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Sample records for myocardial ischemia

  1. Silent myocardial ischemia.

    PubMed

    Gutterman, David D

    2009-05-01

    Although much progress has been made in reducing mortality from ischemic cardiovascular disease, this condition remains the leading cause of death throughout the world. This might in part be due to the fact that over half of patients have a catastrophic event (heart attack or sudden death) as their initial manifestation of coronary disease. Contributing to this statistic is the observation that the majority of myocardial ischemic episodes are silent, indicating an inability or failure to sense ischemic damage or stress on the heart. This review examines the clinical characteristics of silent myocardial ischemia, and explores mechanisms involved in the generation of angina pectoris. Possible mechanisms for the more common manifestation of injurious reductions in coronary flow; namely, silent ischemia, are also explored. A new theory for the mechanism of silent ischemia is proposed. Finally, the prognostic importance of silent ischemia and potential future directions for research are discussed.

  2. [Ischemia-reperfusion myocardial injury].

    PubMed

    de Micheli, Alfredo; Chávez, Edmundo

    2003-01-01

    In this article, we present some considerations on the myocardial damage due to a deficit of oxygen supply. In fact, this damage properly constitutes a partial diastolic depolarization or injury, i.e., a moderate reduction of the rest transmembrane potential. This phenomenon is characteristic of the acute phase of the myocardial infarction syndrome and is responsible for the main electrical manifestations appearing in this phase: disorders of rhythm and conduction, as well as a reduced contractility of the involved myocardial fibers. All the mentioned phenomena are due to a defect of the myocardial energetic mechanisms, owing to the mitochondrial alterations in myocytes: early reduction of the nicotinamide adenine nucleotides, accumulation of calcium ("calcium overload") into mitochondria, and a drop in oxidative phosphorylation. These changes can present again, more exaggerated, in a following phase of evolution of the myocardial infarction due to myocardial reperfusion. Its severity is related to the duration of the initial ischemia period. Moreover, consequences of the oxidative stress can add producing cellular damage by liberation of reactive oxygen species. Oxidant stress causes also alterations in the mitochondrial DNA, i.e., mutations due to oxidation of nitrogenous bases. During the initial ischemia phase, as well as during reperfusion, metabolic therapy can be very useful as, for example, glucose-insulin-potassium solutions (G-I-K). These could act as scavengers of the free radicals derived from oxygen and avoid or reduce the myocardial damage due to reperfused myocytes. Metabolic drugs, as for example trimetazidine, antioxidants, etc, can also be used in the myocardial reperfusion phase.

  3. Controversies in cardiovascular care: silent myocardial ischemia

    NASA Technical Reports Server (NTRS)

    Hollenberg, N. K.

    1987-01-01

    The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

  4. Echocardiographic assessment of myocardial ischemia

    PubMed Central

    Dworrak, Birgit; Sanchis-Gomar, Fabian; Lucia, Alejandro; Buck, Thomas; Erbel, Raimund

    2016-01-01

    Over the last 60 years, echocardiography has emerged as a dominant and indispensable technique for the detection and assessment of coronary heart disease (CHD). In this review, we will describe and discuss this powerful tool of cardiology, especially in the hands of an experienced user, with a focus on myocardial ischemia. Technical development is still on-going, and various new ultrasound techniques have been established in the field of echocardiography in the last several years, including tissue Doppler imaging (TDI), contrast echocardiography, three-dimensional echocardiography (3DE), and speckle tracking echocardiography (i.e., strain/strain rate-echocardiography). High-end equipment with harmonic imaging, high frame rates and the opportunity to adjust mechanical indices has improved imaging quality. Like all new techniques, these techniques must first be subjected to comprehensive scientific assessment, and appropriate training that accounts for physical and physiological limits should be provided. These limits will constantly be redefined as echocardiographic techniques continue to change, which will present new challenges for the further development of ultrasound technology. PMID:27500160

  5. Echocardiographic assessment of myocardial ischemia.

    PubMed

    Leischik, Roman; Dworrak, Birgit; Sanchis-Gomar, Fabian; Lucia, Alejandro; Buck, Thomas; Erbel, Raimund

    2016-07-01

    Over the last 60 years, echocardiography has emerged as a dominant and indispensable technique for the detection and assessment of coronary heart disease (CHD). In this review, we will describe and discuss this powerful tool of cardiology, especially in the hands of an experienced user, with a focus on myocardial ischemia. Technical development is still on-going, and various new ultrasound techniques have been established in the field of echocardiography in the last several years, including tissue Doppler imaging (TDI), contrast echocardiography, three-dimensional echocardiography (3DE), and speckle tracking echocardiography (i.e., strain/strain rate-echocardiography). High-end equipment with harmonic imaging, high frame rates and the opportunity to adjust mechanical indices has improved imaging quality. Like all new techniques, these techniques must first be subjected to comprehensive scientific assessment, and appropriate training that accounts for physical and physiological limits should be provided. These limits will constantly be redefined as echocardiographic techniques continue to change, which will present new challenges for the further development of ultrasound technology. PMID:27500160

  6. Myocardial perfusion imaging for detection of silent myocardial ischemia

    SciTech Connect

    Beller, G.A.

    1988-04-21

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references.

  7. Thallium-201 myocardial scintigraphy in acute myocardial infarction and ischemia

    SciTech Connect

    Wackers, F.J.

    1982-04-01

    Thallium-201 scintigraphy provides a sensitive and reliable method of detecting acute myocardial infarction and ischemia when imaging is performed with understanding of the temporal characteristics and accuracy of the technique. The results of scintigraphy are related to the time interval between onset of symptoms and time of imaging. During the first 6 hr after chest pain almost all patients with acute myocardial infarction and approximately 50% of the patients with unstable angina will demonstrate /sup 201/TI pefusion defects. Delayed imaging at 2-4 hr will permit distinction between ischemia and infarction. In patients with acute myocardial infarction, the size of the perfusion defect accurately reflects the extent of the infarcted and/or jeopardized myocardium, which may be used for prognostic stratification. In view of the characteristics of /sup 201/TI scintigraphy, the most practical application of this technique is in patients in whom myocardial infarction has to be ruled out, and for early recognition of patients at high risk for complications.

  8. Intracoronary Levosimendan during Ischemia Prevents Myocardial Apoptosis

    PubMed Central

    Malmberg, Markus; Vähäsilta, Tommi; Saraste, Antti; Koskenvuo, Juha W.; Pärkkä, Jussi P.; Leino, Kari; Laitio, Timo; Stark, Christoffer; Heikkilä, Aira; Saukko, Pekka; Savunen, Timo

    2012-01-01

    Background: Levosimendan is a calcium sensitizer that has been shown to prevent myocardial contractile depression in patients post cardiac surgery. This drug exhibits an anti-apoptotic property; however, the underlying mechanism remains elusive. In this report, we characterized the myocardial protective of levosimendan in preventing cardiomyocyte apoptosis and post-operative stunning in an experimental ischemia–reperfusion model. Methods: Three groups of pigs (n = 8 per group) were subjected to 40 min of global, cardioplegic ischemia followed by 240 min of reperfusion. Levosimendan (65 μg/kg body weight) was given to pigs by intravenous infusion (L-IV) before ischemia or intracoronary administration during ischemia (L-IC). The Control group did not receive any levosimendan. Echocardiography was used to monitor cardiac function in all groups. Apoptosis levels were assessed from the left ventricle using the terminal transferase mediated dUTP nick end labeling (TUNEL) assay and immunocytochemical detection of Caspase-3. Results: Pigs after ischemia–reperfusion had a much higher TUNEL%, suggesting that our treatment protocol was effective. Levels of apoptosis were significantly increased in Control pigs that did not receive any levosimendan (0.062 ± 0.044%) relative to those received levosimendan either before (0.02 ± 0.017%, p = 0.03) or during (0.02 ± 0.017%, p = 0.03) the ischemia phase. Longitudinal left ventricular contraction in pigs that received levosimendan before ischemia (0.75 ± 0.12 mm) was significantly higher than those received levosimendan during ischemia (0.53 ± 0.11 mm, p = 0.003) or Control pigs (0.54 ± 0.11 mm, p = 0.01). Conclusion: Our results suggested that pigs received levosimendan displayed a markedly improved cell survival post I–R. The effect on cardiac contractility was only significant in our perfusion heart model when levosimendan was delivered intravenously before

  9. Role of Endothelial Cells in Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Singhal, Arun K.; Symons, J. David; Boudina, Sihem; Jaishy, Bharat; Shiu, Yan-Ting

    2014-01-01

    Minimizing myocardial ischemia-reperfusion injury has broad clinical implications and is a critical mediator of cardiac surgical outcomes. “Ischemic injury” results from a restriction in blood supply leading to a mismatch between oxygen supply and demand of a sufficient intensity and/or duration that leads to cell necrosis, whereas ischemia-reperfusion injury occurs when blood supply is restored after a period of ischemia and is usually associated with apoptosis (i.e. programmed cell death). Compared to vascular endothelial cells, cardiac myocytes are more sensitive to ischemic injury and have received the most attention in preventing myocardial ischemia-reperfusion injury. Many comprehensive reviews exist on various aspects of myocardial ischemia-reperfusion injury. The purpose of this review is to examine the role of vascular endothelial cells in myocardial ischemia-reperfusion injury, and to stimulate further research in this exciting and clinically relevant area. Two specific areas that are addressed include: 1) data suggesting that coronary endothelial cells are critical mediators of myocardial dysfunction after ischemia-reperfusion injury; and 2) the involvement of the mitochondrial permeability transition pore in endothelial cell death as a result of an ischemia-reperfusion insult. Elucidating the cellular signaling pathway(s) that leads to endothelial cell injury and/or death in response to ischemia-reperfusion is a key component to developing clinically applicable strategies that might minimize myocardial ischemia-reperfusion injury. PMID:25558187

  10. Caffeine reduces dipyridamole-induced myocardial ischemia

    SciTech Connect

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T. )

    1989-10-01

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-{sup 201}Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

  11. Transcriptomic Analysis of Myocardial Ischemia Using the Blood of Rat.

    PubMed

    Hou, Jincai; Fu, Jianhua; Li, Dan; Han, Xiao; Li, Lei; Song, Wenting; Yao, Mingjiang; Liu, Jianxun

    2015-01-01

    Myocardial ischemia is a pathological state of heart with reduced blood flow to heart and abnormal myocardial energy metabolism. This disease occurs commonly in middle aged and elderly people. Several studies have indicated that the rat was an appropriate animal model used to study myocardial ischemia. In this study, in order to gain insights into the pathogenesis of myocardial ischemia, we sequenced the transcriptomes of three normal rats as control and the same number of myocardial ischemia rats. We sequenced the genomes of 6 rats, including 3 cases (myocardial ischemia) and 3 controls using Illumina HiSeq 2000. Then we calculated the gene expression values and identified differentially expressed genes based on reads per kilobase transcriptome per million (RPKM). Meanwhile we performed a GO enrichment analysis and predicted novel transcripts. In our study, we found that 707 genes were up-regulated and 21 genes were down-regulated in myocardial ischemia rats by at least 2-fold compared with controls. By the distribution of reads and the annotation of reference genes, we found 1,703 and 1,552 novel transcripts in cases and controls, respectively. At the same time, we refined the structure of 9,587 genes in controls and 10,301 in cases. According to the results of GO term and pathway analysis of differentially expressed genes, we found that the immune response, stimulus response, response to stress and some diseases may be associated with myocardial ischemia. Since many diseases, especially immune diseases, are associated with myocardial ischemia, we should pay more attention to the complications which might result from myocardial ischemia.

  12. Effects of carbon monoxide on myocardial ischemia

    SciTech Connect

    Allred, E.N.; Pagano, M. ); Bleecker, E.R.; Walden, S.M. ); Chaitman, B.R.; Dahms, T.E. ); Hackney, J.D.; Selvester, R.H. ); Warren, J. ); Gottlieb, S.O.

    1991-02-01

    The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre-versus postexposure exercise test at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.

  13. [Myocardial serotonin metabolism after local ischemia and ischemic precondition].

    PubMed

    Naumenko, S E; Latysheva, T V; Gilinskiĭ, M A

    2014-07-01

    To determine the effect of ischemic preconditioning upon myocardial serotonin and 5-hydroxyindolacetic acid (5-HIAA) dynamic in myocardial ischemia and reperfusion. 28 male Wistar rats anesthetized with urethane were randomly divided into 2 groups. In the control group (n = 13) rats were subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. In the ex- perimental group (n = 15) ischemic preconditioning (3 x 3 min ischemia + 3 x 3 min reperfusion) before prolonged ischemia was used. Myocardial interstitial serotonin and 5-HIAA were measured using a microdialysis technique. Myocardial serotonin and 5-HIAA significantly increased af- ter ischemic preconditioning (p = 0.00298; p = 0.00187). In prolonged ischemia interstitial serotonin level was lower in the experimental group vs. control up to 20 min of ischemia (p < 0.05). We conclude that ischemic preconditioning increases interstitial myocardial serotonin, but inhibit serotonin increase in subsequent prolonged myocardial ischemia. After 20 minutes of reperfusion the lack of correlation between serotonin and 5-HIAA levels appeared which may be the evidence of serotonin uptake activation.

  14. Usefulness of MRI to demonstrate the mechanisms of myocardial ischemia in hypertrophic cardiomyopathy with myocardial bridge.

    PubMed

    Thomson, Vivien; Botnar, Rene; Croisille, Pierre

    2007-01-01

    We present a case of symptomatic primary hypertrophic cardiomyopathy (HCM) associated with myocardial bridging of the left anterior descending (LAD) artery and suspected ischemia that could be related either to LAD artery compression or to microvascular perfusion abnormalities. MRI demonstrated the morphological appearance of myocardial hypertrophy, and coronary MR angiography evidenced the myocardial bridge and its functional consequences with stress MR perfusion. In conclusion, as a non-invasive comprehensive imaging technique, MRI should be considered in identifying the mechanisms of myocardial ischemia in HCM with myocardial bridge. PMID:16888385

  15. Met-enkephalin levels during PTCA-induced myocardial ischemia.

    PubMed

    Parlapiano, C; Borgia, M C; Tonnarini, G; Giancaspro, G; Pizzuto, F; Campana, E; Giovanniello, T; Pantone, P; Vincentelli, G M; Alegiani, F; Negri, M

    2001-07-01

    Met-enkephalin (Met-enk) has been demonstrated to modulate myocardial-ischemia mechanisms via the opioid receptors, but no studies are now available on Met-enk levels in the coronary circulation. In this experience Met-enk levels were evaluated in aortic root and in coronary sinus at baseline (T0), during PTCA induced transient ischemia (T1) and during reperfusion (T2). No significant differences were found at any time. Thus, it appears that there is no Met-enk extraction from the coronary circulation during provoked myocardial ischemia and no Met-enk release from the ischemic heart. PMID:11445249

  16. Exercise-induced Myocardial Ischemia Detected by Cardiopulmonary Exercise Testing

    PubMed Central

    Chaudhry, Sundeep; Arena, Ross; Wasserman, Karlman; Hansen, James E.; Lewis, Gregory D.; Myers, Jonathan; Chronos, Nicolas; Boden, William E.

    2010-01-01

    Cardiopulmonary exercise testing (CPET) is a well-accepted physiologic evaluation technique in patients diagnosed with heart failure and in individuals presenting with unexplained dyspnea on exertion. Several variables obtained during CPET, including oxygen consumption relative to heart rate (VO2/HR or O2-pulse) and work rate (VO2/Watt) provide consistent, quantitative patterns of abnormal physiologic responses to graded exercise when left ventricular dysfunction is caused by myocardial ischemia. This concept paper describes both the methodology and clinical application of CPET associated with myocardial ischemia. Initial evidence indicates left ventricular dysfunction induced by myocardial ischemia may be accurately detected by an abnormal CPET response. CPET testing may complement current non-invasive testing modalities that elicit inducible ischemia. It provides a physiologic quantification of the work rate, heart rate and O2 uptake at which myocardial ischemia develops. In conclusion, the potential value of adding CPET with gas exchange measurements is likely to be of great value in diagnosing and quantifying both overt and occult myocardial ischemia and its reversibility with treatment. PMID:19231322

  17. Effects of carbon monoxide on myocardial ischemia.

    PubMed Central

    Allred, E N; Bleecker, E R; Chaitman, B R; Dahms, T E; Gottlieb, S O; Hackney, J D; Pagano, M; Selvester, R H; Walden, S M; Warren, J

    1991-01-01

    The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease. PMID:2040254

  18. Association between Anger and Mental Stress-Induced Myocardial Ischemia

    PubMed Central

    Pimple, Pratik; Shah, Amit; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Kelley, Mary; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Background Mental stress-induced myocardial ischemia is associated with adverse prognosis in coronary artery disease patients. Anger is thought to be a trigger of acute coronary syndromes and is associated with increased cardiovascular risk; however, little direct evidence exists for a link between anger and myocardial ischemia. Methods [99mTc]sestamibi single-photon emission tomography was performed at rest, after mental stress (a social stressor with a speech task), and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed difference score, the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. The Spielberger's State-Trait Anger Expression Inventory was used to assess different anger dimensions. Results The mean age was 50 years, 50% were female and 60% were non-white. After adjusting for demographic factors, smoking, coronary artery disease severity, depressive and anxiety symptoms, each interquartile range increment in state-anger score was associated with 0.36 units adjusted increase in ischemia as measured by the summed difference score (95% CI: 0.14-0.59); the corresponding association for trait-anger was 0.95 (95% CI: 0.21-1.69). Anger expression scales were not associated ischemia. None of the anger dimensions were related to ischemia during exercise/pharmacological stress. Conclusion Anger, both as an emotional state and as a personality trait, is significantly associated with propensity to develop myocardial ischemia during mental stress, but not during exercise/pharmacological stress. Patients with this psychological profile may be at increased risk for silent ischemia induced by emotional stress and this may translate into worse prognosis. PMID:25497256

  19. Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report

    PubMed Central

    2012-01-01

    Background Chest pain, a key element in the investigation of coronary artery disease is often regarded as a benign prognosis when present in panic attacks. However, panic disorder has been suggested as an independent risk factor for long-term prognosis of cardiovascular diseases and a trigger of acute myocardial infarction. Objective Faced with the extreme importance in differentiate from ischemic to non-ischemic chest pain, we report a case of panic attack induced by inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by myocardial perfusion imaging study. Discussion Panic attack is undoubtedly a strong component of mental stress. Patients with coronary artery disease may present myocardial ischemia in mental stress response by two ways: an increase in coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in myocardial oxygen consumption. Coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. Possibly the carbon dioxide challenge test could trigger myocardial ischemia by the same mechanisms. Conclusion The use of mental stress has been suggested as an alternative method for myocardial ischemia investigation. Based on translational medicine objectives the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to allow improved application of research-based knowledge to the medical field, specifically at the interface of PD and cardiovascular disease. PMID:22999016

  20. Energy Drinks and Myocardial Ischemia: A Review of Case Reports.

    PubMed

    Lippi, Giuseppe; Cervellin, Gianfranco; Sanchis-Gomar, Fabian

    2016-07-01

    The use and abuse of energy drinks (EDs) is constantly increasing worldwide. We performed a systematic search in Medline, Scopus and Web of Science to identify evidence about the potential link between these beverages and myocardial ischemia. Overall, 8 case reports could be detected, all of which described a realistic association between large intake of EDs and episodes of myocardial ischemia. Interestingly, no additional triggers of myocardial ischemia other than energy drinks could be identified in the vast majority of cases. Some plausible explanations can be brought in support of this association. Most of the biological effects of EDs are seemingly mediated by a positive inotropic effect on cardiac function, which entails increase in heart rate, cardiac output and contractility, stroke volume and arterial blood pressure. Additional biological abnormalities reported after EDs intake include increased platelet aggregation, endothelial dysfunction, hyperglycemia as well as an increase in total cholesterol, triglycerides and low-density lipoprotein cholesterol. Although a causal relationship between large consumption of EDs and myocardial ischemia cannot be definitely established so far, concerns about the cardiovascular risk of excessive consumption of these beverages are seemingly justified.

