction cases (72) occurring between 1/1/2001 and 12/31/2006 were identified from a cohort of 4549 participants. Outcome measures The proportion of cases that were provided standard quality of care therapy, as defined by the Healthcare Financing Administration and other national organizations. Results The provision of quality services, such as administration of aspirin on admission and at discharge, reperfusion therapy within 24 hours, prescription of beta blocker medication at discharge, and smoking cessation counseling were found to be 94%, 91%, 92%, 86% and 71%, respectively. The unadjusted, 30 day mortality rate was 17%. Conclusion Despite considerable challenges posed by geographic isolation and small facilities, process measures of the quality of acute myocardial infarction care for participants in this American Indian cohort were comparable to that reported for Medicare beneficiaries nationally and within the resident states of this cohort. PMID:21942161

  10. Cardiac Extracellular Vesicles in Normal and Infarcted Heart

    PubMed Central

    Chistiakov, Dimitry A.; Orekhov, Alexander N.; Bobryshev, Yuri V.

    2016-01-01

    Heart is a complex assembly of many cell types constituting myocardium, endocardium and epicardium that intensively communicate to each other in order to maintain the proper cardiac function. There are many types of intercellular intracardiac signals, with a prominent role of extracellular vesicles (EVs), such as exosomes and microvesicles, for long-distant delivering of complex messages. Cardiomyocytes release EVs, whose content could significantly vary depending on the stimulus. In stress, such as hypoxia, inflammation or injury, cardiomyocytes increase secretion of EVs. In hypoxic conditions, cardiac EVs are enriched with angiogenic and prosurvival factors. In acute myocardial infarction (AMI), damaged cardiac muscle cells produce EVs with increased content of angiogenic, anti-apoptotic, mitogenic and growth factors in order to induce repair and healing of the infarcted myocardium. Exosomal microRNAs play a central role in cardiac regeneration. In AMI, circulating cardiac EVs abundantly contain cardiac-specific miRNAs that serve as indicators of cardiac damage and have a big diagnostic potential as AMI biomarkers. Cardioprotective and regenerative properties of exosomes derived from cardiac and non-cardiac stem/progenitor cells are very helpful to be used in cell-free cardiotherapy and regeneration of post-infarct myocardium. PMID:26742038

  11. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    SciTech Connect

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-11-14

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16{sup INK}, p21 and p19{sup ARF}. VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI.

  12. Sensing a heart infarction marker with surface plasmon resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Kunz, Ulrich; Katerkamp, Andreas; Renneberg, Reinhard; Spener, Friedrich; Cammann, Karl

    1995-02-01

    In this study a direct immunosensor for heart-type fatty acid binding protein (FABP) based on surface plasmon resonance spectroscopy (SPRS) is presented. FABP can be used as a heart infarction marker in clinical diagnostics. The development of a simple and cheap direct optical sensor device is reported in this paper as well as immobilization procedures and optimization of the measuring conditions. The correct working of the SPRS device is controlled by comparing the signals with theoretical calculated values. Two different immunoassay techniques were optimized for a sensitive FABP-analysis. The competitive immunoassay was superior to the sandwich configuration as it had a lower detection limit (100 ng/ml), needed less antibodies and could be carried out in one step.

  13. [Mesenchymal stem cells implantation increases the myofibroblasts congregating in infarct region in a rat model of myocardial infarction].

    PubMed

    Du, You-you; Yao, Rui; Pu, Shi; Zhao, Xiao-yan; Liu, Guang-hui; Zhao, Luo-sha; Chen, Qing-hua; Li, Ling

    2012-12-01

    To investigate the modulation effects of mesenchymal stem cells (MSC) implantation on the myofibroblasts congregating in the infarct region after myocardial infarction (MI). MI was induced in SD rats by left anterior descending coronary artery ligation, and the experimental animals were assigned randomly into the sham group, MI + PBS group and MI + MSC group (myocardial injection of 0.1 ml 2×10(7)/ml in four locations in the infarct region). Echocardiography, hemodynamic examinations and Masson trichrome staining were performed. Implanted MSC differentiation and myofibroblasts congregating in infarct region were investigated by immunofluorescence staining. TGF-β(1)-Smad2 signaling pathway was examined by real-time RT-PCR and Western blot. (1) Four weeks late, heart-weight/body-weight ratio [(3.04 ± 0.16) mg/g vs. (3.34 ± 0.14) mg/g, P < 0.01] and myocardial infarction size [(38.72 ± 2.38)% vs. (46.36 ± 2.81)%, P < 0.01] were significantly reduced in MI + MSC group than in MI + PBS group, while scar thickness of infarct region was thicker [(0.93 ± 0.17) mm vs. (0.65 ± 0.16) mm, P = 0.01], and LVEF was higher [LVEF: (32.5 ± 5.9)% vs. (26.5 ± 4.5)%, P = 0.03] in MI + MSC group than in MI + PBS group. (2) Myofibroblasts congregating in the infarct region was significantly enhanced in MI + MSC group compared with MI + PBS group [(196 ± 20) cells/mm(2) vs. (89 ± 25) cells/mm(2), P < 0.01], and part of implanted MSC expressed α-SMA(+). (3) TGF-β(1) expression and the phosphorylating of Smad2 in the infarct region were significantly upregulated in MI + MSC group compared with MI + PBS group (all P < 0.05). MSC could improve myocardial function and promote myofibroblasts congregating in the infarct region via activating the TGF-β(1)-Smad2 signaling pathway in this model.

  14. Autophagy Signaling in Skeletal Muscle of Infarcted Rats

    PubMed Central

    Jannig, Paulo R.; Moreira, Jose B. N.; Bechara, Luiz R. G.; Bozi, Luiz H. M.; Bacurau, Aline V.; Monteiro, Alex W. A.; Dourado, Paulo M.; Wisløff, Ulrik; Brum, Patricia C.

    2014-01-01

    Background Heart failure (HF)-induced skeletal muscle atrophy is often associated to exercise intolerance and poor prognosis. Better understanding of the molecular mechanisms underlying HF-induced muscle atrophy may contribute to the development of pharmacological strategies to prevent or treat such condition. It has been shown that autophagy-lysosome system is an important mechanism for maintenance of muscle mass. However, its role in HF-induced myopathy has not been addressed yet. Therefore, the aim of the present study was to evaluate autophagy signaling in myocardial infarction (MI)-induced muscle atrophy in rats. Methods/Principal Findings Wistar rats underwent MI or Sham surgeries, and after 12 weeks were submitted to echocardiography, exercise tolerance and histology evaluations. Cathepsin L activity and expression of autophagy-related genes and proteins were assessed in soleus and plantaris muscles by fluorimetric assay, qRT-PCR and immunoblotting, respectively. MI rats displayed exercise intolerance, left ventricular dysfunction and dilation, thereby suggesting the presence of HF. The key findings of the present study were: a) upregulation of autophagy-related genes (GABARAPL1, ATG7, BNIP3, CTSL1 and LAMP2) was observed only in plantaris while muscle atrophy was observed in both soleus and plantaris muscles, and b) Cathepsin L activity, Bnip3 and Fis1 protein levels, and levels of lipid hydroperoxides were increased specifically in plantaris muscle of MI rats. Conclusions Altogether our results provide evidence for autophagy signaling regulation in HF-induced plantaris atrophy but not soleus atrophy. Therefore, autophagy-lysosome system is differentially regulated in atrophic muscles comprising different fiber-types and metabolic characteristics. PMID:24427319

  15. Photoacoustic tomography of ex vivo mouse hearts with myocardial infarction

    NASA Astrophysics Data System (ADS)

    Holotta, Markus; Grossauer, Harald; Kremser, Christian; Torbica, Pavle; Völkl, Jakob; Degenhart, Gerald; Esterhammer, Regina; Nuster, Robert; Paltauf, Günther; Jaschke, Werner

    2011-03-01

    In the present study, we evaluated the applicability of ex vivo photoacoustic imaging (PAI) on small animal organs. We used photoacoustic tomography (PAT) to visualize infarcted areas within murine hearts and compared these data to other imaging techniques [magnetic resonance imaging (MRI), micro-computed tomography] and histological slices. In order to induce ischemia, an in vivo ligation of the left anterior descending artery was performed on nine wild-type mice. After varying survival periods, the hearts were excised and fixed in formaldehyde. Samples were illuminated with nanosecond laser pulses delivered by a Nd:YAG pumped optical parametric oscillator. Ultrasound detection was achieved using a Mach-Zehnder interferometer (MZI) working as an integrating line detector. The voxel data were computed using a Fourier-domain based reconstruction algorithm, followed by inverse Radon transforms. The results clearly showed the capability of PAI to visualize myocardial infarction and to produce three-dimensional images with a spatial resolution of approximately 120 μm. Regions of affected muscle tissue in PAI corresponded well with the results of MRI and histology. Photoacoustic tomography utilizing a MZI for ultrasound detection allows for imaging of small tissue samples. Due to its high spatial resolution, good soft tissue contrast and comparatively low cost, PAT offers great potentials for imaging.

  16. The Structural Basis of Functional Improvement in Response to Human Umbilical Cord Blood Stem Cell Transplantation in Hearts with Post-Infarct LV Remodeling

    PubMed Central

    Chen, Yong; Ye, Lei; Zhong, Jia; Li, Xin; Yan, Chen; Chandler, Margaret P.; Calvin, Steve; Xiao, Feng; Negia, Mesfin; Low, Walter C.; Zhang, Jianyi; Yu, Xin

    2015-01-01

    Cellular therapy for myocardial repair has been one of the most intensely investigated interventional strategies for acute myocardium infarction. Although the therapeutic potential of stem cells has been demonstrated in various studies, the underlying mechanisms for such improvement are poorly understood. In the present study, we investigated the long-term effects of stem cell therapy on both myocardial fiber organization and regional contractile function using a rat model of post-infarct remodeling. Human non-hematopoietic umbilical cord blood stem cells (nh-UCBSCs) were administered via tail vein to rats 2 days after infarct surgery. Animals were maintained without immunosuppressive therapy. In vivo and ex vivo MR imaging was performed on infarct hearts ten months after cell transplantation. Compared to the age-matched rats exposed to the identical surgery, both global and regional cardiac function of the nh-UCBSC-treated hearts, such as ejection fraction, ventricular strain and torsion, were significantly improved. More importantly, the treated hearts exhibited preserved fiber orientation and water diffusivities that were similar to those in sham-operated control hearts. These data provide the first evidence that nh-UCBSC treatment may prevent/delay untoward structural remodeling in post-infarct hearts, which supports the improved LV function observed in vivo in the absence of immunosuppression, suggesting a beneficial paracrine effect that occurred with the cellular therapy. PMID:24332083

  17. Protective effect of S-allyl cysteine sulphoxide (alliin) on glycoproteins and hematology in isoproterenol induced myocardial infarction in male Wistar rats.

    PubMed

    Sangeetha, T; Quine, S Darlin

    2008-07-01

    The antihyperlipidemic, antilipoperoxidative and antioxidant effects of S-allyl cysteine sulphoxide (SACS) in myocardial infarcted rats were reported previously. The present study was undertaken to evaluate the preventive role of SACS on some biochemical parameters, glycoproteins and hematology in experimentally induced myocardial infarction in rats. Myocardial infarction was induced in rats by subcutaneous injection of isoproterenol (ISO) (150 mg kg(-1)) at an interval of 24 h for 2 days. ISO-treated rats showed a significant increase in the levels of serum iron, uric acid and blood glucose, Na(+) and Ca(2+) in the heart and a significant decrease in the levels of plasma iron binding capacity, serum total protein, albumin/globulin ratio, heart K(+) and heart glycogen. The levels/concentrations of glycoproteins in serum and the heart were increased in myocardial infarcted rats. Myocardial infarcted rats also showed a significant increase in red blood cells, hemoglobin, packed cell volume, white blood cells, neutrophils, platelet count and fibrinogen level and a significant decrease in erythrocyte sedimentation rate, eosinophils, lymphocytes, bleeding, clotting and prothrombin time. Oral pretreatment with SACS (40 and 80 mg kg(-1)) daily for a period of 35 days showed a positive effect on all the biochemical parameters studied in ISO-induced rats. Thus, the study showed the protective effect of SACS on ISO-induced cardiotoxicity in male Wistar rats.

  18. Comparison of biomaterial delivery vehicles for improving acute retention of stem cells in the infarcted heart.

    PubMed

    Roche, Ellen T; Hastings, Conn L; Lewin, Sarah A; Shvartsman, Dmitry E; Brudno, Yevgeny; Vasilyev, Nikolay V; O'Brien, Fergal J; Walsh, Conor J; Duffy, Garry P; Mooney, David J

    2014-08-01

    Cell delivery to the infarcted heart has emerged as a promising therapy, but is limited by very low acute retention and engraftment of cells. The objective of this study was to compare a panel of biomaterials to evaluate if acute retention can be improved with a biomaterial carrier. Cells were quantified post-implantation in a rat myocardial infarct model in five groups (n = 7-8); saline injection (current clinical standard), two injectable hydrogels (alginate, chitosan/β-glycerophosphate (chitosan/ß-GP)) and two epicardial patches (alginate, collagen). Human mesenchymal stem cells (hMSCs) were delivered to the infarct border zone with each biomaterial. At 24 h, retained cells were quantified by fluorescence. All biomaterials produced superior fluorescence to saline control, with approximately 8- and 14-fold increases with alginate and chitosan/β-GP injectables, and 47 and 59-fold increases achieved with collagen and alginate patches, respectively. Immunohistochemical analysis qualitatively confirmed these findings. All four biomaterials retained 50-60% of cells that were present immediately following transplantation, compared to 10% for the saline control. In conclusion, all four biomaterials were demonstrated to more efficiently deliver and retain cells when compared to a saline control. Biomaterial-based delivery approaches show promise for future development of efficient in vivo delivery techniques.

  19. Effects of ACE2 Inhibition in the Post-Myocardial Infarction Heart

    PubMed Central

    Kim, Myung-A; Yang, Dongheon; Kida, Keisuke; Molotkova, Natalia; Ju Yeo, Seon; Varki, Nissi; Iwata, Michikado; Dalton, Nancy D.; Peterson, Kirk L.; Siems, Wolf-Eberhard; Walther, Thomas; Cowling, Randy T.; Kjekshus, John; Greenberg, Barry

    2010-01-01

    There is evidence that angiotensin-converting enzyme 2 (ACE2) is cardioprotective. To assess this in the post-myocardial infarction (MI) heart, we treated adult male Sprague-Dawley rats with either placebo (PL) or C16, a selective ACE2 inhibitor, following permanent coronary artery ligation or sham operation. Coronary artery ligation resulting in MI between 25–50% of the left ventricular (LV) circumference caused substantial cardiac remodeling. Daily C16 administration from post-operative days 2 to 28 at a dose that inhibited myocardial ACE2 activity was associated with a significant increase in MI size and reduction in LV % fractional shortening. Treatment with C16 did not significantly affect post-MI increases in LV end-diastolic dimension but did inhibit increases in wall thickness and fibrosis in non-infarcted LV. On post-operative day 7, C16 had no significant effect on the increased level of apoptosis in the infarct and border zones nor did it significantly affect capillary density surrounding the MI. It did, however, significantly reduce the number of c-kit+ cells in the border region. These findings support the notion that ACE2 exerts cardioprotective effects by preserving jeopardized cardiomyocytes in the border zone. The reduction in hypertrophy and fibrosis with C16, however, suggests that ACE2 activity has diverse effects on post-MI remodeling. PMID:20797602

  20. Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats

    PubMed Central

    Karim, Nurul; Hossain, Md. Sabir; Alam, Nadia

    2016-01-01

    The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium. PMID:27294126

  1. Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats.

    PubMed

    Afroz, Rizwana; Tanvir, E M; Karim, Nurul; Hossain, Md Sabir; Alam, Nadia; Gan, Siew Hua; Khalil, Md Ibrahim

    2016-01-01

    The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.

  2. Increased risk of congestive heart failure among infarctions with nighttime onset.

    PubMed

    Mukamal, K J; Muller, J E; Maclure, M; Sherwood, J B; Mittleman, M A

    2000-09-01

    The onset of acute myocardial infarction varies by time of day, with a peak in the morning and a trough at night. Whether infarct-related complications differ by the timing of the infarction is unknown. In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 3625 patients with acute myocardial infarction. We assessed the time of onset of symptoms, the presence of ventricular tachycardia or congestive heart failure, and peak creatine kinase levels (in 1043 patients). We found significant circadian variation in the risk of congestive heart failure (P =.001). The risk dropped from 17% for infarctions that began between 6 PM and midnight to 10% for infarctions that began between 6 AM and noon. Adjustment for differences in the time from symptom onset to presentation for care and use of thrombolytic agents did not change the results. We found no circadian variation in the risk of ventricular tachycardia or in peak creatine kinase levels. The risk of congestive heart failure is highest among infarctions that begin at night. Further research may clarify whether this reflects differences in the pathophysiologic characteristics of infarction or the quality of medical care provided for daytime and nighttime infarctions.

  3. Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model.

    PubMed

    Riegler, Johannes; Tiburcy, Malte; Ebert, Antje; Tzatzalos, Evangeline; Raaz, Uwe; Abilez, Oscar J; Shen, Qi; Kooreman, Nigel G; Neofytou, Evgenios; Chen, Vincent C; Wang, Mouer; Meyer, Tim; Tsao, Philip S; Connolly, Andrew J; Couture, Larry A; Gold, Joseph D; Zimmermann, Wolfram H; Wu, Joseph C

    2015-09-25

    Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell-derived cardiomyocyte transplantation, thereby potentially preventing dilative remodeling and progression to heart failure. Assessment of transport stability, long-term survival, structural organization, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction model. We constructed EHMs from human embryonic stem cell-derived cardiomyocytes and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P=0.83, P=0.87). One month after ischemia/reperfusion injury, EHMs were implanted onto immunocompromised rat hearts to simulate chronic ischemia. Bioluminescence imaging showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P=0.67), preserving ≤25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs, -6.7±1.4% versus control, -10.9±1.5%; n>12; P=0.05), we observed no difference between EHMs containing viable and nonviable human cardiomyocytes in this chronic xenotransplantation model (n>12; P=0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring. EHM transplantation led to high engraftment rates, long-term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic myocardial infarction model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation. © 2015 American Heart Association, Inc.

  4. HEART RATE CONDITIONING IN THE RAT,

    DTIC Science & Technology

    PULSE RATE, CONDITIONED RESPONSE), (*CONDITIONED RESPONSE, PULSE RATE), HEART , FEAR, ANXIETY, EMOTIONS, STIMULATION(PHYSIOLOGY), PSYCHOPHYSIOLOGY, AUTONOMIC NERVOUS SYSTEM, ANALYSIS OF VARIANCE, RATS

  5. Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism.

    PubMed

    Sun, Dan; Yang, Fei

    2017-04-29

    To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks. At the same time, Shame group (Sham) was set up. Changes in cardiac function in mice were detected at 4 weeks after operation. Hearts were taken from mice after 4 weeks, and cell apoptosis in myocardial tissue was detected using TUNEL method; fresh mitochondria were taken and changes in oxygen consumption rate (OCR) and respiratory control rate (RCR) of mitochondria in each group were detected using bio-energy metabolism tester, and change in mitochondrial membrane potential (MMP) of myocardial tissue was detected via JC-1 staining; the expressions and changes in Bcl-2, Bax, Sirt3, PGC-1α and acetylated PGC-1α in myocardial tissue were detected by Western blot. RT-PCR was used to detect mRNA levels in Sirt3 in myocardial tissues. Metformin improved the systolic function of heart failure model rats after myocardial infarction and reduced the apoptosis of myocardial cells after myocardial infarction. Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1α in myocardial tissue of heart failure after myocardial infarction. Metformin decreases the

  6. DPP-4 inhibition has beneficial effects on the heart after myocardial infarction.

    PubMed

    Kubota, Akihiko; Takano, Hiroyuki; Wang, Haixiu; Hasegawa, Hiroshi; Tadokoro, Hiroyuki; Hirose, Masanori; Kobara, Yuka; Yamada-Inagawa, Tomoko; Komuro, Issei; Kobayashi, Yoshio

    2016-02-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors are reported to have protective effects on various cells but it is unclear how DPP-4 inhibitors have cardioprotective effects. Our aim was to study the mechanisms of cardioprotective effects by DPP-4 inhibition. C57BL/6 mice and DPP-4 knockout (DPP-4KO) mice were subjected to left coronary artery ligation to produce acute myocardial infarction (MI). C57BL/6 mice were then treated with vehicle or DPP-4 inhibitor. Left ventricular function, infarct size, the number of vessels, and myocardial ischemia were assessed at 5days after MI. The treatment with DPP-4 inhibitor significantly improved cardiac function and decreased the infarct size. DPP-4 inhibitor increased the ratio of endothelial cell numbers to a cardiomyocyte. The extent of myocardial ischemia and the number of TUNEL-positive cells in the border area were significantly decreased by DPP-4 inhibitor. Stromal cell-derived factor-1α (SDF-1α) level in myocardium was significantly increased by DPP-4 inhibitor. Those cardioprotective effects after MI were also recognized in DPP-4KO mice. DPP-4 protein was expressed on rat neonatal cardiomyocytes and DPP-4 inhibitor significantly reduced hypoxia-induced apoptosis in the cardiomyocytes. However, this effect was abolished by the pretreatment with a CXCR4 antagonist or a signal transducer and activator of transcription 3 (STAT3) inhibitor. The beneficial effects of DPP-4 inhibitor on heart failure after MI were abolished by cardiomyocyte-specific deletion of STAT3. DPP-4 inhibition may have direct protective effects on the post-MI heart by inducing an antiapoptotic effect and inhibiting a decrease in vessel number through the SDF-1α/CXCR4-mediated STAT3 signaling pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.

    PubMed

    Upaganlawar, Aman; Gandhi, Chintan; Balaraman, Ramchandran

    2009-03-01

    The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.

  8. Cardioprotective actions of two bioflavonoids, quercetin and rutin, in experimental myocardial infarction in both normal and streptozotocin-induced type I diabetic rats.

    PubMed

    Annapurna, Akula; Reddy, Challa S; Akondi, Raju B; Rao, Sangana R C

    2009-10-01

    Revascularization therapy is the mainstay of treatment in the management of myocardial infarction in normal and diabetic patients. We attempted to evaluate the cardioprotective actions of quercetin and rutin in ischaemia-reperfusion-induced myocardial infarction in both normal and diabetic rats. Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazoliumchloride. Serum and tissue malondialdehyde levels and superoxide dismutase and catalase in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Results demonstrated the larger infarct size, enhanced lipid peroxidation, partial depletion of antioxidant enzymes and drastic drop in heart rate in diabetic hearts subjected to in-vivo ischaemia-reperfusion in comparison to normal rats subjected to ischaemia-reperfusion. Furthermore, quercetin and rutin significantly limit the infarct size in both normal and diabetic animals in a similar fashion. However, rutin offered complete cardioprotection at a dose of 10 mg/kg in terms of limiting infarct size. Both flavonoids could partially but significantly attenuate the lipid peroxidation. In addition, treatment has shown moderate improvement in heart rate in both normal and diabetic rats. Our data suggest the possible cardioprotective effects of quercetin and rutin in ischaemia-reperfusion injury in both normal and diabetic rats, and that protection might be in part due to the attenuation of oxidative stress and moderate increment in antioxidant reserves.

  9. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

    PubMed Central

    Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

    2014-01-01

    Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

  10. Effects of histidine and vitamin C on isoproterenol-induced acute myocardial infarction in rats

    PubMed Central

    Moradi-Arzeloo, Masoumeh; Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Asri-Rezaei, Siamak

    2016-01-01

    In the present study, we investigated the effects of histidine and vitamin C (alone or in combination) treatments against isoproterenol (a β-adrenergic receptor agonist)-induced acute myocardial infarction in rats. We used propranolol (a β-adrenergic receptor blocker) to compare the results. Rats were given intraperitoneal injections of histidine (40 mg kg-1) and vitamin C (40 mg kg-1) alone and combined daily for 21 days. Propranolol (10 mg kg-1) was orally administered daily for 10 days (from day 11 to day 21). Myocardial infarction was induced by subcutaneous injections of 150 mg kg-1 of isoproterenol at an interval of 24 hr on days 20 and 21. Blood and tissue samples were taken for histopathological and biochemical evaluations following electrocardiography recording on day 21. Isoproterenol elevated ST segment, increased heart weight, heart rate, serum activities of aspartate transaminase, lactate dehydrogenase, creatine kinase-MB and heart tissue content of malondialdehyde, and decreased R wave amplitude and superoxide dismutase and catalase activities of heart tissue. Necrosis, edema and inflammatory cells infiltration were observed in myocardial tissue sections. Our results indicated that histidine and vitamin C alone, and especially in combination prevent isoproterenol-induced cardiotoxicity and have similar protective effects with propranolol. Cardioprotective effects of histidine and vitamin C may be associated with their ability to reduce free radical-induced toxic effects. PMID:27226887

  11. Post-infarct sleep disruption and its relation to cardiac remodeling in a rat model of myocardial infarction.

    PubMed

    Aghajani, Marjan; Faghihi, Mahdieh; Imani, Alireza; Vaez Mahdavi, Mohammad Reza; Shakoori, Abbas; Rastegar, Tayebeh; Parsa, Hoda; Mehrabi, Saman; Moradi, Fatemeh; Kazemi Moghaddam, Ehsan

    2017-02-03

    Sleep disruption after myocardial infarction (MI) by affecting ubiquitin-proteasome system (UPS) is thought to contribute to myocardial remodeling and progressive worsening of cardiac function. The aim of current study was to test the hypothesis about the increased risk of developing heart failure due to experience of sleep restriction (SR) after MI. Male Wistar rats (n = 40) were randomly assigned to four experimental groups: (1) Sham, (2) MI, (3) MI and SR (MI + SR) (4) Sham and SR (Sham + SR). MI was induced by permanent ligation of left anterior descending coronary artery. Twenty-four hours after surgery, animals were subjected to chronic SR paradigm. Blood sampling was performed at days 1, 8 and 21 after MI for determination of serum levels of creatine kinase-MB (CK-MB), corticosterone, malondialdehyde (MDA) and nitric oxide (NO). Finally, at 21 days after MI, echocardiographic parameters and expression of MuRF1, MaFBx, A20, eNOS, iNOS and NF-kB in the heart were evaluated. We used H&E staining to detect myocardial hypertrophy. We found out that post infarct SR increased corticosterone levels. Our results highlighted deteriorating effects of post-MI SR on NO production, oxidative stress, and echocardiographic indexes (p < 0.05). Moreover, its detrimental effects on myocardial damage were confirmed by overexpression of MuRF1, MaFBx, iNOS and NF-kB (p < 0.001) in left ventricle and downregulation of A20 and eNOS (p < 0.05). Furthermore, histological examination revealed that experience of SR after MI increased myocardial diameter as compared to Sham subjects (p < 0.05). Our data suggest that SR after MI leads to an enlargement of the heart within 21 days, marked by an increase in oxidative stress and NO production as well as an imbalance in UPS that ultimately results in cardiac dysfunction and heart failure.

  12. Symbolic dynamics for arrhythmia identification from heart variability of rats with cardiac failures

    NASA Astrophysics Data System (ADS)

    Letellier, C.; Roulin, E.; Loriot, S.; Morin, J.-P.; Dionnet, F.

    2004-12-01

    Heart rate variability of rats is investigated using concepts from the nonlinear dynamical system theory. Among the important techniques offered, symbolic dynamics is very appealing by its power to investigate patterns which can be repeated in a time series. The present analysis was performed in six control rats and six chronic cardiac insufficient rats (myocardial infarction due to left descendent coronary artery ligation). Rats are left in clean atmosphere or exposed to atmosphere containing diluted engine emission pollutants. The evolution of the heart rate variability is then investigated with a three element symbolic dynamics which allows to distinguish extrasystoles from tachycardia or bradycardia using the symbol sequences.

  13. Protective Effects of Repetitive Injections of Radiographic Contrast Media on the Subsequent Tolerance to Ischemia in the Isolated Rat Heart

    SciTech Connect

    Falck, Geir; Bruvold, Morten; Schjott, Jan; Jynge, Per

    2000-11-15

    Purpose: Despite detailed knowledge of the effects of X-ray contrast media on cardiac function, no studies have examined the effect of contrast media injections on the subsequent tolerance to ischemia in the heart.Methods: Isolated perfused rat hearts were exposed to repetitive injections of iohexol, iodixanol, or ioxaglate before 30 min of global ischemia and 120 min of reperfusion. These groups were compared with control (no pretreatment) and ischemic preconditioning known to reduce infarct size. Physiologic variables and infarct size were measured. Results: Pretreatment with iodixanol reduced infarct size significantly compared with control and thus afforded protection against ischemia. Injections with iohexol and ioxaglate reduced infarct size, although not significantly, compared with control.Conclusion: Pretreatment of the isolated rat heart with commonly used contrast media enhances the cardiac tolerance to subsequent ischemia. The mechanism behind this protective effect could not be determined, but could involve stretching of the heart and/or generation of nitric oxide.

  14. Increased ANF secretion after volume expansion is preserved in rats with heart failure

    SciTech Connect

    Chien, Young Wei; Barbee, R.W.; MacPhee, A.L.; Frohlich, E.D.; Trippodo, N.C. )

    1988-02-01

    To examine whether the failing heart has reached a maximal capacity to increase plasma atrial natriuretic factor (ANF) concentration, the change in plasma immunoreactive ANF, measured by radioimmunoassay level due to acute blood volume expansion was determined in conscious rats with chronic heart failure. Varying degrees of myocardial infarction and thus heart failure were induced by coronary artery ligation 3 wk before study. Compared with controls, infarcted rats had decreases in mean arterial pressure cardiac index, renal blood flow, and peak left ventricle-developed pressure after aortic occlusion, and increases in central venous pressure, left ventricular end-diastolic pressure, total peripheral resistance, plasma ANF level. Plasma ANF was correlated with infarct size, cardiac filling pressures, and left ventricle pressure-generating ability. At 5 min after 25% blood volume expansion, plasma ANF in rats with heart failure increased by 2,281 {plus minus} 345 pg/ml; the magnitude of the changes in circulating ANF and hemodynamic measurements was similar in controls. The results suggest that plasma ANF level can be used as a reliable index of the severity of heart failure, and that the capacity to increase plasma ANF concentration after acute volume expansion is preserved in rats with heart failure. There was no evidence of a relative deficiency of circulating ANF in this model of heart failure.

  15. Coconut Haustorium Maintains Cardiac Integrity and Alleviates Oxidative Stress in Rats Subjected to Isoproterenol-induced Myocardial Infarction

    PubMed Central

    Chikku, A. M.; Rajamohan, T.

    2012-01-01

    The present study evaluates the effect of aqueous extract of coconut haustorium on isoproterenol-induced myocardial infarction in Sprague Dawley rats. Rats were pretreated with aqueous extract of coconut haustorium (40 mg/100 g) orally for 45 days. After pretreatment, myocardial infarction was induced by injecting isoproterenol subcutaneously (20 mg/100 g body weight) twice at an interval of 24 h. Activity of marker enzymes like lactate dehydrogenase, creatinine kinase-MB, aspartate transaminase and alanine transaminase were increased in the serum and decreased in the heart of isoproterenol treated rats indicating cardiac damage. These changes were significantly reduced in haustorium pretreated rats. Moreover, an increase in the activities of antioxidant enzymes and decrease in the levels of peroxidation products were observed in the myocardium of coconut haustorium pretreated rats. Histopathology of the heart of these rats showed almost normal tissue morphology. From these results, it is clear that aqueous extract of coconut haustorium possess significant cardioprotective and antioxidant properties during isoproterenol-induced myocardial infarction in rats. PMID:23716867

  16. Mechanisms that initiate ventricular tachycardia in the infarcted human heart

    PubMed Central

    Segal, Oliver R.; Chow, Anthony W.C.; Peters, Nicholas S.; Davies, D. Wyn

    2010-01-01

    Background Precise mechanisms that initiate ventricular tachycardia (VT) in the intact infarcted human heart have not been defined. Objective The purpose of this study was to investigate the mechanisms that underlie human postinfarct VT initiation. Methods Noncontact mapping of the left ventricle was performed in 9 patients (age 67.1 ± 7.8 years, ejection fraction 34.4% ± 5%) with previous myocardial infarction and sustained monomorphic VT. Results Circuits in which ≥30% of the diastolic pathway (DP) could be defined were identified in 12 VTs (cycle length 357 ± 60 ms). Eighteen VT episodes were initiated with pacing, and one occurred spontaneously. Ten complete and two partial circuits were mapped (89% ± 25% of the DP). In all complete circuits, pacing led to the development of unidirectional conduction block at the location of the subsequent VT exit site and the formation of functional block creating a border(s) for subsequent DP. Wavefront velocity in the DP region slowed from 1.22 ± 0.2 m/s during sinus rhythm to 0.59 ± 0.14 m/s during VT (P <.005). In 11 initiation episodes, lines of functional block and areas of slow conduction developed progressively over one to six reentrant cycles before a stable DP was established and sustained monomorphic VT ensued. The formation of unidirectional or functional lines of block was not identified during identical pacing protocols that failed to initiate VT (n = 14). Conclusion Initiation of sustained monomorphic VT requires the development of unidirectional block and formation of lines of functional block creating borders for a DP in areas of slow conduction. A transitional stage often exists during the initiation process before a stable VT circuit is established. PMID:20129286

  17. Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.

    PubMed

    Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Lacchini, Silvia; Kallás, Esper Georges; Irigoyen, Maria Cláudia; Consolim-Colombo, Fernanda M

    2016-04-15

    We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. Copyright © 2016 the American Physiological Society.

  18. Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

    PubMed Central

    Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Kallás, Esper Georges; Irigoyen, Maria Cláudia

    2016-01-01

    We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg−1·day−1) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups—denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups—were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3+ cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4+CD25+FOXP3+), and a less extreme decrease in conventional T cells (CD25+FOXP3−) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. PMID:26791829

  19. Genetically manipulated progenitor cell sheet with diprotin A improves myocardial function and repair of infarcted hearts

    PubMed Central

    Zhang, Dongsheng; Huang, Wei; Dai, Bo; Zhao, Tiemin; Ashraf, Atif; Millard, Ronald W.; Ashraf, Muhammad

    2010-01-01

    We postulated that the combination of overexpression of CXCR4 in mesenchymal stem cells (MSC) with diprotin A would enhance MSC recruitment and penetration into ischemic myocardium, leading to an improvement in heart function after myocardial infarction (MI). Male rat MSC were genetically engineered with adenoviral vectors coexpressing CXCR4 and enhanced green fluorescent protein (EGFP) (MSCCXCR4), GFP alone (MSCNull, control), or siRNA-targeted CXCR4 (MSCsiRNA). Cell sheets were applied over the surface of infarcted left ventricle (LV) in female rats 7 days after ligation of the left anterior descending coronary artery (LAD) pretreated with either vehicle (VEH) or diprotin A (DIP). At 28 days after cell sheet implantation, echocardiography was performed. Hearts were harvested for histological analysis 7 days after LAD ligation or 28 days after cell sheet implantation. DPP-IV and stroma-derived factor-1α (SDF-1α) in the LV were analyzed. Efficacy of engraftment was determined by the presence of Y chromosome in nuclei (Ych+). LV blood vessel density and apoptosis were also analyzed. Myocardial SDF-1α was elevated before placement of the cell sheet in the DIP group compared with vehicle group on day 7 after LAD. On day 28 after cell sheet transplantation, the number of Ych+ was increased in the MSCCXCR4 + VEH group compared with the MSCNull + VEH group and further increased in the MSCCXCR4 + DIP treated group. This enhanced response was associated with increased angiogenesis in both sides of epicardium and improvement of LV function. Combination of gene-manipulated MSCCXCR4 patch with DIP pretreatment inhibits myocardial ischemia-induced apoptosis, promotes tissue angiogenesis, and enhances cell engraftment, leading to improved LV mechanical function after MI. PMID:20802132

  20. Genetically manipulated progenitor cell sheet with diprotin A improves myocardial function and repair of infarcted hearts.

    PubMed

    Zhang, Dongsheng; Huang, Wei; Dai, Bo; Zhao, Tiemin; Ashraf, Atif; Millard, Ronald W; Ashraf, Muhammad; Wang, Yigang

    2010-11-01

    We postulated that the combination of overexpression of CXCR4 in mesenchymal stem cells (MSC) with diprotin A would enhance MSC recruitment and penetration into ischemic myocardium, leading to an improvement in heart function after myocardial infarction (MI). Male rat MSC were genetically engineered with adenoviral vectors coexpressing CXCR4 and enhanced green fluorescent protein (EGFP) (MSC(CXCR4)), GFP alone (MSC(Null), control), or siRNA-targeted CXCR4 (MSC(siRNA)). Cell sheets were applied over the surface of infarcted left ventricle (LV) in female rats 7 days after ligation of the left anterior descending coronary artery (LAD) pretreated with either vehicle (VEH) or diprotin A (DIP). At 28 days after cell sheet implantation, echocardiography was performed. Hearts were harvested for histological analysis 7 days after LAD ligation or 28 days after cell sheet implantation. DPP-IV and stroma-derived factor-1α (SDF-1α) in the LV were analyzed. Efficacy of engraftment was determined by the presence of Y chromosome in nuclei (Y(ch+)). LV blood vessel density and apoptosis were also analyzed. Myocardial SDF-1α was elevated before placement of the cell sheet in the DIP group compared with vehicle group on day 7 after LAD. On day 28 after cell sheet transplantation, the number of Y(ch+) was increased in the MSC(CXCR4) + VEH group compared with the MSC(Null) + VEH group and further increased in the MSC(CXCR4) + DIP treated group. This enhanced response was associated with increased angiogenesis in both sides of epicardium and improvement of LV function. Combination of gene-manipulated MSC(CXCR4) patch with DIP pretreatment inhibits myocardial ischemia-induced apoptosis, promotes tissue angiogenesis, and enhances cell engraftment, leading to improved LV mechanical function after MI.

  1. Cardioprotective effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats.

    PubMed

    Gao, Yan; Gao, Jianping; Chen, Changxun; Wang, Huilin; Guo, Juan; Wu, Rong

    2015-05-01

    The purpose of this study was to explore the effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats and to elucidate the underlying mechanisms. A rat model of ventricular remodeling after myocardial infarction was established by left coronary artery ligation. Rats with coronary artery ligation were randomly divided into five groups: control, plus 40 mg/kg captopril, plus 25 mg/kg polydatin, plus 50 mg/kg polydatin, and plus 100 mg/kg polydatin. The sham-operated group was used as a negative control. Rats were administered intragastrically with the corresponding drugs or drinking water for seven weeks. At the end of the treatment, the left ventricular weight index and heart weight index were assessed. The cross-sectional size of cardiomyocytes was measured by staining myocardium tissue with hematoxylin and eosin. Collagen content was counted by Sirius red in aqueous saturated picric acid. The concentrations of angiotensin I, angiotensin II, aldosterone, and endothelin 1 in myocardium or serum were determined by radioimmunoassay. Hydroxyproline and nitric oxide concentrations and glutathione peroxidase and catalase activities in serum were measured by ultraviolet spectrophotometry. Our results showed that seven weeks of polydatin treatment resulted in a significantly reduced left ventricular weight index, heart weight index, serum concentrations of hydroxyproline and aldosterone, an increased concentration of nitric oxide as well as enhanced activities of glutathione peroxidase and catalase. Myocardial angiotensin I, angiotensin II, and endothelin 1 levels were also reduced. The cardiomyocyte cross-sectional area and collagen deposition diminished. This study suggests that polydatin may attenuate ventricular remodeling after myocardial infarction in coronary artery ligation rats through restricting the excessive activation of the renin-angiotensin-aldosterone system and inhibiting peroxidation. Georg Thieme

  2. PROTECTIVE EFFECT OF HESPERIDIN ON CARDIOVASCULAR COMPLICATION IN EXPERIMENTALLY INDUCED MYOCARDIAL INFARCTION IN DIABETES IN RATS

    PubMed Central

    Kakadiya, Jagdish; Mulani, Haresh; Shah, Nehal

    2010-01-01

    Present study was designed to evaluate effect Hesperidin on Cardiovascular Complication in isoproterenol induced myocardial infarction in normal and Streptozotocin-Nicotinamide induced in diabetic rats. Hesperidin (100 mg/kg, p.o) was administered for 28 days in rats injected with single dose of Streptozotocin (65 mg/kg, i.p, STZ) and Nicotinamide (110 mg/kg, i.p, NIC) and after isoproterenol (200 mg/kg, s.c.) induced myocardial infarction in rats on 29th and 30th day. At the end of experimental period (i.e. on the day 31) serum and heart tissues sample were collected, and glucose, HbA1c and Total Cholesterol (TC), Triglycerides (TG) and High density lipoprotein (HDL) and cholesterol ester synthetase (CES), lecithin Cholesterol acyl transferase (LCAT), lipoprotein lipase (LPL), systolic and diastolic blood pressure were find out. Administration of STZ–NIC in rats showed a significant (p<0.001) increased in the levels of serum glucose, glycosylated heamoglobin (HbA1c), Total Cholesterol (TC), Triglycerides (TG) and Low density lipoprotein (LDL) whereas the levels of High density lipoprotein (HDL) were found to be non significant but significant (p<0.001) increased in the level of heart tissues CES and significant (p<0.001, p<0.01) decreased LCAT and LPL, significantly (p<0.01) increased systolic and diastolic blood pressure as compared to respective control groups. Treatment with Hesperidin significantly (P<0.05) decreased HbA1c, glucose, CES level and significantly (P<0.01) decreased LDL, TC, TG, systolic and diastolic blood pressure and significant (P<0.01) increased LCAT and LPL level but no significantly change HDL in compared to diabetic control group. We concluded that HES (100 mg/kg) is effective in controlling blood glucose levels and reduced cardiac complication in experimentally induced myocardial infarction diabetic rats. PMID:24825971

  3. Acute myocardial infarction: the first manifestation of ischemic heart disease and relation to risk factors.

    PubMed

    Manfroi, Waldomiro Carlos; Peukert, Carolina; Berti, Clarissa Bacha; Noer, Clarissa; Gutierres, Danielle de Avila; Silva, Felipe Theodoro Bezerra Gaspar Carvalho da

    2002-04-01

    To assess the association between cardiovascular risk factors and acute myocardial infarction as the first manifestation of ischemic heart disease, correlating them with coronary angiographic findings. We carried out a cross-sectional study of 104 patients with previous acute myocardial infarction, who were divided into 2 groups according to the presence or absence of angina prior to acute myocardial infarction. We assessed the presence of angina preceding acute myocardial infarction and risk factors, such as age >55 years, male sex, smoking, systemic arterial hypertension, lipid profile, diabetes mellitus, obesity, sedentary lifestyle, and familial history of ischemic heart disease. On coronary angiography, the severity of coronary heart disease and presence of left ventricular hypertrophy were assessed. Of the 104 patients studied, 72.1% were males, 90.4% were white, 73.1% were older than 55 years, and 53.8% were hypertensive. Acute myocardial infarction was the first manifestation of ischemic heart disease in 49% of the patients. The associated risk factors were systemic arterial hypertension (RR=0.19; 95% CI=0.06-0.59; P=0.04) and left ventricular hypertrophy (RR=0.27; 95% CI=0,.8-0.88; P=0.03). The remaining risk factors were not statistically significant. Prevalence of acute myocardial infarction as the first manifestation of ischemic heart disease is high, approximately 50%. Hypertensive individuals more frequently have symptoms preceding acute myocardial infarction, probably due to ventricular hypertrophy associated with high blood pressure levels.

  4. PET/MRI in the infarcted mouse heart with the Cambridge split magnet

    NASA Astrophysics Data System (ADS)

    Buonincontri, Guido; Sawiak, Stephen J.; Methner, Carmen; Krieg, Thomas; Hawkes, Robert C.; Adrian Carpenter, T.

    2013-02-01

    Chronic heart failure, as a result of acute myocardial infarction, is a leading cause of death worldwide. Combining diagnostic imaging modalities may aid the direct assessment of experimental treatments targeting heart failure in vivo. Here we present preliminary data using the Cambridge combined PET/MRI imaging system in a mouse model of acute myocardial infarction. The split-magnet design can deliver uncompromised MRI and PET performance, for better assessment of disease and treatment in a preclinical environment.

  5. Intramyocardial injection of platelet gel promotes endogenous repair and augments cardiac function in rats with myocardial infarction.

    PubMed

    Cheng, Ke; Malliaras, Konstantinos; Shen, Deliang; Tseliou, Eleni; Ionta, Vittoria; Smith, Jeremy; Galang, Giselle; Sun, Baiming; Houde, Christiane; Marbán, Eduardo

    2012-01-17

    This study sought to explore the therapeutic potential of platelet gel for the treatment of myocardial infarction. Cardiac dysfunction after acute myocardial infarction is a major cause of heart failure. Current therapy relies on prompt reperfusion and blockage of secondary maladaptive pathways by small molecules. Platelet gels are biomaterials rich in cytokines and growth factors, which can be manufactured in an autologous manner and are effective in various models of wound healing. However, the potential utility of platelet gel in cardiac regeneration has yet to be tested. Platelet gel was derived from syngeneic rats and its morphology, biocompatibility, secretion of beneficial factors, and in vivo degradation profile were characterized. After delivery into infarcted rat hearts, the gel was efficiently infiltrated by cardiomyocytes and endothelial cells. Gel-treated hearts exhibited enhanced tissue protection, greater recruitment of endogenous regeneration, higher capillary density, and less compensatory myocyte hypertrophy. The cardiac function of control-injected animals deteriorated over the 6-week time course, while that of platelet gel-injected animals did not. In addition, the gel did not exacerbate inflammation in the heart. Intramyocardial injection of autologous platelet gel ameliorated cardiac dysfunction after myocardial infarction. The striking functional benefits, the simplicity of manufacturing, and the potentially autologous nature of this biomaterial provide impetus for further translation. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. Cardioprotective potential of Punica granatum extract in isoproterenol-induced myocardial infarction in Wistar rats

    PubMed Central

    Mohan, Mahalaxmi; Patankar, Pankaj; Ghadi, Prakash; Kasture, Sanjay

    2010-01-01

    Objective: To determine the protective role of Punica granatum L. (Punicaceae) seed juice extract and its butanolic fraction on heart rate, electrocardiographic patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphologic and histopathological changes in isoproterenol-induced myocardial infarction in male Wistar rats. Materials and Methods: The effects of Punica granatum seed juice extract (100 mg/kg, p.o. and 300 mg/kg, p.o.) and butanolic fraction of Punica granatum seed juice extract (100 mg/kg., p.o.) on cardiac parameters were studied. Isoproterenol hydrochloride was used to induce myocardial infarction in Wistar rats. At the end of the experiment, heart rate, ECG, pressure rate index and cardiac marker enzyme levels were assessed. Results: Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate, ST elevation in ECG, pressure rate index and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum. Isoproterenol significantly reduced superoxide dismutase and catalase activity and increased vascular reactivity to various catecholamines. Pretreatment with PJ (100 mg/kg, p.o. and 300 mg/kg, p.o.) and B-PJ (100 mg/kg., p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, PRI, ECG patterns, levels of LDH, CK, SOD, CAT, and vascular reactivity changes. Treatment with PJ (100 mg/kg and 300 mg/kg) and B-PJ (100 mg/kg., p.o.) alone did not alter any of the parameters as compared to vehicle-treated Wistar rats. Punica granatum-treated animals showed a lesser degree of cellular infiltration in histopathological studies. Conclusion: Punica granatum ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of MI. PMID:21808588

  7. [Digitalization for acute myocardial infarction: haemodynamic changes in patients with heart failure at rest (author's transl)].

