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Sample records for infarcted rat heart

  1. The isolated working heart model in infarcted rat hearts.

    PubMed

    Itter, G; Jung, W; Schoelkens, B A; Linz, W

    2005-04-01

    Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties.CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall. We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8-12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd). The

  2. Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

    PubMed Central

    Polegato, Bertha F.; Minicucci, Marcos F.; Azevedo, Paula S.; Gonçalves, Andréa F.; Lima, Aline F.; Martinez, Paula F.; Okoshi, Marina P.; Okoshi, Katashi; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Background Heart failure prediction after acute myocardial infarction may have important clinical implications. Objective To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. Methods The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. Results Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. Conclusion In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset. PMID:26815462

  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. Metabolic imaging of acute and chronic infarction in the perfused rat heart using hyperpolarised [1-13C]pyruvate.

    PubMed

    Ball, Daniel R; Cruickshank, Rachel; Carr, Carolyn A; Stuckey, Daniel J; Lee, Philip; Clarke, Kieran; Tyler, Damian J

    2013-11-01

    Hyperpolarised (13)C MRI can be used to generate metabolic images of the heart in vivo. However, there have been no similar studies performed in the isolated perfused heart. Therefore, the aim of this study was to develop a method for the creation of (13)C metabolite maps of the perfused rat heart and to demonstrate the technique in a study of acute and chronic myocardial infarction. Male Wistar rat hearts were isolated, perfused and imaged before and after occlusion of the left anterior descending (LAD) coronary artery, creating an acute infarct group. In addition, a chronic infarct group was generated from hearts which had their LAD coronary artery occluded in vivo. Four weeks later, hearts were excised, perfused and imaged to generate metabolic maps of infused pyruvate and its metabolites lactate and bicarbonate. Myocardial perfusion and energetics were assessed by first-pass perfusion imaging and (31)P MRS, respectively. In both acute and chronically infarcted hearts, perfusion was reduced to the infarct region, as revealed by reduced gadolinium influx and lower signal intensity in the hyperpolarised pyruvate images. In the acute infarct region, there were significant alterations in the lactate (increased) and bicarbonate (decreased) signal ratios. In the chronically infarcted region, there was a significant reduction in both bicarbonate and lactate signals. (31)P-derived energetics revealed a significant decrease between control and chronic infarcted hearts. Significant decreases in contractile function between control and both acute and chronic infracted hearts were also seen. In conclusion, we have demonstrated that hyperpolarised pyruvate can detect reduced perfusion in the rat heart following both acute and chronic infarction. Changes in lactate and bicarbonate ratios indicate increased anaerobic metabolism in the acute infarct, which is not observed in the chronic infarct. Thus, this study has successfully demonstrated a novel imaging approach to assess

  5. Preconditioning ischemia time determines the degree of glycogen depletion and infarct size reduction in rat hearts.

    PubMed

    Barbosa, V; Sievers, R E; Zaugg, C E; Wolfe, C L

    1996-02-01

    The cardioprotective effect of preconditioning is associated with glycogen depletion and attenuation of intracellular acidosis during subsequent prolonged ischemia. This study determined the effects of increasing preconditioning ischemia time on myocardial glycogen depletion and on infarct size reduction. In addition, this study determined whether infarct size reduction by preconditioning correlates with glycogen depletion before prolonged ischemia. Anesthetized rats underwent a single episode of preconditioning lasting 1.25, 2.5, 5, or 10 minutes or multiple episodes cumulating in 10 (2 x 5 min) or 20 minutes (4 x 5 or 2 x 10 min) of preconditioning ischemia time, each followed by 5 minutes of reperfusion. Then both preconditioned and control rats underwent 45 minutes of ischemia induced by left coronary artery (LCA) occlusion and 120 minutes of reperfusion. After prolonged ischemia, infarct size was determined by dual staining with triphenyltetrazolium chloride and phthalocyanine blue dye. Glycogen levels were determined by an enzymatic assay in selected rats from each group before prolonged ischemia. We found that increasing preconditioning ischemia time resulted in glycogen depletion and infarct size reduction that could both be described by exponential functions. Furthermore, infarct size reduction correlated with glycogen depletion before prolonged ischemia (r = 0.98; p < 0.01). These findings suggest a role for glycogen depletion in reducing ischemic injury in the preconditioned heart. PMID:8579012

  6. MODIFICATION OF OXIDATIVE STRESS ON GENE EXPRESSION PROFILING IN THE RAT INFARCTED HEART

    PubMed Central

    Zhao, Wenyuan; Zhao, Tieqiang; Chen, Yuanjian; Qu, Yanhua; Gerling, Ivan C; Sun, Yao

    2013-01-01

    Cardiac oxidative stress is developed following myocardial infarction (MI) particularly in the first week of MI. The influence of reactive oxygen species (ROS) on gene expression profiling and molecular pathways in the infarcted myocardium remains uncertain and is explored in the present study. Rats with MI were treated with or without antioxidants for one week. Normal rats served as controls. Cardiac oxidative stress and gene profiling were investigated. Compared to normal hearts, malondialdehyde (MDA), a marker of oxidative stress, was significantly increased in the infarcted myocardium, which was significantly suppressed by antioxidants. Microarray assay showed that over a thousand genes were differentially expressed in the infarcted myocardium. Antioxidants significantly altered the expression of 159 genes compared to untreated MI rats. Ingenuity pathway analysis (IPA) indicated that multiple pathway networks were affected by antioxidants, including those related to cell movement, growth/development, death, and inflammatory/fibrotic responses. IPA further identified that these changes were primarily related to NFκB, p38 MAPK, and ERκ1/2 pathways. Hub genes were identified in the associated gene networks. This study reveals the gene networks associated with cardiac oxidative stress postMI. These observations indicate that ROS regulate various molecular and cellular actions related to cardiac repair/remodeling through multiple gene networks. PMID:23716180

  7. Modification of oxidative stress on gene expression profiling in the rat infarcted heart.

    PubMed

    Zhao, Wenyuan; Zhao, Tieqiang; Chen, Yuanjian; Qu, Yanhua; Gerling, Ivan C; Sun, Yao

    2013-07-01

    Cardiac oxidative stress is developed following myocardial infarction (MI) particularly in the first week of MI. The influence of reactive oxygen species (ROS) on gene expression profiling and molecular pathways in the infarcted myocardium remains uncertain and is explored in the present study. Rats with MI were treated with or without antioxidants for 1 week. Normal rats served as controls. Cardiac oxidative stress and gene profiling were investigated. Compared to normal hearts, malondialdehyde, a marker of oxidative stress, was significantly increased in the infarcted myocardium, which was significantly suppressed by antioxidants. Microarray assay showed that over a thousand genes were differentially expressed in the infarcted myocardium. Antioxidants significantly altered the expression of 159 genes compared to untreated MI rats. Ingenuity pathway analysis indicated that multiple pathway networks were affected by antioxidants, including those related to cell movement, growth/development, death, and inflammatory/fibrotic responses. IPA further identified that these changes were primarily related to NFκB, p38 MAPK, and ERκ1/2 pathways. Hub genes were identified in the associated gene networks. This study reveals the gene networks associated with cardiac oxidative stress postMI. These observations indicate that ROS regulate various molecular and cellular actions related to cardiac repair/remodeling through multiple gene networks. PMID:23716180

  8. Streptomycin inhibits electrophysiological changes induced by stretching of chronically infarcted rat hearts*

    PubMed Central

    Cao, Jun-xian; Fu, Lu; Gao, Qian-ping; Xie, Rong-sheng; Qu, Fan

    2014-01-01

    Objective: To investigate stretch-induced electrophysiological changes in chronically infarcted hearts and the effect of streptomycin (SM) on these changes in vivo. Methods: Sixty Wistar rats were divided randomly into four groups: a control group (n=15), an SM group (n=15), a myocardial infarction (MI) group (n=15), and an MI+SM group (n=15). Chronic MI was obtained by ligating the left anterior descending branch (LAD) of rat hearts for eight weeks. The in vivo blockade of stretch-activated ion channels (SACs) was achieved by intramuscular injection of SM (180 mg/(kg∙d)) for seven days after operation. The hearts were stretched for 5 s by occlusion of the aortic arch. Suction electrodes were placed on the anterior wall of left ventricle to record the monophasic action potential (MAP). The effect of stretching was examined by assessing the 90% monophasic action potential duration (MAPD90), premature ventricular beats (PVBs), and ventricular tachycardia (VT). Results: The MAPD90 decreased during stretching in both the control (from (50.27±5.61) ms to (46.27±4.51) ms, P<0.05) and MI groups (from (65.47±6.38) ms to (57.47±5.76 ms), P<0.01). SM inhibited the decrease in MAPD90 during inflation ((46.27±4.51) ms vs. (49.53±3.52) ms, P<0.05 in normal hearts; (57.47±5.76) ms vs. (61.87±5.33) ms, P<0.05 in MI hearts). The occurrence of PVBs and VT in the MI group increased compared with that in the control group (PVB: 7.93±1.66 vs. 1.80±0.86, P<0.01; VT: 7 vs. 1, P<0.05). SM decreased the occurrence of PVBs in both normal and MI hearts (0.93±0.59 vs. 1.80±0.86 in normal hearts, P<0.05; 5.40±1.18 vs. 7.93±1.66 in MI hearts, P<0.01). Conclusions: Stretch-induced MAPD90 changes and arrhythmias were observed in chronically infarcted myocardium. The use of SM in vivo decreased the incidence of PVBs but not of VT. This suggests that SACs may be involved in mechanoelectric feedback (MEF), but that there might be other mechanisms involved in causing VT in chronic MI

  9. Long-term evaluation of myoblast seeded patches implanted on infarcted rat hearts.

    PubMed

    Giraud, Marie-Noëlle; Flueckiger, Remy; Cook, Stéphane; Ayuni, Erick; Siepe, Matthias; Carrel, Thierry; Tevaearai, Hendrik

    2010-06-01

    Cell transplantation presents great potential for treatment of patients with severe heart failure. However, its clinical application was revealed to be more challenging than initially expected in experimental studies. Further investigations need to be undertaken to define the optimal treatment conditions. We previously reported on the epicardial implantation of a bio-engineered construct of skeletal myoblast-seeded polyurethane and its preventive effect on progression toward heart failure. In the present study, we present a long-term evaluation of this functional outcome. Left anterior descending coronary ligation was performed in female Lewis rats. Two weeks later, animals were treated with either epicardial implantation of biograft, acellular scaffold, sham operation, or direct intramyocardial skeletal myoblast injection. Functional assessments were performed with serial echocardiographies every 3 months and end point left ventricle pressure was assessed. Hearts were then harvested for histological examinations. Myocardial infarction induced a slow and progressive reduction in fractional shortening after 3 months. Progression toward heart failure was significantly prevented for up to 6 months after injection of myoblasts and for up to 9 months following biograft implantation. Nevertheless, this effect vanished after 12 months, with immunohistological examinations revealing an absence of the transplanted myoblasts within the scaffold. We demonstrated that tissue therapy is superior to cell therapy for stabilization of heart function. However, beneficial effects are transient. PMID:20482708

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. Adenylyl cyclase regulation in heart failure due to myocardial infarction in rats.

    PubMed

    Bräunig, Jörg H; Albrecht-Küpper, Barbara; Seifert, Roland

    2014-04-01

    Cardiac adenylyl cyclase (AC) activity was described to be differentially regulated in left and right ventricles (LVs and RVs) of rats with heart failure (HF) due to LV myocardial infarction (MI) (Sethi et al. Am J Physiol 272:H884-H893, 1997). AC activities in LVs and RVs were increased and decreased respectively in rats 8 and 16 weeks post MI under basal and stimulatory conditions including AC activation via β-adrenergic receptors (β-ARs), stimulatory G protein (Gs), and direct AC activation with forskolin (FS). The current study aimed to detect alterations in rat heart AC activities in a comparable model of HF 9 weeks post LV MI. Therefore, cardiac AC activities were measured under basal and β-AR-, Gs-, or FS-stimulated conditions as well as under inhibition with various MANT [2'(3')-O-(N-methylanthraniloyl)]-nucleotide AC inhibitors and the P-site AC inhibitors NKY80 [2-amino-7-(2-furanyl)-7,8-dihydro-5(6H)-quinazolinone] and vidarabine (9-β-D-arabinosyladenine, AraAde). Basal and stimulated AC activities along with AC inhibition experiments did not reveal evidence for changes in AC activity in LVs and RVs from MI group animals despite the presence of congestive HF. However, our study is indeterminate. Further studies are required to identify the factors responsible for previously described changes in cardiac AC activity in MI induced HF and to elucidate the role of altered AC regulation in the pathophysiology of HF. In order to detect small changes in AC regulation, larger group sizes than the ones used in our present study are required. PMID:24276219

  13. Cardiac effects of the extract and active components of radix stephaniae tetrandrae. II. Myocardial infarct, arrhythmias, coronary arterial flow and heart rate in the isolated perfused rat heart.

    PubMed

    Yu, X C; Wu, S; Wang, G Y; Shan, J; Wong, T M; Chen, C F; Pang, K T

    2001-05-11

    The primary purpose of the present study was to compare the cardioprotective effects of the extract from radix stephaniae tetrandrae (RST) and its individual compounds, tetrandrine (Tet) and fanchinoline (Fan). Secondly, we also compared the cardiac effects of the individual compounds and the RST extract with those of verapamil, a classical Ca2+ channel blocker. The Langendorff isolated perfused rat heart preparation was used. Regional ischaemia and reperfusion was employed to induce myocardial infarct and arrhythmia. Infarct, arrhythmia, heart rate and coronary artery flow were determined in hearts treated with vehicle, RST extract, Tet, Fan, or verapamil. It was found that RST extract, of which only 9% was Tet, and Tet alone produced equally potent ameliorating effects on arrhythmia and infarct induced by ischaemia and reperfusion without further inhibiting ischaemia-reduced heart rate and coronary artery flow. Fan had no effects on arrhythmia and infarct induced by ischaemia and reperfusion; but it induced S-T segment elevation and further reduced heart rate and coronary artery flow during ischaemia. Verapamil also ameliorated the effects of ischaemia and reperfusion on arrhythmia and infarct. It should be noted that 1 microM verapamil, that produced comparable effects on infarct and arrhythmia to the RST extract and Tet, further inhibited heart rate during ischaemia. The results indicate that the RST extract produces equally potent cardioprotective and anti-arrhythmic effects as Tet alone. Both RST extract and Tet may be better choices for the treatment of arrhythmia and infarct induced by myocardial ischaemia and reperfusion than the classical Ca2+ channel blocker, verapamil as they do not further reduce heart rate during ischaemia. PMID:11432452

  14. Baroreflex sensitivity and heart rate variability in conscious rats with myocardial infarction.

    PubMed

    Krüger, C; Kalenka, A; Haunstetter, A; Schweizer, M; Maier, C; Rühle, U; Ehmke, H; Kübler, W; Haass, M

    1997-11-01

    The baroreflex sensitivity (BRS) and the heart rate variability (HRV) were studied in conscious rats after myocardial infarction (MI; induced by coronary artery ligation) and after sham operation (SH). BRS was determined by linear regression of R-R interval vs. arterial pressure changes induced by nitroprusside or methoxamine (intravenous bolus). HRV was calculated from 3-min electrocardiogram recordings. Left ventricular end-diastolic pressure and plasma atrial natriuretic peptide were increased after MI; plasma norepinephrine and basal heart rate (HR) remained unchanged. At 3 and 28 days after MI, BRS was reduced as indicated by decreased reflex bradycardia (RB) (MI, 0.66 +/- 0.13 and 0.78 +/- 0.07 ms/mmHg; SH, 1.27 +/- 0.16 and 1.48 +/- 0.14 ms/mmHg, respectively; P < 0.05 MI vs. SH). At 56 days after MI, BRS was normalized. RB was unaffected by atropine 3 and 28 days after MI but reduced in all other groups. The increase of basal HR by atropine 3 and 28 days after MI was less than in all other groups. HRV (SD of mean N-N interval, coefficient of variance, low- and high-frequency power; studied at 28 and 56 days) was similar in all groups. It is concluded that BRS is transiently depressed in rats with left ventricular dysfunction after MI probably due to a reduced reflex vagal activity. Even though basal HR and HRV are unchanged after MI, a temporary attenuation of tonic vagal activity is unmasked after autonomic blockade. PMID:9374759

  15. Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen species and interstitial adenosine in infarcted rat hearts

    PubMed Central

    Lee, Tsung-Ming; Chen, Wei-Ting; Yang, Chen-Chia; Lin, Shinn-Zong; Chang, Nen-Chung

    2015-01-01

    We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in post-infarcted normoglycemic rats, focusing on adenosine and reactive oxygen species production. DPP-4 bound adenosine deaminase has been shown to catalyse extracellular adenosine to inosine. DPP-4 inhibitors increased adenosine levels by inhibiting the complex formation. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline or sitagliptin in in vivo and ex vivo studies. Post-infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine and dihydroethidium fluorescent staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with sitagliptin significantly increased interstitial adenosine levels and attenuated oxidative stress. Sympathetic hyperinnervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed a similar effect of erythro-9-(2-hydroxy-3-nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on superoxide anion production and NGF levels can be reversed by 8-cyclopentyl-1,3-dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation via adenosine A1 receptor and xanthine oxidase-dependent pathways, which converge through the attenuated formation of superoxide in the non-diabetic infarcted rats. PMID:25388908

  16. Differential microRNA Expression and Regulation in the Rat Model of Post-Infarction Heart Failure

    PubMed Central

    Liu, Xueyan; Meng, Heyu; Jiang, Chao; Yang, Sibao; Cui, Fengwen; Yang, Ping

    2016-01-01

    Background Heart failure is a complex end stage of various cardiovascular diseases with a poor prognosis, and the mechanisms for development and progression of heart failure have always been a hot point. However, the molecular mechanisms underlying the post transcriptional regulation of heart failure have not been fully elucidated. Current data suggest that microRNAs (miRNAs) are involved in the pathogenesis of heart failure and could serve as a new biomarker, but the precise regulatory mechanisms are still unclear. Methods The differential miRNA profile in a rat model of post-infarction heart failure was determined using high throughout sequencing and analyzed through bioinformatics approaches. The results were validated using qRT-PCR for 8 selected miRNAs. Then the expression patterns of 4 miRNAs were analyzed in different periods after myocardial infarction. Finally, gain- and loss-of-function experiments of rno-miR-122-5p and rno-miR-184 were analyzed in H2O2 treated H9c2 cells. Results In the heart failure sample, 78 miRNAs were significantly upregulated and 28 were downregulated compared to the controls. GO and KEGG pathway analysis further indicated the likely roles of these miRNAs in heart failure. Time-course analysis revealed different expression patterns of 4 miRNAs: rno-miR-122-5p, rno-miR-199a-5p, rno-miR-184 and rno-miR-208a-3p. Additionally, rno-miR-122-5p and rno-miR-184 were proved to promote apoptosis in vitro. Conclusions Differential profile and expression patterns of miRNAs in the rats model of post-infarction heart failure were found, and the pro-apoptotic roles of rno-miR-122-5p and rno-miR-184 were revealed. These findings may provide a novel way that may assist in heart failure diagnosis and treatment. PMID:27504893

  17. 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.

  18. Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction.

    PubMed

    de Castro, Alexandre Luz; Fernandes, Rafael Oliveira; Ortiz, Vanessa D; Campos, Cristina; Bonetto, Jéssica H P; Fernandes, Tânia R G; Conzatti, Adriana; Siqueira, Rafaela; Tavares, Angela Vicente; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

    2016-02-01

    Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction. PMID:26659365

  19. 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

    2016-02-17

    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. PMID:26661577

  20. Dietary Phenolic Acids of Macrotyloma uniflorum (Horse Gram) Protect the Rat Heart Against Isoproterenol-Induced Myocardial Infarction.

    PubMed

    Panda, Vandana; Laddha, Ankit; Nandave, Mukesh; Srinath, Sudhamani

    2016-07-01

    The present study investigates the cardioprotective activity of the Macrotyloma uniflorum seed extract (MUSE) and its phenolic acids (p-coumaric acid and ferulic acid) in isoproterenol (ISO)-induced myocardial infarction in rats. The previously mentioned phenolic acids were isolated and quantified from MUSE by HPLC. Pretreatment of gemfibrozil (reference standard), MUSE (250 and 500 mg/kg) and the phenolic acids for 30 days to rats treated with ISO (85 mg/kg) on the last 2 days resulted in a significant attenuation of the ISO-elevated levels of serum marker enzymes (aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase MB), total cholesterol, triglycerides, uric acid, C-reactive protein and malondialdehyde and a restoration of the levels of the ISO-depleted marker enzymes, reduced glutathione and the antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in heart. Restoration of the ISO-altered electrocardiogram pattern and haemodynamic parameters (left ventricular end diastolic pressure, heart rate, systolic, diastolic and mean arterial pressure) was also brought about by treatment with MUSE and the phenolic acids. It may be concluded that MUSE treatment to ISO-challenged rats exhibits a significant cardioprotective effect probably because of the potent antioxidant activity of its phenolic acids that salvage the myocardium from the deleterious effects of ISO. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27091200

  1. 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

  2. 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

  3. Protective effect of betaine on changes in the levels of lysosomal enzyme activities in heart tissue in isoprenaline-induced myocardial infarction in Wistar rats

    PubMed Central

    Anandan, Rangasamy

    2009-01-01

    Myocardial infarction is one of the most common manifestations of cardiovascular disease. In the present study, we investigated the protective effect of betaine, a potent lipotropic molecule, on changes in the levels of lysosomal enzymes and lipid peroxidation in isoprenaline-induced myocardial infarction in Wistar rats, an animal model of myocardial infarction in man. Male albino Wistar rats were pretreated with betaine (250 mg/kg body weight) daily for a period of 30 days. After the treatment period, isoprenaline (11 mg/100 g body weight) was intraperitoneally administered to rats at intervals of 24 h for 2 days. The activities of lysosomal enzymes (β-glucuronidase, β-galactosidase, β-glucosidase, and acid phosphatase) were significantly (p < 0.05) increased in plasma with a concomitant decline in the activities of these enzymes in heart tissue of isoprenaline-administered rats. Also, the level of lipid peroxidation was higher in heart lysosomes of isoprenaline-injected rats. Pretreatment with betaine daily for a period of 30 days to isoprenaline-induced rats prevented the changes in the activities of these lysosomal enzymes. Oral treatment with betaine (250 mg/kg body weight) to normal control rats did not show any significant effect in all the biochemical parameters studied. Thus, the results of our study show that betaine protects the lysosomal membrane against isoprenaline-induced myocardial infarction. The observed effects might be due to the free radical-scavenging and membrane-stabilizing properties of betaine. PMID:19294532

  4. 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. PMID:17204911

  5. Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction.

    PubMed

    Ranjbar, Kamal; Rahmani-Nia, Farhad; Shahabpour, Elham

    2016-09-01

    Arteriogenesis is a main defense mechanism to prevent heart and local tissues dysfunction in occlusive artery disease. TGF-β and angiostatin have a pivotal role in arteriogenesis. We tested the hypothesis that aerobic training and l-arginine supplementation promotes cardiac and skeletal muscles arteriogenesis after myocardial infarction (MI) parallel to upregulation of TGF-β and downregulation of angiostatin. For this purpose, 4 weeks after LAD occlusion, 50 male Wistar rats were randomly distributed into five groups: (1) sham surgery without MI (sham, n = 10), (2) control-MI (Con-MI, n = 10), (3) l-arginine-MI (La-MI, n = 10), (4) exercise training-MI (Ex-MI, n = 10), and (5) exercise and l-arginine-MI (Ex + La-MI). Exercise training groups running on a treadmill for 10 weeks with moderate intensity. Rats in the l-arginine-treated groups drank water containing 4 % l-arginine. Arteriolar density with different diameters (11-25, 26-50, 51-75, and 76-150 μm), TGF-β, and angiostatin gene expression were measured in cardiac (area at risk) and skeletal (soleus and gastrocnemius) muscles. Smaller arterioles decreased in cardiac after MI. Aerobic training and l-arginine increased the number of cardiac arterioles with 11-25 and 26-50 μm diameters parallel to TGF-β overexpression. In gastrocnemius muscle, the number of arterioles/mm(2) was only increased in the 11 to 25 μm in response to training with and without l-arginine parallel to angiostatin downregulation. Soleus arteriolar density with different size was not different between experimental groups. Results showed that 10 weeks aerobic exercise training and l-arginine supplementation promotes arteriogenesis of heart and gastrocnemius muscles parallel to overexpression of TGF-β and downregulation of angiostatin in MI rats. PMID:27121159

  6. Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways

    PubMed Central

    Wei, Peng; Yang, Xiang-Jun; Fu, Qiang; Han, Bing; Ling, Lin; Bai, Jie; Zong, Bin; Jiang, Chun-Ying

    2015-01-01

    Intermedin is a proopiomelanocortin-derived peptide before opioid promoting cortical hormone, its main function embodies in mononuclear macrophages and neutrophilic granulocytes to inhibit the proinflammatory cytokines. The aim of this study is to determine intermedin attenuates myocardial infarction and its related mechanisms in a rat model of ischemic heart failure. After rat model of ischemic heart failure was set up, myocardial infarction, blood levels of activities of creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were effectively reduced by treatment with intermedin. Tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in a rat model of ischemic heart failure were recovered by pretreatment with intermedin. Administrate of intermedin availably promoted cAMP contents and suppressed caspase-3 protein in ischemic heart failure rat. ERK1/2 and LC3 protein expression were significantly activated and autophagy was significantly promoted by intermedin in a rat model of ischemic heart failure. These results indicate that intermedin protected rat heart, attenuates myocardial infarction from ischemic heart failure in the rat model. The underlying mechanisms may include upregulation of cAMP, ERK1/2 and LC3 protein expression and activating of autophagy. PMID:26617693

  7. Preservation of the cardiac function in infarcted rat hearts by the transplantation of adipose-derived stem cells with injectable fibrin scaffolds.