  1. Energy Drinks and Myocardial Ischemia: A Review of Case Reports.

    PubMed

    Lippi, Giuseppe; Cervellin, Gianfranco; Sanchis-Gomar, Fabian

    2016-07-01

    The use and abuse of energy drinks (EDs) is constantly increasing worldwide. We performed a systematic search in Medline, Scopus and Web of Science to identify evidence about the potential link between these beverages and myocardial ischemia. Overall, 8 case reports could be detected, all of which described a realistic association between large intake of EDs and episodes of myocardial ischemia. Interestingly, no additional triggers of myocardial ischemia other than energy drinks could be identified in the vast majority of cases. Some plausible explanations can be brought in support of this association. Most of the biological effects of EDs are seemingly mediated by a positive inotropic effect on cardiac function, which entails increase in heart rate, cardiac output and contractility, stroke volume and arterial blood pressure. Additional biological abnormalities reported after EDs intake include increased platelet aggregation, endothelial dysfunction, hyperglycemia as well as an increase in total cholesterol, triglycerides and low-density lipoprotein cholesterol. Although a causal relationship between large consumption of EDs and myocardial ischemia cannot be definitely established so far, concerns about the cardiovascular risk of excessive consumption of these beverages are seemingly justified. PMID:26320007

  2. Purkinje fibers after myocardial ischemia-reperfusion.

    PubMed

    García Gómez-Heras, Soledad; Álvarez-Ayuso, Lourdes; Torralba Arranz, Amalia; Fernández-García, Héctor

    2015-07-01

    The purpose of this study was to evaluate the effects of ischemia-reperfusion on Purkinje fibers, comparing them with the adjacent cardiomyocytes. In a model of heterotopic heart transplantation in pigs, the donor heart was subjected to 2 hours of ischemia (n=9), preserved in cold saline, and subjected to 24 hours of ischemia with preservation in Wisconsin solution, alone (n=6), or with an additive consisting of calcium (n=4), Nicorandil (n=6) or Trolox (n=7). After 2 hours of reperfusion, we evaluated the recovery of cardiac electrical activity and took samples of ventricular myocardium for morphological study. The prolonged ischemia significantly affected atrial automaticity and A-V conduction in all the groups subjected to 24 hours of ischemia, as compared to 2 hours. There were no significant differences among the groups that underwent prolonged ischemia. Changes in the electrical activity did not correlate with the morphological changes. In the Purkinje fibers, ischemia-reperfusion produced a marked decrease in the glycogen content in all the groups. In the gap junctions the immunolabeling of connexin-43 decreased significantly, adopting a dispersed distribution, and staining the sarcolemma adjacent to the connective tissue. These changes were less marked in the group preserved exclusively with Wisconsin solution, despite the prolonged ischemia. The addition of other substances did not improve the altered morphology. In all the groups, the injury appeared to be more prominent in the Purkinje fibers than in the neighboring cardiomyocytes, indicating the greater susceptibility of the former to ischemia-reperfusion injury. PMID:25648569

  3. Incidence of acute myocardial infarction in patients with exercise-induced silent myocardial ischemia

    SciTech Connect

    Assey, M.E.; Walters, G.L.; Hendrix, G.H.; Carabello, B.A.; Usher, B.W.; Spann, J.F. Jr.

    1987-03-01

    Fifty-five patients with angiographically proved coronary artery disease (CAD) underwent Bruce protocol exercise stress testing with thallium-201 imaging. Twenty-seven patients (group I) showed myocardial hypoperfusion without angina pectoris during stress, which normalized at rest, and 28 patients (group II) had a similar pattern of reversible myocardial hypoperfusion but also had angina during stress. Patients were followed for at least 30 months. Six patients in group I had an acute myocardial infarction (AMI), 3 of whom died, and only 1 patient in group II had an AMI (p = 0.05), and did not die. Silent myocardial ischemia uncovered during exercise stress thallium testing may predispose to subsequent AMI. The presence of silent myocardial ischemia identified in this manner is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.

  4. Depressive Symptoms Are Associated with Mental Stress-Induced Myocardial Ischemia after Acute Myocardial Infarction

    PubMed Central

    Wei, Jingkai; Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon A.; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Objectives Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI. Methods We studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores. Results There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress. Conclusion Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress. PMID:25061993

  5. Lidocaine Enhances Contractile Function of Ischemic Myocardial Regions in Mouse Model of Sustained Myocardial Ischemia

    PubMed Central

    Kania, Gabriela; Osto, Elena; Jakob, Philipp; Krasniqi, Nazmi; Beck-Schimmer, Beatrice; Blyszczuk, Przemyslaw; Eriksson, Urs

    2016-01-01

    Rationale Perioperative myocardial ischemia is common in high-risk patients. The use of interventional revascularisation or even thrombolysis is limited in this patient subset due to exceedingly high bleeding risks. Blockade of voltage-gated sodium channels (VGSC) with lidocaine had been suggested to reduce infarct size and cardiomyocyte cell death in ischemia/reperfusion models. However, the impact of lidocaine on cardiac function during sustained ischemia still remains unclear. Methods Sustained myocardial ischemia was induced by ligation of the left anterior descending artery in 12–16 weeks old male BALB/c mice. Subcutaneous lidocaine (30 mg/kg) was used to block VGSC. Cardiac function was quantified at baseline and at 72h by conventional and speckle-tracking based echocardiography to allow high-sensitivity in vivo phenotyping. Infarct size and cardiomyocyte cell death were assessed post mortem histologically and indirectly using troponin measurements. Results Ischemia strongly impaired both, global systolic and diastolic function, which were partially rescued in lidocaine treated in mice. No differences regarding infarct size and cardiomyocyte cell death were observed. Mechanistically, and as shown with speckle-tracking analysis, lidocaine specifically improves residual contractility in the ischemic but not in the remote, non-ischemic myocardium. Conclusion VGSC blockade with lidocaine rescues function of ischemic myocardium as a potential bridging to revascularisation in the setting of perioperative myocardial ischemia. PMID:27140425

  6. Myocardial Ischemia: Lack of Coronary Blood Flow or Myocardial Oxygen Supply/Demand Imbalance?

    PubMed

    Heusch, Gerd

    2016-07-01

    Regional myocardial blood flow and contractile function in ischemic myocardium are well matched, and there is no evidence for an oxygen supply/demand imbalance. Thus, myocardial ischemia is lack of coronary blood flow with electric, functional, metabolic, and structural consequences for the myocardium. All therapeutic interventions must aim to improve blood flow to ischemic myocardium as much and as quickly as possible. PMID:27390331

  7. In vivo study of myocardial elastography under graded ischemia conditions

    NASA Astrophysics Data System (ADS)

    Lee, Wei-Ning; Provost, Jean; Fujikura, Kana; Wang, Jie; Konofagou, Elisa E.

    2011-02-01

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  8. Asymptomatic myocardial ischemia following cold provocation

    SciTech Connect

    Shea, M.J.; Deanfield, J.E.; deLandsheere, C.M.; Wilson, R.A.; Kensett, M.; Selwyn, A.P.

    1987-09-01

    Cold is thought to provoke angina in patients with coronary disease either by an increase in myocardial demand or an increase in coronary vascular resistance. We investigated and compared the effects of cold pressor stimulation and symptom-limited supine bicycle exercise on regional myocardial perfusion in 35 patients with stable angina and coronary disease and in 10 normal subjects. Regional myocardial perfusion was assessed with positron emission tomography and rubidium-82. Following cold pressor stimulation 24 of 35 patients demonstrated significant abnormalities of regional myocardial perfusion with reduced cation uptake in affected regions of myocardium: 52 +/- 9 to 43 +/- 9 (p less than 0.001 vs normal subjects). Among these 24 patients only nine developed ST depression and only seven had angina. In contrast, 29 of 35 patients underwent supine exercise, and abnormal regional myocardial perfusion occurred in all 29, with a reduction in cation intake from 48 +/- 10 to 43 +/- 14 (p less than 0.001 vs normal subjects). Angina was present in 27 of 29 and ST depression in 25 of 29. Although the absolute decrease in cation uptake was somewhat greater following cold as opposed to exercise, the peak heart rate after cold was significantly lower than that after exercise (82 +/- 12 vs 108 +/- 16 bpm, p less than 0.05). Peak systolic blood pressures after cold and exercise were similar (159 +/- 24 vs 158 +/- 28). Thus, cold produces much more frequent asymptomatic disturbances of regional myocardial perfusion in patients with stable angina and coronary disease than is suggested by pain or ECG changes.

  9. [Perioperative myocardial ischemia in patients with peripheral arterial occlusive diseases].

    PubMed

    Rapp, H J; Buselmeier, P; Gasteiger, P; Hoberg, E; Striebel, J P

    1990-04-01

    Patients with peripheral vascular disease (PVD) often have coronary artery disease (CAD) which means an increased risk during anesthesia. The prevalence of CAD is nearly 50% among such patients. Owing to claudication, diagnostic stress tests can rarely be performed in PVD patients. In order to evaluate the frequency of transient perioperative myocardial ischemia, Holter monitoring was performed in 30 consecutive PVD patients with ASA II-III and AVK scale (Fontaine) II-IV who were undergoing femoropopliteal bypass surgery. Patients who had left bundle branch block and left ventricular hypertrophy or were taking digitalis medication were excluded from Holter monitoring. The ST-segment analysis of the frequency modulated recordings (n = 19) revealed episodes of myocardial ischemia in 26% of the patients. Most (75%) of the episodes occurred preoperatively, and 25%, during or after the anesthesia or during preparation for it. Risk factors for CAD were more often found in patients with ST segment alterations than in patients without ST segment deviations, even though the preoperative antianginal medication administered was comparable in the two subgroups. It is concluded that in a considerable subset of PVD patients silent myocardial ischemia occurs, which can be related to the different perioperative intervals by means of ST segment analyses of Holter recordings. The ST segment may allow a better insight into the cardiac state of PVD patients. Further studies are necessary in larger populations to test our suspicion.

  10. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure.

    PubMed

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-12-14

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF.

  11. Myocardial functional preservation during ischemia: influence of beta blocking agents.

    PubMed

    Toleikis, P M; Tomlinson, C W

    1997-11-01

    To determine whether prior acute Beta blockade protects the heart against the deleterious effects of normothermic low flow global ischemia on myocardial function, aortic pressure, developed pressure, dP/dtmax and end diastolic pressure were monitored in isolated perfused rabbit hearts prior to, during and following 30 and 60 min ischemia, during which either Krebs-Henseleit (control) or Beta blocking agents. Bevantolol (cardioselective) or Propranolol (non-selective) were perfused through the heart. Control hearts made ischemic for 30 min and then reperfused had significantly elevated end diastolic (p < .01) and aortic pressures (p < .01) and reduced developed pressure relative to baseline (p < .05). Hearts treated with Bevantolol or Propranolol (3 x 10(-5) m/l) 5 min prior to and during 30 min ischemia recovered preischemic developed pressure and dP/dtmax (p > 0.05), while end diastolic pressure was elevated (p < .01, p < .05 respectively). Aortic pressure was unchanged relative to baseline (p > .05). Comparison of indices from hearts under Beta blockade with controls showed that following 30 min ischemia and recovery, the Bevantolol treated group had reduced aortic pressure (p < .01) and end diastolic pressure (p < .05) and increased percent developed pressure and percent dP/dtmax (p < .001) relative to control. In the propranolol treated group, end diastolic pressure was reduced and percent developed pressure (p < .01) and percent dP/dtmax (p < .001) were increased relative to unblocked hearts. Following 60 min ischemia and 30 min reperfusion, reduction in all functional indices occurred, however dP/dtmax was unchanged from baseline in the Propranolol and Bevantolol treated groups. Comparison between groups showed that the Bevantolol treated group had significantly better dP/dtmax and developed pressure (p < .05), whereas the Propranolol group shows no significant difference from baseline (p > .05) (K-H). We conclude that following short periods of ischemia

  12. Protective effect of tetramethylpyrazine on myocardial ischemia-reperfusion injury.

    PubMed

    Qian, Weidong; Xiong, Xingjiang; Fang, Zhuyuan; Lu, Haiting; Wang, Zhensheng

    2014-01-01

    Myocardial ischemia-reperfusion injury (MIRI) is a common pathological and physiological phenomenon. Tetramethylpyrazine is the extract of the traditional Chinese medicine Chuanxiong, which can exert protective effects on MIRI in multiple ways. This paper reviewed the current research progress and evidence about the cardiovascular effects of tetramethylpyrazine, which included protecting mitochondria and improving energy metabolism, scavenging oxygen free radicals (OFRs) to inhibit lipid peroxidation, attenuating calcium (Ca(2+)) overload and maintaining Ca(2+) homeostasis in cells, inhibiting apoptosis and protecting myocardial cells, interfering with the inflammatory reaction and mitigating cell injury, interfering with cell signaling pathways, and improving function of endothelial cells and protecting myocardial cells. However, further rigorously designed randomized controlled trials are warranted. PMID:25152756

  13. Adenosine triphosphate stress echocardiography in the detection of myocardial ischemia.

    PubMed

    Fukai, T; Koyanagi, S; Tashiro, H; Ichiki, T; Tsutsui, H; Matsumoto, T; Takeshita, A

    1995-10-01

    The purpose of this study was to assess feasibility and safety in the diagnosis of coronary artery in the diagnosis of coronary artery disease and myocardial ischemia using adenosine triphosphate (ATP) stress echocardiography. ATP, a product of human myocardial tissue, is more potent than adenosine in increasing coronary blood flow. Like adenosine, ATP also has a short half-life (<10 s). Left ventricular echocardiograms were recorded during step-wise infusions of ATP in 86 patients who underwent coronary angiography and stress thallium 201 scintigraphy. No serious complications occurred with ATP infusion and most of the side effects were mild and transient. Significant coronary artery disease (>75% diameter stenosis) was present in 34 of 48 patients who had normal echocardiograms at rest. The sensitivity and specificity of ATP-induced wall motion abnormalities for coronary artery disease was 65% (22 of 34) and 100% (14 of 14), respectively. The sensitivity was 50% (10 of 20) in those with one-vessel disease and 86% (12 of 14) in those with multivessel disease (P < .05). In patients with normal echocardiograms at rest and without prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of myocardial ischemia assessed by 201Tl single proton emission computed tomography was 58%, with a specificity of 76%, and a diagnostic accuracy of 66%. The sensitivity was 43% in those with one-vessel disease, and 86% in those with multivessel disease (P = .05). In patients with prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of viable but jeopardized myocardium was 81%, with a specificity of 91%. The patients with well-developed collateral circulation had a higher incidence of developing wall motion abnormality than those without collaterals (70% v 40%, P < .01). ATP stress echocardiography is valuable for the assessment of coronary artery disease in patients with multivessel disease, coronary

  14. Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation

    PubMed Central

    Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

    2016-01-01

    Purpose: The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. Methods: A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Results: Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Conclusions: Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease.

  15. An uncommon cause of myocardial ischemia after coronary artery bypass grafting: "the dangerous drainage".

    PubMed

    Beiras-Fernandez, Andres; Möhnle, Patrick; Kopf, Carsten; Vicol, Calin; Kur, Felix; Reichart, Bruno

    2011-06-01

    The most common causes of myocardial ischemia and myocardial infarction early after coronary artery bypass grafting surgery are early graft occlusion/thrombosis or occlusion/ thrombosis of coronary arteries due to advanced coronary heart disease. We describe a case of postoperative myocardial ischemia due to an uncommon and quickly reversible cause: mechanical compression of a vein graft by a 19F flexible silicone mediastinal drainage tube.

  16. Sum of effects of myocardial ischemia followed by electrically induced tachycardia on myocardial function

    PubMed Central

    Díez, José Luis; Hernándiz, Amparo; Cosín-Aguilar, Juan; Aguilar, Amparo; Portolés, Manuel

    2013-01-01

    Background The alteration of contractile function after tachyarrhythmia ceases is influenced by the type of prior ischemia (acute coronary syndrome or ischemia inherent in a coronary revascularization procedure). We aimed to analyze cardiac dysfunction in an acute experimental model of supraphysiological heart rate preceded by different durations and types of ischemia. Material/Methods Twenty-four pigs were included in: (S1) series of ventricular pacing; (S2, A and B) series with 10 or 20 min, respectively, of coronary occlusion previous to ventricular pacing; S3 with 20 brief, repeated ischemia/reperfusion processes prior to ventricular pacing and; (S4) control series. Overall cardiac function parameters and regional myocardial contractility at the apex and base of the left ventricle were recorded, as were oxidative stress markers (glutathione and lipid peroxide serum levels). Left ventricular pacing at 60% over baseline heart rate was performed for 2 h followed by 1 h of recovery. Results High ventricular pacing rates preceded by short, repeated periods of coronary ischemia/reperfusion resulted in worse impairment of overall cardiac and regional function that continued to be altered 1 h after tachycardia ceased. There was significant reduction of stroke volume (26.9±5.3 basal vs. 16±6.2 ml; p<0.05), LVP; dP/dt and LAD flow (13.1±1.5 basal vs. 8.4±1.6 ml/min; p<0.05); the base contractility remained altered when recovering compared to baseline (base SF: 5.6±2.8 vs. 2.2±0.7%; p<0.05); and LPO levels were higher than less aggressive series at the end of recovery. Conclusions Ischemia and tachycardia accumulate their effects, with increased cardiac involvement depending on the type of ischemia. PMID:23722244

  17. [Practical value of the detection of silent myocardial ischemia in patients with coronary disease using Holters].

    PubMed

    Jan, F; Monin, J L; Leichter, S; Pochmalicki, G

    1994-02-01

    The prognosis of painless myocardial ischemia is similar to that of symptomatic ischemia. The Holter technique (and solid memory Holter in particular) is a simple method of detection which, taken together with exercise testing, enables the identification among coronary disease patients of a high risk group in whom effort ischemia is accompanied by episodes of ischemia under everyday conditions and in whom additional investigations (exercise thallium scan then coronary arteriography) and appropriate treatment, including transluminal angioplasty and aorto-coronary bypass if necessary, may be required. The role of drug treatment in silent ischemia has not yet been clearly defined. While electrical ischemia regresses significantly with the majority of standard drug regimens, and beta-blockers in particular, none has yet been confirmed as having a preventive effect against serious events following on from silent myocardial ischemia.

  18. Angina and exertional myocardial ischemia in diabetic and nondiabetic patients: assessment by exercise thallium scintigraphy

    SciTech Connect

    Nesto, R.W.; Phillips, R.T.; Kett, K.G.; Hill, T.; Perper, E.; Young, E.; Leland, O.S. Jr.

    1988-02-01

    Patients with diabetes mellitus and coronary artery disease are thought to have painless myocardial ischemia more often than patients without diabetes. We studied 50 consecutive patients with diabetes and 50 consecutive patients without diabetes, all with ischemia, on exercise thallium scintigraphy to show the reliability of angina as a marker for exertional ischemia. The two groups had similar clinical characteristics, treadmill test results, and extent of infarction and ischemia, but only 7 patients with diabetes compared with 17 patients without diabetes had angina during exertional ischemia. In diabetic patients the extent of retinopathy, nephropathy, or peripheral neuropathy was similar in patients with and without angina. Angina is an unreliable index of myocardial ischemia in diabetic patients with coronary artery disease. Given the increased cardiac morbidity and mortality in such patients, periodic objective assessments of the extent of ischemia are warranted.