    PubMed

    Bachour, G; Hochrein, H

    1975-11-21

    Haemodynamic changes after intravenous administration of 0.4 mg beta-methyldigoxin or 0.4 mg digoxin daily were measured on the first to fourth day in 42 patients in heart failure after onset of transmural myocardial infarction. Regular reduction in filling pressure and increased stroke volume while arterial blood pressure remained unaltered pointed to improved contractility. Digitalization in the first few days after infarction achieved sustained tendency towards improved haemodynamics. It is concluded that early digitalization is indicated in patients with acute myocardial infarction if there are signs of heart failure.

  8. Sequential delivery of angiogenic growth factors improves revascularization and heart function after myocardial infarction

    PubMed Central

    Awada, Hassan K.; Johnson, Noah R.; Wang, Yadong

    2015-01-01

    Treatment of ischemia through therapeutic angiogenesis faces significant challenges. Growth factor (GF)-based therapies can be more effective when concerns such as GF spatiotemporal presentation, bioactivity, bioavailability, and localization are addressed. During angiogenesis, vascular endothelial GF (VEGF) is required early to initiate neovessel formation while platelet-derived GF (PDGF-BB) is needed later to stabilize the neovessels. The spatiotemporal delivery of multiple bioactive GFs involved in angiogenesis, in a close mimic to physiological cues, holds great potential to treat ischemic diseases. To achieve sequential release of VEGF and PDGF, we embed VEGF in fibrin gel and PDGF in a heparin-based coacervate that is distributed in the same fibrin gel. In vitro, we show the benefits of this controlled delivery approach on cell proliferation, chemotaxis, and capillary formation. A rat myocardial infarction (MI) model demonstrated the effectiveness of this delivery system in improving cardiac function, ventricular wall thickness, angiogenesis, cardiac muscle survival, and reducing fibrosis and inflammation in the infarct zone compared to saline, empty vehicle, and free GFs. Collectively, our results show that this delivery approach mitigated the injury caused by MI and may serve as a new therapy to treat ischemic hearts pending further examination. PMID:25836592

  9. Cardioprotective effect of ethanolic extract of Urtica parviflora Roxb. against isoproterenol induced myocardial infarction in rats

    PubMed Central

    Barman, Nishith Ranjan; Nandy, Subhangkar; Datta, Rana; Kar, Prasanna Kumar

    2013-01-01

    Objective: The objective of this study is to evaluate the effect of ethanolic extract of Urtica parviflora Roxb. in isoproterenol (ISO) induced myocardial infarction (MI) in rats. Materials and Methods: U. parviflora Roxb. (350 mg/kg and 500 mg/kg, p.o) was administered for 15 days in rats. MI was induced with a single dose of ISO (200 mg/kg, s.c.) on the 14th and 15th day. At the end of the experimental period (i.e., on the day 16), serum and heart tissues were collected and total cholesterol (TC), high density lipoprotein, triglyceride and malondialdehyde, superoxide dismutase, catalase (CAT), reduced glutathione (GSH) and body weight were determined. Results: Administration of ISO in control rats showed a significant (P < 0.001) increase serum cholesterol alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and low density lipoprotein (LDL). There was a significant increase (P < 0.01) in the levels of heart tissues as compared with respective control groups. Rats treated with U. parviflora significantly (P < 0.01) decreased ALT, AST, ALP, LDL and TC. Moreover, there was an increased CAT and GSH levels in rat treated with U. parviflora Roxb. as compared with the control group. Conclusion: U. parviflora (350 and 500 mg/kg p.o.) is effective in controlling serum LDL levels and reduced cardiac complication in experimentally induced MI in rats. PMID:24130389

  10. Cardiomyopathy development protection after myocardial infarction in rats: Successful competition for major dihydropyridines' common metabolite against captopril.

    PubMed

    Mitręga, Katarzyna A; Spałek, Adrianna M; Nożyński, Jerzy; Porc, Maurycy; Stankiewicz, Magdalena; Krzemiński, Tadeusz F

    2017-01-01

    During the last 25 years angiotensin-converting enzyme inhibitors spectacularly conquered the field of cardiovascular diseases therapy. Nevertheless, lack of new studies concerning side effects associated with their chronic administration seems to be rather confusing. In our previous research, we proved that the main furnidipines' metabolite (M-2) possess multiple cardioprotective actions. Currently, we compared effects of post-infarction long-term oral treatment with M-2 and captopril on hemodynamic parameters and "ischemic cardiomyopathy" development in rats. Myocardial infarction was evoked by permanent left anterior descending coronary artery occlusion for 35 days. Surviving rats were treated with captopril (2 × 25 mg/kg) or M-2 (4 mg/kg) from 6th- 35th day. At 35th day rats' hearts were tested on working heart setup, where following parameters were measured: heart rate, preload pressure, aortic systolic and diastolic pressures, aortic maximum rise and fall, aortic and coronary flow, myocardial oxygen consumption and oximetry in perfusate. Subsequently, heart tissue specimens were assessed during morphological estimation. Captopril caused significant heart rate increase and markedly diminished preload pressure in comparison to M-2. Both drugs evoked essential aortic pressure increase. Aortic flow was significantly decreased after M-2, whereas captopril increased this parameter in comparison to M-2. Both agents caused marked coronary flow increase. Morphologic examination in captopril revealed cardiomyopathic process in 70% of hearts, whereas in M-2 this value reached 30%. Neovascularization of post-infarcted myocardium was visible only after M-2 therapy. Concluding, M-2 presented itself as more attractive agent in long-term post-infarction treatment by preventing cardiomyopathy development, angiogenesis stimulation and preserving cardiac performance.

  11. Preventive effect of phytic acid on lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats.

    PubMed

    Brindha, E; Rajasekapandiyan, M

    2015-02-01

    This study was aimed to evaluate the preventive role of phytic acid on lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for two days showed a significant increase in the activities of lysosomal enzymes (glucuronidase, N-acetyl glucosaminidase, galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with phytic acid (25 and 50 mg/kg) daily for a period of 56 d positively altered activities of lysosomal hydrolases in ISO-induced rats. Thus, phytic acid possesses a cardioprotective effect in ISO-induced MI in rats.

  12. Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure.

    PubMed

    Manchini, Martha T; Antônio, Ednei L; Silva Junior, José Antônio; de Carvalho, Paulo de Tarso C; Albertini, Regiane; Pereira, Fernando C; Feliciano, Regiane; Montemor, Jairo; Vieira, Stella S; Grandinetti, Vanessa; Yoshizaki, Amanda; Chaves, Marcio; da Silva, Móises P; de Lima, Rafael do Nascimento; Bocalini, Danilo S; de Melo, Bruno L; Tucci, Paulo J F; Serra, Andrey J

    2017-01-01

    Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and -dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt1/VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be

  13. Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure

    PubMed Central

    Manchini, Martha T.; Antônio, Ednei L.; Silva Junior, José Antônio; de Carvalho, Paulo de Tarso C.; Albertini, Regiane; Pereira, Fernando C.; Feliciano, Regiane; Montemor, Jairo; Vieira, Stella S.; Grandinetti, Vanessa; Yoshizaki, Amanda; Chaves, Marcio; da Silva, Móises P.; de Lima, Rafael do Nascimento; Bocalini, Danilo S.; de Melo, Bruno L.; Tucci, Paulo J. F.; Serra, Andrey J.

    2017-01-01

    Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and −dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt1/VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may

  14. Coenzyme Q10 protects against acute consequences of experimental myocardial infarction in rats

    PubMed Central

    Eleawa, Samy M; Alkhateeb, Mahmoud; Ghosh, Sanjoy; Al-Hashem, Fahaid; Shatoor, Abdullah S; Alhejaily, Abdulmohsen; Khalil, Mohammad A

    2015-01-01

    Aim: Myocardial infarction (MI) due to sudden occlusion of a major coronary artery leads to a complex series of events that result in left ventricle (LV) impairment eventual heart failure. Therapeutic options are limited to reverse such trends post MI. The aim of this study was to compare the acute cardioprotective effects of the antioxidants, resveratrol (RES) and coenzyme Q10 (CoQ10), either individually or in combination, on infracts size, LV hemodynamics, inflammation and oxidative stress markers in rats with experimentally induced MI. Methods: Male Wistar rats were randomly divided into six groups: control without surgery, sham without occlusion, MI without antioxidants, RES pre-treated then MI (20 mg/kg, orally), CoQ10 then MI (20 mg/kg, intramuscular.), and combined RES and CoQ10 then MI with (each group n = 10). Pretreatment commenced 7 days prior to the permanent occlusion of the left anterior descending (LAD) coronary artery. Infarct area, hemodynamics, inflammation and oxidative stress markers were assessed 24 hours post-MI. Results: Compared to RES alone, CoQ10 pre-administration either by itself or in combination with RES, significantly reduced LV infarct area (57%), and normalized LV hemodynamic parameters like LVEDP (100%), LVSP (95.4%), LV +dp/dt and -dp/dt (102 and 73.1%, respectively). CoQ10 also decreased serum levels of brain natriuretic peptide (70%), and various circulating inflammatory markers like TNF-α (83.2%) and IL-6 (83.2%). Regarding oxidative stress, TBARS scores were lowered with a concurrent increase in both superoxide dismutase and glutathione peroxidase activities with CoQ10 alone or in combination with RES. Conclusion: Coenzyme Q10 protects against the acute sequelae of myocardial infarction. It profoundly reduced infarct area, inflammation and oxidative stress while normalizing LV hemodynamics post MI. PMID:26069524

  15. Early treatment with hepatocyte growth factor improves cardiac function in experimental heart failure induced by myocardial infarction.

    PubMed

    Jin, Hongkui; Yang, Renhui; Li, Wei; Ogasawara, Annie K; Schwall, Ralph; Eberhard, David A; Zheng, Zhong; Kahn, David; Paoni, Nicholas F

    2003-02-01

    Plasma levels of hepatocyte growth factor (HGF) are increased within hours of cardiac ischemia/reperfusion in rats, and HGF has been shown to be cardioprotective toward acute ischemic injury. Myocardial levels of HGF mRNA and protein are increased for several days after myocardial infarction (MI), however, indicating a possible additional protective effect of HGF toward the progression of MI to heart failure. The purpose of this study was to determine whether HGF administration during the time course of endogenous cardiac HGF induction would lead to long-term improvement in cardiac function in rats with MI. MI was induced by 2-h occlusion of the left coronary artery, followed by reperfusion. HGF was given by intravenous infusion at 0.45 mg/kg/day for 6 days beginning on the day after surgery. Cardiac function and hemodynamic parameters were measured by using indwelling catheters and perivascular flow probes in conscious animals 8 weeks post-MI. Myocardial infarcts were approximately 30% of the left ventricle, and there was no difference in infarct size between the vehicle-treated and HGF-treated groups. Compared with untreated sham-operated rats, vehicle-treated MI animals had significantly lower cardiac index and stroke volume index and higher systemic vascular resistance, indicating heart failure developed. Treatment with HGF caused a significant increase in cardiac index and stroke volume index and a reduction in systemic vascular resistance in rats with MI, restoring these parameters close to those observed in sham-operated control animals. These results provide direct evidence that HGF may be of benefit to cardiovascular function in ischemic cardiomyopathy.

  16. Heart regeneration and repair after myocardial infarction: translational opportunities for novel therapeutics.

    PubMed

    Cahill, Thomas J; Choudhury, Robin P; Riley, Paul R

    2017-10-01

    Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix. These findings have revealed novel pathways that could be therapeutically targeted to stimulate repair following myocardial infarction and have provided lessons to guide future efforts towards heart regeneration through cellular reprogramming or cardiomyocyte transplantation.

  17. Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction.

    PubMed

    Zhu, Guiyue; Yao, Yucai; Pan, Lingyun; Zhu, Wei; Yan, Suhua

    2015-12-17

    BACKGROUND This study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions. MATERIAL AND METHODS AMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction. RESULTS Leukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (p<0.05). However, Hu treatment decreased their counts significantly (p<0.05). sICAM, P-selectin, and PAF level in vehicle AMI group were significantly higher than those of the normal group, and their level was also decreased by Hu treatment (p<0.05). Echocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (p<0.05). Histopathological examination showed that Hu significantly reduced the swelling of the heart muscle fiber in necrotic foci and the number of inflammatory cells infiltrated into myocardial interstitium compared to vehicle AMI group. CONCLUSIONS Decrease leukocytes counts by Hu significantly reduced inflammatory reaction and improved cardiac functions in AMI rats.

  18. Hematopoietic stem cells do not repair the infarcted mouse heart.

    PubMed

    Deten, Alexander; Volz, Hans Christian; Clamors, Sören; Leiblein, Sabine; Briest, Wilfried; Marx, Grit; Zimmer, Heinz-Gerd

    2005-01-01

    Recent reports suggest that hematopoietic stem cells (HSC) can transdifferentiate into cardiomyoctes and contribute to myocardial regeneration after injury. This concept has recently been challenged by studies in which bone-marrow (BM)-derived cells do not acquire a cardiac phenotype after direct injection into ischemic myocardium. In this study, we analyzed the effect of increased circulating adult BM cells by stimulation with stem cell factor (SCF; 200 microg/kg/d for 7 days) and granulocyte-colony stimulating factor (G-CSF, 50 microg/kg/d for 7 days) or by peripheral delivery of isolated adult BM cells on morphological and hemodynamic parameters of mouse hearts 6 weeks after induction of chronic myocardial infarction (MI). All animals were splenectomized to prevent sequestration of BM cells 2 weeks prior to the induction of MI. Cytokine treatment was initiated either 3 days prior to or 6 h after MI. Isolated, either whole or by magnetic beads lineage-depleted BM cells were injected via a tail vein 6 h after MI. Left and right ventricular (LV and RV) function revealed no improvement in any treatment group when compared to untreated MI animals at baseline resting conditions as well as after stimulation with norepinephrine (NE; 1, 5, 10, 25, 50, and 100 ng bolus i.v. in 10 microl each) as measured by catherization with ultraminiature 1.4 F tip pressure transducers 6 weeks after MI. Moreover, there was no sign of myocardial regeneration in histological or gene expression analyses. Mobilization or i.v. injection of BM cells do not have a measurable effect on cardiac regeneration.

  19. Human heart valve-derived scaffold improves cardiac repair in a murine model of myocardial infarction

    PubMed Central

    Wan, Long; Chen, Yao; Wang, Zhenhua; Wang, Weijun; Schmull, Sebastian; Dong, Jun; Xue, Song; Imboden, Hans; Li, Jun

    2017-01-01

    Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction. PMID:28051180

  20. Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction.

    PubMed

    Sun, Jian; Huang, Shan Hong; Tan, Benny K-H; Whiteman, Matt; Zhu, Yi Chun; Wu, Ya Jun; Ng, Yeekong; Duan, Wei; Zhu, Yi Zhun

    2005-04-29

    In the current study, we compared purified Salvia miltiorrhiza extract (PSME) with Angiotensin-converting enzyme inhibitor, Ramipril, in in vitro experiments and also in vivo using animal model of myocardial infarction. PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals. PSME could also prevent pyrogallo red bleaching and DNA damage. After 2 weeks treatment with PSME or Ramipril, survival rates of rats with experimental myocardial infarction were marginally increased (68.2% and 71.4%) compared with saline (61.5%). The ratios of infarct size to left ventricular size in both PSME-and Ramipril-treated rats were significantly less than that in the saline-treated group. Activity of cardiac antioxidant enzyme superoxide dismutase (SOD) was significant higher while level of Thiobarbituric acid-reactive substances (TBARs) was lower in the PSME treated group. Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.

  1. Number of Coronary Heart Disease Risk Factors and Mortality in Patients With First Myocardial Infarction

    PubMed Central

    Canto, John G.; Kiefe, Catarina I.; Rogers, William J.; Peterson, Eric D.; Frederick, Paul D.; French, William J.; Gibson, C. Michael; Pollack, Charles V.; Ornato, Joseph P.; Zalenski, Robert J.; Penney, Jan; Tiefenbrunn, Alan J.; Greenland, Philip

    2013-01-01

    Context Few studies have examined the association between the number of coronary heart disease risk factors and outcomes of acute myocardial infarction in community practice. Objective To determine the association between the number of coronary heart disease risk factors in patients with first myocardial infarction and hospital mortality. Design Observational study from the National Registry of Myocardial Infarction, 1994-2006. Patients We examined the presence and absence of 5 major traditional coronary heart disease risk factors (hypertension, smoking, dyslipidemia, diabetes, and family history of coronary heart disease) and hospital mortality among 542 008 patients with first myocardial infarction and without prior cardiovascular disease. Main Outcome Measure All-cause in-hospital mortality. Results A majority (85.6%) of patients who presented with initial myocardial infarction had at least 1 of the 5 coronary heart disease risk factors, and 14.4% had none of the 5 risk factors. Age varied inversely with the number of coronary heart disease risk factors, from a mean age of 71.5 years with 0 risk factors to 56.7 years with 5 risk factors (P for trend <.001). The total number of in-hospital deaths for all causes was 50 788. Unadjusted in-hospital mortality rates were 14.9%, 10.9%, 7.9%, 5.3%, 4.2%, and 3.6% for patients with 0, 1, 2, 3, 4, and 5 risk factors, respectively. After adjusting for age and other clinical factors, there was an inverse association between the number of coronary heart disease risk factors and hospital mortality adjusted odds ratio (1.54; 95% CI, 1.23-1.94) among individuals with 0 vs 5 risk factors. This association was consistent among several age strata and important patient subgroups. Conclusion Among patients with incident acute myocardial infarction without prior cardiovascular disease, in-hospital mortality was inversely related to the number of coronary heart disease risk factors. PMID:22089719

  2. MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart

    PubMed Central

    Dakhlallah, Duaa; Zhang, Jianying; Yu, Lianbo; Marsh, Clay B.; Angelos, Mark G.; Khan, Mahmood

    2015-01-01

    Cardiovascular disease is the number one cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure (CHF). Cell therap (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA in the cardiac muscle and is down-regulated in patients with MI. We hypothesized that reprogramming MSCs using microRNA-mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs and the levels of miR-133a were measured by qRT-PCR. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic heart. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels and apoptosis related genes (Apaf-1, Capase-9 and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, qRT-PCR data demonstrated a significant decrease in expression of the pro-apoptotic genes; Apaf-1, caspase-9 and caspase-3 in the miR-133a mimic transplanted group. Further, luciferase reporter assay confirmed that miR- 133a is a direct target for Apaf-1. Overall, bioengineering of stem cells through miRNAs manipulation could potentially improve the therapeutic outcome of

  3. Electroacupuncture improves cardiac function and remodeling by inhibition of sympathoexcitation in chronic heart failure rats.

    PubMed

    Ma, Luyao; Cui, Baiping; Shao, Yongfeng; Ni, Buqing; Zhang, Weiran; Luo, Yonggang; Zhang, Shijiang

    2014-05-15

    Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.

  4. Astragaloside IV enhances cardioprotection of remote ischemic conditioning after acute myocardial infarction in rats

    PubMed Central

    Cheng, Songyi; Yu, Peng; Yang, Li; Shi, Haibo; He, Anxia; Chen, Hanyu; Han, Jie; Xie, Liang; Chen, Jiandong; Chen, Xiaohu

    2016-01-01

    Background: Remote ischemic conditioning (RIC) has been shown to be a practical method for protecting the heart from ischemic/reperfusion (I/R) injury. In the present study, we investigated whether or not the combination of RIC and Astragaloside IV (AS-IV) could improve cardioprotection against acute myocardial infarction (AMI)-induced heart failure (HF) when compared with individual treatments. Material and Methods: A rat model of AMI was established via permanent ligation of the left anterior descending coronary artery (LAD). Postoperatively, the rats were randomly grouped into a sham group (n=10), a model group (n=15), an AS-IV alone group (n=15), an RIC alone group (n=15) and a combined treatment group (AS-IV+RIC; n=15). All treatments were administered for 2 weeks. Results: After treatment for 2 weeks, the survival rate was improved, the cardiac function was preserved and the infarcted size was limited in AS-IV alone and RIC alone treatment groups compared to the model group, whereas the combined treatment yielded the most optimal protective effects. Additional studies suggested that AS-IV enhanced the cardioprotective effects of RIC by alleviating myocardial fibrosis, suppressing inflammation, attenuating apoptosis and ameliorating impairment of the myocardial ultrastructural. Conclusion: AS-IV enhances the cardioprotective effects of RIC against AMI-induced HF and ventricular remodeling, which represents a potential therapeutic approach for preserving cardiac function and improving the prognosis of AMI. PMID:27904669

  5. Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats.

    PubMed

    Maranhão, Raul C; Guido, Maria C; de Lima, Aline D; Tavares, Elaine R; Marques, Alyne F; Tavares de Melo, Marcelo D; Nicolau, Jose C; Salemi, Vera Mc; Kalil-Filho, Roberto

    2017-01-01

    Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment. Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery) or with LDE without drug (MI-controls). A sham-surgery group (n=12) was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy. LDE-MTX treatment achieved a 40% improvement in left ventricular (LV) systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine bioavailability in the LV by increasing adenosine receptors and modulating adenosine catabolic enzymes. LDE-MTX increased the expression of myocardial vascular endothelium growth factor (VEGF) associated with adenosine release; this correlated not only with an increase in angiogenesis, but also with other parameters improved by LDE-MTX, suggesting that VEGF increase played an important role in the beneficial effects of LDE-MTX. Overall effects of

  6. Influence of heart size on mortality and reinfarction in patients treated with timolol after myocardial infarction.

    PubMed Central

    Gundersen, T

    1983-01-01

    The influence of heart size on the effect of long term timolol treatment with regard to mortality and reinfarction after myocardial infarction was examined among 1881 patients randomised to either active or placebo treatment. The patients were followed for 12 to 33 months. At the baseline, heart size was determined by x-ray film in two projections: 1199 patients had normal heart size, 262 had borderline heart size, and 420 had enlarged hearts. The incidence of total cardiac death was three times greater in patients with enlarged hearts compared with patients with normal size hearts. The incidence of non-fatal reinfarctions, however, was independent of heart size at baseline. The timolol related reduction of total cardiac death compared with placebo was 40.7% in patients with normal heart size, 47.8% in patients with borderline heart size, and 38.2% in patients with enlarged hearts at baseline (intention to treat approach). The reduction of first non-fatal reinfarctions in the timolol group compared with placebo was, respectively, 31.7%, 41.2%, and 25.9%. Thus, timolol treatment appears to reduce cardiac death and non-fatal reinfarctions after myocardial infarction independent of heart size at baseline. Timolol treatment may be of special importance in patients with cardiomegaly, because of the very high incidence of cardiac mortality in this group of patients, and consequently a larger number of cardiac deaths may be prevented. PMID:6224500

  7. Protective efficacy of ellagic acid on glycoproteins, hematological parameters, biochemical changes, and electrolytes in myocardial infarcted rats.

    PubMed

    Kannan, M Mari; Quine, S Darlin; Sangeetha, T

    2012-07-01

    The cardioprotective property of ellagic acid in rats has been reported previously. The present study reveals the protective role of ellagic acid in biochemical parameters including serum iron, plasma iron binding capacity, uric acid, glycoprotein, and electrolytes along with hematological parameters. Rats were subcutaneously injected with isoproterenol (ISO) (100 mg/kg) for 2 days to induce myocardial infarction. ISO-induced rats showed a significant increase in their levels of serum iron, serum uric acid, and blood glucose, and a significant decrease in their levels of plasma iron binding capacity, serum total protein, albumin/globulin ratio, and heart glycogen, when compared with normal control rats. The altered hematological parameters were also observed in ISO-induced rats when compared with normal control rats. Pretreatment with ellagic acid at doses of 7.5 and 15 mg/kg produced significant beneficial effect by returning all the above-mentioned biochemical and hematological parameters to near normal levels.

  8. Antilipoperoxidative and antioxidant effects of S-allyl cysteine sulfoxide on isoproterenol-induced myocardial infarction in Wistar rats.

    PubMed

    Sangeetha, T; Quine, S Darlin

    2006-01-01

    Our study evaluates the preventive effect of S-allyl cysteine sulfoxide (SACS) on lipid peroxidative products and enzymic and nonenzymic antioxidants in isoproterenol (ISO) induced myocardial infarction in rats. The male Wistar rats were rendered myocardial infarction by ISO (150 mg kg(-1), once a day for two days). The concentrations of thiobarbituric acid reactive substances and lipid hydroperoxides were increased in hearts from ISO-treated rats, whereas the content of enzymic and nonenzymic antioxidants were declined in rats administered ISO. Oral pretreatment with SACS (40 mg kg(-1) and 80 mg kg(-1) daily for a period of 35 days) significantly (p < 0.05) decreased the lipid peroxidative products and significantly (p < 0.05) increased antioxidants in ISO-induced rats. Oral administration of SACS (40 mg kg(-1) and 80 mg kg(-1)) did not show any significant effect in normal rats. Thus, the present study shows that SACS exhibits antilipoperoxidative and antioxidant effects in experimental myocardial infarction.

  9. Cardioprotective potential of myricetin in isoproterenol-induced myocardial infarction in Wistar rats.

    PubMed

    Tiwari, Roshan; Mohan, Mahalaxmi; Kasture, Sanjay; Maxia, Andrea; Ballero, Mauro

    2009-10-01

    The study aimed to evaluate the protective role of myricetin obtained from Vitis vinifera (Vitaceae) on heart rate, electrocardiographic (ECG) patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphological and histopathological changes in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats. Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate and ST elevation in ECG, and a significant increase in the levels of cardiac marker enzymes - lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) in serum. Isoproterenol significantly reduced superoxide dismutase (SOD) and catalase (CAT) activity and increased vascular reactivity to various catecholamines. Pretreatment with myricetin (100 mg/kg, p.o. and 300 mg/kg, p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, levels of LDH, CK, AST, SOD, CAT, vascular reactivity changes and ECG patterns. Treatment with myricetin (100 mg/kg and 300 mg/kg) alone did not alter any of the parameters compared with vehicle treated Wistar rats. Myricetin treated animals showed a lesser degree of cellular infiltration in histopathological studies. Thus, myricetin (100 mg/kg and 300 mg/kg) ameliorates the cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

  10. Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction.

    PubMed

    Chuva de Sousa Lopes, Susana M; Feijen, Alie; Korving, Jeroen; Korchynskyi, Olexander; Larsson, Jonas; Karlsson, Stefan; ten Dijke, Peter; Lyons, Karen M; Goldschmeding, Roel; Doevendans, Pieter; Mummery, Christine L

    2004-11-01

    Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response.

  11. Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association.

    PubMed

    Mehta, Laxmi S; Beckie, Theresa M; DeVon, Holli A; Grines, Cindy L; Krumholz, Harlan M; Johnson, Michelle N; Lindley, Kathryn J; Vaccarino, Viola; Wang, Tracy Y; Watson, Karol E; Wenger, Nanette K

    2016-03-01

    Cardiovascular disease is the leading cause of mortality in American women. Since 1984, the annual cardiovascular disease mortality rate has remained greater for women than men; however, over the last decade, there have been marked reductions in cardiovascular disease mortality in women. The dramatic decline in mortality rates for women is attributed partly to an increase in awareness, a greater focus on women and cardiovascular disease risk, and the increased application of evidence-based treatments for established coronary heart disease. This is the first scientific statement from the American Heart Association on acute myocardial infarction in women. Sex-specific differences exist in the presentation, pathophysiological mechanisms, and outcomes in patients with acute myocardial infarction. This statement provides a comprehensive review of the current evidence of the clinical presentation, pathophysiology, treatment, and outcomes of women with acute myocardial infarction. © 2016 American Heart Association, Inc.

  12. NADPH oxidase hyperactivity induces plantaris atrophy in heart failure rats.

    PubMed

    Bechara, Luiz R G; Moreira, Jose B N; Jannig, Paulo R; Voltarelli, Vanessa A; Dourado, Paulo M; Vasconcelos, Andrea R; Scavone, Cristoforo; Ramires, Paulo R; Brum, Patricia C

    2014-08-20

    Skeletal muscle wasting is associated with poor prognosis and increased mortality in heart failure (HF) patients. Glycolytic muscles are more susceptible to catabolic wasting than oxidative ones. This is particularly important in HF since glycolytic muscle wasting is associated with increased levels of reactive oxygen species (ROS). However, the main ROS sources involved in muscle redox imbalance in HF have not been characterized. Therefore, we hypothesized that NADPH oxidases would be hyperactivated in the plantaris muscle of infarcted rats, contributing to oxidative stress and hyperactivation of the ubiquitin-proteasome system (UPS), ultimately leading to atrophy. Rats were submitted to myocardial infarction (MI) or Sham surgery. Four weeks after surgery, MI and Sham groups underwent eight weeks of treatment with apocynin, a NADPH oxidase inhibitor, or placebo. NADPH oxidase activity, oxidative stress markers, NF-κB activity, p38 MAPK phosphorylation, mRNA and sarcolemmal protein levels of NADPH oxidase components, UPS activation and fiber cross-sectional area were assessed in the plantaris muscle. The plantaris of MI rats displayed atrophy associated with increased Nox2 mRNA and sarcolemmal protein levels, NADPH oxidase activity, ROS production, lipid hydroperoxides levels, NF-κB activity, p38 MAPK phosphorylation and UPS activation. NADPH oxidase inhibition by apocynin prevented MI-induced skeletal muscle atrophy by reducing ROS production, NF-κB hyperactivation, p38 MAPK phosphorylation and proteasomal hyperactivity. Our data provide evidence for NADPH oxidase hyperactivation as an important source of ROS production leading to plantaris atrophy in heart failure rats, suggesting that this enzyme complex plays key role in skeletal muscle wasting in HF. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice.

    PubMed

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy.

  14. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice

    PubMed Central

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy. PMID:28386378

  15. [Effect of autologous platelet-rich plasma on heart infarction in sheep].

    PubMed

    Gallo, Ignacio; Sáenz, Alberto; Arévalo, Adolfo; Roussel, Sonia; Pérez-Moreiras, Ignacio; Artiñano, Edurne; Martínez-Peñuela, Ana; Esquide, Javier; Aspiroz, Antonio; Camacho, Ignacio

    2013-01-01

    Myocardial infarction is the most common cause of congestive heart failure. The objective of this work is to evaluate, in experimental animals, morphological and histological effects of the implantation of autologous platelet-rich plasma in infarcted heart sheep. Twenty-four ewes were used, they were surgically infarcted through left thoracotomy and two coronary arteries were ligated (first and second diagonal). After coronary artery ligation three sheep died of ventricular fibrillation. Three weeks after coronary ligation, sheep were reoperated through median sternotomy. Normal saline solution was injected in the infarcted zone in 6 of them (control group) whereas platelet gel was injected in 15 of them. All sheep were euthanized at 9 weeks of evolution of the second surgery. Noteworthy is the formation of new vessels in hematoxylin-eosin-stained sections and factor viii in plasma rich in growth-factors (PRGF)-treated hearts. Injection of platelet growth factors, PRGF, in previously infarcted sheep hearts promotes mitogenesis and angiogenesis. The use of autologous PRGF is simple and safe, causing no toxicity or immune-inflammatory reactions. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  16. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    PubMed Central

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  17. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Stoops, Thorne S; D'Souza, Manoranjan S

    2017-01-01

    We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  18. Human Engineered Heart Muscles Engraft and Survive Long-Term in a Rodent Myocardial Infarction Model

    PubMed Central

    Riegler, Johannes; Tiburcy, Malte; Ebert, Antje; Tzatzalos, Evangeline; Raaz, Uwe; Abilez, Oscar J.; Shen, Qi; Kooreman, Nigel G.; Neofytou, Evgenios; Chen, Vincent C.; Wang, Mouer; Meyer, Tim; Tsao, Philip S.; Connolly, Andrew J.; Couture, Larry A.; Gold, Joseph D.; Zimmermann, Wolfram H.; Wu, Joseph C.

    2015-01-01

    Rational Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell-derived cardiomyocte (ESC-CM) transplantation, thereby potentially preventing dilative remodelling and progression to heart failure. Objective Assessment of transport stability, long term survival, structural organisation, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction (MI) model. Methods and Results We constructed EHMs from ESC-CMs and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P=0.83, P=0.87). After ischemia/reperfusion (I/R) injury, EHMs were implanted onto immunocompromised rat hearts at 1 month to simulate chronic ischemia. Bioluminescence imaging (BLI) showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P=0.67), preserving up to 25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs −6.7±1.4% vs control −10.9±1.5%, n>12, P=0.05), we observed no difference between EHMs containing viable or non-viable human cardiomyocytes in this chronic xenotransplantation model (n>12, P=0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring. Conclusions EHM transplantation led to high engraftment rates, long term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic MI model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation. PMID:26291556

  19. Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat.

    PubMed

    Mnafgui, Kais; Hajji, Raouf; Derbali, Fatma; Gammoudi, Anis; Khabbabi, Gaddour; Ellefi, Hedi; Allouche, Noureddine; Kadri, Adel; Gharsallah, Neji

    2016-10-01

    This study aimed to evaluate the antithrombotic, anti-inflammatory and anti-cardiac remodeling properties of eugenol in isoproterenol-induced myocardial infarction in rats. Male Wistar rats were randomly divided into four groups, control, iso [100 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI] and pretreated animals with clopidogrel (0.2 mg/kg) and eugenol (50 mg/kg) orally for 7 days and intoxicated with isoproterenol (Iso + Clop) and (Iso + EG) groups. Isoproterenol-induced myocardial infarcted rats showed notable changes in the ECG pattern, increase in heart weight index, deterioration in the hemodynamic function and rise in plasma level of troponin-T, CK-MB and LDH and ALT by 316, 74, 172 and 45 %, respectively, with histological myocardium necrosis and cells inflammatory infiltration. In addition, significant increases in plasma levels of inflammatory biomarkers such as fibrinogen, α1, α2, β1, β2 and γ globulins with decrease level of albumin were observed in infarcted rats as compared to normal ones. Else, the angiotensin-converting enzyme (ACE) activity in plasma, kidney and heart of the isoproterenol-induced rats was significantly increased by 34, 47 and 93 %, respectively, as compared to normal group. However, the administration of eugenol induced a clear improvement in cardiac biomarkers injury, reduced inflammatory mediators proteins, increased heart activities of superoxide dismutase and glutathione peroxidase with reduce in thiobarbituric acid-reactive substances content and inhibition of ventricular remodeling process through inhibition of ACE activity. Overall, eugenol evidences high preventive effects from cardiac remodeling process.

  20. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-03-11

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.

  1. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    PubMed

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats.

  2. CARDIOPROTECTIVE ROLES OF THE CHINESE MEDICINAL FORMULA BAO-XIN-TANG ON ACUTE MYOCARDIAL INFARCTION IN RATS

    PubMed Central

    Wang, Yang; Wang, Weihao; Peng, Weijun; Liu, Weiping; Cai, Weijun; Xia, Zian; Zhang, Honggeng; Xing, and Zhihua

    2017-01-01

    Background: Bao-Xin-Tang (BXT) is a traditional Chinese medicinal formula used for the treatment of coronary heart disease and known to have favorable therapeutic benefits. The current study was designed to determine whether BXT has a cardioprotective role for acute myocardial infarction. The underlying mechanisms were also explored. Materials and Methods: The Sprague-Dawley rat model of acute myocardial infarction was established by occluding the left anterior descending branch of the coronary artery. After a 3-h ischemic period, we determined the myocardial infarction size, inflammatory components, and antioxidant activities. Results: The data showed that BXT could reduce the infarction size and lower the levels of C-reactive protein, interleukin-6, and myeloperoxidase, and increase the activities of superoxide dismutase and the anti-inflammatory cytokine, interleukin-10. These results indicate that administration of BXT, following acute myocardial infarction, could reduce infarct size. Conclusion: The effects of BXT may be related to its anti-inflammatory and anti-oxidative properties. PMID:28573223

  3. Protective mechanism of quercetin on acute myocardial infarction in rats.

    PubMed

    Li, B; Yang, M; Liu, J W; Yin, G T

    2016-03-11

    To investigate the protective mechanism of quercetin on acute myocardial infarction (AMI) rats, an AMI rat model was established by ligating the left coronary anterior descending branch. The rats were randomly divided into the model group and low- and high-dose quercetin groups. The control group comprised sham-operated rats. The rats in the low- and high-dose quercetin groups were administered 100 and 400 mg/kg quercetin, respectively, by gavage. The rats in the control and model groups were administered isometric normal saline once daily for one week. The mRNA and protein levels of TNF-α and IL-1β in the myocardial tissue of rats were detected in each group by real time polymerase chain reaction and enzyme-linked immunosorbent assay. Malondialdehyde (MDA) content in the myocardial tissue and superoxide dismutase (SOD) and catalase (CAT) activities were detected using a colorimetric method. The level of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with those in the control group, the mRNA and protein levels of TNF-α, IL-1β and MDA content in the model, low-, and high-dose groups significantly increased. SOD and CAT activities decreased significantly. The cell apoptosis index increased significantly  (P < 0.05). Compared with those in the model group, the mRNA and protein levels of TNF-α and IL-1β and MDA content in myocardial tissue of rats in the low-dose and high-dose groups decreased significantly. SOD and CAT activities increased significantly. The cell apoptosis index significantly reduced (P < 0.05). In conclusion, quercetin has significant anti-inflammatory, antioxidant, and anti-apoptotic effects on AMI rats and can effectively protect against myocardium damage.

  4. Nobiletin attenuates adverse cardiac remodeling after acute myocardial infarction in rats via restoring autophagy flux.

    PubMed

    Wu, Xiaoqian; Zheng, Dechong; Qin, Yuyan; Liu, Zumei; Zhang, Guiping; Zhu, Xiaoyan; Zeng, Lihuan; Liang, Zhenye

    2017-10-14

    Our previous study showed that autophagy flux was impaired with sustained heart ischemia, which exacerbated adverse cardiac remodeling after acute myocardial infarction (AMI). Here we investigated whether Nobiletin, a citrus polymethoxylated flavonoids, could restore the autophagy flux and improve cardiac prognosis after AMI. AMI was induced by ligating left anterior descending (LAD) coronary artery in rats. Nobiletin improved the post-infarct cardiac dysfunction significantly and attenuated adverse cardiac remodeling. Meanwhile, Nobiletin protected H9C2 cells against oxygen glucose deprivation (OGD) in vitro. The impaired autophagy flux due to ischemia was ameliorated after Nobiletin treatment by testing the autophagy substrate, LC3BⅡ and P62 protein level both in vivo and in vitro. GFP-mRFP-LC3 adenovirus transfection also supported that Nobiletin restored the impaired autophagy flux. Specifically, the autophagy flux inhibitor, chloroquine, but not 3 MA, alleviated Nobiletin-mediated protection against OGD. Notably, Nobiletin does not affect the activation of classical upstream autophagy signaling pathways. However, Nobiletin increased the lysosome acidation which also supported that Nobiletin accelerated autophagy flux. Taken together, our findings suggested that Nobiletin restored impaired autophagy flux and protected against acute myocardial infarction, suggesting a potential role of autophagy flux in Nobiletin-mediated myocardial protection. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Cardioprotective effect of linseed oil against isoproterenol-induced myocardial infarction in Wistar rats: a biochemical and electrocardiographic study.

    PubMed

    Derbali, Amal; Mnafgui, Kais; Affes, Marwa; Derbali, Fatma; Hajji, Raouf; Gharsallah, Neji; Allouche, Noureddine; El Feki, Abdelfattah

    2015-06-01

    The present study was designed to evaluate the cardioprotective effect of Tunisian flaxseed oil (Linum usitatissimum) against isoproterenol-induced myocardial infarction in rats by studying hypertensive and cardiac damage markers especially electrocardiographic changes and troponin T serum level. In vitro, the extracted oil showed an important inhibition of angiotensin converting enzyme (ACE) with an IC50 = 85.96 μg/ml. According to chemical analysis, this extract is composed essentially of alpha linolenic acid (ALA), an n-3 polyunsaturated fatty acid (58.59 %). Male rats were randomly divided into three groups, namely control (C), isoproterenol (ISO), and isoproterenol-treated group with flaxseed oil (FO + ISO). Isoproterenol injection showed changes in ECG pattern, including ST-segment elevation (diagnostic of myocardial infarction), increase in the serum levels of Troponin T and cardiac injury markers (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT)). However, Linum oil pre-co-treatment prevented almost all the parameters isoproterenol-induced myocardial infarction in rats. Results of the present study proved that flaxseed oil has a significant effect by heart protection against isoproterenol-induced myocardial infarction through beneficial effect of the important fraction of ALA.

  6. Effects of exercise of different intensities on the angiogenesis, infarct healing, and function of the left ventricle in postmyocardial infarction rats.

    PubMed

    Tang, Xiang-Yu; Hong, Hua-Shan; Chen, Liang-Long; Lin, Xiao-Hong; Lin, Jun-Hua; Lin, Zhang

    2011-11-01

    Lifestyle interventions, including physical exercise, are feasible options for the prevention and treatment of cardiovascular diseases. In this study, the effects of exercise of different intensities on the infarct region, function, and angiogenesis of the left ventricle (LV) in postmyocardial infarction (MI) rats were investigated and the levels of vascular endothelial growth factor (VEGF) proteins in the LV and plasma were examined. Male Sprague-Dawley rats were randomly assigned to six groups. The exercise-trained rats observed a daily 60-min treadmill routine 5 days/weeks for 6 weeks. Different treadmill speeds were used in the high-intensity exercise (HIE), moderate-intensity exercise (MIE), and low-intensity exercise (LIE) groups, whereas the untrained rats remained sedentary (Sed). At 6 weeks, all rats underwent either an acute MI operation or a sham (Sh) MI operation 24 h after their last treadmill exercise or the corresponding Sed protocol. They were then killed 7 days after recovery. Echocardiographic and hemodynamic measurements were taken at the end of the experimental protocol. The infarct regions were analyzed using Masson's trichrome staining, whereas intramyocardial microvessels were detected using Factor VIII-related antigen staining. The cardiac VEGF protein levels were determined by western blotting analysis, and plasma VEGF concentrations were examined by enzyme-linked immunosorbent assay. Compared with the corresponding parameters in the Sed-Sh group, LV function did not significantly ameliorate and microvessel density did not increase in the MIE-Sh group. Compared with the Sed-MI group, the MIE-MI and HIE-MI groups had significantly reduced LV infarct size, improved hemodynamic parameters, and increased fractional shortening, scar thickness, and microvessel density, these parameters did not significantly change in the LIE-MI group. In addition, the MIE-MI and HIE-MI rats had significant differences in hemodynamic parameters and microvessel

  7. The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities.

    PubMed

    Frangogiannis, Nikolaos G

    2014-03-01

    Extensive necrosis of ischemic cardiomyocytes in the infarcted myocardium activates the innate immune response triggering an intense inflammatory reaction. Release of danger signals from dying cells and damaged matrix activates the complement cascade and stimulates Toll-like receptor/interleukin-1 signaling, resulting in the activation of the nuclear factor-κB system and induction of chemokines, cytokines, and adhesion molecules. Subsequent infiltration of the infarct with neutrophils and mononuclear cells serves to clear the wound from dead cells and matrix debris, while stimulating reparative pathways. In addition to its role in repair of the infarcted heart and formation of a scar, the immune system is also involved in adverse remodeling of the infarcted ventricle. Overactive immune responses and defects in suppression, containment, and resolution of the postinfarction inflammatory reaction accentuate dilative remodeling in experimental models and may be associated with chamber dilation, systolic dysfunction, and heart failure in patients surviving a myocardial infarction. Interventions targeting the inflammatory response to attenuate adverse remodeling may hold promise in patients with myocardial infarction that exhibit accentuated, prolonged, or dysregulated immune responses to the acute injury.