    PubMed

    Zhang, Xuelian; Wang, Haibin; Ma, Xiang; Adila, Azhati; Wang, Baozhu; Liu, Fen; Chen, Bangdang; Wang, Changyong; Ma, Yitong

    2010-12-01

    Cell-based therapy can improve cardiac function but is limited by the low cell retention and survival within ischemic tissues. Injectable cardiac tissue engineering aims to support cell-based therapies and enhance their efficacy for cardiac diseases. So far, no research has been devoted to studying the usefulness of the combination of fibrin glue (as scaffold) and adipose-derived stem cells (ADSCs) to treat myocardial infarction. In our study, the rat ADSCs were isolated from subcutaneous adipose tissues. The surface phenotype of these cells was analyzed by flow cytometry. The fibrin glue was then co-injected with ADSCs into the left ventricular wall of rat infarction models. The structure and functional consequences of transplantation were determined by detailed histological analysis and echocardiography. Most cultured ADSCs expressed CD105 and CD90, and were negative for CD34 and CD45. After injection, both the 24-h cell retention and four-week graft size were significantly higher and larger in the Fibrin + ADSCs group than those of the ADSCs group alone (P < 0.01). The heart function improved significantly in the Fibrin + ADSCs group compared with that of the ADSCs group four weeks after transplantation (P < 0.01). In addition, the arteriole densities within the infarcted area improved significantly in the Fibrin + ADSCs group compared with those in the ADSCs group four weeks after transplantation (P < 0.01). In conclusion, the ADSCs with the fibrin glue has the therapeutic potential to improve the function of infarcted hearts. The method of in situ injectable tissue engineering combining fibrin glue with ADSCs is promising clinically. PMID:21127347

  8. Partially Silencing Brain Toll-Like Receptor 4 Prevents in Part Left Ventricular Remodeling with Sympathoinhibition in Rats with Myocardial Infarction-Induced Heart Failure

    PubMed Central

    Ogawa, Kiyohiro; Hirooka, Yoshitaka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

    2013-01-01

    Background Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure. Methodology/Principal Findings MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks. Conclusions Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure. PMID:23874864

  9. 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

  10. Thyroid Hormone Replacement Therapy Attenuates Atrial Remodeling and Reduces Atrial Fibrillation Inducibility in a Rat Myocardial Infarction-Heart Failure Model

    PubMed Central

    Zhang, Youhua; Dedkov, Eduard I.; Lee, Bianca; Li, Ying; Pun, Khusbu; Gerdes, A. Martin

    2014-01-01

    Introduction Heart failure (HF) is associated with increased atrial fibrillation (AF) risk. Accumulating evidence suggests the presence of myocardial tissue hypothyroidism in HF, which may contribute to HF development. Our recent report demonstrated that hypothyroidism, like hyperthyroidism, leads to increased AF inducibility. This study was designed to investigate the effect of thyroid hormone (TH) replacement therapy on AF arrhythmogenesis in HF. Methods and Results Myocardial infarction (MI) was produced in rats by coronary artery ligation. Rats with large MIs (>40%) were randomized into L-thyroxine (T4, n=14) and placebo (n=15) groups 2 weeks after MI. Rats received 3.3 mg T4 (in 60-day release form) or placebo pellets in respective groups for 2 months. Compared with the placebo, T4 treatment improved cardiac function and decreased left ventricular internal diameters as well as left atrial diameter. T4 treatment attenuated atrial effective refractory period prolongation (45±1.5 ms in placebo group vs 37±1.6 ms in T4 group, P<0.01) and reduced AF inducibility (AF/atrial flutter /tachycardia were inducible in 11/15 rats, or 73% in placebo vs 4/14 rats, or 29% in the T4 treated group, P<0.05). Arrhythmia reduction was associated with decreased atrial fibrosis but was not associated with connexin 43 changes. Conclusion To our knowledge this is the first study demonstrating that TH replacement therapy in HF attenuates atrial remodeling and reduces AF inducibility post MI-HF. Clinical studies are needed to confirm such benefits in patients. PMID:25305503

  11. Cardio-protecteffect of qiliqiangxin capsule on left ventricular remodeling, dysfunction and apoptosis in heart failure rats after chronic myocardial infarction

    PubMed Central

    Liang, Tuo; Zhang, Yuhui; Yin, Shijie; Gan, Tianyi; An, Tao; Zhang, Rongcheng; Wang, Yunhong; Huang, Yan; Zhou, Qiong; Zhang, Jian

    2016-01-01

    Background: Qiliqiangxin (QL) capsule is a traditional Chinese medicine which has been approved for the treatment of chronic heart failure. Evidences proved that QL capsules further reduced the NT-proBNP levels and improved left ventricular ejection fraction in CHF patients but the evidence supporting its underlying mechanism is still unclear. Methods and Results: Myocardial infarction (MI) -Heart failure (HF) Sprague-Dawley ratsmodel and neonatal rat cardiac myocytes (NRCMs) were used. Animals were assigned into 4 groups, normal group (n=6), shame-operation group (n=6), MI rats 4 weeks after left anterior descending coronary artery ligation were randomized into vehicle group (n=8), QL group (n=8). QL significantly attenuated cardiac dysfunction and ventricle remodeling as echocardiography and hemodynamic measurements showed improvement in left ventricular ejection fraction, fractional shortening, ±dp/dt and left ventricular end diastolic and systolic diameters in QL treated group compared with the vehicle group. Improvements ininterstitial fibrosisand mitochondrial structures were also exhibited by Sirius Red staining, RT-PCR and electron microscopy. QL treatment improved apoptosis and VEGF expression in rats marginal infract area. Complementary experiments analyzed the improved apoptosis and up-regulate of VEGF in ischemia-hypoxia cultivated NRCMs is in an Akt dependent manner and can be reversed by Akt inhibitor. Conclusion: QL capsule can improve cardiac dysfunction and ventricular remodeling in MI-HF ratsmodel, this cardiac protective efficacy may be concerned with attenuated apoptosis and cardiac fibrosis. Up-regulated VEGF expression and Akt phosphorylation may take part in this availability. PMID:27347313

  12. Roles of endothelial nitric oxide synthase (eNOS) and mitochondrial permeability transition pore (MPTP) in epoxyeicosatrienoic acid (EET)-induced cardioprotection against infarction in intact rat hearts.

    PubMed

    Gross, Garrett J; Hsu, Anna; Pfeiffer, Adam W; Nithipatikom, Kasem

    2013-06-01

    We previously demonstrated that 11,12 and 14,15-epoxeicosatrienoic acids (EETs) produce cardioprotection against ischemia-reperfusion injury in dogs and rats. Several signaling mechanisms have been implicated in the cardioprotective actions of the EETs; however, their mechanisms remain largely elusive. Since nitric oxide (NO) plays a significant role in cardioprotection and EETs have been demonstrated to induce NO production in various tissues, we hypothesized that NO is involved in mediating the EET actions in cardioprotection. To test this hypothesis, we used an in vivo rat model of infarction in which intact rat hearts were subjected to 30-min occlusion of the left coronary artery and 2-hr reperfusion. 11,12-EET or 14,15-EET (2.5mg/kg) administered 10min prior to the occlusion reduced infarct size, expressed as a percentage of the AAR (IS/AAR), from 63.9±0.8% (control) to 45.3±1.2% and 45.5±1.7%, respectively. A nonselective nitric oxide synthase (NOS) inhibitor, L-NAME (1.0mg/kg) or a selective endothelial NOS inhibitor, L-NIO (0.30mg/kg) alone did not affect IS/AAR but they completely abolished the cardioprotective effects of the EETs. On the other hand, a selective neuronal NOS inhibitor, nNOS I (0.03mg/kg) and a selective inducible NOS inhibitor, 1400W (0.10mg/kg) did not affect IS/AAR or block the cardioprotective effects of the EETs. Administration of 11,12-EET (2.5mg/kg) to the rats also transiently increased the plasma NO concentration. 14,15-EET (10μM) induced the phosphorylation of eNOS (Ser(1177)) as well as a transient increase of NO production in rat cardiomyoblast cell line (H9c2 cells). When 11,12-EET or 14,15-EET was administered at 5min prior to reperfusion, infarct size was also reduced to 42.8±2.2% and 42.6±1.9%, respectively. Interestingly, L-NAME (1.0mg/kg) and a mitochondrial KATP channel blocker, 5-HD (10mg/kg) did not abolish while a sarcolemmal KATP channel blocker, HMR 1098 (6.0mg/kg) and a mitochondrial permeability transition

  13. 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. PMID:27378063

  14. Tumorigenesis of nuclear transfer-derived embryonic stem cells is reduced through differentiation and enrichment following transplantation in the infarcted rat heart.

    PubMed

    Fu, Qiang; Su, Dechun; Wang, Ke; Zhao, Yingjun

    2016-06-01

    The aim of the present study was to evaluate the tumorigenic potential of nuclear transfer-derived (nt) mouse embryonic stem cells (mESCs) transplanted into infarcted rat hearts. The nt‑mESCs were cultured using a bioreactor system to develop embryoid bodies, which were induced with 1% ascorbic acid to differentiate into cardiomyocytes. The nt‑mESC‑derived cardiomyocytes (nt‑mESCs‑CMs) were enriched using Percoll density gradient separation to generate nt‑mESCs‑percoll‑enriched (PE)‑CMs. Ischemia was induced by ligating the left anterior descending coronary artery in female Sprague‑Dawley rats. Immunosuppressed rats (daily intraperitoneal injections of cyclosporine A and methylprednisolone) were randomly assigned to receive an injection containing 5x106 mESCs, nt‑mESCs, nt‑mESC‑CMs or nt‑mESC‑PE‑CMs. Analysis performed 8 weeks following transplantation revealed teratoma formation in 80, 86.67 and 33.33% of the rats administered with the mESCs, nt‑mESCs and nt‑mESC‑CMs, respectively, indicating no significant difference between the mESCs and nt‑mESCs; but significance (P<0.05) between the nt‑mESC‑CMs and nt‑mESCs. The mean tumor volumes were 82.72±6.52, 83.17±3.58 and 50.40±5.98 mm3, respectively (P>0.05 mESCs, vs. nt‑mESCs; P<0.05 nt‑mESC‑CMs, vs. nt‑mESCs). By contrast, no teratoma formation was detected in the rats, which received nt‑mESC‑PE‑CMs. Octamer‑binding transcription factor‑4, a specific marker of undifferentiated mESCs, was detected using polymerase chain reaction in the rats, which received nt‑mESCs and nt‑mESC‑CMs, but not in rats administered with nt‑mESC‑PE‑CMs. In conclusion, nt‑mESCs exhibited the same pluripotency as mESCs, and teratoma formation following nt‑mESC transplantation was reduced by cell differentiation and enrichment. PMID:27082733

  15. Fibroblast KATP currents modulate myocyte electrophysiology in infarcted hearts.

    PubMed

    Benamer, Najate; Vasquez, Carolina; Mahoney, Vanessa M; Steinhardt, Maximilian J; Coetzee, William A; Morley, Gregory E

    2013-05-01

    Cardiac metabolism remains altered for an extended period of time after myocardial infarction. Studies have shown fibroblasts from normal hearts express KATP channels in culture. It is unknown whether fibroblasts from infarcted hearts express KATP channels and whether these channels contribute to scar and border zone electrophysiology. KATP channel subunit expression levels were determined in fibroblasts isolated from normal hearts (Fb), and scar (sMI-Fb) and remote (rMI-Fb) regions of left anterior descending coronary artery (LAD) ligated rat hearts. Whole cell KATP current density was determined with patch clamp. Action potential duration (APD) was measured with optical mapping in myocyte-only cultures and heterocellular cultures with fibroblasts with and without 100 μmol/l pinacidil. Whole heart optical mapping was used to assess KATP channel activity following LAD ligation. Pinacidil activated a potassium current (35.4 ± 7.5 pA/pF at 50 mV) in sMI-Fb that was inhibited with 10 μmol/l glibenclamide. Kir6.2 and SUR2 transcript levels were elevated in sMI-Fb. Treatment with Kir6.2 short interfering RNA decreased KATP currents (87%) in sMI-Fb. Treatment with pinacidil decreased APD (26%) in co-cultures with sMI-Fb. APD values were prolonged in LAD ligated hearts after perfusion with glibenclamide. KATP channels are present in fibroblasts from the scar and border zones of infarcted hearts. Activation of fibroblast KATP channels could modulate the electrophysiological substrate beyond the acute ischemic event. Targeting fibroblast KATP channels could represent a novel therapeutic approach to modify border zone electrophysiology after cardiac injury. PMID:23436329

  16. 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.

  17. Cardiac PET imaging of 18F-FDG metabolism: study of healthy and infarcted hearts of rats.

    PubMed

    Mabrouk, R; Dubeau, F; Bentabet, L

    2013-01-01

    This paper, considers the evolution of a method presented previously by authors to correct for cross contamination effect on the dynamic image sequences and shows how this development allows for a robust voxel by voxel implementation yielding parametric images for healthy and unhealthy subjects. Our approach is based on the decomposition of image pixel intensity into blood and tissue components using Bayesian statistics. The method uses an a priori knowledge of the probable distribution of blood and tissue in the images. Likelihood measures are computed by a General Gaussian Distribution (GGD) model. Bayes' rule is then applied to compute weights that account for the concentrations of the radiotracer in blood and tissue and their relative contributions in each image pixel. We tested the method on a set of dynamic cardiac (18)F-fluoro-deoxy-d-glucose PET of healthy rats and unhealthy rats. The results show the benefit of our correction on the generation of parametric images of myocardial metabolic rates for glucose (MMRG). PMID:24110230

  18. Attenuated response to atrial natriuretic peptide in rats with myocardial infarction.

    PubMed

    Kohzuki, M; Hodsman, G P; Johnston, C I

    1989-02-01

    The natriuretic, diuretic, and hypotensive effects of atrial natriuretic peptide (ANP) were examined in rats 4 wk after myocardial infarction induced by left coronary artery ligation. Synthetic rat ANP (fragment 1-28) was infused intravenously in doses of 0.1, 0.3, and 1.0 micrograms.kg-1.min-1 for 30 min. There was a significant decrease in systolic blood pressure in controls and rats with infarction, although only in control rats was there a significant decrease in diastolic blood pressure. Changes in systolic and diastolic blood pressure were attenuated in rats with infarction compared with controls (P less than 0.01). The diuretic and natriuretic effects of ANP were observed in both groups of rats, but the effects were significantly less in rats with infarction (P less than 0.01). The ANP infusion did not induce significant changes in heart rate or hematocrit in controls or rats with infarction. The results indicate that rats with chronic left heart failure are less sensitive to the natriuretic, diuretic, and hypotensive effects of ANP when compared with controls. The attenuated renal response to ANP may contribute to the impaired sodium and water excretion in chronic heart failure, although other mechanisms are involved. PMID:2521777

  19. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

  20. The myocardial infarct size-limiting and antiarrhythmic effects of acyl-CoA:cholesterol acyltransferase inhibitor VULM 1457 protect the hearts of diabetic-hypercholesterolaemic rats against ischaemia/reperfusion injury both in vitro and in vivo.

    PubMed

    Adameová, Adriana; Ravingerová, Tána; Svec, Pavel; Faberová, Viera; Kuzelová, Magdaléna

    2007-12-01

    The study was designed to characterise the influence of a novel acyl-CoA:cholesterol acyltransferase inhibitor, VULM 1457, on the severity of myocardial ischaemia-reperfusion injury in a model of diabetes mellitus and hypercholesterolaemia induced by co-administration of streptozotocin and a high fat-cholesterol diet. We used Langendorff-perfused rat hearts to measure the size of myocardial infarction after 30 min of regional ischaemia, followed by a 2-h reperfusion period, and open-chest rats were exposed to 6 min of ischaemia and 10 min of reperfusion to analyse ventricular arrhythmias. In addition to the high fat-cholesterol diet, VULM 1457 was administered to the diabetic-hypercholesterolaemic rats for 5 days. Decreased plasma and liver cholesterol levels and a significantly reduced occurrence of ventricular fibrillation (29% vs. 100%, P<0.01), determined via the mean number and duration of episodes (0.6+/-0.4 and 2.1+/-1.4 s vs. 2.8+/-0.8 and 53.5+/-14.4 s in diabetic-hypercholesterolaemic rats, both P<0.01), were observed in these animals. Lethal ventricular fibrillation was suppressed, and arrhythmia severity was also significantly decreased in these animals as compared to the non-treated animals (2.9+/-0.6 vs. 4.9+/-0.2; P<0.05). A smaller infarct size, normalised to the size of area at risk, was observed in the treated diabetic-hypercholesterolaemic group as compared to the non-treated group (16.3+/-1.9% vs. 37.3+/-3.1%; P<0.01). Aside from remarkable hypolipidaemic activity, VULM 1457 improved the overall myocardial ischaemia-reperfusion injury outcomes in the diabetic-hypercholesterolaemic rats by suppressing arrhythmogenesis as well as by reducing myocardial necrosis. PMID:17764671

  1. Optical projection tomography permits efficient assessment of infarct volume in the murine heart postmyocardial infarction

    PubMed Central

    Zhao, X.; Wu, J.; Gray, C. D.; McGregor, K.; Rossi, A. G.; Morrison, H.; Jansen, M. A.

    2015-01-01

    The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective, and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion-fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. Two-dimensional infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r2 = 0.99, P < 0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (r2 = 0.7608, P < 0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a nondestructive, efficient, and accurate approach for routine in vitro assessment of murine myocardial infarct volume. PMID:26071543

  2. Enhanced thromboxane synthesis in atria from infarcted rabbit hearts

    SciTech Connect

    Dunkel, C.G.; Evers, A.S.; Needleman, P.

    1986-03-05

    The authors have previously shown that left ventricular myocardial infarction (MI) results in enhanced thromboxane (Tx) synthesis in response to n-formylmethionyl-leucyl-phenylalanine (fMLP). To anatomically localize this response, cardiac atria and ventricles were removed from normal rabbits and rabbits subjected 4 days previously to MI. Atria were placed in a tissue bath, ventricles were perfused with buffer via the vasculature and both preparations were challenged with fMLP. TxB/sub 2/ in the bath media or ventricular effluent was measured by specific RIA. Atria from normal and infarcted hearts produced similar basal levels of Tx. Following fMLP stimulation, atria from infarcted hearts produced 10X more Tx than normal atria. Ventricles from normal and infarcted hearts produced no Tx basally and only small quantities with fMLP stimulation. Incubation of microsomes prepared from the various chambers of the heart with (/sup 14/-C) arachidonate showed that Tx synthetic capacity in both normal and infarcted hearts resides almost exclusively in the right cardiac atria. These results show that cardiac Tx synthesis is largely an atrial phenomenon and that left ventricular myocardial infarction results in enhanced fMLP-stimulated Tx synthesis.

  3. Heart Rate Turbulence as Risk-Predictor after Myocardial Infarction

    PubMed Central

    Zuern, Christine S.; Barthel, Petra; Bauer, Axel

    2011-01-01

    Heart rate turbulence (HRT) is the baroreflex-mediated short-term oscillation of cardiac cycle lengths after spontaneous ventricular premature complexes. HRT is composed of a brief heart rate acceleration followed by a gradual heart rate deceleration. In high risk patients after myocardial infarction (MI) HRT is blunted or diminished. Since its first description in 1999 HRT emerged as one of the most potent risk factors after MI. Predictive power of HRT has been studied in more than 10,000 post-infarction patients. This review is intended to provide an overview of HRT as risk-predictor after MI. PMID:22180744

  4. RNA interference targeting SHP-1 attenuates myocardial infarction in rats.

    PubMed

    Sugano, Masahiro; Tsuchida, Keiko; Hata, Tomoji; Makino, Naoki

    2005-12-01

    The Src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1) plays a key role in apoptosis and decreases phosphorylation of Akt. Apoptosis of cardiomyocytes is thought to contribute to the increased area of acute myocardial infarction (AMI), and Akt activation exerts a powerful cardioprotective effect after ischemia. Thus, a therapeutic strategy designed to inhibit expression of SHP-1 would be beneficial in AMI. Here we report that siRNA targeting SHP-1 reduced infarct size in a rat model of AMI. Upon injection into the ischemic left ventricular wall, the vector-based siRNA significantly suppressed the increase in the SHP-1 mRNA and the SHP-1 protein levels. The siRNA vector also significantly reduced the SHP-1 that bound to Fas-R. The SHP-1 siRNA vector increased phospho-Akt and reduced DNA fragmentation and caspase activity compared with the scramble siRNA vector. Finally, the area of myocardial infarction was significantly smaller with the SHP-1 siRNA vector than with the scramble siRNA vector at 2 days after LCA ligation. In conclusion, SHP-1 in the heart increased from the early stage of AMI, and this increase was thought to contribute to the increased area of myocardial infarction. Suppression of SHP-1 with the SHP-1 siRNA vector markedly reduced the infarct size in AMI. PMID:16223786

  5. Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart

    PubMed Central

    Khan, Mahmood; Meduru, Sarath; Mohan, Iyyapu K.; Kuppusamy, M. Lakshmi; Wisel, Sheik; Kulkarni, Aditi; Rivera, Brian K.; Hamlin, Robert L.; Kuppusamy, Periannan

    2009-01-01

    A major limitation to the application of stem-cell therapy to repair ischemic heart damage is the low survival of transplanted cells in the heart, possibly due to poor oxygenation. We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant treatment to augment stem-cell therapy. Therefore, the goal of this study was to evaluate the effect of HBO on the engraftment of rat bone-marrow-derived mesenchymal stem cells (MSCs) transplanted in infarct rat hearts. Myocardial infarction (MI) was induced in Fisher-344 rats by permanently ligating the left-anterior-descending coronary artery. MSCs, labeled with fluorescent superparamagnetic iron oxide (SPIO) particles, were transplanted in the infarct and peri-infarct regions of the MI hearts. HBO (100% oxygen at 2 ATA for 90 min) was administered daily for 2 weeks. Four MI groups were used: untreated (MI); HBO; MSC; MSC+HBO. Echocardiography, electro-vectorcardiography, and magnetic resonance imaging were used for functional evaluations. The engraftment of transplanted MSCs in the heart was confirmed by SPIO fluorescence and Prussian-blue staining. Immunohistochemical staining was used to identify key cellular and molecular markers including CD29, troponin-T, connexin-43, VEGF, α-smooth-muscle actin, and von-Willebrand factor in the tissue. Compared to MI and MSC groups, the MSC+HBO group showed a significantly increased recovery of cardiac function including left-ventricular (LV) ejection fraction, fraction-shortening, LV wall-thickness, and QRS vector. Further, HBO treatment significantly increased the engraftment of CD29-positive cells, expression of connexin-43, troponin-T and VEGF, and angiogenesis in the infarct tissue. Thus, HBO appears to be a potential and clinically-viable adjuvant treatment for myocardial stem-cell therapy. PMID:19376124

  6. 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. PMID:27434651

  7. 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.

  8. 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. PMID:27181040

  9. 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

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

    PubMed

    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

    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 was

  11. Infarcted rat myocardium: Data from biaxial tensile and uniaxial compressive testing and analysis of collagen fibre orientation.

    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

    2016-09-01

    Myocardial infarction was experimentally induced in rat hearts and harvested immediately, 7, 14 and 28 days after the infarction induction. Anterior wall infarct samples underwent biaxial tensile and uniaxial compressive testing. Orientation of collagen fibres was analysed following mechanical testing. In this paper, we present the tensile and compressive stress-strain raw data, the calculated tensile and compressive moduli and the measured angles of collagen orientation. The presented data is associated with the research article titled "Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression" (Sirry et al., 2016) [1]. PMID:27579338

  12. [Painless anterior acute myocardial infarction in a transplanted heart].

    PubMed

    Poyet, R; Capilla, E; Tortat, A V; Brocq, F X; Pons, F; Kerebel, S; Jego, C; Cellarier, G R

    2015-11-01

    Cardiac allograft vasculopathy is the major determinant of long-term survival in patients after heart transplantation. Clinical presentations are congestive heart failure, ventricular arrhythmias and sudden cardiac death. Acute coronary syndrome is a rare presentation of cardiac allograft vasculopathy due to myocardial denervation. We present the case of a 31-year-old patient, who had undergone heart transplantation 6 months earlier and who developed a painless anterior myocardial infarction revealed by syncope. He was successfully treated by percutaneous coronary intervention with drug eluting stent implantation. PMID:26472502

  13. Circadian Dependence of Infarct Size and Acute Heart Failure in ST Elevation Myocardial Infarction

    PubMed Central

    Devi, Anju; Carvalho, Leonardo P.; Chua, Terrance; Koh, Tian-Hai; Tan, Huay-Cheem; Foo, David; Tong, Khim-Leng; Ong, Hean-Yee; Richards, A. Mark; Yew, Chow Khuan; Chan, Mark Y.

    2015-01-01

    Objectives There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI. Methods We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight–6:00 A.M., 6:00 A.M.–noon, noon–6:00 P.M. and 6:00 P.M.–midnight. We used peak creatine kinase as a surrogate marker of infarct size. Results Midnight–6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight–6:00 A.M. patients and lowest among 6:00 A.M.–noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight–6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.–noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001). Conclusion We observed a circadian peak and nadir in infarct size during STEMI onset from midnight–6:00A.M and 6:00A.M.–noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian

  14. In vivo transfer of soluble TNF-alpha receptor 1 gene improves cardiac function and reduces infarct size after myocardial infarction in rats.

    PubMed

    Sugano, Masahiro; Tsuchida, Keiko; Hata, Tomoji; Makino, Naoki

    2004-05-01

    Increased circulating and cardiac TNF-alpha levels during myocardial ischemia have been found in both experimental animals and patients with ischemic heart disease and advanced heart failure. Soluble TNF-alpha receptor 1 (sTNFR1) is an antagonist to TNF-alpha. In the present study, we examined whether sTNFR1 improves cardiac function in rats after myocardial infarction. Male Wistar rats were subjected to left coronary artery (LCA) ligation. Immediately after the ligation, a total of 200 microg of either the sTNFR1 or LacZ plasmid was injected into three different sites in the left ventricular wall. From 1 to 21 days after LCA ligation, TNF-alpha bioactivity in the heart was higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase. The LV diastolic dimension was significantly lower, and the fractional shortening was significantly higher in rats treated with the sTNFR1 plasmid than in those treated with the LacZ plasmid. At 21 days after LCA ligation, the LV end-diastolic pressure was also significantly lower in the rats treated with the sTNFR1 plasmid. In addition, the sTNFR1 expression plasmid had significantly reduced the infarct size. In conclusion, TNF-alpha bioactivity in the heart increased during the early stage of infarction and remained elevated. This elevation seemed partially responsible for the impairment of LV function and the increased infarct size. Suppression of TNF-alpha bioactivity from the early stage of infarction with the sTNFR1 plasmid improved cardiac function and reduced infarct size. PMID:15117889

  15. Dental Calculus Is Associated with Death from Heart Infarction

    PubMed Central

    Söder, Birgitta; Meurman, Jukka H.; Söder, Per-Östen

    2014-01-01

    Objectives. We studied whether the amount of dental calculus is associated with death from heart infarction in the dental infection—atherosclerosis paradigm. Materials. Participants were 1676 healthy young Swedes followed up from 1985 to 2011. At the beginning of the study all subjects underwent oral clinical examination including dental calculus registration scored with calculus index (CI). Outcome measure was cause of death classified according to WHO International Classification of Diseases. Unpaired t-test, Chi-square tests, and multiple logistic regressions were used. Results. Of the 1676 participants, 2.8% had died during follow-up. Women died at a mean age of 61.5 years and men at 61.7 years. The difference in the CI index score between the survivors versus deceased patients was significant by the year 2009 (P < 0.01). In multiple regression analysis of the relationship between death from heart infarction as a dependent variable and CI as independent variable with controlling for age, gender, dental visits, dental plaque, periodontal pockets, education, income, socioeconomic status, and pack-years of smoking, CI score appeared to be associated with 2.3 times the odds ratio for cardiac death. Conclusions. The results confirmed our study hypothesis by showing that dental calculus indeed associated statistically with cardiac death due to infarction. PMID:24511535

  16. EFFECTS OF CHRONIC ACTIVATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA OR HIGH-FAT FEEDING IN A RAT INFARCT MODEL OF HEART FAILURE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intracardiac accumulation of lipid and related intermediates (e.g., ceramide) is associated with cardiac dysfunction and may contribute to the progression of heart failure (HF). Overexpression of nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) increases intramyocellula...