  19. Baicalein Reduces Liver Injury Induced by Myocardial Ischemia and Reperfusion.

    PubMed

    Lai, Chang-Chi; Huang, Po-Hsun; Yang, An-Han; Chiang, Shu-Chiung; Tang, Chia-Yu; Tseng, Kuo-Wei; Huang, Cheng-Hsiung

    2016-01-01

    Baicalein is a component of the root of Scutellaria baicalensis Georgi, which has traditionally been used to treat liver disease in China. In the present study, we investigated baicalein' ability to reduce the liver injury induced by myocardial ischemia and reperfusion (I/R). Myocardial I/R was induced in this experiment by a 40[Formula: see text]min occlusion of the left anterior descending coronary artery and a 3[Formula: see text]h reperfusion in rats. The induced myocardial I/R significantly increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), indicating the presence of liver injury. Hepatic apoptosis was significantly increased. The serum levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interleukin-6 (IL-6) were significantly elevated, as was the TNF-[Formula: see text] level in the liver. Intravenous pretreatment with baicalein (3, 10, or 30[Formula: see text]mg/kg) 10[Formula: see text]min before myocardial I/R significantly reduced the serum level increase of AST and ALT, apoptosis in the liver, and the elevation of TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 levels. Moreover, baicalein increased Bcl-2 and decreased Bax in the liver. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was also increased. In conclusion, we found that baicalein can reduce the liver injury induced by myocardial I/R. The underlying mechanisms are likely related to the inhibition of the extrinsic and intrinsic apoptotic pathways, possibly via the inhibition of TNF-[Formula: see text] production, the modulation of Bcl-2 and Bax, and the activation of Akt and ERK1/2. Our findings may provide a rationale for the application of baicalein or traditional Chinese medicine containing large amounts of baicalein to prevent liver injury in acute myocardial infarction and cardiac

  20. Electrocardiography as a tool for validating myocardial ischemia-reperfusion procedures in mice.

    PubMed

    Preda, Mihai B; Burlacu, Alexandrina

    2010-12-01

    This paper evaluates the modifications induced by ischemia and ischemia-reperfusion in mice after permanent or transient, respectively, ligation of the left coronary artery and establishes a correlation among the extent of ischemia, electrocardiograph features, and infarct size. The left coronary artery was ligated 1 mm distal from the tip of the left auricle. Histologic analysis revealed that 30-min ischemia (n = 9) led to infarction involving 9.7% ± 0.5% of the left ventricle, whereas 1-h ischemia (n = 9) resulted in transmural infarction of 16.1% ± 4.6% of the left ventricle. In contrast, 24-h ischemia (n = 8) and permanent ischemia (n = 8) induced similarly sized infarcts (33% ± 2% and 31.8% ± 0.7%, respectively), suggesting ineffective reperfusion after 24-h ischemia. Electrocardiography revealed that ligation of the left coronary artery led to ST height elevation (204 compared with 14 μV) and QTc prolongation (136 compared with 76 ms). Both parameters rapidly normalized on reperfusion, demonstrating that electrocardiography was important for validating correct ligation and reperfusion. In addition, electrocardiography predicted the severity of the myocardial damage induced by ischemia. Our results show that electrocardiographic changes present after 30-min ischemia were reversed on reperfusion; however, prolonged ischemia induced pathologic electrocardiographic patterns that remained even after reperfusion. The mouse model of myocardial ischemia-reperfusion can be improved by using electrocardiography to validate ligation and reperfusion during surgery and to predict the severity of infarction.

  1. Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation

    PubMed Central

    Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

    2016-01-01

    Purpose: The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. Methods: A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Results: Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Conclusions: Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease. PMID:27648122

  2. Imaging of cocaine-induced global and regional myocardial ischemia

    SciTech Connect

    Oster, Z.H.; Som, P.; Wang, G.J.; Weber, D.A. )

    1991-08-01

    Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. The authors have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine.

  3. [Effect and mechanism of icariin on myocardial ischemia-reperfusion injury model in diabetes rats].

    PubMed

    Hu, Yan-wu; Liu, Kai; Yan, Meng-tong

    2015-11-01

    To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury ( MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective role against ischemia reperfusion myocardial injury in diabetes rats by resisting oxidative stress and inhibiting cell apoptosis. PMID:27071263

  4. Effect and mechanism of miR-126 in myocardial ischemia reperfusion.

    PubMed

    Li, B; Tao, Y; Huang, Q

    2015-12-29

    Multiple studies have shown microRNAs to play an important role in disease occurrence and development. The role of miRNAs in ischemia-reperfusion injury, however, requires further investigation and the aim of this study was therefore to assess miR-126 expression in myocardial ischemia reperfusion and the effects of miR-126 on myocardial ischemia-reperfusion injury. An in vitro model of ischemia-reperfusion injury was established using rat myocardial H9c2 cells and miR-126 expression in these cells was assessed by real-time PCR. The miR-126 mimic and inhibitor were transfected into H9c2 cells before the injury was induced. Flow cytometry and western blotting were used to assess myocardial cell apoptosis. The triphenyltetrazolium chloride method was used to assess the infarction area and a TUNEL assay was used to analyze myocardial cell apoptosis. The results of the western blot analyses indicate that the miR-126 mimic and inhibitor increase and decrease caspase 3 degradation in myocardial cells, respectively. The in vivo experiments, moreover, revealed that the miR-126 mimic and inhibitor increase and reduce the myocardial infarction area, respectively. The TUNEL assay results showed increases and decreases in apoptotic myocardial cell numbers after infusion with the miR-126 mimic or inhibitor, respectively. These findings indicate that miR-126 is down-regulated in myocardial ischemia-reperfusion injury and that the inhibition of miR-126 may protect against myocardial cell apoptosis caused by ischemia-reperfusion.

  5. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage

    NASA Astrophysics Data System (ADS)

    Webb, Andrew; Bond, Richard; McLean, Peter; Uppal, Rakesh; Benjamin, Nigel; Ahluwalia, Amrita

    2004-09-01

    Nitric oxide (NO) is thought to protect against the damaging effects of myocardial ischemia-reperfusion injury, whereas xanthine oxidoreductase (XOR) normally causes damage through the generation of reactive oxygen species. In the heart, inorganic nitrite has the potential to act as an endogenous store of NO, liberated specifically during ischemia. Using a detection method that we developed, we report that under ischemic conditions both rat and human homogenized myocardium and the isolated perfused rat heart (Langendorff preparation) generate NO from in a reaction that depends on XOR activity. Functional studies of rat hearts in the Langendorff apparatus showed that nitrite (10 and 100 µM) reduced infarct size from 47.3 ± 2.8% (mean percent of control ± SEM) to 17.9 ± 4.2% and 17.4 ± 1.0%, respectively (P < 0.001), and was associated with comparable improvements in recovery of left ventricular function. This protective effect was completely blocked by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO). In summary, the generation of NO from •, rather than damaging.

  6. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

    PubMed Central

    Bani, D.; Masini, E.; Bello, M. G.; Bigazzi, M.; Sacchi, T. B.

    1998-01-01

    Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9588905

  7. Potential role of renin-angiotensin system blockade for preventing myocardial ischemia/reperfusion injury and remodeling after myocardial infarction.

    PubMed

    Dai, Wangde; Kloner, Robert A

    2011-03-01

    Experimental and clinical studies have demonstrated that myocardial ischemia induces activation of various components of the renin-angiotensin system (RAS), including angiotensinogen, renin, angiotensin-converting enzyme (ACE), angiotensins, and angiotensin receptors, in the acute phase of myocardial infarction and the postinfarction remodeling process. Pharmacological inhibition of the RAS by administration of renin inhibitors, ACE inhibitors, and angiotensin receptor blockers has shown beneficial effects on the pathological processes of myocardial infarction in both experimental animal studies and clinical trials. However, the potential mechanisms responsible for the cardioprotection of RAS inhibition remain unclear. In this review, we discuss roles of RAS blocking in the prevention of myocardial ischemia/reperfusion injury and postinfarction remodeling.

  8. Acute myocardial infarction and myocardial ischemia-reperfusion injury: a comparison.

    PubMed

    Hashmi, Satwat; Al-Salam, Suhail

    2015-01-01

    Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a period of coronary occlusion. Reperfusion has the potential to salvage ischemic myocardium but paradoxically can cause injury, a phenomenon called as 'reperfusion injury' (IR). Standard histologic, immunohistochemical and Elisa techniques were used to study the histopathologic, oxidative, apoptotic and inflammatory changes in MI and IR. The IL-6 levels in the LV of the MI group were significantly raised as compared to the IR group (P=0.0008). Plasma IL-6 was also significantly increased in the MI group as compared to the IR group (P=0.031). MI model was also associated with increase in the neutrophil polymorphs number in the infarction related myocardium as compared to the re-perfused myocardium. A significant increase in troponin I level in the MI group as compared to the IR group is also seen (P=0.0001). Our IR model showed enhanced pro-apoptotic mediators like cleaved caspase-3 (P=0.005) and cytochrome c in the myocardium as compared to the MI model. In conclusion, myocardial damage in MI is mainly due to ischemic necrosis and inflammatory mechanisms while apoptosis is the main mechanism of cell death in IR in addition to limited ischemic necrosis.

  9. Myocardial ischemia is a key factor in the management of stable coronary artery disease

    PubMed Central

    Iwasaki, Kohichiro

    2014-01-01

    Previous studies demonstrated that coronary revascularization, especially percutaneous coronary intervention (PCI), does not significantly decrease the incidence of cardiac death or myocardial infarction in patients with stable coronary artery disease. Many studies using myocardial perfusion imaging (MPI) showed that, for patients with moderate to severe ischemia, revascularization is the preferred therapy for survival benefit, whereas for patients with no to mild ischemia, medical therapy is the main choice, and revascularization is associated with increased mortality. There is some evidence that revascularization in patients with no or mild ischemia is likely to result in worsened ischemia, which is associated with increased mortality. Studies using fractional flow reserve (FFR) demonstrate that ischemia-guided PCI is superior to angiography-guided PCI, and the presence of ischemia is the key to decision-making for PCI. Complementary use of noninvasive MPI and invasive FFR would be important to compensate for each method’s limitations. Recent studies of appropriateness criteria showed that, although PCI in the acute setting and coronary bypass surgery are properly performed in most patients, PCI in the non-acute setting is often inappropriate, and stress testing to identify myocardial ischemia is performed in less than half of patients. Also, some studies suggested that revascularization in an inappropriate setting is not associated with improved prognosis. Taken together, the presence and the extent of myocardial ischemia is a key factor in the management of patients with stable coronary artery disease, and coronary revascularization in the absence of myocardial ischemia is associated with worsened prognosis. PMID:24772253

  10. Impact of an Interleukin-1 Receptor Antagonist and Erythropoietin on Experimental Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Grothusen, Christina; Hagemann, Angelika; Attmann, Tim; Braesen, Jan; Broch, Ole; Cremer, Jochen; Schoettler, Jan

    2012-01-01

    Background. Revascularization of infarcted myocardium results in release of inflammatory cytokines mediating myocardial reperfusion injury and heart failure. Blockage of inflammatory pathways dampens myocardial injury and reduces infarct size. We compared the impact of the interleukin-1 receptor antagonist Anakinra and erythropoietin on myocardial ischemia/reperfusion injury. In contrast to others, we hypothesized that drug administration prior to reperfusion reduces myocardial damage. Methods and Results. 12–15 week-old Lewis rats were subjected to myocardial ischemia by a 1 hr occlusion of the left anterior descending coronary artery. After 15 min of ischemia, a single shot of Anakinra (2 mg/kg body weight (bw)) or erythropoietin (5000 IE/kg bw) was administered intravenously. In contrast to erythropoietin, Anakinra decreased infarct size (P < 0.05, N = 4/group) and troponin T levels (P < 0.05, N = 4/group). Conclusion. One-time intravenous administration of Anakinra prior to myocardial reperfusion reduces infarct size in experimental ischemia/reperfusion injury. Thus, Anakinra may represent a treatment option in myocardial infarction prior to revascularization. PMID:22649318

  11. Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia

    PubMed Central

    JianXin, Chen; Xue, Xu; ZhongFeng, Li; Kuo, Gao; FeiLong, Zhang; ZhiHong, Li; Xian, Wang; HongCai, Shang

    2016-01-01

    Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. 1H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine. PMID:27075394

  12. Effect of eating on thallium-201 myocardial redistribution after myocardial ischemia

    SciTech Connect

    Angello, D.A.; Wilson, R.A.; Palac, R.T.

    1987-09-01

    To determine whether eating a high-carbohydrate meal between initial and delayed postexercise thallium-201 (Tl-201) imaging affects detection of Tl-201 redistribution during exercise stress testing, 16 patients with stable angina performed 2 Tl-201 treadmill exercise stress tests within a 14-day interval. Immediately after initial postexercise imaging, patients either drank a commercially available instant breakfast preparation for the intervention test or drank an equivalent volume of water for the control test. Comparable exercise workloads were achieved by exercising patients to the same heart rate for both tests. The order of the 2 (intervention and control) tests were randomized. All patients had at least 1 region of Tl-201 myocardial redistribution on either their eating or control test scans, although only 7 of the 16 had positive treadmill exercise test responses. Forty-six regions showing Tl-201 myocardial redistribution were identified in all 144 regions examined. Significantly more of these regions were identified on control test scans than on eating test scans: 11 of 46 on both test scans, 6 of 46 only on eating test scans and 29 of 46 only on control scans (p less than 0.001). Consistent with results of the quantitative regional analysis, the percentage of Tl-201 clearance over 4 hours in the 46 Tl-201 myocardial redistribution regions was 39 +/- 8% for the eating tests and 29 +/- 8% for control tests (mean +/- standard deviation, p less than 0.003). In 4 patients diagnosis of transient ischemia would have been missed because their 14 Tl-201 myocardial redistribution regions were detected only on the control test scans.

  13. Crocin-Elicited Autophagy Rescues Myocardial Ischemia/Reperfusion Injury via Paradoxical Mechanisms.

    PubMed

    Zeng, Chao; Li, Hu; Fan, Zhiwen; Zhong, Lei; Guo, Zhen; Guo, Yaping; Xi, Yusheng

    2016-01-01

    Crocin, the main effective component of saffron, exerts protective effects against ischemia/reperfusion injury during strokes. However, the effects of crocin in myocardial ischemia/reperfusion injury, and the mechanisms involved, remain unknown. Pretreated with crocin for 7 days, C57BL/6N mice were subjected to 30 min of myocardial ischemia followed by 12[Formula: see text]h of reperfusion (for cardiac function and infarct size, cell apoptosis and necrosis). Neonatal mouse cardiomyocytes were subjected to 2 h of hypoxia followed by 4 h of reoxygenation. NMCM's survival was assessed during hypoxia and reoxygenation in the presence or absence of the autophagy inhibitor 3-methyladenine or the inducer rapamycin. Western blotting was used to evaluate AMPK, Akt, and autophagy-related proteins. Autophagosome was observed using electron microscopy. In the in vivo experiment, crocin pretreatment significantly attenuated infarct size, myocardial apoptosis and necrosis, and improved left ventricular function following ischemia/reperfusion. In vitro data revealed that autophagy was induced during hypoxia, the levels of which were intensely elevated during reoxygenation. Crocin significantly promoted autophagy during ischemia, accompanied with the activation of AMPK. In contrast, crocin overtly inhibited autophagy during reperfusion, accompanied with Akt activation. Induction and inhibition of autophagy mitigated crocin induced protection against NMCMs injury during hypoxia and reoxygenation, respectively. Our data suggest that crocin demonstrated a myocardial protective effect via AMPK/mTOR and Akt/mTOR regulated autophagy against ischemia and reperfusion injury, respectively. PMID:27109157

  14. [Pulmonary hemodynamics following experimental myocardial ischemia after the blockade of adrenergic receptors].

    PubMed

    Evlakhov, V I; Poiasov, I Z

    2015-01-01

    In acute experiments in anesthetized rabbits the changes of the pulmonary hemodynamics following 60 s myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the blockade of α-adrenoreceptors by phentolamine or β-adrenoreceptors by propranolol. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance did not change, the left atrial pressure elevated; the cardiac output decreased more than pulmonary artery flow. Following myocardial ischemia after the blockade of β-adrenoreceptors the pulmonary artery pressure decreased more than in control animals, the pulmonary artery flow was decreased in the same level as in the last case. The pulmonary vascular resistance was diminished, the left atrial pressure increased; the pulmonary artery flow and cardiac output decreased in the same level. Following myocardial ischemia after the blockade of β-adrenoreceptors the pulmonary artery pressure and pulmonary vascular resistance decreased more than after the blockade of α-adrenoreceptors, the left atrial pressure did not change. In both cases the pulmonary artery flow decreased in the same level and its changes were correlated with venous return shifts. The differences of the pulmonary artery changes following myocardial ischemia after the blockade of α- and β-adrenoreceptors are caused not only the different pulmonary vascular resistance changes, but also the left atrial pressure.

  15. Impact of myocardial ischemia on myocardial revascularization in stable ischemic heart disease. Lessons from the COURAGE and FAME 2 trials.

    PubMed

    Torosoff, M T; Sidhu, M S; Boden, W E

    2013-06-01

    In patients with stable ischemic heart disease (SIHD), myocardial revascularization should be performed to either improve survival or improve symptoms and functional status among patients who are not well controlled with optimal medical therapy (OMT). A general consensus exists on the core elements of OMT, which include both lifestyle intervention and intensive secondary prevention with proven pharmacotherapies. By contrast, however, there is less general agreement as to what constitutes the optimal approach to revascularization in SIHD patients. The COURAGE and FAME 2 randomized trials form the foundation of the current clinical evidence base and raise the important question: "What is the impact of myocardial ischemia on myocardial revascularization in stable ischemic heart disease?"

  16. Myocardial perfusion and contraction in acute ischemia and chronic ischemic heart disease.

    PubMed

    Canty, John M; Suzuki, Gen

    2012-04-01

    A large body of evidence has demonstrated that there is a close coupling between regional myocardial perfusion and contractile function. When ischemia is mild, this can result in the development of a new balance between supply and energy utilization that allows the heart to adapt for a period of hours over which myocardial viability can be maintained, a phenomenon known as "short-term hibernation". Upon reperfusion after reversible ischemia, regional myocardial function remains depressed. The "stunned myocardium" recovers spontaneously over a period of hours to days. The situation in myocardium subjected to chronic repetitive ischemia is more complex. Chronic dysfunction can initially reflect repetitive stunning with insufficient time for the heart to recover between episodes of spontaneous ischemia. As the frequency and/or severity of ischemia increases, the heart undergoes a series of adaptations which downregulate metabolism to maintain myocyte viability at the expense of contractile function. The resulting "hibernating myocardium" develops regional myocyte cellular hypertrophy as a compensatory response to ischemia-induced apoptosis along with a series of molecular adaptations that while regional, are similar to global changes found in advanced heart failure. As a result, flow-function relations become independently affected by tissue remodeling and interventions that stimulate myocyte regeneration. Similarly, chronic vascular remodeling may alter flow regulation in a fashion that increases myocardial vulnerability to ischemia. Here we review our current understanding of myocardial flow-function relations during acute ischemia in normal myocardium and highlight newly identified complexities in their interpretation in viable chronically dysfunctional myocardium with myocyte cellular and molecular remodeling. This article is part of a Special Issue entitled "Coronary Blood Flow".

  17. Effect of hydrogen sulfide on inflammatory cytokines in acute myocardial ischemia injury in rats

    PubMed Central

    LIU, FANG; LIU, GUANG-JIE; LIU, NA; ZHANG, GANG; ZHANG, JIAN-XIN; LI, LAN-FANG

    2015-01-01

    Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. PMID:25667680

  18. Effect of regional myocardial ischemia on sympathetic nervous system as assessed by fluorine-18-metaraminol

    SciTech Connect

    Schwaiger, M.; Guibourg, H.; Rosenspire, K.; McClanahan, T.; Gallagher, K.; Hutchins, G.; Wieland, D.M. )

    1990-08-01

    With the introduction of radiolabeled catecholamine analogues, the noninvasive evaluation of the cardiac sympathetic nervous system has become possible. This study evaluated the effect of regional ischemia on myocardial retention of the new norepinephrine analogue 6-({sup 18}F) fluorometaraminol (FMR) in the open chest dog model. Six dogs were injected intravenously with FMR following 30-min occlusion of the left anterior descending artery. Six sham animals served as control group. Regional myocardial blood flow as determined by microspheres decreased 87% during ischemia (p less than 0.01), but was not significantly different from control myocardium following reperfusion. Regional myocardial 18F activity as determined postmortem was significantly reduced in reperfused myocardium (-34%), which paralleled an 18% reduction of tissue norepinephrine concentration. Thus, short time periods of coronary occlusion affect neuronal function indicating the sensitivity of the sympathetic nerve terminals to ischemia. FMR provides a new tracer approach for the characterization of neuronal integrity in postischemic myocardium.

  19. The role of met-enkephalin in silent myocardial ischemia in diabetic patients.

    PubMed

    Parlapiano, C; Borgia, M C; Tonnarini, G; Campana, E; Giancaspro, G; Pantone, P; Giovanniello, T; Cardarelli, G; Vincentelli, G M; Alegiani, F; Negri, M

    2001-01-01

    Met-enkephalin plasma levels were evaluated in 20 cardioischemic diabetic patients. All the patients had ECG ischemic signs. Ten patients with diabetic autonomic neuropathy, experienced no pain during myocarial ischemia. Met-enkephalin levels in the diabetic patients with silent myiocardial ischemia were significantly lower compared to those in the symptomatic patients. This demonstrates that the absence of myocardial ischemic pain in neuropathic diabetic patients is not accounted for by met-enkephalin action. PMID:11958273

  20. Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

    PubMed

    Birnbaum, Yochai; Mahaffey, Kenneth W; Criger, Douglas A; Gates, Kathy B; Barbash, Gabriel I; Barbagelata, Alejandro; Clemmensen, Peter; Sgarbossa, Elena B; Gibbons, Raymond J; Rahman, M Atiar; Califf, Robert M; Granger, Chistopher B; Wagner, Galen S

    2002-01-01

    We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion. PMID:12077570

  1. Acute myocardial ischemia and reperfusion: MR imaging with albumin-Gd-DTPA

    SciTech Connect

    Schmiedl, U.; Sievers, R.E.; Brasch, R.C.; Wolfe, C.L.; Chew, W.M.; Ogan, M.D.; Engeseth, H.; Lipton, M.J.; Moseley, M.E.