  8. Comparison of cumulative planimetry versus manual dissection to assess experimental infarct size in isolated hearts.

    PubMed

    Riess, Matthias L; Rhodes, Samhita S; Stowe, David F; Aldakkak, Mohammed; Camara, Amadou K S

    2009-01-01

    Infarct size (IS) is an important variable to estimate cardiac ischemia/reperfusion injury in animal models. Triphenyltetrazolium chloride (TTC) stains viable cells red while leaving infarcted cells unstained. To quantify IS, infarcted and non-infarcted tissue is often manually dissected and weighed (IS-DW). An alternative is to measure infarcted areas by cumulative planimetry (IS-CP). We prospectively compared these two methods in 141 Langendorff-prepared guinea pig hearts (1.44+/-0.02 g) that were part of different studies on mechanisms of cardioprotection. Hearts were perfused with Krebs-Ringer's and subjected to 30 min global ischemia after various cardioprotective treatments. Two hours after reperfusion hearts were cut into 6-7 transverse sections (3mm) and stained for 5 min in 1% TTC and 0.1M KH2PO4 buffer (pH 7.4, 38 degrees C). Each slice was first scanned and its infarcted area measured with Image 1.62 software (NIH). Infarctions in individual slices of each heart were averaged (IS-CP) on the basis of their weight. After scanning, IS-DW was determined by careful manual dissection of infarcted from non-infarcted tissue and measuring their respective total weight. We found limited tissue permeation of TTC in relation to the slice thickness leaving tissue in the center unstained, as well as significant cross-contamination of stained vs. unstained tissue after manual dissection. IS-CP and IS-DW ranged from 6.0 to 73.1% and 19.4 to 70.5%, respectively, and correlated as follows: IS-DW=(27.6+/-1.4)+(0.518+/-0.038) * IS-CP; r=0.75 (Pearson), p<0.001. In addition, IS-CP correlated better with return of function after reperfusion like developed left ventricular pressure, contractility and relaxation, and myocardial oxygen consumption. Despite a good correlation between both methods, limited tissue permeation by TTC diffusion and limited precision in the ability to manually dissect stained from unstained tissue leads to an overestimation of infarct size by

  9. MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart.

    PubMed

    Dakhlallah, Duaa; Zhang, Jianying; Yu, Lianbo; Marsh, Clay B; Angelos, Mark G; Khan, Mahmood

    2015-03-01

    : Cardiovascular disease is the number 1 cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure. Cell therapy (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA (miRNA) in the cardiac muscle and is downregulated in patients with MI. We hypothesized that reprogramming MSCs using miRNA mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs, and the levels of miR-133a were measured by quantitative real-time polymerase chain reaction. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic hearts. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels, and apoptosis-related genes (Apaf-1, Caspase-9, and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function, and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, quantitative real-time polymerase chain reaction data demonstrated a significant decrease in expression of the proapoptotic genes; Apaf-1, caspase-9, and caspase-3 in the miR-133a mimic transplanted group. Furthermore, luciferase reporter assay confirmed that miR-133a is a direct target for Apaf-1. Overall, bioengineering of stem

  10. Exercise training reduces cardiac dysfunction and remodeling in ovariectomized rats submitted to myocardial infarction.

    PubMed

    Almeida, Simone Alves de; Claudio, Erick Roberto Gonçalves; Mengal, Vinícius; Mengal, Vinícius Franskoviaky; Oliveira, Suelen Guedes de; Merlo, Eduardo; Podratz, Priscila Lang; Gouvêa, Sônia Alves; Graceli, Jones Bernardes; de Abreu, Gláucia Rodrigues

    2014-01-01

    The aim of this study was to evaluate whether exercise training (ET) prevents or minimizes cardiac dysfunction and pathological ventricular remodeling in ovariectomized rats subjected to myocardial infarction (MI) and to examine the possible mechanisms involved in this process. Ovariectomized Wistar rats were subjected to either MI or fictitious surgery (Sham) and randomly divided into the following groups: Control, OVX+SHAMSED, OVX+SHAMET, OVX+MISED and OVX+MIET. ET was performed on a motorized treadmill (5x/wk, 60 min/day, 8 weeks). Cardiac function was assessed by ventricular catheterization and Dihydroethidium fluorescence (DHE) was evaluated to analyze cardiac oxidative stress. Histological analyses were made to assess collagen deposition, myocyte hypertrophy and infarct size. Western Blotting was performed to analyze the protein expression of catalase and SOD-2, as well as Gp91phox and AT1 receptor (AT1R). MI-trained rats had significantly increased in +dP/dt and decreased left ventricular end-diastolic pressure compared with MI-sedentary rats. Moreover, oxidative stress and collagen deposition was reduced, as was myocyte hypertrophy. These effects occurred in parallel with a reduction in both AT1R and Gp91phox expression and an increase in catalase expression. SOD-2 expression was not altered. These results indicate that ET improves the functional cardiac parameters associated with attenuation of cardiac remodeling in ovariectomized rats subjected to MI. The mechanism seems to be related to a reduction in the expression of both the AT1 receptor and Gp91phox as well as an increase in the antioxidant enzyme catalase, which contributes to a reduction in oxidative stress. Therefore, ET may be an important therapeutic target for the prevention of heart failure in postmenopausal women affected by MI.

  11. Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

    PubMed Central

    Wu, Aiming; Zhai, Jianying; Zhang, Dongmei; Lou, Lixia; Zhu, Haiyan; Gao, Yonghong; Chai, Limin; Xing, Yanwei; Lv, Xiying; Zhu, Lingqun; Zhao, Mingjing; Wang, Shuoren

    2013-01-01

    Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI). Methods. Male Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group) with sample size (n) of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion). Wenxin Granule (1.35 g/kg/day), metoprolol (12 mg/kg/day), and distilled water (5 mL/kg/day for the control and model groups) were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E) dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Serum angiotensin II (Ang II) concentration was measured using the enzyme-linked immunosorbent assay (ELISA). Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI. PMID:23997803

  12. Impaired baroreflex control of vascular resistance and heart rate in acute myocardial infarction.

    PubMed Central

    Imaizumi, T; Takeshita, A; Makino, N; Ashihara, T; Yamamoto, K; Nakamura, M

    1984-01-01

    The baroreflex control of vascular resistance and heart rate was studied in 11 patients to determine whether it is impaired in patients with acute myocardial infarction. Reflex forearm vasoconstriction in response to lower body negative pressure at 40 mm Hg was less in the early convalescent phase (mean seven days) than in the late convalescent phase (mean 41 days). Pressor as well as vasoconstricting responses to the cold pressor test did not differ between the early and late convalescent phases. The slope of the regression line relating systolic blood pressure and the RR interval during a transient rise in blood pressure produced by intravenous phenylephrine was appreciably reduced in the early convalescent phase of myocardial infarction. These results suggest that baroreflex control of vascular resistance and heart rate is impaired in patients with acute myocardial infarction. PMID:6477780

  13. [Changes in heart rate variability after myocardial infarction. Value of Poincareé's diagram].

    PubMed

    Copie, X; Le Heuzey, J Y; Iliou, M C; Pousset, F; Lavergne, T; Guize, L

    1995-11-01

    The variability of the heart rate is reduced after myocardial infarction. It then progressively increases, to return to near normal values after several months. However, these changes in heart rate variability occur at the same time as slowing of the heart rate which makes interpretation difficult. Poincaré's diagram is constructed from a Holter recording plotting each RR interval against the preceding RR interval. The authors have developed a geometric approach to this diagram to evaluate parasympathetic tone for a given heart rate. By measuring the dispersion in height of the Poincaré's diagram, the authors evaluate the shor-term variability for a given RR interval. Two 24 hr Holter recordings were performed in 52 patients at one and two weeks after a myocardial infarction. The dispersion in the height of the Poincaré's diagrams was measured at the 10th, 25th, 50th, 75th and 90th percentiles of the total dispersion. The authors have shown an increase in the short-term variability of the shortest RR intervals (1th, 25th and 50th percentiles) which is not observed in the longer RR intervals (75th and 90th percentiles). In conclusion, theres is an increase in the heart rate variability at the shortest RR intervals. This suggests that the recovery of parasympathic tone after myocardial infarction occurs mainly at the fastest heart rates.

  14. Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats

    PubMed Central

    2013-01-01

    Background Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. Methods MI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. Results T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to −4 expression was also observed in T4 treated MI rats. Conclusions These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area

  15. Eplerenone: new drug. Recent myocardial infarction with heart failure: a spironolactone me too.

    PubMed

    2006-04-01

    (1) Heart failure is diagnosed on the basis of both clinical symptoms and evaluation of cardiac function (preferably measured by echocardiography). Left ventricular dysfunction is defined as a left ventricular ejection fraction (LVEF) below 40%. The drugs of choice for chronic heart failure are certain angiotensin-converting-enzyme (ACE) inhibitors, some diuretics, some betablockers, and spironolactone. In one trial, spironolactone greatly reduced mortality at 24 months (35%, compared with 46% on placebo, p <0.001). (2) Eplerenone, a spironolactone derivative, is marketed for the treatment of left ventricular dysfunction in heart failure patients with recent myocardial infarction. (3) The EPHESUS study, a double-blind, placebo-controlled trial involving 6632 patients, showed a significant reduction in the overall mortality rate among patients with heart failure and recent myocardial infarction treated with eplerenone for 16 months (16.7% versus 14.4%; p = 0.008). This improvement was mainly due to a reduction in mortality during the first month of treatment. Eplerenone has not been compared with spironolactone, although the latter was known to be effective before the EPHESUS trial was conducted. (4) Severe hyperkalemia is frequent with eplerenone, occurring in 5.5% of patients. The risk of hyperkalaemia increases with renal failure and co-administration of potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists and nonsteroidal antiinflammatory drugs. (5) In the short term, the incidence of gynecomastia in patients taking eplerenone seems to be low. (6) In patients who develop heart failure after myocardial infarction, an indirect comparison of available data favours spironolactone over eplerenone (better efficacy, lower risk of hyperkalemia). (7) In France, treatment with eplerenone is about 9 times more expensive than spironolactone. (8) Spironolactone remains the treatment of choice for patients with heart failure and incapacitating

  16. Comparison of Cumulative Planimetry versus Manual Dissection to Assess Experimental Infarct Size in Isolated Hearts

    PubMed Central

    Riess, Matthias L.; Rhodes, Samhita S.; Stowe, David F.; Aldakkak, Mohammed; Camara, Amadou K.S.

    2013-01-01

    Introduction Infarct size (IS) is an important variable to estimate cardiac ischemia/reperfusion injury in animal models. Triphenyltetrazoliumchloride (TTC) stains viable cells red while leaving infarcted cells unstained. To quantify IS, infarcted and non-infarcted tissue is often manually dissected and weighed (IS-DW). An alternative is to measure infarcted areas by cumulative planimetry (IS-CP). Methods We prospectively compared these two methods in 141 Langendorff-prepared guinea pig hearts (1.44±0.02 g) that were part of different studies on mechanisms of cardioprotection. Hearts were perfused with Krebs-Ringer’s and subjected to 30 min global ischemia after various cardioprotective treatments. Two hours after reperfusion hearts were cut into 6-7 transverse sections (3 mm) and stained for 5 min in 1% TTC and 0.1 M KH2PO4 buffer (pH 7.4, 38°C). Each slice was first scanned and its infarcted area measured with Image 1.62 software (NIH). Infarctions in individual slices of each heart were averaged (IS-CP) on the basis of their weight. After scanning, IS-DW was determined by careful manual dissection of infarcted from noninfarcted tissue and measuring their respective total weight. Results We found limited tissue permeation of TTC in relation to the slice thickness leaving tissue in the center unstained, as well as significant cross-contamination of stained vs. unstained tissue after manual dissection. IS-CP and IS-DW ranged from 6.0 to 73.1% and 19.4 to 70.5%, respectively, and correlated as follows: IS-DW = (27.6±1.4) + (0.518±0.038) • IS-CP; r = 0.75 (Pearson), P<0.001. In addition, IS-CP correlated better with return of function after reperfusion like developed left ventricular pressure, contractility and relaxation, and myocardial oxygen consumption. Discussion Despite a good correlation between both methods, limited tissue permeation by TTC diffusion and limited precision in the ability to manually dissect stained from unstained tissue leads to an

  17. Radiation-induced heart disease in rats

    SciTech Connect

    Lauk, S.; Kiszel, Z.; Buschmann, J.; Trott, K.R.

    1985-04-01

    After local irradiation of the rat heart with X ray doses of over 10 Gy (single dose), animals developed symptoms of radiation-induced heart disease, which at higher doses would lead to fatal cardiac failure. The LD 50 at 1 year was between 15 Gy and 20 Gy. The pericardium and epicardium responded to irradiation with exudative pericarditis after 4 months. Focal myocardial damage was secondary to progressive capillary damage.

  18. Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart

    PubMed Central

    Shi, Jianru; Dai, Wangde; Hale, Sharon L.; Brown, David A.; Wang, Miao; Han, Xianlin; Kloner, Robert A.

    2016-01-01

    Aims We have observed that Bendavia, a mitochondrial-targeting peptide that binds the phospholipid cardiolipin and stabilizes the components of electron transport and ATP generation, improves cardiac function and prevents left ventricular remodeling in a 6 week rat myocardial infarction (MI) model. We hypothesized that Bendavia restores mitochondrial biogenesis and gene expression, suppresses cardiac fibrosis, and preserves sarco/endoplasmic reticulum (SERCA2a) level in the noninfarcted border zone of infarcted hearts. Main methods Starting 2 hours after left coronary artery ligation, rats were randomized to receive Bendavia (3 mg/kg/day), water or sham operation. At 6 weeks, PCR array and qRT-PCR was performed to detect gene expression. Picrosirius red staining was used to analyze collagen deposition. Key findings There was decreased expression of 70 out of 84 genes related to mitochondrial energy metabolism in the border zone of untreated hearts. This down-regulation was largely reversed by Bendavia treatment. Downregulated mitochondrial biogenesis and glucose & fatty acid (FA) oxidation related genes were restored by administration of Bendavia. Matrix metalloproteinase (MMP9) and tissue inhibitor of metalloproteinase (TIMP1) gene expression were significantly increased in the border zone of untreated hearts. Bendavia completely prevented up-regulation of MMP9, but maintained TIMP1 gene expression. Picrosirius red staining demonstrated that Bendavia suppressed collagen deposition within border zone. In addition, Bendavia showed a trend toward restoring SERCA2a expression. Significance Bendavia restored expression of mitochondrial energy metabolism related genes, prevented myocardial matrix remodeling and preserved SERCA2a expression in the noninfarcted border, which may have contributed to the preservation of cardiac structure and function. PMID:26431885

  19. Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats.

    PubMed

    Pasqualin, Rubens Campana; Mostarda, Cristiano Teixeira; Souza, Leandro Ezequiel de; Vane, Matheus Fachini; Sirvente, Raquel; Otsuki, Denise Aya; Torres, Marcelo Luís Abramides; Irigoyen, Maria Cláudia Costa; Auler, José Otávio Costa

    2016-05-01

    To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.

  20. CXCR4 expression is associated with time-course permanent and temporary myocardial infarction in rats.

    PubMed

    Kiani, Ali Asghar; Babaei, Fereshteh; Sedighi, Mehrnoosh; Soleimani, Azam; Ahmadi, Kolsum; Shahrokhi, Somayeh; Anbari, Khatereh; Nazari, Afshin

    2017-06-01

    Experimental myocardial infarction triggers secretion of Stromal cell-derived factor1 and lead to increase in the expression of its receptor "CXCR4" on the surface of various cells. The aim of this study was to evaluate the expression pattern of CXCR4 in peripheral blood cells following time-course permanent and temporary ischemia in rats. Fourteen male Wistar rats were divided into two groups of seven and were placed under permanent and transient ischemia. Peripheral blood mononuclear cells were isolated at different time points, RNAs extracted and applied to qRT-PCR analysis of the CXCR4 gene. Based on repeated measures analysis of variance, the differences in the expression levels of the gene in each of the groups were statistically significant over time (the effect of time) (P<0.001). Additionally, the difference in gene expression between the two groups was statistically significant (the effect of group), such that at all times, the expression levels of the gene were significantly higher in the permanent ischemia than in the transient ischemia group (P<0.001). Moreover, the interactive effect of time-group on gene expression was statistically significant (P<0.001). CXCR4 is modulated in an induced ischemia context implying a possible association with myocardial infarction. Checking of CXCR4 expression in the ischemic changes shows that damage to the heart tissue trigger the secretion of inflammatory chemokine SDF, Followed by it CXCR4 expression in blood cells. These observations suggest that changes in the expression of CXCR4 may be considered a valuable marker for monitoring myocardial infarction.

  1. Determination of myocardial infarction size in rats by echocardiography and tetrazolium staining: correlation, agreements, and simplifications.

    PubMed

    dos Santos, L; Mello, A F S; Antonio, E L; Tucci, P J F

    2008-03-01

    Triphenyltetrazolium chloride (TTC) staining and echocardiography (ECHO) are methods used to determine experimental myocardial infarction (MI) size, whose practical applicability should be expanded. Our objectives were to analyze the accuracy of ECHO in determining infarction size in rats during the first days following coronary occlusion and to test whether a simplified single measurement by TTC correctly indicates MI size, as determined by the average value for multiple slices. Infarction was induced in female Wistar rats by coronary artery occlusion and MI size analysis was performed after the acute (7th day) and chronic periods (after 4 weeks) by ECHO matched with TTC. ECHO and TTC showed similar values of MI size (% of left ventricle perimeter) in acute (ECHO: 33 +/- 11, TTC: 35 +/- 14) and chronic (ECHO: 38 +/- 14, TTC: 39 +/- 13 periods), and also presented an excellent correlation (r = 0.92, P < 0.001). Although measurements from different heart planes showed discrepancies, a single measurement acquired from the mid-ventricular level by TTC was a good estimate of MI size calculated by the average of multiple planes, with minimal disagreement (Bland-Altman test with mean ratio bias of 0.99 +/- 0.07) and close to an ideal correlation (r = 0.99, P < 0.001). In the present study, ECHO was confirmed as a useful method for the determination of MI size even in the acute phase. Also, the single measure of a mid-ventricular section proposed as a simplification of the TTC method is a satisfactory prediction of average MI extension.

  2. Tachycardia in post-infarction hearts: insights from 3D image-based ventricular models.

    PubMed

    Arevalo, Hermenegild; Plank, Gernot; Helm, Patrick; Halperin, Henry; Trayanova, Natalia

    2013-01-01

    Ventricular tachycardia, a life-threatening regular and repetitive fast heart rhythm, frequently occurs in the setting of myocardial infarction. Recently, the peri-infarct zones surrounding the necrotic scar (termed gray zones) have been shown to correlate with ventricular tachycardia inducibility. However, it remains unknown how the latter is determined by gray zone distribution and size. The goal of this study is to examine how tachycardia circuits are maintained in the infarcted heart and to explore the relationship between the tachycardia organizing centers and the infarct gray zone size and degree of heterogeneity. To achieve the goals of the study, we employ a sophisticated high-resolution electrophysiological model of the infarcted canine ventricles reconstructed from imaging data, representing both scar and gray zone. The baseline canine ventricular model was also used to generate additional ventricular models with different gray zone sizes, as well as models in which the gray zone was represented as different heterogeneous combinations of viable tissue and necrotic scar. The results of the tachycardia induction simulations with a number of high-resolution canine ventricular models (22 altogether) demonstrated that the gray zone was the critical factor resulting in arrhythmia induction and maintenance. In all models with inducible arrhythmia, the scroll-wave filaments were contained entirely within the gray zone, regardless of its size or the level of heterogeneity of its composition. The gray zone was thus found to be the arrhythmogenic substrate that promoted wavebreak and reentry formation. We found that the scroll-wave filament locations were insensitive to the structural composition of the gray zone and were determined predominantly by the gray zone morphology and size. The findings of this study have important implications for the advancement of improved criteria for stratifying arrhythmia risk in post-infarction patients and for the development of

  3. Intracoronary hypothermia for acute myocardial infarction in the isolated beating pig heart

    PubMed Central

    Otterspoor, Luuk C; van Nunen, Lokien X; Rosalina, Tilaï T; Veer, Marcel van’t; Tuijl, Sjoerd Van; Stijnen, Marco; Rutten, Marcel CM; van de Vosse, Frans N; Pijls, Nico HJ

    2017-01-01

    Hypothermia may attenuate reperfusion injury and thereby improve acute myocardial infarction therapy. Systemic cooling trials failed to reduce infarct size, perhaps because the target temperature was not reached fast enough. The use of selective intracoronary hypothermia combined with intracoronary temperature monitoring allows for titrating to target temperature and optimizing the cooling rate. We aimed to the test the feasibility of intracoronary cooling for controlled, selective myocardial hypothermia in an isolated beating pig heart. In five porcine hearts the left anterior descending artery (LAD) was occluded by an over-the-wire balloon (OTWB). After occlusion, saline at 22°C was infused through the OTWB lumen for 5 minutes into the infarct area at a rate of 30 ml/min. Thereafter the balloon was deflated but infusion continued with saline at 4°C for 5 minutes. Distal coronary temperature was continuously monitored by a pressure/temperature guidewire. Myocardial temperature at several locations in the infarct and control areas was recorded using needle thermistors. In the occlusion phase, coronary temperature decreased by 11.4°C (range 9.4-12.5°C). Myocardial temperature throughout the infarct area decreased by 5.1°C (range 1.8-8.1°C) within three minutes. During the reperfusion phase, coronary temperature decreased by 6.2°C (range 4.1-10.3°C) and myocardial temperature decreased by 4.5°C (range 1.5-7.4°C). Myocardial temperature outside the infarct area was not affected. In the isolated beating pig heart with acute occlusion of the LAD, we were able to rapidly “induce, maintain, and control” a stable intracoronary and myocardial target temperature of at least 4°C below body temperature without side effects and using standard PCI equipment, justifying further studies of this technique in humans. PMID:28337283

  4. Influence of coronary architecture on the variability in myocardial infarction induced by coronary ligation in rats.

    PubMed

    Kainuma, Satoshi; Miyagawa, Shigeru; Fukushima, Satsuki; Tsuchimochi, Hirotsugu; Sonobe, Takashi; Fujii, Yutaka; Pearson, James T; Saito, Atsuhiro; Harada, Akima; Toda, Koichi; Shirai, Mikiyasu; Sawa, Yoshiki

    2017-01-01

    It has been shown that the size of myocardial infarction in rats created by coronary ligation technique is not uniform, varying from 4% to 65%. We hypothesized that infarct size variability induced by coronary artery ligation might be caused by coronary artery branching pattern. Coronary artery angiography was performed in 50 normal Lewis rats and in chronic myocardial infarction models in which coronary artery was ligated immediately below the left atrial appendage or 2mm distal to the left atrial appendage (n = 25 for each), followed by histological analysis. Unlike the human, the rats had a single major septal artery arising from the proximal part of the left coronary artery (n = 30) or right coronary artery (n = 20). There were three branching patterns of left circumflex artery (LCX): 33 (66%) had LCX branching peripherally from a long left main coronary artery (LMCA), while the remainder 17 (34%) had the LCX branching from the proximal part of the septal artery or a short LMCA. The rats with distal coronary ligation presented myocardial infarction localized to an anterior territory irrespective of LCX branching pattern. In the rats with proximal coronary ligation, 64% (n = 16) had broad myocardial infarction involving the anterior and lateral territories, while the remainder (36%, n = 9) had myocardial infarction localized to an anterior territory with the intact LCX arising proximally from a short LMCA. The interventricular septum was spared from infarction in all rats because of its anatomical location. Infarct size variations were caused not only by ligation site but also by varying LCX branching patterns. There are potential risks to create different sizes of myocardial infarction, particularly when targeting a broad range of myocardial infarction. The territory of the septal artery always appears to be spared from myocardial infarction induced by the coronary ligation technique.

  5. Heart fatty acid binding protein in the diagnosis of myocardial infarction: where do we stand today?

    PubMed

    Colli, Andrea; Josa, Miguel; Pomar, Jose Luis; Mestres, Carlos Alberto; Gherli, Tiziano

    2007-01-01

    Heart fatty acid binding protein (hFABP) is a novel small cytosolic protein that is abundant in the heart. It is highly cardiac-specific (i.e. expressed primarily in cardiac tissue), but is also expressed at low concentrations in tissues outside the heart. After myocardial ischemic damage, hFABP can be detected in the blood as early as 1-3 h after onset of chest pain, with peak values reached at 6-8 h and plasma levels returning to normal within 24-30 h. hFABP's clinical diagnostic value is very limited in the presence of renal failure and skeletal muscle diseases as it is completely renally eliminated. In these conditions, the diagnosis of acute myocardial infarction (AMI) may be overestimated. The combination of initial hFABP release after symptom onset, rapid kidney clearance from the circulation and high cardiac specificity suggests great potential for clinical use. Serial measurements of hFABP in the first 24 h after onset of symptoms in AMI patients can: (a) identify patients who are susceptible to reperfusion strategies, (b) detect perioperative AMIs, (c) distinguish patients who reperfuse their infarct-related artery from those who do not, as early as 30 min after starting thrombolytic treatment, (d) detect re-infarction if it occurs within 10 h after symptom onset, and (e) permit an accurate estimation of myocardial infarct size providing important prognosis information.

  6. Intramyocardial sustained delivery of basic fibroblast growth factor improves angiogenesis and ventricular function in a rat infarct model.

    PubMed

    Iwakura, Atsushi; Fujita, Masatoshi; Kataoka, Kazuaki; Tambara, Keiichi; Sakakibara, Yutaka; Komeda, Masashi; Tabata, Yasuhiko

    2003-05-01

    Recently we have demonstrated that the release of basic fibroblast growth factor (bFGF) from a biodegradable gelatin hydrogel carrier depends on the degradation of hydrogel in vivo. The purpose of our study was to assess whether bFGF-incorporating gelatin hydrogels induce myocardial angiogenesis and improve left ventricular function in the infarcted myocardium of rats. Studies were conducted in 22 Lewis rats after a 4-week ligation of the proximal left anterior descending coronary artery. The rats were randomized into the following two groups: the control group (n = 11) had an intramyocardial injection of saline alone, and the FGF group (n = 11) had gelatin hydrogel microspheres containing 100 microg of bFGF injected into the border zone of the infarct area after the repeat left thoracotomy. For visualization of the regional myocardial blood flow in the rat heart, (201)Tl images were taken just before and 4 weeks after the treatment using a 4-head single photon emission computed tomography scanner with pinhole collimators. Left ventricular function was also assessed with echocardiography and a micromanometer-tipped catheter. Finally, the extent of myocardial angiogenesis was evaluated quantitatively in the postmortem analysis. The (201)Tl defect score in the control group remained unchanged before and after the treatment, whereas it decreased significantly in the FGF group. Both regional and global left ventricular function was significantly better in the FGF group compared with the control group. The vascular density in the border zone of the infarct in the FGF group was significantly higher than that in the control group. In conclusion, intramyocardial injection of bFGF-impregnated gelatin hydrogels induces functionally significant angiogenesis and improves left ventricular systolic and diastolic function in the infarcted myocardium of rats.

  7. Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction

    PubMed Central

    HUO, LIANYING; SHI, WENBING; CHONG, LING; WANG, JINLONG; ZHANG, KAI; LI, YUFENG

    2016-01-01

    Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID:26889217

  8. Effect of endothelin receptor antagonist bosentan on plasma leptin concentration in acute myocardial infarction in rats.

    PubMed

    Ostrowski, Robert P.; Januszewski, Sławomir; Kowalska, Zdzisława; Kapuściński, Andrzej

    2003-09-01

    The aim of the study was to evaluate the effect of endothelin receptor antagonism on plasma leptin level after myocardial infarction (MI). In Wistar rats under chloral hydrate anesthesia, MI was performed by ligation of the left coronary artery. The animals were divided into the following groups: control-sham (thoracotomy only), and two MI groups with or without bosentan treatment. Bosentan was given daily by gavage at the dose of 100 mg/kg. Treatment of animals started 2 days before MI and continued up to the fifth day. Concentration of leptin was measured by radioimmunoassay by means of 125I labeled antigen in the following time intervals: before MI or sham operation, 4, 24 and 48 h after surgery. Electrocardiogram (ECG), blood pressure, heart rate, arterial pO(2), pCO(2) and pH were periodically monitored. Two days after the MI animals were perfused retrograde into descending aorta with 2% triphenyltetrazolium chloride (TTC) and hearts were fixed by immersion in formalin for microscopic examination. Hearts were sectioned transaxially and size of MI was quantitated with morphometric methods. ECG, TTC staining and microscopic results confirmed development of MI. Morphometric methods did not show significant differences in infarct size between bosentan treated and untreated groups. Concentration of leptin in plasma in untreated group significantly increased already 4 h after MI. In bosentan treated animals this increase appeared only after 24 h. In animals treated with bosentan also a significant diminution of MI mortality was observed. Our results indicate that bosentan has an important effect on leptin concentration in ischemic cardiovascular pathology.

  9. Effects of a protocol of ischemic postconditioning and/or captopril in hearts of normotensive and hypertensive rats.

    PubMed

    Penna, Claudia; Tullio, Francesca; Moro, Francesca; Folino, Anna; Merlino, Annalisa; Pagliaro, Pasquale

    2010-03-01

    Brief periods (a few seconds) of cyclic coronary occlusions applied early in reperfusion induce a cardioprotection against infarct size, called postconditioning (PostC) in which B(2)-bradykinin receptors play a pivotal role. Since angiotensin-converting enzyme (ACE) inhibitors reduce degradation of kinins, we studied the effects of PostC on infarct size and postischemic myocardial dysfunction in both normotensive (WKY) and spontaneously hypertensive rats (SHR) acutely or chronically treated with the ACE inhibitor Captopril. Isolated hearts from SHR and WKY rats were subjected to the following protocols: (a) ischemia for 30- and 120-min reperfusion (I/R); (b) I/R + PostC protocol (5-cycles 10-s I/R); (c) pretreatment with Captopril for 4-weeks before to subject the hearts to I/R with or without PostC maneuvers. Some SHR hearts were treated with Captopril during the 20- or 40-min early reperfusion with or without PostC maneuvers. Cardiac function was assessed in vivo with echocardiography. Left ventricular pressure and infarct size were measured ex vivo. Chronic Captopril significantly reduced left ventricular hypertrophy in SHR, and reduced infarct size in both WKY and SHR hearts. PostC maneuvers significantly reduced infarct size in WKY, but not in SHR hearts. Yet, PostC slightly improved postischemic systolic function in untreated SHR. Captopril given in reperfusion was unable to limit I/R injury in SHR hearts. Data show that PostC protection against infarct size is blunted in SHR and that PostC is unable to add its protective effect to those of chronic Captopril, which per se reduces cardiac hypertrophy and heart susceptibility to I/R insult.

  10. Thymol attenuates inflammation in isoproterenol induced myocardial infarcted rats by inhibiting the release of lysosomal enzymes and downregulating the expressions of proinflammatory cytokines.

    PubMed

    Nagoor Meeran, Mohamed Fizur; Jagadeesh, Govindan Sangaran; Selvaraj, Palanisamy

    2015-05-05

    Inflammation plays an important role in the development of myocardial infarction (MI). The current study dealt with the protective effects of thymol on inflammation in isoproterenol (ISO) induced myocardial infarcted rats. Male albino Wistar rats were pre and co-treated with thymol (7.5mg/kg body weight) daily for 7 days. ISO (100mg/kg body weight) was injected subcutaneously into rats at an interval of 24h for two days (6th and 7th day) to induce MI. ISO induced myocardial infarcted rats showed increased levels of serum cardiac troponin-T, high sensitive C-reactive protein (hsCRP), lysosomal thiobarbituric acid reactive substances (TBARS) and elevated ST-segments. Also, the activities of lysosomal enzymes such as β-glucuronidase, β-galactosidase, cathepsin-B and D, the stimulators of inflammatory mediators were increased in the serum and heart of ISO induced myocardial infarcted rats. Furthermore, ISO up regulates the expressions of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) genes in the myocardium of rats analyzed by reverse transcription polymerase chain reaction (RT-PCR). Pre and co-treatment with thymol (7.5mg/kg body weight) near normalized the levels of lysosomal TBARS, activities of serum and heart lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines in the myocardium of ISO induced myocardial infarcted rats. Histopathological and transmission electron microscopic findings were also found in line with biochemical findings. Thus, the results of our study revealed that thymol attenuates inflammation by inhibiting the release of lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines by its potent anti-inflammatory effect.

  11. Myocardial infarction in Mexican-Americans and non-Hispanic whites. The San Antonio Heart Study.

    PubMed

    Mitchell, B D; Hazuda, H P; Haffner, S M; Patterson, J K; Stern, M P

    1991-01-01

    Mexican-American men experience reduced cardiovascular mortality compared with non-Hispanic white men. There is no corresponding ethnic difference in cardiovascular mortality in women. The difference in men could result either from a lower incidence of cardiovascular disease or a lower case fatality rate among Mexican-Americans. Although the incidence of cardiovascular disease in Mexican-Americans is unknown, we have collected data on prevalence of myocardial infarction in 5,148 individuals examined in the San Antonio Heart Study, a population-based survey of cardiovascular disease conducted between 1979 and 1988 in Mexican-Americans and non-Hispanic whites aged 25-64 years. Myocardial infarction was assessed by Minnesota-coded electrocardiograms and by a self-reported history of a physician-diagnosed heart attack. For both end points, the age-adjusted prevalence of myocardial infarction was lower in Mexican-American men than in non-Hispanic white men. After adjustment for age and diabetes status (present/absent), the odds of a myocardial infarction, as defined by either criterion, was approximately one third lower in Mexican-American men than in non-Hispanic white men (p = 0.06). In women, the prevalence of both myocardial infarction end points was slightly higher in Mexican-Americans than in non-Hispanic whites, although neither of these differences was significant. Although the ethnic differences in prevalence in this study were not statistically significant, their pattern parallels the pattern in the mortality due to cardiovascular diseases. Therefore, the results support the hypothesis that the reduced cardiovascular mortality rate observed in Mexican-American men reflects a lower incidence of myocardial infarction rather than a reduced case fatality rate because the latter would result in a higher prevalence.

  12. [The relation between the low T3 syndrome in the clinical course of myocardial infarction and heart failure].

    PubMed

    Frączek, Magdalena Maria; Gackowski, Andrzej; Przybylik-Mazurek, Elwira; Nessler, Jadwiga

    2016-06-01

    It has been proven that either excess or deficiency of thyroid hormones has harmful influence on the cardiovascular system function. On the other hand, severe systemic conditions like myocardial infarction or severe heart failure may affect thyroid hormones secretion and their peripheral conversion, leading to low T3 syndrome. Amongst many mechanisms causing T4 to T3 conversion disturbances, important role plays decreased activity of D1 deiodinase and increased activity of D3 deiodinase. The animal research confirmed that thyroid hormones influence cardiomiocytes phenotype and morphology. They inhibit inflammation, apoptosis and cardiac remodelling after myocardial infarction. It was also proven that free triiodothyronine similarly to brain natriuretic peptide predict long-term prognosis in chronic and acute heart failure patients. Potential influence of low T3 syndrome on the course of myocardial infarction and heart failure may have significant impact on the future research on individualization of myocardial infarction and heart failure treatment depending on patient's thyroid status.

  13. Krill oil attenuates left ventricular dilatation after myocardial infarction in rats

    PubMed Central

    2011-01-01

    Background In the western world, heart failure (HF) is one of the most important causes of cardiovascular mortality. Supplement with n-3 polyunsaturated fatty acids (PUFA) has been shown to improve cardiac function in HF and to decrease mortality after myocardial infarction (MI). The molecular structure and composition of n-3 PUFA varies between different marine sources and this may be of importance for their biological effects. Krill oil, unlike fish oil supplements, contains the major part of the n-3 PUFA in the form of phospholipids. This study investigated effects of krill oil on cardiac remodeling after experimental MI. Rats were randomised to pre-treatment with krill oil or control feed 14 days before induction of MI. Seven days post-MI, the rats were examined with echocardiography and rats in the control group were further randomised to continued control feed or krill oil feed for 7 weeks before re-examination with echocardiography and euthanization. Results The echocardiographic evaluation showed significant attenuation of LV dilatation in the group pretreated with krill oil compared to controls. Attenuated heart weight, lung weight, and levels of mRNA encoding classical markers of LV stress, matrix remodeling and inflammation reflected these findings. The total composition of fatty acids were examined in the left ventricular (LV) tissue and all rats treated with krill oil showed a significantly higher proportion of n-3 PUFA in the LV tissue, although no difference was seen between the two krill oil groups. Conclusions Supplement with krill oil leads to a proportional increase of n-3 PUFA in myocardial tissue and supplement given before induction of MI attenuates LV remodeling. PMID:22206454

  14. Litsea Deccanensis Ameliorates Myocardial Infarction in Wistar Rats: Evidence from Biochemical and Histological Studies

    PubMed Central

    Kumar, Bharath P; Kannan, Mari M; Quine, Darlin S

    2011-01-01

    The present study was designed to evaluate the cardioprotective effects of methanolic extract of Litsea deccanensis (MELD) against isoproterenol-induced myocardial infarction in rats by studying cardiac markers, lipid peroxidation, lipid profile, and histological changes. Male Wistar rats were treated orally with MELD (100 and 200 mg/kg) daily for a period of 21 days. After 21 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed significant (P < 0.05) increase in the levels of serum creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances, and lipid hydro peroxides. The serum lipid levels were altered in the isoproterenol-induced myocardial infarcted rats. The histopathological findings of the myocardial tissue evidenced myocardial damage in isoproterenol-induced rats. The oral pretreatment with MELD restored the pathological alterations in the isoproterenol-induced myocardial infarcted rats. The MELD pretreatment significantly reduced the levels of biochemical markers, lipid peroxidation and regulated the lipid profile of the antioxidant system in the isoproterenol-induced rats. An inhibited myocardial necrosis was evidenced by the histopathological findings in MELD pretreated isoproterenol-induced rats. Our study shows that oral pretreatment with MELD prevents isoproterenol-induced oxidative stress in myocardial infarction. The presence of phenolic acid and flavonoid contents were confirmed by preliminary phytochemical tests. The reducing power and free radical scavenging activities of the MELD may be the possible reason for it pharmacological actions. PMID:22224035

  15. Litsea deccanensis ameliorates myocardial infarction in wistar rats: evidence from biochemical and histological studies.

    PubMed

    Kumar, Bharath P; Kannan, Mari M; Quine, Darlin S

    2011-10-01

    The present study was designed to evaluate the cardioprotective effects of methanolic extract of Litsea deccanensis (MELD) against isoproterenol-induced myocardial infarction in rats by studying cardiac markers, lipid peroxidation, lipid profile, and histological changes. Male Wistar rats were treated orally with MELD (100 and 200 mg/kg) daily for a period of 21 days. After 21 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed significant (P < 0.05) increase in the levels of serum creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances, and lipid hydro peroxides. The serum lipid levels were altered in the isoproterenol-induced myocardial infarcted rats. The histopathological findings of the myocardial tissue evidenced myocardial damage in isoproterenol-induced rats. The oral pretreatment with MELD restored the pathological alterations in the isoproterenol-induced myocardial infarcted rats. The MELD pretreatment significantly reduced the levels of biochemical markers, lipid peroxidation and regulated the lipid profile of the antioxidant system in the isoproterenol-induced rats. An inhibited myocardial necrosis was evidenced by the histopathological findings in MELD pretreated isoproterenol-induced rats. Our study shows that oral pretreatment with MELD prevents isoproterenol-induced oxidative stress in myocardial infarction. The presence of phenolic acid and flavonoid contents were confirmed by preliminary phytochemical tests. The reducing power and free radical scavenging activities of the MELD may be the possible reason for it pharmacological actions.

  16. Preconditioning of mesenchymal stem cells with 2,4-dinitrophenol improves cardiac function in infarcted rats.

    PubMed

    Khan, Irfan; Ali, Anwar; Akhter, Muhammad Aleem; Naeem, Nadia; Chotani, Maqsood Ahmed; Mustafa, Tuba; Salim, Asmat

    2016-10-01

    The aim of this study is to determine if preconditioning of bone marrow derived mesenchymal stem cells (MSCs) with 2,4-dinitrophenol (DNP) improves survival of transplanted stem cells in a rat model of myocardial infarction (MI), and to asses if this strategy has measurable impact on cardiac function. MSCs were preconditioned with DNP. In vitro cell adhesion assay and qRT-PCR were performed to analyze the expression of genes involved in cardiomyogenesis, cell adhesion and angiogenesis. MI was produced by occlusion of left anterior descending coronary artery. One million cells were transplanted by intramyocardial injection into the infarcted myocardium. Echocardiography was performed after two and four weeks of cellular transplantation. Hearts were harvested after four weeks and processed for histological analysis. DNP treated MSCs adhered to the surface more (p<0.001) as compared to the normal MSCs. Gene expression levels were significantly upregulated in case of DNP treatment. The number of viable MSCs was more (p<0.001) in animals that received DNP treated MSCs, leading to significant improvement in cardiac function. Histological analysis revealed significant reduction in scar formation (p<0.001), maintenance of left ventricular wall thickness (p<0.001), and increased angiogenesis (p<0.01). The study evidenced for the first time that MSCs preconditioned with DNP improved cardiac function after transplantation. This can be attributed to improved survival, homing, adhesion, and cardiomyogenic and angiogenic differentiation of DNP treated MSCs in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Evening primrose oil ameliorates platelet aggregation and improves cardiac recovery in myocardial-infarct hypercholesterolemic rats

    PubMed Central

    Abo-Gresha, Noha M; Abel-Aziz, Eman Z; Greish, Sahar M

    2014-01-01

    Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their role in cardiovascular disease (CVD). We proposed that Evening prime rose oil (EPO) can improve the outcome of a heart with myocardial infarction (MI) in the presence of diet-induced hyperaggregability. This study was designed to examine its cholesterol lowering, antithrombotic and anti-inflammatory effects. High fat diet was administered for 4 weeks then MI was induced by isoproterenol (85 mg/kg/s.c./24 h). Treatment with EPO (5 or 10 gm/kg/day) for 6 weeks improved the electrocardiographic pattern, serum lipid profile, cardiac biomarkers as well as Platelet aggregation percent. We reported decreased serum level of TNF-α, IL-6 and COX-2 with attenuation of TNF-α and TGF-β in the cardiac homogenate. Moreover, histopathology revealed marked amelioration. Finally, we provide evidence that EPO improve cardiac recovery in hypercholesterolemic myocardial infarct rats. These effects are attributed to direct hypocholesterolemic effect and indirect effect on the synthesis of eicosanoids (prostaglandins, cytokines). PMID:24665356

  18. Association between low-dose acetylsalicylic acid reinitiation and the risk of myocardial infarction or coronary heart disease death.

    PubMed

    Sáez, María E; González-Pérez, Antonio; Johansson, Saga; Himmelmann, Anders; García Rodríguez, Luis A

    2016-07-01

    In secondary cardiovascular prevention, discontinuation of acetylsalicylic acid (ASA) is associated with an increased risk of cardiovascular events. This study assessed the impact of ASA reinitiation on the risk of myocardial infarction and coronary heart disease death. Patients prescribed ASA for secondary cardiovascular prevention and who had had a period of ASA discontinuation of ≥90 days in 2000-2007 were identified from The Health Improvement Network (N = 10,453). Incidence of myocardial infarction/coronary heart disease death was calculated. Survival analyses using adjusted Cox proportional hazard models were performed to calculate hazard ratios and 95% confidence intervals for the risk of myocardial infarction/coronary heart disease death associated with ASA use patterns after the initial period of discontinuation. Individuals who were prescribed ASA during follow-up were considered reinitiators. The incidence of myocardial infarction/coronary heart disease death was 8.90 cases per 1000 person-years. Risk of myocardial infarction/coronary heart disease death was similar for current ASA users, who had been continuously exposed since reinitiation, and patients who had not reinitiated ASA (hazard ratio 1.27, 95% confidence interval 0.93-1.73). Among reinitiators, an additional period of ASA discontinuation was associated with increased risk of myocardial infarction/coronary heart disease death compared with no reinitiation (current users: hazard ratio 1.46, 95% confidence interval 1.13-1.90; noncurrent users: hazard ratio 1.70, 95% confidence interval 1.31-2.21). ASA reinitiation was not associated with a decreased risk of myocardial infarction/coronary heart disease death. This may be explained by confounding by indication/comorbidity, whereby higher-risk patients are more likely to reinitiate therapy. An additional period of ASA discontinuation among reinitiators was associated with an increased risk of myocardial infarction/coronary heart disease death

  19. Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats

    PubMed Central

    Goyal, Sameer N.; Sharma, Charu; Mahajan, Umesh B.; Patil, Chandragouda R.; Agrawal, Yogeeta O.; Kumari, Santosh; Arya, Dharamvir Singh; Ojha, Shreesh

    2015-01-01

    Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities. PMID:26593900

  20. Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats.

    PubMed

    Goyal, Sameer N; Sharma, Charu; Mahajan, Umesh B; Patil, Chandragouda R; Agrawal, Yogeeta O; Kumari, Santosh; Arya, Dharamvir Singh; Ojha, Shreesh

    2015-11-17

    Cardamom is a popular spice that has been commonly used in cuisines for flavor since ancient times. It has copious health benefits such as improving digestion, stimulating metabolism, and exhibits antioxidant and anti-inflammatory effects. The current study investigated the effect of cardamom on hemodynamic, biochemical, histopathological and ultrastructural changes in isoproterenol (ISO)-induced myocardial infarction. Wistar male albino rats were randomly divided and treated with extract of cardamom (100 and 200 mg/kg per oral) or normal saline for 30 days with concomitant administration of ISO (85 mg/kg, subcutaneous) on 29th and 30th days, at 24 h interval. ISO injections to rats caused cardiac dysfunction evidenced by declined arterial pressure indices, heart rate, contractility and relaxation along with increased preload. ISO also caused a significant decrease in endogenous antioxidants, superoxide dismutase, catalase, glutathione peroxidase, depletion of cardiomyocytes enzymes, creatine kinase-MB, lactate dehydrogenase and increase in lipid peroxidation. All these changes in cardiac and left ventricular function as well as endogenous antioxidants, lipid peroxidation and myocyte enzymes were ameliorated when the rats were pretreated with cardamom. Additionally, the protective effects were strengthened by improved histopathology and ultrastructural changes, which specifies the salvage of cardiomyocytes from the deleterious effects of ISO. The present study findings demonstrate that cardamom significantly protects the myocardium and exerts cardioprotective effects by free radical scavenging and antioxidant activities.