  17. 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.

  18. 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

  19. Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts.

    PubMed

    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 Mesp1(Cre/+); Rosa26(EYFP/+) 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. 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

    2016-01-01

    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

  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. 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

  3. Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart

    PubMed Central

    Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

    2012-01-01

    Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

  4. PDE5 inhibitors protect against post-infarction heart failure.

    PubMed

    Li, Na; Yuan, Yuan; Li, Shuang; Zeng, Cao; Yu, Wenjun; Shen, Mingzhi; Zhang, Rongqing; Li, Congye; Zhang, Yingmei; Wang, Haichang

    2016-01-01

    Heart failure (HF) is one of the main causes for cardiovascular morbidity and mortality. This study was designed to examine the effect of PDE-5 inhibition on cardiac geometry, function and apoptosis in post-infarct HF. Our data revealed that treatment of the PDE-5 inhibitor sildenafil, beginning 3 days after left anterior descending coronary artery ligation, attenuated LV remodeling, cardiac dysfunction, cardiomyocyte apoptosis and mitochondrial anomalies including ATP production, mitochondrial respiratory defects, decline of mitochondrial membrane potential (MMP) and compromised mitochondrial ultrastructure. Sildenafil partially ameliorated the downregulation of Sirt3 protein and acetylation of PGC-1alpha in peri-infarct myocardial regions. In cultured neonatal mouse ventricular myocytes subjected to hypoxia for 24 hrs, sildenafil suppressed apoptosis, promoted ATP production and elevated MMP, along with the increased Sirt3 protein expression and decreased PGC-1alpha acetylation. Interestingly, knock down of Sirt3 attenuated or nullified sildenafil-offered beneficial effects. Our findings demonstrated that sildenafil exerts its cardioprotective effect against post-infarction injury by improving mitochondrial ultrastructure and function via the Sirt3/PGC-1alpha pathway. This observation should shed some lights towards application of sildenafil in energy-related cardiovascular diseases. PMID:27100500

  5. 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

  6. 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

  7. 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.

  8. Improved survival with simendan after experimental myocardial infarction in rats.

    PubMed

    Levijoki, J; Pollesello, P; Kaheinen, P; Haikala, H

    2001-05-11

    This study compared the effects of simendan, a calcium sensitizer, with those of milrinone and enalapril on survival of rats with healed myocardial infarction. Seven days after ligation-induced myocardial infarction, the rats were randomized to control, milrinone, enalapril, or simendan groups. All compounds were administered via the drinking water for 312 days, at which time there was 80% mortality in the control group--the study's primary endpoint. The infarct sizes were similar across all groups. At endpoint, the mortality rates were: 63% (milrinone), 56% (enalapril) and 53% (simendan); the risk reductions were 25% (P = 0.04 vs. control) and 28% (P = 0.02 vs. control) with enalapril and simendan, respectively. Milrinone had no statistically significant effect on the survival rate. These findings suggest that, like enalapril, simendan improved survival in rats with healed myocardial infarction. PMID:11426847

  9. 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

  10. 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.

  11. Antiarrhythmic effect of growth factor-supplemented cardiac progenitor cells in chronic infarcted heart.

    PubMed

    Savi, Monia; Bocchi, Leonardo; Rossi, Stefano; Frati, Caterina; Graiani, Gallia; Lagrasta, Costanza; Miragoli, Michele; Di Pasquale, Elisa; Stirparo, Giuliano G; Mastrototaro, Giuseppina; Urbanek, Konrad; De Angelis, Antonella; Macchi, Emilio; Stilli, Donatella; Quaini, Federico; Musso, Ezio

    2016-06-01

    c-Kit(pos) cardiac progenitor cells (CPCs) represent a successful approach in healing the infarcted heart and rescuing its mechanical function, but electrophysiological consequences are uncertain. CPC mobilization promoted by hepatocyte growth factor (HGF) and IGF-1 improved electrogenesis in myocardial infarction (MI). We hypothesized that locally delivered CPCs supplemented with HGF + IGF-1 (GFs) can concur in ameliorating electrical stability of the regenerated heart. Adult male Wistar rats (139 rats) with 4-wk-old MI or sham conditions were randomized to receive intramyocardial injection of GFs, CPCs, CPCs + GFs, or vehicle (V). Enhanced green fluorescent protein-tagged CPCs were used for cell tracking. Vulnerability to stress-induced arrhythmia was assessed by telemetry-ECG. Basic cardiac electrophysiological properties were examined by epicardial multiple-lead recording. Hemodynamic function was measured invasively. Hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. Compared with V and at variance with individual CPCs, CPCs + GFs approximately halved arrhythmias in all animals, restoring cardiac anisotropy toward sham values. GFs alone reduced arrhythmias by less than CPCs + GFs, prolonging ventricular refractoriness without affecting conduction velocity. Concomitantly, CPCs + GFs reactivated the expression levels of Connexin-43 and Connexin-40 as well as channel proteins of key depolarizing and repolarizing ion currents differently than sole GFs. Mechanical function and anatomical remodeling were equally improved by all regenerative treatments, thus exhibiting a divergent behavior relative to electrical aspects. Conclusively, we provided evidence of distinctive antiarrhythmic action of locally injected GF-supplemented CPCs, likely attributable to retrieval of Connexin-43, Connexin-40, and Cav1.2 expression, favoring intercellular coupling and spread of excitation in mended heart. PMID:26993221

  12. 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

  13. Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction.

    PubMed

    Apaijai, Nattayaporn; Inthachai, Tharnwimol; Lekawanvijit, Suree; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-06-01

    Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adverse remodeling after MI in obese-insulin-resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant rats with MI. Rats were fed either normal diet (ND) or high-fat diet (HFD) for 12 weeks to induce obese-insulin resistance, followed by left anterior descending coronary artery ligation to induce MI. Then, rats in each dietary group were divided into five subgroups to receive vehicle, enalapril (10mg/kg/day), metformin (30mg/kg/day), DPP4 inhibitor vildagliptin (3mg/kg/day), or combined metformin and vildagliptin for 8 weeks. Heart rate variability (HRV), LV function, pathological and biochemical studies for LV remodeling, and cardiomyocyte apoptosis were determined. Obese-insulin-resistant rats had severe insulin resistance and LV dysfunction. HFD rats had a higher mortality rate than ND rats, and all treatments reduced the mortality rate in obese-insulin-resistant rats. Although all drugs improved insulin resistance, HRV, LV function as well as reduced cardiac hypertrophy and fibrosis, vildagliptin effectively reduced cardiomyocyte cross-sectional areas more than enalapril and was related to markedly decreased ERK1/2 phosphorylation. In ND rats with MI, metformin neither improved LV ejection fraction nor reduced cardiac fibrosis. The infarct size and transforming growth factor-β expression were not different among groups. In obese-insulin-resistant rats with chronic MI, DPP4 inhibitor vildagliptin exerts better cardioprotection than enalapril in attenuating adverse LV remodeling. PMID:27044778

  14. 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. PMID:24862441

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

    PubMed Central

    Lewin, Sarah A.; Shvartsman, Dmitry; Brudno, Yevgeny; Vasilyev, Nikolay V.; O'Brien, Fergal J.; Walsh, Conor J.; Duffy, Garry P.; Mooney, David J.

    2014-01-01

    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 the 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) and two epicardial patches (alginate, collagen). Human mesenchymal stem cells (hMSCs) were delivered to the infarct border zone with each biomaterial. At 24 hours, retained cells were quantified by fluorescence. All biomaterials had superior fluorescence to saline control, with 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 injectable hydrogels and epicardial patches 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. PMID:24862441

  16. 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

  17. 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. PMID:27294126

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

    PubMed

    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

    2013-10-01

    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 Ly6C(hi) 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

  19. 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.

  20. 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.

  1. 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

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

    PubMed

    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

  3. A model of chronic heart failure in spontaneous hypertensive rats (SHR).

    PubMed

    Itter, G; Jung, W; Juretschke, P; Schoelkens, B A; Linz, W

    2004-04-01

    Common models of chronic heart failure (CHF) do not always result in parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The aim of this study was to establish and validate a new model of CHF in the rat. CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive (SHR/NHsd) rats by creating a permanent (8-week) occlusion of the left coronary artery 2 mm distal to the origin from the aorta by a modified technique. This resulted in a large infarction of the free left ventricular wall. The focus of attention was the validation of the geometric properties of the left ventricle and its contractility. The validation of the geometric properties of the left ventricle was done by a non-invasive magnetic resonance imaging (MRI) technique and by planimetry (stereology). Cardiodynamics (e.g. contractility) were evaluated in the isolated 'working heart' model. We were able to establish a new and predictive model of heart failure in the spontaneously hypertensive rat 8 weeks after coronary artery ligation. At this time point, the WKY rat did not show any symptoms of CHF. The model represents characteristic parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of congestive heart failure were prominent, such as dyspnoea, subcutaneous oedema, pale-bluish limbs and impaired motion. Non-invasive sequential measurements by NMR techniques showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. The infarcted animals showed a reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd rat than in the WKY/NHsd rat. Furthermore the infarcted animals showed enhanced levels of hydroxyproline/proline ratios, again much more so in the SHR/NHsd rat than in the WKY/NHsd rat. PMID:15070453

  4. When heart goes “BOOM” to fast. Heart rate greater than 80 as mortality predictor in acute myocardial infarction

    PubMed Central

    Davidovic, Goran; Iric-Cupic, Violeta; Milanov, Srdjan; Dimitijevic, Aleksandra; Petrovic-Janicijevic, Mirjana

    2013-01-01

    Many prospective studies established association between high heart rate and increased cardiovascular morbidity and mortality, independently of other risk factors. Heart rate over 80 beats per minute more often leads to atherosclerotic plaque disruption, the main step in developing acute coronary syndrome. Purpose was to investigate the incidence of higher heart rate levels in patients with anterior wall acute myocardial infarction with ST-segment elevation and the influence of heart rate on mortality. Research included 140 patients with anterior wall acute myocardial infarction with ST-segment elevation treated in Coronary Unit, Clinical Center Kragujevac in the period from January 2001-June 2006. Heart rate was calculated as the mean value of baseline and heart rate in the first 30 minutes after admission. Other risk factors were also followed to determine their connection with elevated heart rate. Results showed that the majority of patients survived (over 70%). In a total number of patients, more than 75% had a heart rate levels greater than 80 beats per minute. There was a significant difference in heart rate on addmision between survivors and patients who died, with a greater levels in patients with fatal outcome. Both, univariate and multivariate regression analysis singled out heart rate greater than 80 beats per minute as independent mortality predictor in these patients. Heart rate greater than 80 beats per minute is a major, independent risk factor for morbidity and important predictor of mortality in patients with acute myocardial infarction. PMID:23991346

  5. GLUTAMINE CYCLING IN ISOLATED WORKING RAT HEART

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To what extent does glutamine turnover keep pace with oxidative metabolism in the rat heart? To address this question, the following substrates were presented to the isolated, working rat heart: (1) glucose (5 mM), insulin (40 mU/ml) and [2-13C]acetate (5mM) (high workload, n= 5); (2) pyruvate (2....

  6. 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.

  7. 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

  8. 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. PMID:26791829

  9. Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats

    PubMed Central

    Fernandes, S; Naumova, AV; Zhu, WZ; Laflamme, MA; Gold, J; Murry, CE

    2010-01-01

    Background Previous studies indicated that, in an acute myocardial infarction model, human embryonic stem cell-derived cardiomyocytes (hESC-CM) injected with a pro-survival cocktail (PSC) can preserve contractile function. Because patients with established heart failure may also benefit from cell transplantation, we evaluated the physiological effects of hESC-CM transplanted into a chronic model of myocardial infarction. Methods and Results Intramyocardial injection of hESC-CM with PSC was performed in nude rats at 1 month following ischemia-reperfusion. The left ventricular function of hESC-CM injected rats was evaluated at 1, 2 and 3 months after the cell injection procedure and was compared to 3 control groups (rats injected with serum-free media, PSC-only, or non-cardiac human cells in PSC). Histology at 3 months revealed that human cardiomyocytes survive, develop increased sarcomere organization and are still proliferating. Despite successful engraftment, both echocardiography and MRI analyses showed no significant difference in left ventricular structure or function between these 4 groups at any time point of the study, suggesting that human cardiomyocytes do not affect cardiac remodeling in a rat model of chronic myocardial infarction. Conclusion When injected into a chronic infarct model, hESC-CM can engraft, survive and form grafts with striated cardiomyocytes at least as well as was previously observed in an acute myocardial infarction model. However, although hESC-CM transplantation can attenuate the progression of heart failure in an acute model, the same hESC-CM injection protocol is insufficient to restore heart function or to alter adverse remodeling of a chronic myocardial infarction model. PMID:20854826

  10. Thrombospondin-1 is induced in rat myocardial infarction and its induction is accelerated by ischemia/reperfusion.

    PubMed

    Sezaki, Satoshi; Hirohata, Satoshi; Iwabu, Akihiro; Nakamura, Keigo; Toeda, Kenichi; Miyoshi, Toru; Yamawaki, Hitoshi; Demircan, Kadir; Kusachi, Shozo; Shiratori, Yasushi; Ninomiya, Yoshifumi

    2005-10-01

    Thrombospondin-1 (TSP-1) is a multifunctional, rapid-turnover matricellular protein. Recent studies demonstrated that TSP-1 has a role in regulating inflammatory reactions. Myocardial infarction (MI) is associated with an inflammatory response, ultimately leading to healing and scar formation. In particular, an enhanced inflammatory reaction and a massive accumulation of monocytes/macrophages is seen with reperfusion after MI. To examine the role of TSP-1 in MI, we isolated rat TSP-1 complementary DNA (cDNA) and analyzed the level and distribution of the mRNA expression. In infarcted rat hearts, TSP-1 mRNA increased markedly at 6 and 12 hrs after coronary artery ligation (27.97 +/- 3.40-fold and 22.77 +/- 1.83-fold, respectively, compared with sham-operated hearts). Western blot analysis revealed that TSP-1 protein was transiently induced in the infarcted heart. Using in situ hybridization analysis, TSP-1 mRNA signals were observed in the infiltrating cells at the border area of infarction. We then examined the effect of ischemia/reperfusion (I/R) on TSP-1 mRNA induction in the rats with infarcted hearts. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated that I/R enhanced the TSP-1 mRNA expression approximately 4-fold, as compared with the level in the permanently ligated heart. Finally, we examined the effect of TSP-1 on proinflammatory cytokine release in mononuclear cells. The releases of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) from human mononuclear cells were enhanced by TSP-1 in a dose-dependent manner. Thus, the immediate and marked increase of TSP-1 expression suggests that TSP-1 has an inflammatory-associated role in MI. PMID:16179730

  11. 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

  12. Efficient Differentiation of Human Induced Pluripotent Stem Cells Generates Cardiac Cells That Provide Protection Following Myocardial Infarction in the Rat

    PubMed Central

    Carr, Carolyn; Yang, Cheng Tao; Stuckey, Daniel J.; Clarke, Kieran; Watt, Suzanne M.

    2012-01-01

    Induced pluripotent stem (iPS) cells are being used increasingly to complement their embryonic counterparts to understand and develop the therapeutic potential of pluripotent cells. Our objectives were to identify an efficient cardiac differentiation protocol for human iPS cells as monolayers, and demonstrate that the resulting cardiac progenitors could provide a therapeutic benefit in a rodent model of myocardial infarction. Herein, we describe a 14-day protocol for efficient cardiac differentiation of human iPS cells as a monolayer, which routinely yielded a mixed population in which over 50% were cardiomyocytes, endothelium, or smooth muscle cells. When differentiating, cardiac progenitors from day 6 of this protocol were injected into the peri-infarct region of the rat heart; after coronary artery ligation and reperfusion, we were able to show that human iPS cell-derived cardiac progenitor cells engrafted, differentiated into cardiomyocytes and smooth muscle, and persisted for at least 10 weeks postinfarct. Hearts injected with iPS-derived cells showed a nonsignificant trend toward protection from decline in function after myocardial infarction, as assessed by magnetic resonance imaging at 10 weeks, such that the ejection fraction at 10 weeks in iPS treated hearts was 62%±4%, compared to that of control infarcted hearts at 45%±9% (P<0.2). In conclusion, we demonstrated efficient cardiac differentiation of human iPS cells that gave rise to progenitors that were retained within the infarcted rat heart, and reduced remodeling of the heart after ischemic damage. PMID:22182484

  13. Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart.

    PubMed

    Hosoyama, Tohru; Samura, Makoto; Kudo, Tomoaki; Nishimoto, Arata; Ueno, Koji; Murata, Tomoaki; Ohama, Takashi; Sato, Koichi; Mikamo, Akihito; Yoshimura, Koichi; Li, Tao-Sheng; Hamano, Kimikazu

    2015-01-01

    Cardiosphere-derived cells (CDCs) isolated from postnatal heart tissue are a convenient and efficientresource for the treatment of myocardial infarction. However, poor retention of CDCs in infarcted hearts often causes less than ideal therapeutic outcomes. Cell sheet technology has been developed as a means of permitting longer retention of graft cells, and this therapeutic strategy has opened new avenues of cell-based therapy for severe ischemic diseases. However, there is still scope for improvement before this treatment can be routinely applied in clinical settings. In this study, we investigated whether hypoxic preconditioning enhances the therapeutic efficacy of CDC monolayer sheets. To induce hypoxia priming, CDC monolayer sheets were placed in an incubator adjusted to 2% oxygen for 24 hours, and then preconditioned mouse CDC sheets were implanted into the infarcted heart of old myocardial infarction mouse models. Hypoxic preconditioning of CDC sheets remarkably increased the expression of vascular endothelial growth factor through the PI3-kinase/Akt signaling pathway. Implantation of preconditioned CDC sheets improved left ventricular function inchronically infarcted hearts and reduced fibrosis. The therapeutic efficacy of preconditioned CDC sheets was higher than the CDC sheets that were cultured under normaxia condition. These results suggest that hypoxic preconditioning augments the therapeutic angiogenic and anti-fibrotic activity of CDC sheets. A combination of cell sheets and hypoxic preconditioning offers an attractive therapeutic protocol for CDC transplantation into chronically infarcted hearts. PMID:26885271

  14. Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart

    PubMed Central

    Hosoyama, Tohru; Samura, Makoto; Kudo, Tomoaki; Nishimoto, Arata; Ueno, Koji; Murata, Tomoaki; Ohama, Takashi; Sato, Koichi; Mikamo, Akihito; Yoshimura, Koichi; Li, Tao-Sheng; Hamano, Kimikazu

    2015-01-01

    Cardiosphere-derived cells (CDCs) isolated from postnatal heart tissue are a convenient and efficientresource for the treatment of myocardial infarction. However, poor retention of CDCs in infarcted hearts often causes less than ideal therapeutic outcomes. Cell sheet technology has been developed as a means of permitting longer retention of graft cells, and this therapeutic strategy has opened new avenues of cell-based therapy for severe ischemic diseases. However, there is still scope for improvement before this treatment can be routinely applied in clinical settings. In this study, we investigated whether hypoxic preconditioning enhances the therapeutic efficacy of CDC monolayer sheets. To induce hypoxia priming, CDC monolayer sheets were placed in an incubator adjusted to 2% oxygen for 24 hours, and then preconditioned mouse CDC sheets were implanted into the infarcted heart of old myocardial infarction mouse models. Hypoxic preconditioning of CDC sheets remarkably increased the expression of vascular endothelial growth factor through the PI3-kinase/Akt signaling pathway. Implantation of preconditioned CDC sheets improved left ventricular function inchronically infarcted hearts and reduced fibrosis. The therapeutic efficacy of preconditioned CDC sheets was higher than the CDC sheets that were cultured under normaxia condition. These results suggest that hypoxic preconditioning augments the therapeutic angiogenic and anti-fibrotic activity of CDC sheets. A combination of cell sheets and hypoxic preconditioning offers an attractive therapeutic protocol for CDC transplantation into chronically infarcted hearts. PMID:26885271

  15. 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

  16. 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

  17. 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

  18. In Vivo Detection of Stem Cells Grafted in Infarcted Rat Myocardium

    PubMed Central

    Zhou, Rong; Thomas, Daniel H.; Qiao, Hui; Bal, Harshali S.; Choi, Seok-Rye; Alavi, Abass; Ferrari, Victor A.; Kung, Hank F.; Acton, Paul D.

    2008-01-01

    The evaluation of stem cell–mediated cardiomyoplasty by noninvasive in vivo imaging is critical for its clinical application. We hypothesized that dual-tracer small-animal SPECT would allow simultaneous imaging of 99mTc-sestamibi to assess myocardial perfusion and of 111In-labeled stem cells to delineate stem cell engraftment. Methods Three to 4 million rat embryonic cardiomyoblasts (H9c2 cells) were labeled with 11.1–14.8 MBq (0.3–0.4 mCi) of 111In-oxyquinoline and then injected into the border zones of infarcted myocardium of rats. 111In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h after the stem cells were injected into the infarcted myocardium. To visualize the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of 99mTc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope pinhole SPECT was used to image 99mTc-sestamibi uptake simultaneously with 111In to delineate retention of 111In-labeled stem cells. The presence of labeled stem cells was confirmed by autoradiography and histology. Results SPECT of 99mTc-sestamibi was used to delineate perfusion deficits and infarcted myocardium. Bull's-eye plots indicated that the 111In signal from the labeled stem cells overlapped the perfusion deficits identified from the 99mTc-sestamibi images. The 111In signal associated with the radiolabeled stem cells could be detected with SPECT of the heart for 96 h after engraftment. Conclusion This study demonstrated the feasibility of using dual-isotope pinhole SPECT for high-resolution detection of perfusion deficits with 99mTc-sestamibi and with 111In-labeled stem cells grafted into the region of the infarct. PMID:15872356

  19. A "second window of protection" occurs 24 h after ischemic preconditioning in the rat heart.

    PubMed

    Yamashita, N; Hoshida, S; Taniguchi, N; Kuzuya, T; Hori, M

    1998-06-01

    We and others found that cardioprotection is acquired not only soon after, but also 24 h after ischemic preconditioning in canine and rabbit myocardial infarction models (second window of protection). However, a second window phenomenon against myocardial infarction was dependent on species limitations and has not been observed in porcine hearts. In this study, we examined whether the "second window of protection" against myocardial infarction is observed in the rat heart. In the ischemic preconditioning (IP) group, the left main coronary artery (LCA) of rats was occluded four times for 3 min. each separated by reperfusion for 10 min. After 0, 3, and 24 h, the rats were subjected to a 20-min LCA occlusion followed by 48-h reperfusion. At 0 and 24 h after IP, infarct size and the incidence of ventricular fibrillation (VF) during ischemia were significantly reduced compared with corresponding sham-operated groups without preconditioning. After 3 h of IP, there were no differences either in the incidence of VF during ischemia or in infarct size. Manganese superoxide dismutase (Mn-SOD) content in ischemic (LCA) region of myocardium significantly increased as compared with that of sham-operated rats 24 h after IP. Treatment with N-2-mercaptopropionyl glycine, an antioxidant and a hydroxyl radical scavenger, during IP abolished the early-phase (0 h after IP) and late-phase (24 h after IP) cardioprotection and the corresponding late increase in Mn-SOD content. These results indicate that a "second window of protection" against myocardial infarction also exists in rat hearts and the induction of an intrinsic scavenger, Mn-SOD, via free radical production during IP may be important in the second window of protection. PMID:9689592

  20. 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

  1. Effect of verapamil on heart rate variability after an acute myocardial infarction. Danish Verapamil Infarction Trial II.

    PubMed

    Vaage-Nilsen, M; Rasmussen, V

    1998-07-01

    Because decreased heart rate variability measured after an acute myocardial infarction (AMI) has been demonstrated to predict subsequent mortality and sudden death, and an efficacy analysis of the Danish Verapamil Infarction Trial II (DAVIT II) demonstrated that long-term postinfarction treatment with verapamil significantly reduced sudden death, the aim of the present substudy was to evaluate the effect of verapamil on heart-rate variability in the time and frequency domain, measured in two 5-minute segments during the day and night. Thirty-eight patients were examined by Holter monitoring, at 1 week, that is, before randomization, and at 1 month after infarction; 22 of the patients were examined 12-16 months after infarction as well. In both treatment groups (verapamil and placebo) no significant alteration of heart rate variability during the day-time was demonstrated from before to after 1 and 12-16 months of treatment. In accord with the known reduction of overall heart rate by verapamil, a significant increase of mean NN interval from before to after 1 (P = 0.0004) and 12-16 months (P = 0.004) of treatment was seen in the verapamil, but not in the placebo, group at night. Parameters generally interpreted as an index of parasympathetic modulation, that is, RMSSD, pNN50, and high-frequency power, increased significantly at 1 month (P = 0.04, P = 0.03, NS, respectively) and 12-16 months (P = 0.03, P = 0.04, P < 0.05) after AMI in the verapamil, but not in the placebo, group. In conclusion, the present study indicates that verapamil shifts the autonomic balance to a vagal preponderance or sympathetic attenuation in the postinfarction period. PMID:9784908

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

    PubMed Central

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

    2015-01-01

    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/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. PMID:26675565

  3. Purinoceptors in the rat heart.

    PubMed Central

    Fleetwood, G.; Gordon, J. L.

    1987-01-01

    The effects of an intracoronary bolus of adenosine triphosphate (ATP), alpha, beta-methylene ATP (APCPP), beta, gamma-methylene ATP (APPCP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine on coronary tone and ventricular myocardial contraction were investigated in the perfused rat heart. Adenine nucleotides, given by bolus injection were negatively inotropic in amounts greater than 3 X 10(-7) mol. The potency order was ATP greater than ADP greater than AMP. Adenosine (less than 1 X 10(-5)mol) had no effect on ventricular myocardial contraction. Adenine nucleotides and adenosine (1 X 10(-10)-1 X 10(-7) mol) reduced coronary tone. The potency order was ATP greater than ADP greater than AMP = adenosine. The ATP analogue APPCP was less active than ATP at reducing coronary tone, and APCPP had no vasodilator effect. This suggests the presence of a P2-purinoceptor, subclass P2Y, which mediates vasodilation. ATP and ADP increased the concentration of prostacyclin (measured as 6-keto prostaglandin F1 alpha) in the perfusate, but only after injection of greater than 3 X 10(-7) mol, suggesting that the vasodilator responses to ATP and ADP were not mediated by prostacyclin. AMP and adenosine had no effect, even at 1 X 10(-5) mol. At a dose of 3 X 10(-9) mol, approximately 40% of ATP and 70% of ADP was converted to AMP and adenosine whilst passing through the heart. The amounts of AMP and adenosine formed, however, were insufficient to account for the vasodilator effects of ATP and ADP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3814919

  4. Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction

    PubMed Central

    Serrano, Rosa; Tejera, Agueda; Ayuso, Eduard; Jimenez, Veronica; Formentini, Ivan; Bobadilla, Maria; Mizrahi, Jacques; de Martino, Alba; Gomez, Gonzalo; Pisano, David; Mulero, Francisca; Wollert, Kai C.; Bosch, Fatima; Blasco, Maria A.