    1989-02-01

    The utility of a macromolecular, intravascular contrast agent, albumin-gadolinium diethylenetriaminepentaacetic acid (DTPA), for the differentiation of acutely ischemic and reperfused myocardium on magnetic resonance (MR) images was investigated. Regional, reversible myocardial ischemia was produced in rats and confirmed. After reperfusion, flow to the compromised myocardial segment returned to baseline. Normal myocardium could not be differentiated from ischemic myocardium on nonenhanced MR images (n = 12). After 5 minutes of myocardial ischemia and after administration of albumin-Gd-DTPA, the ischemic zone involving the free wall of the left ventricle was characterized by the absence of significant enhancement. Normal myocardium appeared homogeneously enhanced (by 145%). This pattern persisted for up to 1 hour of myocardial ischemia. In six rats that underwent myocardial reperfusion after 5 minutes of ischemia, the normal and reperfused myocardium became isointense. Radiotracer studies with albumin-Gd-153-DTPA confirmed the decreased distribution of contrast agent to the ischemic myocardium, possibly due to decreased blood pool or a blocked primary delivery system in the ischemic myocardium.

  2. Quantifying QRS changes during myocardial ischemia: Insights from high frequency electrocardiography.

    PubMed

    Amit, Guy; Granot, Yair; Abboud, Shimon

    2014-01-01

    Over four decades of high frequency electrocardiography research have provided a body of knowledge about QRS changes during myocardial ischemia, and the techniques to measure and quantify them. High-frequency QRS (HFQRS) components, being closely related to the pattern of ventricular depolarization, carry valuable clinical information. Changes in HFQRS amplitude and morphology have been shown to be sensitive diagnostic markers of myocardial ischemia, often superior to measures of ST-T segment changes. Clinical studies in patients undergoing exercise testing have consistently demonstrated the incremental diagnostic value of HFQRS analysis in detection of demand ischemia. In 6 studies that evaluated the HyperQ™ technology, the average sensitivity and specificity of HFQRS analysis were 75%±6% and 80%±6%, respectively, compared to average sensitivity 48%±16% and average specificity 70%±15% of ST segment analysis. In patients with acute supply ischemia, recent studies characterized and quantified the ischemic HFQRS patterns. HFQRS morphology index was found to be higher in patients with acute coronary syndrome (ACS), compared to non-ischemic, with good sensitivity in patients without ST elevation. These research findings may be translated into commercially-available ECG systems and be used in clinical practice for improved diagnosis and monitoring of myocardial ischemia.

  3. Three-Dimensional Visualization of Myocardial Ischemia Based on the Standard Twelve-Lead Electrocardiogram

    PubMed Central

    Ruixia, Tian; Xun, Chen

    2016-01-01

    A novel method was proposed for transforming the ischemic information in the 12-lead electrocardiogram (ECG) into the pseudo-color pattern displayed on a 3D heart model based on the projection of a ST injury vector in this study. The projection of the ST injury vector at a point on the heart surface was used for identifying the presence of myocardial ischemia by the difference between the projection value and the detection threshold. Supposing that myocardial ischemia was uniform and continuous, the location and range of myocardial ischemia could be accurately calculated and visually displayed in a color-encoding way. The diagnoses of the same patient were highly consistent (kappa coefficient k = 0.9030) between the proposed method used by ordinary people lacking medical knowledge and the standard 12-lead ECG used by experienced cardiologists. In addition, the diagnostic accuracy of the proposed method was further confirmed by the coronary angiography. The results of this study provide a new way to promote the development of the 3D visualization of the standard 12-lead ECG, which has a great help for inexperienced doctors or ordinary family members in their diagnosis of patients with myocardial ischemia. PMID:27433278

  4. Induced coronary spasm without electrocardiographic signs or symptoms of myocardial ischemia

    SciTech Connect

    Cipriano, P.R.

    1983-03-01

    Angiographic studies have shown that coronary artery spasm can be induced with ergonovine maleate. Coronary artery spasm induced by ergonovine maleate in these studies was nearly always accompanied by chest pain and electrocardiographic changes of myocardial ischemia. This report demonstrates that coronary artery spasm induced by ergonovine maleate may be diagnosed by angiography in the absence of these signs or symptoms.

  5. Multiple coronary arterial loops as a cause of myocardial ischemia

    NASA Technical Reports Server (NTRS)

    Bashour, Tali T.; Mansour, Nagi N.; Lee, Damon

    1993-01-01

    A case of long-standing angina with ischemia documented by exercise testing and thallium scintigraphy in a patient who had multiple proximal loops in all three major coronary arteries in the absence of luminal stenosis, is reported.

  6. The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury.

    PubMed

    Ong, Sang-Bing; Samangouei, Parisa; Kalkhoran, Siavash Beikoghli; Hausenloy, Derek J

    2015-01-01

    Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide. For patients presenting with an acute myocardial infarction, the most effective treatment for limiting myocardial infarct (MI) size is timely reperfusion. However, in addition to the injury incurred during acute myocardial ischemia, the process of reperfusion can itself induce myocardial injury and cardiomyocyte death, termed 'myocardial reperfusion injury', the combination of which can be referred to as acute ischemia-reperfusion injury (IRI). Crucially, there is currently no effective therapy for preventing this form of injury, and novel cardioprotective therapies are therefore required to protect the heart against acute IRI in order to limit MI size and preserve cardiac function. The opening of the mitochondrial permeability transition pore (MPTP) in the first few minutes of reperfusion is known to be a critical determinant of IRI, contributing up to 50% of the final MI size. Importantly, preventing its opening at this time using MPTP inhibitors, such as cyclosporin-A, has been reported in experimental and clinical studies to reduce MI size and preserve cardiac function. However, more specific and novel MPTP inhibitors are required to translate MPTP inhibition as a cardioprotective strategy into clinical practice. In this article, we review the role of the MPTP as a mediator of acute myocardial IRI and as a therapeutic target for cardioprotection. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". PMID:25446182

  7. Cardiovascular risk evaluation and prevalence of silent myocardial ischemia in subjects with asymptomatic carotid artery disease

    PubMed Central

    Ciccone, Marco Matteo; Niccoli-Asabella, Artor; Scicchitano, Pietro; Gesualdo, Michele; Notaristefano, Antonio; Chieppa, Domenico; Carbonara, Santa; Ricci, Gabriella; Sassara, Marco; Altini, Corinna; Quistelli, Giovanni; Lepera, Mario Erminio; Favale, Stefano; Rubini, Giuseppe

    2011-01-01

    Introduction: Silent ischemia is an asymptomatic form of myocardial ischemia, not associated with angina or anginal equivalent symptoms, which can be demonstrated by changes in ECG, left ventricular function, myocardial perfusion, and metabolism. The aim of this study was to evaluate the prevalence of silent myocardial ischemia in a group of patients with asymptomatic carotid stenosis. Methods: A total of 37 patients with asymptomatic carotid plaques, without chest pain or dyspnea, was investigated. These patients were studied for age, sex, hypertension, diabetes, dyslipidemia, smoking, and family history of cardiac disease, and underwent technetium-99 m sestamibi myocardial stress-rest scintigraphy and echo-color Doppler examination of carotid arteries. Results: A statistically significant relationship (P = 0.023) was shown between positive responders and negative responders to scintigraphy test when both were tested for degree of stenosis. This relationship is surprising in view of the small number of patients in our sample. Individuals who had a positive scintigraphy test had a mean stenosis degree of 35% ± 7% compared with a mean of 44% ± 13% for those with a negative test. Specificity of our detection was 81%, with positive and negative predictive values of 60% and 63%, respectively. Conclusion: The present study confirms that carotid atherosclerosis is associated with coronary atherosclerosis and highlights the importance of screening for ischemic heart disease in patients with asymptomatic carotid plaques, considering eventually plaque morphology (symmetry, composition, eccentricity or concentricity of the plaque, etc) for patient stratification. PMID:21468172

  8. Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by Suppression of Microvascular Thrombosis

    PubMed Central

    Liu, Xiaohui; Xu, Dongzhou; Wang, Yuxin; Chen, Ting; Wang, Qi; Zhang, Jian; You, Tao; Zhu, Li

    2016-01-01

    Background The aim of this study was to evaluate the cardio-protective roles of glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore the underlying mechanism. Material/Methods Myocardial ischemia-reperfusion in wild-type C57BL/6J mice was induced by transient ligation of the left anterior descending artery. GLA or vehicle (solvent) was administrated intraperitoneally to the mice before reperfusion started. After 24 h of myocardial reperfusion, ischemic size was revealed by Evans blue/TTC staining. Cardiac function was evaluated by echocardiography and microvascular thrombosis was assessed by immunofluorescence staining of affected heart tissue. We also measured the phosphorylation of AKT, ERK, P-GSK-3β, and cleaved caspase 3 in the myocardium. Results Compared to the solvent-treated control group, GLA administration significantly reduced infarct size (GLA 13.85±2.08% vs. Control 18.95±0.97%, p<0.05) and improved left ventricular ejection fraction (LVEF) (GLA 53.13±1.11% vs. Control 49.99±1.25%, p<0.05) and left ventricular fractional shortening (LVFS) (28.34±0.71% vs. Control 25.11±0.74%, p<0.05) in mice subjected to myocardial ischemia-reperfusion. GLA also attenuated microvascular thrombosis (P<0.05) and increased the phosphorylation of pro-survival kinase AKT (P<0.05) and GSK-3β (P<0.05) in the myocardium upon reperfusion injury. Conclusions Administration of GLA before reperfusion ameliorates myocardial ischemia-reperfusion injury in mice. The cardio-protective roles of GLA may be mediated through the attenuation of microvascular thrombosis. PMID:27716735

  9. Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury.

    PubMed

    Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

    2016-01-01

    Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects. PMID:27469291

  10. Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

    PubMed Central

    Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

    2016-01-01

    Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects. PMID:27469291

  11. [The effect of metformin on myocardial tolerance to ischemia in rats with diabetes mellitus type 2].

    PubMed

    Kravchuk, E N; Grineva, E N; Galagudza, M M; Bairamov, A A

    2013-01-01

    The effect of metformin on myocardial sensitivity to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion in the isolated perfused heart. Metformin administration had no effect on infarct size. At the same time, infarct size in T2DM was significantly lower than in controls, which is indicative of the phenomenon of metabolic preconditioning in T2DM. The protocol of metformin administration used in this study had not afforded a significant cardioprotective effect in animals with T2DM.

  12. ST monitoring for myocardial ischemia during and after coronary angioplasty.

    PubMed

    Mizutani, M; Ben Freedman, S; Barns, E; Ogasawara, S; Bailey, B P; Bernstein, L

    1990-08-15

    We performed 12-lead electrocardiographic monitoring in 97 patients during coronary angioplasty (PTCA) of a single vessel to correlate ischemic ST changes with clinical, angiographic and coronary hemodynamic variables and to determine the optimum lead or combination of leads for their detection. Ischemia (chest pain or ST change, group A) occurred in 79 patients (80%), but in only 15 of 23 patients (65%) with collaterals (p less than 0.05). Ischemia occurred more often in left anterior descending and left circumflex PTCA than right coronary PTCA, but pain was the only manifestation more often in left circumflex and right coronary PTCA. Ischemic ST change was silent in 16% and this proportion did not differ in clinical or angiographic groups except for diabetes with 3 of 5 (60%) having silent ischemia (p less than 0.05). Patients in group A (ischemia) compared to group B (no ischemia) had less severe lesions (85 +/- 9 vs 91 +/- 7%, p less than 0.01), higher transstenotic gradients (62 +/- 19 vs 53 +/- 9 mm Hg, p less than 0.05) and lower distal occluded pressures (24 +/- 11 vs 33 +/- 10 mm Hg, p less than 0.01), suggesting less collateral flow. Compared with a 12-lead electrocardiogram, the best single lead for detecting ST change during PTCA in each artery had a sensitivity of 80% and this increased to 93% using the best 2 leads. The best 3 leads (V3/III/V5 for left anterior descending and III/V2/V5 for right coronary and left circumflex) increased sensitivity to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Prognostic significance of early ischemia after acute myocardial infarction in low-risk patients. IRES (Ischemia Residua) Study Group.

    PubMed

    Silva, P; Galli, M; Campolo, L

    1993-05-15

    Early postinfarction angina is generally believed to imply an unfavorable prognosis. However, most of the published information devices from data collected in the prethrombolytic era, with widely differing populations and definitions of early angina, and very little data pertinent to low-risk patients are available. This collaborative study prospectively assessed the incidence of early recurrent ischemia after thrombolysis, as well as its prognostic significance, in 453 consecutive patients aged < or = 70 years with an uncomplicated course in the first 24 hours of a first myocardial infarction participating in the second Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial. Early recurrent ischemia (spontaneous, transient ST depression or elevation of > 1 mm and/or T-wave inversion), assessed in the coronary care unit with continuous clinical and electrocardiographic monitoring, was documented in 35 of 453 patients (8%) and was unrelated to sex, age, electrocardiographic location, Q-wave or non-Q-wave infarction, thrombolytic agent and time to its administration. In-hospital cardiac events (7 deaths, 19 nonfatal reinfarctions and 8 urgent revascularizations) occurred in 15 of 35 patients (43%) with versus 19 of 418 without (4.5%) recurrent ischemia (p < 0.001). At the 6-month follow-up of 352 medically treated patients who did not have in-hospital events, the incidence of death, reinfarction and recurrent angina was comparable between patients with (2 of 18, 11%) and without (62 of 334, 19%) early ischemia (p = NS). With use of stepwise multivariate analysis, early ischemia was the only significant predictor of in-hospital cardiac events (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Dictionary-Driven Ischemia Detection From Cardiac Phase-Resolved Myocardial BOLD MRI at Rest.

    PubMed

    Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A

    2016-01-01

    Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP-BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP-BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson's r=0.84) with respect to infarct size. When advances in automated registration and segmentation of CP-BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique.

  15. Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

    PubMed

    Stanley, W C; Hall, J L; Smith, K R; Cartee, G D; Hacker, T A; Wisneski, J A

    1994-01-01

    We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. [Histoautoradiographic study of the heart in experimental myocardial ischemia].

    PubMed

    Makhova, A N; Shliapnikov, V N

    1979-01-01

    Autoradiographic examinations of the heart muscle in experimental myocardial necroses using 3H-thymidine, revealed a high DNA synthesis in the connective tissue cells in the zone of necrosis in the acute period of infarction and its subsequent decrease. Deviations from this regularity were observed when relapses of necrosis developed. The activation of DNA synthesis occurred to a lesser extent in stromal cells of the periinfarction and remote zones of the heart. Muscle cells incorporated 3H-thymidine extremely rarely. When myocardial infarction was combined with aterosclerosis, relapses of necrosis occurred frequently, and morphological changes in many arteries and veins were accompanied by 3H-thymidine incorporation into the nuclei of the endothelium, smooth cells and adventitial cells. Inhibition of DNA synthesis in connective tissue cells of various heart zones was observed in cases of combined myocardial infarction and aterosclerosis and hypertension.

  17. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

    PubMed

    Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

    2013-01-01

    This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.

  18. Iron chelation in myocardial preservation after ischemia-reperfusion injury: the importance of pretreatment and toxicity.

    PubMed

    DeBoer, D A; Clark, R E

    1992-03-01

    Oxygen-derived free radicals have been implicated in myocardial ischemia-reperfusion injury. It has been proposed that deferoxamine, an iron chelator, improves myocardial preservation by reducing the iron-catalyzed production of the hydroxyl radical. The objectives of this study were to define the appropriate timing of iron chelation therapy and the dose-response properties of deferoxamine. Isolated working rat hearts were subjected to 25 minutes of normothermic global ischemia. Deferoxamine was given as pretreatment (n = 39; doses of 10 or 30 mg/kg), added to cardioplegic solution (n = 43; doses 0.46 to 1.90 mmol/L), or administered upon reperfusion (n = 52; doses 0.15 to 0.76 mmol/L) and compared with saline controls (n = 25). Deferoxamine pretreatment improved survival at each dose from a control value of 44% to 71% and 72% (p less than 0.05), respectively. A cardioplegia dose of 0.46 mmol/L improved survival from 48% to 75%. Higher doses reduced survival and implied a toxic effect. Reperfusion therapy did not alter survival. Regardless of time of administration, deferoxamine did not improve ventricular function or adenosine triphosphate levels. Deferoxamine given as pretreatment 1 hour before ischemia at doses of 30 mg/kg, and perhaps as low as 10 mg/kg, significantly improved survival. The addition of deferoxamine to cardioplegic solution was safe and may be protective at approximately 0.50 mmol/L; however, toxicity should be considered at concentrations greater than 0.76 mmol/L. These data support the postulate that iron catalysis is involved in the production of oxygen-derived free radicals during ischemia-reperfusion injury. We conclude that pretreatment before ischemia is an important component of iron chelation therapy in myocardial preservation.

  19. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

    PubMed

    Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

    2013-01-01

    This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes. PMID:23936589

  20. A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion

    PubMed Central

    Kim, Se-Chan; Boehm, Olaf; Meyer, Rainer; Hoeft, Andreas; Knüfermann, Pascal; Baumgarten, Georg

    2012-01-01

    Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ischemia and reperfusion. Immune response includes cytokine expression and release or secretion of endogenous ligands of innate immune receptors. Activation of innate immunity can potentially modulate infarct size. We have modified an existing murine closed-chest model using hanging weights which could be useful for studying myocardial pre- and postconditioning and the role of innate immunity in myocardial ischemia and reperfusion. This model allows animals to recover from surgical trauma before onset of myocardial ischemia. Volatile anesthetics have been intensely studied and their preconditioning effect for the ischemic heart is well known. However, this protective effect precludes its use in open chest models of coronary artery ligation. Thus, another advantage could be the use of the well controllable volatile anesthetics for instrumentation in a chronic closed-chest model, since their preconditioning effect lasts up to 72 hours. Chronic heart diseases with intermittent ischemia and multiple hit models are other possible applications of this model. For the chronic closed-chest model, intubated and ventilated mice undergo a lateral blunt thoracotomy via the 4th intercostal space. Following identification of the left anterior descending a ligature is passed underneath the vessel and both suture ends are threaded through an occluder. Then, both suture ends are passed through the chest wall, knotted to form a loop and left in the subcutaneous tissue. After chest closure and recovery for 5 days, mice are anesthetized again, chest skin is reopened and hanging weights are hooked up to the loop under ECG control. At the end of the ischemia/reperfusion protocol, hearts can be stained with TTC for infarct size assessment or undergo perfusion fixation to allow morphometric studies in addition to histology and

  1. Sex Differences in Mental Stress-Induced Myocardial Ischemia in Young Survivors of an Acute Myocardial Infarction

    PubMed Central

    Vaccarino, Viola; Shah, Amit J.; Rooks, Cherie; Ibeanu, Ijeoma; Nye, Jonathon A.; Pimple, Pratik; Salerno, Amy; D'Marco, Luis; Karohl, Cristina; Bremner, J. Douglas; Raggi, Paolo

    2014-01-01

    Objectives Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress-induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than men. Methods We studied 98 post-MI patients (49 women and 49 men) aged 38-60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent [99mTc]sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. Results Women aged 50 or younger, but not older women, showed a more adverse psychosocial profile than age-matched men, but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease (CAD). Compared with age-matched men, women aged 50 or younger exhibited a higher SDS with mental stress (3.1 vs. 1.5, p=0.029) and had twice the rate of MSIMI (SDS ≥3), 52% vs. 25%, while ischemia with physical stress did not differ (36% vs 25%). In older patients there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and lifestyle factors, CAD severity and depression. Conclusions MSIMI post-MI is more common in women aged 50 or younger compared to age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years. PMID:24608039

  2. Pyrroloquinoline quinone (PQQ) decreases myocardial infarct size and improves cardiac function in rat models of ischemia and ischemia/reperfusion.