  1. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    PubMed

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

  2. Hypercholesterolemia downregulates autophagy in the rat heart.

    PubMed

    Giricz, Zoltán; Koncsos, Gábor; Rajtík, Tomáš; Varga, Zoltán V; Baranyai, Tamás; Csonka, Csaba; Szobi, Adrián; Adameová, Adriana; Gottlieb, Roberta A; Ferdinandy, Péter

    2017-03-23

    We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart. Male Wistar rats were fed either normal chow (NORM; n = 9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n = 9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09 mmol/L vs. 2.89 mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot. Isolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments. This is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the

  3. Sirtuin1-p53, forkhead box O3a, p38 and post-infarct cardiac remodeling in the spontaneously diabetic Goto-Kakizaki rat

    PubMed Central

    2010-01-01

    Background Diabetes is associated with changes in myocardial stress-response pathways and is recognized as an independent risk factor for cardiac remodeling. Using spontaneously diabetic Goto Kakizaki rats as a model of type 2 DM we investigated whether post-translational modifications in the Akt - FOXO3a pathway, Sirt1 - p53 pathway and the mitogen activated protein kinase p38 regulator are involved in post-infarct cardiac remodeling Methods Experimental myocardial infarction (MI) was induced by left anterior descending coronary artery ligation in spontaneously diabetic Goto-Kakizaki rats and non-diabetic Wistar controls. Cardiac function was studied by echocardiography. Myocardial hypertrophy, cardiomyocyte apoptosis and cardiac fibrosis were determined histologically 12 weeks post MI or Sham operation. Western blotting was used to study Caspase-3, Bax, Sirt1, acetylation of p53 and phosphorylation of p38, Akt and FOXO3a. Electrophoretic mobility shift assay was used to assess FOXO3a activity and its nuclear localization. Results Post-infarct heart failure in diabetic GK rats was associated with pronounced cardiomyocyte hypertrophy, increased interstitial fibrosis and sustained cardiomyocyte apoptosis as compared with their non-diabetic Wistar controls. In the GK rat myocardium, Akt- and FOXO3a-phosphorylation was decreased and nuclear localization of FOXO3a was increased concomitantly with increased PTEN protein expression. Furthermore, increased Sirt1 protein expression was associated with decreased p53 acetylation, and phosphorylation of p38 was increased in diabetic rats with MI. Conclusions Post-infarct heart failure in diabetic GK rats was associated with more pronounced cardiac hypertrophy, interstitial fibrosis and sustained cardiomyocyte apoptosis as compared to their non-diabetic controls. The present study suggests important roles for Akt-FOXO3a, Sirt1 - p53 and p38 MAPK in the regulation of post-infarct cardiac remodeling in type 2 diabetes. PMID

  4. Erythropoietin responsive cardiomyogenic cells contribute to heart repair post myocardial infarction.

    PubMed

    Zafiriou, Maria Patapia; Noack, Claudia; Unsöld, Bernhard; Didie, Michael; Pavlova, Elena; Fischer, Henrike J; Reichardt, Holger M; Bergmann, Martin W; El-Armouche, Ali; Zimmermann, Wolfram-Hubertus; Zelarayan, Laura Cecilia

    2014-09-01

    The role of erythropoietin (Epo) in myocardial repair after infarction remains inconclusive. We observed high Epo receptor (EPOR) expression in cardiac progenitor cells (CPCs). Therefore, we aimed to characterize these cells and elucidate their contribution to myocardial regeneration on Epo stimulation. High EPOR expression was detected during murine embryonic heart development followed by a marked decrease until adulthood. EPOR-positive cells in the adult heart were identified in a CPC-enriched cell population and showed coexpression of stem, mesenchymal, endothelial, and cardiomyogenic cell markers. We focused on the population coexpressing early (TBX5, NKX2.5) and definitive (myosin heavy chain [MHC], cardiac Troponin T [cTNT]) cardiomyocyte markers. Epo increased their proliferation and thus were designated as Epo-responsive MHC expressing cells (EMCs). In vitro, EMCs proliferated and partially differentiated toward cardiomyocyte-like cells. Repetitive Epo administration in mice with myocardial infarction (cumulative dose 4 IU/g) resulted in an increase in cardiac EMCs and cTNT-positive cells in the infarcted area. This was further accompanied by a significant preservation of cardiac function when compared with control mice. Our study characterized an EPO-responsive MHC-expressing cell population in the adult heart. Repetitive, moderate-dose Epo treatment enhanced the proliferation of EMCs resulting in preservation of post-ischemic cardiac function.

  5. Effects of autonomic balance and fluid and electrolyte changes on cardiac function in infarcted rats: A serial study of sexual dimorphism.

    PubMed

    Souza, N S; Dos-Santos, R C; Silveira, Anderson Luiz Bezerra da; R, Sonoda-Côrtes; Gantus, Michel Alexandre Villani; Fortes, F S; Olivares, Emerson Lopes

    2016-04-01

    Premenopausal women are known to show lower incidence of cardiovascular disease than men. During myocardial infarction (MI), homeostatic responses are activated, including the sympathetic autonomic nervous system and the rennin-angiotensin-aldosterone system, which is related to the fluid and electrolyte balance, both aiming to maintain cardiac output. This study sought to perform a serial evaluation of sexual dimorphism in cardiac autonomic control and fluid and electrolyte balance during the development of MI-induced heart failure in rats. Experimental MI was induced in male (M) and female (F) adult (7-9 weeks of age) Wistar rats. The animals were placed in metabolic cages to assess fluid intake and urine volume 1 and 4 weeks after inducing MI (male myocardial infarction (MMI) and female myocardial infarction (FMI) groups). They subsequently underwent echocardiographic evaluation and spectral analysis of heart rate variability. After completing each protocol, the animals were killed for postmortem evaluation and histology. The MMI group showed earlier and more intense cardiac morphological and functional changes than the FMI group, although the extent of MI did not differ between groups (P > 0.05). The MMI group showed higher sympathetic modulation and sodium and water retention than the FMI group (P < 0.05), which may partly explain both the echocardiographic and pathological findings. Females subjected to infarction seem to show attenuation of sympathetic modulation, more favourable fluid and electrolyte balances, and better preserved cardiac function compared to males subjected to the same infarction model. © 2016 John Wiley & Sons Australia, Ltd.

  6. Finite Element Analysis of Ventricular Wall Motion and Intra-Ventricular Blood Flow in Heart with Myocardial Infarction

    NASA Astrophysics Data System (ADS)

    Watanabe, Hiroshi; Sugano, Takeshi; Sugiura, Seiryo; Hisada, Toshiaki

    To study the wall motion abnormality and characteristic flow distribution observed in the heart with myocardial infarction, we modified our finite element model of left ventricle and performed simulations at two different phases after the onset of the disease by applying characteristic material property to the infarcted region. The model could not only reproduce the hemodynamic change in myocardial infarction but also give mechanistic insight into the following complicating problems. 1) Stagnation of blood as the cause of clot formation 2) Extra energy wasted for the stretch of infarcted tissue. The effect of compensatory enhancement of the force generation in normal myocardial tissue is also discussed.

  7. Effects of Intracoronary Infusion of Escalating Doses of Cardiac Stem Cells in Rats With Acute Myocardial Infarction.

    PubMed

    Tang, Xian-Liang; Rokosh, Gregg; Sanganalmath, Santosh K; Tokita, Yukichi; Keith, Matthew C L; Shirk, Gregg; Stowers, Heather; Hunt, Gregory N; Wu, Wenjian; Dawn, Buddhadeb; Bolli, Roberto

    2015-07-01

    Although c-kit(pos) cardiac stem cells (CSCs) preserve left ventricular (LV) function and structure after myocardial infarction, CSC doses have been chosen arbitrarily, and the dose-effect relationship is unknown. Rats underwent a 90-minute coronary occlusion followed by 35 days of reperfusion. Vehicle or CSCs at 5 escalating doses (0.3×10(6), 0.75×10(6), 1.5×10(6), 3.0×10(6), and 6.0×10(6) cells/heart) were given intracoronarily 4 h after reperfusion. The lowest dose (0.3×10(6)) had no effect on LV function and morphology, whereas 0.75, 1.5, and 3.0×10(6) significantly improved regional and global LV function (echocardiography and hemodynamic studies). These 3 doses had similar effects on echocardiographic parameters (infarct wall thickening fraction, LV end-systolic and end-diastolic volumes, LV ejection fraction) and hemodynamic variables (LV end-diastolic pressure, LV dP/dtmax, preload adjusted maximal power, end-systolic elastance, preload recruitable stroke work) and produced similar reductions in apoptosis, scar size, infarct wall thinning, and LV expansion index and similar increases in viable myocardium in the risk region (morphometry). Infusion of 6.0×10(6) CSCs markedly increased postprocedural mortality. Green fluorescent protein and 5-bromo-2'-deoxyuridine staining indicated that persistence of donor cells and formation of new myocytes were negligible with all doses. Surprisingly, in this rat model of acute myocardial infarction, the dose-response relationship for intracoronary CSCs is flat. A minimal dose between 0.3 and 0.75×10(6) is necessary for efficacy; above this threshold, a 4-fold increase in cell number does not produce greater improvement in LV function or structure. Further increases in cell dose are harmful. © 2015 American Heart Association, Inc.

  8. Effects of dual endothelin receptor blockade on sympathetic activation and arrhythmogenesis during acute myocardial infarction in rats.

    PubMed

    Kolettis, Theofilos M; Baltogiannis, Giannis G; Tsalikakis, Dimitrios G; Tzallas, Alexandros T; Agelaki, Maria G; Fotopoulos, Andreas; Fotiadis, Dimitrios I; Kyriakides, Zenon S

    2008-02-02

    The effects of dual (ETA and ETB) endothelin receptor blockade on ventricular arrhythmogenesis during acute myocardial infarction are not well defined. We randomly allocated Wistar rats to bosentan (100 mg/kg daily, n=24), a dual endothelin receptor antagonist, or vehicle (n=23). After 7 days of treatment, myocardial infarction was induced by permanent coronary ligation. Ventricular tachyarrhythmias were evaluated for 24 h following ligation, using a miniature telemetry electrocardiogram recorder. Action potential duration was measured from monophasic epicardial recordings and sympathetic activation was assessed by heart rate variability and catecholamine serum level measurements. Compared to controls (1012+/-185 s), bosentan (59+/-24 s) markedly decreased (P<0.00001) the total duration of ventricular tachyarrhythmias during the delayed (1-24 h) phase post-ligation, with a modest effect during the early (0-1 h) phase (132+/-38 s, versus 43+/-18 s, respectively, P=0.053). Treatment did not affect infarct size or total mortality. Action potential duration at 90% repolarization prolonged in controls (from 93.1+/-4.7 ms to 117.6+/-6.9 ms), displaying increased temporal dispersion (from 4.14+/-0.45 ms to 10.42+/-2.51 ms, both P<0.001), but was preserved in treated animals. Bosentan decreased norepinephrine, but increased epinephrine levels 24 h post-ligation. Low frequency spectra of heart rate variability, an index of net sympathetic tone, were lower in bosentan-treated rats. Dual endothelin-1 receptor blockade decreases ventricular tachyarrhythmias during myocardial infarction without reperfusion, by preventing repolarization inhomogeneity. Diverse treatment effects on sympathetic activation may ameliorate the antiarrhythmic action.

  9. Brain Perivascular Macrophages and the Sympathetic Response to Inflammation in Rats after Myocardial Infarction

    PubMed Central

    Yu, Yang; Zhang, Zhi-Hua; Wei, Shun-Guang; Serrats, Jordi; Weiss, Robert M; Felder, Robert B

    2010-01-01

    Inflammation is associated with increased sympathetic drive in cardiovascular diseases. Blood-borne pro-inflammatory cytokines, markers of inflammation, induce cyclooxygenase-2 (COX-2) activity in perivascular macrophages of the blood-brain barrier. COX-2 generates prostaglandin E2 (PGE2), which may enter the brain and increase sympathetic nerve activity. We examined the contribution of this mechanism to augmented sympathetic drive in rats following myocardial infarction (MI). Approximately 24h after acute MI, rats received an intracerebroventricular (ICV) injection (1 μl/min over 40 minutes) of clodronate liposomes (MI+CLOD) to eliminate brain perivascular macrophages, liposomes alone (MI+LIPO) or artificial cerebrospinal fluid (MI+aCSF). A week later, COX-2 immunoreactivity in perivascular macrophages and COX-2 mRNA and protein had increased in hypothalamic paraventricular nucleus (PVN) of MI+aCSF and MI+LIPO, compared with sham-operated (SHAM) rats. In MI+CLOD, neither perivascular macrophages nor COX-2 immunoreactivity was seen in PVN, and COX-2 mRNA and protein were similar to SHAM. PGE2 in cerebrospinal fluid, PVN neuronal excitation, and plasma norepinephrine were less in MI+CLOD than MI+aCSF and MI+LIPO but more than in SHAM. ICV CLOD had no effect on interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mRNA and protein in PVN or plasma IL-1β and TNF-α, which were increased in MI compared with SHAM rats. In normal rats, pretreatment with ICV CLOD reduced (P<0.05) renal sympathetic, blood pressure and heart rate responses to intracarotid artery injection of TNF-α (0.5 μg/kg); ICV LIPO had no effect. The results suggest that pro-inflammatory cytokines stimulate sympathetic excitation after MI by inducing COX-2 activity and PGE2 production in perivascular macrophages of the blood-brain barrier. PMID:20142564

  10. Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction.

    PubMed

    Heidt, Timo; Courties, Gabriel; Dutta, Partha; Sager, Hendrik B; Sebas, Matt; Iwamoto, Yoshiko; Sun, Yuan; Da Silva, Nicolas; Panizzi, Peter; van der Laan, Anja M; van der Lahn, Anja M; Swirski, Filip K; Weissleder, Ralph; Nahrendorf, Matthias

    2014-07-07

    Macrophages populate the steady-state myocardium. Previously, all macrophages were thought to arise from monocytes; however, it emerged that, in several organs, tissue-resident macrophages may self-maintain through local proliferation. Our aim was to study the contribution of monocytes to cardiac-resident macrophages in steady state, after macrophage depletion in CD11b(DTR/+) mice and in myocardial infarction. Using in vivo fate mapping and flow cytometry, we estimated that during steady state the heart macrophage population turns over in ≈1 month. To explore the source of cardiac-resident macrophages, we joined the circulation of mice using parabiosis. After 6 weeks, we observed blood monocyte chimerism of 35.3±3.4%, whereas heart macrophages showed a much lower chimerism of 2.7±0.5% (P<0.01). Macrophages self-renewed locally through proliferation: 2.1±0.3% incorporated bromodeoxyuridine 2 hours after a single injection, and 13.7±1.4% heart macrophages stained positive for the cell cycle marker Ki-67. The cells likely participate in defense against infection, because we found them to ingest fluorescently labeled bacteria. In ischemic myocardium, we observed that tissue-resident macrophages died locally, whereas some also migrated to hematopoietic organs. If the steady state was perturbed by coronary ligation or diphtheria toxin-induced macrophage depletion in CD11b(DTR/+) mice, blood monocytes replenished heart macrophages. However, in the chronic phase after myocardial infarction, macrophages residing in the infarct were again independent from the blood monocyte pool, returning to the steady-state situation. In this study, we show differential contribution of monocytes to heart macrophages during steady state, after macrophage depletion or in the acute and chronic phase after myocardial infarction. We found that macrophages participate in the immunosurveillance of myocardial tissue. These data correspond with previous studies on tissue-resident macrophages

  11. Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury.

    PubMed

    Wang, Peng-Fei; Jiang, Li-Sheng; Bu, Jun; Huang, Xiao-Jin; Song, Wei; Du, Yong-Ping; He, Ben

    2012-04-01

    Endocannabinoid system is reported to be activated during myocardial ischemia-reperfusion (IR) injury and protects against heart injury. We, therefore, observed changes in endocannabinoids levels during acute myocardial infarction (AMI) and myocardial IR injury and evaluated the role of cannabinoid-2 (CB2) receptor in infarct and IR heart injury. In contrast to 16 control patients with normal coronary artery angiogram, the endocannabinoid 2-arachidonoylglycerol level in the infarct-side coronary artery of 23 AMI patients increased significantly, with increased reactive oxygen species and tumor necrosis factor-α levels in both infarct-side coronary artery and radial artery. Then, 35 C57BL/6J mice were made into SHAM, AMI, or IR models. AMI and IR groups were treated with CB2-selective agonist HU308 ((+)-(1aH,3H,5aH)-4-[2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbinol), with or without CB2-selective antagonist AM630 [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone through intraperitoneal injection. Compared with the SHAM, expressions of cannabinoid CB1/CB2 receptor proteins in AMI/IR animals were upregulated; production of 2-arachidonoylglycerol and anandamide and release of reactive oxygen species and tumor necrosis factor-α also increased. HU308 significantly decreased the infarct size and the levels of reactive oxygen species and tumor necrosis factor-α in AMI/IR animals. However, these effects were blocked by AM630. In conclusion, the endocannabinoid system was activated during AMI and IR, and CB2 receptor activation produces a protective role, thus offering a novel pharmaceutical target for treating these diseases.

  12. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  13. Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction.

    PubMed

    Chen, Leilei; Zhang, Yuan; Tao, Liangliang; Yang, Zhijian; Wang, Liansheng

    2017-02-01

    Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction. We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery. Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo. In a rat model of acute myocardial infarction, the transplantation of eNOS-overexpressing BM-MSCs significantly reduced myocardial infarct size, corrected hemodynamic parameters and increased capillary density. We also found that the synergistic effects were consistently better than either treatment alone. These findings reveal a positive role of elevated eNOS expression in cardiac repair, and suggest the combination of eNOS and MSC transplant therapy as a potential approach for treating myocardial infarction.

  14. Ginsenoside Rg1 and Rb1, in combination with salvianolic acid B, play different roles in myocardial infarction in rats.

    PubMed

    Deng, Yanping; Zhang, Tingting; Teng, Fukang; Li, Defang; Xu, Feng; Cho, Kenka; Xu, Jinghua; Yin, Jun; Zhang, Li; Liu, Qian; Yang, Ming; Wu, Wanying; Liu, Xuan; Guo, De-An; Jiang, Baohong

    2015-02-01

    The herb pair of Salvia miltiorrhiza and Panax notoginseng has widely been used for improving coronary and cerebral circulation in China. However, the exact contribution of the major active components of S. miltiorrhiza and P. notoginseng to cardioprotection is far from clear. In the present study, three representative ingredients, salvianolic acid B (SalB) from S. miltiorrhiza and ginsenoside Rg1 (Rg1) and ginsenoside Rb1 (Rb1) from P. notoginseng, were selected to elucidate the mechanism of the herb pair at the ingredient level. The purity of SalB, Rg1, and Rb1 was >99%, as detected by high-performance liquid chromatography. Acute myocardial infarction was introduced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Cardiac contractility was detected through a Mikro-tipped catheter, and cardiac infarct size was determined using triphenyltetrazolium chloride stain. The combination of SalB and Rg1, and not the combination of SalB and Rb1, improved heart contractility in rats with myocardial infarction. The different contributions of Rg1 and Rb1, in combination with SalB, to cardioprotection provides further direction to optimize and modernize the herbal medicines containing S. miltiorrhiza and P. notoginseng. The combination of SalB and Rg1 may provide potential protection against myocardial infarction. Copyright © 2014. Published by Elsevier Taiwan.

  15. The beneficial effects of ranolazine on cardiac function after myocardial infarction are greater in diabetic than in nondiabetic rats.

    PubMed

    Mourouzis, Iordanis; Mantzouratou, Polixeni; Galanopoulos, Georgios; Kostakou, Erietta; Dhalla, Arvinder K; Belardinelli, Luiz; Pantos, Constantinos

    2014-09-01

    Ranolazine (RAN) is known to exert both anti-ischemic and antidiabetic actions. Thus, this study has explored the hypothesis that RAN would have greater effect on the recovery of cardiac function in diabetic mellitus (DM) rat hearts following myocardial infarction (MI). Myocardial infarction was induced in nondiabetic (MI, n = 14) and diabetic (streptozotocin induced; DM-MI, n = 13) Wistar rats by permanent ligation of the left coronary artery. Cardiac function was evaluated using echocardiography (left ventricular ejection fraction %) and in isolated heart preparations by measuring left ventricular developed pressure (LVDP), and the positive and negative first derivative of LVDP (± dp/dt). Ranolazine (20 mg/kg, ip once a day) was administered 24 hours after surgical procedure for 4 weeks to nondiabetic (MI + RAN, n = 17) and diabetic rats (DM-MI + RAN, n = 15). The RAN improved the recovery of function in both the nondiabetic and the diabetic postinfarcted hearts but this effect was greater and achieved statistical significance only in the diabetic group. The RAN resulted in increased levels of phosphorylated protein kinase B (Akt) and mammalian target of rapamycin (mTOR, a component of Akt signaling) in both nondiabetic and diabetic infarcted hearts without changes in the activation of mitogen-activated protein kinases (MAPKs; p38 MAPK, c-Jun N-terminal kinase, and extracellular signal-regulated kinase). In addition, in diabetic hearts, RAN resulted in a significant increase in the ratio of sarcoplasmic Ca(2+)-ATPase/phospholamban (a target of Akt signaling, 2.0-fold increase) and increased levels of phosphorylated calcium-regulated adenosine monophosphate-activated protein kinase (AMPK; 2.0-fold increase). In diabetic animals, RAN increased insulin and lowered glucose levels in serum. In conclusion, the beneficial effect of RAN on the recovery of cardiac function after MI was greater in DM rats. This response was associated with activation of Akt/mTOR and AMPK

  16. Detection of catalase in rat heart mitochondria.

    PubMed

    Radi, R; Turrens, J F; Chang, L Y; Bush, K M; Crapo, J D; Freeman, B A

    1991-11-15

    The presence of heme-containing catalase in rat heart mitochondria (20 +/- 5 units/mg) was demonstrated by biochemical and immunocytochemical analysis. Intact rat heart mitochondria efficiently consumed exogenously added H2O2. The rate of H2O2 consumption was not influenced by succinate, glutamate/malate, or N-ethylmaleimide but was significantly inhibited by cyanide. Hydrogen peroxide decomposition by mitochondria yielded molecular oxygen in a 2:1 stoichiometry, consistent with a catalytic mechanism. Mitochondrial fractionation studies and quantitative electron microscopic immunocytochemistry revealed that most catalase was matrix-associated. Electrophoretic analysis and Western blotting of the mitochondrial matrix fraction indicated the presence of a protein with similar electrophoretic mobility to bovine and rat liver catalase and immunoreactive to anti-catalase antibody. Myocardial tissue has a lower catalase-specific activity and a greater mitochondrial H2O2 production/g of tissue than most organs. Thus catalase, representing 0.025% of heart mitochondrial protein, is important for detoxifying mitochondrial derived H2O2 and represents a key antioxidant defense mechanism for myocardial tissue.

  17. Effect of basic fibroblast growth factor on angiogenesis in the infarcted porcine heart.

    PubMed

    Watanabe, E; Smith, D M; Sun, J; Smart, F W; Delcarpio, J B; Roberts, T B; Van Meter, C H; Claycomb, W C

    1998-02-01

    Administration of growth factors is emerging as a new therapeutic approach for the enhancement of collateral vessel formation in the ischemic heart. We have investigated the effects of intramyocardial delivery of FGF-2 in the presence and absence of heparin on angiogenesis in a porcine model of myocardial infarction. Yorkshire pigs were subjected to myocardial infarction by the placement of an embolization coil in the left anterior descending artery (n = 5). Four to five weeks after creation of an infarct, FGF-2 (10 micrograms) alone or in complex with heparin, heparan sulfate, or heparin agarose beads was injected either into the normal myocardium or along the infarct border area. Histologic evaluation of each injection site was performed 4 to 5 weeks post-injection. The effect of FGF-2 on angiogenesis was evaluated by determining the number of capillaries (diameter < 20 microns (and arterioles (> 20 microns with tunica media) in each area observed. The number of capillaries were not affected by the treatment of FGF-2 both in normal myocardium and infarct border area. However, in the normal myocardium, the number of arterioles were increased with the treatment of FGF-2 alone (85 +/- 59%, P < 0.04), FGF-2 plus heparin (281 +/- 193%, P < 0.004) and FGF-2-coated heparin beads (241 +/- 141%, P < 0.01), as compared to control. Delivery of FGF-2 into the infarct border area, also increased the number of arterioles when FGF-2 was given with heparin (736 +/- 154%, P < 0.001) or heparin beads (700 +/- 109%, P < 0.001), as compared to control. FGF-2 administered with heparin was the most effective method of enhancing angiogenesis as compared to FGF-2 alone, FGF-2 plus heparan sulfate, or FGF-2 coated heparin agarose beads.

  18. A routine electrocardiogram cannot be used to determine the size of myocardial infarction in the rat.

    PubMed

    Bonilha, A M M; Saraiva, R M; Kanashiro, R M; Portes, L A; Antonio, E L; Tucci, P J F

    2005-04-01

    Nine lead electrocardiograms of non-infarcted (N = 61) and infarcted (N = 71) female Wistar rats (200-250 g) were analyzed in order to distinguish left ventricle myocardial infarction (MI) larger than 40% (LMI) from MI smaller than 40% (SMI). MI larger than 40% clearly caused a deviation of AQRS and AT from normal values of 270-360 degrees to 90-270 degrees. Infarcted rats showed Q wave in D1 larger than 1 mm with 94% sensitivity and 100% specificity. The sum of QRS positivity in V1, V2 and V6 lower than 10 mm identified MI with 82% sensitivity and 100% specificity. The data showed that MI can be easily and reliably diagnosed by electrocardiogram in the rat. However, contradicting what is frequently believed, when specificity and sensitivity were analyzed focusing on MI size, none of these current electrocardiographic indices of MI size adequately discriminates LMI from SMI.

  19. Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model.

    PubMed

    Binsalamah, Ziyad Mohammed; Paul, Arghya; Khan, Afshan Afsar; Prakash, Satya; Shum-Tim, Dominique

    2011-01-01

    Acute myocardial ischemia results in scar formation with ventricular dilatation and eventually heart failure. Placental growth factor (PlGF) is reported to stimulate angiogenesis and improve cardiac function. In this study, it was hypothesized that intramyocardial injection of PlGF contained in nanoparticles can be released at the site of action for an extended time period as a sustained slow-release protective mechanism that accelerates myocardial recovery in a rat model of ischemic cardiomyopathy. PlGF-loaded chitosan-alginate nanoparticles were injected into an acute myocardial infarction model in rats (n = 10 per group). Transthoracic echocardiography was performed at different time intervals. Enzyme-linked immunosorbent assay was used to measure the serum cytokines levels at 8 weeks. Hearts were stained with Masson's trichrome for scar area analysis. Immunofluorostaining was performed to evaluate the extent of myocardial angiogenesis at the infarction border. PlGF enzyme-linked immunosorbent assay was used to measure the in vitro release kinetics of PlGF-loaded nanoparticles. At 8 weeks after coronary ligation, hearts that were treated with PlGF-loaded chitosan-alginate nanoparticles had significant increases in left-ventricular function (P < 0.01), vascular density (P < 0.01), and in the serum level of the anti-inflammatory cytokine interleukin-10 (P < 0.05). There was significant decrease in scar area formation (P < 0.05) and in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 (P < 0.01). In vitro PlGF-release kinetic studies showed a sustained release of PlGF from the particles over a 120-hour period. The use of nanoparticles as a vehicle for PlGF delivery, as opposed to the direct injection of the growth factor after acute myocardial infarction, can provide sustained slow-release PlGF therapy, enhancing the positive effects of the growth factor in the setting of acute myocardial ischemia.

  20. Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

    PubMed Central

    Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, Ramasamy; Mao, Hai-Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

    2009-01-01

    Background Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). Methods and Findings Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. Conclusion Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID:19809493

  1. Infarct Size, Shock, and Heart Failure: Does Reperfusion Strategy Matter in Early Presenting Patients With ST-Segment Elevation Myocardial Infarction?

    PubMed

    Shavadia, Jay; Zheng, Yinggan; Dianati Maleki, Neda; Huber, Kurt; Halvorsen, Sigrun; Goldstein, Patrick; Gershlick, Anthony H; Wilcox, Robert; Van de Werf, Frans; Armstrong, Paul W

    2015-08-24

    A pharmacoinvasive (PI) strategy for early presenting ST-segment elevation myocardial infarction nominally reduced 30-day cardiogenic shock and congestive heart failure compared with primary percutaneous coronary intervention (PPCI). We evaluated whether infarct size (IS) was related to this finding. Using the peak cardiac biomarker in patients randomized to PI versus PPCI within the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial, IS was divided into 3 groups: small (≤2 times the upper limit normal [ULN]), medium (>2 to ≤5 times the upper limit normal) and large (>5 times the upper limit normal). The association between IS and 30-day shock and congestive heart failure was subsequently examined. Data on 1701 of 1892 (89.9%) patients randomized to PI (n=853, 50.1%) versus PPCI (n=848, 49.9%) within STREAM were evaluated. A higher proportion of PPCI patients had a large IS (PI versus PPCI: small, 49.8% versus 50.2%; medium, 56.9% versus 43.1%; large, 48.4% versus 51.6%; P=0.035), despite comparable intergroup ischemic times for each reperfusion strategy. As IS increased, a parallel increment in shock and congestive heart failure occurred in both treatment arms, except for the small IS group. The difference in shock and congestive heart failure in the small IS group (4.4% versus 11.6%, P=0.026) in favor of PI likely relates to higher rates of aborted myocardial infarction with the PI strategy (72.7% versus 54.3%, P=0.005). After adjustment, a trend favoring PI persisted in this subgroup (relative risk 0.40, 95% CI 0.15 to 1.06, P=0.064); no difference in treatment-related outcomes was evident in the other 2 groups. A PI strategy appears to alter the pattern of IS after ST-segment elevation myocardial infarction, resulting in more medium and fewer large infarcts compared with PPCI. Despite a comparable number of small infarcts, PI patients in this group had more aborted myocardial infarctions and less 30-day shock and congestive heart failure

  2. Cortical infarction of the right parietal lobe and neurogenic heart disease: A report of three cases.

    PubMed

    Li, Fang; Jia, Yujie

    2012-04-25

    Three male patients were diagnosed with new cortical infarctions of the right parietal lobe on the basis of head magnetic resonance imaging; high-intensity signals indicating lesions in the right parietal lobe were noted on diffusion-weighted images at admission. Two of them presented with left hand weakness, and one exhibited left upper limb weakness. Treatment for improving blood supply to the brain was administered. One patient died suddenly because of ventricular fibrillation 3 days after admission. The other two patients had increased troponin levels and abnormal electrocardiograms, and were diagnosed with acute myocardial infarction half a month after admission. When lesions exist in field 7 of the parietal cortex (resulting in paralysis of the contralateral hand), the sympathetic center of the posterior lateral nucleus of the hypothalamus demonstrates compensatory excitement, which easily causes tachyarrhythmia and sudden death. Our experimental findings indicate that close electrocardiograph monitoring and cerebral infarction treatment should be standard procedures to predict and help prevent heart disease in patients with cerebral infarction in the right parietal lobe and left upper limb weakness as the main complaint.

  3. Evaluation and simplified measurement of infarct size by myocardial contrast echocardiography in a rat model of myocardial infarction.

    PubMed

    Chen, Xianghui; Cui, Kai; Xiu, Jiancheng; Lin, Huanbing; Lao, Yi; Zhou, Biying; Liang, Feixue; Zha, Daogang; Bin, Jianping; Liu, Yili

    2009-10-01

    To test the feasibility and accuracy of myocardial contrast echocardiography (MCE) for predicting infarct size (IS) in a rat model of myocardial infarction (MI) and to compare a simplified single plane-based measurement of IS with the conventional three plane-based approach. Fifty male SD rats underwent left anterior descending artery ligation and were evaluated by MCE 8 h post MI. IS was calculated by the single and three plane-based approaches, compared to that determined by triphenyltetrazolium chloride (TTC) staining method. Simplified single plane-based MCE approach and TTC method showed similar IS values (38.48 +/- 16.80% vs. 35.72 +/- 15.33%, P > 0.05) and presented a favorable positive correlation (r = 0.851, P < 0.001). IS values derived from simplified single plane-based approach was also highly significantly correlated with that by the conventional MCE method (r = 0.973, P < 0.001). Bland-Altman plots also displayed satisfactory agreement between them. MCE was validated as a novel technique to quantify infarct area in rats with MI. A single measurement at the mid-papillary muscle level may become a simple, efficient and reliable approach for in vivo IS assessment.

  4. Myocardial infarction does not preclude electrical and hemodynamic benefits of cardiac resynchronization therapy in dyssynchronous canine hearts.

    PubMed

    Rademakers, Leonard M; van Kerckhoven, Roeland; van Deursen, Caroline J M; Strik, Marc; van Hunnik, Arne; Kuiper, Marion; Lampert, Anniek; Klersy, Catherine; Leyva, Francisco; Auricchio, Angelo; Maessen, Jos G; Prinzen, Frits W

    2010-08-01

    Several studies suggest that patients with ischemic cardiomyopathy benefit less from cardiac resynchronization therapy. In a novel animal model of dyssynchronous ischemic cardiomyopathy, we investigated the extent to which the presence of infarction influences the short-term efficacy of cardiac resynchronization therapy. Experiments were performed in canine hearts with left bundle branch block (LBBB, n=19) and chronic myocardial infarction, created by embolization of the left anterior descending or left circumflex arteries followed by LBBB (LBBB+left anterior descending infarction [LADi; n=11] and LBBB+left circumflex infarction [LCXi; n=7], respectively). Pacing leads were positioned in the right atrium and right ventricle and at 8 sites on the left ventricular (LV) free wall. LV pump function was measured using the conductance catheter technique, and synchrony of electrical activation was measured using epicardial mapping and ECG. Average and maximal improvement in electric resynchronization and LV pump function by right ventricular+LV pacing was similar in the 3 groups; however, the site of optimal electrical and mechanical benefit was LV apical in LBBB hearts, LV midlateral in LBBB+LCXi hearts and LV basal-lateral in LBBB+LADi hearts. The best site of pacing was not the site of latest electrical activation but that providing the largest shortening of the QRS complex. During single-site LV pacing the range of atrioventricular delays yielding > or =70% of maximal hemodynamic effect was approximately 50% smaller in infarcted than noninfarcted LBBB hearts (P<0.05). Cardiac resynchronization therapy can improve resynchronization and LV pump function to a similar degree in infarcted and noninfarcted hearts. Optimal lead positioning and timing of LV stimulation, however, require more attention in the infarcted hearts.

  5. Review on CFD simulation in heart with dilated cardiomyopathy and myocardial infarction.

    PubMed

    Chan, Bee Ting; Lim, Einly; Chee, Kok Han; Abu Osman, Noor Azuan

    2013-05-01

    The heart is a sophisticated functional organ that plays a crucial role in the blood circulatory system. Hemodynamics within the heart chamber can be indicative of exert cardiac health. Due to the limitations of current cardiac imaging modalities, computational fluid dynamics (CFD) have been widely used for the purposes of cardiac function assessment and heart disease diagnosis, as they provide detailed insights into the cardiac flow field. An understanding of ventricular hemodynamics and pathological severities can be gained through studies that employ the CFD method. In this research the hemodynamics of two common myocardial diseases, dilated cardiomyopathy (DCM) and myocardial infarction (MI) were investigated, during both the filling phase and the whole cardiac cycle, through a prescribed geometry and fluid structure interaction (FSI) approach. The results of the research indicated that early stage disease identification and the improvement of cardiac assisting devices and therapeutic procedures can be facilitated through the use of the CFD method. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Exercise training reduces insulin resistance in postmyocardial infarction rats

    PubMed Central

    Wang, Youhua; Tian, Zhenjun; Zang, Weijin; Jiang, Hongke; Li, Youyou; Wang, Shengpeng; Chen, Shengfeng

    2015-01-01

    Myocardial infarction (MI) induces cardiac dysfunction and insulin resistance (IR). This study examines the effects of MI-related IR on vasorelaxation and its underlying mechanisms, with a specific focus on the role of exercise in reversing the impaired vasorelaxation. Adult male Sprague–Dawley rats were divided into three groups: Sham, MI, and MI+Exercise. MI+Exercise rats were subjected to 8 weeks of treadmill training. Cardiac contraction, myocardial and arterial structure, vasorelaxation, levels of inflammatory cytokines, expression of eNOS and TNF-α, and activation of PI3K/Akt/eNOS and p38 mitogen-activated protein kinase (p38 MAPK) were determined in aortas. MI significantly impaired endothelial structure and vasodilation (P < 0.05–0.01), as indicated by decreased arterial vasorelaxation to ACh and insulin. MI also attenuated the myocardial contractile response, decreased aortic PI3K/Akt/eNOS expression and phosphorylation by insulin, and increased IL-1β, IL-6, and TNF-α expression and p38 MAPK activity (P < 0.05–0.01). Exercise improved insulin sensitivity in aortas, facilitated myocardial contractile response and arterial vasorelaxation to ACh and insulin, and increased arterial PI3K/Akt/eNOS activity. Moreover, exercise markedly reversed increased p38 MAPK activity and normalized inflammatory cytokines in post-MI arteries. Inhibition of PI3K with LY-294002, and eNOS with L-NAME significantly blocked arterial vasorelaxation and PI3K/Akt/eNOS phosphorylation in response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin plays an important role in MI-related IR. The reversal of IR by exercise is most likely associated with normalizing inflammatory cytokines, increasing the activation of PI3K/Akt/eNOS, and reducing the activation of p38 MAPK. PMID:25907785

  7. N-acetylcysteine prevents low T3 syndrome and attenuates cardiac dysfunction in a male rat model of myocardial infarction.

    PubMed

    Lehnen, Tatiana Ederich; Santos, Marcus Vinicius; Lima, Adrio; Maia, Ana Luiza; Wajner, Simone Magagnin

    2017-02-17

    Nonthyroidal illness syndrome (NTIS) affects patients with myocardial infarction (MI). Oxidative stress has been implicated as a causative factor of NTIS, and reversed via N-acetylcysteine (NAC). Male Wistar rats submitted to left anterior coronary artery occlusion received NAC or placebo. Decreases in T3 levels were noted in MI-placebo at 10 and 28 days post-MI, but not in MI-NAC. Groups exhibited similar infarct areas whereas MI-NAC exhibited higher ejection fraction (EF) than MI-placebo. Left ventricular systolic (LVSd) and diastolic (LVDd) diameters were also preserved in MI-NAC, but not in MI-placebo. EF was positively correlated with T3 levels. Oxidative balance was deranged only in MI-placebo animals. Increased D3 expression was detected in the cardiomyocytes of MI-placebo compared with normal heart tissue. NAC was shown to diminish D3 expression and activity in MI-NAC. These results show that restoring redox balance by NAC treatment prevents NTIS- related thyroid hormone derangement and preserve heart function in rats subjected to MI.

  8. Cardioprotective Effects of Lagenaria siceraria Fruit Juice on Isoproterenol-induced Myocardial Infarction in Wistar Rats: A Biochemical and Histoarchitecture Study.

    PubMed

    Upaganlawar, A; Balaraman, R

    2011-10-01

    The present study was designed to evaluate the cardioprotective effects of Lagenaria siceraria fruit juice in isoproterenol-induced myocardial infarction. Rats injected with isoproterenol (200 mg/kg, s.c.) showed a significant increase in the levels of serum uric acid, tissue Na(++) and Ca(++) ions and membrane-bound Ca(+2)-ATPase activity. A significant decrease in the levels of serum protein, tissue K(+) ion, vitamin E level, and the activities of Na(+)/K(+)-ATPase and mg(+2)-ATPase was observed. Isoproterenol injected rats also showed a significant increase in the intensity of lactate dehydrogenase isoenzyme and histopathologic alterations in the heart. Treatment with L. siceraria fruit juice (400 mg/kg/day, p.o.) for 30 days and administration of isoproterenol on 29(th) and 30(th) days showed a protective effect on altered biochemical and histopathologic changes. These findings indicate the cardioprotective effect of L. siceraria fruit juice in isoproterenol-induced myocardial infarction in rats.

  9. The stem cell adjuvant with Exendin-4 repairs the heart after myocardial infarction via STAT3 activation

    PubMed Central

    Liu, Jianfeng; Wang, Haibin; Wang, Yan; Yin, Yujing; Du, Zhiyan; Liu, Zhiqiang; Yang, Junjie; Hu, Shunying; Wang, Changyong; Chen, Yundai

    2014-01-01

    The poor survival of cells in ischaemic myocardium is a major obstacle for stem cell therapy. Exendin-4 holds the potential of cardioprotective effect based on its pleiotropic activity. This study investigated whether Exendin-4 in conjunction with adipose-derived stem cells (ADSCs) could improve the stem cell survival and contribute to myocardial repairs after infarction. Myocardial infarction (MI) was induced by the left anterior descending artery ligation in adult male Sprague-Dawley rats. ADSCs carrying double-fusion reporter gene [firefly luciferase and monomeric red fluorescent protein (fluc-mRFP)] were quickly injected into border zone of MI in rats treated with or without Exendin-4. Exendin-4 enhanced the survival of transplanted ADSCs, as demonstrated by the longitudinal in vivo bioluminescence imaging. Moreover, ADSCs adjuvant with Exendin-4 decreased oxidative stress, apoptosis and fibrosis. They also improved myocardial viability and cardiac function and increased the differentiation rates of ADSCs into cardiomyocytes and vascular smooth muscle cells in vivo. Then, ADSCs were exposed to hydrogen peroxide/serum deprivation (H2O2/SD) to mimic the ischaemic environment in vitro. Results showed that Exendin-4 decreased the apoptosis and enhanced the paracrine effect of ADSCs. In addition, Exendin-4 activated signal transducers and activators of transcription 3 (STAT3) through the phosphorylation of Akt and ERK1/2. Furthermore, Exendin-4 increased the anti-apoptotic protein Bcl-2, but decreased the pro-apoptotic protein Bax of ADSCs. In conclusion, Exendin-4 could improve the survival and therapeutic efficacy of transplanted ADSCs through STAT3 activation via the phosphorylation of Akt and ERK1/2. This study suggests the potential application of Exendin-4 for stem cell–based heart regeneration. PMID:24779911

  10. [Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats].

    PubMed

    Kong, Ling-Heng; Gu, Xiao-Ming; Su, Xing-Li; Sun, Na; Wei, Ming; Zhu, Juan-Xia; Chang, Pan; Zhou, Jing-Jun

    2016-05-01

    To investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms. Thirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c. Compared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (P<0.01), an increased myocardial apoptosis index (P<0.01), and up-regulated expressions of cleaved caspase-3 and cytochrome c (P<0.01). BDM (20 mmol/L) significantly attenuated these effects induced by calcium paradox, and markedly down-regulated the levels of LVEDP and LDH (P<0.01), lowered myocardial apoptosis index, decreased the content of cleaved caspase-3 and cytochrome c (P<0.01), increased LVDP, and reduced the infarct size (P<0.01). BDM suppresses cell apoptosis and contracture and improves heart function and cell survival in rat hearts exposed to calcium paradox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.

  11. Changes in Sympathetic Innervation of Rat Caudal Artery in Experimental Myocardial Infarction. Effect of Semax Peptide.

    PubMed

    Gorbacheva, A M; Berdalin, A B; Stulova, A N; Nikogosova, A D; Lin, M D; Buravkov, S V; Gavrilova, S A; Koshelev, V B

    2016-08-01

    Activation of the sympathetic nervous system aggravates the course of myocardial infarction. Semax peptide moderated the degree of this activation and prevented the increase in the density of sympathetic endings in rat caudal artery in 28 days after ischemia or ischemia/reperfusion. The peptide reduced the density of α-adrenoreceptors in the caudal artery of rats with myocardial infarction. Semax produced no effect on β-adrenoreceptors in both experimental models. The experiments on isolated segments of the caudal artery revealed reduced vascular responsiveness to electrical stimulation and norepinephrine infusion in rats treated with Semax after ischemia/reperfusion injury.

  12. Neural mechanisms and delayed gastric emptying of liquid induced through acute myocardial infarction in rats.

    PubMed

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de

    2015-02-01

    In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1 mA/10 s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

  13. Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart.

    PubMed

    Buccini, Stephanie; Haider, Khawaja Husnain; Ahmed, Rafeeq P H; Jiang, Shujia; Ashraf, Muhammad

    2012-11-01

    The strategy to reprogram somatic stem cells to pluripotency status has provided an alternative source of surrogate ES cells (ESC). We report efficient reprogramming of multipotent bone marrow (BM) mesenchymal stem cells (MSC) to pluripotent status and the resultant MSC derived iPS cells (MiPS) and their derived progenitors effectively repaired the infarcted heart. MSC from young, male, Oct4-GFP transgenic mice were reprogrammed by retroviral transduction with Oct4, Sox2, Klf4, and c-Myc stemness factors. MiPS thus generated displayed characteristics of mouse ESC including morphology, surface antigens, gene and miR expression profiles. MiPS also formed spontaneously beating cardiac progenitors which expressed cardiac specific transcription factors and protein markers including Gata4, Mef2c, Nkx2.5, myosin heavy chain, troponin-I, and troponin-T, and showed ultra structural characteristics typical of cardiomyocytes. Intramyocardial delivery of MiPS (group-2) and their derivative cardiac-like cells (MiPS-CP; group-3) in a mouse model of acute myocardial infarction showed extensive survival and engraftment at 4 weeks with resultant attenuation of infarct size (p < 0.001 vs. DMEM injected control; n = 4). Engraftment of MiPS-CP was without cardiac tumorigenesis as compared to 21 % in MiPS transplanted animals. Furthermore, angiogenesis was improved in groups-2 and 3 (p < 0.001 vs. control). Transthoracic echocardiography revealed significantly preserved indices of cardiac contractility (ejection fraction p < 0.001 and fractional shortening p < 0.001 vs. control; n = 7). MSC were successfully reprogrammed into MiPS that displayed ESC-like characteristics and differentiated into spontaneously beating cardiomyocytes. Cardiac progenitors derived from MiPS repopulated the infarcted heart without tumorigenesis and improved global cardiac function.

  14. Up-regulation of cardiac nitric oxide synthase 1-derived nitric oxide after myocardial infarction in senescent rats.

    PubMed

    Damy, Thibaud; Ratajczak, Philippe; Robidel, Estelle; Bendall, Jennifer K; Oliviéro, Patricia; Boczkowski, Jorge; Ebrahimian, Talin; Marotte, Françoise; Samuel, Jane-Lise; Heymes, Christophe

    2003-10-01

    Nitric oxide (NO) has been implicated in the development of heart failure, although the source, significance, and functional role of the different NO synthase (NOS) isoforms in this pathology are controversial. The presence of a neuronal-type NOS isoform (NOS1) in the cardiac sarcoplasmic reticulum has been recently discovered, leading to the hypothesis that NOS1-derived NO may notably alter myocardial inotropy. However, the regulation and role(s) of NOS1 in cardiac diseases remain to be determined. Using an experimental model of myocardial infarction (MI) in senescent rats, we demonstrated a significant increase in cardiac NOS1 expression and activity in MI, coupled with the translocation of this enzyme to the sarcolemma through interactions with caveolin-3. The enhanced NOS1 activity counteracts the decrease in cardiac NOS3 expression and activity observed in heart failure. We demonstrated an increased interaction between NOS1 and its regulatory protein HSP90 in post-MI hearts, a potential mechanism for the higher NOS1 activity in this setting. Finally, preferential in vivo inhibition of NOS1 activity enhanced basal post-MI left ventricular dysfunction in senescent rats. These results provide the first evidence that increased NOS1-derived NO production may play a significant role in the autocrine regulation of myocardial contractility after MI in aging rats.