    2016-01-01

    Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI. PMID:25519492

  5. Short-term pretreatment with atorvastatin attenuates left ventricular dysfunction, reduces infarct size and apoptosis in acute myocardial infarction rats

    PubMed Central

    Chen, Tie-Long; Zhu, Guang-Li; He, Xiao-Long; Wang, Jian-An; Wang, Yu; Qi, Guo-An

    2014-01-01

    Background: Atorvastatin showed a number of cardiovascular benefits, however, the role and underlying molecular mechanisms of short-term atorvastatin-mediated protection remain unclear. Methods: 30 rats were randomly divided into 3 groups: sham group, acute myocardial infarction model group and atorvastatin group. The rats of acute myocardial infarction model were established by ligation of the left anterior descending of coronary arteries. Before surgery, rats in the atorvastatin group received 20 mg/kg/d atorvastatin for 7 days in atorvastatin group. After 4 hours of model established, changes in hemodynamics parameters were recorded and myocardial infarct size was achieved by Evans blue-TTC staining. Myocardium apoptosis was evaluated by TUNEL. The expression of FAS, FAS-L, Bcl-2, Bax, p-BAD, Caspase-8 and Caspase-3 in myocardium were examined by Western blot. Results: In the atorvastatin group, left ventricular function was elevated and infarct size was decreased compared with the model group. Moreover, in the atorvastatin group, the cell apoptosis index was reduced in response to myocardial infarction. The expressions of Bcl-2 were increased and Bax, p-BAD, Fas, Fas-L, caspase-8 and caspase-3 in myocardium were decreased in atorvastatin group. Conclusions: Short-term atorvastatin pretreatment restored left ventricular function and limited infarct size in acute myocardial infarction, which were associated with reduction of the apoptosis in myocardium through Bcl-2 and Fas pathway. PMID:25663976

  6. Heart Block in Acute Myocardial Infarction: Prognostic Factors and Role of Transvenous Catheter Pacemaker

    PubMed Central

    Narvas, R. M.; Kilgour, J. M.; Basu, S. K.

    1970-01-01

    A prospective study was carried out to determine the prognostic factors in patients with second-degree and complete heart block following acute myocardial infarction and to re-examine the indications for artificial transvenous pacing. Of the 117 consecutive patients with proved acute myocardial infarction, 15 developed advanced heart block (second degree and complete). The presence of the following factors, either alone or in combinations, were attended with poor prognosis: preceding Stokes-Adams syndrome, cardiogenic shock, congestive heart failure, complications secondary to cardiac arrest, anterior infarction and wide QRS complex. In the nine cases requiring artificial transvenous pacemaker because of Stokes-Adams attacks, congestive heart failure or frequent multifocal ventricular ectopic beats, there were five deaths. The remaining six patients, who were without complications and were not paced, all survived; these patients had normal QRS duration with heart rates above 60 per minute. This study indicates that prophylactic transvenous catheter insertion in acute heart block does not appear justified unless specific indication(s) arise. Postmortem studies revealed significant narrowing of all the major coronary vessels in all five fatalities. The overall mortality in this series of cases of acute heart block was 33%. PMID:5410415

  7. Decreased sulfhydryl groups in the reperfused myocardial tissue of a rat model of myocardial infarction.

    PubMed

    Maezawa, H; Manaka, K; Yamakawa, K; Ogawa, K; Iizuka, M

    1997-02-01

    The aim of this study was to determine whether myocardial injury resulting from temporary ischemia followed by reperfusion can be measured by assaying sulfhydryl groups in the affected tissue of a rat model of myocardial infarction. We studied 3 groups: a control group (n = 6), which underwent surgery without left coronary artery (LCA) ligation; group NoR (n = 9), in which the LCA was ligated for 3 h; and group I + R (n = 7), in which 30 min LCA ligation was followed by 3 h reperfusion. The sulfhydryl group content of myocardial tissue was assayed by measuring the fluorescence produced by incubating heart sections with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM), which binds sulfhydryl groups. The fluorescence intensity (FI) of normal and infarcted myocardium was quantified by our computerized system of microscopic fluorophotometry. Indices such as sulfhydryl group content, the size of the low-FI area [% AREA(lower FI)] and the relative decrease in FI [%FI(decrease)]) in the infarct zone were calculated. Both %AREA(lower FI) and %FI(decrease) were significantly higher in the infarcted zone of animals in NoR and I + R groups than in control animals. Both indices were higher in infarct tissue from animals in the I + R group than in the NoR group. These changes suggest that sulfhydryl group content is significantly reduced in tissue that has been subjected to ischemia-reperfusion. Microscopic fluorophotometry, as defined by DACM staining of myocardial tissue, may help to delineate areas of myocardial reperfusion injury. PMID:9070971

  8. Matrix metalloproteinase inhibition after myocardial infarction: a new approach to prevent heart failure?

    PubMed

    Creemers, E E; Cleutjens, J P; Smits, J F; Daemen, M J

    2001-08-01

    Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular disease, including atherosclerosis, restenosis, dilated cardiomyopathy, and myocardial infarction. Administration of synthetic MMP inhibitors in experimental animal models of these cardiovascular diseases significantly inhibits the progression of, respectively, atherosclerotic lesion formation, neointima formation, left ventricular remodeling, pump dysfunction, and infarct healing. This review focuses on the role of MMPs in cardiovascular disease, in particular myocardial infarction and the subsequent progression to heart failure. MMPs, which are present in the myocardium and capable of degrading all the matrix components of the heart, are the driving force behind myocardial matrix remodeling. The recent finding that acute pharmacological inhibition of MMPs or deficiency in MMP-9 attenuates left ventricular dilatation in the infarcted mouse heart led to the proposal that MMP inhibitors could be used as a potential therapy for patients at risk for the development of heart failure after myocardial infarction. Although these promising results encourage the design of clinical trials with MMP inhibitors, there are still several unresolved issues. This review describes the biology of MMPs and discusses new insights into the role of MMPs in several cardiovascular diseases. Attention will be paid to the central role of the plasminogen system as an important activator of MMPs in the remodeling process after myocardial infarction. Finally, we speculate on the use of MMP inhibitors as potential therapy for heart failure. PMID:11485970

  9. Activation of β1-adrenoceptor triggers oxidative stress mediated myocardial membrane destabilization in isoproterenol induced myocardial infarcted rats: 7-hydroxycoumarin and its counter action.

    PubMed

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

    2016-04-15

    Activation of β1-adrenoceptor stimulates myocardial membrane destabilization in isoproterenol induced rats. Male albino Wistar rats were pre and co-treated with 7-hydroxycoumarin (16mg/kg body weight) daily for 8 days. Myocardial infarction was induced into rats by the subcutaneous administration of isoproterenol (100mg/kg body weight) at an interval of 24h daily for a period of two days (7th and 8th day). The levels/activities of serum cardiac troponin-T, lactate dehydrogenase and the concentrations of heart lipid peroxidation products were significantly increased and the antioxidant status was significantly decreased in isoproterenol induced rats. Furthermore, the activity of sodium/potassium-dependent adenosine triphosphatase was significantly decreased and the activities of calcium and magnesium-dependent adenosine triphosphatases were significantly increased in the heart of isoproterenol induced myocardial infarcted rats. Isoproterenol induced rats also revealed increased concentrations of sodium and calcium and decreased concentrations of potassium in the heart. 7-hydroxycoumarin pre- and co-treatment showed considerable impact on all biochemical parameters assessed. Also, 7-HC greatly reduced the infarct size of the myocardium. The in vitro study confirmed its potent free radical scavenging activity. Thus, the present study revealed that 7-HC attenuates myocardial membrane destabilization by reinstating the activities/levels of adenosine triphosphatases and minerals in isoproterenol induced rats by inhibiting oxidative stress. These effects are attributed to the membrane stabilizing and free radical scavenging properties of 7-hydroxycoumarin. PMID:26930228

  10. Post-Infarct biomaterials, left ventricular remodeling, and heart failure: Is good good enough?

    PubMed Central

    Zouein, Fouad A.; Zgheib, Carlos; Liechty, Kenneth W.; Booz, George W.

    2012-01-01

    Infarct expansion and extension of the border zone play a key role in the progression of heart failure after myocardial infarction. Increased wall stress, along with complex cellular and extracellular changes in the surviving myocardium, underlie these events and contributes to the adverse cardiac remodeling that drives ventricular dilation and progression of heart failure. Recently, there has been much interest in the development of biopolymers that can be injected into the infarcted myocardium in order to increase its stiffness and thus reduce mechanical stress on the surrounding myocardium. Here we discuss the findings of recent animal studies that have noted improvements in contractile function or cardiac remodeling using either natural or synthetic biomaterials, as well as several that did not. Besides offering physical support to the injured myocardium, injectable biomaterials could also serve the purpose of fostering cardiac repair by functioning as a protective scaffold for stem cell or drug delivery. PMID:22612796

  11. Role of Training and Detraining on Inflammatory and Metabolic Profile in Infarcted Rats: Influences of Cardiovascular Autonomic Nervous System

    PubMed Central

    Santana, Aline Alves; Santamarina, Aline Boveto; Oyama, Lila Missae; Caperuto, Érico Chagas; de Souza, Cláudio Teodoro; Barboza, Catarina de Andrade; Rocha, Leandro Yanase; Figueroa, Diego; Mostarda, Cristiano; Irigoyen, Maria Cláudia; Lira, Fábio Santos

    2014-01-01

    The aim of this study was to evaluate the effects of exercise training (ET, 50–70% of VO2 max, 5 days/week) and detraining (DT) on inflammatory and metabolic profile after myocardial infarction (MI) in rats. Male Wistar rats were divided into control (C, n = 8), sedentary infarcted (SI, n = 9), trained infarcted (TI, n = 10; 3 months of ET), and detrained infarcted (DI, n = 11; 2 months of ET + 1 month of DT). After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis), and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI. PMID:25045207

  12. [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. PMID:8745997

  13. High- versus moderate-intensity aerobic exercise training effects on skeletal muscle of infarcted rats.

    PubMed

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

    2013-04-01

    Poor skeletal muscle performance was shown to strongly predict mortality and long-term prognosis in a variety of diseases, including heart failure (HF). Despite the known benefits of aerobic exercise training (AET) in improving the skeletal muscle phenotype in HF, the optimal exercise intensity to elicit maximal outcomes is still under debate. Therefore, the aim of the present study was to compare the effects of high-intensity AET with those of a moderate-intensity protocol on skeletal muscle of infarcted rats. Wistar rats underwent myocardial infarction (MI) or sham surgery. MI groups were submitted either to an untrained (MI-UNT); moderate-intensity (MI-CMT, 60% Vo(2)(max)); or matched volume, high-intensity AET (MI-HIT, intervals at 85% Vo(2)(max)) protocol. High-intensity AET (HIT) was superior to moderate-intensity AET (CMT) in improving aerobic capacity, assessed by treadmill running tests. Cardiac contractile function, measured by echocardiography, was equally improved by both AET protocols. CMT and HIT prevented the MI-induced decay of skeletal muscle citrate synthase and hexokinase maximal activities, and increased glycogen content, without significant differences between protocols. Similar improvements in skeletal muscle redox balance and deactivation of the ubiquitin-proteasome system were also observed after CMT and HIT. Such intracellular findings were accompanied by prevented skeletal muscle atrophy in both MI-CMT and MI-HIT groups, whereas no major differences were observed between protocols. Taken together, our data suggest that despite superior effects of HIT in improving functional capacity, skeletal muscle adaptations were remarkably similar among protocols, leading to the conclusion that skeletal myopathy in infarcted rats was equally prevented by either moderate-intensity or high-intensity AET. PMID:23429866

  14. Quality of life in patients with coronary heart disease after myocardial infarction and with ischemic heart failure

    PubMed Central

    Bellwon, Jerzy; Höfer, Stefan; Rynkiewicz, Andrzej; Gruchała, Marcin

    2015-01-01

    Introduction Quality of life measures are useful when interventions or treatments are indicated for several reasons such as improvement of physical functioning, pain relief, to estimate the effectiveness of therapies or to predict mortality. The aim of the current study was to describe quality of life in patients with stable coronary artery disease, myocardial infarction and heart failure and to evaluate the relationship between depression and health-related quality of life. Material and methods Patients after STEMI, with stable coronary artery disease, and heart failure (n = 332) completed the MacNew Heart Disease Health-related Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale. Results Patients with myocardial infarction had significantly higher scores than patients with stable coronary artery disease or heart failure on the MacNew global scale (p < 0.001) and the physical (p < 0.001), emotional (p < 0.001) and social (p < 0.001) subscales. The anxiety scores were significantly higher in the group of patients with stable coronary artery disease than in patients with myocardial infarction (p < 0.05). The depression scores were significantly higher in patients with heart failure (p < 0.01). Conclusions In patients with stable CAD, anxiety correlated mainly with symptoms, i.e. angina, than with the history of MI. Patients with symptoms of angina react to the illness with anxiety more than depression, whereas patients with heart failure with dyspnea react to the illness with depressive symptoms more than anxiety. In patients after MI and with stable CAD, cognitive-behavioral techniques could be useful to quickly reduce the level of anxiety, while patients with heart failure require long-term support therapy to reduce the risk of depressive symptoms. PMID:27186176

  15. Exercise Training Reduces Cardiac Dysfunction and Remodeling in Ovariectomized Rats Submitted to Myocardial Infarction

    PubMed Central

    de Almeida, Simone Alves; Claudio, Erick Roberto Gonçalves; Mengal, Vinícius Franskoviaky; de Oliveira, Suelen Guedes; 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. PMID:25551214

  16. 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

  17. MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4

    PubMed Central

    Zhou, Chaoyuan; Cui, Qintao; Su, Guobao; Guo, Xiaoliang; Liu, Xiaochen; Zhang, Jie

    2016-01-01

    Background Myocardial infarction affects the health of many people. Post-infarction myocardial fibrosis has attracted much attention, but details of the mechanism remain elusive. In this study, the role of microRNA-208b (miR-208b) in modulating post-infarction myocardial fibrosis and the related mechanism were investigated. Material/Methods A rat model of myocardial infarction induced by ligating the left anterior descending artery was used to analyze the expression and roles of miR-208b by overexpression with the lentivirus vector of pre-miR-208b. Myocardial function was assessed and the expression of fibrosis-related factors type I collagen (COL1) and ACTA2 (alias αSMA) was detected. Myocardial fibroblasts isolated from newborn rats were transfected with luciferase reporter vectors containing wild-type or mutant Gata4 3′ UTR to verify the relationship between Gata4 and miR-208b. We then transfected the specific small interference RNA of Gata4 to detect changes in COL1 and ACTA2. Results miR-208b was down-regulated in hearts of model rats (P<0.01). Overexpressing miR-208b improved myocardial functions, such as reducing the infarction area (P<0.05) and promoting LVEF and LVFS (P<0.01), and inhibited COL1 and ACTA2 (P<0.01). Luciferase reporter assay proved Gata4 to be the direct target of miR-208b, with the target sequence in the 3′UTR. Inhibiting GATA4 resulted in the down-regulation of COL1 and ACTA2, suggesting that the role of miR-208b was achieved via regulating GATA4. Conclusions This study demonstrates the protective function of miR-208b via GATA4 in post-infarction myocardial fibrosis, providing a potential therapeutic target for treating myocardial fibrosis. PMID:27236543

  18. Expression of phospholipase D isozymes in scar and viable tissue in congestive heart failure due to myocardial infarction.

    PubMed

    Dent, Melissa R; Singal, Tushi; Dhalla, Naranjan S; Tappia, Paramjit S

    2004-01-01

    The phospholipase D (PLD) associated with the cardiac sarcolemmal (SL) membrane hydrolyses phosphatidylcholine to produce phosphatidic acid, an important phospholipid signaling molecule known to influence cardiac function. The present study was undertaken to examine PLD isozyme mRNA expression, protein contents and activities in congestive heart failure (CHF) subsequent to myocardial infarction (MI). MI was induced in rats by occlusion of the left anterior descending coronary artery. At 8 weeks after the surgical procedure, hemodynamic assessment revealed that these experimental rats were at a moderate stage of CHF. Semi-quantitative reverse transcriptase-polymerase chain reaction revealed that PLD1 and PLD2 mRNA amounts were unchanged in viable left ventricular (LV) tissue of the failing heart. Furthermore, this technique demonstrated the presence of PLD1 and PLD2 mRNA in the scar tissue. While SL PLD1 and PLD2 protein contents were elevated in the viable LV tissue of the failing heart, SL PLD1 activity was significantly decreased, whereas SL PLD2 activity was significantly increased. On the other hand, although PLD1 protein was undetectable, PLD2 protein and activity were detected in the scar tissue. Our findings suggest that differential changes in PLD isozymes may contribute to the pathophysiology of CHF and may also be involved in the processes of scar remodeling. PMID:15601581

  19. Hypercholesterolaemia exacerbates ventricular remodelling after myocardial infarction in the rat: role of angiotensin II type 1 receptors

    PubMed Central

    Mączewski, M; Mączewska, J; Duda, M

    2008-01-01

    Background and purpose: Diet-induced hypercholesterolaemia exacerbates post-myocardial infarction (MI) ventricular remodelling and heart failure, but the mechanism of this phenomenon remains unknown. This study examined whether worsening of post-MI ventricular remodelling induced by dietary hypercholesterolaemia was related to upregulation of angiotensin II type 1 (AT1) receptor in the rat heart. Experimental approach: MI was induced surgically in rats fed normal or high cholesterol diet. Both groups of rats were then assigned to control, atorvastatin, losartan or atorvastatin+losartan-treated subgroups and followed for 8 weeks. Left ventricular (LV) function was assessed with echocardiography. In isolated hearts, LV pressures were measured with a latex balloon and a tip catheter. AT1-receptor density was assessed in LV membranes with radioligand-binding assays. Key results: High cholesterol diet exacerbated LV dilation and dysfunction in post-MI hearts. Atorvastatin or losartan prevented these hypercholesterolaemia-induced effects, whereas their combination was not more effective than each drug alone. AT1 receptors were upregulated 8 weeks after MI, this was further increased by hypercholesterolaemia and restored to baseline levels by atorvastatin. Conclusions and implications: Hypercholesterolaemia exacerbated LV remodelling and dysfunction in post-MI rat hearts and upregulated cardiac AT1 receptors. All these effects were effectively prevented by atorvastatin. Thus, the pleiotropic statin effects may include interference with the renin-angiotensin system through downregulation of AT1 receptors. PMID:18536757

  20. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models

    PubMed Central

    Arevalo, Hermenegild J.; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C.; Trayanova, Natalia A.

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  1. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models.

    PubMed

    Arevalo, Hermenegild J; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C; Trayanova, Natalia A

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  2. Factors determining case fatality in myocardial infarction "who dies in a heart attack"?

    PubMed Central

    Wannamethee, G.; Whincup, P. H.; Shaper, A. G.; Walker, M.; MacFarlane, P. W.

    1995-01-01

    OBJECTIVE--To examine the determinants of case fatality in the first major ischaemic heart disease event (heart attack) after screening. METHODS--Prospective study of 7735 middle aged men drawn from general practices in 24 British towns. RESULTS--During 11.5 years follow up there were 743 major ischaemic heart disease events of which 302 (40.6%) were fatal within 28 days of onset. Previous definite myocardial infarction or stroke and age at time of event were most strongly associated with case fatality. In men with no previous myocardial infarction or stroke, after adjustment for a range of risk factors, antihypertensive treatment (odds ratio (OR) = 1.97, P < 0.05), arrhythmia (OR = 1.93, P = 0.06), increased heart rate (OR = 2.03, P = 0.06), and diabetes (OR = 2.61, P = 0.07) were associated with increased case fatality. High levels of physical activity (OR = 0.53, P < 0.05) and moderate drinking (16-42 units/week) (OR = 0.61, P < 0.05) were associated with lower case fatality, although moderate drinking was not associated with a lower incidence of major ischaemic heart disease events. Current smoking, serum total cholesterol, and systolic blood pressure were not significantly associated with case fatality. In men with previous myocardial infarction or stroke, arrhythmia and to a lesser degree antihypertensive treatment, moderate or heavy drinking, and diabetes were associated with higher case fatality. CONCLUSION--These findings suggest that physical activity may be an important modifiable factor influencing the incidence of ischaemic heart disease and the chance of survival in men without a previous heart attack or stroke. Arrhythmia, increased heart rate, diabetes, and treatment for hypertension are also areas of concern. PMID:7547031

  3. 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. PMID:26423303

  4. Prenatal cocaine exposure increases apoptosis of neonatal rat heart and heart susceptibility to ischemia–reperfusion injury in 1-month-old rat

    PubMed Central

    Bae, Soochan; Zhang, Lubo

    2005-01-01

    Maternal cocaine administration during pregnancy increased apoptosis in near-term fetal rat heart. The present study tested the hypothesis that prenatal cocaine exposure increases the heart susceptibility to ischemia/reperfusion injury in the offspring. Pregnant Sprague–Dawley rats received cocaine (30 mg kg−1 day−1) or saline from days 15 to 21 of gestational age. Maternal body weights were not significantly different at the end of cocaine treatment, but body weights of offspring were decreased slightly at ages of 1, 3, and 7 days. Although heart-to-body weight ratio was not affected at all ages examined, prenatal cocaine significantly increased left ventricular myocyte size at an age of 30 days. Additionally, prenatal cocaine increased DNA fragmentation measured in the hearts isolated from offspring of 1, 3, 7, and 21 days, but not of 30 days, with the peak at 3-day neonates. Antiapoptotic (Bcl-2 and Bcl-XL) and proapoptotic (Bax and Bad) proteins were expressed in neonatal rat hearts of both groups. Prenatal cocaine exposure decreased levels of Bcl-2 in 21-day and increased Bax in 21- and 30-day rat hearts. In addition, hearts of 30-day-old male progeny were studied using the Langendorff preparation, and were subjected to 25 min of ischemia and 60 min of reperfusion. Preischemic baseline values of left ventricular (LV) function were the same between the two groups. However, prenatal cocaine exposure significantly attenuated postischemic recovery of LV function, and significantly increased elevated LV end diastolic pressure during reperfusion. This was associated with a significant increase in ischemia/reperfusion-induced LV myocardial infarct size. The results suggest that prenatal cocaine exposure induces abnormal apoptosis and myocyte hypertrophy in postnatal heart, leading to an increased heart susceptibility to ischemic insults in postnatal life. PMID:15685203

  5. Inhibition of the nitric oxide/cyclic guanosine monophosphate pathway limited the cardioprotective effect of post-conditioning in hearts with apical myocardial infarction.

    PubMed

    Correa, Francisco; Buelna-Chontal, Mabel; Chagoya, Victoria; García-Rivas, Gerardo; Vigueras, Rosa María; Pedraza-Chaverri, José; García-Niño, Wylly Ramsés; Hernández-Pando, Rogelio; León-Contreras, Juan Carlos; Zazueta, Cecilia

    2015-10-15

    Reperfusion damage involves opening of the mitochondrial permeability transition pore (mPTP) and loss of ATP synthesis. Several cardioprotective pathways are activated by ischemic or pharmacological post-conditioning (PC). The mechanisms that are activated by PC in no co-morbidity murine models include: activation of rescue kinases, oxidative stress reduction, glycolytic flux regulation and preservation of ATP synthesis. However, relatively scarce efforts have been made to define whether the efficacy of PC signaling is blunted by risk factors or systemic diseases associated with ischemic heart pathology. Experimental evidence has shown that the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling is a main mechanism activated by PC in hearts without pathological history. In this work we evaluated the participation of the NO pathway, through downstream kinase activation and inhibition of mPTP in hearts with previous infarct. Myocardial infarction was induced with a single dose of isoproterenol (85 mg/kg i.p.) to male Wistar rats. After 24 h, the hearts were mounted into the Langendorff system and subjected to 30 min of ischemia and 60 min of reperfusion. PC consisted of 5 cycles of 30 s of reperfusion/30 s of ischemia, then the hearts were reperfused with or without inhibitors of the NO/cGMP pathway. PC activates the NO/cGMP pathway, as increased cGMP and NO levels were detected in isoproterenol-treated hearts. The cardioprotective effect of PC was abolished with both L-NAME (inhibitor of constitutive NO synthase) and ODQ (inhibitor of soluble guanylate cyclase), whereas the NO donor (DETA-NO) restored cardioprotection even in the presence of L-NAME or ODQ. We also found that mitochondrial structure and function was preserved in PC hearts. We conclude that PC exerts cardioprotection in hearts with previous infarct by maintaining mitochondrial structure and function through NO-dependent pathway. PMID:26387613

  6. [Comparative cytophotometric analysis of the nucleic acid content in the cardiomyocytes of normal rats and following experimental infarct].

    PubMed

    Selivanova, G V; Nilova, V K; Vlasova, T D; Bushmarina, M S; Rumiantsev, P P

    1988-12-01

    The cytophotometrical investigation of gallocyanine-chrome alum stained cardiac muscle cells allows to ascertain that a mean content of the nucleic acids calculated for a single nucleus is essentially higher in the left ventricle myocytes in comparison with the left auricle cells of healthy adult rats. These values in 1-, 2- and 3-nuclear cells of the ventricle are, respectively, 21.3, 19.3, and 18.0, and 14.1, 13.7, 13.5 of arbitrary units (a. u.) in the auricle cells. A difference in cytoplasmic RNA contents of the same cells is more significant, these values are 65.7, 116.4, and 158.9 a. u. in ventricle myocytes, and 33.4, 60.8 and 95.2 a. u. in auricle cells. The nucleic acids content in the nuclei and RNA content in the cytoplasm increase with the development of proliferation in myocytes after experimental myocardial infarction. A relative increase in the nucleic acids content in the nuclei of the same cell types reaches 50, 24, and 10% 11 days after infarction and 56, 38, and 45% 31 days after infarction. A relative increase in cytoplasmic RNA of the same cells reaches, respectively, 52, 17, and 25%, and 70, 57, and 53% 11 and 31 days after infarction. These findings evidence on the greatest synthetic activity of the single-nuclear auricle muscle cells in the process of heart restoration after infarction. PMID:2470177

  7. Comparison of cardioprotective effects using ramipril and DanShen for the treatment of acute myocardial infarction in rats.