    PubMed

    Zhu, Bo-Qing; Zhou, Hui-Zhong; Teerlink, John R; Karliner, Joel S

    2004-11-01

    As pyrroloquinoline quinone (PQQ) is a redox cofactor in mammals, we asked if it is cardioprotective. Rats were subjected to 2 h of left anterior descending (LAD) coronary artery ligation without reperfusion (model 1, ischemia). In model 2 (ischemia/reperfusion), rats were subjected to 17 or 30 min of LAD occlusion and 2 h of reperfusion. PQQ (15-20 mg/kg) was given i.p., either 30 min before LAD occlusion (Pretreatment) or i.v. at the onset of reperfusion (Treatment). In model 1, PQQ reduced infarct size (10.0 +/- 1.5 vs 19.1 +/- 2.1%, P < 0.01). In model 2, either PQQ Pretreatment or Treatment also reduced infarct size (18.4 +/- 2.3 and 25.6 +/- 3.5% vs 38.1 +/- 2.6%, P < 0.01). PQQ resulted in higher LV developed pressure and LV (+)dP/dt after 1-2 h of reperfusion (P < 0.05), and fewer ventricular fibrillation episodes. PQQ dose (5-20 mg/kg) was inversely related to infarct size. PQQ reduced myocardial tissue levels of malondialdehyde (MDA), an indicator of lipid peroxidation (316 +/- 88 vs 99 +/- 14 nmol/g, P < 0.01). PQQ given either as Pretreatment or as Treatment at the onset of reperfusion is highly effective in reducing infarct size and improving cardiac function in a dose-related manner in rat models of ischemia and ischemia/reperfusion. The optimal dose in this study, which exhibited neither renal nor hepatic toxicity, was 15 mg/kg, but lower doses may also be efficacious. We conclude that PQQ, which appears to act as a free radical scavenger in ischemic myocardium, is a highly effective cardioprotective agent.

  3. Green tea extract given before regional myocardial ischemia-reperfusion in rats improves myocardial contractility by attenuating calcium overload.

    PubMed

    Liou, Ying-Ming; Hsieh, Shih-Rong; Wu, Tsu-Juey; Chen, Jan-Yow

    2010-11-01

    There is evidence for a negative correlation between green tea consumption and cardiovascular diseases. The aim of the present study was to examine whether green tea extract (GTE) given before regional myocardial ischemia could improve depression of myocardial contractility by preventing cytosolic Ca(2+) overload. Regional ischemia-reperfusion (IR) was induced in rats by ligating the left anterior descending branch for 20 min, then releasing the ligature. Ligation induced ventricular arrhythmias in rats without GTE pretreatment, but decreased arrhythmogenesis was seen in rats pretreated 30 min earlier with GTE (400 mg/kg). During reperfusion, arrhythmias only occurred during the initial 5 min, and GTE pretreatment had no effect. After overnight recovery, serum cTnI levels were greatly increased in control post-IR rats but only slightly elevated in GTE-pretreated post-IR rats. Myocardial contractility measured by echocardiography was still depressed after 3 days in control post-IR rats, but not in GTE-pretreated post-IR rats. No myocardial ischemic injury was seen in post-IR rats with or without GTE pretreatment. Using freshly isolated single heart myocytes, GTE was found to attenuate the post-IR injury-associated cytosolic Ca(2+) overload and modulate changes in the levels and distribution of myofibril, adherens junction, and gap junction proteins. In summary, GTE pretreatment protects cardiomyocytes from IR injury by preventing cytosolic Ca(2+) overload, myofibril disruption, and alterations in adherens and gap junction protein expression and distribution. PMID:20922441

  4. Exogenous NAD(+) administration significantly protects against myocardial ischemia/reperfusion injury in rat model.

    PubMed

    Zhang, Youjun; Wang, Ban; Fu, Xingli; Guan, Shaofeng; Han, Wenzheng; Zhang, Jie; Gan, Qian; Fang, Weiyi; Ying, Weihai; Qu, Xinkai

    2016-01-01

    Acute myocardial infarction is one of the leading causes for death around the world. Although essential for successful interventional therapy, it is inevitably complicated by reperfusion injury. Thus effective approaches to reduce ischemia/reperfusion (I/R) injury are still critically needed. To test our hypothesis that intravenous administration of NAD(+) can attenuate I/R injury by reducing apoptotic damage and enhancing antioxidant capacity, we used a rat mode of myocardial I/R. Our study found that administration of 10-20 mg/kg NAD(+) can dose dependently reduce myocardial infarct induced by I/R, with an approximately 85% reduction of the infarct at the dosage of 20 mg/kg NAD(+). We further found that the injection of NAD(+) can significantly decrease I/R-induced apoptotic damage in the heart: NAD(+) administration can both decrease the TUNEL signals, Bax, cleaved caspase-3 levels and increase the Bcl-XL levels in the rats that are subjected to myocardial I/R injury. NAD(+) administration can also significantly attenuate I/R-induced decreases in SOD activity and SOD-2 protein levels in the hearts. NAD(+) can profoundly decrease myocardial I/R injury at least partially by attenuating apoptotic damage and enhancing the antioxidant capacity, thus suggesting that NAD(+) may become a promising therapeutic agent for myocardial I/R injury. PMID:27648125

  5. Exogenous NAD+ administration significantly protects against myocardial ischemia/reperfusion injury in rat model

    PubMed Central

    Zhang, Youjun; Wang, Ban; Fu, Xingli; Guan, Shaofeng; Han, Wenzheng; Zhang, Jie; Gan, Qian; Fang, Weiyi; Ying, Weihai; Qu, Xinkai

    2016-01-01

    Acute myocardial infarction is one of the leading causes for death around the world. Although essential for successful interventional therapy, it is inevitably complicated by reperfusion injury. Thus effective approaches to reduce ischemia/reperfusion (I/R) injury are still critically needed. To test our hypothesis that intravenous administration of NAD+ can attenuate I/R injury by reducing apoptotic damage and enhancing antioxidant capacity, we used a rat mode of myocardial I/R. Our study found that administration of 10-20 mg/kg NAD+ can dose dependently reduce myocardial infarct induced by I/R, with an approximately 85% reduction of the infarct at the dosage of 20 mg/kg NAD+. We further found that the injection of NAD+ can significantly decrease I/R-induced apoptotic damage in the heart: NAD+ administration can both decrease the TUNEL signals, Bax, cleaved caspase-3 levels and increase the Bcl-XL levels in the rats that are subjected to myocardial I/R injury. NAD+ administration can also significantly attenuate I/R-induced decreases in SOD activity and SOD-2 protein levels in the hearts. NAD+ can profoundly decrease myocardial I/R injury at least partially by attenuating apoptotic damage and enhancing the antioxidant capacity, thus suggesting that NAD+ may become a promising therapeutic agent for myocardial I/R injury. PMID:27648125

  6. Exogenous NAD+ administration significantly protects against myocardial ischemia/reperfusion injury in rat model

    PubMed Central

    Zhang, Youjun; Wang, Ban; Fu, Xingli; Guan, Shaofeng; Han, Wenzheng; Zhang, Jie; Gan, Qian; Fang, Weiyi; Ying, Weihai; Qu, Xinkai

    2016-01-01

    Acute myocardial infarction is one of the leading causes for death around the world. Although essential for successful interventional therapy, it is inevitably complicated by reperfusion injury. Thus effective approaches to reduce ischemia/reperfusion (I/R) injury are still critically needed. To test our hypothesis that intravenous administration of NAD+ can attenuate I/R injury by reducing apoptotic damage and enhancing antioxidant capacity, we used a rat mode of myocardial I/R. Our study found that administration of 10-20 mg/kg NAD+ can dose dependently reduce myocardial infarct induced by I/R, with an approximately 85% reduction of the infarct at the dosage of 20 mg/kg NAD+. We further found that the injection of NAD+ can significantly decrease I/R-induced apoptotic damage in the heart: NAD+ administration can both decrease the TUNEL signals, Bax, cleaved caspase-3 levels and increase the Bcl-XL levels in the rats that are subjected to myocardial I/R injury. NAD+ administration can also significantly attenuate I/R-induced decreases in SOD activity and SOD-2 protein levels in the hearts. NAD+ can profoundly decrease myocardial I/R injury at least partially by attenuating apoptotic damage and enhancing the antioxidant capacity, thus suggesting that NAD+ may become a promising therapeutic agent for myocardial I/R injury.

  7. Prevention of ischemia-induced myocardial platelet deposition by exogenous prostacyclin

    SciTech Connect

    Aherne, T.; Price, D.C.; Yee, E.S.; Hsieh, W.R.; Ebert, P.A.

    1986-07-01

    The antithrombotic effects of prostacyclin infusion on myocardial platelet deposition were studied in a canine model during and after global ischemia. Eleven isolated heart preparations were subjected to 1 hour of cardioplegic arrest under moderate hypothermia (27 to 28/sup 0/C), including a control group (n = 7) and a prostacyclin-treated group (n = 4). The hearts of four other dogs were continuously perfused for 180 minutes. Platelet deposition was measured at 15 minute intervals throughout the 3 hour study. Serial full-thickness myocardial biopsy specimens were analyzed for activity of /sup 111/In-labeled platelets with /sup 99m/Tc-labeled erythrocyte correction for tissue blood content. The pattern of platelet distribution was determined by scintiscans of each heart, taken with a gamma camera at the end of the 60 minute reperfusion period. Substantial myocardial platelet deposition was found in the control hearts after ischemia but not in the prostacyclin-treated group (p less than 0.05). Furthermore, prostacyclin infusion had a significant disaggregatory effect on intracoronary platelet deposits when the precardioplegic and postcardioplegic biopsy specimens were analyzed (p less than 0.05). Three hours of continuous perfusion did not increase tissue /sup 111/In-labeled platelet activity. Ex vivo images showed platelet deposition to be a diffuse patchy process with significantly more /sup 111/In activity in the endocardium than in the epicardium after global ischemia (p less than 0.05). These data show the potent antithrombotic properties of prostacyclin in preventing and disaggregating ischemia-induced intracoronary platelet deposition during and after cardioplegic arrest.

  8. Mass spectrometry for the measurement of intramyocardial gas tensions: methodology and application to the study of myocardial ischemia.

    PubMed

    Khuri, S F; O'Riordan, J; Flaherty, J T; Brawley, R K; Donahoo, J S; Gott, V L

    1975-01-01

    The methodology for use of the mass spectrometer for the measurement of intramyocardial gas tensions in the canine preparation is described. Baseling studies were carried out initially in 36 animals, and control levels for myocardial oxygen tension and myocardial carbon dioxide tension were 19 mm Hg (S.D. 6 mm Hg) and 43 mm Hg (S.D. 10 mm Hg), respectively. Myocardial oxygen tension was not altered significantly by varying the arterial oxygen tension between 65 and 300 mm Hg. However, myocardial carbon dioxide tension increased linearly with increased arterial carbon dioxide tension. In 15 dogs placed on total cardiopulmonary bypass, a perfusion pressure 40-60 mm lower than the control mean arterial pressure resulted in myocardial ischemia with a decrease in myocardial oxygen tension and an increase in myocardial carbon dioxide tension. A subsequent increase in perfusion pressure to control levels resulted in resolution of ischemia and return of myocardial oxygen and carbon dioxide tensions to their control level. In another series of open-chest dogs on cardiopulmonary bypass, a proximal constriction applied to the left coronary circumflex artery resulted in a marked decrease in myocardial oxygen tensions and a marked increase in myocardial carbon dioxide tensions in the region supplied by the constricted vessel. In yet another series of open-chest dogs, it was found that incremental decreases in coronary flow established by constriction of the circumflex artery resulted in an exponential increase in both myocardial carbon dioxide tensions and ST-segment elevation as determined by a 25-gauge multi-contact plunge electrode placed in the posterior left ventricular wall. It appears that mass spectrometry techniques for evaluating myocardial ischemia have several advantages over myocardial biopsy techniques for assay of ATP and lactate, and also over the technique of coronary sinus lactate determination. PMID:1209001

  9. Dietary lipid modification of myocardial eicosanoids following ischemia and reperfusion in the rat.

    PubMed

    Abeywardena, M Y; Charnock, J S

    1995-12-01

    Several different edible oils were compared for their ability to modify eicosanoid biosynthesis following experimentally-induced myocardial ischemia and reperfusion in the rat. Two types of palm oil [neutralized, bleached, and deodorized (NBDPO) and refined, bleached, and deodorized (RBDPO)] and partially hydrogenated soybean oil (SBO) were tested against a diet supplemented with sunflower seed oil (SSO) rich in n-6 polyunsaturated fatty acids (PUFA). Fish oil (FO) rich in n-3 PUFA, with its known cardioprotective actions, served as an internal reference point for the study. Test oils were fed as a 12% (w/w) supplement for nine months before the induction of myocardial ischemia and reperfusion. Palm oil diets exerted effects indistinguishable from the SBO group against cardiac arrhythmia, which occurred following alterations to coronary blood flow. Arrhythmic potentials, as expressed by a hierarchical scale (0-9) of arrhythmia score, were: SSO, 1.5 +/- 0.5; FO, 0.9 +/- 0.4; SBO, 3.1 +/- 0.5*; NBDPO, 3.2 +/- 0.5*; RBDPO, 3.3 +/- 0.6*; *P < 0.05 vs. SSO. Following ischemia and reperfusion, both SSO and RBDPO groups tended to show an increase in myocardial prostacyclin, with the effect being more prominent in the RBDPO group (SSO, 10%; RBDPO, 25%). Thromboxane production was reduced in the FO group. Interestingly, cardiac muscle from both FO and palm oil groups displayed a reduced capacity to produce 12-hydroxyeicosatetraenoic acid SSO, 591 +/- 95.8; SBO, 375.5 +/- 48.9; NBDPO, 287.2 +/- 64.7*; RBDPO, 230.9 +/- 80.2**; FO, 203.7 +/- 81.4** (ng/g dry wt, *P < 0.05, **P < 0.01). No clear relationship was seen between the availability of 20:4n-6 in myocardial phospholipids and eicosanoid profile. Data suggests that fatty acid composition of edible oils is not the only determinant of arrhythmic vulnerability and eicosanoid production.

  10. Halothane inhibits calcium accumulation following myocardial ischemia and calcium paradox in guinea pig hearts

    SciTech Connect

    Hoka, S.; Bosnjak, Z.J.; Kampine, J.P.

    1987-08-01

    This study was performed to test the hypothesis that halothane inhibits calcium accumulation associated with myocardial ischemia and calcium paradox. Using a Langendorff preparation in isolated guinea pig hearts, tissue /sup 45/Ca was measured after 40 and 60 min of loading with /sup 45/Ca, followed by 20 min of washout period. Myocardial ischemia was produced by a 30-min occlusion of the left anterior descending coronary artery (LAD). LAD occlusion caused an increase in /sup 45/Ca content in the anterior left ventricular muscle (ischemic area) of 215% compared to that of the posterior left ventricular muscle (normal myocardium). The increase in /sup 45/Ca content in the ischemic area was significantly less (P less than 0.05) in the presence of halothane (1%) compared to the non-halothane group. Halothane did not significantly alter /sup 45/Ca content in the non-ischemic myocardium. Myocardial injury associated with calcium paradox, which was produced by a 10-min perfusion of the heart with calcium-free Krebs solution followed by normal calcium repletion, caused a significant increase (P less than 0.05) in the /sup 45/Ca content compared to control. Addition of halothane (1%) significantly depressed (P less than 0.05) the increase in /sup 45/Ca content caused by calcium paradox. It is suggested that halothane might inhibit calcium accumulation associated with myocardial ischemia and calcium paradox under certain experimental situations. The inhibitory effect of halothane on calcium accumulation may be beneficial for the ischemic heart during halothane anesthesia.

  11. Effect of Hypercholesterolemia on Myocardial Necrosis and Apoptosis in the Setting of Ischemia-Reperfusion

    PubMed Central

    Osipov, Robert M.; Bianchi, Cesario; Feng, Jun; Clements, Richard T.; Liu, Yuhong; Robich, Michael P.; Glazer, Hilary P.; Sodha, Neel R.; Sellke, Frank W.

    2009-01-01

    Background Hypercholesterolemia is prevalent in patients who experience myocardial ischemia-reperfusion injury (IR). We investigate the impact of dietary induced hypercholesterolemia on the myocardium in the setting of acute IR. Methods and Results In normocholesterolemic (NC,n=7) and hypercholesterolemic (HC,n=7) Yucatan male pigs, the left anterior descending coronary artery was occluded for 60 min, followed by reperfusion for 120 min. Hemodynamic values were recorded and TTC staining was used to assess necrosis. Oxidative stress was measured. Specific cell death and survival signaling pathways were assessed by Western blot and TUNEL staining. Infarct size was 45% greater in HC vs. NC (42% vs. 61%,p<.05), whereas the area at risk (AAR) was similar in both groups (p=0.61). While global LV function (+dP/dt,p<.05) was higher during entire period of IR in HC vs. NC, regional function deteriorated more following reperfusion in HC (p<.05). Ischemia increased indices of myocardial oxidative stress such as protein oxidation (p<.05), lipid peroxidation (p<.05), and nitrotyrosylation in HC vs. NC, as well as the expression of phospho-eNOS (p<.05). The expression of myeloperoxidase, p38 MAPK, and phospho-p38 MAPK was higher in HC vs. NC (all p<05). Ischemia caused higher expression of the pro-apoptotic protein PARP (p<.05), and lower expression of the pro-survival proteins Bcl2 (p<.05), phospho-Akt, (p<.05), and phospho-PKCε (p<.05) in the HC vs. NC. TUNEL positive cell count was 3.8 fold (p<.05) higher in the AAR of HC vs. NC. Conclusions This study demonstrates that experimental hypercholesterolemia is associated with increased myocardial oxidative stress and inflammation, attenuation of cell survival pathways and induction of apoptosis in the ischemic territory, which together may account for the expansion of myocardial necrosis in the setting of acute IR. PMID:19752371

  12. Prevalence of and variables associated with silent myocardial ischemia on exercise thallium-201 stress testing

    SciTech Connect

    Gasperetti, C.M.; Burwell, L.R.; Beller, G.A. )

    1990-07-01

    The prevalence of silent myocardial ischemia was prospectively assessed in a group of 103 consecutive patients (mean age 59 +/- 10 years, 79% male) undergoing symptom-limited exercise thallium-201 scintigraphy. Variables that best correlated with the occurrence of painless ischemia by quantitative scintigraphic criteria were examined. Fifty-nine patients (57%) had no angina on exercise testing. A significantly greater percent of patients with silent ischemia than of patients with angina had a recent myocardial infarction (31% versus 7%, p less than 0.01), had no prior angina (91% versus 64%, p less than 0.01), had dyspnea as an exercise test end point (56% versus 35%, p less than 0.05) and exhibited redistribution defects in the supply regions of the right and circumflex coronary arteries (50% versus 35%, p less than 0.05). The group with exercise angina had more ST depression (64% versus 41%, p less than 0.05) and more patients with four or more redistribution defects. However, there was no difference between the two groups with respect to mean total thallium-201 perfusion score, number of redistribution defects per patient, multi-vessel thallium redistribution pattern or extent of angiographic coronary artery disease. There was also no difference between the silent ischemia and angina groups with respect to antianginal drug usage, prevalence of diabetes mellitus, exercise duration, peak exercise heart rate, peak work load, peak double (rate-pressure) product and percent of patients achieving greater than or equal to 85% of maximal predicted heart rate for age. Thus, in this study group, there was a rather high prevalence rate of silent ischemia (57%) by exercise thallium-201 criteria.