  15. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    SciTech Connect

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  16. Effect of myocardial infarction on the function and metabolism of the non-infarcted muscle

    SciTech Connect

    Hansen, C.A.

    1985-01-01

    Rat hearts were infarcted in vivo by ligation of the left ventricular coronary artery. After one or three weeks, the hearts were isolated and perfused in vitro. Despite the onset of hypertrophy, ventricular function was more depressed in the one- and three-week infarcted hearts than in acutely ligated hearts. These data suggested that the depressed mechanical function was due not only to the loss of viable tissue, but also to alterations occurring in the non-infarcted tissue. The inotropic response to extracellular calcium was depressed in infarcted hearts, such that the mechanical performance of the infarcted heart was likely to be limited by the availability of extracellular calcium under physiological conditions. No limitation in energy production was found as indicated by the maintenance of ATP levels, the creatine phosphate/creatine ratio and normal lactate concentrations in the infarcted hearts. Comparison of the rates of substrate oxidation with MVO/sub 2/ revealed that, in both the sham and infarcted hearts, substrate oxidation, as estimated by /sup 14/CO/sub 2/ production, could not account for the observed MVO/sub 2/. It was found that the rate of /sup 14/CO/sub 2/ production from exogenous labeled palmitate underestimated the actual rate of fatty acid oxidation. This resulted from incomplete equilibration of added (/sup 14/C)-palmitate with the fatty acyl moieties present in acyl carnitine. However, the rate of /sup 14/CO/sub 2/ production from exogenous palmitate was lower in the infarcted than sham hearts.

  17. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats.

    PubMed

    Lam, Vy; Su, Jidong; Hsu, Anna; Gross, Garrett J; Salzman, Nita H; Baker, John E

    2016-01-01

    Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host's metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in

  18. Prevention of brain infarction by postischemic administration of histidine in rats.

    PubMed

    Adachi, Naoto; Liu, Keyue; Arai, Tatsuru

    2005-03-28

    Focal cerebral ischemia for 2 h by occlusion of the right middle cerebral artery provoked severe brain infarction in the rat brain after 24 h. Intraperitoneal administration of histidine, a precursor of histamine, immediately and 6 h after reperfusion, alleviated brain infarction. The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. Although intracerebroventricular administration of mepyramine (3 nmol), an H1 antagonist, did not affect the morphologic outcome in histidine-treated rats, ranitidine (30 nmol), an H2 antagonist, completely abolished the alleviation caused by histidine. These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors.

  19. Cardiac function and remodeling is attenuated in transgenic rats expressing the human kallikrein-1 gene after myocardial infarction.

    PubMed

    Koch, Matthias; Spillmann, Frank; Dendorfer, Andreas; Westermann, Dirk; Altmann, Christine; Sahabi, Merdad; Linthout, Sophie Van; Bader, Michael; Walther, Thomas; Schultheiss, Heinz-Peter; Tschöpe, Carsten

    2006-11-21

    Bradykinin coronary outflow, left ventricular performance and left ventricular dimensions of transgenic rats harboring the human tissue kallikrein-1 gene TGR(hKLK1) were investigated under basal and ischemic conditions. Bradykinin content in the coronary outflow of buffer-perfused, isolated hearts of controls and TGR(hKLK1) was measured by specific radioimmunoassay before and after global ischemia. Left ventricular function and left ventricular dimensions were determined in vivo using a tip catheter and echocardiography 6 days and 3 weeks after induction of myocardial infarction. Left ventricular type I collagen mRNA expression was analyzed by RNase protection assay. Compared to controls, basal bradykinin outflow was 3.5 fold increased in TGR(hKLK1). Ischemia induced an increase of bradykinin coronary outflow in controls but did not induce a further increase in TGR(hKLK1). However, despite similar unchanged infarction sizes, left ventricular function and remodeling improved in TGR(hKLK1) after myocardial infarction, indicated by an increase in left ventricular pressure (+34%; P<0.05), contractility (dp/dt max. +25%; P<0.05), and in ejection fraction (+20%; P<0.05) as well as by a reduction in left ventricular enddiastolic pressure (-49%, P<0.05), left ventricular enddiastolic diameter (-20%, P<0.05), and collagen mRNA expression (-15%, P<0.05) compared to controls. A chronically activated transgenic kallikrein kinin system with expression of human kallikrein-1 gene counteracts the progression of left ventricular contractile dysfunction after experimental myocardial infarction. Further studies have to show whether these results can be caused by other therapeutically options. Long acting bradykinin receptor agonists might be an alternative option to improve ischemic heart disease.

  20. Inhibition of RhoA/Rho kinase by ibuprofen exerts cardioprotective effect on isoproterenol induced myocardial infarction in rats.

    PubMed

    Patel, Prexita; Parikh, Mihir; Shah, Hital; Gandhi, Tejal

    2016-11-15

    Myocardial infarction (MI) and hypertension are the leading cause of death worldwide so protection of heart is focus of intense research. Rho-kinase, a downstream effector of protein involved in MI and hypertension, is inhibited by ibuprofen. This study aims to elucidate cardioprotective effect of ibuprofen in rats. MI was produced in rats with 85mg/kg isoproterenol (ISO) administered s.c. twice at an interval of 24h. The rats were randomized into six groups: (I) Normal; (II) ISO; (III) ISO + ascorbic acid (250mg/kg p.o.); (IV-VI) ISO + ibuprofen (30, 60 and 90mg/kg p.o). After the completion of the study period of 21 days, cardiac function and biomarkers were assessed. Pre-treatment with ibuprofen (30, 60 and 90mg/kg p.o) ameliorated high BP and left ventricular dysfunction, furthermore it prevented the rise in CKMB, LDH and α-HBDH, suggesting the effect of ibuprofen in maintenance of cell membrane integrity. In addition, it also prevented alteration in the levels of electrolytes, ATPase activity and antioxidant status. Ibuprofen suppressed ISO-induced ROCK-1 mRNA expression and histological changes. Ibuprofen provided cardioprotection in a model of myocardial infarction, by restoring most of the altered physical, physiological, biochemical, haemodynamic parameters, antioxidant status, and histological changes and by inhibiting ROCK-1 mRNA expression. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Eplerenone: the evidence for its place in the treatment of heart failure after myocardial infarction

    PubMed Central

    Nadin, Carole

    2005-01-01

    Introduction: Heart failure is a frequent complication after acute myocardial infarction (MI) and carries a poor prognosis. Current treatments inhibit the renin-angiotensin-aldosterone system but suppression of aldosterone may be incomplete. The aldosterone antagonist spironolactone has been shown to improve survival in patients with chronic, severe heart failure. Eplerenone is a selective aldosterone antagonist expected to have a lower incidence of hormonal side effects than spironolactone. Aims: To assess the evidence on the therapeutic value of eplerenone for treatment of heart failure in adults. Evidence review: The evidence base consists of one large double-blind placebo-controlled multicenter randomized trial in over 6000 patients with postmyocardial infarction (MI) heart failure, comparing eplerenone plus standard therapy with placebo plus standard therapy. All the main outcomes were patient-oriented. Evidence from this trial shows that eplerenone improves survival and reduces cardiovascular hospitalization/mortality, compared with standard treatment alone. The incidence of hormonal side effects is no greater than with placebo. The risk of hyperkalemia is significantly increased, especially in patients with low creatinine clearance. Eplerenone was both more effective and more costly than standard treatment alone. The cost-effectiveness ratio has been estimated at $US10 402–21 876 per life-year gained. Place in therapy: Eplerenone reduces mortality compared with current treatment alone in patients with post-MI heart failure, at additional cost. Direct comparative evidence is needed to assess its efficacy versus spironolactone. It may be valuable in patients who are intolerant to the hormonal side effects of spironolactone. PMID:22500149

  2. Sufentanil-medetomidine anaesthesia compared with fentanyl/fluanisone-midazolam is associated with fewer ventricular arrhythmias and death during experimental myocardial infarction in rats and limits infarct size following reperfusion.

    PubMed

    Ter Horst, Ellis N; Krijnen, Paul A J; Flecknell, Paul; Meyer, Klaas W; Kramer, Klaas; van der Laan, Anja M; Piek, Jan J; Niessen, Hans W M

    2017-01-01

    To improve infarct healing following myocardial infarction in humans, therapeutic interventions can be applied during the inflammatory response. Animal models are widely used to study this process. However, induction of MI in rodents is associated with high mortality due to ventricular fibrillation (VF) during coronary artery ligation. The anaesthetic agent used during the procedure appears to influence the frequency of this complication. In this retrospective study, the effect on ventricular arrhythmia incidence during ligation and infarct size following in vivo reperfusion of two anaesthetic regimens, sufentanil-medetomidine (SM) and fentanyl/fluanisone-midazolam (FFM) was evaluated in rats. Anaesthetics were administered subcutaneously using fentanyl/fluanisone (0.5 mL/kg) with midazolam (5 mg/kg) (FFM group, n = 48) or sufentanil (0.05 mg/kg) with medetomidine (0.15 mg/kg) (SM group, n = 47). The coronary artery was ligated for 40 min to induce MI. Heart rate and ventricular arrhythmias were recorded during ligation, and infarct size was measured via histochemistry after three days of reperfusion. In the SM group, heart rate and VF incidence were lower throughout the experiment compared with the FFM group (6% versus 30%) ( P < 0.01). Fatal VF did not occur in the SM group whereas this occurred in 25% of the animals in the FFM group. Additionally, after three days of reperfusion, the infarcted area following SM anaesthesia was less than half as large as that following FFM anaesthesia (8.5 ± 6.4% versus 20.7 ± 5.6%) ( P < 0.01). Therefore, to minimize the possibility of complications related to VF and acute death arising during ligation, SM anaesthesia is recommended for experimental MI in rats.

  3. Rubidium-82 PET imaging is feasible in a rat myocardial infarction model.

    PubMed

    Ghotbi, Adam Ali; Clemmensen, Andreas; Kyhl, Kasper; Follin, Bjarke; Hasbak, Philip; Engstrøm, Thomas; Ripa, Rasmus Sejersten; Kjaer, Andreas

    2017-07-18

    Small-animal myocardial infarct models are frequently used in the assessment of new cardioprotective strategies. A validated quantification of perfusion using a non-cyclotron-dependent PET tracer would be of importance in monitoring response to therapy. We tested whether myocardial PET perfusion imaging is feasible with Rubidium-82 ((82)Rb) in a small-animal scanner using a rat myocardial infarct model. 18 Sprague-Dawley rats underwent permanent coronary artery ligation (infarct group), and 11 rats underwent ischemia-reperfusion (reperfusion group) procedure. (82)Rb-PET and magnetic resonance imaging (MRI) were conducted before and after the intervention. Perfusion was compared to both left ventricle ejection fraction (LVEF) and infarct size assessed by MRI. Follow-up global (82)Rb-uptake correlated significantly with infarct size (infarct group: r = -0.81, P < 0.001 and reperfusion group: r = -0.61, P = 0.04). Only (82)Rb-uptake in the infarct group correlated with LVEF. At follow-up, a higher segmental (82)Rb-uptake in the infarct group was associated with better wall motion (β = 0.034, CI [0.028;0.039], P < 0.001, R (2) = 0.30), and inversely associated with scar transmurality (β = -2.4 [-2.6; -2.2], P < 0.001, R (2) = 0.59). The associations were similar for the reperfusion group. (82)Rb-PET is feasible in small animal scanners despite the long positron range and enables fast and time-efficient myocardial perfusion imaging in rat models.

  4. Haemodynamic unloading increases the survival and affects the differentiation of cardiac stem cells after implantation into an infarcted heart.

    PubMed

    Kurazumi, Hiroshi; Li, Tao-Sheng; Takemoto, Yoshihiro; Suzuki, Ryo; Mikamo, Akihito; Guo, Chang-Ying; Murata, Tomoaki; Hamano, Kimikazu

    2014-06-01

    It has been anticipated that stem cell therapy is capable of repairing an injured heart but is currently limited by its marginal efficacy. We believe that mechanical stress due to haemodynamic loading may negate the therapeutic potency of stem cells and therefore investigated how haemodynamic unloading affects the survival and differentiation of stem cells after implantation into an infarcted heart. A left ventricular (LV) haemodynamic unloading model was implemented by heterotopic transplantation of an infarcted donor heart into another healthy mouse. An in situ infarcted heart with general haemodynamic loading was used as control. A total of 5 million cardiac stem cells expanded from green fluorescence protein (GFP)-transgenic mouse were intramyocardially implanted into the infarcted LVs of haemodynamically unloaded donor heart or general haemodynamic loaded heart. The survival and differentiation of the implanted cardiac stem cells were evaluated by histological analyses at 3 and 21 days after cell implantation (n = 5-6 in each time points per group). Compared with the general haemodynamic loading condition, haemodynamic unloading of the infarcted hearts significantly improved the survival, increased the proliferation and inhibited the apoptosis of cardiac stem cells at 21 days after cell implantation (P < 0.05). In addition, the number of GFP(+)/Sca-1(+) cells was much higher in the unloaded hearts than in the loaded hearts at 21 days after cell implantation, although the difference was not statistically significant (5.67 ± 5.10 vs 0.75 ± 0.50, P = 0.051). Among the surviving GFP(+) donor cells 21 days after implantation, the expressions of platelet endothelial cell adhesion molecule-1, smooth muscle actin and sarcomeric alpha actin were ~7, 38 and 27% in the loaded heart and ~19, 14 and 55% in the unloaded heart, respectively. Haemodynamic unloading favours the survival/engraftment of donor stem cells and affects their differentiation after implantation into

  5. Epac-Rap1-activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction.

    PubMed

    Khan, Irfan; Ali, Anwar; Akhter, Muhammad Aleem; Naeem, Nadia; Chotani, Maqsood Ahmed; Iqbal, Hana'a; Kabir, Nurul; Atiq, Mehnaz; Salim, Asmat

    2017-04-01

    Rap1, a member of Ras superfamily of small GTP-binding proteins, is involved in cardiovascular biology in numerous ways. It is an evolutionary conserved regulator of adhesion, polarity, differentiation and growth. Our aim was to analyze Rap1-activated rat bone marrow mesenchymal stem cells (MSCs) for their potential role in adhesion and cardiac differentiation. Myocardial infarction (MI) was produced in Sprague Dawley (SD) rats through occlusion of the left anterior descending coronary artery. MSCs were treated with 8-pCPT-2'-O-Me-cAMP (CPT) to activate Rap1. Normal (untreated) and CPT-treated MSCs were transplanted through intramyocardial injection in respective groups. Cardiac function was assessed by echocardiography at 2 and 4 weeks after cell transplantation. Histological analysis was performed to observe changes at tissue level. Homing of CPT-treated MSCs was significantly (***P<.001) higher as compared to normal MSCs in the infarcted hearts. This may be due to increase in the gene expression of some of the cell adhesion molecules as evident by qRT-PCR analysis. Significant (***P<.001) improvement in the restoration of heart function in terms of left ventricular diastolic and systolic internal diameters (LVIDd, LVIDs), % ejection fraction, % fraction shortening and end-systolic and end-diastolic volumes were observed in CPT-treated MSCs as compared to the MI model. Histological analyses showed significant (***P<.001) reduction in scar formation in the CPT-treated group. Differentiation of treated MSCs into functional cardiomyocytes was evident through immunohistochemical staining. LV wall thickness was also preserved significantly (***P<.001). Blood vessel formation was more pronounced in CPT-treated group although both cell therapy groups showed significant increase as compared to MI model. Our findings showed that pharmacological activation of Epac-Rap1 improves cardiac function through better survival, adhesion and differentiation of transplanted cells

  6. Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral infarction rat model.

    PubMed

    Zhou, Liang; Zhang, Jie; Wang, Chao; Sun, Qiangsan

    2017-06-01

    We aimed to investigate the effect and mechanisms of tanshinone (TSN) IIA in cerebral infarction. The cerebral infarction rat model was established by middle cerebral artery occlusion (MCAO). After pretreatment with TSN, cerebral infarct volume, cerebral edema, and neurological deficits score were evaluated, as well as cell apoptosis in hippocampus and cortex of the brain was examined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). In addition, rat primary neuronal cells were isolated and cultured in oxygen-glucose deprivation (OGD) conditions. After pretreatment with TSN, cell viability and apoptosis were observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. The expressions of Bax and B-cell lymphoma 2 (Bcl-2) were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. Compared with untreated cerebral infarction rat, TSN treatment significantly reduced cerebral infarct volume, cerebral edema, and neurological deficits score ( P < 0.05). Cell apoptosis as well as the levels of IL-6, TNF-α, and CRP in hippocampus and cortex of cerebral infarction rat were inhibited after pretreatment with TSN ( P < 0.05). Furthermore, TSN remarkably increased cell viability and inhibited cell apoptosis ratio ( P < 0.05) in OGD-induced rat neuronal cells. Besides, TSN significantly downregulated the expression of Bax and upregulated Bcl-2 ( P < 0.05). TSN IIA has a preventive effect on cerebral infarction by inhibiting neuronal cell apoptosis and inflammatory response in vitro and in vivo.

  7. Endoscopic Time-Lapse Imaging of Immune Cells in Infarcted Mouse Hearts

    PubMed Central

    Leuschner, Florian; Gorbatov, Rostic; Kim, Jun Ki; Ueno, Takuya; Nahrendorf, Matthias; Yun, Seok Hyun

    2013-01-01

    Rationale High-resolution imaging of the heart in vivo is challenging due to the difficulty in accessing the heart and the tissue motion caused by the heartbeat. Objective Here, we describe a suction-assisted endoscope for visualizing fluorescently labeled cells and vessels in the beating heart tissue through a small incision made in the intercostal space. Methods and Results A suction tube with a diameter of 2-3 mm stabilizes the local tissue motion safely and effectively at a suction pressure of 50 mmHg. Using a minimally invasive endoscope integrated into a confocal microscope, we performed fluorescence cellular imaging in both normal and diseased hearts in live mice for an hour per session repeatedly over a few weeks. Real-time imaging revealed the surprisingly rapid infiltration of CX3CR1+ monocytes into the injured site within several minutes after acute myocardial infarction (MI). Conclusions The time-lapse analysis of flowing and rolling (patrolling) monocytes in the heart and the peripheral circulation provide evidence that the massively recruited monocytes come first from the vascular reservoir and later from the spleen. The imaging method requires minimal surgical preparation and can be implemented into standard intravital microscopes. Our results demonstrate the applicability of our imaging method for a wide range of cardiovascular research. PMID:23392842

  8. Acute Effects of Vagotomy on Baroreflex Equilibrium Diagram in Rats with Chronic Heart Failure

    PubMed Central

    Kawada, Toru; Li, Meihua; Zheng, Can; Sugimachi, Masaru

    2016-01-01

    The arterial baroreflex system can be divided into the neural arc, from pressure input to efferent sympathetic nerve activity (SNA), and the peripheral arc, from SNA to arterial pressure (AP). Plotting the neural and peripheral arcs on a pressure–SNA plane yields a baroreflex equilibrium diagram. We examined the effects of vagotomy on the open-loop static characteristics of the carotid sinus baroreflex in normal control rats (NC, n = 10) and rats with heart failure after myocardial infarction (MI, n = 10). In the NC group, vagotomy shifted the neural arc toward higher SNA and decreased the slope of the peripheral arc. Consequently, the operating-point SNA increased without a significant change in the operating-point AP on the baroreflex equilibrium diagram. These vagotomy-induced effects were not observed in the MI group, suggesting a loss of vagal modulation of the carotid sinus baroreflex function in heart failure. PMID:27594790

  9. An improved automated method to quantitate infarct volume in triphenyltetrazolium stained rat brain sections.

    PubMed

    Regan, Hillary K; Detwiler, Theodore J; Huang, Judy C; Lynch, Joseph J; Regan, Christopher P

    2007-01-01

    The identification of acute neuroprotectants relies heavily on rodent stroke models. It is well know that some of the more common models used can exhibit a relatively high degree of inter animal variability. This necessitates the need to increase the sample size per group and to run concomitant positive and negative control groups with each study in order to increase the consistency and reproducibility of the model. As such, one aspect of these studies that has become more labor intensive is the measurement of infarct volume post study. Herein, we describe a simple method to determine stroke infarct volume in triphenyltetrazolium (TTC) stained brain sections utilizing an automated set of routines using standard software. The method was first validated by determining the correlation of infarct volumes derived from the manual measurements vs the automated method for the same samples across a wide range of infarcts. This comparison resulted in a significant correlation (r=0.99) indicating that the automated method was a valid method to assess infarct volume across a wide range in lesion volumes. Next, the automated infarct analysis tool was used to determine the effect of (+)-MK801, a well known neuroprotectant, on infarct volume after cerebral ischemia. This study demonstrated a significant reduction in infarct volume in (+)-MK801 treated rats. These data demonstrate a simple, accurate automated routine to measure lesion volume in TTC stained sections.

  10. Accelerated infarct development, cytogenesis and apoptosis following transient cerebral ischemia in aged rats.

    PubMed

    Popa-Wagner, Aurel; Badan, Irina; Walker, Lary; Groppa, Sergiu; Patrana, Nicoleta; Kessler, Christof

    2007-03-01

    Old age is associated with a deficient recovery from stroke, but the cellular mechanisms underlying such phenomena are poorly understood. To address this issue, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. Aged rats showed a delayed and suboptimal functional recovery in the post-stroke period. Using BrdU-labeling, quantitative immunohistochemistry and 3-D reconstruction of confocal images, we found that aged rats are predisposed to rapidly develop an infarct within the first few days after ischemia. The emergence of the necrotic zone is associated with a high rate of cellular degeneration, premature accumulation of proliferating BrdU-positive cells that appear to emanate from capillaries in the infarcted area, and a large number of apoptotic cells. With double labeling techniques, we were able to identify, for the first time, over 60% of BrdU-positive cells either as reactive microglia (45%), oligodendrocyte progenitors (17%), astrocytes (23%), CD8+ lymphocytes (4%), or apoptotic cells (<1%). Paradoxically, despite a robust reactive phenotype of microglia and astrocytes in aged rats, at 1-week post-stroke, the number of proliferating microglia and astrocytes was lower in aged rats than in young rats. Our data indicate that aging is associated with rapid infarct development and a poor prognosis for full recovery from stroke that is correlated with premature cellular proliferation and increased cellular degeneration and apoptosis in the infarcted area.

  11. Novel approaches to the post-myocardial infarction/heart failure neural remodeling.

    PubMed

    D'Elia, Emilia; Pascale, Alessia; Marchesi, Nicoletta; Ferrero, Paolo; Senni, Michele; Govoni, Stefano; Gronda, Edoardo; Vanoli, Emilio

    2014-09-01

    The review aims to discuss the role of nerve growth factor (NGF) as a potential novel biomarker in post-myocardial infarction (MI) and in heart failure (HF), with a specific focus on neural remodeling and sprouting processes occurring after tissue damage. Many experimental data show that MI induces nerve sprouting, leading to increased sympathetic outflow and higher risk of ventricular arrhythmias and sudden cardiac death. In this framework, cardiac and circulating NGF might be an indicator of the innervation process and neural remodeling: it dramatically increases after MI, while it declines along with advanced HF and ventricular dysfunction. The bimodal behavior of NGF in acute and chronic settings leads to the speculation that NGF modulation may be a pharmacological target for intervention in different stages of the ischemic heart disease. Specifically, a fascinating possibility is to support or to inhibit NGF receptors, in order to prevent negative cardiac remodeling after MI and consequent ventricular dysfunction.

  12. Preservation of pre-excitation despite acute myocardial infarction complicated by complete heart block.

    PubMed Central

    Boroomand, K.; Armstrong, P. W.

    1978-01-01

    In a 53-year-old man with ventricular pre-excitation (normal PR interval, QRS interval of 0.12 seconds and delta-waves) acute inferior wall myocardial infarction was complicated by, successively, first-degree atrioventricular block, second-degree atrioventricular block (Wenckebach type) and complete heart block. The QRS pattern of pre-excitation was preserved throughout these events. The classification of ventricular pre-excitation is reviewed and the correlation between the various electrocardiographic patterns (the Wolff-Parkinson-White syndrome and its variants and the Lown-Ganong-Levine syndrome) and the anomalous conduction pathways of Kent, James and Mahaim are discussed. In this case the best possible explanation for preservation of pre-excitation during complete heart block was the existence of accessory fibres of Mahaim. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 PMID:679113

  13. β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study.

    PubMed

    Puymirat, Etienne; Riant, Elisabeth; Aissoui, Nadia; Soria, Angèle; Ducrocq, Gregory; Coste, Pierre; Cottin, Yves; Aupetit, Jean François; Bonnefoy, Eric; Blanchard, Didier; Cattan, Simon; Steg, Gabriel; Schiele, François; Ferrières, Jean; Juillière, Yves; Simon, Tabassome; Danchin, Nicolas

    2016-09-20

     To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction.  Multicentre prospective cohort study.  Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005.  2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction.  Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use.  β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results.  Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction.Trial registration Clinical trials NCT00673036. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study

    PubMed Central

    Riant, Elisabeth; Aissoui, Nadia; Soria, Angèle; Ducrocq, Gregory; Coste, Pierre; Cottin, Yves; Aupetit, Jean François; Bonnefoy, Eric; Blanchard, Didier; Cattan, Simon; Steg, Gabriel; Schiele, François; Ferrières, Jean; Juillière, Yves; Simon, Tabassome; Danchin, Nicolas

    2016-01-01

    Objective To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction. Design Multicentre prospective cohort study. Setting Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005. Participants 2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction. Main outcome measures Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use. Results β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results. Conclusions Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction. Trial registration Clinical trials NCT00673036. PMID:27650822

  15. Beneficial effects of exercise training in heart failure are lost in male diabetic rats.

    PubMed

    Boudia, Dalila; Domergue, Valérie; Mateo, Phlippe; Fazal, Loubina; Prud'homme, Mathilde; Prigent, Heloise; Delcayre, Claude; Cohen-Solal, Alain; Garnier, Anne; Ventura-Clapier, Renee; Samuel, Jane-Lise

    2017-09-07

    Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n= 53) or high-fat, high-sucrose (HFHS) diet (D, n=66) for 6 months. After 2 months of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation (Sham). Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for eight additional weeks or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 weeks resulted in a higher working power developed by MI animals with diabetes, and improved glycaemia but not ejection fraction or pathological phenotype. In contrast exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean- but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. Copyright © 2017, Journal of Applied Physiology.

  16. Multiparametric analysis of heart rate variability used for risk stratification among survivors of acute myocardial infarction.

    PubMed

    Voss, A; Hnatkova, K; Wessel, N; Kurths, J; Sander, A; Schirdewan, A; Camm, A J; Malik, M

    1998-01-01

    A multiparametric heart rate variability analysis was performed to prove if combined heart rate variability (HRV) measures of different domains improve the result of risk stratification in patients after myocardial infarction. In this study, standard time domain, frequency domain and non-linear dynamics measures of HRV assessment were applied to 572 survivors of acute myocardial infarction. Three parameter sets each consisting of 4 parameters were applied and compared with the standard measurement of global heart rate variability HRVi. Discriminant analysis technique and t-test were performed to separate the high risk groups from the survivors. The predictive value of this approach was evaluated with receiver operator (ROC) and positive predictive accuracy (PPA) curves. Results--The discriminant analysis shows a separation of patients suffered by all cause mortality in 80% (best single parameter 74%) and sudden arrhythmic death in 86% (73%). All parameters of set 1 show a high significant difference (p < 0.001) between survivors and non-survivors based on two-tailed t-test. The specificity level of the multivariate parameter sets is at the 70% sensitivity level (ROC) about 85-90%, whereas HRVi shows maximum levels of 70%. The PPA in the all cause mortality group is at the 70% sensitivity level twice as high as the univariate HRV measure and increases to more than fourfold as high within the VT/VF group. In conclusion, in this population, the multiparametric approach with the combination of four parameters from all domains especially from NLD seems to be a better predictor of high arrhythmia risk than the standard measurement of global heart rate variability.

  17. Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study.

    PubMed

    Olivares, Emerson L; Marassi, Michelle P; Fortunato, Rodrigo S; da Silva, Alba C M; Costa-e-Sousa, Ricardo H; Araújo, Iracema G; Mattos, Elisabete C; Masuda, Masako O; Mulcahey, Michelle A; Huang, Stephen A; Bianco, Antonio C; Carvalho, Denise P

    2007-10-01

    In humans, there is a significant decrease in serum T(3) and increase in rT(3) at different time points after myocardial infarction, whereas serum TSH and T(4) remain unaltered. We report here a time course study of pituitary-thyroid function and thyroid hormone metabolism in rats subjected to myocardial infarction by left coronary ligation (INF). INF- and sham-operated animals were followed by serial deiodination assays and thyroid function tests, just before, and 1, 4, 8, and 12 wk after surgery. At 4 and 12 wk after INF, liver type 1 deiodinase activity was significantly lower, confirming tissue hypothyroidism. Type 3 deiodinase (D3) activity was robustly induced 1 wk after INF only in the infarcted myocardium. Reminiscent of the consumptive hypothyroidism observed in patients with large D3-expressing tumors, this induction of cardiac D3 activity was associated with a decrease in both serum T(4) ( approximately 50% decrease) and T(3) (37% decrease), despite compensatory stimulation of the thyroid. Thyroid stimulation was documented by both hyperthyrotropinemia and radioiodine uptake. Serum TSH increased by 4.3-fold in the first and 3.1-fold in the fourth weeks (P < 0.01), returning to the basal levels thereafter. Thyroid sodium/iodide-symporter function increased 1 wk after INF, accompanying the increased serum TSH. We conclude that the acute decrease in serum T(4) and T(3) after INF is due to increased thyroid hormone catabolism from ectopic D3 expression in the heart.

  18. Measures of brain morphology and infarction in the framingham heart study: establishing what is normal.

    PubMed

    DeCarli, Charles; Massaro, Joseph; Harvey, Danielle; Hald, John; Tullberg, Mats; Au, Rhoda; Beiser, Alexa; D'Agostino, Ralph; Wolf, Philip A

    2005-04-01

    Numerous anatomical and brain imaging studies find substantial differences in brain structure between men and women across the span of human aging. The ability to extend the results of many of these studies to the general population is limited, however, due to the generally small sample size and restrictive health criteria of these studies. Moreover, little attention has been paid to the possible impact of brain infarction on age-related differences in regional brain volumes. Given the current lack of normative data on gender and aging related differences in regional brain morphology, particularly with regard to the impact of brain infarctions, we chose to quantify brain MRIs from more than 2200 male and female participants of the Framingham Heart Study who ranged in age from 34 to 97 years. We believe that MRI analysis of the Framingham Heart Study more closely represents the general population enabling more accurate estimates of regional brain changes that occur as the consequence of normal aging. As predicted, men had significantly larger brain volumes than women, but these differences were generally not significant after correcting for gender related differences in head size. Age explained approximately 50% of total cerebral brain volume differences, but age-related differences were generally small prior to age 50, declining substantially thereafter. Frontal lobe volumes showed the greatest decline with age (approximately 12%), whereas smaller differences were found for the temporal lobes (approximately 9%). Age-related differences in occipital and parietal lobe were modest. Age-related gender differences were generally small, except for the frontal lobe where men had significantly smaller lobar brain volumes throughout the age range studied. The prevalence of MRI infarction was common after age 50, increased linearly with age and was associated with significantly larger white matter hyperintensity (WMH) volumes beyond that associated with age

  19. Non-photic solar associations of heart rate variability and myocardial infarction

    NASA Astrophysics Data System (ADS)

    Cornélissen, Germaine; Halberg, Franz; Breus, Tamara; Syutkina, Elena V.; Baevsky, Roman; Weydahl, Andi; Watanabe, Yoshihiko; Otsuka, Kuniaki; Siegelova, Jarmila; Fiser, Bohumil; Bakken, Earl E.

    2002-03-01

    Alignment of serial epidemiological, physiological, including electrocardiographic data with variations in galactic cosmic rays, geomagnetic activity, and atmospheric pressure suggests the possibility of links among these physical environmental variations and health risks, such as myocardial infarctions and ischemic strokes, among others. An increase in the incidence of myocardial infarction in association with magnetic storms, reported by several investigators from Russia, Israel, Italy and Mexico, accounts in Minnesota for a 5% (220cases/year) increase in mortality during years of maximal solar activity by comparison with years of minimal solar activity. Magnetic storms are also found to decrease heart rate variability (HRV), indicating a possible mechanism since a reduced HRV is a prognostic factor for coronary artery disease and myocardial infarction. Longitudinal electrocardiographic monitoring for a week or much longer spans in different geographic locations, notably in the auroral oval, further suggests that the decrease in HRV affects spectral regions other than that around 3.6s (0.15-0.40Hz), reportedly associated with the parasympathetic nervous system. Differences in some associations are observed from solar cycle to solar cycle, and as a function of solar cycle stage, a finding resolving controversies. Coordinated physiological and physical monitoring, the scope of an international project on the Biosphere and the Cosmos, seeks reference values for a better understanding of environmental effects on human health and for testing the merit of space weather reports that could prompt countermeasures in space and on earth. Physiological data being collected systematically worldwide and morbidity/mortality statistics from causes such as myocardial infarction and stroke constitute invaluable data bases for assessing changes within the physiological range, for detecting environmental effects and for recognizing endogenous as well as exogenous disease

  20. Serial heart rhythm complexity changes in patients with anterior wall ST segment elevation myocardial infarction

    NASA Astrophysics Data System (ADS)

    Chiu, Hung-Chih; Ma, Hsi-Pin; Lin, Chen; Lo, Men-Tzung; Lin, Lian-Yu; Wu, Cho-Kai; Chiang, Jiun-Yang; Lee, Jen-Kuang; Hung, Chi-Sheng; Wang, Tzung-Dau; Daisy Liu, Li-Yu; Ho, Yi-Lwun; Lin, Yen-Hung; Peng, Chung-Kang

    2017-03-01

    Heart rhythm complexity analysis has been shown to have good prognostic power in patients with cardiovascular disease. The aim of this study was to analyze serial changes in heart rhythm complexity from the acute to chronic phase of acute myocardial infarction (MI). We prospectively enrolled 27 patients with anterior wall ST segment elevation myocardial infarction (STEMI) and 42 control subjects. In detrended fluctuation analysis (DFA), the patients had significantly lower DFAα2 in the acute stage (within 72 hours) and lower DFAα1 at 3 months and 12 months after MI. In multiscale entropy (MSE) analysis, the patients had a lower slope 5 in the acute stage, which then gradually increased during the follow-up period. The areas under the MSE curves for scale 1 to 5 (area 1-5) and 6 to 20 (area 6-20) were lower throughout the chronic stage. Area 6-20 had the greatest discriminatory power to differentiate the post-MI patients (at 1 year) from the controls. In both the net reclassification improvement and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of the linear parameters to differentiate the post-MI patients from the controls. In conclusion, the patients with STEMI had serial changes in cardiac complexity.

  1. Serial heart rhythm complexity changes in patients with anterior wall ST segment elevation myocardial infarction

    PubMed Central

    Chiu, Hung-Chih; Ma, Hsi-Pin; Lin, Chen; Lo, Men-Tzung; Lin, Lian-Yu; Wu, Cho-Kai; Chiang, Jiun-Yang; Lee, Jen-Kuang; Hung, Chi-Sheng; Wang, Tzung-Dau; Daisy Liu, Li-Yu; Ho, Yi-Lwun; Lin, Yen-Hung; Peng, Chung-Kang

    2017-01-01

    Heart rhythm complexity analysis has been shown to have good prognostic power in patients with cardiovascular disease. The aim of this study was to analyze serial changes in heart rhythm complexity from the acute to chronic phase of acute myocardial infarction (MI). We prospectively enrolled 27 patients with anterior wall ST segment elevation myocardial infarction (STEMI) and 42 control subjects. In detrended fluctuation analysis (DFA), the patients had significantly lower DFAα2 in the acute stage (within 72 hours) and lower DFAα1 at 3 months and 12 months after MI. In multiscale entropy (MSE) analysis, the patients had a lower slope 5 in the acute stage, which then gradually increased during the follow-up period. The areas under the MSE curves for scale 1 to 5 (area 1–5) and 6 to 20 (area 6–20) were lower throughout the chronic stage. Area 6–20 had the greatest discriminatory power to differentiate the post-MI patients (at 1 year) from the controls. In both the net reclassification improvement and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of the linear parameters to differentiate the post-MI patients from the controls. In conclusion, the patients with STEMI had serial changes in cardiac complexity. PMID:28252107

  2. Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats

    PubMed Central

    Veiga, Eduardo C A; Antonio, Ednei L; Bocalini, Danilo S; Murad, Neif; Abreu, Luiz C; Tucci, Paulo J F; Sato, Monica A

    2011-01-01

    OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean ± SEM) were analyzed using a two-way ANOVA model followed by Tukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58±3.04 vs. 37.59±3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73±1.52 vs. 45.48±3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36±2% and 39±3%, respectively) were smaller than those for the exercise sham surgery (ES, 67±1%) and sedentary sham surgery (SS, 69±2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4±0.3) and exercised myocardial infarction (5.5±0.3) rats than in the SS (2.4±0.1) and ES (2.2±0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model. PMID:21789396

  3. Prevention of anemia alleviates heart hypertrophy in copper deficient rats

    SciTech Connect

    Lure, M.D.; Fields, M.; Lewis, C.G. Univ. of Maryland, College Park Georgetown Univ., Washington, DC )

    1991-03-11

    The present investigation was designed to examine the role of anemia in the cardiomegaly and myocardial pathology of copper deficiency. Weanling rats were fed a copper deficient diet containing either starch (ST) or fructose (FRU) for five weeks. Six rats consuming the FRU diet were intraperitoneally injected once a week with 1.0 ml/100g bw of packed red blood cells (RBC) obtained from copper deficient rats fed ST. FRU rats injected with RBC did not develop anemia. Additionally, none of the injected rats exhibited heart hypertrophy or gross pathology and all survived. In contrast, non-injected FRU rats were anemic, exhibited severe signs of copper deficiency which include heart hypertrophy with gross pathology, and 44% died. Maintaining the hematocrit with RBC injections resulted in normal heart histology and prevented the mortality associated with the fructose x copper interaction. The finding suggest that the anemia associated with copper deficiency contributes to heart pathology.

  4. Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs.

    PubMed

    Zheng, Xiaoxin; Li, Xiaoyan; Lyu, Yongnan; He, Yiyu; Wan, Weiguo; Jiang, Xuejun

    2016-08-04

    BACKGROUND The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. MATERIAL AND METHODS MI and RSD were induced in Sprague-Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. RESULTS In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats. CONCLUSIONS The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21.

  5. Analysis on mechanism of ATP-sensitive K+ channel opener natakalim improving congestive heart failure after myocardial infarction

    PubMed Central

    Jin, Feng

    2016-01-01

    The action mechanism of natakalim, a novel ATP-sensitive potassium channel opener, was studied in ameliorating the congestive heart failure (CHF) after myocardial infarction. A total of 25 healthy Wistar male rats (age, 10 weeks; average weight, 300 g) were selected, and the CHF models after acute myocardial infarction (AMI) were prepared by ligation of left anterior descending branch. They were randomly divided into the sham operation group, the model group and the groups of 1, 3 and 9 mg/kg/day natakalims. Each group had 5 mice that were sacrificed after 8 weeks. We compared left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), left ventricular mass index, myocardial cell cross-sectional area, myocardial collagen content, plasma endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) levels. Compared with the sham operation, the LVEDD and NT-proBNP in the model group and each natakalim group were elevated. LVEF decreased significantly, while the left ventricular mass index, myocardial cell cross-sectional area, myocardial collagen content, plasma ET-1 and eNOS levels increased. Natakalim intervention improved the above changes and the improvement effect of 3 mg/kg/day group was the highest. The mechanism of natakalim against the endothelin system can be explained by the fact that inhibiting ET-1 synthesis can reduce the ET-1 levels in circulation leading to the release of NO and PGI2. Inhibition of the vasoconstriction effect of ET-1 can improve the hemodynamics of high-load status and ameliorate the cardiac systolic and diastolic functions. In conclusion, natakalim can improve the ventricular remodeling of CHF after AMI, and 3 mg/kg/day was the most effective dose. PMID:28101177

  6. Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via NF-kappaB signaling.

    PubMed

    Afzal, Muhammad R; Haider, Husnain Kh; Idris, Niagara Muhammad; Jiang, Shujia; Ahmed, Rafeeq P H; Ashraf, Muhammad

    2010-03-15

    We proposed that pharmacological manipulation of mesenchymal stem cells (MSCs) with diazoxide enhanced their survival and regenerative potential via NFkappaB regulation. MSCs preconditioned ((PC)MSCs) with diazoxide and later subjected to oxidant stress with 100 micromol/L H(2)O(2) either immediately or after 24 h exhibited higher survival (p < 0.01 vs nonpreconditioned MSCs; (Non-PC)MSCs) with concomitantly increased phosphorylation of PI3K, Akt, GSK3beta (cytoplasmic), and NF-kappaB (p65) (nuclear). Akt kinase activity was determined as a function of GSK3beta activity. Pretreatment of (PC)MSCs with Wortmannin (Wt), NEMO-binding domain (NBD), or NF-kappaB (p50) siRNA abolished NF-kappaB (p65) activity. Preconditioning increased NF-kappaB-dependent elevation of secretable growth factors associated with their paracrine effects. Inhibition of PI3K activity with Wt reduced (PC)MSCs viability at both early and 24 h time-points. However, inhibition of NF-kappaB reduced viability of (PC)MSCs only at 24 h time-point. For in vivo studies, DMEM without cells (group-1) or containing 1 x 10(6) male (Non-PC)MSCs (group-2), (PC)MSCs (group-3), (PC)MSCs pretreated with Wortmannin (group-4) or NF-kappaB decoy (group-5) were transplanted in a female rat model of acute myocardial infarction. Group-3 showed highest cell survival and growth factor expression, increased angiomyogenesis, and functional improvement. We conclude that activation of NF-kappaB by preconditioning promoted (PC)MSCs survival and angiomyogenic potential in the infarcted heart.

  7. Preconditioning Promotes Survival and Angiomyogenic Potential of Mesenchymal Stem Cells in the Infarcted Heart via NF-κB Signaling

    PubMed Central

    Afzal, Muhammad R.; Haider, Husnain Kh.; Idris, Niagara Muhammad; Jiang, Shujia; Ahmed, Rafeeq P.H.

    2010-01-01

    Abstract We proposed that pharmacological manipulation of mesenchymal stem cells (MSCs) with diazoxide enhanced their survival and regenerative potential via NFκB regulation. MSCs preconditioned (PCMSCs) with diazoxide and later subjected to oxidant stress with 100 μmol/L H2O2 either immediately or after 24 h exhibited higher survival (p < 0.01 vs nonpreconditioned MSCs; Non-PCMSCs) with concomitantly increased phosphorylation of PI3K, Akt, GSK3β (cytoplasmic), and NF-κB (p65) (nuclear). Akt kinase activity was determined as a function of GSK3β activity. Pretreatment of PCMSCs with Wortmannin (Wt), NEMO-binding domain (NBD), or NF-κB (p50) siRNA abolished NF-κB (p65) activity. Preconditioning increased NF-κB-dependent elevation of secretable growth factors associated with their paracrine effects. Inhibition of PI3K activity with Wt reduced PCMSCs viability at both early and 24 h time-points. However, inhibition of NF-κB reduced viability of PCMSCs only at 24 h time-point. For in vivo studies, DMEM without cells (group-1) or containing 1 × 106 male Non-PCMSCs (group-2), PCMSCs (group-3), PCMSCs pretreated with Wortmannin (group-4) or NF-κB decoy (group-5) were transplanted in a female rat model of acute myocardial infarction. Group-3 showed highest cell survival and growth factor expression, increased angiomyogenesis, and functional improvement. We conclude that activation of NF-κB by preconditioning promoted PCMSCs survival and angiomyogenic potential in the infarcted heart. Antioxid. Redox Signal. 12, 693–702. PMID:19751147

  8. Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice

    PubMed Central

    Chen, Jinmiao; Hong, Tao; Ding, Suling; Deng, Long; Abudupataer, Mieradilijiang; Zhang, Weiwei; Tong, Minghong; Jia, Jianguo; Gong, Hui; Zou, Yunzeng; Wang, Timothy C.; Ge, Junbo; Yang, Xiangdong

    2017-01-01

    Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC−/−) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC−/− mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3/STAT6 signaling selective antagonist. STAT6-knockout (STAT6−/−) mice had a phenotype similar to that of HDC−/− mice post-MI; however, in contrast to HDC−/− mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6−/− mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway. PMID:28272448

  9. Usefulness of the heart-rate variability complex for predicting cardiac mortality after acute myocardial infarction

    PubMed Central

    2014-01-01

    Background Previous studies indicate that decreased heart-rate variability (HRV) is related to the risk of death in patients after acute myocardial infarction (AMI). However, the conventional indices of HRV have poor predictive value for mortality. Our aim was to develop novel predictive models based on support vector machine (SVM) to study the integrated features of HRV for improving risk stratification after AMI. Methods A series of heart-rate dynamic parameters from 208 patients were analyzed after a mean follow-up time of 28 months. Patient electrocardiographic data were classified as either survivals or cardiac deaths. SVM models were established based on different combinations of heart-rate dynamic variables and compared to left ventricular ejection fraction (LVEF), standard deviation of normal-to-normal intervals (SDNN) and deceleration capacity (DC) of heart rate. We tested the accuracy of predictors by assessing the area under the receiver-operator characteristics curve (AUC). Results We evaluated a SVM algorithm that integrated various electrocardiographic features based on three models: (A) HRV complex; (B) 6 dimension vector; and (C) 8 dimension vector. Mean AUC of HRV complex was 0.8902, 0.8880 for 6 dimension vector and 0.8579 for 8 dimension vector, compared with 0.7424 for LVEF, 0.7932 for SDNN and 0.7399 for DC. Conclusions HRV complex yielded the largest AUC and is the best classifier for predicting cardiac death after AMI. PMID:24886422

  10. Analysis of the Influence of the Electrical Asynchrony on Regional Mechanics of the Infarcted Left Ventricle Using Electromechanical Heart Models

    NASA Astrophysics Data System (ADS)

    Liu, Feng; Xia, Ling; Zhang, Xin

    Asynchronous electrical activation, as induced by myocardial infarction, causes various abnormalities in left ventricle function. The influence of the electrical asynchrony on regional mechanics of the left ventricle is simulated using a mechanical heart model and an electrical heart model. The mechanical model accounts for the ventricular geometry, the fiber nature of the myocardial tissue, and the dependency of the activation sequence of the ventricular wall. The electrical model is based on a heart-torso model with realistic geometry, and different action potential waveforms with variables in duration are used to simulate the abnormal electrical activation after myocardial infarction. Regional deformation, strain and stress are calculated during systole phase. The preliminary results show that asynchronous electrical activation, as an important factor, significantly affects regional mechanical performance of the infarcted left ventricle, it indicates heterogeneous contraction pattern and elevated systolic stresses near the injured region. The simulated results are compared with solutions obtained in the literature. This simulation suggests that such coupled heart models can be used to assess the mechanical function of the left ventricle with diseases such as myocardial infarction, and more realistic models of cardiac function are essential for clinical evaluation of heart disease.