    PubMed

    Ji, XinYan; Tan, Benny K-H; Zhu, Yi Chun; Linz, Wolfgang; Zhu, Yi Zhun

    2003-08-01

    In the present study, we compared cardioprotective effects of DanShen (an extract from Salvia miltiorrhiza) and the angiotensin-converting enzyme inhibitor, ramipril, in rats. With both treatment regimens, DanShen- and ramipril similar effects were observed: (1) a higher survival rate, (2) a significant reduction of infarct size, (3) significantly lower ratios of heart weight to the body weight as well as the left and right ventricular weights to body weight. DanShen showed some unique effects in the following aspects: (1) higher activities of antioxidant defense enzymes such as superoxide dismutase (SOD), catalase (CAT), glutatione perioxidase (GSH-Px) and glutathione S-transferase (GST) in the liver of rats with acute myocardial infarction (AMI), (2) lower myocardial and hepatic TBARS values; (3) augmented VEGF mRNA expressions in the non-ischemic parts of rat hearts with AMI. These results were consistent with the findings of a slight increase in myocardial capillary density and the special distribution pattern of coronary blood vessels in DanShen-treated rats. PMID:12850502

  8. Anti-Inflammatory Effects of the Chinese Herbal Formula Sini Tang in Myocardial Infarction Rats

    PubMed Central

    Liu, Jiangang; Peter, Karoline; Shi, Dazhuo; Zhang, Lei; Dong, Guoju; Zhang, Dawu; Breiteneder, Heimo; Bauer, Rudolf; Ma, Yan

    2014-01-01

    The aim of this study was to evaluate the anti-inflammatory profiling of the Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a decoction consisting of four herbs: Aconitum carmichaelii, Cinnamomum cassia, Zingiber officinale, and Glycyrrhiza uralensis, was characterized as a remedy to treat syndromes corresponding to heart failure and MI in China. Potential biomarkers, which reflect the extent of myocardial necrosis and correlate with cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β (TNF-α, IL-6, and IL-1β) were determined in plasma, serum, and in myocardial tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased significantly the levels of hs-CRP, TNF-α, IL-6, and IL-1β in MI rats. SNT decreased the expression of ANP levels in plasma and increased the vascular active marker nitric oxide, which limits vascular inflammation. In addition, SNT could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our data suggest that the Chinese herbal formula SNT has the potential to improve cardiac function after MI. SNT may be a candidate for treating MI and its associated inflammatory responses. PMID:24723959

  9. Trajectories of risk after hospitalization for heart failure, acute myocardial infarction, or pneumonia: retrospective cohort study

    PubMed Central

    Hsieh, Angela F; Kulkarni, Vivek T; Lin, Zhenqiu; Ross, Joseph S; Horwitz, Leora I; Kim, Nancy; Suter, Lisa G; Lin, Haiqun; Normand, Sharon-Lise T; Krumholz, Harlan M

    2015-01-01

    Objective To characterize the absolute risks for older patients of readmission to hospital and death in the year after hospitalization for heart failure, acute myocardial infarction, or pneumonia. Design Retrospective cohort study. Setting 4767 hospitals caring for Medicare fee for service beneficiaries in the United States, 2008-10. Participants More than 3 million Medicare fee for service beneficiaries, aged 65 years or more, surviving hospitalization for heart failure, acute myocardial infarction, or pneumonia. Main outcome measures Daily absolute risks of first readmission to hospital and death for one year after discharge. To illustrate risk trajectories, we identified the time required for risks of readmission to hospital and death to decline 50% from maximum values after discharge; the time required for risks to approach plateau periods of minimal day to day change, defined as 95% reductions in daily changes in risk from maximum daily declines after discharge; and the extent to which risks are higher among patients recently discharged from hospital compared with the general elderly population. Results Within one year of hospital discharge, readmission to hospital and death, respectively, occurred following 67.4% and 35.8% of hospitalizations for heart failure, 49.9% and 25.1% for acute myocardial infarction, and 55.6% and 31.1% for pneumonia. Risk of first readmission had declined 50% by day 38 after hospitalization for heart failure, day 13 after hospitalization for acute myocardial infarction, and day 25 after hospitalization for pneumonia; risk of death declined 50% by day 11, 6, and 10, respectively. Daily change in risk of first readmission to hospital declined 95% by day 45, 38, and 45; daily change in risk of death declined 95% by day 21, 19, and 21. After hospitalization for heart failure, acute myocardial infarction, or pneumonia, the magnitude of the relative risk for hospital admission over the first 90 days was 8, 6, and 6 times greater than that

  10. Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: role of NO.

    PubMed

    Asanuma, Hiroshi; Sanada, Shoji; Asakura, Masanori; Asano, Yoshihiro; Kim, Jiyoong; Shinozaki, Yoshiro; Mori, Hidezo; Minamino, Tetsuo; Takashima, Seiji; Kitakaze, Masafumi

    2014-08-01

    Carperitide is effective for heart failure (HF) owing to its diuretic and vasodilatory effects. This recombinant peptide may also have direct cardioprotective effects because carperitide reduces the severity of heart failure and limits infarct size. Because coronary vasodilation is an important cardioprotective treatment modality, we investigated whether carperitide increased coronary blood flow (CBF) and improved myocardial metabolic and contractile dysfunction during ischemia in canine hearts. We also tested whether carperitide is directly responsible for limiting the infarct size. We infused carperitide at 0.025-0.2 μg kg(-1) min(-1) into the canine coronary artery. A minimum dose of 0.1 μg kg(-1) min(-1) was required to obtain maximal vasodilation. To test the effects of carperitide on ischemic hearts, we reduced perfusion pressure in the left anterior descending coronary artery such that CBF decreased to one-third of the baseline value. At 10 min after carperitide was infused at a dose of 0.1 μg kg(-1) min(-1), we observed increases in CBF, fractional shortening (FS) and pH levels in coronary venous blood without concomitant increases in cardiac nitric oxide (NO) levels; these changes were attenuated using either the atrial natriuretic peptide receptor antagonist HS-142-1 or the NO synthase inhibitor L(ω)-nitroarginine methyl ester (L-NAME). Cyclic guanosine monophosphate (GMP) levels in the coronary artery were elevated in response to carperitide that also limited the infarct size after 90 min of ischemia and subsequent reperfusion. Again, these effects were blunted by L-NAME. Carperitide increases CBF, reduces myocardial contractile and metabolic dysfunction and limits infarct size. In addition, NO is necessary for carperitide-induced vasodilation and cardioprotection in ischemic hearts. PMID:24694647

  11. Long-Term Left Ventricular Remodelling in Rat Model of Nonreperfused Myocardial Infarction: Sequential MR Imaging Using a 3T Clinical Scanner

    PubMed Central

    Saleh, Muhammad G.; Sharp, Sarah-Kate; Alhamud, Alkathafi; Spottiswoode, Bruce S.; van der Kouwe, Andre J. W.; Davies, Neil H.; Franz, Thomas; Meintjes, Ernesta M.

    2012-01-01

    Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI. PMID:23118511

  12. Control of ribosome formation in rat heart

    SciTech Connect

    Russo, L.A.

    1987-01-01

    Diabetes of 9 days duration produced a 17% diminution in the rate of total protein synthesis in rat hearts perfused as Langendorff preparations supplied with glucose, plasma levels of amino acids, and 400 ..mu..U/ml insulin. This reduction was attributable to a decrease in efficiency of protein synthesis and total RNA content. Total messenger RNA content decreased in diabetic hearts in proportion to the reduction in total RNA. Diabetes also resulted in diminished ribosome content as reflected by the induction in total RNA. Ribosome production was investigated by monitoring incorporation of (/sup 3/H)phenylalanine into the proteins of cytoplasmic ribosomes. Rates of ribosome formation in diabetic hearts were as fast as control rates in the presence of insulin, and were faster than control rates in the absence of the hormone. These results indicated that ribosome content fell in diabetic hearts despite unchanged or faster rates of ribosome formation.

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

    PubMed

    Frączek, Magdalena M Aria; 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. PMID:27403906

  14. 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

  15. Local delivery of soluble TNF-alpha receptor 1 gene reduces infarct size following ischemia/reperfusion injury in rats.

    PubMed

    Sugano, Masahiro; Hata, Tomoji; Tsuchida, Keiko; Suematsu, Nobuhiro; Oyama, Jun-Ichi; Satoh, Shinji; Makino, Naoki

    2004-11-01

    Apoptosis in the myocardium is linked to ischemia/reperfusion injury, and TNF-alpha induces apoptosis in cardiomyocytes. A significant amount of TNF-alpha is detected after ischemia and reperfusion. Soluble TNF-alpha receptor 1 (sTNFR1) is an extracellular domain of TNF-alpha receptor 1 and is an antagonist to TNF-alpha. In the present study, we examined the effects of sTNFR1 on infarct size in acute myocardial infarction (AMI) following ischemia/reperfusion. Male Wistar rats were subjected to left coronary artery (LCA) ligation. After 30 min of LCA occlusion, the temporary ligature on the LCA was released and blood flow was restored. Immediately after reperfusion, a total of 200 microg of sTNFR1 or LacZ plasmid was injected into three different sites of the left ventricular wall. At 6 h, 1 and 2 days after reperfusion, the TNF-alpha bioactivity in the myocardium was significantly higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase in the TNF-alpha bioactivity. The sTNFR1 plasmid significantly reduced DNA fragmentation and caspase activity compared to the LacZ plasmid. Finally, the sTNFR1 expression-plasmid treatment significantly reduced the area of myocardial infarction at 2 days after ischemia/reperfusion compared to LacZ plasmid. In conclusion, the TNF-alpha bioactivity in the heart increased from the early stage of ischemia/reperfusion, and this increase was thought to contribute in part to the increased area of myocardial infarction. Suppression of TNF-alpha bioactivity with the sTNFR1 plasmid reduced the infarct size in AMI following ischemia and reperfusion. PMID:15646033

  16. 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. PMID:25743572

  17. Statin and Resveratrol in Combination induces Cardioprotection against Myocardial Infarction in Hypercholesterolemic Rat

    PubMed Central

    Penumathsa, Suresh Varma; Thirunavukkarasu, Mahesh; Koneru, Srikanth; Juhasz, Bela; Zhan, Lijun; Pant, Rima; Menon, Venugopal P; Otani, Hajime; Maulik, Nilanjana

    2007-01-01

    Hypercholesterolemia (HC) is a common health problem that significantly increases risk of cardiovascular disease. Both statin (S) and resveratrol (R) demonstrated cardioprotection through nitric oxide dependent mechanism. Therefore the present study was undertaken to determine whether combination therapy with statin and resveratrol are more cardioprotective than individual treatment groups in ischemic rat heart model. The rats were fed rats with 2% high cholesterol diet and after 8 weeks of high cholesterol diet the animals were treated with statin (1mg/kg bw/day) and resveratrol (20mg/kg bw/day) for 2 weeks. The rats were assigned to: 1) Control (C) 2) HC 3) HCR 4) HCS and 5) HCRS. The hearts, subjected to 30 min global ischemia followed by 120 min reperfusion were used as experimental model. The left ventricular functional recovery (+dp/dt) was found to be significantly better in the HCRS (1926±43), HCR (1556±65) and HCS (1635±40) compared to HC group (1127±16). The infarct size in the HCRS, HCS and HCR groups were 37±3.6, 43±3.3 and 44±4.2 respectively compared to 53±4.6 in HC. The lipid level was found to be decreased in all the treatment groups when compared to HC more significantly in HCS and HCRS groups when compared to HCR. Increased phosphorylation of Akt and eNOS was also observed in all the treatment groups resulting in decreased extent of cardiomyocyte apoptosis but the extent of reduction in apoptosis was more significant in HCRS group compared to all other groups. In-vivo rat myocardial infarction (MI) model subjected to one week of permanent left descending coronary artery (LAD) occlusion documented increased capillary density in HCR and HCRS treated group when compared to HCS treatment group. We also documented increased β-catenin translocation and increased VEGF mRNA expression in all treatment groups. Thus, we conclude that the acute as well as chronic protection afforded by combination treatment with statin and resveratrol may be due to

  18. Characterization of mitochondria isolated from normal and ischemic hearts in rats utilizing atomic force microscopy.

    PubMed

    Lee, Gi-Ja; Chae, Su-Jin; Jeong, Jae Hoon; Lee, So-Ra; Ha, Sang-Jin; Pak, Youngmi Kim; Kim, Weon; Park, Hun-Kuk

    2011-04-01

    Mitochondria play critical roles in both the life and the death of cardiac myocytes. Various factors, such as the loss of ATP synthesis and increase of ATP hydrolysis, impairment in ionic homeostasis, formation of reactive oxygen species (ROS), and release of proapoptotic proteins are related to the generation of irreversible damage. It has been proposed that the release of cytochrome c is caused by a swelling of the mitochondrial matrix triggered by the apoptotic stimuli. However, there is a controversy about whether or not the mitochondria, indeed, swell during apoptosis. The major advantages of atomic force microscopy (AFM) over conventional optical and electron microscopes for bio-imaging include the fact that no special coating and vacuum are required and imaging can be done in all environments--air, vacuum or aqueous conditions. In addition, AFM force-distance curve measurements have become a fundamental tool in the fields of surface chemistry, biochemistry, and material science. In this study, we used AFM to observe the morphological and property changes in heart mitochondria that were isolated from a rat myocardial infarction model. From the shape parameters of the mitochondria in the AFM topographic image, it seemed that myocardial infarction caused the mitochondrial swelling. Also, the results of force-distance measurements showed that the adhesion force of heart mitochondria was significantly decreased by myocardial in infarction. Therefore, we suggested that myocardial infarction might be the cause of mitochondrial swelling and the changes in outer membrane of heart mitochondria. PMID:21050769

  19. Advanced Heart Block During Acute Myocardial Infarction Treated with an Electrode Pacing Catheter

    PubMed Central

    Peretz, Dwight I.

    1967-01-01

    The mortality rate is high from advanced atrioventricular block associated with acute myocardial infarction. There is reason to believe that if in these patients the hearts are electrically paced with an endocardial pacing catheter, the mortality rate can be considerably decreased. Five patients in second- and third-degree heart block associated with acute myocardial infarction were paced with a considerable lowering of the expected mortality rate. Twenty-three cases from the literature are also presented and discussed. A silastic bipolar electrode catheter was used in these five cases. Four of the five cases returned to normal sinus rhythm within the first 10 days. The average duration of pacing was 6.7 days. It is the opinion of the author that second- and third-degree heart block associated with acute myocardial infarction should have a pacing catheter introduced at the earliest possible moment for continuous or demand endocardial pacing. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:6019960

  20. Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury.

    PubMed

    Hedegaard, Elise R; Johnsen, Jacob; Povlsen, Jonas A; Jespersen, Nichlas R; Shanmuganathan, Jeffrey A; Laursen, Mia R; Kristiansen, Steen B; Simonsen, Ulf; Bøtker, Hans Erik

    2016-04-01

    The voltage-gated KV7 (KCNQ) potassium channels are activated by ischemia and involved in hypoxic vasodilatation. We investigated the effect of KV7 channel modulation on cardiac ischemia and reperfusion injury and its interaction with cardioprotection by ischemic preconditioning (IPC). Reverse-transcription polymerase chain reaction revealed expression of KV7.1, KV7.4, and KV7.5 in the left anterior descending rat coronary artery and all KV7 subtypes (KV7.1-KV7.5) in the left and right ventricles of the heart. Isolated hearts were subjected to no-flow global ischemia and reperfusion with and without IPC. Infarct size was quantified by 2,3,5-triphenyltetrazolium chloride staining. Two blockers of KV7 channels, XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone] (10 µM) and linopirdine (10 µM), reduced infarct size and exerted additive infarct reduction to IPC. An opener of KV7 channels, flupirtine (10 µM) abolished infarct size reduction by IPC. Hemodynamics were measured using a catheter inserted in the left ventricle and postischemic left ventricular recovery improved in accordance with reduction of infarct size and deteriorated with increased infarct size. XE991 (10 µM) reduced coronary flow in the reperfusion phase and inhibited vasodilatation in isolated small branches of the left anterior descending coronary artery during both simulated ischemia and reoxygenation. KV7 channels are expressed in rat coronary arteries and myocardium. Inhibition of KV7 channels exerts cardioprotection and opening of KV7 channels abrogates cardioprotection by IPC. Although safety issues should be further addressed, our findings suggest a potential role for KV7 blockers in the treatment of ischemia-reperfusion injury. PMID:26869667

  1. Blueberry-Enriched Diet Protects Rat Heart from Ischemic Damage

    PubMed Central

    Ahmet, Ismayil; Spangler, Edward; Shukitt-Hale, Barbara; Juhaszova, Magdalena; Sollott, Steven J.; Joseph, James A.; Ingram, Donald K.; Talan, Mark

    2009-01-01

    Objectives to assess the cardioprotective properties of a blueberry enriched diet (BD). Background Reactive oxygen species (ROS) play a major role in ischemia-related myocardial injury. The attempts to use synthetic antioxidants to block the detrimental effects of ROS have produced mixed or negative results precipitating the interest in natural products. Blueberries are readily available product with the highest antioxidant capacity among fruits and vegetables. Methods and Results Following 3-mo of BD or a regular control diet (CD), the threshold for mitochondrial permeability transition (tMPT) was measured in isolated cardiomyocytes obtained from young male Fischer-344 rats. Compared to CD, BD resulted in a 24% increase (p<0.001) of ROS indexed tMPT. The remaining animals were subjected to a permanent ligation of the left descending coronary artery. 24 hrs later resulting myocardial infarction (MI) in rats on BD was 22% less than in CD rats (p<0.01). Significantly less TUNEL(+) cardiomyocytes (2% vs 9%) and 40% less inflammation cells were observed in the myocardial area at risk of BD compared to CD rats (p<0.01). In the subgroup of rats, after coronary ligation the original diet was either continued or switched to the opposite one, and cardiac remodeling and MI expansion were followed by serial echocardiography for 10 weeks. Measurements suggested that continuation of BD or its withdrawal after MI attenuated or accelerated rates of post MI cardiac remodeling and MI expansion. Conclusion A blueberry-enriched diet protected the myocardium from induced ischemic damage and demonstrated the potential to attenuate the development of post MI chronic heart failure. PMID:19536295

  2. Late prognostic value of scintigraphic parameters of acute myocardial infarction size in complicated myocardial infarction without heart failure

    SciTech Connect

    Botvinick, E.H.; Perez-Gonzalez, J.F.; Dunn, R.; Ports, T.; Chatterjee, K.; Parmley, W.

    1983-04-01

    Perfusion scintigraphy with thallium-201, infarct scintigraphy with technetium-99m pyrophosphate (TcPYP), and equilibrium blood pool scintigraphy were performed during the initial hospitalization for acute myocardial infarction (MI) in 25 patients without evidence of heart failure who presented with advanced electrocardiographic rhythm and conduction disturbances requiring treatment. Scintigraphic findings during short-term hospitalization were related to the late clinical follow-up performed an average of 14 months later, where patients were grouped as asymptomatic, 8 patients; symptomatic, 9 patients; and deceased, 8 patients. Quantitation of perfusion abnormalities, TcPYP image abnormalities, and left ventricular ejection fraction (EF) revealed that the deceased group had significantly larger TcPYP abnormalities (36 +/- 20 cm2), absolute perfusion abnormalities (32 +/- 16 cm2), and perfusion abnormalities expressed as a percentage of the projected left ventricular area (42 +/- 8%) than the asymptomatic group (13 +/- 8 cm2, 14 +/- 6 cm2, and 20 +/- 9%; p less than 0.05, p greater than 0.05, and p less than 0.01, respectively). The percent perfusion abnormality was significantly larger in the deceased group (42 +/- 8%, p less than 0.01) than in either the symptomatic group (35 +/- 13%, p less than 0.01) or the asymptomatic group (20 +/- 9%), and this parameter in the symptomatic group also differed from that in the asymptomatic group (p less than 0.01). The study indicates that patients with rhythm and conduction disturbances and without congestive heart failure during acute MI may follow an uncomplicated or a complicated late clinical course. Early scintigraphic measurements of MI and perfusion correlate well with this outcome; however, EF could not differentiate among prognostic subgroups.

  3. hHGF Overexpression in Myoblast Sheets Enhances Their Angiogenic Potential in Rat Chronic Heart Failure

    PubMed Central

    Siltanen, Antti; Kitabayashi, Katsukiyo; Lakkisto, Päivi; Mäkelä, Johanna; Pätilä, Tommi; Ono, Masamichi; Tikkanen, Ilkka; Sawa, Yoshiki; Kankuri, Esko; Harjula, Ari

    2011-01-01

    After severe myocardial infarction (MI), heart failure results from ischemia, fibrosis, and remodeling. A promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in MI is myoblast sheet transplantation. We hypothesized that in a rat model of MI-induced chronic heart failure, this therapy could be further improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF) in the myoblast sheets. We studied the ability of wild type (L6-WT) and human HGF-expressing (L6-HGF) L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression profiles by use of microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD) ligation and allowed heart failure to develop for 4 weeks. Thereafter, we administered L6-WT (n = 15) or L6-HGF (n = 16) myoblast sheet therapy. Control rats (n = 13) underwent LAD ligation and rethoracotomy without therapy, and five rats underwent a sham operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy, and analyzed cardiac angiogenesis and left ventricular architecture from histological sections at 4 weeks. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further enhanced by h

  4. 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

  5. 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

    2015-01-01

    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

  6. 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. PMID:26748814

  7. 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

  8. Low-Dose Bisphenol A and Estrogen Increase Ventricular Arrhythmias Following Ischemia-Reperfusion in Female Rat Hearts

    PubMed Central

    Yan, Sujuan; Song, Weizhong; Chen, Yamei; Hong, Kui; Rubinstein, Jack; Wang, Hong-Sheng

    2013-01-01

    Bisphenol A (BPA) is an environmental estrogenic endocrine disruptor that may have adverse health impacts on a range of tissue/systems. In previous studies, we reported that BPA rapidly promoted arrhythmias in female rodent hearts through alteration of myocyte calcium handling. In the present study we investigated the acute effects of BPA on ventricular arrhythmias and infarction following ischemia-reperfusion in rat hearts. Rat hearts were subjected to 20 minutes of global ischemia followed by reperfusion. In female, but not male hearts, acute exposure to 1 nM BPA, either alone or combined with 1 nM 17β-estradiol (E2), during reperfusion resulted in a marked increase in the duration of sustained ventricular arrhythmias. BPA plus E2 increased the duration ventricular fibrillation, and the duration of VF as a fraction of total duration of sustained ventricular arrhythmia. The pro-arrhythmic effects of estrogens were abolished by MPP combined with PHTPP, suggesting the involvements of both ERα and ERβ signaling. In contrast to their pro-arrhythmic effects, BPA and E2 reduced infarction size, agreeing with previously described protective effect of estrogen against cardiac infarction. In conclusion, rapid exposure to low dose BPA, particularly when combined with E2, exacerbates ventricular arrhythmia following IR injury in female rat hearts. PMID:23429042

  9. SRF binding to SRE in the rat heart: influence of age.

    PubMed

    Lu, X G; Azhar, G; Liu, L; Tsou, H; Wei, J Y

    1998-01-01

    One important promoter element at the 5' end of the c-fos gene is the serum response element (SRE). SRE is the site of attachment of the 67-kDa protein serum response factor (SRF) and several accessory proteins (Elk1, SAP1, SAP2/NET), termed the ternary complex factors. The binding of SRF to SRE plays an integral role in c-fos transcription and may occur independently of the association of the ternary complex factors. In the current study, we found that SRF protein expression was increased in the hearts of the old vs young adult rats in the basal condition. The hearts of old rats may have posttranslationally modified SRF proteins that are different compared to that of the young adults. The SRF increase was present both in the cytoplasm as well as in the nucleus in the old hearts. To test whether SRF protein levels in response to acute stress might be altered with age, we studied hearts of young adult and old rats during myocardial infarction. The young adult rat hearts responded to acute ischemic stress with an increase in both p62 and p67 SRF. The hearts of the old rats, however, did not exhibit a significant change in SRF protein expression. These findings demonstrate qualitative as well as quantitative age differences in SRF protein levels, both at baseline and following stimulation. The reduced SRF expression in response to acute cardiac ischemic stress in the old rats might contribute to the observed age-related decrease in the induction of immediate early genes such as c-fos in the heart. PMID:9467416

  10. Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure

    PubMed Central

    2013-01-01

    Background Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. The aim of this study was to investigate gene expression in the LV and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs). Methods MI was induced in rats by ligation of the proximal left coronary artery. Rats with small, moderate, and large MI size were included into the experiment two months after the operation. The development of heart failure was estimated by echocardiography and catheterization. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals. Results Only rats with a large MI developed extensive LV remodeling and heart failure. 840 transcripts were altered in LV of failing hearts, and especially numerous were those associated with the extracellular matrix. In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury. We showed that ceruloplasmin was similarly overexpressed in the heart and blood in response to HF, whereas downregulation of tetraspanin 12 was significant only in the PBMCs. Conclusion A large size of infarcted area is critical for progression of LV remodeling and HF development, associated with altered gene expression in the heart. Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs. PMID:24206753

  11. MALDI Mass Spectrometric Imaging of Cardiac Tissue Following Myocardial Infarction in a Rat Coronary Artery Ligation Model

    PubMed Central

    Menger, Robert F.; Stutts, Whitney L.; Anbukumar, Dhanam S.; Bowden, John A.; Ford, David A.; Yost, Richard A.