  13. Protection against myocardial ischemia-reperfusion injury in clinical practice.

    PubMed

    Garcia-Dorado, David; Rodríguez-Sinovas, Antonio; Ruiz-Meana, Marisol; Inserte, Javier

    2014-05-01

    Even when reperfusion therapy is applied as early as possible, survival and quality of life are compromised in a considerable number of patients with ST-segment elevation acute myocardial infarction. Some cell death following transient coronary occlusion occurs during reperfusion, due to poor handling of calcium in the sarcoplasmic reticulum-mitochondria system, calpain activation, oxidative stress, and mitochondrial failure, all promoted by rapid normalization of intracellular pH. Various clinical trials have shown that infarct size can be limited by nonpharmacological strategies--such as ischemic postconditioning and remote ischemic conditioning--or by drugs--such as cyclosporine, insulin, glucagon-like peptide-1 agonists, beta-blockers, or stimulation of cyclic guanosine monophosphate synthesis. However, some clinical studies have yielded negative results, largely due to a lack of consistent preclinical data or a poor design, especially delayed administration. Large-scale clinical trials are therefore necessary, particularly those with primary clinical variables and combined therapies that consider age, sex, and comorbidities, to convert protection against reperfusion injury into a standard treatment for patients with ST-segment elevation acute myocardial infarction. PMID:24774733

  14. Protection against myocardial ischemia-reperfusion injury in clinical practice.

    PubMed

    Garcia-Dorado, David; Rodríguez-Sinovas, Antonio; Ruiz-Meana, Marisol; Inserte, Javier

    2014-05-01

    Even when reperfusion therapy is applied as early as possible, survival and quality of life are compromised in a considerable number of patients with ST-segment elevation acute myocardial infarction. Some cell death following transient coronary occlusion occurs during reperfusion, due to poor handling of calcium in the sarcoplasmic reticulum-mitochondria system, calpain activation, oxidative stress, and mitochondrial failure, all promoted by rapid normalization of intracellular pH. Various clinical trials have shown that infarct size can be limited by nonpharmacological strategies--such as ischemic postconditioning and remote ischemic conditioning--or by drugs--such as cyclosporine, insulin, glucagon-like peptide-1 agonists, beta-blockers, or stimulation of cyclic guanosine monophosphate synthesis. However, some clinical studies have yielded negative results, largely due to a lack of consistent preclinical data or a poor design, especially delayed administration. Large-scale clinical trials are therefore necessary, particularly those with primary clinical variables and combined therapies that consider age, sex, and comorbidities, to convert protection against reperfusion injury into a standard treatment for patients with ST-segment elevation acute myocardial infarction.

  15. Effects of endomorphin-1 postconditioning on myocardial ischemia/reperfusion injury and myocardial cell apoptosis in a rat model.

    PubMed

    Zhang, Wei-Ping; Zong, Qiao-Feng; Gao, Qin; Yu, Ying; Gu, Xiao-Yu; Wang, Ya; Li, Zheng-Hong; Ge, Min

    2016-10-01

    Endomorphins (EMs) have important roles in the body with regards to analgesia, feeding behavior, gastrointestinal movement and inflammatory reaction. Recent studies have reported that EMs may also participate in chronic hypoxia in the protection of rat myocardial ischemia/reperfusion; however, the mediator and underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the effects of EM‑1 postconditioning on myocardial ischemia/reperfusion injury (MIRI) and myocardial cell apoptosis in a rat model, and to assess its likely mechanisms. A total of 48 male Sprague Dawley rats were randomly divided into four groups: Sham group, ischemia/reperfusion group (IR group), ischemic postconditioning group (IPO group) and EM‑1 postconditioning group (EM50 group). A MIRI model was established via occlusion of the left anterior descending branch of the coronary artery for 30 min, followed by reperfusion for 120 min in vivo. Hemodynamic indexes were recorded and analyzed. Following reperfusion, plasma lactate dehydrogenase (LDH), creatine kinase‑MB (CK‑MB), malondialdehyde (MDA), superoxide dismutase (SOD), interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α) contents or activities were measured, infarct size was determined, and the expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) mRNA and cleaved caspase‑3 protein were assessed. In the IR group, mean arterial pressure (MAP) and heart rate (HR) were decreased compared with in the sham group. In addition, LDH and CK‑MB levels were increased; IL‑6, TNF‑α and MDA content was increased; SOD activity was decreased; the Bcl‑2/Bax ratio was decreased; and cleaved caspase‑3 protein expression levels were increased in the IR group. Compared with in the IR group, in the IPO and EM50 groups, MAP and heart rate (HR) were recovered to various extents post‑reperfusion; LDH and CK‑MB levels were decreased; IL‑6, TNF‑α and MDA

  16. The CD133+ cell as advanced medicinal product for myocardial and limb ischemia.

    PubMed

    Bongiovanni, Dario; Bassetti, Beatrice; Gambini, Elisa; Gaipa, Giuseppe; Frati, Giacomo; Achilli, Felice; Scacciatella, Paolo; Carbucicchio, Corrado; Pompilio, Giulio

    2014-10-15

    Ischemic diseases are the major cause of death and morbidity in Western countries. In the last decade, cell therapy has been suggested to be a promising treatment both in acute/chronic myocardial and peripheral ischemia. Different cell lineages have been tested, including endothelial progenitor cells. A subpopulation of bone marrow-derived immature ECPs, expressing the highly conserved stem cell glycoprotein antigen prominin-1 or CD133 marker, was shown to possess pro-angiogenic and antiapoptotic effects on ischemic tissues. The mechanisms implicated in CD133+ cells ability to contribute to neovascularization processes have been attributed to their ability to directly differentiate into newly forming vessels and to indirectly activate pro-angiogenic signaling by paracrine mechanisms. A large body of in vivo experimental evidences has demonstrated the potential of CD133+ cells to reverse ischemia. Moreover, several clinical trials have reported promising beneficial effects after infusion of autologous CD133+ into ischemic heart and limbs exploiting various delivery strategies. These trials have contributed to characterize the CD133+ manufacturing process as an advanced cell product (AMP). The aim of this review is to summarize available experimental and clinical data on CD133+ cells in the context of myocardial and peripheral ischemia, and to focus on the development of the CD133+ cell as an anti-ischemic AMP.

  17. Left ventricular energy model predicts adverse events in women with suspected myocardial ischemia: results from the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE) study

    PubMed Central

    Weinberg, Nicole; Pohost, Gerald M.; Bairey Merz, C. Noel; Shaw, Leslee J.; Sopko, George; Fuisz, Anthon; Rogers, William J.; Walsh, Edward G.; Johnson, B. Delia; Sharaf, Barry L.; Pepine, Carl J.; Mankad, Sunil; Reis, Steven E.; Rayarao, Geetha; Vido, Diane A.; Bittner, Vera; Tauxe, Lindsey; Olson, Marian B.; Kelsey, Sheryl F.; Biederman, Robert WW

    2013-01-01

    Objectives To assess the prognostic value of a left ventricular energy-model in women with suspected myocardial ischemia. Background The prognostic value of internal energy utilization (IEU) of the left ventricle in women with suspected myocardial ischemia is unknown. Methods Women [n=227, mean age 59±12 years (range, 31-86 years)], with symptoms of myocardial ischemia, underwent myocardial perfusion imaging (MPI) assessment for regional perfusion defects along with measurement of ventricular volumes separately by gated Single Photon Emission Computed Tomography (SPECT) (n=207) and magnetic resonance imaging (MRI) (n=203). During follow-up (40±17 months), time to first major adverse cardiovascular event (MACE, death, myocardial infarction or hospitalization for congestive heart failure) was analyzed using MRI and gated SPECT variables. Results Adverse events occurred in 31 (14%). Multivariable Cox models were formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, P<0.005) and IEU and systolic blood pressure by gated SEPCT (Chi-squared 34, P<0.005). The models remained predictive after adjustment for age, disease history and Framingham risk score. For each Cox model, patients were categorized as high-risk if the model hazard was positive and not high-risk otherwise. Kaplan-Meier analysis of time to MACE was performed for high-risk vs. not high-risk for MR (log rank 25.3, P<0.001) and gated SEPCT (log rank 18.2, P<0.001) models. Conclusions Among women with suspected myocardial ischemia a high internal energy utilization has higher prognostic value than either a low EF or the presence of a myocardial perfusion defect assessed using two independent modalities of MR or gated SPECT. PMID:24015377

  18. Do antioxidant vitamins reduce infarct size following acute myocardial ischemia/reperfusion?

    PubMed

    Bellows, S D; Hale, S L; Simkhovich, B Z; Kay, G L; Kloner, R A

    1995-02-01

    There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size. PMID:7540423

  19. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-01-01

    Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice. PMID:26950150

  20. The emergency department ECG and immediately life-threatening complications in initially uncomplicated suspected myocardial ischemia.

    PubMed

    Zalenski, R J; Sloan, E P; Chen, E H; Hayden, R F; Gold, I W; Cooke, D

    1988-03-01

    The emergency physician's disposition of patients with suspected myocardial ischemia is currently debated; some physicians believe that a subgroup of patients can be managed safely outside the coronary care unit. Clinical predictors are needed in assessing the patient with suspected myocardial ischemia to help identify this subgroup. Through a retrospective cohort study, we investigated the value of the initial emergency department ECG in discriminating between chest pain patients with low and high risk for immediately life-threatening complications. Two hundred eleven initially uncomplicated consecutive coronary care unit admissions with suspected unstable angina or myocardial infarction were studied. Patient outcome, including the incidence of myocardial infarction, complications, and mechanical and pharmacologic interventions, was reviewed. Immediately life-threatening complications included ventricular fibrillation, ventricular tachycardia, shock, 2 degrees and 3 degrees block, and death. Mechanical interventions included electrocardioversion or defibrillation, endotracheal intubation, intra-aortic balloon pump, Swan-Ganz catheter, or pacemaker insertion. Pressors, antiarrhythmics, and vasodilators were the reviewed pharmacologic interventions. A positive ECG was defined by the presence of ST elevation or depression, T wave inversion, left ventricular hypertrophy, left bundle branch block, paced rhythm, or new Q waves. All other ECG interpretations were considered negative. Patients were divided into two groups based on this initial emergency physician ECG interpretation and their complication incidences compared. Of the 211 patients, 96 had a positive ECG; 115 had negative ECGs. Patients with positive ECGs were older, had a greater history and concurrent incidence of myocardial infarction, and more complications and intensive interventions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3345014

  1. Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction.

    PubMed

    Ekeløf, Sarah V; Halladin, Natalie L; Jensen, Svend E; Zaremba, Tomas; Aarøe, Jens; Kjærgaard, Benedict; Simonsen, Carsten W; Rosenberg, Jacob; Gögenur, Ismail

    2016-01-01

    Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

  2. Prognostic importance of silent myocardial ischemia detected by intravenous dipyridamole thallium myocardial imaging in asymptomatic patients with coronary artery disease

    SciTech Connect

    Younis, L.T.; Byers, S.; Shaw, L.; Barth, G.; Goodgold, H.; Chaitman, B.R. )

    1989-12-01

    One hundred seven asymptomatic patients who underwent intravenous dipyridamole thallium imaging were evaluated to determine prognostic indicators of subsequent cardiac events over an average follow-up period of 14 +/- 10 months. Univariate analysis of 18 clinical, scintigraphic and angiographic variables revealed that a reversible thallium defect, a combined fixed and reversible thallium defect, number of segmental thallium defects and extent of coronary artery disease were significant predictors of subsequent cardiac events. Of the 13 patients who died or had a nonfatal infarction, 12 had a reversible thallium defect. Stepwise logistic regression analysis selected a reversible thallium defect as the only significant predictor of cardiac events. When death or myocardial infarction was the outcome variable, a combined fixed and reversible thallium defect was the only predictor of outcome. In patients without previous myocardial infarction, the cardiac event rate was significantly greater in those with an abnormal versus normal thallium scan (55% versus 12%, p less than 0.001). Thus, intravenous dipyridamole thallium scintigraphy is a useful noninvasive test to risk stratify asymptomatic patients with coronary artery disease. A reversible thallium defect most likely indicates silent myocardial ischemia in a sizable fraction of patients in this clinical subset and is associated with an unfavorable prognosis.

  3. [Newly developed stenocardia: lack of ventricular electrical instability in the absence of acute myocardial ischemia].

    PubMed

    Areshev, G P; Agapov, A A; Gratsianskiĭ, N A; Ananich, V A

    1988-02-01

    A total of 130 patients with angina of new onset were examined within first 3 months of the disease. Macrofocal myocardial infarction survivors were not admitted to the study. The investigation included selective coronaro-angiography and ventriculography, Holter's ECG monitoring over 24 to 48 hours and bicycle ergometry. Programmed right-ventricular electric stimulation was conducted in 41 patients. Only one major coronary artery was affected in 78% of patients. Left-ventricular ejection fraction nearly always exceeded 50%. Groups of ventricular extrasystoles were detected by ECG monitoring in 10.8% and by bicycle ergometry in 2.5%. No signs of electrical instability were ever detected at programmed stimulation, done in the absence of anginal attacks. Groups of ventricular extrasystoles were more common, as compared to single extrasystoles (p less than 0.001), in acute myocardial ischemia, being more frequently associated with unstable rather than stable angina of new onset (p less than 0.05). In early coronary heart disease, signs of electric ventricular instability are not detectable in the absence of myocardial ischemia.

  4. The role of positron emission tomography in the evaluation of myocardial ischemia in women.

    PubMed

    Taqueti, Viviany R; Dorbala, Sharmila

    2016-10-01

    Cardiovascular disease continues to be the number one cause of death in women, yet most women are unaware of their risk. Over the last decade, radionuclide myocardial perfusion imaging with positron emission tomography (PET) has become a powerful tool for the diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). This editorial viewpoint will review the maturing role of PET imaging in women, particularly as applied to the evaluation of ischemic heart disease. Specifically, we focus on distinct advantages offered by PET imaging in the evaluation of myocardial ischemia in women: (1) improved diagnostic accuracy, including in the presence of breast or adipose tissue and small left ventricular cavity size, (2) decreased radiation exposure through the use of short-lived radiopharmaceuticals, and (3) the ability to quantify myocardial blood flow and coronary flow reserve to diagnose ischemia, even in the absence of obstructive CAD. As such, cardiac PET perfusion imaging stands to play a unique role in defining the diagnosis and prognosis of women with ischemic heart disease, while also guiding new treatment strategies for their more prevalent cardiovascular disease phenotypes. PMID:27488383

  5. Early detection of acute transmural myocardial ischemia by the phasic systolic-diastolic changes of local tissue electrical impedance.

    PubMed

    Jorge, Esther; Amorós-Figueras, Gerard; García-Sánchez, Tomás; Bragós, Ramón; Rosell-Ferrer, Javier; Cinca, Juan

    2016-02-01

    Myocardial electrical impedance is influenced by the mechanical activity of the heart. Therefore, the ischemia-induced mechanical dysfunction may cause specific changes in the systolic-diastolic pattern of myocardial impedance, but this is not known. This study aimed to analyze the phasic changes of myocardial resistivity in normal and ischemic conditions. Myocardial resistivity was measured continuously during the cardiac cycle using 26 different simultaneous excitation frequencies (1 kHz-1 MHz) in 7 anesthetized open-chest pigs. Animals were submitted to 30 min regional ischemia by acute left anterior descending coronary artery occlusion. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow were recorded simultaneously. Baseline myocardial resistivity depicted a phasic pattern during the cardiac cycle with higher values at the preejection period (4.19 ± 1.09% increase above the mean, P < 0.001) and lower values during relaxation phase (5.01 ± 0.85% below the mean, P < 0.001). Acute coronary occlusion induced two effects on the phasic resistivity curve: 1) a prompt (5 min ischemia) holosystolic resistivity rise leading to a bell-shaped waveform and to a reduction of the area under the LV pressure-impedance curve (1,427 ± 335 vs. 757 ± 266 Ω·cm·mmHg, P < 0.01, 41 kHz) and 2) a subsequent (5-10 min ischemia) progressive mean resistivity rise (325 ± 23 vs. 438 ± 37 Ω·cm at 30 min, P < 0.01, 1 kHz). The structural and mechanical myocardial dysfunction induced by acute coronary occlusion can be recognized by specific changes in the systolic-diastolic myocardial resistivity curve. Therefore these changes may become a new indicator (surrogate) of evolving acute myocardial ischemia.

  6. Penehyclidine Hydrochloride Preconditioning Provides Cardioprotection in a Rat Model of Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Lin, Duomao; Ma, Jun; Xue, Yanyan; Wang, Zhaoqi

    2015-01-01

    To investigate the impacts and related mechanisms of penehyclidine hydrochloride (PHC) on ischemia/reperfusion (I/R)-induced myocardial injury. A rat model of myocardial I/R injury was established by the ligation of left anterior descending coronary artery for 30 min followed by 3 h perfusion. Before I/R, the rats were pretreated with or without PHC. Cardiac function was measured by echocardiography. The activities/levels of myocardial enzymes, oxidants and antioxidant enzymes were detected. Evans blue/TTC double staining was performed to assess infarct size. Cardiomyocyte apoptosis was evaluated by TUNEL assay. The release of inflammatory cytokines and inflammatory mediators was detected by ELISA. Western blot was performed to analyze the expression of COX-2, IκB, p-IκB and NF-κB. Meanwhile, the rats were given a single injection of H-PHC before I/R. The effects of PHC on myocardial infarct and cardiac function were investigated after 7 days post-reperfusion. We found that PHC remarkably improved cardiac function, alleviated myocardial injury by decreasing myocardial enzyme levels and attenuated oxidative stress in a dose-dependent manner. Additionally, PHC preconditioning significantly reduced infarct size and the apoptotic rate of cardiomyocytes. Administration of PHC significantly decreased serum TNF-α, IL-1β, IL-6 and PGE2 levels and myocardium COX-2 level. Meanwhile, the expression levels of p-IκB and NF-κB were downregulated, while IκB expression was upregulated. H-PHC also exerted long-term cardioprotection in a rat model of I/R injury by decreasing infarct size and improving cardiac function. These results suggest that PHC can efficiently protect the rats against I/R-induced myocardial injury. PMID:26632817

  7. FMLP provokes coronary vasoconstriction and myocardial ischemia in rabbits

    SciTech Connect

    Gillespie, M.N.; Booth, D.C.; Friedman, B.J.; Cunningham, M.R.; Jay, M.; De Maria, A.N. )

    1988-03-01

    Recent pathological studies of coronary arteries from humans with suspected coronary spasm have revealed an augmented intramural burden of inflammatory cells. To test the hypothesis than inappropriate activation of inflammatory cells participates in the evolution of coronary vasospasm, the present experiment employed a newly developed coronary arteriographic technique for use in pentobarbital-anesthetized rabbits to evaluate the coronary vasomotor actions of the nonselective inflammatory cell stimulant, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). In 10 of 10 animals, selective left intracoronary injection of 200 ng fMLP evoked profound left coronary narrowing accompanied in all cases by ST segment deviation and dysrhythmias. Thallium-201 scintigraphy demonstrated hypoperfusion of the left ventricular free wall and septum supplied by the spastic coronary artery. The fMLP-induced epicardial vasoconstriction, ischemic electrocardiogram (ECG) changes, and thallium perfusion defects were reversed by intravenous nitroglycerin. Neither the right coronary artery nor its distribution were influenced by left coronary injection of fMLP. Additional experiments in isolated, salt solution-perfused rabbit hearts demonstrated that fMLP failed to exert direct coronary vasoconstrictor effects. These observations indicate that the nonselective inflammatory cell stimulant, fMLP, provokes arteriographically demonstrable coronary spasm with attendant myocardial hypoperfusion and ischemic ECG changes in anesthetized rabbits. Such a model may be useful in exploring the dynamic role of inflammatory cells in development of coronary spasm.

  8. Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs.

    PubMed Central

    Wellenius, Gregory A; Coull, Brent A; Godleski, John J; Koutrakis, Petros; Okabe, Kazunori; Savage, Sara T; Lawrence, Joy E; Murthy, G G Krishna; Verrier, Richard L

    2003-01-01

    Short-term increases in ambient air pollution have been associated with an increased incidence of acute cardiac events. We assessed the effect of inhalation exposure to concentrated ambient particles (CAPs) on myocardial ischemia in a canine model of coronary artery occlusion. Six mongrel dogs underwent thoracotomy for implantation of a vascular occluder around the left anterior descending coronary artery and tracheostomy to facilitate particulate exposure. After recovery (5-13 weeks), pairs of subjects were exposed for 6 hr/day on 3 or 4 consecutive days. Within each pair, one subject was randomly assigned to breathe CAPs on the second exposure day and filtered air at other times. The second subject breathed CAPs on the third exposure day and filtered air at other times. Immediately after each exposure, subjects underwent 5-min coronary artery occlusion. We determined ST-segment elevation, a measure of myocardial ischemia heart rate, and arrhythmia incidence during occlusion from continuous electrocardiograms. Exposure to CAPs (median, 285.7; range, 161.3-957.3 microg/m3) significantly (p = 0.007) enhanced occlusion-induced peak ST-segment elevation in precordial leads V4 (9.4 +/- 1.7 vs. 6.2 +/- 0.9 mm, CAPs vs. filtered air, respectively) and V5 (9.2 +/- 1.3 vs. 7.5 +/- 0.9 mm). ST-segment elevation was significantly correlated with the silicon concentration of the particles and other crustal elements possibly associated with urban street dust (p = 0.003 for Si). No associations were found with CAPs mass or number concentrations. Heart rate was not affected by CAPs exposure. These results suggest that exacerbation of myocardial ischemia during coronary artery occlusion may be an important mechanism of environmentally related acute cardiac events. PMID:12676590

  9. The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

    PubMed Central

    Kurian, Gino A.; Rajagopal, Rashmi; Vedantham, Srinivasan; Rajesh, Mohanraj

    2016-01-01

    Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions. PMID:27313825

  10. The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited.

    PubMed

    Kurian, Gino A; Rajagopal, Rashmi; Vedantham, Srinivasan; Rajesh, Mohanraj

    2016-01-01

    Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions. PMID:27313825

  11. Internal countershock produces myocardial damage and lactate production without myocardial ischemia in anesthetized dogs

    SciTech Connect

    Gaba, D.M.; Maxwell, M.S.; Merlone, S.; Smith, C.