  11. Combined remote perconditioning and postconditioning failed to attenuate infarct size and contractile dysfunction in a rat model of coronary artery occlusion.

    PubMed

    Sachdeva, Jaspreet; Dai, Wangde; Gerczuk, Paul Z; Kloner, Robert A

    2014-11-01

    Although preconditioning remains one of the most powerful maneuvers to reduce myocardial infarct size, it is not feasible in the clinical setting to pretreat patients prior to acute myocardial infarction (MI). The purpose of this study was to investigate the effect of more clinically relevant therapies of remote perconditioning, postconditioning, and the combined effect of remote perconditioning and postconditioning on myocardial infarct size in an anesthetized rat model. Anesthetized rats were subjected to 45 minutes of proximal left coronary artery occlusion followed by 2 hours of reperfusion. Remote perconditioning was performed 5 minutes after left coronary occlusion with 4 cycles of 5 minutes of occlusion and reperfusion of both the femoral arteries. Postconditioning was applied immediately prior to 2 hours of full reperfusion with 6 cycles of 10 seconds occlusion-reperfusion of the coronary artery. The combined effect was produced by preceding the postconditioning regimen with remote perconditioning, after 5 minutes of left coronary occlusion. Remote perconditioning and postconditioning alone failed to reduce infarct size expressed as percentage of the risk zone (42.2% ± 3.9% and 45.0% ± 4.3%). The combination of remote perconditioning and postconditioning also failed to reduce infarct size (45.3% ± 4.1%) as compared to the untreated ischemia-reperfusion group (48.7% ± 3.4%). Hemodynamics including left ventricular end-systole and end-diastolic pressures, +dP/dt, -dP/dt, and heart rate did not show any improvement in the conditioning groups. This study shows that remote perconditioning and postconditioning alone or combined neither improve hemodynamics nor reduce infarct size in the rat model of MI. © The Author(s) 2014.

  12. Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen

    PubMed Central

    Hatayama, Naoyuki; Inubushi, Masayuki; Naito, Munekazu; Hirai, Shuichi; Jin, Yong-Nan; Tsuji, Atsushi B.; Seki, Kunihiro; Itoh, Masahiro; Saga, Tsuneo; Li, Xiao-Kang

    2016-01-01

    We recently succeeded in resuscitating an extracted rat heart following 24–48 hours of preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O2). This study aimed to examine the function of rat hearts transplanted after being preserved in the high-pressure CO and O2 gas mixture. The hearts of donor rats were preserved in a chamber filled with CO and O2 under high pressure for 24 h (CO24h) or 48 h at 4 °C. For the positive control (PC) group, hearts immediately extracted from donor rats were used for transplantation. The preserved hearts were transplanted into recipient rats by heterotopic cervical heart transplantation. CO toxicity does not affect the grafts or the recipients. Light microscopy and [18F]-fluorodeoxyglucose positron emission tomography revealed that there were no significant differences in the size of the myocardial infarction or apoptosis of myocardial cells in post-transplant hearts between the PC and CO24h groups. Furthermore, at 100 days after the transplantation, the heart rate, weight and histological staining of the post-transplanted hearts did not differ significantly between the PC and CO24h groups. These results indicate that the function of rat hearts is well preserved after 24 hours of high-pressure preservation in a CO and O2 gas mixture. Therefore, high-pressure preservation in a gas mixture can be a useful method for organ preservation. PMID:27562456

  13. Side effects of using nitrates to treat heart failure and the acute coronary syndromes, unstable angina and acute myocardial infarction.

    PubMed

    Thadani, Udho; Ripley, Toni L

    2007-07-01

    Nitrates are potent venous dilators and anti-ischemic agents. They are widely used for the relief of chest pain and pulmonary congestion in patients with acute coronary syndromes and heart failure. Nitrates, however, do not reduce mortality in patients with acute coronary syndromes. Combination of nitrates and hydralazine when given in addition to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors reduce mortality and heart failure hospitalizations in patients with heart failure due to left ventricular systolic dysfunction who are of African-American origin. Side effects during nitrate therapy are common but are less well described in the literature compared with the reported side effects in patients with stable angina pectoris. The reported incidence of side effects varies highly among different studies and among various disease states. Headache is the most commonly reported side effect with an incidence of 12% in acute heart failure, 41-73% in chronic heart failure, 3-19% in unstable angina and 2-26% in acute myocardial infarction. The reported incidence of hypotension also differs: 5-10% in acute heart failure, 20% in chronic heart failure, 9% in unstable angina and < 1-48% in acute myocardial infarction, with the incidence being much higher with concomitant nitrate therapy plus angiotensin-converting enzyme inhibitors. Reported incidence of dizziness is as low as 1% in patients with acute myocardial infarction to as high as 29% in patients with heart failure. Severe headaches and/or symptomatic hypotension may necessitate discontinuation of nitrate therapy. Severe life threatening hypotension or even death may occur when nitrates are used in patients with acute inferior myocardial infarction associated with right ventricular dysfunction or infarction, or with concomitant use of phosphodiesterase-5 inhibitors or N-acetylcysteine. Despite the disturbing observational reports in the literature that continuous and prolonged use of nitrates may lead to

  14. Survival and Cardioprotective Benefits of Long-Term Blueberry Enriched Diet in Dilated Cardiomyopathy Following Myocardial Infarction in Rats

    PubMed Central

    Ahmet, Ismayil; Spangler, Edward; Shukitt-Hale, Barbara; Joseph, James A.; Ingram, Donald K.; Talan, Mark

    2009-01-01

    Background Despite remarkable progress in treatment of chronic heart failure (CHF) over the last two decades, mortality, personal suffering and cost remain staggering, and effective interventions are still a challenge. Previously we reported that a blueberry-enriched diet (BD) attenuated necroapoptosis and inflammation in periinfarct area in a rat model of myocardial infarction (MI). Objectives To test the hypothesis that BD will attenuate the course of CHF, including mortality and cardiac remodeling during the first year after induction of MI in rats. Method and Results Two weeks after coronary artery ligation, rats were divided into two groups of similar average MI size, measured by echocardiography, and then12-mo dietary regimens were initiated as follows: ad libitum regular diet (control, CD, n = 27) and isocaloric food with 2% blueberry supplement (BD, n = 27) also available ad libitum. These dietary groups were compared to each other and to sham group (SH). Mortality over the 12 mo was reduced by 22% in BD compared with CD (p<0.01). In the course of developing CHF, BD had no effect on the body weight, heart rate or blood pressure. Bi-monthly Echo revealed significant attenuation of the LV chamber remodeling, LV posterior wall thinning, and MI expansion in BD compared with CD. In fact, BD arrested the MI expansion. Conclusion This is the first experimental evidence that a blueberry-enriched diet has positive effects on the course of CHF and thus warrants consideration for clinical evaluation. PMID:19936253

  15. Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction

    PubMed Central

    Hall, A R; Burke, N; Dongworth, R K; Kalkhoran, S B; Dyson, A; Vicencio, J M; Dorn II, G W; Yellon, D M; Hausenloy, D J

    2016-01-01

    Mitochondria alter their shape by undergoing cycles of fusion and fission. Changes in mitochondrial morphology impact on the cellular response to stress, and their interactions with other organelles such as the sarcoplasmic reticulum (SR). Inhibiting mitochondrial fission can protect the heart against acute ischemia/reperfusion (I/R) injury. However, the role of the mitochondrial fusion proteins, Mfn1 and Mfn2, in the response of the adult heart to acute I/R injury is not clear, and is investigated in this study. To determine the effect of combined Mfn1/Mfn2 ablation on the susceptibility to acute myocardial I/R injury, cardiac-specific ablation of both Mfn1 and Mfn2 (DKO) was initiated in mice aged 4–6 weeks, leading to knockout of both these proteins in 8–10-week-old animals. This resulted in fragmented mitochondria (electron microscopy), decreased mitochondrial respiratory function (respirometry), and impaired myocardial contractile function (echocardiography). In DKO mice subjected to in vivo regional myocardial ischemia (30 min) followed by 24 h reperfusion, myocardial infarct size (IS, expressed as a % of the area-at-risk) was reduced by 46% compared with wild-type (WT) hearts. In addition, mitochondria from DKO animals had decreased MPTP opening susceptibility (assessed by Ca2+-induced mitochondrial swelling), compared with WT hearts. Mfn2 is a key mediator of mitochondrial/SR tethering, and accordingly, the loss of Mfn2 in DKO hearts reduced the number of interactions measured between these organelles (quantified by proximal ligation assay), attenuated mitochondrial calcium overload (Rhod2 confocal microscopy), and decreased reactive oxygen species production (DCF confocal microscopy) in response to acute I/R injury. No differences in isolated mitochondrial ROS emissions (Amplex Red) were detected in response to Ca2+ and Antimycin A, further implicating disruption of mitochondria/SR tethering as the protective mechanism. In summary, despite apparent

  16. Short-term fasting reduces the extent of myocardial infarction and incidence of reperfusion arrhythmias in rats.

    PubMed

    Snorek, M; Hodyc, D; Sedivý, V; Durišová, J; Skoumalová, A; Wilhelm, J; Neckář, J; Kolář, F; Herget, J

    2012-01-01

    The effect of three-day fasting on cardiac ischemic tolerance was investigated in adult male Wistar rats. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min left anterior descending coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischemia and at the beginning (3 min) of reperfusion. Myocardial concentrations of beta-hydroxybutyrate and acetoacetate were measured to assess mitochondrial redox state. Short-term fasting limited the infarct size (48.5+/-3.3 % of the area at risk) compared to controls (74.3+/-2.2 %) and reduced the total number of premature ventricular complexes (12.5+/-5.8) compared to controls (194.9+/-21.9) as well as the duration of ventricular tachycardia (0.6+/-0.4 s vs. 18.8+/-2.5 s) occurring at early reperfusion. Additionally, fasting increased the concentration of beta-hydroxybutyrate and beta-hydroxybutyrate/acetoacetate ratio (87.8+/-27.0) compared to controls (7.9+/-1.7), reflecting altered mitochondrial redox state. It is concluded that three-day fasting effectively protected rat hearts against major endpoints of acute I/R injury. Further studies are needed to find out whether these beneficial effects can be linked to altered mitochondrial redox state resulting from increased ketogenesis.

  17. Hydrogen sulfide post-conditioning preserves interfibrillar mitochondria of rat heart during ischemia reperfusion injury.

    PubMed

    Banu, Shakila A; Ravindran, Sriram; Kurian, Gino A

    2016-07-01

    Cardiac mitochondrial dysfunction is considered to be the main manifestation in the pathology of ischemia reperfusion injury, and by restoring its functional activity, hydrogen sulfide (H2S), a novel endogenous gaseotransmitter renders cardioprotection. Given that interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria are the two main types in the heart, the present study investigates the specific H2S-mediated action on IFM and SSM during ischemic reperfusion in the Langendorff rat heart model. Rats were randomly divided into five groups, namely normal, ischemic control, reperfusion control (I/R), ischemic post-conditioning (POC), and H2S post-conditioning (POC_H2S). In reperfusion control, cardiac contractility decreased, and lactate dehydrogenase, creatine kinase, and infracted size increased compared to both normal and ischemic group. In hearts post-conditioned with H2S and the classical method improved cardiac mechanical function and decreased cardiac markers in the perfusate and infarct size significantly. Both POC and POC_H2S exerts its cardioprotective effect of preserving the IFM, as evident by significant improvement in electron transport chain enzyme activities and mitochondrial respiration. The in vitro action of H2S on IFM and SSM from normal and I/R rat heart supports H2S and mediates cardioprotection via IFM preservation. Our study indicates that IFM play an important role in POC_H2S mediated cardioprotection from reperfusion injury.

  18. Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution.

    PubMed Central

    Fishbein, M. C.; Maclean, D.; Maroko, P. R.

    1978-01-01

    Surgical occlusion of the left coronary artery of the rat is a relatively simple, economical technique for producing experimental myocardial infarction (MI). Histologic study of 1- to 21-day-old MI in rats showed that following a mild and brief acute inflammatory response at the margins of the necrotic myocardium, there is chronic inflammation, vascular and collagenous proliferation, and resorption of necrostic tissue which progresses until scar formation is complete, usually by 21 days. From Day 1 to Day 21 the volume of infarcted myocardium decreases from 45.9 +/- 5.9% (mean +/- SEM) to 26.1 +/- 3.2% of the left ventricle and infarct thickness decreases from 1.30 +/- 0.06 mm to 0.47 +/- 0.02 mm. Concomitantly, the percent of the surface area of the left ventricle which is infarcted decreases insignificantly from 55.7 +/- 7.2% to 48.3 +/- 4.2%, indicating that the decrease in volume of the infarcted tissue occurs primarily as a result of thinning of the MI. This study provides qualitative and quantitative information on the natural history of MI in rats, which should be useful as a baseline for future studies. Images Figure 1 Figure 6 Figure 2 Figure 3 Figure 4 Figure 5 PMID:619696

  19. Effect of Inducible Co-Stimulatory Molecule siRNA in Cerebral Infarction Rat Models

    PubMed Central

    Luo, Yingquan; Yang, Yu; Zhang, Hui; Zhang, Ting; Wang, Yina; Tan, Shengyu; Xu, Yan; Li, Dan; Ye, Ling; Chen, Ping

    2015-01-01

    Background T cell-induced inflammatory response and related cytokine secretion at the injury site may participate in the pathogenesis of cerebral infarction. Recent studies established inducible co-stimulatory molecule (ICOS) as a novel T cell-related factor for its activation and functions. We thus investigate the role of ICOS in cerebral infarction. Material/Methods The siRNA of ICOS was first used to suppress the gene expression in cultured lymphocytes. An in vivo study was then performed by intravenous application of ICOS siRNA in cerebral infarction rats. Survival rates, neurological scores, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 levels were observed. Results The expression of ICOS in cultured lymphocytes was significantly suppressed by siRNA. In the in vivo study, the application of siRNA effectively lowered mortality rates of rats, in addition to the improvement of neurological behaviors and amelioration of cerebral tissue damage. Serum levels of TNF-α, IL-1 and IL-17 were all significantly suppressed after siRNA injection. Conclusions ICOS siRNA can protect brain tissues from ischemia injuries after cerebral infarction, improve limb movement and coordination, lower the mortality rate of rats, and inhibit T cell-induced cytokines. These results collectively suggest the potential treatment efficacy of ICOS siRNA against cerebral infarction. PMID:26436531

  20. Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction.

    PubMed

    Heusch, Gerd; Skyschally, Andreas; Gres, Petra; van Caster, Patrick; Schilawa, Dustin; Schulz, Rainer

    2008-09-01

    Effects of the bradycardic agent ivabradine on regional blood flow, contractile function, and infarct size were studied in a pig model of myocardial ischaemia/reperfusion. Heart rate reduction by beta-blockade is associated with negative inotropism and unmasked alpha-adrenergic coronary vasoconstriction. Ivabradine is the only available bradycardic agent for clinical use. Anaesthetized pigs were subjected to 90 min controlled left anterior descending coronary artery hypoperfusion and 120 min reperfusion. Regional blood flow was measured with microspheres, regional function with sonomicrometry, and infarct size with triphenyl tetrazolium chloride staining. Pigs received placebo or ivabradine (0.6 mg/kg i.v.) before or during ischaemia or before reperfusion, respectively. Pre-treatment with ivabradine reduced infarct size from 35 +/- 4 (SEM) to 19 +/- 4% of area at risk (AAR). Ivabradine 15-20 min after the onset of ischaemia increased regional myocardial blood flow from 2.12 +/- 0.31 to 3.55 +/- 0.56 microL/beat/g and systolic wall thickening from 6.7 +/- 1.0 to 16.3 +/- 3.0%; infarct size was reduced from 12 +/- 4 to 2 +/- 1% of AAR. Ivabradine 5 min before reperfusion still reduced infarct size from 36 +/- 4 to 21 +/- 5% of AAR. The benefit of ivabradine on flow and function was eliminated by atrial pacing, but part of the reduction of infarct size by ivabradine was not. Ivabradine's protection goes beyond heart rate reduction.

  1. Effect of decellularized tissue powders on a rat model of acute myocardial infarction.

    PubMed

    Tabuchi, Masaki; Negishi, Jun; Yamashita, Akitatsu; Higami, Tetsuya; Kishida, Akio; Funamoto, Seiichi

    2015-11-01

    Many research groups are currently investigating new treatment modalities for myocardial infarction. Numerous aspects need to be considered for the clinical application of these therapies, such as low cell integration and engraftment rates of cell injection techniques. Decellularized tissues are considered good materials for promoting regeneration of traumatic tissues. The properties of the decellularized tissues are sustained after processing to powder form. In this study, we examined the use of decellularized tissue powder in a rat model of acute myocardial infarction. The decellularized tissue powders, especially liver powder, promoted cell integration and neovascularization both in vitro and in vivo. Decellularized liver powder induced neovascularization in the infarct area, resulting in the suppression of myocardial necrosis. The results of this study suggest that decellularized liver powder has good potential for application as a blood supply material for the treatment of myocardial infarction. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure.

    PubMed

    Zheng, Hong; Li, Yi-Fan; Zucker, Irving H; Patel, Kaushik P

    2006-12-01

    Experiments were performed to test the postulate that exercise training (ExT) improves the blunted renal excretory response to acute volume expansion (VE), in part, by normalizing the neural component of the volume reflex typically observed in chronic heart failure (HF). Diuretic and natriuretic responses to acute VE were examined in sedentary and ExT groups of rats with either HF or sham-operated controls. Experiments were performed in anesthetized (Inactin) rats 6 wk after coronary ligation surgery. Histological data indicated that there was a 34.9 +/- 3.0% outer and 42.5 +/- 3.2% inner infarct of the myocardium in the HF group. Sham rats had no observable damage to the myocardium. In sedentary rats with HF, VE produced a blunted diuresis (46% of sham) and natriuresis (35% of sham) compared with sham-operated control rats. However, acute VE-induced diuresis and natriuresis in ExT rats with HF were comparable to sham rats and significantly higher than sedentary HF rats. Renal denervation abolished the salutary effects of ExT on renal excretory response to acute VE in HF. Since glomerular filtration rates were not significantly different between the groups, renal hemodynamic changes may not account for the blunted renal responses in rats with HF. Additional experiments confirmed that renal sympathetic nerve activity responses to acute VE were blunted in sedentary HF rats; however, ExT normalized the renal sympathoinhibition in HF rats. These results confirm an impairment of neurally mediated excretory responses to acute VE in rats with HF. ExT restored the blunted excretory responses as well as the renal sympathoinhibitory response to acute VE in HF rats. Thus the beneficial effects of ExT on cardiovascular regulation in HF may be partly due to improvement of the neural component of volume reflex.

  3. Maladaptive effects of learning with the less-affected forelimb after focal cortical infarcts in rats

    PubMed Central

    Allred, Rachel P.; Jones, Theresa A.

    2009-01-01

    It is common following stroke to focus early rehabilitation efforts on developing compensatory use of the less-affected body side. Here we used a rat model of focal cortical infarct to examine how motor skill acquisition with the less-affected (“intact”) forelimb influences sensorimotor function of the infarct-impaired forelimb and neural activity in peri-infarct cortex. Rats proficient in skilled reaching with one forelimb were given focal ischemic lesions in the contralateral sensorimotor cortex (SMC). Recovery in this forelimb was tested following a period of reach training focused on the intact forelimb or control procedures. Quantitative measures of the cumulatively expressed transcription factor, FosB/ΔFosB, were used to assay intact forelimb training effects on neuronal activity in remaining SMC of the infarcted hemisphere. Intact forelimb training worsened behavioral recovery in the impaired forelimb following unilateral focal ischemia. Furthermore, it decreased neuronal FosB/ΔFosB expression in layer II/III of peri-infarct SMC. These effects were not found in sham-operated rats trained sequentially with both forelimbs or in animals receiving bilateral forelimb training after unilateral infarcts. Thus, focused use of the intact forelimb has detrimental effects on recovery of impaired forelimb function following a focal ischemic injury and this is linked to reduced neuronal activation in remaining cortex. These results suggest that peri-infarct cortex becomes vulnerable to early post-stroke experience with the less-affected forelimb and that this experience may drive neural plasticity here in a direction that is maladaptive for functional outcome. PMID:18054917

  4. Tocilizumab inhibits neuronal cell apoptosis and activates STAT3 in cerebral infarction rat model.

    PubMed

    Wang, Shaojun; Zhou, Jun; Kang, Weijie; Dong, Zhaoni; Wang, Hezuo

    2016-01-15

    Cerebral infarction is a severe hypoxic ischemic necrosis with accelerated neuronal cell apoptosis in the brain. As a monoclonal antibody against interleukin 6, tocilizumab (TCZ) is widely used in immune diseases, whose function in cerebral infarction has not been studied. This study aims to reveal the role of TCZ in regulating neuronal cell apoptosis in cerebral infarction. The cerebral infarction rat model was constructed by middle cerebral artery occlusion and treated with TCZ. Cell apoptosis in hippocampus and cortex of the brain was examined with TUNEL method. Rat neuronal cells cultured in oxygen-glucose deprivation (OGD) conditions and treated with TCZ were used to compare cell viability and apoptosis. Apoptosis-related factors including B-cell lymphoma extra large (Bcl-xL) and Caspase 3, as well as the phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in brain cortex were analyzed from the protein level. Results indicated that TCZ treatment could significantly prevent the promoted cell apoptosis caused by cerebral infarction or OGD (P < 0.05 or P < 0.01). In brain cortex of the rat model, TCZ up-regulated Bcl-xL and down-regulated Caspase 3, consistent with the inhibited cell apoptosis. It also promoted tyrosine 705 phosphorylation of STAT3, which might be the potential regulatory mechanism of TCZ in neuronal cells. This study provided evidence for the protective role of TCZ against neuronal cell apoptosis in cerebral infarction. Based on these fundamental data, TCZ is a promising option for treating cerebral infarction, but further investigations on related mechanisms are still necessary.

  5. Tocilizumab inhibits neuronal cell apoptosis and activates STAT3 in cerebral infarction rat model

    PubMed Central

    Wang, Shaojun; Zhou, Jun; Kang, Weijie; Dong, Zhaoni; Wang, Hezuo

    2016-01-01

    Cerebral infarction is a severe hypoxic ischemic necrosis with accelerated neuronal cell apoptosis in the brain. As a monoclonal antibody against interleukin 6, tocilizumab (TCZ) is widely used in immune diseases, whose function in cerebral infarction has not been studied. This study aims to reveal the role of TCZ in regulating neuronal cell apoptosis in cerebral infarction. The cerebral infarction rat model was constructed by middle cerebral artery occlusion and treated with TCZ. Cell apoptosis in hippocampus and cortex of the brain was examined with TUNEL method. Rat neuronal cells cultured in oxygen-glucose deprivation (OGD) conditions and treated with TCZ were used to compare cell viability and apoptosis. Apoptosis-related factors including B-cell lymphoma extra large (Bcl-xL) and Caspase 3, as well as the phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in brain cortex were analyzed from the protein level. Results indicated that TCZ treatment could significantly prevent the promoted cell apoptosis caused by cerebral infarction or OGD (P < 0.05 or P < 0.01). In brain cortex of the rat model, TCZ up-regulated Bcl-xL and down-regulated Caspase 3, consistent with the inhibited cell apoptosis. It also promoted tyrosine 705 phosphorylation of STAT3, which might be the potential regulatory mechanism of TCZ in neuronal cells. This study provided evidence for the protective role of TCZ against neuronal cell apoptosis in cerebral infarction. Based on these fundamental data, TCZ is a promising option for treating cerebral infarction, but further investigations on related mechanisms are still necessary. PMID:26773188

  6. The effect of blockade of the central V1 vasopressin receptors on anhedonia in chronically stressed infarcted and non-infarcted rats.

    PubMed

    Cudnoch-Jedrzejewska, A; Puchalska, L; Szczepanska-Sadowska, E; Wsol, A; Kowalewski, S; Czarzasta, K

    2014-08-01

    Chronic mild stress (CMS) and myocardial infarction (MI) induce anhedonia, which is one of the symptoms of depression. The purpose of this study was to determine the role of the central V1 vasopressin receptors (V1R) in post-CMS and post-MI anhedonia. To this end, we investigated the effect of blockage the central V1R [28days of intracerebroventricular (ICV) infusion of V1 receptors antagonist (V1RANT)] on CMS-induced and the post-infarct anhedonia. The experiments were conducted on conscious MI or sham-operated (SO) rats that were either exposed to CMS for 20days or remained at rest. The sucrose/water intake ratio (S/W) was measured to determine hedonic behavior. Seven days after MI, the S/W was reduced. This effect was no longer present 37days after the infarction and was also absent in the SO rats. Exposure to CMS reduced the S/W in SO rats also. In the CMS-exposed MI rats, the S/W was similar to that in the CMS-exposed SO rats. ICV administration of V1RANT abolished reductions in the S/W in the CMS-exposed MI rats, however, it did not influence S/W in the SO rats exposed to CMS and in the MI and SO rats not exposed to CMS. We conclude that: (1) myocardial infarction and chronic stressing cause anhedonia, (2) myocardial infarction-induced anhedonia appears to be transient, (3) myocardial infarction does not potentiate CMS-induced anhedonia, and (4) CMS-induced anhedonia critically depends on the stimulation of the central V1 receptors.

  7. Left and Right Ventricle Late Remodeling Following Myocardial Infarction in Rats

    PubMed Central

    Stefanon, Ivanita; Valero-Muñoz, María; Fernandes, Aurélia Araújo; Ribeiro, Rogério Faustino; Rodríguez, Cristina; Miana, Maria; Martínez-González, José; Spalenza, Jessica S.; Lahera, Vicente; Vassallo, Paula F.; Cachofeiro, Victoria

    2013-01-01

    Background The mechanisms involved in cardiac remodeling in left (LV) and right ventricles (RV) after myocardial infarction (MI) are still unclear. We assayed factors involved in collagen turnover in both ventricles following MI in rats either presenting signs of heart failure (pulmonary congestion and increased LVEDP) or not (INF-HF or INF, respectively). Methods MI was induced in male rats by ligation of the left coronary artery. Four weeks after MI gene expression of collagen I, connective tissue growth factor (CTGF), transforming growth factor β (TGF-β) and lysyl oxidase (LOX), metalloproteinase-2 (MMP2) and tissue inhibitor metalloproteinase-2 (TIMP2) as well as cardiac hemodynamic in both ventricles were evaluated. Results Ventricular dilatation, hypertrophy and an increase in interstitial fibrosis and myocyte size were observed in the RV and LV from INF-HF animals, whereas only LV dilatation and fibrosis in RV was present in INF. The LV fibrosis in INF-HF was associated with higher mRNA of collagen I, CTGF, TGF-β and LOX expressions than in INF and SHAM animals, while MMP2/TIMP2 mRNA ratio did not change. RV fibrosis in INF and INF-HF groups was associated with an increase in LOX mRNA and a reduction in MMP2/TIMP2 ratio. CTGF mRNA was increased only in the INF-HF group. Conclusions INF and INF-HF animals presented different patterns of remodeling in both ventricles. In the INF-HF group, fibrosis seems to be consequence of collagen production in LV, and by reductions in collagen degradation in RV of both INF and INF-HF animals. PMID:23741440

  8. Comparative effects of cortisone, dianabol and enovid on isoprenaline-induced myocardial infarction in arteriosclerotic vs nonarteriosclerotic rats.

    PubMed

    Wexler, B C

    1976-12-01

    Male and female nonarteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were subjected to acute myocardial infarction with isoprenaline. When myocardial necrosis was most intense, animals were given cortisone (high and low doses), Dianabol, or Enovid. Animals receiving large doses of cortisone manifested the best survival rate during the early stages of myocardial infarction. Although their serum enzyme levels were least elevated and their hearts showed tha least amount of damage, these animals had undergone the most intense body weight loss and began to die suddenly during the later stages of the experiment. These animals also manifested hyperlipidaemia, hyperglycaemia, septicaemia, severe disuse atrophy of their adrenal glands, and reduced Cmpd. B production. Animals treated with low doses of cortisone or with the anabolic and androgenic steroid, Dianabol, manifested none of the myocardial pretective effects of the larger dose of cortisone. These animals displayed a high incidence of left ventricular aneurysm formation concomitant with extensive cartilaginous metaplasia within the aneurysmal sites. Treatment with the contraceptive drug, Enovid, caused body weight loss, hyperlipidaemia, hyperglycaemia, gonadal atrophy and reduction of Cmpd. B production. Although the high dose of cortisone exercised definite salutary effects during early myocardial infarction, chronic treatment led to adrenal disuse atrophy and hypoadrenocorticism associated with sudden death during the later stages of myocardial repair. These findings indicate that proper adjustment of the dose and chronicity of corticosteroids used for treating the crisis of acute myocardial infarction must be made in order to provide effective protection against untoward pathophysiological conditions, acceleration of myocardial repair, but without suppression of adrenal function.

  9. Comparative effects of cortisone, dianabol and enovid on isoprenaline-induced myocardial infarction in arteriosclerotic vs nonarteriosclerotic rats.

    PubMed Central

    Wexler, B. C.

    1976-01-01

    Male and female nonarteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were subjected to acute myocardial infarction with isoprenaline. When myocardial necrosis was most intense, animals were given cortisone (high and low doses), Dianabol, or Enovid. Animals receiving large doses of cortisone manifested the best survival rate during the early stages of myocardial infarction. Although their serum enzyme levels were least elevated and their hearts showed tha least amount of damage, these animals had undergone the most intense body weight loss and began to die suddenly during the later stages of the experiment. These animals also manifested hyperlipidaemia, hyperglycaemia, septicaemia, severe disuse atrophy of their adrenal glands, and reduced Cmpd. B production. Animals treated with low doses of cortisone or with the anabolic and androgenic steroid, Dianabol, manifested none of the myocardial pretective effects of the larger dose of cortisone. These animals displayed a high incidence of left ventricular aneurysm formation concomitant with extensive cartilaginous metaplasia within the aneurysmal sites. Treatment with the contraceptive drug, Enovid, caused body weight loss, hyperlipidaemia, hyperglycaemia, gonadal atrophy and reduction of Cmpd. B production. Although the high dose of cortisone exercised definite salutary effects during early myocardial infarction, chronic treatment led to adrenal disuse atrophy and hypoadrenocorticism associated with sudden death during the later stages of myocardial repair. These findings indicate that proper adjustment of the dose and chronicity of corticosteroids used for treating the crisis of acute myocardial infarction must be made in order to provide effective protection against untoward pathophysiological conditions, acceleration of myocardial repair, but without suppression of adrenal function. Images Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 PMID:1008997

  10. Predictive value of advanced glycation end products for the development of post-infarction heart failure: a preliminary report

    PubMed Central

    2012-01-01

    Background Since post-infarction heart failure (HF) determines a great morbidity and mortality, and given the physiopathology implications of advanced glycation end products (AGE) in the genesis of myocardial dysfunction, it was intended to analyze the prognostic value of these molecules in order to predict post-infarction HF development. Methods A prospective clinical study in patients after first acute coronary syndrome was conducted. The follow-up period was consisted in 1 year. In 194 patients consecutively admitted in the coronary unit for myocardial infarct fluorescent AGE levels were measured. The association between glycaemic parameters and the development of post-infarction HF were analyzed in those patients. Finally, we identified the variables with independent predictor value by performing a multivariate analysis of Hazard ratio for Cox regression. Results Eleven out of 194 patients (5.6%) developed HF during follow-up (median: 1.0 years [0.8 - 1.5 years]). Even though basal glucose, fructosamine and glycated haemoglobin were significant predictive factors in the univariate analysis, after being adjusted by confounding variables and AGE they lost their statistical signification. Only AGE (Hazard Ratio 1.016, IC 95%: 1.006-1.026; p<0,001), together with NT-proBNP and the infarct extension were predictors for post-infarction HF development, where AGE levels over the median value 5-fold increased the risk of HF development during follow-up. Conclusions AGE are an independent marker of post-infarction HF development risk. PMID:22909322

  11. Cardioprotective Effects of Essential Oil of Lavandula angustifolia on Isoproterenol-induced Acute Myocardial Infarction in Rat

    PubMed Central

    Ziaee, Mojtaba; Khorrami, Arash; Ebrahimi, Maryam; Nourafcan, Hassan; Amiraslanzadeh, Masoumeh; Rameshrad, Maryam; Garjani, Mehraveh; Garjani, Alireza

    2015-01-01

    Myocardial infarction (MI) is a common presentation of the ischemic heart disease. Lavandula angustifolia is an herbaceous plant with antioxidative effects. This study was designed to investigate the cardioprotective effects of lavandula angustifolia essential oil against isoproterenol-induced MI in rats. The dried sample was subjected to hydrodistillation by using a Clevenger and the oils were dried over anhydrous Na2SO4. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol and treatment with 5, 10, 20 mg/Kg of the essential oil. MI was induced by subcutaneous injection of Isoproterenol (100 mg/Kg) for 3 consecutive days at an interval of 24 h. The essential oil was given intraperitoneally every 24 h started at MI induction. Following anesthesia, hemodynamic parameters were measured. After sacrificing the animals, the hearts were removed to measure the heart to body weight ratio and histopathological examination. Myeloperoxidase (MPO) and Malondialdehyde (MDA) were measured in heart tissues for evaluating the activity of neutrophils and lipid peroxidation, respectively. The essential oil amended ECG pattern by suppressing ST-segment elevation and increasing R-amplitude. 10 mg/Kg of the essential oil significantly decreased heart to body weight ratio (P<0.001) and the elevation of MDA and MPO in myocardium, it also increased dp/dtmax from 2793 ± 210 to 4488 ± 253 mmHg/sec (P<0.001), and 20 mg/Kg of it significantly lowered LVEDP from 14 ± 3.43 to 4.3 ± 0.83 mmHg (P<0.001).The results demonstrated that L. angustifolia protects myocardium against isoproterenol-induced MI that it could be related to its antioxidant properties. PMID:25561934

  12. Cardioprotective Effects of Essential Oil of Lavandula angustifolia on Isoproterenol-induced Acute Myocardial Infarction in Rat.

    PubMed

    Ziaee, Mojtaba; Khorrami, Arash; Ebrahimi, Maryam; Nourafcan, Hassan; Amiraslanzadeh, Masoumeh; Rameshrad, Maryam; Garjani, Mehraveh; Garjani, Alireza

    2015-01-01

    Myocardial infarction (MI) is a common presentation of the ischemic heart disease. Lavandula angustifolia is an herbaceous plant with antioxidative effects. This study was designed to investigate the cardioprotective effects of lavandula angustifolia essential oil against isoproterenol-induced MI in rats. The dried sample was subjected to hydrodistillation by using a Clevenger and the oils were dried over anhydrous Na2SO4. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol and treatment with 5, 10, 20 mg/Kg of the essential oil. MI was induced by subcutaneous injection of Isoproterenol (100 mg/Kg) for 3 consecutive days at an interval of 24 h. The essential oil was given intraperitoneally every 24 h started at MI induction. Following anesthesia, hemodynamic parameters were measured. After sacrificing the animals, the hearts were removed to measure the heart to body weight ratio and histopathological examination. Myeloperoxidase (MPO) and Malondialdehyde (MDA) were measured in heart tissues for evaluating the activity of neutrophils and lipid peroxidation, respectively. The essential oil amended ECG pattern by suppressing ST-segment elevation and increasing R-amplitude. 10 mg/Kg of the essential oil significantly decreased heart to body weight ratio (P<0.001) and the elevation of MDA and MPO in myocardium, it also increased dp/dtmax from 2793 ± 210 to 4488 ± 253 mmHg/sec (P<0.001), and 20 mg/Kg of it significantly lowered LVEDP from 14 ± 3.43 to 4.3 ± 0.83 mmHg (P<0.001).The results demonstrated that L. angustifolia protects myocardium against isoproterenol-induced MI that it could be related to its antioxidant properties.

  13. Wenxin-Keli Regulates the Calcium/Calmodulin-Dependent Protein Kinase II Signal Transduction Pathway and Inhibits Cardiac Arrhythmia in Rats with Myocardial Infarction

    PubMed Central

    Xing, Yanwei; Gao, Yonghong; Chen, Jianxin; Zhu, Haiyan; Wu, Aiming; Yang, Qing; Teng, Fei; Zhang, Dong-mei; Xing, Yanhui; Gao, Kuo; He, Qingyong; Zhang, Zhenpeng; Wang, Jie; Shang, Hongcai

    2013-01-01

    Wenxin-Keli (WXKL) is a Chinese herbal compound reported to be of benefit in the treatment of cardiac arrhythmia, cardiac inflammation, and heart failure. Amiodarone is a noncompetitive inhibitor of the α- and β-adrenergic receptors and prevents calcium influx in the slow-response cells of the sinoatrial and atrioventricular nodes. Overexpression of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias. We hypothesised that administration of WXKL and amiodarone can reduce the incidence of arrhythmias by regulating CaMKII signal transduction. A total of 100 healthy Sprague Dawley rats were used in the study. The rats were randomly divided into four groups (a sham group, a myocardial infarction (MI) group, a WXKL-treated group, and an amiodarone-treated group). A myocardial infarction model was established in these rats by ligating the left anterior descending coronary artery for 4 weeks. Western blotting was used to assess CaMKII, p-CaMKII (Thr-286), PLB, p-PLB (Thr-17), RYR2, and FK binding protein 12.6 (FKBP12.6) levels. The Ca2+ content in the sarcoplasmic reticulum (SR) and the calcium transient amplitude were studied by confocal imaging using the fluorescent indicator Fura-4. In conclusion, WXKL may inhibit heart failure and cardiac arrhythmias by regulating the CaMKII signal transduction pathway similar to amiodarone. PMID:23781262

  14. Wenxin-Keli Regulates the Calcium/Calmodulin-Dependent Protein Kinase II Signal Transduction Pathway and Inhibits Cardiac Arrhythmia in Rats with Myocardial Infarction.

    PubMed

    Xing, Yanwei; Gao, Yonghong; Chen, Jianxin; Zhu, Haiyan; Wu, Aiming; Yang, Qing; Teng, Fei; Zhang, Dong-Mei; Xing, Yanhui; Gao, Kuo; He, Qingyong; Zhang, Zhenpeng; Wang, Jie; Shang, Hongcai

    2013-01-01

    Wenxin-Keli (WXKL) is a Chinese herbal compound reported to be of benefit in the treatment of cardiac arrhythmia, cardiac inflammation, and heart failure. Amiodarone is a noncompetitive inhibitor of the α - and β -adrenergic receptors and prevents calcium influx in the slow-response cells of the sinoatrial and atrioventricular nodes. Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias. We hypothesised that administration of WXKL and amiodarone can reduce the incidence of arrhythmias by regulating CaMKII signal transduction. A total of 100 healthy Sprague Dawley rats were used in the study. The rats were randomly divided into four groups (a sham group, a myocardial infarction (MI) group, a WXKL-treated group, and an amiodarone-treated group). A myocardial infarction model was established in these rats by ligating the left anterior descending coronary artery for 4 weeks. Western blotting was used to assess CaMKII, p-CaMKII (Thr-286), PLB, p-PLB (Thr-17), RYR2, and FK binding protein 12.6 (FKBP12.6) levels. The Ca(2+) content in the sarcoplasmic reticulum (SR) and the calcium transient amplitude were studied by confocal imaging using the fluorescent indicator Fura-4. In conclusion, WXKL may inhibit heart failure and cardiac arrhythmias by regulating the CaMKII signal transduction pathway similar to amiodarone.

  15. Beneficial effect of zinc chloride and zinc ionophore pyrithione on attenuated cardioprotective potential of preconditioning phenomenon in STZ-induced diabetic rat heart.

    PubMed

    Jamwal, Sumit; Kumar, Kushal; Reddy, B V Krishna

    2016-05-01

    Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection by phosphorylation and subsequent inactivation of glycogen synthase kinase-3β (GSk-3β) in the normal rat heart, but its effect is attenuated in the diabetic rat heart. This study was designed to investigate the effect of zinc chloride and zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The isolated perfused rat heart was subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the coronary effluent. Also, GSK-3β was measured and neutrophil accumulation was measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased the myocardial infarct size, the release of LDH and CK-MB, the GSK-3β levels and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat hearts significantly decreased the myocardial infarct size, the level of CK-MB and LDH in the coronary effluent and GSK-3β and MPO levels. Our results suggest that pharmacological preconditioning with zinc chloride and ZIP significantly restored the attenuated cardioprotective potential of IPC in the diabetic rat heart. © The Author(s) 2015.

  16. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    PubMed Central

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; de Almeida, Eros Antonio

    2015-01-01

    Background In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. PMID:25494017

  17. Tongxinluo Enhances Neurogenesis and Angiogenesis in Peri-Infarct Area and Subventricular Zone and Promotes Functional Recovery after Focal Cerebral Ischemic Infarction in Hypertensive Rats

    PubMed Central

    Chen, Li; Wang, Xiaoting; Zhang, Jian; Dang, Chao; Liu, Gang; Liang, Zhijian; Huang, Gelun; Zhao, Weijia; Zeng, Jinsheng

    2016-01-01

    Background. Tongxinluo is a traditional Chinese medicine compound with the potential to promote the neuronal functional recovery in cerebral ischemic infarction. Objective. This study aimed to disclose whether tongxinluo promotes neurological functional recovery and neurogenesis and angiogenesis in the infarcted area and SVZ after cerebral ischemic infarction in hypertensive rats. Methods. The ischemic model was prepared by distal middle cerebral artery occlusion (MCAO) in hypertensive rats. Tongxinluo was administrated 24 h after MCAO and lasted for 3, 7, or 14 days. Behavioral tests were performed to evaluate the protection of tongxinluo. Immunochemical staining was applied on brain tissue to evaluate the effects of tongxinluo on neurogenesis and vascularization in the MCAO model rats. Results. Postinjury administration of tongxinluo ameliorated the neuronal function deficit in the MCAO model rats. As evidenced by the immunochemical staining, BrdU+/DCX+, BrdU+/nestin+, and BrdU+ vascular endothelial cells were promoted to proliferate in SVZ after tongxinluo administration. The matured neurons stained by NeuN and vascularization by laminin staining were observed after tongxinluo administration in the peri-infarct area. Conclusion. Tongxinluo postischemia administration could ameliorate the neurological function deficit in the model rats. Possible mechanisms are related to neurogenesis and angiogenesis in the peri-infarct area and SVZ. PMID:27069496

  18. [The characteristics of the psychological reactions to stress situations caused by acute myocardial infarct and surgery for acquired heart defect].

    PubMed

    Parkhomenko, A N; Burlachuk, L F; Korzhova, E Iu

    1990-05-01

    The authors compare the psychologic reactions to acute stress situations due to acute myocardial infarction and in patients operated on for acquired heart disease. To evaluate the emotional experience of the patients psychodiagnostic methods were used. Some of them were specially developed by the authors. New data were obtained on the specific psychosocial adaptation and psychosocial defense of these categories of patients.

  19. Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats.

    PubMed

    Nozawa, E; Kanashiro, R M; Murad, N; Carvalho, A C C; Cravo, S L D; Campos, O; Tucci, P J F; Moises, V A

    2006-05-01

    Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the myocardial infarct size, and to evaluate anatomic and functional variables of the left ventricle. Myocardial infarction was produced in 43 female Wistar rats by ligature of the left coronary artery. Echocardiography was performed 5 weeks later to measure left ventricular diameter and transverse area (mean of 3 transverse planes), infarct size (percentage of the arc with infarct on 3 transverse planes), systolic function by the change in fractional area, and diastolic function by mitral inflow parameters. The histologic measurement of myocardial infarction size was similar to the echocardiographic method. Myocardial infarct size ranged from 4.8 to 66.6% when determined by histology and from 5 to 69.8% when determined by echocardiography, with good correlation (r = 0.88; P < 0.05; Pearson correlation coefficient). Left ventricular diameter and mean diastolic transverse area correlated with myocardial infarct size by histology (r = 0.57 and r = 0.78; P < 0.0005). The fractional area change ranged from 28.5 +/- 5.6 (large-size myocardial infarction) to 53.1 +/- 1.5% (control) and correlated with myocardial infarct size by echocardiography (r = -0.87; P < 0.00001) and histology (r = -0.78; P < 00001). The E/A wave ratio of mitral inflow velocity for animals with large-size myocardial infarction (5.6 +/- 2.7) was significantly higher than for all others (control: 1.9 +/- 0.1; small-size myocardial infarction: 1.9 +/- 0.4; moderate-size myocardial infarction: 2.8 +/- 2.3). There was good agreement between echocardiographic and histologic estimates of myocardial infarct size in rats.

  20. Tumour necrosis factor-α and its receptors in the beneficial effects of vagal stimulation after myocardial infarction in rats.