    2011-01-01

    Although acute myocardial infarction (MI) is consistently among the top causes of death in the United States, the spatial distribution of lipids and metabolites following MI remains to be elucidated. This work presents the investigation of an in vivo rat model of MI using mass spectrometric imaging (MSI) and multivariate data analysis. MSI was conducted on cardiac tissue following a 24-hour left anterior descending coronary artery ligation in order to analyze multiple compound classes. First, the spatial distribution of a small metabolite, creatine, was used to identify areas of infarcted myocardium. Second, multivariate data analysis and tandem mass spectrometry were used to identify phospholipid (PL) markers of MI. A number of lysophospholipids demonstrated increased ion signal in areas of infarction. In contrast, select intact PLs demonstrated decreased ion signal in the area of infarction. The complementary nature of these two lipid classes suggest increased activity of phospholipase A2, an enzyme that has been implicated in coronary heart disease and inflammation. PMID:22141424

  12. FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post-Myocardial Infarction Rats.

    PubMed

    Xi, Yue; Gong, Da-Wei; Tian, Zhenjun

    2016-01-01

    Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI), but the underlying mechanisms are poorly understood. Follistatin-like1 (FSTL1) is a cardioprotective factor against ischemic injury and is induced in cardiomyocytes and skeletal muscle in ischemic and hypoxic conditions. To test the hypothesis that FSTL1 may be a molecular link between exercise and improved heart function post MI, we subjected MI-rats, induced by left coronary artery ligation, to two modes of exercise: intermittent aerobic exercise (IAE) or mechanical vibration training (MVT), for four weeks and examined the relevance of FSTL1 to exercise-mediated cardiac effects. Exercise improved the functional performance, reduced fibrosis of MI-hearts and induced FSTL1 expression, the TGFβ-Smad2/3 signaling and angiogenesis in myocardium. In gastrocnemius, exercise increased the cross-sectional area of myocytes and FSTL1 expression. Importantly, exercise increased circulating FSTL1 levels, which were positively correlated with the skeletal muscle FSTL1 expression and negatively correlated with heart fibrosis. Overall, the IAE was more effective than that of MVT in cardioprotection. Finally, exogenous FSTL1 administration directly improved angiogenesis as well as functionality of post-MI hearts. Taken together, we have demonstrated that FSTL1 is a potential mediator of exercise-induced cardioprotection in post-MI rats. PMID:27561749

  13. FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post-Myocardial Infarction Rats

    PubMed Central

    Xi, Yue; Gong, Da-Wei; Tian, Zhenjun

    2016-01-01

    Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI), but the underlying mechanisms are poorly understood. Follistatin-like1 (FSTL1) is a cardioprotective factor against ischemic injury and is induced in cardiomyocytes and skeletal muscle in ischemic and hypoxic conditions. To test the hypothesis that FSTL1 may be a molecular link between exercise and improved heart function post MI, we subjected MI-rats, induced by left coronary artery ligation, to two modes of exercise: intermittent aerobic exercise (IAE) or mechanical vibration training (MVT), for four weeks and examined the relevance of FSTL1 to exercise-mediated cardiac effects. Exercise improved the functional performance, reduced fibrosis of MI-hearts and induced FSTL1 expression, the TGFβ-Smad2/3 signaling and angiogenesis in myocardium. In gastrocnemius, exercise increased the cross-sectional area of myocytes and FSTL1 expression. Importantly, exercise increased circulating FSTL1 levels, which were positively correlated with the skeletal muscle FSTL1 expression and negatively correlated with heart fibrosis. Overall, the IAE was more effective than that of MVT in cardioprotection. Finally, exogenous FSTL1 administration directly improved angiogenesis as well as functionality of post-MI hearts. Taken together, we have demonstrated that FSTL1 is a potential mediator of exercise-induced cardioprotection in post-MI rats. PMID:27561749

  14. Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol.

    PubMed

    Ghanayem, B I; Long, P H; Ward, S M; Chanas, B; Nyska, M; Nyska, A

    2001-06-01

    2-butoxyethanol (BE; ethylene glycol monobutyl ether) is used extensively in the manufacture of a wide range of domestic and industrial products which may result in human exposure and toxicity. BE causes severe hemolytic anemia in male and female rats and mice. In a recent report, female F344 rats exposed to 500 ppm BE by inhalation and sacrificed moribund on day 4 of treatment exhibited disseminated thrombosis associated with infarction in several organs. In contrast, no such lesions were observed in male rats similarly exposed to BE. Additional studies were therefore undertaken to compare the effects of BE in rats of both sexes. Rats received 250 mg BE/kg/day by gavage for 1, 2 or 3 days and were sacrificed 24 or 48 hr after the last dose. Control rats received 5 ml/kg water. Progressive time-dependent hemolytic anemia--macrocytic, hypochromic, and regenerative--was observed in both sexes of rats exposed to BE. Additionally, BE caused significant morphological changes in erythrocytes, first observed 24 hr after a single dose, including stomatocytosis, macrocytosis with moderate rouleaux formation, and spherocytosis. These morphological changes became progressively more severe as BE dosing continued and included the occasional occurrence of schistocytes and ghost cells, rouleaux formation in rats of both sexes, and an increased number of red blood cells with micronuclei in female rats. Overall, the progression of hemolytic anemia and morphological changes as a function of the number of days of exposure varied with gender and suggested a faster onset of hemolysis in female rats. The range of BE-related histopathological changes noted in both sexes was comparable; however, while these lesions were observed in female rats following a single dose, similar effects were first observed in males after 3 consecutive days of exposure to BE. Pathological changes involved disseminated thrombosis in the lungs, nasal submucosa, eyes, liver, heart, bones and teeth, with evidence

  15. 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. PMID:25722680

  16. Atrial natriuretic peptide infusion in chronic heart failure in the rat.

    PubMed

    Kohzuki, M; Hodsman, G P; Harrison, R W; Western, P S; Johnston, C I

    1989-01-01

    The natriuretic, diuretic, and hypotensive responses to infused atrial natriuretic peptide (ANP) were measured in rats 4 weeks after myocardial infarction induced by coronary artery ligation. Rat [1-28]-ANP was infused intravenously in doses of 0.1, 0.3, and 1.0 microgram/kg/min for 30 min each under pentobarbital anesthesia. There was a marked natriuresis, diuresis, and fall in blood pressure in rats with infarction but each response was significantly attenuated when compared with sham-operated controls (ANOVA: p less than 0.01, p less than 0.05, and p less than 0.01, respectively). Urinary cyclic guanosine monophosphate (cGMP) excretion in rats with infarction was higher than that of controls but rose to the same absolute level in both groups in response to ANP infusion (0.3 microgram/kg/min). Reduced ANP responsiveness may result from impaired postreceptor mechanisms or from physiological antagonism by angiotensin II. Reduced ANP responsiveness may partly explain impaired salt handling in heart failure. PMID:2473348

  17. 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. PMID:23428371

  18. Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats.

    PubMed

    Lee, Young Sook; Choi, Joung-Woo; Oh, Jung-Eun; Yun, Chae-Ok; Kim, Sung Wan

    2016-08-01

    In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM. PMID:27174688

  19. Overexpression of protein kinase C ɛ improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction

    PubMed Central

    He, H; Zhao, Z-H; Han, F-S; Liu, X-H; Wang, R; Zeng, Y-J

    2016-01-01

    We assessed the effects of protein kinase C ɛ (PKCɛ) for improving stem cell therapy for acute myocardial infarction (AMI). Primary mesenchymal stem cells (MSCs) were harvested from rat bone marrow. PKCɛ-overexpressed MSCs and control MSCs were transplanted into infarct border zones in a rat AMI model. MSCs and PKCɛ distribution and expression of principal proteins involved in PKCɛ signaling through the stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4) axis and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway were analyzed by immunofluorescence and western blot 1 day after transplantation. Echocardiographic measurements and histologic studies were performed at 4 weeks after transplantation, and MSC survival, expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGFβ), cardiac troponin I (cTnI), von Willebrand factor (vWF), smooth muscle actin (SMA) and factor VIII and apoptosis in infarct border zones were assessed. Rat heart muscles retained more MSCs and SDF-1, CXCR4, PI3K and phosphorylated AKT increased with PKCɛ overexpression 1 day after transplantation. MSC survival and VEGF, bFGF, TGFβ, cTnI, vWF, SMA and factor VIII expression increased in animals with PKCɛ-overexpressed MSCs at 4 weeks after transplantation and cardiac dysfunction and remodeling improved. Infarct size and apoptosis decreased as well. Inhibitory actions of CXCR4 or PI3K partly attenuated the effects of PKCɛ. Activation of PKCɛ may improve retention, survival and differentiation of transplanted MSCs in myocardia. Augmentation of PKCɛ expression may enhance the therapeutic effects of stem cell therapy for AMI. PMID:26775707

  20. Graded exercise in three cases of heart rupture after acute myocardial infarction.

    PubMed

    Mineo, K; Takizawa, A; Shimamoto, M; Yamazaki, F; Kimura, A; Chino, N; Izumi, S

    1995-01-01

    Despite advances in the study of exercise for acute myocardial infarction (AMI) patients, few studies on exercise for post-AMI heart rupture patients have been reported. We assessed three cases of heart rupture (of the left ventricular free wall in two cases and of the ventricular septum in one case) in post-AMI patients who underwent three-graded exercise. Two of the three patients were operated on, whereas one patient was managed conservatively for heart rupture. Two of the three cases had also suffered cerebral infarction post-AMI. The exercise program was composed of three grades, slow level walking (grade 1), mild reconditioning and activities of daily living (ADL) exercises (grade 2), and optional endurance training using machines below 75% of predicted maximal heart rate (grade 3). Electrocardiograms and blood pressure were monitored during all exercises. All patients had muscle weakness, poor endurance capacity, as well as low cardiac function (28-47% of left ventricular ejection fraction). Two patients underwent grades 1 and 2 exercise programs, and the other performed grades 1, 2, and 3 exercise programs over a 3- to 10-wk period. We observed improvement in the double product, work capacity, and ADL without congestive heart failure, ischemic attack, or serious arrhythmias. However, the youngest patient, who underwent the grade 3 exercise program, died from a cardiac event 10 mo after onset of AMI. We conclude that post-AMI heart rupture patients should undergo delayed, gradual, low-level graded exercise (4-6 metabolic equivalents), with monitoring of blood pressure and electrocardiograms to improve work capacity, ADL, and the quality of life. However, daily activity and exercise intensity should be promptly supervised for those with severely deteriorated cardiac functions to prevent sudden cardiac event. PMID:8534391

  1. 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

  2. Protective effects of drag-reducing polymers on ischemic reperfusion injury of isolated rat heart.

    PubMed

    Hu, Feng; Wang, Yali; Gong, Kaizheng; Ge, Gaoyuan; Cao, Mingqiang; Zhao, Pei; Sun, Xiaoning; Zhang, Zhengang

    2016-01-01

    Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on ischemic reperfusion (I/R) injury of isolated rat hearts. Experiments were performed on isolated rat hearts subjected to 30 min of ischemia followed by 90 min of reperfusion in Langendorff preparations. Adult Wistar rats were divided into the following five groups: control group, I/R group, group III (I/R and 2×10(-7)  g/ml PEO reperfusion), group IV (I/R and 1×10(-6)  g/ml PEO reperfusion), and group V (I/R and 5×10(-6)  g/ml PEO reperfusion). Left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum rate of ventricular pressure increase and decrease ( ± dp/dtmax), heart rate (HR) and coronary flow were measured. Lactate dehydrogenase (LDH) and creatine kinase (CK) activity and coronary flow, myocardial infarction size and cardiomyocytes apoptosis were also assayed. Our results showed that PEO decreased LVEDP and increased LVSP, ± dP/dtmax in group IV and group V compared with the I/R group (all P <  0.05). The coronary flow significantly increased and the activities of LDH and CK in the coronary flow significantly decreased in group IV and group V compared with those in the I/R group (all P <  0.05). Cell apoptosis and myocardial infarction size were reduced in group IV and group V compared with the I/R group (all P <  0.05). Collectively, these results suggested that DRPs had a protective effect on cardiac I/R injury of isolated rat hearts and it may offer a new potential approach for the treatment of acute ischemic heart diseases. PMID:25633566

  3. 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

  4. Exendin-4 induces myocardial protection through MKK3 and Akt-1 in infarcted hearts.

    PubMed

    Du, Jianfeng; Zhang, Ling; Wang, Zhengke; Yano, Naohiro; Zhao, Yu Tina; Wei, Lei; Dubielecka-Szczerba, Patrycja; Liu, Paul Y; Zhuang, Shougang; Qin, Gangjian; Zhao, Ting C

    2016-02-15

    We have demonstrated that glucagon like peptide-1 (GLP-1) protects the heart against ischemic injury. However, the physiological mechanism by which GLP-1 receptor (GLP-1R) initiates cardioprotection remains to be determined. The objective of this study is to elucidate the functional roles of MAPK kinase 3 (MKK3) and Akt-1 in mediating exendin-4-elicited protection in the infarcted hearts. Adult mouse myocardial infarction (MI) was created by ligation of the left descending artery. Wild-type, MKK3(-/-), Akt-1(-/-), and Akt-1(-/-);MKK3(-/-) mice were divided into one of several groups: 1) sham: animals underwent thoracotomy without ligation; 2) MI: animals underwent MI and received a daily dose of intraperitoneal injection of vehicle (saline); 3) MI + exendin-4: infarcted mice received daily injections of exendin-4, a GLP-1R agonist (0.1 mg/kg, ip). Echocardiographic measurements indicate that exendin-4 treatment resulted in the preservation of ventricular function and increases in the survival rate, but these effects were diminished in MKK3(-/-), Akt-1(-/-), and Akt-1(-/-);MKK3(-/-) mice. Exendin-4 treatments suppressed cardiac hypotrophy and reduced scar size and cardiac interstitial fibrosis, respectively, but these beneficial effects were lost in genetic elimination of MKK3, Akt-1, or Akt-1(-/-);MKK3(-/-) mice. GLP-1R stimulation stimulated angiogenic responses, which were also mitigated by deletion of MKK3 and Akt-1. Exendin-4 treatment increased phosphorylation of MKK3, p38, and Akt-1 at Ser129 but decreased levels of active caspase-3 and cleaved poly (ADP-ribose) polymerase; these proteins were diminished in MKK3(-/-), Akt-1(-/-), and Akt-1(-/-);MKK3(-/-) mice. These results reveal that exendin-4 treatment improves cardiac function, attenuates cardiac remodeling, and promotes angiogenesis in the infarcted myocardium through MKK3 and Akt-1 pathway. PMID:26739490

  5. Bone marrow mononuclear cells enhance anti-inflammatory effects of pravastatin against isoproterenol-induced myocardial infarction in rats.

    PubMed

    El-Mahdy, Nageh; Salem, Mohamed L; El-Sayad, Magda; El-Desouky, Karima I; Zaghow, Nesma

    2016-05-01

    The current study investigated the combinatorial effect of pravastatin (PRAV) and bone marrow mononuclear cells (BM-MNC) on acute myocardial infarction (AMI) induced experimentally in rats. After induction of MI, rats were given oral PRAV (20 mg/kg/day) for 28 days or a bolus intravenous injection (via lateral vein) of a total of 14 × 10(6) autologous BM-MNC or a combination of both. Serum brain natriuretic peptide (BNP) and histologic changes in cardiac tissues were assessed. Cardiac contents of lipid peroxides, superoxide dismutase (SOD) and inflammatory biomarkers including tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) were also measured. Combined PRAV and BM-MNC treatment significantly suppressed serum BNP. Cardiac cell apoptosis and inflammatory cell infiltration in heart tissue decreased significantly in both the PRAV and the PRAV + BM-MNC groups. Cardiac lipid peroxides along with TNFα and IL-1β levels were significantly reduced in both the PRAV and PRAV + BM-MNC hosts with an increase in SOD levels. However, the combined treatment increased cardiac NO levels and did not modify cardiac VEGF levels. The current results indicated that administration of BM-MNC improved the therapeutic efficacy of PRAV treatment by improving the morphology of infarcted hearts as well as decreasing inflammation in a host, but did not do so by inducing therapeutic angiogenesis. PMID:26606075

  6. Role of Cardiac Myocytes Heart Fatty Acid Binding Protein Depletion (H-FABP) in Early Myocardial Infarction in Human Heart (Autopsy Study)

    PubMed Central

    Shabaiek, Amany; Ismael, Nour El-Hoda; Elsheikh, Samar; Amin, Hebat Allah

    2016-01-01

    BACKGROUND: Many immunohistochemical markers have been used in the postmortem detection of early myocardial infarction. AIM: In the present study we examined the role of Heart-type fatty acid binding protein (H-FABP), in the detection of early myocardial infarction. MATERIAL AND METHODS: We obtained samples from 40 human autopsy hearts with/without histopathological signs of ischemia. RESULTS: All cases of definite and probable myocardial infarction showed a well-defined area of H-FABP depletion. All of the control cases showed strong H-FABP expression, except two markedly autolysed myocardial samples that showed affected antigenicity. CONCLUSION: Thus, we suggest H-FABP as being one of the valuable tools facing the problem of postmortem detection of early myocardial infarction/ischemia, but not in autolysis.

  7. Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction

    PubMed Central

    Richards, A; Nicholls, M; Yandle, T; Ikram, H; Espiner, E; Turner, J; Buttimore, R; Lainchbury, J; Elliott, J; Frampton, C; Crozier, I; Smyth, D

    1999-01-01

    independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

 Keywords: cardiac natriuretic peptides; noradrenaline; myocardial infarction; heart failure PMID:9922344

  8. ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity

    PubMed Central

    Porritt, Michelle J; Chen, Michelle; Rewell, Sarah S J; Dean, Rachael G; Burrell, Louise M; Howells, David W

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR. PMID:20407464

  9. 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.

  10. Hypercholesterolemia abrogates an increased resistance of diabetic rat hearts to ischemia-reperfusion injury.

    PubMed

    Adameová, A; Kuzelová, M; Andelová, E; Faberová, V; Pancza, D; Svec, P; Ziegelhöffer, A; Ravingerová, T

    2007-01-01

    Both, diabetes mellitus (DM) and hypercholesterolemia (HCH) are known as risk factors of ischemic heart disease, however, the effects of experimental DM, as well as of HCH alone, on ischemia/reperfusion-induced myocardial injury are not unequivocal. We have previously demonstrated an enhanced resistance to ischemia-induced arrhythmias in rat hearts in the acute phase of DM. Our objectives were thus to extend our knowledge on how DM in combination with HCH, a model that is relevant to diabetic patients with altered lipid metabolism, may affect the size of myocardial infarction and susceptibility to arrhythmias. A combination of streptozotocin (STZ; 80 mg/kg, i.p.) and the fat-cholesterol diet (1% cholesterol, 1% coconut oil; FCHD) was used as a double-disease model mimicking DM and HCH simultaneosly occurring in humans. Following 5 days after STZ injection and FCHD leading to increased blood glucose and cholesterol levels, anesthetized open-chest diabetic, diabetic-hypercholesterolemic (DM-HCH) and age-matched control rats were subjected to 6-min ischemia (occlusion of LAD coronary artery) followed by 10 reperfusion to test susceptibility to ventricular arrhythmias in the in vivo experiments and to 30-min ischemia and subsequent 2-h reperfusion for the evaluation of the infarct size (IS) in the Langendorff-perfused hearts. The incidence of the most life-threatening ventricular arrhythmia, ventricular fibrillation, was significantly increased in the DM-HCH rats as compared with non-diabetic control animals (100% vs. 50%; p<0.05). Likewise, arrhythmia severity score (AS) was significantly higher in the DM-HCH rats than in the controls (4.9+/-0.2 vs. 3.5+/-0.5; p<0.05), but was not increased in the diabetic animals (AS 3.7+/-0.9; p>0.05 vs. controls). Diabetic hearts exhibited a reduced IS (15.1+/-3.0% of the area at risk vs. 37.6+/-2.8% in the control hearts; p<0.05), however, a combination of DM and HCH increased the size of myocardial infarction to that observed in

  11. 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

  12. Sympathetic Hyperinnervation and Inflammatory Cell NGF Synthesis Following Myocardial Infarction in Rats

    PubMed Central

    Hasan, Wohaib; Jama, Abdi; Donohue, Timothy; Wernli, Gwenaelle; Onyszchuk, Gregory; Al-Hafez, Baraa; Bilgen, Mehmet; Smith, Peter G.

    2006-01-01

    Sympathetic hyperinnervation occurs in human ventricular tissue after myocardial infarction and may contribute to arrhythmias. Aberrant sympathetic sprouting is associated with elevated nerve growth factor (NGF) in many contexts, including ventricular hyperinnervation. However, it is unclear whether cardiomyocytes or other cell types are responsible for increased NGF synthesis. In this study, left coronary arteries were ligated and ventricular tissue examined in rats 1-28 days post-infarction. Infarct and peri-infarct tissue was essentially devoid of sensory and parasympathetic nerves at all time points. However, areas of increased sympathetic nerve density were observed in the peri-infarct zone between post-ligation days 4-14. Hyperinnervation occurred in regions containing accumulations of macrophages and myofibroblasts. To assess whether these inflammatory cells synthesize NGF, sections were processed for NGF in situ hybridization and immunohistochemistry. Both macrophage1 antigen-positive macrophages and α-smooth muscle actin immunoreactive myofibroblasts expressed NGF in areas where they were closely proximate to sympathetic nerves. To investigate whether NGF produced by peri-infarct cells induces sympathetic outgrowth, we co-cultured adult sympathetic ganglia with peri-infarct explants. Neurite outgrowth from sympathetic ganglia was significantly greater at post-ligation days 7-14 as compared to control tissue. Addition of an NGF function-blocking antibody prevented the increased neurite outgrowth induced by peri-infarct tissue. These findings provide evidence that inflammatory cell NGF synthesis plays a causal role in sympathetic hyperinnervation following myocardial infarction. Section: Disease-Related Neuroscience PMID:17084822

  13. Scutellarin alleviates interstitial fibrosis and cardiac dysfunction of infarct rats by inhibiting TGFβ1 expression and activation of p38-MAPK and ERK1/2

    PubMed Central

    Pan, Zhenwei; Zhao, Weiming; Zhang, Xiangying; Wang, Bing; Wang, Jinghao; Sun, Xuelin; Liu, Xuantong; Feng, Shuya; Yang, Baofeng; Lu, Yanjie

    2011-01-01

    BACKGROUND AND PURPOSE Interstitial fibrosis plays a causal role in the development of heart failure after chronic myocardial infarction (MI), and anti-fibrotic therapy represents a promising strategy to mitigate this pathological process. The purpose of this study was to investigate the effect of long-term administration of scutellarin (Scu) on cardiac interstitial fibrosis of myocardial infarct rats and the underlying mechanisms. EXPERIMENTAL APPROACH Scu was administered to rats that were subjected to coronary artery ligation. Eight weeks later, its effects on cardiac fibrosis were assessed by examining cardiac function and histology. The number and collagen content of cultured cardiac fibroblasts exposed to angiotensin II (Ang II) were determined after the administration of Scu in vitro. Protein expression was detected by Western blot technique, and mRNA levels by quantitative reverse transcription-PCR. KEY RESULTS The echocardiographic and haemodynamic measurements showed that Scu improved the impaired cardiac function of infarct rats and decreased interstitial fibrosis. Scu inhibited the expression of FN1 and TGFβ1, but produced no effects on inflammatory cytokines (TNFα, IL-1β and IL-6) in the 8 week infarct hearts. Scu inhibited the proliferation and collagen production of cardiac fibroblasts (CFs) and the up-regulation of FN1 and TGFβ1 induced by Ang II. The enhanced phosphorylation of p38-MAPK and ERK1/2 in both infarct cardiac tissue and cultured CFs challenged by Ang II were suppressed by Scu. CONCLUSIONS AND IMPLICATIONS Long-term administration of Scu improved the cardiac function of MI rats by inhibiting interstitial fibrosis, and the mechanisms may involve the suppression of pro-fibrotic cytokine TGFβ1 expression and inhibition of p38 MAPK and ERK1/2 phosphorylation. PMID:20942814

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

    PubMed

    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

  15. 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

  16. 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

  17. Size of myocardial infarction induced by ischaemia/reperfusion is unaltered in rats with metabolic syndrome.

    PubMed

    Thim, Troels; Bentzon, Jacob F; Kristiansen, Steen B; Simonsen, Ulf; Andersen, Heidi L; Wassermann, Karsten; Falk, Erling

    2006-06-01

    Obesity is associated with metabolic syndrome and increased incidence of and mortality from myocardial infarction. The aim of the present study was to develop an animal model with metabolic syndrome and examine how that influences size of myocardial infarcts induced by occlusion and reperfusion of the left anterior descending coronary artery. Sprague-Dawley rats (n = 105) were fed either LF (low-fat) or MHF (moderately high-fat) diets for 13 weeks before coronary occlusion for 45 min, followed by reperfusion for 60 min. Compared with LF-fed and lean MHF-fed rats, obese MHF-fed rats developed metabolic disturbances similar to those seen in the metabolic syndrome, including being overweight by 24% (compared with lean MHF-fed rats), having 74% more visceral fat (compared with LF-fed rats), 15% higher blood pressure (compared with LF-fed rats), 116% higher plasma insulin (compared with lean MHF-fed rats), 10% higher fasting plasma glucose (compared with LF-fed rats), 35% higher non-fasting plasma glucose (compared with lean MHF-fed rats), 36% higher plasma leptin (compared with lean MHF-fed rats) and a tendency to lower plasma adiponectin and higher plasma non-esterified fatty acids. Infarct size was similar in the three groups of rats (36+/-14, 42+/-18 and 41+/-14% in obese MHF-fed, lean MHF-fed and LF-fed rats respectively). In conclusion, rats fed a MHF diet developed metabolic syndrome, but this did not influence myocardial infarct size. PMID:16448385

  18. Preparation of Highly Coupled Rat Heart Mitochondria

    PubMed Central

    Gostimskaya, Irina; Galkin, Alexander

    2010-01-01

    The function of mitochondria in generation of cellular ATP in the process of oxidative phosphorylation is widely recognised. During the past decades there have been significant advances in our understanding of the functions of mitochondria other than the generation of energy. These include their role in apoptosis, acting as signalling organelles, mammalian development and ageing as well as their contribution to the coordination between cell metabolism and cell proliferation. Our understanding of biological processes modulated by mitochondria is based on robust methods for isolation and handling of intact mitochondria from tissues of the laboratory animals. Mitochondria from rat heart is one of the most common preparations for past and current studies of cellular metabolism including studies on knock-out animals. Here we describe a detailed rapid method for isolation of intact mitochondria with a high degree of coupling. Such preparation of rat heart mitochondria is an excellent object for functional and structural research on cellular bioenergetics, transport of biomolecules, proteomic studies and analysis of mitochondrial DNA, proteins and lipids. PMID:20972393

  19. Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles.

    PubMed

    Giricz, Zoltán; Varga, Zoltán V; Baranyai, Tamás; Sipos, Péter; Pálóczi, Krisztina; Kittel, Ágnes; Buzás, Edit I; Ferdinandy, Péter

    2014-03-01

    Remote ischemic preconditioning (RIPC) of the heart is exerted by brief ischemic insults affected on a remote organ or a remote area of the heart before a sustained cardiac ischemia. To date, little is known about the inter-organ transfer mechanisms of cardioprotection by RIPC. Exosomes and microvesicles/microparticles are vesicles of 30-100 nm and 100-1000 nm in diameter, respectively (collectively termed extracellular vesicles [EVs]). Their content of proteins, mRNAs and microRNAs, renders EV ideal conveyors of inter-organ communication. However, whether EVs are involved in RIPC, is unknown. Therefore, here we investigated whether (1) IPC induces release of EVs from the heart, and (2) EVs are necessary for cardioprotection by RIPC. Hearts of male Wistar rats were isolated and perfused in Langendorff mode. A group of donor hearts was exposed to 3 × 5-5 min global ischemia and reperfusion (IPC) or 30 min aerobic perfusion, while coronary perfusates were collected. Coronary perfusates of these hearts were given to another set of recipient isolated hearts. A group of recipient hearts received IPC effluent depleted of EVs by differential ultracentrifugation. Infarct size was determined after 30 min global ischemia and 120 min reperfusion. The presence or absence of EVs in perfusates was confirmed by dynamic light scattering, the EV marker HSP60 Western blot, and electron microscopy. IPC markedly increased EV release from the heart as assessed by HSP60. Administration of coronary perfusate from IPC donor hearts attenuated infarct size in non-preconditioned recipient hearts (12.9 ± 1.6% vs. 25.0 ± 2.7%), similarly to cardioprotection afforded by IPC (7.3 ± 2.7% vs. 22.1 ± 2.9%) on the donor hearts. Perfusates of IPC hearts depleted of EVs failed to exert cardioprotection in recipient hearts (22.0 ± 2.3%). This is the first demonstration that EVs released from the heart after IPC are necessary for cardioprotection by RIPC, evidencing the importance of vesicular

  20. 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.