    1987-04-01

    The global myocardial extraction of lactate was measured in 13 halothane anesthetized dogs to assess the effect of electric countershock applied directly to the heart. Seven animals received two countershocks of 30 delivered joules each, while six animals were not shocked but were atrially paced to a rate of 190-200, both with and without occlusion of the vena cava to produce a mean arterial pressure of 40-50 mmHg. All animals had substantially positive lactate extraction in the baseline state (36 +/- 10% for countershock group vs. 41 +/- 3% for pacing group). Myocardial lactate extraction reached a markedly negative nadir 2.5 min after countershock (-19 +/- 15%), but returned toward normal by 6 min (10 +/- 6%). Lactate extraction was not significantly changed from baseline in the pacing group. The relationship between changes in regional myocardial blood flow (radiolabeled microspheres) and post-countershock myocardial damage (technetium pyrophosphate uptake) was assessed in six dogs shocked as above. Mean myocardial blood flow was increased minimally immediately after countershock (0.78 +/- 0.08 ml X min-1 X g-1 vs. 1.16 +/- 0.3), but there was no difference in blood flow between damaged and undamaged tissue at either time point. The epicardial-to-endocardial ratio of blood flow was unchanged after countershock (0.97 +/- 0.05 vs. 0.99 +/- 0.08). There was no relationship between myocardial damage and either the absolute amount of blood flow after countershock (r = -0.03) or the change in blood flow compared with the pre-shock period (r = 0.01).

  12. Silent myocardial ischemia and infarction in diabetics with peripheral vascular disease: Assessment by dipyridamole thallium-201 scintigraphy

    SciTech Connect

    Nesto, R.W.; Watson, F.S.; Kowalchuk, G.J.; Zarich, S.W.; Hill, T.; Lewis, S.M.; Lane, S.E. )

    1990-11-01

    We investigated the incidence of silent myocardial ischemia and infarction as assessed by dipyridamole thallium scintigraphy in 30 diabetic patients with peripheral vascular disease and without clinical suspicion of coronary artery disease. Seventeen patients (57%) had thallium abnormalities, with reversible thallium defects compatible with ischemia in 14 patients (47%) and evidence of prior, clinically silent myocardial infarction in 11 patients (37%). Thallium abnormalities were most frequent in patients with concomitant hypertension and cigarette smoking (p = 0.001). These results suggest that unsuspected coronary artery disease is common in this particular group of patients with diabetes mellitus.

  13. Acute Humanin Therapy Attenuates Myocardial Ischemia and Reperfusion Injury in Mice

    PubMed Central

    Muzumdar, Radhika H.; Huffman, Derek M.; Calvert, John W.; Jha, Saurabh; Weinberg, Yoni; Cui, Lingguang; Nemkal, Anjana; Atzmon, Gil; Klein, Laura; Gundewar, Susheel; Ji, Sang Yong; Lavu, Madhav; Predmore, Benjamin L.; Lefer, David J.

    2010-01-01

    Objective Humanin, an endogenous anti-apoptotic peptide, has previously been shown to protect against Alzheimer’s disease and a variety of cellular insults. We evaluated the effects of a potent analog of humanin, HNG, in an in vivo murine model of myocardial ischemia and reperfusion (MI-R). Methods Male C57BL6/J mice (8–10 week old) were subjected to 45 min of left coronary artery occlusion followed by 24 hr reperfusion. HNG or vehicle was administered intra-peritoneally one hour prior or at the time of reperfusion. The extent of myocardial infarction per area-at-risk was evaluated at 24 hrs using Evans Blue dye and 2,3,5 triphenyltetrazolium chloride (TTC) staining. Left ventricular (LV) function was evaluated at one week post ischemia using high-resolution, 2- D echocardiography (VisualSonics Vevo 770). Myocardial cell signaling pathways and apoptotic markers were assessed at various time points (0–24 hrs) following reperfusion. Cardiomyocyte survival and apoptosis in response to HNG were assessed in vitro. Results HNG reduced infarct size relative to the area-at-risk in a dose dependent fashion, with a maximal reduction at the dose of 2 mg/kg. HNG therapy enhanced LV ejection fraction and preserved post-ischemic LV dimensions (end-diastolic and end-systolic), resulting in improved cardiac function. Treatment with HNG significantly increased the expression of pAMPK and p-eNOS in the heart and attenuated Bax and Bcl-2 levels following MI-R. HNG improved cardiomyocyte survival and decreased apoptosis in response to daunorubicin in vitro. Conclusions These data show that HNG provides cardioprotection in a mouse model of MI-R potentially through activation of AMPK-eNOS mediated signaling and regulation of apoptotic factors. HNG may represent a novel agent for the treatment of acute myocardial infarction. PMID:20651283

  14. Ginkgolide B Reduces the Degradation of Membrane Phospholipids to Prevent Ischemia/Reperfusion Myocardial Injury in Rats.

    PubMed

    Pei, Hong-Xia; Hua, Rong; Guan, Cha-Xiang; Fang, Xiang

    2015-01-01

    Platelet-activating factor (PAF), a bioactive phospholipid, plays an important role in the integrity of the cellular membrane structure, and is involved in the pathogenesis of myocardial ischemia/reperfusion (IR) injuries. In this study, we tested the hypothesis that blockage of PAF receptor by BN 52021 (Ginkgolide B) can prevent IR-induced degradation of the myocardial membrane phospholipid, and deterioration of the cardiac function. Rat hearts in situ were subjected to 5 min ischemia and followed by 10 min reperfusion. Cardiac performances during periods of ischemia and reperfusion were monitored, and the amount of membrane phospholipids was analyzed. Myocardial total phospholipids, phosphatidylcholine, and phosphatidylethanolamine were decreased significantly in ischemia-reperfusion rat hearts compared with those of sham-operated rat hearts. Degradation of the membrane phospholipid was accompanied by the deterioration of cardiac functions and increase in serum lactate dehydrogenase (LDH) activity. BN 52021 (15 mg/kg), given by intravenous infusion 10 min prior to the left anterior descending coronary artery occlusion, reduced IR-related degradation of the myocardial phospholipids, the activity of serum LDH, and was concomitant with improvement of cardiac function. Furthermore, we demonstrated that the production of PAF was increased and BN 52021 decreased cellular damage in cultured anoxic cardiomyocytes. These results indicated that PAF antagonist BN 52021 has a protective effect against IR-induced myocardial dysfunction and degradation of the membrane phospholipids. PMID:26382046

  15. Plumbagin Mediates Cardioprotection Against Myocardial Ischemia/Reperfusion Injury Through Nrf-2 Signaling

    PubMed Central

    Wang, Shi-Xun; Wang, Jian; Shao, Jing-Bo; Tang, Wei-ning; Zhong, Jing-Quan

    2016-01-01

    Background Plumbagin is a potent antioxidant with anti-inflammatory and anti-carcinogenic action. Myocardial ischemia/reperfusion injury results in organ damage through oxidative stress and inflammatory mechanisms. In this study, we analyzed the potential role of plumbagin against myocardial I/R injury in Wistar rats. Material/Methods Oxidative stress was measured through ROS, lipid peroxide content, and antioxidant enzyme activities. The expression of redox signaling and inflammatory proteins was analyzed through Western blotting. Inflammatory cytokine expressions were determined through ELISA. Results Oxidative stress status was reduced by plumbagin by decreasing ROS and lipid peroxide levels in rats with myocardial I/R (MI/R) injury. Plumbagin regulated redox imbalance induced by I/R injury by modulating the transcription factors NF-κB and Nrf-2. Further, downstream targets of NF-κB (COX-2, iNOS) and Nrf-2 (HO-1, NQO1 and GST) expression were significantly downregulated by plumbagin treatment. Pro-inflammatory cytokine expressions were significantly abrogated by plumbagin treatment. Conclusions This study shows the protective role of plumbagin against myocardial I/R injury by regulating antioxidant and inflammatory mechanisms. PMID:27078001

  16. Cellular and molecular mechanisms of endothelial ischemia/reperfusion injury: perspectives and implications for postischemic myocardial protection

    PubMed Central

    Yang, Qin; He, Guo-Wei; Underwood, Malcolm John; Yu, Cheuk-Man

    2016-01-01

    Ischemia/reperfusion (I/R) injury is a major cause of myocardial damage. Despite continuous efforts, minimizing I/R injury still represents a great challenge in standard medical treatments of ischemic heart disease, i.e., thrombolytic therapy, primary percutaneous coronary intervention, and coronary arterial bypass grafting. Development of effective interventions and strategies to prevent or reduce myocardial I/R injury is therefore of great clinical significance. Endothelial dysfunction plays a significant role in myocardial I/R injury, which renders endothelial cells an attractive target for postischemic myocardial protection. The rapidly evolving knowledge of the mechanisms of endothelial I/R injury helps broaden perspective for future development of novel strategies targeting endothelium for alleviating myocardial I/R damage. This review provides a comprehensive summary of the cellular and molecular mechanisms of endothelial I/R injury. Current perspectives and future directions for developing endothelium targeting therapeutics for postischemic myocardial protection are further discussed. PMID:27158368

  17. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Suchal, Kapil; Malik, Salma; Gamad, Nanda; Malhotra, Rajiv Kumar; Goyal, Sameer N.; Chaudhary, Uma; Bhatia, Jagriti; Ojha, Shreesh; Arya, Dharamvir Singh

    2016-01-01

    Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway. PMID:27087891

  18. Protective effect of active perfusion in porcine models of acute myocardial ischemia.

    PubMed

    Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui

    2016-10-01

    Mortality rates associated with off‑pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor‑α (TNF‑α), cardiac troponin (cTnI), creatine kinase‑myocardial band (CK‑MB), interleukin (IL)‑6, IL‑10, B‑cell lymphoma 2 (Bcl‑2), and caspase‑3 were detected using enzyme‑linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, an increased rate of myocardial apoptosis, and a decreased expression level of anti‑apoptotic protein, Bcl‑2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl‑2. Furthermore, the current study indicated that active perfusion was more efficacious

  19. Protective effect of active perfusion in porcine models of acute myocardial ischemia

    PubMed Central

    Feng, Zanxiang; Mao, Zhifu; Dong, Shengjun; Liu, Baohui

    2016-01-01

    Mortality rates associated with off-pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor-α (TNF-α), cardiac troponin (cTnI), creatine kinase-myocardial band (CK-MB), interleukin (IL)-6, IL-10, B-cell lymphoma 2 (Bcl-2), and caspase-3 were detected using enzyme-linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, an increased rate of myocardial apoptosis, and a decreased expression level of anti-apoptotic protein, Bcl-2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF-α, cTnI, CK-MB, IL-6, IL-10 and caspase-3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl-2. Furthermore, the current study indicated that active perfusion was more efficacious in maintaining myocardial perfusion and alleviating

  20. Myocardial contrast echocardiography to assess perfusion in a mouse model of ischemia/reperfusion injury

    NASA Astrophysics Data System (ADS)

    Hossack, John A.; Li, Yinbo; Christensen, Jonathan P.; Yang, Zequan; French, Brent A.

    2004-04-01

    Noninvasive approaches for measuring anatomical and physiological changes resulting from myocardial ischemia / reperfusion injury in the mouse heart have significant value since the mouse provides a practical, low-cost model for modeling human heart disease. In this work, perfusion was assessed before, during and after an induced closed- chest, coronary ischemic event. Ultrasound contrast agent, similar to MP1950, in a saline suspension, was injected via cannulated carotid artery as a bolus and imaged using a Siemens Sequoia 512 scanner and a 15L8 intraoperative transducer operating in second harmonic imaging mode. Image sequences were transferred from the scanner to a PC for analysis. Regions of interest were defined in septal and anterior segments of the myocardium. During the ischemic event, when perfusion was diminished in the anterior segment, mean video intensity in the affected segment was reduced by one half. Furthermore, following reperfusion, hyperemia (enhanced blood flow) was observed in the anterior segment. Specifically, the mean video intensity in the affected segment was increased by approximately 50% over the original baseline level prior to ischemia. Following the approach of Kaul et al., [1], gamma variate curves were fitted to the time varying level of mean video intensity. This foundation suggests the possibility of quantifying myocardial blood flow in ischemic regions of a mouse heart using automated analysis of contrast image data sets. An improved approach to perfusion assessment using the destruction-reperfusion approach [2] is also presented.

  1. Assessment of Myocardial Ischemia in Obese Individuals Undergoing Physical Stress Echocardiography (PSE)

    PubMed Central

    Silveira, Mara Graziele Maciel; Sousa, Antônio Carlos Sobral; Santos, Marcos Antônio Almeida; Tavares, Irlaneide da Silva; Andrade, Stephanie Macedo; Melo, Luiza Dantas; de Andrade, Loren Suyane Oliveira; Santos, Emmanuel Lima Almeida; Oliveira, Joselina Luzia Menezes

    2015-01-01

    Background Physical stress echocardiography is an established methodology for diagnosis and risk stratification of coronary artery disease in patients with physical capacity. In obese (body mass index ≥ 30 kg/m2) the usefulness of pharmacological stress echocardiography has been demonstrated; however, has not been reported the use of physical stress echocardiography in this growing population group. Objective To assess the frequency of myocardial ischemia in obese and non-obese patients undergoing physical stress echocardiography and compare their clinical and echocardiographic differences. Methods 4,050 patients who underwent treadmill physical stress echocardiography were studied according to the Bruce protocol, divided into two groups: obese (n = 945; 23.3%) and non-obese (n = 3,105; 76.6%). Results There was no difference regarding gender. Obese patients were younger (55.4 ± 10.9 vs. 57.56 ± 11.67) and had a higher frequency of hypertension (75.2% vs. 57, 2%; p < 0.0001), diabetis mellitus (15.2% vs. 10.9%; p < 0.0001), dyslipidemia (59.5% vs 51.9%; p < 0.0001), family history of coronary artery disease (59.3% vs. 55.1%; p = 0.023) and physical inactivity (71.4% vs. 52.9%, p < 0.0001). The obese had greater aortic dimensions (3.27 vs. 3.14 cm; p < 0.0001), left atrium (3.97 vs. 3.72 cm; p < 0.0001) and the relative thickness of the ventricule (33.7 vs. 32.8 cm; p < 0.0001). Regarding the presence of myocardial ischemia, there was no difference between groups (19% vs. 17.9%; p = 0.41). In adjusted logistic regression, the presence of myocardial ischemia remained independently associated with age, female gender, diabetes and hypertension. Conclusion Obesity did not behave as a predictor of the presence of ischemia and the physical stress echocardiography. The application of this assessment tool in large scale sample demonstrates the feasibility of the methodology, also in obese. PMID:25714197

  2. Relation between regional myocardial uptake of /sup 82/Rb and perfusion: absolute reduction of cation uptake in ischemia

    SciTech Connect

    Selwyn, A.P.; Allan, R.M.; L'Abbate, A.; Horlock, P.; Camici, P.; Clark, J.; O'Brien, H.A.; Grant, P.M.

    1982-07-01

    Experiments were undertaken using /sup 82/Rb and position tomography to examine the relation between myocardial perfusion and cation uptake during acute ischemia. /sup 82/Rb was repeatedly eluted from a /sup 82/Sr-/sup 82/Rb generator. In six dogs emission tomograms were used to measure the delivered arterial and myocardial concentrations at rest and after coronary stenosis, stress and ischemia. There was a poor overall relation between regional myocardial uptake and flow measured by microspheres and a large individual variability. Extraction of /sup 82/Rb was inversely related to flow. Significant regional reduction of cation uptake was detected in the tomograms when regional flow decreased by more than 35 percent. This reduction was significantly greater when ischemia was present. A small but significantly greater when ischemia was present. A small but significant decrease (33.0 +/- 9.1 percent, mean +/- standard deviation) in the myocardial uptake of /sup 82/Rb was detected only when flow was increased by more than 120 percent in relation to a control area after administration of dypiridamole. The technique using /sup 82/Rb and tomography was applied in five volunteers and five patients with angina pectoris and coronary artery disease. Myocardial tomograms recorded at rest and after exercise in the volunteers showed homogeneous uptake of cation in reproducible and repeatable scans. In contrast, the patients with coronary artery disease showed an absolute mean decrease of 36 +/- 14 percent in regional myocardial uptake of /sup 82/Rb after exercise. These abnormalities persisted in serial tomograms for more than 20 minutes after the symptoms and electrocardiographic signs of ischemia.

  3. Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

    PubMed Central

    Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian; Shahzamani, Mehran; Takhtfooladi, Mohammad Ashrafzadeh; Allahverdi, Amin; Khansari, Mohammadreza

    2015-01-01

    Background Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries. Objective This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Methods Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. Results The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II. Conclusion From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model. PMID:26039663

  4. Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury

    PubMed Central

    Conklin, Daniel J.; Guo, Yiru; Jagatheesan, Ganapathy; Kilfoil, Peter; Haberzettl, Petra; Hill, Bradford G.; Baba, Shahid P.; Guo, Luping; Wetzelberger, Karin; Obal, Detlef; Rokosh, D. Gregg; Prough, Russell A.; Prabhu, Sumanth D.; Velayutham, Murugesan; Zweier, Jay L.; Hoetker, David; Riggs, Daniel W.; Srivastava, Sanjay; Bolli, Roberto; Bhatnagar, Aruni

    2016-01-01

    Rationale Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. Objective We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury. Methods and Results In adult male C57BL/6 mouse hearts, Gstp1/2 was the most abundant GST transcript followed by Gsta4 and Gstm4.1, and GSTP activity was a significant fraction of the total GST activity. mGstp1/2 deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type (WT) mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism 4-hydroxy-trans-2-nonenal (HNE) or trans-2-hexanal; and, upon ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than WT hearts. GSTP-deficiency did not affect I/R-induced free radical generation, JNK activation or depletion of reduced glutathione. Acrolein-exposure induced a hyperpolarizing shift in INa, and acrolein-induced cell death was delayed by SN-6, a Na+/Ca++ exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than WT myocytes to acrolein-induced protein crosslinking and cell death. Conclusions GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes such as acrolein. PMID:26169370

  5. [Changes in acetylcholinesterase and ATPase activity and certain structural features of the erythrocyte membrane in experimental myocardial ischemia].

    PubMed

    Chernukh, A M; Kopteva, L A; Shevchenko, A S

    1980-09-01

    Acute heart ischemia induced by ligation of the left coronary artery is associated with variation in the activity of acetylcholinesterase, Na, K-ATPase and Ca, Mg-ATPase in rat erythrocytes. The maximum pronounced variations in the enzymatic activity and in the membrane capacity of erythroblasts for binding direct turquoise are recorded on the 7th day of the experimental myocardial infarction.

  6. Critical finger ischemia and myocardial fibrosis development after sudden interruption of sildenafil treatment in a systemic sclerosis patient.

    PubMed

    Bruni, C; Bellando-Randone, S; Gargani, L; Picano, E; Pingitore, A; Matucci-Cerinic, M; Guiducci, S

    2016-01-01

    Systemic sclerosis (SSc) is a connective tissue disease frequently associated with Raynaud's Phenomenon (RP). Among possible pharmacological treatments, phosphodiesterase 5 inhibitors are considered in cases of severe non -responsive RP. We present the case of a male SSc patient wh presented with critical finger ischemia and concomitant appearance of myocardial fibrosis after sudden interruption of sildenafil treatment. PMID:27608801

  7. Critical finger ischemia and myocardial fibrosis development after sudden interruption of sildenafil treatment in a systemic sclerosis patient.

    PubMed

    Bruni, C; Bellando-Randone, S; Gargani, L; Picano, E; Pingitore, A; Matucci-Cerinic, M; Guiducci, S

    2016-01-01

    Systemic sclerosis (SSc) is a connective tissue disease frequently associated with Raynaud's Phenomenon (RP). Among possible pharmacological treatments, phosphodiesterase 5 inhibitors are considered in cases of severe non -responsive RP. We present the case of a male SSc patient wh presented with critical finger ischemia and concomitant appearance of myocardial fibrosis after sudden interruption of sildenafil treatment.