    PubMed

    Kong, Shan-Shan; Liu, Jin-Jun; Hwang, Tyzh-Chang; Yu, Xiao-Jiang; Lu, Yi; Zang, Wei-Jin

    2011-05-01

    1. Acute myocardial infarction (AMI) often activates the sympathetic system and inhibits the vagal system. Long-term vagal nerve stimulation (VNS) exerts several beneficial effects on the ischaemic heart, including an anti-inflammatory effect. The aim of the present study was to investigate whether short-term VNS during AMI could inhibit tumour necrosis factor (TNF)-α expression and the effect of TNF receptor (TNFR), key components in inflammatory responses to AMI, in a rodent model. 2. Adult male Sprague-Dawley rats were divided into four groups, namely a control (C), VNS (S), AMI (M) and an AMI group subjected to prior VNS (MS). In the S and MS groups, the right vagus nerve was stimulated electrically for 4 h; in the M and MS groups, AMI was induced by occlusion of the left anterior descending coronary artery. Haemodynamic data were monitored continuously using a multichannel physiological recorder. Lactate dehydrogenase (LDH) leakage, creatine kinase (CK) leakage and infarct size were determined. The expression of TNF-α and its receptors were analysed by reverse transcription-polymerase chain reaction, western blotting and ELISA. 3. Compared with the control group, rats in the M group had low blood pressure, high left ventricular (LV) end-diastolic pressure, a depressed maximum dP/dt of LV pressure, higher LDH and CK leakage, a larger infarct size, increased TNF-α levels and an increased TNFR1/TNFR2 ratio. However, these presumably harmful effects of AMI were all significantly ameliorated by VNS during AMI (MS group). 4. In conclusion, VNS can rectify ischaemia-induced cardiac dysfunction partly via inhibition of a TNF-α-mediated signalling pathway.

  1. Long-term treatment with ivabradine in post-myocardial infarcted rats counteracts f-channel overexpression

    PubMed Central

    Suffredini, S; Stillitano, F; Comini, L; Bouly, M; Brogioni, S; Ceconi, C; Ferrari, R; Mugelli, A; Cerbai, E

    2012-01-01

    BACKGROUND AND PURPOSE Recent clinical data suggest beneficial effects of ivabradine, a specific heart rate (HR)-lowering drug, in heart failure patients. However, the mechanisms responsible for these effects have not been completely clarified. Thus, we investigated functional/molecular changes in If, the specific target of ivabradine, in the failing atrial and ventricular myocytes where this current is up-regulated as a consequence of maladaptive remodelling. EXPERIMENTAL APPROACH We investigated the effects of ivabradine (IVA; 10 mg·kg−1·day−1 for 90 days) on electrophysiological remodelling in left atrial (LA), left ventricular (LV) and right ventricular (RV) myocytes from post-mycardial infarcted (MI) rats, with sham-operated (sham or sham + IVA) rats as controls. If current was measured by patch-clamp; hyperpolarization-activated cyclic nucleotide-gated (HCN) channel isoforms and microRNA (miRNA-1 and miR-133) expression were evaluated by reverse transcription quantitative PCR. KEY RESULTS Maximal specific conductance of If was increased in MI, versus sham, in LV (P < 0.01) and LA myocytes (P < 0.05). Ivabradine reduced HR in both MI and sham rats (P < 0.05). In MI + IVA, If overexpression was attenuated and HCN4 transcription reduced by 66% and 54% in LV and RV tissue, respectively, versus MI rats (all P < 0.05). miR-1 and miR-133, which modulate post-transcriptional expression of HCN2 and HCN4 genes, were significantly increased in myocytes from MI + IVA. CONCLUSION AND IMPLICATION The beneficial effects of ivabradine may be due to the reversal of electrophysiological cardiac remodelling in post-MI rats by reduction of functional overexpression of HCN channels. This is attributable to transcriptional and post-transcriptional mechanisms. PMID:21838751

  2. Cholinergic stimulation with pyridostigmine protects myocardial infarcted rats against ischemic-induced arrhythmias and preserves connexin43 protein.

    PubMed

    Santos-Almeida, Fernanda Machado; Girão, Henrique; da Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens

    2015-01-15

    We investigated the effects of acute pyridostigmine (PYR) treatment, an acetylcholinesterase inhibitor, on arterial pressure (AP), heart rate (HR), cardiac sympathovagal balance, and the incidence of arrhythmias during the first 4 h after myocardial infarction (MI) in anesthetized rats. Male Wistar rats were implanted with catheters into the femoral artery and vein for AP recordings and drug administration. Rats received the autonomic receptor blockers methyl-atropine (1 mg/kg iv) and propranolol (2 mg/kg iv) at intervals of 15 min, 1 h after saline (n=16) or PYR (0.25 mg/kg iv, n=18), to indirectly assess sympathovagal balance. Acute treatment with PYR increased cardiac vagal (86±7 vs. 44±5 beats/min) and decreased sympathetic tone (-31±8 vs. -69±7 beats/min). Different animals were implanted with ECG electrodes and catheters. A large MI was induced via left coronary artery ligation after basal recordings. Rats received PYR (n=14) or saline (n=14) 10-15 min after MI, and the recordings lasted up to 4 h. In part of the animals, hearts were removed for connexin43 quantification after all procedures. MI elicited a fall in AP (-45±5 mmHg), a progressive rise in HR (26±14 beats/min), and an increase in corrected QT interval (33±13 ms). PYR elicited a prompt bradycardia (-50±14 beats/min) that returned to basal levels over time, and it prevented the lengthening of the corrected QT interval. Treatment with PYR increased by ∼20% the occurrence of rats free of arrhythmias after MI. MI markedly decreased connexin43 in left ventricles, and PYR treatment partially prevented this decrease. Copyright © 2015 the American Physiological Society.

  3. Endothelin-B Receptors and Left Ventricular Dysfunction after Regional versus Global Ischaemia-Reperfusion in Rat Hearts.

    PubMed

    Bibli, Sofia-Iris; Toli, Eleni V; Vilaeti, Agapi D; Varnavas, Varnavas C; Baltogiannis, Giannis G; Papalois, Apostolos; Kyriakides, Zenon S; Kolettis, Theofilos M

    2012-01-01

    Background. Endothelin-1 (ET-1) is implicated in left ventricular dysfunction after ischaemia-reperfusion. ETA and ETB receptors mediate diverse actions, but it is unknown whether these actions depend on ischaemia type and duration. We investigated the role of ETB receptors after four ischaemia-reperfusion protocols in isolated rat hearts. Methods. Left ventricular haemodynamic variables were measured in the Langendorff-perfused model after 40- and 20-minute regional or global ischaemia, followed by 30-minute reperfusion. Wild-type (n = 39) and ETB-deficient (n = 41) rats were compared. Infarct size was measured using fluorescent microspheres after regional ischaemia-reperfusion. Results. Left ventricular dysfunction was more prominent in ETB-deficient rats, particularly after regional ischaemia. Infarct size was smaller (P = 0.006) in wild-type (31.5 ± 4.4%) than ETB-deficient (45.0 ± 7.3%) rats after 40 minutes of regional ischaemia-reperfusion. Although the recovery of left ventricular function was poorer after 40-minute ischaemia-reperfusion, end-diastolic pressure in ETB-deficient rats was higher after 20 than after 40 minutes of regional ischaemia-reperfusion. Conclusion. ETB receptors exert cytoprotective effects in the rat heart, mainly after regional ischaemia-reperfusion. Longer periods of ischaemia suppress the recovery of left ventricular function after reperfusion, but the role of ETB receptors may be more important during the early phases.

  4. Endothelin-B Receptors and Left Ventricular Dysfunction after Regional versus Global Ischaemia-Reperfusion in Rat Hearts

    PubMed Central

    Bibli, Sofia-Iris; Toli, Eleni V.; Vilaeti, Agapi D.; Varnavas, Varnavas C.; Baltogiannis, Giannis G.; Papalois, Apostolos; Kyriakides, Zenon S.; Kolettis, Theofilos M.

    2012-01-01

    Background. Endothelin-1 (ET-1) is implicated in left ventricular dysfunction after ischaemia-reperfusion. ETA and ETB receptors mediate diverse actions, but it is unknown whether these actions depend on ischaemia type and duration. We investigated the role of ETB receptors after four ischaemia-reperfusion protocols in isolated rat hearts. Methods. Left ventricular haemodynamic variables were measured in the Langendorff-perfused model after 40- and 20-minute regional or global ischaemia, followed by 30-minute reperfusion. Wild-type (n = 39) and ETB-deficient (n = 41) rats were compared. Infarct size was measured using fluorescent microspheres after regional ischaemia-reperfusion. Results. Left ventricular dysfunction was more prominent in ETB-deficient rats, particularly after regional ischaemia. Infarct size was smaller (P = 0.006) in wild-type (31.5 ± 4.4%) than ETB-deficient (45.0 ± 7.3%) rats after 40 minutes of regional ischaemia-reperfusion. Although the recovery of left ventricular function was poorer after 40-minute ischaemia-reperfusion, end-diastolic pressure in ETB-deficient rats was higher after 20 than after 40 minutes of regional ischaemia-reperfusion. Conclusion. ETB receptors exert cytoprotective effects in the rat heart, mainly after regional ischaemia-reperfusion. Longer periods of ischaemia suppress the recovery of left ventricular function after reperfusion, but the role of ETB receptors may be more important during the early phases. PMID:22844633

  5. Involvement of Proteasome and Macrophages M2 in the Protection Afforded by Telmisartan against the Acute Myocardial Infarction in Zucker Diabetic Fatty Rats with Metabolic Syndrome

    PubMed Central

    Di Filippo, C.; Rossi, C.; Ferraro, B.; Maisto, R.; De Angelis, A.; Ferraraccio, F.; Rotondo, A.; D'Amico, M.

    2014-01-01

    This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF) rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R). At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg) reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7%) and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R. PMID:25110402

  6. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo.

    PubMed

    Herrmann, Julia E; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L; Vickers, Alison E M

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24h. In this in vivo rat study (0.5mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices.

  7. Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure

    PubMed Central

    Wei, Qun; Liu, Haiyan; Liu, Miao; Yang, Chunyan; Yang, Jie; Liu, Zhonghui; Yang, Ping

    2016-01-01

    Prior studies have shown that overexpression of ACT A can lead to ventricular remodeling in rat models of heart failure. Furthermore, recently work studying demonstrated that stimulation of activin An expression in rat aortic smooth muscle (RASM) cells by angiotensin II (Ang II). Ramipril is a recently developed angiotensin converting enzyme (ACE) inhibitor. To investigate the effects of Ramipril on expression of ACT A-FS, we established the rat model of heart failure after myocardial infarction (MI), and divided into either a sham operation (SO), MI, or MI-Ramipril group. We found that Ramipril significantly attenuates collagen-I and III deposition (col-I and III). Notably, we determined that expression of ACT A and II activin receptor (ActRII) were significantly down-regulated in the non-infarcted area of the left ventricle in the Ramipril group, whereas the mRNA and protein levels of FS were markedly up-regulated. Our data suggested that Ramipril benefited left ventricular remodeling by reducing fibrosis and collagen accumulation in the left ventricle of rats after myocardial infarction. This observation was also associated with down-regulation of ACT A expression. This study elucidated a new protective mechanism of Ramipril and suggests a novel strategy for treatment of post-infarct remodeling and subsequent heart failure. PMID:27642098

  8. Lysophosphatidic Acid Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury in the Immature Hearts of Rats

    PubMed Central

    Chen, Haibo; Liu, Si; Liu, Xuewen; Yang, Jinjing; Wang, Fang; Cong, Xiangfeng; Chen, Xi

    2017-01-01

    The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1–LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury. The results showed that in Langendorff-perfused immature rat hearts (2 weeks), compared to I/R group, LPA pretreatment significantly enhanced the cardiac function, attenuated myocardial infarct size and CK-MB release, decreased myocardial apoptosis and increased the expression of pro-survival signaling molecules. All these effects could be abolished by Ki16425, an antagonist to LPA1 and LPA3. Similarly, LPA pretreatment protected H9C2 from hypoxia-reoxygenation (H/R) induced apoptosis and necrosis in vitro. The mechanisms underlying the anti-apoptosis effects were related to activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (AKT) signaling pathways as well as phosphorylation of the downstream effector of AKT, glycogen synthase kinase 3 beta (GSK3β), through LPA1 and/or LPA3. What's more, we found that LPA preconditioning increased glucose uptake of H9C2 subjected to H/R by the activation of AMP-Activated Protein Kinase (AMPK) but not the translocation of GLUT4. In conclusion, our study indicates that LPA is a potent survival factor for immature hearts against I/R injuries and has the potential therapeutic function as a cardioplegia additive for infantile cardiac surgery. PMID:28377726

  9. An autopsy report of acute myocardial infarction with hypertrophic obstructive cardiomyopathy-like heart.

    PubMed

    Ushikoshi, Hiroaki; Okada, Hideshi; Morishita, Kentaro; Imai, Hajime; Tomita, Hiroyuki; Nawa, Takahide; Suzuki, Kodai; Ikeshoji, Haruka; Kato, Hisaaki; Yoshida, Takahiro; Yoshida, Shozo; Shirai, Kunihiro; Toyoda, Izumi; Hara, Akira; Ogura, Shinji

    2015-01-01

    An 84-year-old woman, who was followed up as hypertrophic obstructive cardiomyopathy (HOCM) in a local hospital, was transferred to our center because of anterior chest pain and diagnosed with acute myocardial infarction (MI). Coronary angiography showed total occlusion of the mid-left anterior descending, and flow was restored after endovascular thrombectomy. An autopsy was performed after she died on hospital day 6. At autopsy, there was no significant stenosis in this vessel and the absence of plaque rupture was confirmed. Likewise, it was unclear asymmetric hypertrophy at autopsy, it could not deny that a sigmoid deformity of the basal septum occurs in elderly patients and can mimic the asymmetric septal hypertrophy of hypertrophic cardiomyopathy. MI was thought to be caused by coronary spasm or squeezing in HOCM-like heart. Therefore, it may be necessary antithrombosis therapy in HOCM-like patients with no history of paroxysmal atrial fibrillation.

  10. The fall in mortality from ischemic heart disease in Australia: has survival after myocardial infarction improved?

    PubMed

    Martin, C A; Hobbs, M S; Armstrong, B K

    1984-08-01

    Trends in mortality and survival after myocardial infarction (MI) were studied by use of computerised death and hospital discharge records for 25 to 64 year old residents of the Perth Statistical Division between 1971 and 1979. Highly significant falls in ischemic heart disease (IHD) mortality rates were found for men (18%) and women (29%) but 4, 26 and 52 week survival after hospital admission for MI remained constant at around 88%, 84% and 81% respectively. Further, as 75% of all IHD deaths between 1971 and 1979 occurred before the victim was admitted to hospital, the survival of those receiving treatment would have had to be greatly improved to influence total mortality from IHD appreciably. As the age and sex composition of persons hospitalised for MI and the proportion of MI victims hospitalised did not change during the study period it would seem that improved survival after hospital admission for MI did not contribute to the fall in IHD deaths between 1971 and 1979.

  11. Myocardial infarction in an adult with cystic fibrosis and heart and lung transplant

    PubMed Central

    2013-01-01

    We present a case of myocardial infarction in a 19 year old female with cystic fibrosis who had a heart and lung transplant performed at the age of four years old. She presented atypically with a one day history of severe, intermittent, central, sharp chest pain, radiating to her back and down her left arm. A coronary angiogram showed proximal stenosis of the left anterior descending artery and right coronary artery. She was treated with percutaneous coronary intervention, involving drug eluting stents to the left anterior descending artery (LAD) and the right coronary artery (RCA). In this study we discuss the pathophysiology, investigations and treatment of cardiac transplant vasculopathy. Although complete reversal of LAD and RCA stenosis was achieved, routine follow-up with coronary angiography and careful control of cardiac risk factors will be important to identify and reduce future restenosis and adverse cardiac events. PMID:23759073

  12. Native cardiac reserve predicts survival in acute post infarction heart failure in mice

    PubMed Central

    Täng, Margareta Scharin; Råmunddal, Truls; Lindbom, Malin; Omerovic, Elmir

    2007-01-01

    Cardiac reserve can be used to predict survival and outcome in patients with heart failure. The aim of this study was to investigate if native cardiac reserve could predict survival after myocardial infarction (MI) in mice. Method We investigated 27 healthy C57Bl6 mice (♂10–12 weeks old) with echocardiography using a high-frequency 15-MHz linear transducer. Investigations were performed both at rest and after pharmacological stress induced by dobutamine (1 μg/g body weight i.p.). The day after the echocardiography examination, a large MI was induced by ligation of the left anterior descending (LAD) coronary artery for evaluation of mortality rate. Results Two weeks after induction of MI, 7 mice were alive (26%). Evaluation of the difference between the surviving and deceased animals showed that the survivors had a better native ability to increase systolic performance (ΔLVESd -1.86 vs -1.28mm p = 0.02) upon dobutamine challenge, resulting in a better cardiac reserve (ΔFS 37 vs 25% p = 0.02 and ΔCO 0.27 vs -0.10 ml/min p = 0.02) and a better chronotropic reserve (ΔR-R interval -68 vs -19 ms p < 0.01). A positive relationship was found between ability to survive and both cardiac (p < 0.05) and chronotropic reserve (p < 0.05) when the mice were divided into three groups: survivors, surviving < 7 days, and surviving < 1 day. Conclusion We conclude that before MI induction the surviving animals had a better cardiac function compared with the deceased. This indicates that native cardiac and chronotropic reserve may be an important determinant and predictor of survival in the setting of large MI and post-infarction heart failure. PMID:18053159

  13. Spontaneous infarcted adenoma of the mammary gland in a Wistar Hannover GALAS rat

    PubMed Central

    Matsushita, Kohei; Toyoda, Takeshi; Inoue, Kaoru; Morikawa, Tomomi; Sone, Mizuki; Ogawa, Kumiko

    2016-01-01

    Spontaneous massive infarction of mammary gland tumors has been reported to occur infrequently in humans. A subcutaneous mass (18 × 17 × 10 mm) was observed in the right axilla extending to the chest region of a 110-week-old female Wistar Hannover GALAS rat. Histopathologically, a well-circumscribed mass with lobular structures was present in the subcutis. Most of the mass was occupied by extensive coagulative necrosis of neoplastic cells with relatively uniform acinar and ductal structures. Although each necrotic acinar structure was separated by reticular fibers, periacinar stromal collagen fibers were not abundant. Considering the site of occurrence and histological features, the necrotic tissue was diagnosed as adenoma of the mammary gland. The necrotic region lacked hemorrhage and obvious inflammatory cell infiltration, indicating the necrosis was caused by infarction. Although multiple necrosis and focal infarction are occasionally observed in large-sized tumors in rodents, especially in adenocarcinomas, the present case was characteristic, with the massive infarction involving most parts of the tumor despite the relatively small size and low atypia of neoplastic cells. This is a rare case of spontaneous infarcted adenoma of the mammary gland in rats histologically resembling human cases. PMID:28190925

  14. Oleuropein attenuates the progression of heart failure in rats by antioxidant and antiinflammatory effects.

    PubMed

    Janahmadi, Zeinab; Nekooeian, Ali Akbar; Moaref, Ali Reza; Emamghoreishi, Masoomeh

    2017-03-01

    Much of the beneficial effects of olive products have been attributed to oleuropein. This study examined the effects of oleuropein in rats with heart failure induced by permanent ligation of left coronary arteries. Twenty-four hours after the operation, the rats were assigned to five groups including a sham assigned to receive vehicle (1 ml/day) and four coronary ligated groups assigned to receive vehicle or oleuropein at 5, 10, or 20 mg/kg/day. Five weeks later, echocardiographic and hemodynamic parameters, serum concentrations of oxidative stress, and inflammatory markers were determined. Myocardial infarction group receiving vehicle showed impaired hemodynamic and echocardiographic parameters as evidenced by decreased left ventricular systolic pressure, rate of rise and decrease of left ventricular pressure, stroke volume, ejection fraction, and cardiac output. In addition, significant reduction in superoxide dismutase and glutathione reductase was observed. Oleuropein treatment prevented the reduction of these variables. Moreover, the group had a significantly higher infarct size and serum malondialdehyde, interleukin-1β, and tumor necrosis factor-α than those of the sham group. Treatment with oleuropein prevented the increase of these variables. The results show that oleuropein attenuates the progression of heart failure, possibly by antioxidative and antiinflammatory effects.

  15. Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

    PubMed Central

    Binsalamah, Ziyad Mohammed; Paul, Arghya; Khan, Afshan Afsar; Prakash, Satya; Shum-Tim, Dominique

    2011-01-01

    Background Acute myocardial ischemia results in scar formation with ventricular dilatation and eventually heart failure. Placental growth factor (PlGF) is reported to stimulate angiogenesis and improve cardiac function. In this study, it was hypothesized that intramyocardial injection of PlGF contained in nanoparticles can be released at the site of action for an extended time period as a sustained slow-release protective mechanism that accelerates myocardial recovery in a rat model of ischemic cardiomyopathy. Methods PlGF-loaded chitosan-alginate nanoparticles were injected into an acute myocardial infarction model in rats (n = 10 per group). Transthoracic echocardiography was performed at different time intervals. Enzyme-linked immunosorbent assay was used to measure the serum cytokines levels at 8 weeks. Hearts were stained with Masson’s trichrome for scar area analysis. Immunofluorostaining was performed to evaluate the extent of myocardial angiogenesis at the infarction border. PlGF enzyme-linked immunosorbent assay was used to measure the in vitro release kinetics of PlGF-loaded nanoparticles. Results At 8 weeks after coronary ligation, hearts that were treated with PlGF-loaded chitosan-alginate nanoparticles had significant increases in left-ventricular function (P < 0.01), vascular density (P < 0.01), and in the serum level of the anti-inflammatory cytokine interleukin-10 (P < 0.05). There was significant decrease in scar area formation (P < 0.05) and in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 (P < 0.01). In vitro PlGF-release kinetic studies showed a sustained release of PlGF from the particles over a 120-hour period. Conclusion The use of nanoparticles as a vehicle for PlGF delivery, as opposed to the direct injection of the growth factor after acute myocardial infarction, can provide sustained slow-release PlGF therapy, enhancing the positive effects of the growth factor in the setting of acute

  16. A biochemical, electrocardiographic, electrophoretic, histopathological and in vitro study on the protective effects of (-)epicatechin in isoproterenol-induced myocardial infarcted rats.

    PubMed

    Prince, Ponnian Stanely Mainzen

    2011-12-05

    (-) Epicatechin rich foods and (-) epicatechin improve cardiovascular function. Consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular diseases. Oxidative stress resulting from increased production of free radicals associated with decreased levels of antioxidants in the myocardium plays a major role in the pathogenesis of myocardial infarction. This study aims to evaluate the preventive effects of (-) epicatechin on oxidative stress in isoproterenol-induced myocardial infarcted rats. Male Wistar rats were pretreated with (-) epicatechin (20mg/kg body weight) daily for 21 days. After pretreatment, isoproterenol (100mg/kg body weight) was injected into the rats at an interval of 24h for two days to induce myocardial infarction. Isoproterenol induced rat's electrocardiogram showed elevated ST segments and significant increase in the activity of serum creatine kinase-MB, level of serum troponin-T and increased intensities of serum lactate dehydrogenase 1 and 2-isoenzymes. The rats also showed significant increased levels of heart lipid peroxidation products and significant decreased activities of heart superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and levels of reduced glutathione. Pretreatment with (-) epicatechin revealed significant protective effects on all the biochemical parameters and electrocardiogram investigated. Histopathology of myocardium confirmed the present findings. The in vitro study on the effects of (-) epicatechin on scavenging free radical 1,1-diphenyl-2-picrylhydrazyl revealed the free radical scavenging potential of (-) epicatechin. Thus, (-) epicatechin exerts protective effects against isoproterenol-induced oxidative stress thereby reducing cardiac tissue damage by its free radical scavenging and antioxidant effects. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat

    PubMed Central

    Sun, Shen-Jie; Wu, Xiao-Peng; Song, Heng-Liang; Li, Gui-Qi

    2015-01-01

    Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver-protection, gallbladder-protection, anti-bacteria, anti-inflammation, etc. The aim of this study was to investigate the potential cardioprotective effects of baicalin ameliorates isoproterenol-induced acute myocardial infarction (AMI) through inducible nitric oxide synthase (iNOS), inflammation, oxidative stress and P38MAPK passageway in rat. Rat model of AMI was induced by isoproterenol (100 mg/kg) and then treated baicalin (various does of baicalin: 1 mg/kg, 10 mg/kg and 100 mg/kg, respectively) for 24 h. Infarct size, the heart weight to body weight ratio and creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) of rats with AMI induced by isoproterenol were used to evaluate curative effect of baicalin on AMI. Meanwhile, iNOS and phosphorylation-p38 MAPK (p-p38) protein expressions, inflammatory factor and oxidative stress were inspected using western blot and commercial kits, respectively. In the present study, pre-treatment with baicalin (10 or 100 mg/kg) significantly ameliorated infarct size, the heart weight to body weight ratio and CK, CK-MB, LDH and cTnT levels in rats with AMI induced by isoproterenol. iNOS protein expression, the serum TNF-α, IL-6, MDA and SOD levels and p-38 protein expressions were significantly suppressed by treatment with baicalin (10 or 100 mg/kg). These results suggest that acute treatment with baicalin ameliorates AMI, iNOS, inflammation, oxidative stress and P38MAPK pathway in rat with AMI induced by isoproterenol. PMID:26885181

  18. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat.

    PubMed

    Sun, Shen-Jie; Wu, Xiao-Peng; Song, Heng-Liang; Li, Gui-Qi

    2015-01-01

    Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver-protection, gallbladder-protection, anti-bacteria, anti-inflammation, etc. The aim of this study was to investigate the potential cardioprotective effects of baicalin ameliorates isoproterenol-induced acute myocardial infarction (AMI) through inducible nitric oxide synthase (iNOS), inflammation, oxidative stress and P38MAPK passageway in rat. Rat model of AMI was induced by isoproterenol (100 mg/kg) and then treated baicalin (various does of baicalin: 1 mg/kg, 10 mg/kg and 100 mg/kg, respectively) for 24 h. Infarct size, the heart weight to body weight ratio and creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) of rats with AMI induced by isoproterenol were used to evaluate curative effect of baicalin on AMI. Meanwhile, iNOS and phosphorylation-p38 MAPK (p-p38) protein expressions, inflammatory factor and oxidative stress were inspected using western blot and commercial kits, respectively. In the present study, pre-treatment with baicalin (10 or 100 mg/kg) significantly ameliorated infarct size, the heart weight to body weight ratio and CK, CK-MB, LDH and cTnT levels in rats with AMI induced by isoproterenol. iNOS protein expression, the serum TNF-α, IL-6, MDA and SOD levels and p-38 protein expressions were significantly suppressed by treatment with baicalin (10 or 100 mg/kg). These results suggest that acute treatment with baicalin ameliorates AMI, iNOS, inflammation, oxidative stress and P38MAPK pathway in rat with AMI induced by isoproterenol.

  19. Adenosine A2A receptor agonist prevents cardiac remodeling and dysfunction in spontaneously hypertensive male rats after myocardial infarction

    PubMed Central

    da Silva, Jaqueline S; Gabriel-Costa, Daniele; Sudo, Roberto T; Wang, Hao; Groban, Leanne; Ferraz, Emanuele B; Nascimento, José Hamilton M; Fraga, Carlos Alberto M; Barreiro, Eliezer J; Zapata-Sudo, Gisele

    2017-01-01

    Background This work evaluated the hypothesis that 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294), an agonist of adenosine A2A receptor, could be beneficial for preventing cardiac dysfunction due to hypertension associated with myocardial infarction (MI). Methods Male spontaneously hypertensive rats (SHR) were randomly divided into four groups (six animals per group): sham-operation (SHR-Sham), and myocardial infarction rats (SHR-MI) were treated orally either with vehicle or LASSBio-294 (10 and 20 mg.kg−1.d−1) for 4 weeks. Echocardiography and in vivo hemodynamic parameters measured left ventricle (LV) structure and function. Exercise tolerance was evaluated using a treadmill test. Cardiac remodeling was accessed by LV collagen deposition and tumor necrosis factor α expression. Results Early mitral inflow velocity was significantly reduced in the SHR-MI group, and there was significant recovery in a dose-dependent manner after treatment with LASSBio-294. Exercise intolerance observed in the SHR-MI group was prevented by 10 mg.kg−1.d−1 of LASS-Bio-294, and exercise tolerance exceeded that of the SHR-Sham group at 20 mg.kg−1.d−1. LV end-diastolic pressure increased after MI, and this was prevented by 10 and 20 mg.kg−1.d−1 of LASSBio-294. Sarcoplasmic reticulum Ca2+ ATPase levels were restored in a dose-dependent manner after treatment with LASSBio-294. Fibrosis and inflammatory processes were also counteracted by LASSBio-294, with reductions in LV collagen deposition and tumor necrosis factor α expression. Conclusion In summary, oral administration of LASSBio-294 after MI in a dose-dependent manner prevented the development of cardiac dysfunction, demonstrating this compound’s potential as an alternative treatment for heart failure in the setting of ischemic heart disease with superimposed chronic hypertension. PMID:28293100

  20. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats

    PubMed Central

    Lam, Vy; Su, Jidong; Hsu, Anna; Gross, Garrett J.; Salzman, Nita H.

    2016-01-01

    Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host’s metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in

  1. Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats

    PubMed Central

    Schubring-Giese, Maximilian; Leemburg, Susan; Luft, Andreas Rüdiger; Hosp, Jonas Aurel

    2016-01-01

    Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session. PMID:27314672

  2. Human erythropoietin gene delivery for cardiac remodeling of myocardial infarction in rats.

    PubMed

    Lee, Youngsook; McGinn, Arlo N; Olsen, Curtis D; Nam, Kihoon; Lee, Minhyung; Shin, Sug Kyun; Kim, Sung Wan

    2013-10-10

    Considerable efforts have been made to exploit cardioprotective drugs and gene delivery systems for myocardial infarction (MI). The promising cardioprotective effects of recombinant human erythropoietin (rHuEPO) protein in animal experiments have not been consistently reproduced in clinical human trials of acute MI; however, the mechanisms underlying the inconsistent discrepancies are not yet fully understood. We hypothesized that the plasmid human erythropoietin gene (phEPO) delivered by our bioreducible polymer might produce cardioprotective effects on post-infarct cardiac remodeling. We demonstrated that intramyocardial delivery of phEPO by an arginine-grafted poly(disulfide amine) (ABP) polymer in infarcted rats preserves cardiac geometry and systolic function. The reduced infarct size of phEPO/ABP delivery was followed by decrease in fibrosis, protection from cardiomyocyte loss, and down-regulation of apoptotic activity. In addition, the increased angiogenesis and decreased myofibroblast density in the border zone of the infarct support the beneficial effects of phEPO/ABP administration. Furthermore, phEPO/ABP delivery induced prominent suppression on Ang II and TGF-β activity in all subdivisions of cardiac tissues except for the central zone of infarct. These results of phEPO gene therapy delivered by a bioreducible ABP polymer provide insight into the lack of phEPO gene therapy translation in the treatment of acute MI to human trials. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Human Erythropoietin Gene Delivery for Cardiac Remodeling of Myocardial Infarction in Rats

    PubMed Central

    Lee, Youngsook; McGinn, Arlo N.; Olsen, Curtis D.; Nam, Kihoon; Lee, Minhyung; Shin, Sug Kyun; Kim, Sung Wan

    2013-01-01

    Considerable efforts have been made to exploit cardioprotective drugs and gene delivery systems for myocardial infarction (MI). The promising cardioprotective effects of recombinant human erythropoietin (rHuEPO) protein in animal experiments have not been consistently reproduced in clinical human trials of acute MI; however, the mechanisms underlying the inconsistent discrepancies are not yet fully understood. We hypothesized that the plasmid human erythropoietin gene (phEPO) delivered by our bioreducible polymer might produce cardioprotective effects on post-infarct cardiac remodeling. We demonstrated that intramyocardial delivery of phEPO by an arginine-grafted poly(disulfide amine) (ABP) polymer in infarcted rats preserves cardiac geometry and systolic function. The reduced infarct size of phEPO/ABP delivery was followed by decrease in fibrosis, protection from cardiomyocyte loss, and down-regulation of apoptotic activity. In addition, the increased angiogenesis and decreased myofibroblast density in the border zone of the infarct support the beneficial effects of phEPO/ABP administration. Furthermore, phEPO/ABP delivery induced prominent suppression on Ang II and TGF-β activity in all subdivisions of cardiac tissues except for the central zone of infarct. These results of phEPO gene therapy delivered by a bioreducible ABP polymer provide insight into the lack of phEPO gene therapy translation in the treatment of acute MI to human trials. PMID:23806842

  4. [Effects of Chinese herbal medicines Shengmai injection and Xuesaitong injection on ventricular fibrillation threshold and connexin 43 expression in rats with myocardial infarction].

    PubMed

    Wu, Ai-Ming; Zhang, Dong-Mei; Lou, Li-Xia; Zhai, Jian-Ying; Lü, Xi-Ying; Chai, Li-Min; Wang, Shuo-Ren

    2011-07-01

    To explore the effects of Shengmai injection and Xuesaitong injection, compound Chinese herbal medicines for replenishing qi and activating blood, on ventricular fibrillation threshold, heart structure and connexin 43 (Cx43) expression in rats with myocardial infarction (MI). One hundred male SD rats were randomly divided into sham operation group, model group, Yiqi Huoxue (YQHX) group (Shengmai injection plus Xuesaitong injection) and captopril group. MI model of rats was established by ligating left anterior descending coronary artery, and rats in sham operation group were prepared in the same way except for the ligation of coronary artery. Rats were treated with corresponding drugs for 1 month from next day after modeling. After treatment ventricular fibrillation threshold was detected, and heart weight index, left ventricular internal diameter and percentage of myocardial infarction were measured. Expression of Cx43 mRNA in myocardium was detected by real-time fluorescent quantitative polymerase chain reaction, and expression of Cx43 protein was observed by immunohistochemical method. Compared with the sham operation group, ventricular fibrillation threshold decreased significantly, heart weight index and left ventricular internal diameter increased, while expressions of Cx43 mRNA and protein decreased remarkably in the model group (P<0.01). Compared with the model group, ventricular fibrillation threshold was increased significantly, heart weight index, left ventricular internal diameter and percentage of myocardial infarction were decreased significantly in the YQHX group and captopril group (P<0.05 or P<0.01). When it comes to expression of Cx43, both Cx43 mRNA and protein expressions were increased remarkably in the YQHX group compared with the model group (P<0.05 or P<0.01), while only density mean and integral optical density of Cx43 protein expression were increased significantly in the captopril group (P<0.05). The enhancements on Cx43 mRNA and positive

  5. Sublytic complement attack reduces infarct size in rabbit isolated hearts: evidence for C5a-mediated cardioprotection.

    PubMed

    Tanhehco, E J; Lee, H; Lucchesi, B R

    2000-09-01

    Sublytic complement attack can elicit protective cellular responses without precipitating cell death. Our investigation examined the effects of non-lethal complement activation in isolated hearts. New Zealand white rabbit hearts were subjected to 30 min of ischemia followed by 1 h of reperfusion. Prior to ischemia, hearts were perfused for 20 min with 0.5% normal human plasma (NHP). Hearts treated with NHP developed significantly (p<0.05) smaller infarcts compared with controls, expressed as percent of area at risk (AAR) (25.3+/-4.0% vs. 40.9+/-4.3%, respectively). Heat-inactivation, soluble complement receptor 1 (sCR1; 20 nM), and anti-C5a antibody reversed the protective effect of NHP (39.0+/-3.1%, 41.7+/-5.1% and 38.4+/-2.3% AAR, respectively). Hearts treated with 3 nM C5a exhibited infarct sizes similar to those exposed to NHP (27.6+/-5.0% AAR). sCR1 alone did not affect infarct size (37.9+/-4.5% AAR). The results suggest that non-lethal complement activation attenuates reperfusion injury through formation of C5a.

  6. Mild heart failure is a mortality marker after a non-ST-segment acute myocardial infarction.

    PubMed

    Núñez-Gil, Iván J; García-Rubira, Juan C; Luaces, María; Vivas, David; De Agustín, Jose Alberto; González-Ferrer, Juan J; Bordes, Sara; Macaya, Carlos; Fernández-Ortiz, Antonio

    2010-10-01

    The Killip classification categorizes heart failure (HF) in acute myocardial infarction, and has a prognostic value. Although non-ST-elevation myocardial infarction (NSTEMI) is increasing steadily, little information is available about the prognostic value of low Killip class in this scenario. Our aim was to assess the prognostic value of mild HF in NSTEMI. 835 patients with NSTEMI between 2005 and 2007 were prospectively recruited. Patients in Killip-1 (K1=684) or Killip-2 class (K2=113) were selected (38, with K>2, excluded). Clinical, angiographic, treatment strategies, and 30-day all-cause mortality, together with other cardiovascular outcomes were recorded. K2 patients were mostly women (K1 27.9% vs K2 48.0%, p<0.001) and older (K1 66.6years vs K2 73.8years, p<0.001) with a higher frequency of diabetes mellitus (p<0.001) and hypertension (p<0.001). Smoking was less frequent in the K2-group (p=0.003). A previous infarction/revascularization history was similar in both groups. The infarction size, assessed by Troponin I/Creatin kinase, did not differ between groups (p=0.378 and p=0.855). Multivessel coronary disease and revascularization procedures were less common in group K2 (p=0.015 and p=0.005 vs group K1, respectively). Patients in K2 had a worse prognosis in terms of maximum Killip class, death and major adverse cardiovascular events (p<0.001). After multivariate analysis, mild HF at presentation was an independent risk factor for mortality (OR=6.50; IC 95%: 2.48-16.95; p<0.001). Mild HF at presentation in NSTEMI is linked to a poor prognosis, with increased short-term mortality. Thus, a more aggressive approach including early cardiac catheterization and revascularization should be considered. Copyright (c) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  7. Coronary artery calcification and family history of myocardial infarction in the Dallas heart study.

    PubMed

    Paixao, Andre R M; Berry, Jarett D; Neeland, Ian J; Ayers, Colby R; Rohatgi, Anand; de Lemos, James A; Khera, Amit

    2014-07-01

    This study aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD). FH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for. Among 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC. The mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile. FH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats.

    PubMed Central

    Wexler, B. C.

    1985-01-01

    Young adult, male and female, normotensive Sprague-Dawley (S-D) and spontaneously hypertensive rats (SHR) were injected with propranolol three times daily for 3 weeks. None of the animals manifested signs of withdrawal when the injections were terminated. Seven days later, the animals were challenged with a dose of isoproterenol which would produce massive myocardial infarction and 50-60% mortality in non-treated animals. The propranolol pretreatment caused marked tranquilizing and blood pressure lowering effects in SHR exclusively. Despite the 7-day propranolol withdrawal period, very few animals died and myocardial damage was minimal. However, blood pressure levels dropped to shock-like levels, blood CPK and LDH levels showed dynamic increases, there was marked hypertriglyceridaemia, and plasma corticosterone rose to supranormal levels. Microscopically, the hearts of the propranolol pretreated animals showed little evidence of necrosis but the SHR hearts manifested large atrial and ventricular thrombi. It is suggested that in the rat, propranolol treatment causes positive myocardial protective effects mediated through hormonal and metabolic changes and propranolol withdrawal does not lead to hypersensitivity to catecholamines. In fact, the beta-blocking effects of propranolol remain effective for some time after withdrawal. Images Fig. 7 Fig. 8 PMID:4039190

  9. Liguzinediol improved the heart function and inhibited myocardial cell apoptosis in rats with heart failure

    PubMed Central

    Li, Yu; Song, Ping; Zhu, Qing; Yin, Qiu-yi; Ji, Jia-wen; Li, Wei; Bian, Hui-min

    2014-01-01

    Aim: Liguzinediol is a novel derivative of ligustrazine isolated from the traditional Chinese medicine Chuanxiong (Ligusticum wallichii Franch), and produces significant positive inotropic effect in isolated rat hearts. In this study we investigated the effects of liguzinediol on a rat model of heart failure. Methods: To induce heart failure, male SD rats were injected with doxorubicin (DOX, 2 mg/kg, ip) once a week for 4 weeks. Then the rats were administered with liguzinediol (5, 10, 20 mg·kg−1·d−1, po) for 2 weeks. Hemodynamic examination was conducted to evaluate heart function. Myocardial cell apoptosis was examined morphologically. The expression of related genes and proteins were analyzed using immunohistochemical staining and Western blot assays, respectively. Results: Oral administration of liguzinediol dose-dependently improved the heart function in DOX-treated rats. Electron microscopy revealed that liguzinediol (10 mg·kg−1·d−1) markedly attenuated DOX-induced injury of cardiomyocytes, and decreased the number of apoptotic bodies in cardiomyocytes. Furthermore, liguzinediol significantly decreased Bax protein level, and increased Bcl-2 protein level in cardiomyocytes of DOX-treated rats, led to an increase in the ratio of Bcl-2/Bax. Moreover, liguzinediol significantly decreased the expression of both cleaved caspase-3 and NF-κB in cardiomyocytes of DOX-treated rats. Administration of digitalis (0.0225 mg·kg−1·d−1) also markedly improved the heart function and the morphology of cardiomyocytes in DOX-treated rats. Conclusion: Liguzinediol improves the heart function and inhibits myocardial cell apoptosis in the rat model of heart failure, which is associated with regulating Bcl-2, Bax, caspase-3 and NF-κB expression. PMID:25220638

  10. [L-propionylcarnitine taurine amide induces the metabolic recovery of the isolated postischemic rat heart].

    PubMed

    Lazzarino, G; Corsico, N; Tavazzi, B; di Pierro, D; Arrigoni-Martelli, E; Giardina, B

    1992-10-01

    The effect of reperfusion with L-propionyl-carnitine-taurinammide 1 mM was evaluated on the metabolic recovery of the isolated postischemic rat heart. Data referring to the tissue concentration of the high-energy phosphates, oxypurines, nucleosides, nicotinic coenzymes, lactate and pyruvate indicate that L-propionyl-carnitine-taurinammide significantly improves the metabolism of the reperfused myocardium. In particular, ATP, creatinphosphate, GTP, sum of adenine nucleotides and the energy charge resulted 1.80, 1.83, 3.47, 1.47 and 1.20 times higher respectively than the corresponding values recorded in control reperfused heart (p < 0.01 all). These data, out of supplying the necessary biochemical support to the beneficial effects of L-propionyl-carnitine-taurinammide on hemodynamics obtained in previous studies, suggest that L-propionyl-carnitine-taurinammide might represent a useful tool for the pharmacological treatment of myocardial infarction.

  11. Altered carnitine transport in pressure-overload hypertrophied rat hearts

    SciTech Connect

    O'Rourke, B.; Foster, K.; Reibel, D.K.

    1986-03-01

    The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L-/sup 14/C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 ..mu..M carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 ..mu..M carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart.

  12. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

    PubMed

    Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

    2015-01-01

    Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  13. Normobaric hyperoxia retards the evolution of ischemic brain tissue toward infarction in a rat model of transient focal cerebral ischemia.

    PubMed

    Xu, Ji; Zhang, Yuan; Liang, Zhouyuan; Wang, Ting; Li, Weiping; Ren, Lijie; Huang, Shaonong; Liu, Wenlan

    2016-01-01

    Oxygen therapy has been long considered a logical therapy for ischemic stroke. Our previous studies showed that normobaric hyperoxia (normobaric hyperoxia (NBO), 95% O2 with 5% CO2) treatment during ischemia reduced ischemic neuronal death and cerebromicrovascular injury in animal stroke models. In this study, we studied the effects of NBO on the evolution of ischemic brain tissue to infarction in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats were given NBO (95% O2) or normoxia (21% O2) during 90-min filament occlusion of the middle cerebral artery (MCAO), followed by 3 or 22.5 h of reperfusion. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the longitudinal evolution of tissue infarction. Results: In normoxic rats, MCA-supplied cortical and striatal tissue was infarcted after 90-min MCAO with 22.5 h of reperfusion. NBO-treated rats showed a 61.4% reduction in infarct size and tissue infarction mainly occurred in the ischemic striatum. When infarction was assessed at an earlier time point, i.e. at 3 h of reperfusion, normoxic rats showed significantly smaller but mature infarction (no TTC staining, white color), with the infarction mainly occurring in the striatum. Unexpectedly, NBO-treated rats only showed immature lesion (partially stained by TTC, light white color) in the ischemic striatum, indicating that NBO treatment also retarded the process of neuronal death in the ischemic core. Of note, NBO-preserved striatal tissue underwent infarction after prolonged reperfusion. Conclusions: Our results demonstrate that NBO treatment given during cerebral ischemia retards the evolution of ischemic brain tissue toward infarction and NBO-preserved cortical tissue survives better than NBO-preserved striatal tissue during the phase of reperfusion.

  14. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat

    PubMed Central

    Chen, Huaguo; Xu, Yongfu; Wang, Jianzhong; Zhao, Wei; Ruan, Huihui

    2015-01-01

    Baicalin belongs to glucuronic acid glycosides and after hydrolysisbaicalein and glucuronic acid come into being. It has such effects as clearing heat and removing toxicity, anti-inflammation, choleresis, bringing high blood pressure down, diuresis, anti-allergic reaction and so on. In this study, we investigated whether baicalin ameliorates isoproterenol-induced acute myocardial infarction and its mechanism. Rat model of acute myocardial infarction was induced by isoproterenol. Casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT) and infarct size measurement were used to measure the protective effect of baicalin on isoproterenol-induced acute myocardial infarction. iNOS protein expression in rat was analyzed using western blot analysis. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD) and caspase-3 activation levels were explored using commercial ELISA kits. In the acute myocardial infarction experiment, baicalin effectively ameliorates the level of CK, CK-MB, LDH and cTnT, reduced infarct size in acute myocardial infarction rat model. Meanwhile, treatment with baicalin effectively decreased the iNOS protein expression, inflammatory factors and oxidative stresses in a rat model of acute myocardial infarction. However, baicalin emerged that anti-apoptosis activity and suppressed the activation of caspase-3 in a rat model of acute myocardial infarction. The data suggest that the protective effect of baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat. PMID:26617721

  15. Ischemic Postconditioning Does Not Provide Cardioprotection from Long Term Ischemic Injury in Isolated Male or Female Rat Hearts

    PubMed Central

    Lee, Daniel S.; Steinbaugh, Gregory E.; Quarrie, Ricardo; Yang, Fuchun; Talukder, Hassan; Zweier, Jay L.; Crestanello, Juan A.