  1. 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

  2. Granulocyte colony-stimulating factor does not enhance recruitment of bone marrow-derived cells in rats with acute myocardial infarction.

    PubMed

    Sato, Daisuke; Otani, Hajime; Fujita, Masanori; Shimazu, Takayuki; Yoshioka, Kei; Enoki, Chiharu; Minato, Naoki; Iwasaka, Toshiji

    2012-09-01

    Despite the potential benefit of granulocyte colony-stimulating factor (G-CSF) therapy in patients with acute myocardial infarction (MI), the efficacy of G-CSF in regenerating the heart after MI remains controversial. The authors hypothesize that the limited efficacy of G-CSF is related to its inhibitory effect on recruitment of bone marrow-derived cells (BMCs) to the infarcted tissue. MI was induced in rats with intrabone marrow-bone marrow transplantation from syngenic rats expressing green fluorescence protein to track BMCs. G-CSF was administered for five days after the onset of MI. G-CSF increased the number of CD45(+) cells in the peripheral circulation but did not increase their recruitment to the heart. G-CSF had no effect on myocardial stromal-derived factor-1 alpha and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in mononuclear cells in the peripheral blood and CXCR4(+) cells in the heart. G-CSF had no effect on angiogenesis, myocardial fibrosis or left ventricular function four weeks after MI. These results suggest that G-CSF mobilizes BMCs to the peripheral circulation but does not increase recruitment to the infarcted myocardium despite preservation of the stromal-derived factor-1 alpha/CXCR4 axis. PMID:23620693

  3. Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stimulation.

    PubMed

    Otsuki, Yuki; Nakamura, Yoshinobu; Harada, Shingo; Yamamoto, Yasutaka; Ogino, Kazuhide; Morikawa, Kumi; Ninomiya, Haruaki; Miyagawa, Shigeru; Sawa, Yoshiki; Hisatome, Ichiro; Nishimura, Motonobu

    2015-01-01

    Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets. PMID:25749147

  4. Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen.

    PubMed

    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 [(18)F]-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

  5. 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

  6. Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms.

    PubMed

    Sui, Xizhong; Gao, Changqing

    2014-01-01

    Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats. PMID:24190328

  7. Diosmin exhibits anti-hyperlipidemic effects in isoproterenol induced myocardial infarcted rats.

    PubMed

    Queenthy, S Sharmila; John, Babu

    2013-10-15

    The aim of the present study was to evaluate the protective effects of diosmin on experimentally induced myocardial infarcted rats. Diosmin (5 and 10mg/kg body weight) was administered orally as pretreatment daily for a period of 10 days. Then isoproterenol (100mg/kg) was injected subcutaneously into rats at an interval of 24h for 2 days (on 11th and 12th day). Isoproterenol-induced myocardial infarcted rats showed significant changes in electrocardiogram and an increase in the levels of cardiac markers, compared with normal rats. Additionally, increased plasma lipid peroxidation products and altered lipid metabolism in the plasma were observed in the isoproterenol-induced myocardial infarcted rats. Pretreatment with diosmin (5 and 10mg/kg body weight) minimized the electrocardiographic changes, decreased the levels of serum cardiac marker enzymes reduced plasma lipid peroxidation and minimized the alterations in the lipid metabolism of isoproterenol-induced myocardial infarcted rats. Also, diosmin inhibited the enhanced activity of liver HMG CoA reductase. The in vitro study revealed the free radical scavenging activity of diosmin. The free radical scavenging and anti-hyperlipidaemic effects are the reasons for the cardioprotective effects of diosmin. PMID:24036254

  8. 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

  9. Comparing the effects of MSCs and CD34+ cell therapy in a rat model of myocardial infarction.

    PubMed

    Shalaby, Sally M; El-Shal, Amal S; Zidan, Haidy E; Mazen, Nehad F; Abd El-Haleem, Manal R; Abd El Motteleb, Dalia M

    2016-05-01

    Stem cell therapy is considered as a promising approach in the treatment of myocardial infarction (MI). This study was designed as a comparison of human umbilical cord blood (HUCB)-derived CD34+ and HUCB-derived MSCs for the repair of cardiac tissue by induction of the angiogenesis. Forty-eight male rats were randomized into four groups: sham-operated group, MI group, MSCs-treated group, and CD34+ cells-treated group. After 4 weeks, the rats were sacrificed. All sections from left ventricles of all groups were subjected to hematoxylin & eosin, Masson's trichrome, and immunohistochemical stains (CD133, CD44, and α-smooth muscle actin). RNA was extracted for gene expression of the angiogenic markers. A significant reduction of the infarct size and the amplitude of T-wave in the CD34+ cells-treated group when compared with the MSCs-treated group were determined. Histologically, the MI group showed scar tissue, congested blood capillaries around the infarcted area, some necrotic cells, and inflammatory cells. Administration of either MSCs or CD34+ cells had a therapeutic potential to induce regenerative changes in the myocardium with better results in CD34+cells-treated group. Quantitative RT-PCR analysis revealed a significant increase in the expression of vascular endothelial growth factor (VEGF), VEGFR-2, Ang-1, and Tie-2 and a significant decreased expression of Ang-2 in stem cells transplanted groups when compared with the noncell transplanted hearts. A significant increase of VEGF, VEGFR-2, Ang-1, and Tie-2 expression in the group receiving CD34+ cells than those receiving MSCs was found. Finally, there was an upregulation of both human VEGF and human hypoxia-inducible factor 1α in the infarcted hearts treated by CD34+ cells than that treated by MSCs. We first revealed a superior efficacy of CD34+ cells when compared with MSCs in induction of regenerative changes in the MI model. Both cell therapies may repair the damaged heart tissue primarily by secretion of

  10. Protective effect of apigenin on ischemia/reperfusion injury of the isolated rat heart.

    PubMed

    Hu, Jing; Li, Zilin; Xu, Li-ting; Sun, Ai-jun; Fu, Xiao-yan; Zhang, Li; Jing, Lin-lin; Lu, An-dong; Dong, Yi-fei; Jia, Zheng-ping

    2015-07-01

    Apigenin (Api), a mainly bioactive component of Apium graveolens L. var. dulce DC. (a traditional Chinese medicinal herb), possesses a wide range of biological activities, including antioxidant effects. It also has been shown to associate with lower prevalence of cardiovascular diseases, but its mechanisms of action remain unclear. The aim of the present study is to investigate the role of Api in isolated rat heart model of ischemia/reperfusion (I/R). Langendorff-perfused isolated rat hearts were used in our study. Api was added to the perfusate before ischemia and during reperfusion in the isolated pulsed rat heart exposed to 30-min ischemia followed by 50-min reperfusion. The treatment with Api conferred a cardioprotective effect, and the treated hearts demonstrated an improved ischemic cardiac functional recovery, a decreased myocardial infarct size, a reduced activities of creatine kinase isoenzyme and lactate dehydrogenase in the coronary flow, a reduced number of apoptotic cardiomyocytes, a reduced activity of caspase-3, up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic protein Bax. In addition, Api inhibited the phosphorylation of p38 MAPKS during I/R. In conclusion, these observations provide preliminary evidence that Api can protect cardiomyocytes from I-/R-induced injury, at least partially, through the inhibition of p38 MAPKS signaling pathway. PMID:25377428

  11. 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. PMID:26951457

  12. Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction.

    PubMed

    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 Ca(2+)-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 Ca(2+) and Antimycin A, further implicating disruption of mitochondria/SR tethering as the protective mechanism. In summary, despite apparent

  13. 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

  14. [Efficacy of various antioxidants in experimental ischemia and myocardial infarct in the rat].

    PubMed

    Poliukhovich, G S; Vasil'eva, L P; Maslova, G T; Boboriko, T L; Speranskiĭ, S D

    1991-01-01

    Complex of vitamins E and C showed the most effective antinecrotic action in rats with simulated myocardial infarction in series of antioxidants studied: ascorbate, alpha-tocopherol, quercetine, derivatives of o-benzoquinone OBQ2 and OBQ3. Stabilization of lipid peroxidation in cardiomyocytes, increase in biomembranes stability and absence of distinct alterations in the antioxidative enzymatic system were found in rats with ischemia and myocardial infarction after treatment with the complex. Protective effect of the vitamins E and C complex was realised via antiradical mechanism. PMID:1750212

  15. 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

    2016-01-01

    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. PMID:27490896

  16. Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs

    PubMed Central

    Zheng, Xiaoxin; Li, Xiaoyan; Lyu, Yongnan; He, Yiyu; Wan, Weiguo; Jiang, Xuejun

    2016-01-01

    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/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. PMID:27490896

  17. Acute Myocardial Histopathology in Normal and Arteriosclerotic Rats During Isoproterenol-induced Infarction

    PubMed Central

    Wexler, B. C.; Judd, J. T.

    1970-01-01

    Arteriosclerotic and non-arteriosclerotic, male Sprague-Dawley rats were given 2 s.c. injections of isoproterenol known to produce extensive myocardial infarction. The appearance of positive fuchsinophilia was used as an index of focal myocardial acidosis and of anaerobic metabolism. After one injection of isoproterenol, positive fuchsinophilia appeared within 30 min., reached a zenith at 4 hr and then promptly disappeared. Following the second injection of isoproterenol, fuchsinophilia reappeared briefly but was not as intense. The arteriosclerotic animals showed markedly less evidence of heart failure outwardly and less evidence of fuchsinophilia, histopathologically. Apparently, the first episode of cardiac stimulation caused only temporary cardiac ischaemia, positive fuchsinophilia and anaerobic cardiac metabolism. After the second injection, however, irreversible cardiac damage occurred and despite an abortive attempt towards anaerobic metabolic readjustment overt cardiac necrosis became dominant. ImagesFigs. 9-10Figs. 11-12Figs. 1-2Figs. 13-14Figs. 7-8Figs. 5-6Figs. 3-4 PMID:4099593

  18. Chronological and morphological study of heart development in the rat.

    PubMed

    Marcela, Salazar García; Cristina, Revilla Monsalve María; Angel, Palomino Garibay Miguel; Manuel, Arteaga Martínez; Sofía, Díaz-Cintra; Patricia, De La Rosa-Santander; Bladimir, Roque-Ramírez; Concepción, Sánchez Gómez

    2012-08-01

    Adult and embryonic laboratory rats have been used as a mammalian model organism in biomedical research, descriptive and experimental cardiac embryology, and experimental teratology. There have been, however, considerable variations and discrepancies concerning the developmental staging of the rat embryo in the reported literature, which have resulted in several controversies and inconsistencies. Therefore, we carried out a careful anatomical and histological study of rat cardiac morphogenesis from the premorphogenetic period to the mature heart in a newborn pup. A correlation between the chronology and morphological features of the heart and embryo or newborn was made. We provide a simple and comprehensive guide relating the developmental timing and fate of the embryonic components of the heart and their morphological changes in the rat based on in vivo labeling studies in the chick. We also compare the timing of heart development in rats, humans, and mice. PMID:22715162

  19. 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

  20. Inhibition of Histone Deacetylase-induced Myocardial Repair Is Mediated by c-kit in Infarcted Hearts*

    PubMed Central

    Zhang, Ling; Chen, Bing; Zhao, Yu; Dubielecka, Patrycja M.; Wei, Lei; Qin, Gang J.; Chin, Y. Eugene; Wang, Yigang; Zhao, Ting C.

    2012-01-01

    Histone deacetylases (HDACs) play a critical role in the regulation of gene transcription, cardiac development, and diseases. The aim of this study was to test whether inhibition of HDACs induces myocardial repair and cardiac function restoration through c-kit signaling in mouse myocardial infarction models. Myocardial infarction in wild type Kit+/+ and KitW/KitW-v mice was created following thoracotomy by applying permanent ligation to the left anterior descending artery. The HDAC inhibitor, trichostatin A (TSA, 0.1 mg/kg), was intraperitoneally injected daily for a consecutive 8 weeks after myocardial infarction. 5-Bromo-2-deoxyuridine (BrdU, 50 mg/kg) was intraperitoneally delivered every other day to pulse-chase label in vivo endogenous cardiac replication. Eight weeks later, inhibition of HDACs in vivo resulted in an improvement in ventricular functional recovery and the prevention of myocardial remodeling in Kit+/+mice, which was eliminated in KitW/KitW-v mice. HDAC inhibition promoted cardiac repairs and neovascularization in the infarcted myocardium, which were absent in KitW/KitW-v mice. Re-introduction of TSA-treated wild type c-kit+ CSCs into KitW/KitW-v myocardial infarction heart restored myocardial functional improvement and cardiac repair. To further validate that HDAC inhibition stimulates c-kit+ cardiac stem cells (CSCs) to facilitate myocardial repair, GFP+ c-kit+ CSCs were preconditioned with TSA (50 nmol/liter) for 24 h and re-introduced into infarcted hearts for 2 weeks. Preconditioning of c-kit+ CSCs via HDAC inhibition with trichostatin A significantly increased c-kit+ CSC-derived myocytes and microvessels and enhanced functional recovery in myocardial infarction hearts in vivo. Our results provide evidence that HDAC inhibition promotes myocardial repair and prevents cardiac remodeling, which is dependent upon c-kit signaling. PMID:23024362

  1. Exogenous connexin43-expressing autologous skeletal myoblasts ameliorate mechanical function and electrical activity of the rabbit heart after experimental infarction

    PubMed Central

    Antanavičiūtė, Ieva; Ereminienė, Eglė; Vysockas, Vaidas; Račkauskas, Mindaugas; Skipskis, Vilius; Rysevaitė, Kristina; Treinys, Rimantas; Benetis, Rimantas; Jurevičius, Jonas; Skeberdis, Vytenis A

    2015-01-01

    Acute myocardial infarction is one of the major causes of mortality worldwide. For regeneration of the rabbit heart after experimentally induced infarction we used autologous skeletal myoblasts (SMs) due to their high proliferative potential, resistance to ischaemia and absence of immunological and ethical concerns. The cells were characterized with muscle-specific and myogenic markers. Cell transplantation was performed by injection of cell suspension (0.5 ml) containing approximately 6 million myoblasts into the infarction zone. The animals were divided into four groups: (i) no injection; (ii) sham injected; (iii) injected with wild-type SMs; and (iv) injected with SMs expressing connexin43 fused with green fluorescent protein (Cx43EGFP). Left ventricular ejection fraction (LVEF) was evaluated by 2D echocardiography in vivo before infarction, when myocardium has stabilized after infarction, and 3 months after infarction. Electrical activity in the healthy and infarction zones of the heart was examined ex vivo in Langendorff-perfused hearts by optical mapping using di-4-ANEPPS, a potential sensitive fluorescent dye. We demonstrate that SMs in the coculture can couple electrically not only to abutted but also to remote acutely isolated allogenic cardiac myocytes through membranous tunnelling tubes. The beneficial effect of cellular therapy on LVEF and electrical activity was observed in the group of animals injected with Cx43EGFP-expressing SMs. L-type Ca2+ current amplitude was approximately fivefold smaller in the isolated SMs compared to healthy myocytes suggesting that limited recovery of LVEF may be related to inadequate expression or function of L-type Ca2+ channels in transplanted differentiating SMs. PMID:25529770

  2. 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

  3. Lack of cardioprotection by single-dose magnesium prophylaxis on isoprenaline-induced myocardial infarction in adult Wistar rats

    PubMed Central

    Garson, Christie; Kelly-Laubscher, Roisin; Gwanyanya, Asfree; Blackhurst, Dee

    2015-01-01

    Summary Aim Magnesium (Mg2+) is effective in treating cardiovascular disorders such as arrhythmias and pre-eclampsia, but its role during myocardial infarction (MI) remains uncertain. In this study, we investigated the effects of Mg2+ pre-treatment on isoprenaline (ISO)-induced MI in vivo. Methods Rats divided into four groups were each pre-treated with either MgSO4 (270 mg/kg intraperitoneally) or an equivalent volume of physiological saline, prior to the ISO (67 mg/kg subcutaneously) or saline treatments. One day post-treatment, the electrocardiogram and left ventricular blood pressures were recorded. Infarcts were determined using 2,3,5-triphenyltetrazolium chloride staining, and serum markers of lipid peroxidation were measured with spectrophotometric assays. Results Mg2+ pre-treatment neither altered the ISO-induced infarct size compared with ISO treatment alone (p > 0.05), nor reversed the low-voltage electrocardiogram or the prominent Q waves induced by ISO, despite a trend to decreased Q waves. Similarly, Mg2+ did not prevent the ISO-induced decrease in peak left ventricular blood pressure or the decrease in minimal rate of pressure change. Mg2+ did not reverse the ISO-induced gain in heart weight or loss of body weight. Neither ISO nor Mg2+ altered the concentrations of lipid peroxidation markers 24 hours post MI induction. Conclusion Although Mg2+ had no detrimental effects on electrical or haemodynamic activity in ISO-induced MI, the lack of infarct prevention may detract from its utility in MI therapy. PMID:26212925

  4. 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

  5. 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. PMID:25561934

  6. Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction

    PubMed Central

    Gilbert, Kim; Godbout, Roger; Rousseau, Guy

    2016-01-01

    Myocardial infarction (MI) has dramatic mid- and long-term consequences at the physiological and behavioral levels, but the mechanisms involved are still unclear. Our laboratory has developed a rat model of post-MI syndrome that displays impaired cardiac functions, neuronal loss in the limbic system, cognitive deficits and behavioral signs of depression. At the neuronal level, caspase-3 activation mediates post-MI apoptosis in different limbic regions, such as the amygdala – peaking at 3 days post-MI. Cognitive and behavioral impairments appear 2-3 weeks post-MI and these correlate statistically with measures of caspase-3 activity. The protocol described here is used to induce MI, collect amygdala tissue and measure caspase-3 activity using spectrofluorometry. To induce MI, the descending coronary artery is occluded for 40 min. The protocol for evaluation of caspase-3 activation starts 3 days after MI: the rats are sacrificed and the amygdala isolated rapidly from the brain. Samples are quickly frozen in liquid nitrogen and kept at -80 °C until actual analysis. The technique performed to assess caspase-3 activation is based on cleavage of a substrate (DEVD-AMC) by caspase-3, which releases a fluorogenic compound that can be measured by spectrofluorometry. The methodology is quantitative and reproducible but the equipment required is expensive and the procedure for quantifying the samples is time-consuming. This technique can be applied to other tissues, such as the heart and kidneys. DEVD-AMC can be replaced by other substrates to measure the activity of other caspases. PMID:26862955

  7. 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

  8. 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

  9. Quantitative comparison of myocardial blood flow in normal and infarcted hearts by high resolution scintigraphy

    SciTech Connect

    Hung, C.Y.; Burow, R.D.; Scherlag, B.J.; Basmadjian, G.P.; Lazzara, R.

    1984-01-01

    The standard method for measuring myocardial blood flow (MBF) with radioactive microspheres requires processing of selected tissue samples and consequent loss of exact relation to myocardial morphology. Also, in myocardial infarction (MI) there are inaccuracies due to overlap of tissues from borders of normal and MI. A new method uses Tc-99m labeled microspheres (20..mu..) which were injected into the left atrium in 18 normal dogs and 12 dogs with MI (5 had 1 day and 7 had 4 day old MI). The excised hearts were rinsed and frozen before ''bread-loaf'' sections, 3 mm thick, were cut. Images were acquired on a gamma camera with a volume resolution of 12 mm/sup 3/. A computer program for determining MBF was checked against the conventional microsphere method. The volume resolution of the latter method was 100 mm/sup 3/. The correlation coefficient between the two methods was r=0.96. Average MBF for a given section of normal RV and LV was 95 +- 13 and 119 +- 15 ml/min/100 g of tissue, respectively. Average MBF was compared in normal LV and from ischemic epicardium (IsZ) of the central MI and endocardial infarcted zone (IZ). The authors' new method, accurately and with high resolution, delineates zones of differing MBF and confirms the increase of MBF in surviving myocardium with healing.

  10. 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

  11. 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

  12. Reprogramming of skeletal myoblasts for induction of pluripotency for tumor free cardiomyogenesis in the infarcted heart

    PubMed Central

    Ahmed, Rafeeq PH; Haider, Husnain Kh; Buccini, Stephanie; Li, Longhu; Jiang, Shujia; Ashraf, Muhammad

    2011-01-01

    Rationale Skeletal myoblasts (SMs) with inherent myogenic properties are better candidates for reprogramming to pluripotency. Objective To reprogram SMs to pluripotency and show that reprogrammed SMs (SiPs) express embryonic gene and microRNA profiles and transplantation of predifferentiated cardiac progenitors reduce tumor formation. Methods and Results The pMXs vector containing mouse cDNAs for Yamanaka’s quartet of stemness factors were used for transduction of SMs purified from male Oct4-GFP+ transgenic mouse. Three weeks later, GFP+ colonies of SiPS were isolated and propagated in vitro. SiPS were positive for alkaline phosphatase, expressed SSEA1 and displayed a panel of embryonic stem (ES) cell specific pluripotency markers. Embryoid body formation yielded beating cardiomyocyte-like cells which expressed early and late cardiac specific markers. SiPS also had embryonic microRNA profile which was altered during their cardiomyogenic differentiation. Noticeable abrogation of let-7 family and significant upregulation of miR-200a–c and miR-290 to 295 was observed in SiPS and SiPS derived cardiomyocytes respectively. In vivo studies in an experimental model of acute myocardial infarction showed extensive survival of SiPS and SiPS derived cardiomyocytes in mouse heart after transplantation. Our results from 4-week studies in DMEM without cells (group-1), SMs (group-2), SiPS (group-3) and SiPS derived cardiomyocytes (group-4) showed extensive myogenic integration of the transplanted cells in group-4 with attenuated infarct size and improved cardiac function without tumorgenesis. Conclusions Successful reprogramming was achieved in SMs with ES cell-like microRNA profile. Given the tumorgenic nature of SiPS, their pre-differentiation into cardiomyocytes would be important for tumor-free cardiogenesis in the heart. PMID:21566212

  13. Influence of psychiatric comorbidity on 30-day readmissions for heart failure, myocardial infarction, and pneumonia

    PubMed Central

    Ahmedani, Brian K.; Solberg, Leif I.; Copeland, Laurel; Fang, Ying; Stewart, Christine; Hu, Jianhui; Nerenz, David R.; Williams, L. Keoki; Cassidy-Bushrow, Andrea E.; Waxmonsky, Jeanette; Lu, Christine Y.; Waitzfelder, Beth E.; Owen-Smith, Ashli A.; Coleman, Karen J.; Lynch, Frances L.; Ahmed, Ameena T.; Beck, Arne L.; Rossom, Rebecca C.; Simon, Gregory E.

    2014-01-01

    Objective The Centers for Medicare and Medicaid Services (CMS) implemented a policy in 2012 that penalizes hospitals for ‘excessive’ all-cause hospital readmissions within 30 days after discharge for heart failure (HF), acute myocardial infarction (AMI), and pneumonia. The aim of this study is to investigate the influence of psychiatric comorbidities on 30-day all-cause readmissions for heart failure, acute myocardial infarction, and pneumonia. Methods Longitudinal study from 2009-2011 within 11 Mental Health Research Network (MHRN) affiliated health systems. Data were derived from the HMO Research Network Virtual Data Warehouse. Participants were individuals admitted to the hospital for HF, AMI, and pneumonia. All index inpatient hospitalizations for HF, AMI and pneumonia were captured (n=160,169 patient index admissions). Psychiatric diagnoses were measured for the year prior to admission. All-cause readmissions within 30 days of discharge were the outcome variable. Results Approximately 18% of all individuals with these conditions were readmitted within 30-days. The rate was 5% greater for individuals with a past-year psychiatric comorbidity (21.7%) than for those without (16.5%; p<.001). Depression, anxiety, and dementia were associated with more readmissions for those with index hospitalizations for all three conditions independently and combined (p<.05). Substance use and bipolar disorders were linked with higher readmissions for those with initial HF and pneumonia hospitalizations (p<.05). Readmission rates declined overall from 2009-2011. Conclusions Individuals with HF, AMI, and pneumonia experience high rates of readmission, but psychiatric comorbidities appear to increase that risk. Future readmission interventions should consider adding mental health components. PMID:25642610

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Influence of HMGB1 and MSCs transplantation on rat cardiac angiogenesis with acute myocardial infarction.

    PubMed

    Jiang, Youxu; Wang, Xiaoman; Jiang, Xiaodong; Niu, Shaohui; Zhang, Lihua

    2016-07-01

    To observe whether HMGB1could enhance the paracrine effect of MSCs when the Mesenchymal stem cells (Mesenchymal stem cells, MSCs) are pre-proccessed by High Mobility Group Box-1 (High Mobility Group Box-1, HMGB1). And to observe whether it can further increase the quantity of local angiogenesis in myocardial infarcts on the rat model with acute myocardial infarction, HMGB1 was combined with MSCs transplantation. MSCs in rats were cultivated with adherence and centrifugation method. Receptors of TLR4and RAGE in HMGB1 were tested. The MSCs were interfered by HMGB1 with different concentration gradient respectively, then the expression of VEGF was tested with ELISA method. SD male rats were divided into four groups: the model group, the MSCs transplantation group, the HMGB1 injection group, the HMGB1 injection plus MSCs transplantation group (n = 24), preparing rat model with acute myocardial infarction. The serum VEGF concentration levels were detected on the 3rd day, 7th and 28th day with ELISA method. On the 28th day after post operation the density of angiogenesis in infarction area was detected by immunohistochemal. (1) MSCs owned the expression of TLR4 and RAGE. (2) the secretion of VEGF increased significantly after the intervention of HMGB1 with concentration of 12.5 ng/mL, 25 ng/mL, 50 ng/mL, 100 ng/mL and 200ng/ml on MSCs compared with the control group. While the concentration was 400ng/ml or 800ng/ml, the secretion of VEGF decreased compared with the control group (P < 0.05). (3) detection of the serum VEGF on the 3rd or7th day after post operation was arranged: The results showed that: HMGB1 injection plus MSCs transplantation group > MSCs transplantation group >HMGB1 injection group >model group (P < 0.05). (4) the quantity of CD31 stained angiogenesis in HMGB1 injection plus MSCs transplantation group increased obviously. Combining MSCs transplantation, contributed to new angiogenesis of rats with acute myocardial infarction in myocardial infarction

  19. 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

  20. High morbidity in myocardial infarction and heart failure patients after gastric cancer surgery

    PubMed Central

    Jeong, Sang-Ho; Kim, Young-Woo; Yu, Wansik; Lee, Sang Ho; Park, Young Kyu; Park, Seong-Heum; Jeong, In Ho; Lee, Sang Eok; Park, Yongwhi; Lee, Young-Joon

    2015-01-01

    AIM: To evaluate to morbidity and mortality differences between 4 underlying heart diseases, myocardial infarction (MI), angina pectoris (Angina), heart failure (HF), and atrial fibrillation (AF), after radical surgery for gastric cancer. METHODS: We retrospectively collected data from 221 patients of a total of 15167 patients who underwent radical gastrectomy and were preoperatively diagnosed with a history of Angina, MI, HF, or AF in 8 hospitals. RESULTS: We find that the total morbidity rate is significantly higher in the MI group (44%) than the Angina (15.7%), AF (18.8%), and HF (23.1%) groups (P < 0.01). Moreover, we note that the risk for postoperative cardiac problems is higher in patients with a history of HF (23.1%) than patients with a history of Angina (2.2%), AF (4.3%), or MI (6%; P = 0.01). The HF and MI groups each have 1 case of cardiogenic mortality. CONCLUSION: We conclude that MI patients have a higher risk of morbidity, and HF patients have a higher risk of postoperative cardiac problems than Angina or AF. PMID:26074701

  1. 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. PMID:27353089

  2. 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 ...