    2010-01-01

    Background Ischemic postconditioning(PoC) is a cardio-protective strategy in which initial reperfusion is interrupted by episodes of ischemia. It is unclear whether PoC can be achieved in the Langendorff perfused rat heart model. We investigated 1) whether postconditioning occurs in Langendorff perfused rat heart and 2) whether there is a gender specific response to PoC. Materials and methods Male/female rat hearts(n=8/group) were subjected to 30 minutes of equilibration, 30 minutes of ischemia, and 120 minutes of reperfusion (CONTROL). PoC was induced by 6 cycles(PoC 6c10s), 3 cycles(PoC 3c10s), or 2 cycles(PoC 2c10s) of 10 second reperfusion/10 second ischemia. Rate pressure product(RPP) and infarct size were measured. Male rats(n=7/group) were subjected in vivo to 30 minute left coronary ligation followed by 24 hours of reperfusion(CONTROL) or PoC 6c10s and 24 hours of reperfusion. Results Recovery of RPP was 18±4% in male CONTROL vs. 17±2% for 6c10s, 16±1% for 3c10s, and 15±3% for 2c10s. Female CONTROL hearts recovered 25±3% of their RPP vs. 21±2% for 6c10s. Infarct size was 25±3% for male CONTROL vs. 26±3% for 6c10s, 30±2% for 3c10s, 28±1% for 2c10s; and 30±2% for female CONTROL vs. 29±2% in 6c10s. In vivo Infarct size for CONTROL and PoC 6c10s was 44±3% and 28±5%, respectively (p<0.05). Conclusions In the Langendorff perfused rat hearts, none of the PoC protocols improved myocardial tolerance to ischemia reperfusion injury nor decreased infarct size; however, in vivo postconditioning did confer protection. The lack of protection in the isolated hearts was not gender specific. PMID:20934717

  16. Mitochondrial aldehyde dehydrogenase 2 plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK/p53 pathway in mice.

    PubMed

    Sun, Aijun; Zou, Yunzeng; Wang, Ping; Xu, Danling; Gong, Hui; Wang, Shijun; Qin, Yingjie; Zhang, Peng; Chen, Yunqin; Harada, Mutsuo; Isse, Toyoshi; Kawamoto, Toshihiro; Fan, Huizhi; Yang, Pengyuan; Akazawa, Hiroshi; Nagai, Toshio; Takano, Hiroyuki; Ping, Peipei; Komuro, Issei; Ge, Junbo

    2014-09-18

    Increasing evidence suggests a critical role for mitochondrial aldehyde dehydrogenase 2 (ALDH2) in protection against cardiac injuries; however, the downstream cytosolic actions of this enzyme are largely undefined. Proteomic analysis identified a significant downregulation of mitochondrial ALDH2 in the heart of a rat heart failure model after myocardial infarction. The mechanistic insights underlying ALDH2 action were elucidated using murine models overexpressing ALDH2 or its mutant or with the ablation of the ALDH2 gene (ALDH2 knockout) and neonatal cardiomyocytes undergoing altered expression and activity of ALDH2. Left ventricle dilation and dysfunction and cardiomyocyte death after myocardial infarction were exacerbated in ALDH2-knockout or ALDH2 mutant-overexpressing mice but were significantly attenuated in ALDH2-overexpressing mice. Using an anoxia model of cardiomyocytes with deficiency in ALDH2 activities, we observed prominent cardiomyocyte apoptosis and increased accumulation of the reactive aldehyde 4-hydroxy-2-nonenal (4-HNE). We subsequently examined the impacts of mitochondrial ALDH2 and 4-HNE on the relevant cytosolic protective pathways. Our data documented 4-HNE-stimulated p53 upregulation via the phosphorylation of JNK, accompanying increased cardiomyocyte apoptosis that was attenuated by inhibition of p53. Importantly, elevation of 4-HNE also triggered a reduction of the cytosolic HSP70, further corroborating cytosolic action of the 4-HNE instigated by downregulation of mitochondrial ALDH2. Downregulation of ALDH2 in the mitochondria induced an elevation of 4-HNE, leading to cardiomyocyte apoptosis by subsequent inhibition of HSP70, phosphorylation of JNK, and activation of p53. This chain of molecular events took place in both the mitochondria and the cytosol, contributing to the mechanism underlying heart failure. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. Neuroprotective effects of Bcl-2 overexpression on nerve cells of rats with acute cerebral infarction.

    PubMed

    Zhang, H R; Peng, J H; Zhu, G Y; Xu, R X

    2015-07-13

    We aimed to investigate the influence of lentiviral-mediated Bcl-2 overexpression in cerebral tissues of rats with acute cerebral infarction. Forty-five rats were randomly divided into sham, model, and treatment groups. The sham and model groups were administered a control lentiviral vector via the intracranial arteries 10 days before surgery, while the treatment group received lentivirus encoding a Bcl-2 overexpression vector. We induced cerebral artery infarction using a suture-occlusion method and analyzed the cerebral expression levels of apoptosis-related genes (caspase-3, Bax), total cerebral apoptosis, range of cerebral tissue infarction, and changes in nerve cell function after 72 h. The Bcl-2-encoding lentivirus was well expressed in rat cerebral tissues. The treatment group had significantly higher expression levels of Bcl-2 than the other two groups. After cerebral infarction, the model group had significantly increased expression levels of caspase-3 and Bax protein in cerebral tissues than the sham (P < 0.05). Expression of these apoptosis-related proteins in the treatment group was obviously lower than that in the model group (P < 0.05), but significantly higher than in the sham group (P < 0.05). Compared to sham, neuronal apoptosis levels and infarction range of cerebral tissues was increased in the model and treatment groups; however, these values in the treatment group were significantly lower than that in the model group (P < 0.05). Importantly, the treatment group had significantly decreased neurological impairment scores (P < 0.05). In conclusion, Bcl-2 over-expression can decrease neuronal apoptosis in rat cerebral tissue, and thus is neuroprotective after cerebral ischemia.

  18. Complete inhibition of creatine kinase in isolated perfused rat hearts

    SciTech Connect

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.

  19. Remote ischemic preconditioning impairs ventricular function and increases infarct size after prolonged ischemia in the isolated neonatal rabbit heart.

    PubMed

    Schmidt, Michael R; Støttrup, Nicolaj B; Michelsen, Marie M; Contractor, Hussain; Sørensen, Keld E; Kharbanda, Rajesh K; Redington, Andrew N; Bøtker, Hans E

    2014-03-01

    Remote ischemic preconditioning (rIPC) reduces myocardial injury in adults and children undergoing cardiac surgery. We compared the effect of rIPC in adult and neonatal rabbits to investigate whether protection against ischemia-reperfusion injury can be achieved in the newborn heart by (1) in vivo rIPC and (2) dialysate from adult rabbits undergoing rIPC. Isolated hearts from newborn and adult rabbits were randomized into 3 subgroups (control, in vivo rIPC, and dialysate obtained from adult, remotely preconditioned rabbits). Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Left ventricular (LV) function was assessed using a balloon-tipped catheter, glycolytic flux by tracer kinetics, and infarct size by tetrazolium staining. Isolated hearts underwent stabilization while perfused with standard Krebs-Henseleit buffer (control and in vivo rIPC) or Krebs-Henseleit buffer with added dialysate, followed by global no-flow ischemia and reperfusion. Within the age groups, the baseline LV function was similar in all subgroups. In the adult rabbit hearts, rIPC and rIPC dialysate attenuated glycolytic flux and protected against ischemia-reperfusion injury, with better-preserved LV function compared with that of the controls. In contrast, in the neonatal hearts, the glycolytic flux was lower and LV function was better preserved in the controls than in the rIPC and dialysate groups. In the adult hearts, the infarct size was reduced in the rIPC and dialysate groups compared with that in the controls. In the neonatal hearts, the infarct size was smaller in the controls than in the rIPC and dialysate groups. Remote ischemic preconditioning does not protect against ischemia-reperfusion injury in isolated newborn rabbit hearts and might even cause deleterious effects. Similar adverse effects were induced by dialysate from remotely preconditioned adult rabbits. Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.

  20. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function

    PubMed Central

    Linke, Axel; Müller, Patrick; Nurzynska, Daria; Casarsa, Claudia; Torella, Daniele; Nascimbene, Angelo; Castaldo, Clotilde; Cascapera, Stefano; Böhm, Michael; Quaini, Federico; Urbanek, Konrad; Leri, Annarosa; Hintze, Thomas H.; Kajstura, Jan; Anversa, Piero

    2005-01-01

    The purpose of this study was to determine whether the heart in large mammals contains cardiac progenitor cells that regulate organ homeostasis and regenerate dead myocardium after infarction. We report that the dog heart possesses a cardiac stem cell pool characterized by undifferentiated cells that are self-renewing, clonogenic, and multipotent. These clonogenic cells and early committed progeny possess a hepatocyte growth factor (HGF)–c-Met and an insulin-like growth factor 1 (IGF-1)-IGF-1 receptor system that can be activated to induce their migration, proliferation, and survival. Therefore, myocardial infarction was induced in chronically instrumented dogs implanted with sonomicrometric crystals in the region of the left ventricular wall supplied by the occluded left anterior descending coronary artery. After infarction, HGF and IGF-1 were injected intramyocardially to stimulate resident cardiac progenitor cells. This intervention led to the formation of myocytes and coronary vessels within the infarct. Newly generated myocytes expressed nuclear and cytoplasmic proteins specific of cardiomyocytes: MEF2C was detected in the nucleus, whereas α-sarcomeric actin, cardiac myosin heavy chain, troponin I, and α-actinin were identified in the cytoplasm. Connexin 43 and N-cadherin were also present. Myocardial reconstitution resulted in a marked recovery of contractile performance of the infarcted heart. In conclusion, the activation of resident primitive cells in the damaged dog heart can promote a significant restoration of dead tissue, which is paralleled by a progressive improvement in cardiac function. These results suggest that strategies capable of activating the growth reserve of the myocardium may be important in cardiac repair after ischemic injury. PMID:15951423

  1. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction

    PubMed Central

    Richart, Adèle; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Guerin, Coralie; Gautier, Gregory; Blank, Ulrich; Heymes, Christophe; Luche, Elodie; Cousin, Béatrice; Rodewald, Hans-Reimer

    2016-01-01

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit–independent MC-deficient (Cpa3Cre/+) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca2+ desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force–Ca2+ interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. PMID:27353089

  2. Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction.

    PubMed

    Ngkelo, Anta; Richart, Adèle; Kirk, Jonathan A; Bonnin, Philippe; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Le Gall, Sylvain; Renault, Nisa; Guerin, Coralie; Ranek, Mark J; Kervadec, Anaïs; Danelli, Luca; Gautier, Gregory; Blank, Ulrich; Launay, Pierre; Camerer, Eric; Bruneval, Patrick; Menasche, Philippe; Heymes, Christophe; Luche, Elodie; Casteilla, Louis; Cousin, Béatrice; Rodewald, Hans-Reimer; Kass, David A; Silvestre, Jean-Sébastien

    2016-06-27

    Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators.

  3. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  4. Augmented cardiac formation of oxidatively-induced carbonylated proteins accompanies the increased functional severity of post-myocardial infarction heart failure in the setting of type 1 diabetes mellitus.

    PubMed

    Dennis, Kathleen E; Hill, Salisha; Rose, Kristie L; Sampson, Uchechukwu K A; Hill, Michael F

    2013-01-01

    Heart failure (HF) is a dominant cause for the higher mortality of diabetics after myocardial infarction (MI). In the present investigation, we have discovered that higher levels of oxidative stress (OS)-induced carbonylated proteins accompany worsening post-MI HF in the presence of type 1 diabetes. These findings provide a mechanistic link between amplified OS and exacerbation of post-infarction HF in diabetes. Type 1 diabetes mellitus (DM) patients surviving myocardial infarction (MI) manifest an increased incidence of subsequent heart failure (HF). We have previously shown that after MI, type 1 DM is associated with accentuated myocardial oxidative stress (OS) and concomitant worsening of left ventricular (LV) function. However, the precise mechanisms whereby type 1 DM-enhanced OS adversely affects HF after MI remain obscure. As carbonylation of proteins is an irreversible post-translational modification induced only by OS that often leads to the loss of function, we analyzed protein-bound carbonyls in the surviving LV myocardium of MI and DM+MI rats in relation to residual LV function. Type 1 DM was induced in rats via administration of streptozotocin. Two weeks after induction of type 1 DM, MI was produced in DM and non-DM rats by coronary artery ligation. Residual LV function and remodeling was assessed at 4 weeks post-MI by echocardiography. Myocardial carbonylated proteins were detected through OxyBlot analysis, and identified by mass spectrometry. Compared with MI rats, DM+MI rats exhibited significantly poorer residual LV systolic function and elevated wet to dry weight ratios of the lungs. Protein carbonyl content in cardiac tissue and isolated heart mitochondria of DM+MI rats was 20% and 48% higher, respectively, versus MI rats. Anti-oxidative enzymes and fatty acid utilization proteins were among the carbonylated protein candidates identified. These findings implicate myocardial protein carbonylation as part of the molecular pathophysiology of

  5. Neural control of the endocrine rat heart.

    PubMed

    Jiao, J H; Baertschi, A J

    1993-08-15

    Although atrial stretch is the accepted stimulus for atrial natriuretic factor (ANF), in vivo studies suggest a stretch-independent, neurally induced ANF release mechanism. Thus the hypothesis that cardiac nerves can stimulate ANF secretion was tested in the Langendorff-perfused, paced rat heart. Venom from the scorpion Centruroides sculpturatus was used to activate neuronal sodium channels, veratridine was added to activate sodium channels (predominantly in myocytes), and electrical stimulation was applied to the right atrial appendage. The efficacy of nerve stimulation was verified by measurements of increased neuropeptide Y in the effluent. ANF levels in the effluent increased by 120% over baseline with 0.5 microM scorpion venom and by 88% with 0.5 microM veratridine (P < 0.01). Cardiac mechanics did not explain the large, concentration-dependent ANF response to the scorpion venom, since changes in the left ventricular developed pressure were small, opposite to those induced by veratridine, and unaffected by sympathectomy or adrenergic receptor blockade. Prior chemical sympathectomy and adrenergic receptor blockade almost abolished the ANF response to scorpion venom but hardly affected the ANF response to veratridine. Addition of 1 microM tetrodotoxin abolished all ANF responses. Electrical stimulation of the atrial appendage increased the ANF secretion by 60.2% (P < 0.02), in conjunction with neuropeptide Y, whereas control stimulations were ineffective. These studies unequivocally demonstrate that stimulation of cardiac sympathetic nerves potently stimulates ANF secretion.

  6. Caspase-3 inhibitor prevents the apoptosis of brain tissue in rats with acute cerebral infarction.

    PubMed

    Sun, Yuhua; Xu, Yuming; Geng, Lijiao

    2015-07-01

    The aim of the present study was to investigate the effect of the caspase-3 inhibitor z-DEVD-fmk on the apoptosis of the brain tissues of rats with acute cerebral infarction. Middle cerebral artery occlusion was used to establish a rat model of infarction, and the rats were randomly divided into a sham group (n=15), model group (n=15) and treatment group (n=15). z-DEVD-fmk (2.5 µg/kg) was injected into the intracranial artery of rats in the treatment group, while the same volume of phosphate-buffered saline solution was administered to the rats of the sham and model groups. After 48 h, all rats were sacrificed and their brain tissues were removed. The caspase-3 mRNA level, protein level and activity, brain cell apoptosis index and infarction scope of the three groups were analyzed. Neurological impairment was also assessed. At 48 h after model establishment, the caspase-3 mRNA and protein levels in the brain tissues of the model group were significantly higher than those of the sham group, and those in the treatment group were significantly lower than those in the model group (P<0.05); however, they remained significantly higher than those in the sham group. Caspase-3 activity in the model group was significantly higher than that in the sham group, and treatment with the caspase-3 inhibitor significantly reduced caspase-3 activity compared with that in the model group (P<0.05). The apoptosis index and infarction scope in the model and treatment groups were significantly increased compared with those in the sham group, and were significantly lower in the treatment group than in the model group (P<0.05). The neurological impairment of rats in the model and treatment groups was increased significantly compared with that in the sham group, and the treatment group exhibited a significantly lower level of neurological impairment than the model group (P<0.05). In conclusion, the caspase-3 inhibitor z-DEVD-fmk effectively inhibited apoptosis and delayed the necrosis of

  7. Caspase-3 inhibitor prevents the apoptosis of brain tissue in rats with acute cerebral infarction

    PubMed Central

    SUN, YUHUA; XU, YUMING; GENG, LIJIAO

    2015-01-01

    The aim of the present study was to investigate the effect of the caspase-3 inhibitor z-DEVD-fmk on the apoptosis of the brain tissues of rats with acute cerebral infarction. Middle cerebral artery occlusion was used to establish a rat model of infarction, and the rats were randomly divided into a sham group (n=15), model group (n=15) and treatment group (n=15). z-DEVD-fmk (2.5 µg/kg) was injected into the intracranial artery of rats in the treatment group, while the same volume of phosphate-buffered saline solution was administered to the rats of the sham and model groups. After 48 h, all rats were sacrificed and their brain tissues were removed. The caspase-3 mRNA level, protein level and activity, brain cell apoptosis index and infarction scope of the three groups were analyzed. Neurological impairment was also assessed. At 48 h after model establishment, the caspase-3 mRNA and protein levels in the brain tissues of the model group were significantly higher than those of the sham group, and those in the treatment group were significantly lower than those in the model group (P<0.05); however, they remained significantly higher than those in the sham group. Caspase-3 activity in the model group was significantly higher than that in the sham group, and treatment with the caspase-3 inhibitor significantly reduced caspase-3 activity compared with that in the model group (P<0.05). The apoptosis index and infarction scope in the model and treatment groups were significantly increased compared with those in the sham group, and were significantly lower in the treatment group than in the model group (P<0.05). The neurological impairment of rats in the model and treatment groups was increased significantly compared with that in the sham group, and the treatment group exhibited a significantly lower level of neurological impairment than the model group (P<0.05). In conclusion, the caspase-3 inhibitor z-DEVD-fmk effectively inhibited apoptosis and delayed the necrosis of

  8. Income inequality and 30 day outcomes after acute myocardial infarction, heart failure, and pneumonia: retrospective cohort study.

    PubMed

    Lindenauer, Peter K; Lagu, Tara; Rothberg, Michael B; Avrunin, Jill; Pekow, Penelope S; Wang, Yongfei; Krumholz, Harlan M

    2013-02-14

    To examine the association between income inequality and the risk of mortality and readmission within 30 days of hospitalization. Retrospective cohort study of Medicare beneficiaries in the United States. Hierarchical, logistic regression models were developed to estimate the association between income inequality (measured at the US state level) and a patient's risk of mortality and readmission, while sequentially controlling for patient, hospital, other state, and patient socioeconomic characteristics. We considered a 0.05 unit increase in the Gini coefficient as a measure of income inequality. US acute care hospitals. Patients aged 65 years and older, and hospitalized in 2006-08 with a principal diagnosis of acute myocardial infarction, heart failure, or pneumonia. Risk of death within 30 days of admission or rehospitalization for any cause within 30 days of discharge. The potential number of excess deaths and readmissions associated with higher levels of inequality in US states in the three highest quarters of income inequality were compared with corresponding data in US states in the lowest quarter. Mortality analyses included 555,962 admissions (4348 hospitals) for acute myocardial infarction, 1,092,285 (4484) for heart failure, and 1,146,414 (4520); readmission analyses included 553,037 (4262), 1,345,909 (4494), and 1,345,909 (4524) admissions, respectively. In 2006-08, income inequality in US states (as measured by the average Gini coefficient over three years) varied from 0.41 in Utah to 0.50 in New York. Multilevel models showed no significant association between income inequality and mortality within 30 days of admission for patients with acute myocardial infarction, heart failure, or pneumonia. By contrast, income inequality was associated with rehospitalization (acute myocardial infarction, risk ratio 1.09 (95% confidence interval 1.03 to 1.15), heart failure 1.07 (1.01 to 1.12), pneumonia 1.09 (1.03 to 1.15)). Further adjustment for individual income

  9. Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.

    PubMed

    Gautam, Milan; Fujita, Daiki; Kimura, Kazuhiro; Ichikawa, Hinako; Izawa, Atsushi; Hirose, Masamichi; Kashihara, Toshihide; Yamada, Mitsuhiko; Takahashi, Masafumi; Ikeda, Uichi; Shiba, Yuji

    2015-04-01

    The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100μL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n≥12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n≥12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI.

  10. Puerarin accelerate scardiac angiogenesis and improves cardiac function of myocardial infarction by upregulating VEGFA, Ang-1 and Ang-2 in rats

    PubMed Central

    Ai, Fen; Chen, Manhua; Yu, Bo; Yang, Yang; Xu, Guizhong; Gui, Feng; Liu, Zhenxing; Bai, Xiangyan; Chen, Zhen

    2015-01-01

    Objective: The traditional Chinese medicinal puerarin, has long been used to treat cardiovascular diseases, however, the mechanism underlying its effects remain unclear. Here, this study would to investigate the role of puerarin on cardiac angiogenesis and myocardial function induced by myocardial infarction. Methods: Puerarin was treated in rats after left anterior descending coronary artery (LAD) ligation and maintained for 4 weeks (diets containing about 50 mg/kg/day or 100 mg/kg/day). After treatment, cardiac function was evaluated by echocardiography and markers of heart failure. Paraffin sections of the heart tissues were used for isolect in GS-IB4 staining. The Mrna and protein expression levels of VEGFA, Ang-1 and Ang-2 were detected by real-time polymerase chain reaction and western blot. Results: Significantly damaged angiogenesis and slightly increase of VEGFA, Ang-1 and Ang-2 were showed after LAD ligation. Impaired angiogenesis and cardiac function were remarkably improved in puerarin treatment rats with great increase of VEGFA, Ang-1 and Ang-2. Conclusion: The above results demonstrated that puerarin could accelerate cardiac angiogenesis and improve cardiac function of myocardial infarction rats by upregulating VEGFA, Ang-1 and Ang-2. PMID:26885006

  11. Ex Vivo Treatment with a Polyphenol-Enriched Cocoa Extract Ameliorates Myocardial Infarct and Postischemic Mitochondrial Injury in Normotensive and Hypertensive Rats.

    PubMed

    González Arbeláez, Luisa F; Ciocci Pardo, Alejandro; Fantinelli, Juliana C; Caldiz, Claudia; Ríos, José Luis; Schinella, Guillermo R; Mosca, Susana M

    2016-06-29

    Our objective was to determine the effects of a polyphenol-enriched cocoa extract (PCE) on myocardial postischemic alterations in normotensive (Wistar rats, W) and spontaneously hypertensive rats (SHR). Isolated hearts were submitted to 110 min of perfusion or 20 min stabilization, 30 min global ischemia, and 60 min reperfusion (R). Other hearts were treated with PCE at the onset of R. Infarct size, the reduced glutathione (GSH), and the expression of phospho-Akt, P-GSK-3β, and P-eNOS were assessed. In isolated mitochondria, the Ca(2+)-mediated response of mitochondrial permeability transition pore (mPTP), membrane potential (Δψm), and superoxide production were determined. PCE decreased infarct size, partly preserved GSH, increased the P-Akt, P-GSK-3β, and P-eNOS contents, improved mPTP response to Ca(2+), decreased the superoxide production, and restored Δψm. These data show that PCE decreases the cardiac postischemic damage in W rats and SHR and suggest that Akt/GSK-3β/eNOS dependent pathways are involved.

  12. A high-potassium diet reduces infarct size and improves vascular structure in hypertensive rats.

    PubMed

    Dorrance, Anne M; Pollock, David M; Romanko, Olga P; Stepp, David W

    2007-01-01

    High-potassium diets can improve vascular function, yet the effects of potassium supplementation on ischemic stroke have not been studied. We hypothesized that dietary potassium supplementation would reduce ischemic cerebral infarct size by reversing cerebral artery hypertrophy. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed diets containing 0.79% potassium (LK) or 2.11% potassium (HK) for 6 wk; Wistar-Kyoto (WKY) rats were fed the LK diet. The HK diet did not reduce blood pressure, as measured by telemetry, in the SHRSP. Cerebral ischemia was induced by middle cerebral artery (MCA) occlusion. The resultant infarct was smaller in the HK-SHRSP than in the LK-SHRSP: 55.1 +/- 6.3 vs. 71.4 +/- 2.4% of the hemisphere infarcted (P < 0.05). Infarcts were smaller in WKY rats (33.5 +/- 4.8%) than in LK-SHRSP or HK-SHRSP. The vessel wall of MCAs from LK-SHRSP was hypertrophied compared with WKY rats; this was reversed in HK-SHRSP. RT-PCR analysis of the cerebral vessels showed that expression of platelet-derived growth factor receptors-alpha and -beta, epidermal growth factor receptor, and collagen I and III was increased in the vessels from LK-SHRSP compared with WKY rats and reduced in HK-SHRSP. These results suggest that potassium supplementation provides neuroprotection in a model of ischemic stroke independent of blood pressure and possibly through changes in vascular structure.

  13. Heart Failure Predictors in a Group of Patients with Myocardial Infarction

    PubMed Central

    Myftiu, Sokol; Bara, Petrit; Sharka, Ilir; Shkoza, Artan; Belshi, Xhina; Rruci, Edlira; Vyshka, Gentian

    2016-01-01

    AIM: The present study considers of the prevalence of heart failure (HF) in patients suffering from acute myocardial infarction (AMI) in the University Hospital Centre of Tirana (UHCT) “Mother Theresa”; the demographic and clinical characteristics of the sample during hospitalization; and the main predictors of heart failure occurrence inside the group of patients suffering an AMI. MATERIAL AND METHODS: During a period of study from 2013-2015 we studied demographic and clinical data from 587 consecutive patients presenting with AMI; Framingham criteria were adopted for classifying patients with HF upon admission. RESULTS: A Killip class ≥ 2 was the main diagnostic criterion of HF during hospitalisation. HF was identified in 156 patients (26.6%). The subgroup with HF had significant differences when compared with the other patients with regard to age, sex (male), heart rate upon admission, systolic blood pressure on admission, previous episodes of AMI, glycemia on admission, previous antihypertensive treatment, previous revascularization procedures, peripheral vascular disease, chronic renal disease, ejection fraction (EF), anemia, and atrial fibrillation presence. Independent predictors for HF occurrence in the logistic regression model were EF, previous revascularization, peripheral vascular disease, age, sex, previous AMI, systolic blood pressure upon admission, and anaemia. CONCLUSION: As a conclusion, HF seems to be a common occurrence after AMI, in spite of changes in the epidemiological profile of the acute coronary syndrome. An increase in the incidence is registered as well, parallel to a decrease in the mortality following AMI. Attention must be shown for highly risked subpopulations, aged persons, patients with the previous coronary disease, and concomitant conditions. PMID:27703569

  14. Heart healthy diet and risk of myocardial infarction and venous thromboembolism. The Tromsø Study.

    PubMed

    Hansen-Krone, Ida J; Enga, Kristin F; Njølstad, Inger; Hansen, John-Bjarne; Braekkan, Sigrid K

    2012-09-01

    Prudent dietary patterns are associated with reduced risk of arterial cardiovascular diseases (CVD). Limited data exist on the relation between diet and venous thromboembolism (VTE). The aim of our prospective, population based study was to investigate the association of a heart healthy diet on risk of myocardial infarction (MI) and VTE. Information on dietary habits was available in 18,062 subjects, aged 25-69, who participated in the fourth Tromsø study, 1994-1995. Dietary patterns were assessed by a slightly modified version of the validated SmartDiet score; a 13-item questionnaire producing a diet score based on the intakes of fat, fibre, fruit and vegetables. Incident events of MI (n=518) and VTE (n=172) were recorded to the end of follow-up December 31, 2005 (median follow-up 10.8 years). Cox-regression models were used to calculate hazard ratios (HR). A healthy diet score of >27 points (upper tertile) was associated with 17% reduced risk of MI (HR: 0.83, 95% confidence interval [CI]: 0.66-1.06), and no association with VTE (HR: 1.01; 95%CI: 0.66-1.56), compared to <24 points (lower tertile) in multivariable analysis. High intake of fish, fruit, vegetables and polyunsatured fat had a 23% reduced risk of MI (HR 0.77; 95%CI: 0.60-0.98), but no association with VTE (HR 0.95; 95%CI: 0.64-1.40). A heart healthy diet showed an even more favourable association with MI in obese subjects (HR: 0.62; 95%CI: 0.41-0.95), but not with VTE. Our findings suggest that a heart healthy dietary pattern is associated with moderately reduced risk of MI, but not related to risk of VTE.

  15. Myocardial Infarction Area Quantification using High-Resolution SPECT Images in Rats

    PubMed Central

    de Oliveira, Luciano Fonseca Lemos; Mejia, Jorge; de Carvalho, Eduardo Elias Vieira; Lataro, Renata Maria; Frassetto, Sarita Nasbine; Fazan, Rubens; Salgado, Hélio Cesar; Galvis-Alonso, Orfa Yineth; Simões, Marcus Vinícius

    2013-01-01

    Background Imaging techniques enable in vivo sequential assessment of the morphology and function of animal organs in experimental models. We developed a device for high-resolution single photon emission computed tomography (SPECT) imaging based on an adapted pinhole collimator. Objective To determine the accuracy of this system for quantification of myocardial infarct area in rats. Methods Thirteen male Wistar rats (250 g) underwent experimental myocardial infarction by occlusion of the left coronary artery. After 4 weeks, SPECT images were acquired 1.5 hours after intravenous injection of 555 MBq of 99mTc-Sestamibi. The tomographic reconstruction was performed by using specially developed software based on the Maximum Likelihood algorithm. The analysis of the data included the correlation between the area of perfusion defects detected by scintigraphy and extent of myocardial fibrosis assessed by histology. Results The images showed a high target organ/background ratio with adequate visualization of the left ventricular walls and cavity. All animals presenting infarction areas were correctly identified by the perfusion images. There was no difference of the infarct area as measured by SPECT (21.1 ± 21.2%) and by histology (21.7 ± 22.0%; p=0.45). There was a strong correlation between individual values of the area of infarction measured by these two methods. Conclusion The developed system presented adequate spatial resolution and high accuracy for the detection and quantification of myocardial infarction areas, consisting in a low cost and versatile option for high-resolution SPECT imaging of small rodents. PMID:23917507

  16. Human recombinant relaxin reduces heart injury and improves ventricular performance in a swine model of acute myocardial infarction.

    PubMed

    Perna, Avio-Maria; Masini, Emanuela; Nistri, Silvia; Bani Sacchi, Tatiana; Bigazzi, Mario; Bani, Daniele

    2005-05-01

    This study shows that relaxin can be effective in the treatment of acute myocardial infarction. In a swine model of heart ischemia-reperfusion currently used to test cardiotropic drugs because of its similarities with human myocardial infarction, human recombinant relaxin (2.5 and 5 microg/kg body weight), given at reperfusion after a 30-min ischemia, markedly reduced the main serum markers of myocardial damage (myoglobin, CK-MB, and troponin T) and the metabolic and histopathologic parameters of myocardial inflammation and cardiomyocyte injury, resulting in overall improvement of ventricular performance (increased cardiac index) compared to the controls. These results provide a background for future clinical trials with human relaxin as adjunctive therapy to catheter-based coronary angioplasty in patients with acute myocardial infarction.

  17. Heart fatty acid binding protein and myoglobin after reperfusion of acute myocardial infarction.

    PubMed

    Ozdemir, Murat; Durakoğlugil, Emre; Gülbahar, Ozlem; Turkoglu, Sedat; Sancak, Banu; Paşaoğlu, Hatice; Cengel, Atiye

    2007-10-01

    The aim of this study was to disclose the release kinetics of heart fatty acid binding protein (HFABP) and myoglobin in acute myocardial infarction (AMI) reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influence of the quality of coronary flow post PPCI on the release properties of these markers. Twenty-four patients with AMI who underwent successful PPCI and had no evidence of reocclusion within the first 120 minutes were studied. Serum myoglobin and HFABP levels at baseline and at 15, 30, 45, 60, 90 and 120 minutes after reperfusion were measured. Corrected TIMI frame count (CTFC) in the relevant vessel post PPCI was used to categorize patients in group I (CTFC > 21) and group 2 (CTFC < or = 21). Biomarker ratios at each sampling point were calculated by dividing the serum level of the biomarker at the specific sampling time by its baseline level. Baseline myoglobin and HFABP levels rose significantly at 15 minutes (153 +/- 251.5 microg/L vs. 904.3 +/- 542.6 microg/L, 10.9 +/- 8 microg/L vs. 17.8 +/- 9.1 microg/L, both P < 0.0001) after successful PPCI. Group 2 patients tended to have higher biomarker ratios at each time point as compared to group I. Successful PPCI for AMI results in a significant increase of both HFABP and myoglobin levels within 15 minutes of vessel opening and the quality of flow in the infarction-related artery post PCI as evaluated by CTFC does not influence the release kinetics of these biomarkers.

  18. Heart attack

    MedlinePlus

    ... infarction; Non-ST - elevation myocardial infarction; NSTEMI; CAD - heart attack; Coronary artery disease - heart attack ... made up of cholesterol and other cells. A heart attack may occur when: A tear in the ...

  19. Mechanisms for altered carnitine content in hypertrophied rat hearts

    SciTech Connect

    Reibel, D.K.; O'Rourke, B.; Foster, K.A.

    1987-03-01

    Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-(/sup 14/C)carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by approx.20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels.

  20. Near-infrared diffuse reflectance imaging of infarct core and peri-infarct depolarization in a rat middle cerebral artery occlusion model

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Nishidate, Izumi; Nawashiro, Hiroshi; Sato, Shunichi

    2014-03-01

    To understand the pathophysiology of ischemic stroke, in vivo imaging of the brain tissue viability and related spreading depolarization is crucial. In the infarct core, impairment of energy metabolism causes anoxic depolarization (AD), which considerably increases energy consumption, accelerating irreversible neuronal damage. In the peri-infarct penumbra region, where tissue is still reversible despite limited blood flow, peri-infarct depolarization (PID) occurs, exacerbating energy deficit and hence expanding the infarct area. We previously showed that light-scattering signal, which is sensitive to cellular/subcellular structural integrity, was correlated with AD and brain tissue viability in a rat hypoxia-reoxygenation model. In the present study, we performed transcranial NIR diffuse reflectance imaging of the rat brain during middle cerebral artery (MCA) occlusion and examined whether the infarct core and PIDs can be detected. Immediately after occluding the left MCA, light scattering started to increase focally in the occlusion site and a bright region was generated near the occlusion site and spread over the left entire cortex, which was followed by a dark region, showing the occurrence of PID. The PID was generated repetitively and the number of times of occurrence in a rat ranged from four to ten within 1 hour after occlusion (n=4). The scattering increase in the occlusion site was irreversible and the area with increased scattering expanded with increasing the number of PIDs, indicating an expansion of the infarct core. These results suggest the usefulness of NIR diffuse reflectance signal to visualize spatiotemporal changes in the infarct area and PIDs.

  1. Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration.

    PubMed

    Daskalopoulos, Evangelos P; Vilaeti, Agapi D; Barka, Eleonora; Mantzouratou, Polixeni; Kouroupis, Dimitrios; Kontonika, Marianthi; Tourmousoglou, Christos; Papalois, Apostolos; Pantos, Constantinos; Blankesteijn, W Matthijs; Agathopoulos, Simeon; Kolettis, Theofilos M

    2015-01-01

    Prevention of left ventricular remodeling is an important therapeutic target post-myocardial infarction. Experimentally, treatment with growth hormone (GH) is beneficial, but sustained local administration has not been thoroughly investigated. We studied 58 rats (322 ± 4 g). GH was administered via a biomaterial-scaffold, following in vitro and in vivo evaluation of degradation and drug-release curves. Treatment consisted of intra-myocardial injection of saline or alginate-hydrogel, with or without GH, 10 min after permanent coronary artery ligation. Echocardiographic and histologic remodeling-indices were examined 3 weeks post-ligation, followed by immunohistochemical evaluation of angiogenesis, collagen, macrophages and myofibroblasts. GH-release completed at 3 days and alginate-degradation at ∼7 days. Alginate + GH consistently improved left ventricular end-diastolic and end-systolic diameters, ventricular sphericity, wall tension index and infarct-thickness. Microvascular-density and myofibroblast-count in the infarct and peri-infarct areas were higher after alginate + GH. Macrophage-count and collagen-content did not differ between groups. Early, sustained GH-administration enhances angiogenesis and myofibroblast-activation and ameliorates post-infarction remodeling.

  2. Impact of conditioning hyperglycemic on myocardial infarction rats: Cardiac cell survival factors.

    PubMed

    Malfitano, Christiane; de Souza Junior, Alcione Lescano; Irigoyen, Maria Cláudia

    2014-06-26

    While clinical data have suggested that the diabetic heart is more susceptible to ischemic heart disease (IHD), animal data have so far pointed to a lower probability of IHD. Thus, the aim of this present review is to look at these conflicting results and discuss the protective mechanisms that conditioned hyperglycemia may confer to the heart against ischemic injury. Several mechanisms have been proposed to explain the cardioprotective action of high glucose exposure, namely, up-regulation of anti-apoptotic factor Bcl-2, inactivation of pro-apoptotic factor bad, and activation of pro-survival factors such as protein kinase B (Akt), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α and protein kinase C-ε. Indeed, cytosolic increase in Ca(2+) concentration, the mitochondrial permeability transition pore, plays a key role in the genesis of ischemic injury. Previous studies have shown that the diabetic heart decreased Na(+)/Ca(2+) and Na(+)/H(+) exchanger activity and as such it accumulates less Ca(2+) in cardiomyocyte, thus preventing cardiac injury and the associated heart dysfunctions. In addition, the expression of VEGF in diabetic animals leads to increased capillary density before myocardial infarction. Despite poor prognostic in the long-term, all these results suggest that diabetes mellitus and consequently hyperglycemia may indeed play a cardioprotective role against myocardial infarction in the short term.

  3. Sca-1+ stem cell survival and engraftment in the infarcted heart: dual role for preconditioning induced connexin-43

    PubMed Central

    Lu, Gang; Haider, Husnain Kh; Jiang, Shujia; Ashraf, Muhammad

    2009-01-01

    Background We report that elevated connexin-43 (Cx-43) in stem cells preconditioned with insulin like growth factor-1 (IGF-1) is cytoprotective and reprograms the cells for cardiomyogenic differentiation. Methods and Results Sca-1+ cells were preconditioned with 100nM IGF-1 for 30-minutes followed by 8-hours (h) of oxygen glucose deprivation (OGD) to assess the cytoprotective effects of preconditioning. LDH release assay, cytochrome-c release and mitochondrial membrane potential assay showed improved survival of preconditioned Sca-1+ cells (PCSca-1+) under OGD as compared to non-preconditioned Sca-1+ cells (non-PCSca-1+) via PI3K/Akt dependent caspase-3 downregulation. We observed PI3K/Akt dependent upregulation of cardiac specific markers including MEF-2c (2.5-fold), GATA4 (3.1-fold) and Cx-43 (3.5-fold). Cx-43 inhibition with specific RNAi reduced the cell survival under OGD and post-transplantation. In vivo studies were performed in a female rat model of acute myocardial infarction (n=78). Animals were grouped to receive intramyocardially 70μl DMEM without cells (group-1), or containing male 1×106 non-PCSca-1+ (group-2) or PCSca-1+ (group-3) cells labeled with PKH26. Survival of the PCSca-1+ was 5.5-fold higher in group-3 compared to group-2 on 7-days post-transplantation. Confocal imaging after actinin and Cx-43 specific immunostaining showed extensive engraftment and myogenic differentiation of PCSca-1+. As compared to group-2, group-3 showed increased blood vessel density (22.3±1.7/microscopic field, p<0.0001) and attenuated infarction size (23.3±3.6%; p=0.002). Heart function indices including ejection fraction (56.2±3.5; p=0.029) and fractional shortening (24.3±2.1; p=0.03) were improved in group-3 compared to group-2. Conclusions Preconditioning with IGF-1 reprograms Sca-1+ for pro-survival signaling and cardiomyogenic differentiation with an important role for Cx-43 in this process. PMID:19414636

  4. Neuroprotective effect of combined ultrasound and microbubbles in a rat model of middle cerebral artery infarction

    NASA Astrophysics Data System (ADS)

    Fatar, M.; Griebe, M.; Stroick, M.; Kern, R.; Hennerici, M.; Meairs, S.

    2005-03-01

    Ultrasound-mediated microbubble thrombolysis (UMT) was performed in a middle cerebral artery occlusion model in rats to evaluate possible effects upon brain infarct volume, apoptosis, IL-6 and TNF-alpha levels, and disruption of the blood-brain barrier (BBB). The results show that infarct volume was significantly reduced (p<0.04) in the microbubble + ultrasound (MB + US) group as compared to control animals. The levels of IL-6 and TNF-alpha concentrations, as markers of tissue damage, were not significantly different. In trypan blue treated animals, no additional BBB disruption was observed for the UMT group. Likewise, there was no increase in apoptotic cell death outside the infarction area in animals treated with MB + US. The results demonstrate that UMT does not have a harmful effect upon ischemic stroke in a middle cerebral artery occlusion model of the rat. The significant reduction in brain infarction following insonation with ultrasound and microbubbles suggests a novel neuroprotective effect in ischemic stroke.

  5. Reduction of cerebral infarction in rats by biliverdin associated with amelioration of oxidative stress.

    PubMed

    Deguchi, Kentaro; Hayashi, Takeshi; Nagotani, Shoko; Sehara, Yoshihide; Zhang, Hanzhe; Tsuchiya, Atsushi; Ohta, Yasuyuki; Tomiyama, Koji; Morimoto, Nobutoshi; Miyazaki, Masahiro; Huh, Nam-Ho; Nakao, Atsunori; Kamiya, Tatsushi; Abe, Koji

    2008-01-10

    Biliverdin (BV), one of the byproducts of heme catalysis through heme oxygenase (HO) system, is a scavenger of reactive oxygen species (ROS). We hypothesized that BV treatment could protect rat brain cells from oxidative injuries via its anti-oxidant efficacies. Cerebral infarction was induced by transient middle cerebral artery occlusion (tMCAO) for 90 min, followed by reperfusion. BV or vehicle was administered intraperitoneally immediately after reperfusion. The size of the cerebral infarction 2 days after tMCAO was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) stain. Superoxide generation 4 h after tMCAO was determined by detection of oxidized hydroethidine. In addition, the oxidative impairment of neurons were immunohistochemically assessed by stain for lipid peroxidation with 4-hydroxy-2-nonenal (4-HNE) and damaged DNA with 8-hydroxy-2'-deoxyguanosine (8-OHdG). BV treatment significantly reduced infarct volume of the cerebral cortices associated with less superoxide production and decreased oxidative injuries of brain cells. The present study demonstrated that treatment with BV ameliorated the oxidative injuries on neurons and decreased brain infarct size in rat tMCAO model.

  6. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

    PubMed

    Pfeffer, Marc A; McMurray, John J V; Velazquez, Eric J; Rouleau, Jean-Lucien; Køber, Lars; Maggioni, Aldo P; Solomon, Scott D; Swedberg, Karl; Van de Werf, Frans; White, Harvey; Leimberger, Jeffrey D; Henis, Marc; Edwards, Susan; Zelenkofske, Steven; Sellers, Mary Ann; Califf, Robert M

    2003-11-13

    Angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival. Copyright 2003

  7. Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

    PubMed Central

    Khandelwal, Vinoth Kumar Megraj; Balaraman, R.; Pancza, Dezider; Ravingerová, Táňa

    2011-01-01

    Hemidesmus indicus (L.) R. Br. (HI) and Hibiscus rosa-sinensis L. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions. PMID:20953394

  8. Blood Pressure and Heart Rate Measures Associated With Increased Risk of Covert Brain Infarction and Worsening Leukoaraiosis in Older Adults.

    PubMed

    Leung, Lester Y; Bartz, Traci M; Rice, Kenneth; Floyd, James; Psaty, Bruce; Gutierrez, Jose; Longstreth, W T; Mukamal, Kenneth J

    2017-08-01

    In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings. In the CHS (Cardiovascular Health Study), a longitudinal cohort study of older adults, we used relative risk regression to assess the associations of mean, variability, and trend in systolic BP, diastolic BP, and heart rate measured at 4 annual clinic visits between 2 brain MRIs with incident covert brain infarction and worsening white matter grade (using a 10-point scale to characterize leukoaraiosis). We included participants who had both brain MRIs, no stroke before the follow-up MRI, and no change in antihypertensive medication status during follow-up. Among 878 eligible participants, incident covert brain infarction occurred in 15% and worsening white matter grade in 27%. Mean systolic BP was associated with increased risk for incident covert brain infarction (relative risk per 10 mm Hg, 1.28; 95% confidence interval, 1.12-1.47), and mean diastolic BP was associated with increased risk for worsening white matter grade (relative risk per 10 mm Hg, 1.45; 95% confidence interval, 1.24-1.69). These findings persisted in secondary and sensitivity analyses. Elevated mean systolic BP is associated with increased risk for covert brain infarction, and elevated mean diastolic BP is associated with increased risk for worsening leukoaraiosis. These findings reinforce the importance of hypertension in the development of silent cerebrovascular diseases, but the pathophysiologic relationships to BP for each may differ. © 2017 American Heart Association, Inc.

  9. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure.

    PubMed

    Wang, Han-Jun; Wang, Wei; Cornish, Kurtis G; Rozanski, George J; Zucker, Irving H

    2014-10-01

    The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympathoexcitation in chronic heart failure (CHF). Increased sympathoexcitation is positively related to mortality in patients with CHF. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here, we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. To delete the transient receptor potential vanilloid 1 receptor-expressing CSAR afferents selectively, epicardial application of resiniferatoxin (50 μg/mL), an ultrapotent analog of capsaicin, was performed during myocardium infarction surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of resiniferatoxin largely prevented the elevated left ventricle end-diastolic pressure, lung edema, and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart, and increased cardiac contractile reserve in response to β-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that resiniferatoxin attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and transforming growth factor-β receptor I in CHF rats. Pressure-volume loop analysis showed that resiniferatoxin reduced the end-diastolic pressure volume relationships in CHF rats, indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF. © 2014 American Heart Association, Inc.

  10. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid

    PubMed Central

    Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao

    2016-01-01

    This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128

  11. Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction

    PubMed Central

    YU, JUN-MIN; ZHANG, XIAO-BO; JIANG, WEN; WANG, HUI-DONG; ZHANG, YI-NA

    2015-01-01

    The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by l