  3. 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

  4. Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts

    PubMed Central

    Pierre, Sandrine V.; Yang, Changjun; Yuan, Zhaokan; Seminerio, Jennifer; Mouas, Christian; Garlid, Keith D.; Dos-Santos, Pierre; Xie, Zijian

    2007-01-01

    Objective Because ouabain activates several pathways that are critical to cardioprotective mechanisms such as ischemic preconditioning, we tested if this digitalis compound could protect the heart against ischemia-reperfusion injury through activation of the Na+,K+-ATPase/c-Src receptor complex. Methods and Results In Langendorff-perfused rat hearts, a short (4 min) administration of ouabain 10 μM followed by an 8-minute washout before 30 minutes of global ischemia and reperfusion improved cardiac function, decreased lactate dehydrogenase release and reduced infarct size by 40%. Western blot analysis revealed that ouabain activated the cardioprotective phospholipase Cγ1/protein kinase Cε (PLC-γ1/PKCε) pathway. Pre-treatment of the hearts with the Src kinase family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2) blocked not only ouabain-induced activation of PLC-γ1/PKCε pathway, but also cardiac protection. This protection was also blocked by a PKCε translocation inhibitor peptide (PKCε TIP). Conclusion Short exposure to a low concentration of ouabain protects the heart against ischemia/reperfusion injury. This effect of ouabain on the heart is most likely due to the activation of the Na+,K+-ATPase/c-Src receptor complex and subsequent stimulation of key mediators of preconditioning, namely PLC-γ1 and PKCε. PMID:17157283

  5. Plasminogen regulates cardiac repair after myocardial infarction through its non-canonical function in stem cell homing to the infarcted heart

    PubMed Central

    Gong, Yanqing; Zhao, Yujing; Li, Ying; Fan, Yi; Hoover-Plow, Jane

    2014-01-01

    Objective The purpose of this study was to investigate the role of Plasminogen (Plg) in stem cell-mediated cardiac repair and regeneration after myocardial infarction (MI) Background MI induces irreversible tissue damage, eventually leading to heart failure. Bone marrow (BM)-derived stem cells promote tissue repair and regeneration after MI. Thrombolytic treatment with Plg activators significantly improves the clinical outcome in MI by restoring cardiac perfusion. However, the role of Plg in stem cell-mediated cardiac repair remains unclear. Methods MI was induced in Plg deficient (Plg−/−) and wild-type (Plg+/+) mice by ligation of left anterior descending coronary artery (LAD). Stem cells were visualized by in vivo tracking of GFP-expressing BM cells after BM transplantation. Cardiac function, stem cell homing, signaling pathways downstream of Plg were examined. Results G-CSF, a stem cell mobilizer, significantly promoted BM-derived stem cells (GFP+c-kit+ cells) recruitment into infarcted heart and stem cell-meidated cardiac repair in Plg+/+ mice. However, Plg deficiency markedly inhibited stem cell homing and cardiac repair, suggesting that Plg is critical for stem cell-mediated cardiac repair. Moreover, Plg regulated CXCR4 expression in stem cells in vivo and in vitro through MMP-9. Lentiviral reconstitution of CXCR4 expression in BM cells rescued stem cell homing to the infarcted heart in Plg-deficient mice, indicating that a critical role of CXCR4 in Plg-mediated stem cell homing after MI. Conclusions These findings have identified a novel role of Plg in stem cell-mediated cardiac repair after MI. Thus, targeting Plg may offer a new therapeutic strategy for stem cell-mediated cardiac repair after MI. PMID:24681141

  6. Prenatal cocaine exposure increases heart susceptibility to ischaemia–reperfusion injury in adult male but not female rats

    PubMed Central

    Bae, Soochan; Gilbert, Raymond D; Ducsay, Charles A; Zhang, Lubo

    2005-01-01

    The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia–reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg−1) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups. Hearts were isolated from 2-month-old male and female offspring and were subjected to I/R (25 min/60 min) in a Langendorff preparation. Preischaemic values of left ventricular (LV) function were the same between the saline control and cocaine-treated hearts for both male and female rats. Prenatal cocaine exposure significantly increased I/R-induced myocardial apoptosis and infarct size, and significantly attenuated the postischaemic recovery of LV function in adult male offspring. In contrast, cocaine did not affect I/R-induced injury and postischaemic recovery of LV function in the female hearts. There was a significant decrease in PKCɛ and phospho-PKCɛ levels in LV in the male, but not female, offspring exposed to cocaine before birth. These results suggest that prenatal cocaine exposure causes a sex-specific increase in heart susceptibility to I/R injury in adult male offspring, and the decreased PKCɛ gene expression in the male heart may play an important role. PMID:15677681

  7. Constant magnetic field influence on a heart beat in rats

    SciTech Connect

    Lazetic, B.; Pekaric-Nadj, N.; Kasas-Lazetic, K.

    1991-03-11

    The authors used uretan narcose to implant constant magnets of 50 mT under the skin of rats in head region. The ECG was registrated in the next 6 hours. From it they found much slower heart beat which culminated in the first 105 minutes. After 6 weeks of continual exposure the heart beat of the exposed rats was still slower then in the controls. It is concluded that a chronical exposition to the constant magnetic field affected rats organisms and no regulatory mechanism could prevent it.

  8. 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.

  9. Serum complements and heart fatty acid binding protein in Bangladeshi patients with acute myocardial infarction

    PubMed Central

    Akhtar, Nayareen; Taher, Abu; Rahman, Rezwanur; Chowdhury, Ashesh Kumar

    2012-01-01

    The complement system is activated following acute myocardial infarction (AMI). Heart fatty acid binding protein (H-FABP) is a sensitive early biomarker of myocardial necrosis that can be used to confirm or exclude a diagnosis of AMI and to monitor recurrent infarction. This study was designed to detect changes in C3, C4 and H-FABP after AMI. Forty patients with AMI and a control group of 40 apparently healthy people were included. Selections were based on inclusion and exclusion criteria. The baseline characteristics were not significantly different between the groups. Patients’ blood samples were collected within 12 h of admission. Significant increases in C3 (AMI group 1.4260+0.04, healthy group 1.26040+0.04; p<0.05), C4 (AMI group 0.29305±0.013, healthy group 0.20860±0.012; p<0.05) and H-FABP (AMI group 12.3±1.69, healthy group 0.16±0.057; p<0.001) were seen in patients with AMI. The correlation between serum C3 and body mass index (BMI, r=0.33; p<0.05), serum C4 and BMI(r=0.313; p<0.05), serum C3 and total cholesterol high density lipoprotein (HDL, r=0.32; p<0.05), serum C4 and HbA1C (r=0.335; p<0.05) and serum C3 and troponin I (r= 0.325p<0.05) was found to be significant. But the correlation between serum C3 and waist:hip ratio (p=0.56), serum C4 and waist:hip ratio (p=0.83), serum C4 and total cholesterol HDL (p=0.993), serum C3 and HbA1C (p=0.440), serum C3 and random blood sugar (p=0.563), serum C4 and random blood sugar (p=0.828) and serum C4 and troponin I (p=0.373) was not significant. The significant complement activation detected in the plasma of patients with AMI indicated that complement plays a part in the pathogenesis of myocardial infarction. A significant increase of H-FABP improves the diagnosis of AMI.

  10. 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. PMID

  11. 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

  12. 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. PMID:27281548

  13. Kinetics of the electrocardiographic changes after permanent coronary occlusion in rats: Relationship with infarct size.

    PubMed

    Pimentel, Enildo Broetto; de Moraes, Andrea Cruz; Forechi, Ludimila; Machado, Rebeca Caldeira; Baldo, Marcelo Perim; Mill, Jose Geraldo

    2012-09-01

    The electrocardiogram (ECG) has been a useful tool to identify ischemia in humans and laboratory animals. Previous ECG studies showed that presence of pathological Q waves in lead DI in rats submitted to ligature of the left coronary artery (LCA) is a good predictor of successful myocardial infarction (MI). This study aimed to determine the sensitivity and the specificity of these ECG findings to predict successful MI. Male Wistar rats were submitted to surgical ligature of the LCA (N=86) or sham-operation (SO, N=16). ECG was recorded under halothane/ether anesthesia before surgery and 1, 3, 5, 7, and 15 days later. MI was determined by the presence of a transmural fibrous scar. Sixty-nine rats survived and 60 showed fibrous scar indicating a successful production of MI (18 and 42 animals were analyzed 1 or 15 days after MI, respectively). Twenty-four hours after, Q amplitude was linearly related to infarct size (r=-0.778; P<0.01), but not 15 days after (r=-0.416; P>0.05). In 53 out of 60 rats with transmural scar, Q wave in lead DI was identified in the ECG. Absence of Q wave occurred in 7 animals. The sensitivity was 88% (CI(95)=83-93%). Nine animals submitted to coronary ligature did not show infarct scar. One of these animals, however, showed Q wave in DI, indicating a specificity of 77% (CI(95)=65-104%). In conclusion, ECG can be used as a reliable tool to identify MI and can be used to predict the infarct size as earlier as 1 day after LCA ligation in rats. PMID:23037502

  14. Cardioprotection by ranolazine in perfused rat heart.

    PubMed

    Ghelardoni, Sandra; Chiellini, Grazia; Frascarelli, Sabina; Zucchi, Riccardo

    2014-12-01

    : We used the isolated working rat model to evaluate the effect of therapeutic concentrations (5-10 μM) of ranolazine on contractile performance, oxygen consumption, irreversible ischemic injury, and sarcoplasmic reticulum (SR) function. Ischemic injury was induced by 30 minutes of global ischemia followed by 120 minutes of Langendorff reperfusion and evaluated on the basis of triphenyltetrazolium chloride staining. SR function was determined on the basis of [H]-ryanodine binding, the kinetics of calcium-induced calcium release, measured by quick filtration technique, and oxalate-supported calcium uptake. In working hearts, ranolazine significantly reduced oxygen consumption (P = 0.031), in the absence of significant changes in contractile performance, and decreased irreversible ischemic injury (P = 0.011), if administered either before ischemia-reperfusion (25.4% ± 4.7% vs. 42.7% ± 6.0%) or only at the time of reperfusion (20.2% ± 5.2% vs. 43.7% ± 9.9%). In SR experiments, treatment with ranolazine determined a significant reduction in [H]-ryanodine binding (P = 0.029), because of decreased binding site density (369 ± 9 vs. 405 ± 12 fmol/mg), and in the kinetics of SR calcium release (P = 0.011), whose rate constant was decreased, whereas active calcium uptake was not affected. Ranolazine effectiveness at reperfusion and its ability to module SR calcium release suggest that this drug might be particularly useful to induce cardioprotection during coronary revascularization interventions, although the relevance of the effects on calcium homeostasis remains to be determined. PMID:25490416

  15. How Biomaterials Can Influence Various Cell Types in the Repair and Regeneration of the Heart after Myocardial Infarction

    PubMed Central

    Lister, Zachary; Rayner, Katey J.; Suuronen, Erik J.

    2016-01-01

    The healthy heart comprises many different cell types that work together to preserve optimal function. However, in a diseased heart the function of one or more cell types is compromised which can lead to many adverse events, one of which is myocardial infarction (MI). Immediately after MI, the cardiac environment is characterized by excessive cardiomyocyte death and inflammatory signals leading to the recruitment of macrophages to clear the debris. Proliferating fibroblasts then invade, and a collagenous scar is formed to prevent rupture. Better functional restoration of the heart is not achieved due to the limited regenerative capacity of cardiac tissue. To address this, biomaterial therapy is being investigated as an approach to improve regeneration in the infarcted heart, as they can possess the potential to control cell function in the infarct environment and limit the adverse compensatory changes that occur post-MI. Over the past decade, there has been considerable research into the development of biomaterials for cardiac regeneration post-MI; and various effects have been observed on different cell types depending on the biomaterial that is applied. Biomaterial treatment has been shown to enhance survival, improve function, promote proliferation, and guide the mobilization and recruitment of different cells in the post-MI heart. This review will provide a summary on the biomaterials developed to enhance cardiac regeneration and remodeling post-MI with a focus on how they control macrophages, cardiomyocytes, fibroblasts, and endothelial cells. A better understanding of how a biomaterial interacts with the different cell types in the heart may lead to the development of a more optimized biomaterial therapy for cardiac regeneration. PMID:27486578

  16. Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

    PubMed Central

    Qu, Daoxu; Ren, Huanhuan; Yang, Wenxiao; Zhang, Xinjie; Zheng, Qiusheng; Wang, Dong

    2016-01-01

    This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities. PMID:26788251

  17. Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway.

    PubMed

    Han, Dong; Huang, Wei; Li, Xiang; Gao, Lei; Su, Tao; Li, Xiujuan; Ma, Sai; Liu, Tong; Li, Congye; Chen, Jiangwei; Gao, Erhe; Cao, Feng

    2016-03-01

    Mesenchymal stem cells (MSCs)-based therapy provides a promising therapy for the ischemic heart disease (IHD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment, characterized by excessive inflammation and oxidative stress in the host's infarcted myocardium. Melatonin, an indole, which is produced by many organs including pineal gland, has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Using a murine model of myocardial infarction (MI), this study was designed to evaluate the impact of melatonin on adipose-derived mesenchymal stem cells (AD-MSCs)-based therapy for MI and the underlying mechanism involved with a focus on silent information regulator 1(SIRT1) signaling. Our results demonstrated that melatonin promoted functional survival of AD-MSCs in infarcted heart and provoked a synergetic effect with AD-MSCs to restore heart function. This in vivo effect of melatonin was associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart. In vitro studies revealed that melatonin exert cytoprotective effects on AD-MSCs against hypoxia/serum deprivation (H/SD) injury via attenuating inflammation, apoptosis, and oxidative stress. Mechanistically, melatonin enhanced SIRT1 signaling, which was accompanied with the increased expression of anti-apoptotic protein Bcl2, and decreased the expression of Ac-FoxO1, Ac-p53, Ac-NF-ΚB, and Bax. Taken together, our findings indicated that melatonin facilitated AD-MSCs-based therapy in MI, possibly through promoting survival of AD-MSCs via SIRT1 signaling. Our data support the promise of melatonin as a novel strategy to improve MSC-based therapy for IHD, possibly through SIRT1 signaling evocation. PMID:26607398

  18. 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.

  19. Positron emission tomography imaging of CD105 expression in a rat myocardial infarction model with (64)Cu-NOTA-TRC105.

    PubMed

    Orbay, Hakan; Zhang, Yin; Valdovinos, Hector F; Song, Guoqing; Hernandez, Reinier; Theuer, Charles P; Hacker, Timothy A; Nickles, Robert J; Cai, Weibo

    2013-01-01

    Biological changes following myocardial infarction (MI) lead to increased secretion of angiogenic factors that subsequently stimulate the formation of new blood vessels as a compensatory mechanism to reverse ischemia. The goal of this study was to assess the role of CD105 expression during MI-induced angiogenesis by positron emission tomography (PET) imaging using (64)Cu-labeled TRC105, an anti-CD105 monoclonal antibody. MI was induced by ligation of the left anterior descending (LAD) artery in female rats. Echocardiography and (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET scans were performed on post-operative day 3 to confirm the presence of MI in the infarct group and intact heart in the sham group, respectively. Ischemia-induced angiogenesis was non-invasively monitored with (64)Cu-NOTA-TRC105 (an extensively validated PET tracer in our previous studies) PET on post-operative days 3, 10, and 17. Tracer uptake in the infarct zone was highest on day 3 following MI, which was significantly higher than that in the sham group (1.41 ± 0.45 %ID/g vs 0.57 ± 0.07 %ID/g; n=3, p<0.05). Subsequently, tracer uptake in the infarct zone decreased over time to the background level on day 17, whereas tracer uptake in the heart of sham rats remained low at all time points examined. Histopathology documented increased CD105 expression following MI, which corroborated in vivo findings. This study indicated that PET imaging of CD105 can be a useful tool for MI-related research, which can potentially improve MI patient management in the future upon clinical translation of the optimized PET tracers. PMID:24380040

  20. Positron emission tomography imaging of CD105 expression in a rat myocardial infarction model with 64Cu-NOTA-TRC105

    PubMed Central

    Orbay, Hakan; Zhang, Yin; Valdovinos, Hector F; Song, Guoqing; Hernandez, Reinier; Theuer, Charles P; Hacker, Timothy A; Nickles, Robert J; Cai, Weibo

    2014-01-01

    Biological changes following myocardial infarction (MI) lead to increased secretion of angiogenic factors that subsequently stimulate the formation of new blood vessels as a compensatory mechanism to reverse ischemia. The goal of this study was to assess the role of CD105 expression during MI-induced angiogenesis by positron emission tomography (PET) imaging using 64Cu-labeled TRC105, an anti-CD105 monoclonal antibody. MI was induced by ligation of the left anterior descending (LAD) artery in female rats. Echocardiography and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET scans were performed on post-operative day 3 to confirm the presence of MI in the infarct group and intact heart in the sham group, respectively. Ischemia-induced angiogenesis was non-invasively monitored with 64Cu-NOTA-TRC105 (an extensively validated PET tracer in our previous studies) PET on post-operative days 3, 10, and 17. Tracer uptake in the infarct zone was highest on day 3 following MI, which was significantly higher than that in the sham group (1.41 ± 0.45 %ID/g vs 0.57 ± 0.07 %ID/g; n=3, p<0.05). Subsequently, tracer uptake in the infarct zone decreased over time to the background level on day 17, whereas tracer uptake in the heart of sham rats remained low at all time points examined. Histopathology documented increased CD105 expression following MI, which corroborated in vivo findings. This study indicated that PET imaging of CD105 can be a useful tool for MI-related research, which can potentially improve MI patient management in the future upon clinical translation of the optimized PET tracers. PMID:24380040

  1. Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

    PubMed Central

    Naderi, Roya; Mohaddes, Gisou; Mohammadi, Mustafa; Ghaznavi, Rana; Ghyasi, Rafigheh; Vatankhah, Amir Mansour

    2015-01-01

    Purpose: Oxidative stress plays a key role in the onset and development of diabetes complications. In this study, we evaluated whether voluntary exercise could alleviate oxidative stress in the heart and blood of streptozotocin - induced diabetic rats. Methods: 28 male Wistar rats were randomly divided into four groups (n=7): control, exercise, diabetes and exercise + diabetes. Diabetes was induced by injection of streptozotocin in male rats. Rats in the trained groups were subjected to voluntary running wheel exercise for 6 weeks. At the end of six weeks blood and heart tissue samples were collected and used for determination of antioxidant enzymes (including SOD, GPX and CAT activities) and MDA level. Results: Exercise significantly reduced MDA levels both in the heart tissue (p<0.01) and blood samples (p<0.05). In addition, exercise significantly increased SOD (p<0.05), GPX (p<0.001) and CAT (p<0.05) in the heart tissue. Voluntary exercise also significantly increased SOD (p<0.01), GPX (p<0.05) and CAT (p<0.001) in the blood. Conclusion: Voluntary exercise diminishes the MDA level in blood and heart tissue of diabetic rats. It also accentuates activities of SOD, GPX and CAT. Therefore, it may be considered a useful tool for the reduction of oxidative stress in diabetes. PMID:26236662

  2. Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

    SciTech Connect

    De Siena, Rocco; Balducci, Luigi; Blasi, Antonella; Montanaro, Manuela Gessica; Saldarelli, Marilisa; Saponaro, Vittorio; Martino, Carmela; Logrieco, Gaetano; Soleti, Antonio; Fiobellot, Simona; Madeddu, Paolo; Rossi, Giacomo; Ribatti, Domenico; Crovace, Antonio; Cristini, Silvia; Invernici, Gloria; Parati, Eugenio Agostino; Alessandri, Giulio

    2010-07-01

    Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50 x 10{sup 6} of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

  3. The small-molecule fast skeletal troponin activator, CK-2127107, improves exercise tolerance in a rat model of heart failure.

    PubMed

    Hwee, Darren T; Kennedy, Adam R; Hartman, James J; Ryans, Julie; Durham, Nickie; Malik, Fady I; Jasper, Jeffrey R

    2015-04-01

    Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca(2+) sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca(2+) relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 ± 22 versus 193 ± 31 seconds, respectively; mean ± S.E.M.; P = 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 ± 47 versus 116 ± 22 seconds; P = 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance. PMID:25678535

  4. Previous exercise training increases levels of PPAR-α in long-term post-myocardial infarction in rats, which is correlated with better inflammatory response

    PubMed Central

    Santos, Marília Harumi Higuchi; de Lourdes Higuchi, Maria; Tucci, Paulo J F; Garavelo, Shérrira M; Reis, Márcia M; Antonio, Ednei L; Serra, Andrey J; Maranhão, Raul Cavalcante

    2016-01-01

    OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87). CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which

  5. Paeonol and danshensu combination attenuates apoptosis in myocardial infarcted rats by inhibiting oxidative stress: Roles of Nrf2/HO-1 and PI3K/Akt pathway

    PubMed Central

    Li, Hua; Song, Fan; Duan, Lin-Rui; Sheng, Juan-Juan; Xie, Yan-Hua; Yang, Qian; Chen, Ying; Dong, Qian-Qian; Zhang, Bang-Le; Wang, Si-Wang

    2016-01-01

    Paeonol and danshensu is the representative active ingredient of traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae, respectively. Paeonol and danshensu combination (PDSS) has putative cardioprotective effects in treating ischemic heart disease (IHD). However, the evidence for the protective effect is scarce and the pharmacological mechanisms of the combination remain unclear. The present study was designed to investigate the protective effect of PDSS on isoproterenol (ISO)-induced myocardial infarction in rats and to elucidate the potential mechanism. Assays of creatine kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS significantly prevented myocardial injury induced by ISO. The ISO-induced profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS increased phosphorylated PI3K and Akt, which may in turn activate antioxidative and antiapoptotic signaling events in rat. These present findings demonstrated that PDSS exerts significant cardioprotective effects against ISO-induced myocardial infarction in rats. The protective effect is, at least partly, via activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival signaling pathway. PMID:27021411

  6. Lasting pure-motor deficits after focal posterior internal capsule white-matter infarcts in rats.

    PubMed

    Blasi, Francesco; Whalen, Michael J; Ayata, Cenk

    2015-06-01

    Small white-matter infarcts of the internal capsule are clinically prevalent but underrepresented among currently available animal models of ischemic stroke. In particular, the assessment of long-term outcome, a primary end point in clinical practice, has been challenging due to mild deficits and the rapid and often complete recovery in most experimental models. We, therefore, sought to develop a focal white-matter infarction model that can mimic the lasting neurologic deficits commonly observed in stroke patients. The potent vasoconstrictor endothelin-1 (n=24) or vehicle (n=9) was stereotactically injected into the internal capsule at one of three antero-posterior levels (1, 2, or 3 mm posterior to bregma) in male Sprague-Dawley rats. Endothelin-injected animals showed highly focal (~1 mm(3)) and reproducible ischemic infarcts, with severe axonal and myelin loss accompanied by cellular infiltration when examined 2 and 4 weeks after injection. Only those rats injected with endothelin-1 at the most posterior location developed robust and pure-motor deficits in adhesive removal, cylinder and foot-fault tests that persisted at 1 month, without detectable sensory impairments. In summary, we present an internal capsule stroke model optimized to produce lasting pure-motor deficits in rats that may be suitable to study neurologic recovery and rehabilitation after white-matter injury. PMID:25649992

  7. Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo

    PubMed Central

    Jazbutyte, Virginija; Stumpner, Jan; Redel, Andreas; Lorenzen, Johan M.; Roewer, Norbert

    2012-01-01

    The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17β- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94±15.5% vs. 17.1±3.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model. PMID:22876297

  8. Physiologic consequences of local heart irradiation in rats

    SciTech Connect

    Geist, B.J.; Lauk, S.; Bornhausen, M.; Trott, K.R. )

    1990-05-01

    Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions.

  9. Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain.

    PubMed

    Schilichting, C L R; Lima, K C M; Cestari, L A; Sekiyama, J Y; Silva, F M; Milani, H

    2004-04-01

    A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC) staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10% formalin at 0 masculine C until its total mass could be estimated. The mass (mg) of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm(3)), estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg), and reported as a percent (%) of the affected (left) hemisphere, correlated closely with volume (mm(3), also reported as %) estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10) or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41). This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23), and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24). The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke. PMID:15064814

  10. The beginning of the calcium transient in rat embryonic heart.

    PubMed

    Kobayashi, Takeshi; Maeda, Sachiko; Ichise, Nobutoshi; Sato, Tatsuya; Iwase, Takehito; Seki, Sumihiko; Yamada, Yoichi; Tohse, Noritsugu

    2011-03-01

    Although many researchers have tried to observe the beginning of the heartbeat, no study has shown the beginning of the calcium transient. Here, we evaluate the beginning of the calcium transient in the Wistar rat heart. We first tried to reveal when the heart of the Wistar rat begins to contract because no previous study has evaluated the beginning of the heartbeat in Wistar rats. Observation of embryos transferred to a small incubator mounted on a microscope revealed that the heart primordium, the so-called cardiac crescent, began to contract at embryonic day 9.99-10.13. Observation of embryos loaded with fluo-3 AM revealed that the beginning of the calcium transient precedes the initiation of contraction which precedes the appearance of the linear heart tube. Nifedipine (1 μM), but not ryanodine (1 μM), abolished the calcium transients. These results indicate that calcium transients in the early embryonic period involve exclusively calcium entry through L-type calcium channels in contrast to the situation in mature hearts. This study provides the first demonstration of the relationship between morphological changes in the heart primordium and the beginning of the calcium transient and contraction. PMID:21267689