  8. Effect of thrombin fragment (TP508) on myocardial ischemia-reperfusion injury in hypercholesterolemic pigs

    PubMed Central

    Osipov, Robert M.; Robich, Michael P.; Feng, Jun; Clements, Richard T.; Liu, Yuhong; Glazer, Hilary P.; Wagstaff, John; Bianchi, Cesario; Sellke, Frank W.

    2009-01-01

    Myocardial ischemia-reperfusion (IR) injury occurs frequently in the setting of hypercholesterolemia. We investigated the potential efficacy of a novel thrombin fragment (TP508) on IR injury in a hypercholesterolemic porcine model. Twenty-one hypercholesterolemic male Yucatan pigs underwent 60 min of mid-left anterior descending coronary artery occlusion followed by 120 min of reperfusion. Pigs received either placebo (control, n = 7) or TP508 in two doses (TP508 low dose, n = 7, as bolus of 0.5 mg/kg 50 min into ischemia and an infusion of 1.25 mg·kg−1·h−1 during reperfusion period or TP508 high dose, n = 7, a double dose of TP508 low-dose group). Myocardial function was monitored throughout the experiment. The area at risk and myocardial necrosis were determined by Monastryl blue/triphenyl tetrazolium chloride staining. Apoptosis in the ischemic territory was assessed. Coronary microvascular reactivity to endothelium-dependent and -independent factors was measured. Myocardial necrosis was lower in both TP508-treated groups vs. control (P < 0.05). Regional left ventricular function was improved only in the TP508 high-dose group (P < 0.05). Endothelium-dependent coronary microvascular reactivity was greater in both TP508-treated groups (P < 0.05) vs. control. The expression of proteins favoring cell survival, 90-kDa heat shock protein and phospho-Bad (Ser112) was higher in the TP508 high-dose group (P < 0.05). The expression of the cell death signaling proteins, cleaved caspase-3 (P < 0.05), apoptosis-inducing factor (P < 0.05), and poly-ADP ribose polymerase (P = 0.07) was lower in the TP508 low-dose group vs. TP508 high-dose and control. The terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling positive cell count was lower in both TP508 groups compared with the control (P < 0.05). This study demonstrates that, in hypercholesterolemic pigs, TP508 decreases myocardial necrosis and apoptosis after IR. Thus TP508 may offer a novel approach in

  9. Cardiac Microvascular Barrier Function Mediates the Protection of Tongxinluo against Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Qi, Kang; Li, Lujin; Li, Xiangdong; Zhao, Jinglin; Wang, Yang; You, Shijie; Hu, Fenghuan; Zhang, Haitao; Cheng, Yutong; Kang, Sheng; Cui, Hehe; Duan, Lian; Jin, Chen; Zheng, Qingshan; Yang, Yuejin

    2015-01-01

    Objective Tongxinluo (TXL) has been shown to decrease myocardial necrosis after ischemia/reperfusion (I/R) by simulating ischemia preconditioning (IPC). However, the core mechanism of TXL remains unclear. This study was designed to investigate the key targets of TXL against I/R injury (IRI) among the cardiac structure-function network. Materials and Methods To evaluate the severity of lethal IRI, a mathematical model was established according to the relationship between myocardial no-reflow size and necrosis size. A total of 168 mini-swine were employed in myocardial I/R experiment. IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively. Principal component analysis was applied to further determine 9 key targets of IPC in cardioprotection. Then, the key targets of TXL in cardioprotection were confirmed. Results Necrosis size and no-reflow size fit well with the Sigmoid Emax model. Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively). Functional and structural indices correlate positively with NRS (R2=0.64, R2=0.62, P<0.01, respectively). TXL recovers SUR2, iNOS activity, eNOS activity, VE-cadherin, β-catenin, γ-catenin and P-selectin with a trend toward the sham group. Moreover, TXL increases PKA activity and eNOS expression with a trend away from the sham group. Among the above nine indices, eNOS activity, eNOS, VE-cadherin, β-catenin and γ-catenin expression were significantly up-regulated by TXL compared with IPC (P>0.05) or CCB (P<0.05) and these five microvascular barrier-related indices may be the key targets of TXL in minimizing IRI. Conclusions Our study underlines the lethal IRI as one of the causes of myocardial necrosis. Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC. PMID:25781461

  10. Effects of pharmacological suppression of plasminogen activator inhibitor-1 in myocardial remodeling after ischemia reperfusion injury.

    PubMed

    Watanabe, Ryo; Nakajima, Takuya; Ogawa, Masahito; Suzuki, Jun-ichi; Muto, Susumu; Itai, Akiko; Hirata, Yasunobu; Nagai, Ryozo; Isobe, Mitsuaki

    2011-01-01

    Plasminogen activator inhibitor-1 (PAI-1) contributes to cardiac ventricular remodeling because migration of inflammatory cells and attenuation of extracellular matrix degradation are caused by plasmin and matrix metalloproteinase. However, the roles of PAI-1 in myocardial ischemia reperfusion (I/R) injury and the following inflammatory response have not yet been well elucidated. To clarify the role of PAI-1 in myocardial I/R injury, we used a specific PAI-1 inhibitor (IMD-1622) in a rat model. The left anterior descending coronary artery was ligated and reperfusion was performed by loosening the suture after 30 minutes of arterial occlusion. A single administration of IMD-1622 (20 mg/kg) or vehicle was given intraperitoneally and then the rats were sacrificed on day 1 or day 14 after I/R. Blood pressure, echocardiograms, histopathology, and molecular examination were performed. The examinations revealed that PAI-1 inhibitor showed limited effects on cardiac dysfunction and ventricular remodeling after I/R. We conclude that the pharmacological inhibition of PAI-1 may not affect ventricular remodeling after myocardial I/R injury.

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

    PubMed

    Qu, Daoxu; Han, Jichun; 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.

  12. 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

  13. Total flavonoid extract from Coreopsis tinctoria Nutt. protects rats against myocardial ischemia/reperfusion injury

    PubMed Central

    Zhang, Ya; Yuan, Changsheng; Fang, He; Li, Jia; Su, Shanshan; Chen, Wen

    2016-01-01

    Objective(s): This study aimed to evaluate the protective effects of total flavonoid extract from Coreopsis tinctoria Nutt. (CTF) against myocardial ischemia/reperfusion injury (MIRI) using an isolated Langendorff rat heart model. Materials and Methods: Left ventricular developed pressure (LVDP) and the maximum rate of rise and fall of LV pressure (±dp/dtmax) were recorded. Cardiac injury was assessed by analyzing lactate dehydrogenase (LDH) and creatine kinase (CK) released in the coronary effluent. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels were determined. Myocardial inflammation was assessed by monitoring tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), and interleukin-6 (IL-6) levels. Myocardial infarct size was estimated. Cell morphology was assessed by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin (HE) staining. Cardiomyocyte apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Results: Pretreatment with CTF significantly increased the heart rate and increased LVDP, as well as SOD and GSH-Px levels. In addition, CTF pretreatment decreased the TUNEL-positive cell ratio, infarct size, and levels of CK, LDH, MDA, TNF-α, CRP, IL-6, and IL-8. Conclusion: These results suggest that CTF exerts cardio-protective effects against MIRI via anti-oxidant, anti-inflammatory, and anti-apoptotic activities. PMID:27803790

  14. Depolarization changes during acute myocardial ischemia by evaluation of QRS slopes: standard lead and vectorial approach.

    PubMed

    Romero, Daniel; Ringborn, Michael; Laguna, Pablo; Pahlm, Olle; Pueyo, Esther

    2011-01-01

    Diagnosis and risk stratification of patients with acute coronary syndromes can be improved by adding information from the depolarization phase (QRS complex) to the conventionally used ST-T segment changes. In this study, ischemia-induced changes in the main three slopes of the QRS complex, upward ( ℑ(US)) and downward ( ℑ(DS) ) slopes of the R wave as well as the upward ( ℑ(TS)) slope of the terminal S wave, were evaluated as to represent a robust measure of pathological changes within the depolarization phase. From ECG recordings both in a resting state (control recordings) and during percutaneous coronary intervention (PCI)-induced transmural ischemia, we developed a method for quantification of ℑ(US), ℑ(DS), and ℑ(TS) that incorporates dynamic ECG normalization so as to improve the sensitivity in the detection of ischemia-induced changes. The same method was also applied on leads obtained by projection of QRS loops onto their dominant directions. We show that ℑ(US), ℑ(DS), and ℑ(TS) present high stability in the resting state, thus providing a stable reference for ischemia characterization. Maximum relative factors of change ( ℜ(ℑ)) during PCI were found in leads derived from the QRS loop, reaching 10.5 and 13.7 times their normal variations in the control for ℑ(US) and ℑ(DS), respectively. For standard leads, the relative factors of change were 6.01 and 9.31. The ℑ(TS) index presented a similar behavior to that of ℑ(DS). The timing for the occurrence of significant changes in ℑ(US) and ℑ(DS) varied with lead, ranging from 30 s to 2 min after initiation of coronary occlusion. In the present ischemia model, relative ℑ(DS) changes were smaller than ST changes in most leads, however with only modest correlation between the two indices, suggesting they present different information about the ischemic process. We conclude that QRS slopes offer a robust tool for evaluating depolarization changes during myocardial ischemia.

  15. Paracrine systems in the cardioprotective effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury in rats.

    PubMed

    Liu, Y H; Yang, X P; Sharov, V G; Sigmon, D H; Sabbath, H N; Carretero, O A

    1996-01-01

    After transient episodes of ischemia, benefits of thrombolytic or angioplastic therapy may be limited by reperfusion injury. Angiotensin-converting enzyme inhibitors protect the heart against ischemia/reperfusion injury, an effect mediated by kinins. We examined whether the protective effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of prostaglandin and/or nitric oxide release. The left anterior descending coronary artery of Lewis inbred rats was occluded for 30 minutes, followed by 120 minutes of reperfusion. Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan. We tested whether pretreatment with the kinin receptor antagonist Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor indomethacin blocked the effect of ramiprilat on infarct size and reperfusion arrhythmias. In controls, infarct size as a percentage of the area at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (P < .001), but losartan had little effect (74 +/- 6%, P = NS). Pretreatment with Hoe 140, NG-nitro-L-arginine methyl ester, or indomethacin abolished the beneficial effect of ramiprilat. Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 minutes of ischemia had significantly smaller infarct size as a percentage of the area at risk, whereas in the 150-minute ischemia group it was significantly larger. This suggests that reperfusion caused a significant part of the myocardial injury, but it also suggests that compared with prolonged ischemia, reperfusion salvaged some of the myocardium. Ventricular arrhythmias mirrored the changes in infarct size. Thus, angiotensin-converting enzyme inhibitors protect the myocardium against ischemia/reperfusion injury and arrhythmias; these beneficial effects are mediated primarily by a kinin

  16. [Progress in calcium regulation in myocardial and vascular ischemia-reperfusion injury].

    PubMed

    He, Xi; Bi, Xue-Yuan; Wang, Hao; Yu, Xiao-Jiang; Zang, Wei-Jin

    2012-06-25

    Ischemia-reperfusion injury (IRI) has been recognized as a serious problem for therapy of cardiovascular diseases. Calcium regulation appears to be an important issue in the study of IRI. This article reviews calcium regulation in myocardial and vascular IRI, including the calcium overload and calcium sensitivity in IRI. This review is focused on the key players in Ca(2+) handling in IRI, including membrane damage resulting in increase in Ca(2+) influx, reverse-mode of Na(+)-Ca(2+) exchangers leading to increased Ca(2+) entry, the decreased activity of sarcoplasmic reticulum (SR) Ca(2+)-ATPase causing SR Ca(2+) uptake dysfunction, and increased activity of Rho kinase. These key players in Ca(2+) homeostasis will provide promising strategies and potential targets for therapy of cardiovascular IRI. PMID:22717637

  17. Ischemia and reperfusion related myocardial inflammation: A network of cells and mediators targeting the cardiomyocyte.

    PubMed

    Rohrbach, Susanne; Troidl, Christian; Hamm, Christian; Schulz, Rainer

    2015-02-01

    Occlusion of a coronary artery if maintained for longer period of time results in damage of the cardiac tissue. However, restoration of blood flow to previously ischemic tissue can itself induce further cardiac damage, a phenomenon known as myocardial reperfusion injury. Cardiac homoeostasis is supported by a network of direct and indirect interactions between cardiomyocytes and resident cell types such as fibroblasts, adipocytes, and endothelial cells or invading blood cells. This review will discuss the role of the cellular interplay in ischemia-reperfusion injury from a cardiomyocyte-centered view, although we are aware that other cellular interactions are equally important. We will try to work out currently unresolved questions and potential future directions in the field.

  18. Right Ventricular Dysfunction Secondary to Myocardial Ischemia Provoked by Stress Testing.

    PubMed

    Obeid, Anis I.; Battaglia, Joseph; Lozner, Eugene

    1998-07-01

    We present the cases of two patients, aged 59 and 85 years, who were evaluated with stress echocardiography for chest pain. Both patients developed dramatic echocardiographic findings consisting of severe right ventricular enlargement and hypokinesis, as well as enlargement of the right atrium at relatively low-level exercise. One patient collapsed with severe sinus bradycardia, junctional rhythm, ST elevation in the inferior leads, marked hypotension, and neck vein congestion. The other patient developed staggering and symptoms of hypoperfusion. In both patients, correction of critical proximal right coronary artery stenosis by angioplasty resulted in complete resolution of the right ventricular dysfunction on repeat stress testing. We conclude that in some patients, stress-induced myocardial ischemia may involve primarily the right ventricle with little or no evidence of ischemic changes in the left ventricle. An assessment of right ventricular function should be included in stress echocardiographic studies. PMID:11175063

  19. Platelet Aggregation and Mental Stress Induced Myocardial Ischemia: Results from the REMIT Study

    PubMed Central

    Jiang, Wei; Boyle, Stephen H.; Ortel, Thomas L.; Samad, Zainab; Velazquez, Eric J.; Harrison, Robert W.; Wilson, Jennifer; Kuhn, Cynthia; Williams, Redford B.; O’Connor, Christopher M.; Becker, Richard C.

    2015-01-01

    BACKGROUND Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. METHODS Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT (Responses of Myocardial Ischemia to Escitalopram Treatment) study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. RESULTS Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation, 43.33% (N=117) met criteria for MSIMI and 18.15% (N=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10 μM (6.95[5.54] vs. −14.23[8.75].; p=0.045), epinephrine 10 μM (12.84[4.84] vs. −6.40[7.61].; p=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. −27.34[8.34]; p < .001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups. CONCLUSIONS These findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD. PMID:25819856

  20. Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: comparison with intracoronary streptokinase

    SciTech Connect

    Fung, A.Y.; Lai, P.; Juni, J.E.; Bourdillon, P.D.; Walton, J.A. Jr.; Laufer, N.; Buda, A.J.; Pitt, B.; O'Neill, W.W.

    1986-09-01

    To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction.

  1. CT-based myocardial ischemia evaluation: quantitative angiography, transluminal attenuation gradient, myocardial perfusion, and CT-derived fractional flow reserve.

    PubMed

    Koo, Hyun Jung; Yang, Dong Hyun; Kim, Young-Hak; Kang, Joon-Won; Kang, Soo-Jin; Kweon, Jihoon; Kim, Hyun Jung; Lim, Tae-Hwan

    2016-06-01

    The detection of hemodynamically significant stenosis is important because ischemia-guided revascularization improves overall patient outcomes. Fractional flow reserve (FFR), which is measured during invasive coronary angiography, is regarded as the gold standard for determining hemodynamically significant coronary stenosis. Although coronary computed tomography angiography (CCTA) has been widely used to exclude significant coronary artery disease in patients with low to intermediate pretest probability, anatomic assessment by CCTA using diameter stenosis ≥50 % does not correlate well with the functional assessment of FFR. To overcome the weaknesses of conventional CCTA, such as its low specificity and positive predictive value, especially in patients with a small-diameter artery, poor image quality, or high calcium score, more sophisticated CCTA analysis methods have been developed to detect hemodynamically significant coronary stenosis. Studies that use the quantification of coronary plaque, transluminal attenuation gradient (TAG), CT myocardial perfusion (CTP), and CT-derived FFR have been conducted to validate their diagnostic performances, though each method has its pros and cons. This review provides details on the quantification of coronary plaque, TAG, CTP, and CT-derived FFR, including a definition of each, how to gather and interpret data, and the strengths and limitations of each. Further, we provide an overview of recent clinical studies.

  2. Thioredoxin-interacting protein and myocardial mitochondrial function in ischemia-reperfusion injury.

    PubMed

    Yoshioka, Jun; Lee, Richard T

    2014-02-01

    Cellular metabolism and reactive oxygen species (ROS) formation are interrelated processes in mitochondria and are implicated in a variety of human diseases including ischemic heart disease. During ischemia, mitochondrial respiration rates fall. Though seemingly paradoxical, reduced respiration has been observed to be cardioprotective due in part to reduced generation of ROS. Enhanced myocardial glucose uptake is considered beneficial for the myocardium under stress, as glucose is the primary substrate to support anaerobic metabolism. Thus, inhibition of mitochondrial respiration and uncoupling oxidative phosphorylation can protect the myocardium from irreversible ischemic damage. Growing evidence now positions the TXNIP/thioredoxin system at a nodal point linking pathways of antioxidant defense, cell survival, and energy metabolism. This emerging picture reveals TXNIP's function as a regulator of glucose homeostasis and may prove central to regulation of mitochondrial function during ischemia. In this review, we summarize how TXNIP and its binding partner thioredoxin act as regulators of mitochondrial metabolism. While the precise mechanism remains incompletely defined, the TXNIP-thioredoxin interaction has the potential to affect signaling that regulates mitochondrial bioenergetics and respiratory function with potential cardioprotection against ischemic injury.

  3. Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation. PMID:24839599

  4. Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

    PubMed

    Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

    2016-09-01

    The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes. PMID:27574914

  5. Lipoxin A4 Preconditioning and Postconditioning Protect Myocardial Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Zhao, Qifeng; Shao, Lan; Hu, Xingti; Wu, Guowei; Du, Jie; Xia, Jie; Qiu, Huixian

    2013-01-01

    This study aims to investigate the pre- and postconditioning effects of lipoxin A4 (LXA4) on myocardial damage caused by ischemia/reperfusion (I/R) injury. Seventy-two rats were divided into 6 groups: sham groups (C1 and C2), I/R groups (I/R1 and I/R2), and I/R plus LXA4 preconditioning and postconditioning groups (LX1 and LX2). The serum levels of IL-1β, IL-6, IL-8, IL-10, TNF-α, and cardiac troponin I (cTnI) were measured. The content and the activity of Na+-K+-ATPase as well as the superoxide dismutase (SOD), and malondialdehyde (MDA) levels were determined. Along with the examination of myocardium ultrastructure and ventricular arrhythmia scores (VAS), connexin 43 (Cx43) expression were also detected. Lower levels of IL-1β, IL-6, IL-8, TNF-α, cTnI, MDA content, and VAS and higher levels of IL-10, SOD activity, Na+-K+-ATPase content and activity, and Cx43 expression appeared in LX groups than I/R groups. Besides, H&E staining, TEM examination as well as analysis of gene, and protein confirmed that LXA4 preconditioning was more effective than postconditioning in preventing arrhythmogenesis via the upregulation of Cx43. That is, LXA4 postconditioning had better protective effect on Na+-K+-ATPase and myocardial ultrastructure. PMID:23956501

  6. Comparison of endocardial electromechanical mapping with radionuclide perfusion imaging to assess myocardial viability and severity of myocardial ischemia in angina pectoris.

    PubMed

    Fuchs, S; Hendel, R C; Baim, D S; Moses, J W; Pierre, A; Laham, R J; Hong, M K; Kuntz, R E; Pietrusewicz, M; Bonow, R O; Mintz, G S; Leon, M B; Kornowski, R

    2001-04-01

    The assessment of left ventricular electromechanical activity using a novel, nonfluoroscopic 3-dimensional mapping system demonstrates considerable differences in electrical and mechanical activities within regions of myocardial infarction or ischemia. We sought to determine whether these changes correlate with indexes of myocardial perfusion, viability, or ischemia. A 12-segment comparative analysis was performed in 61 patients (45 men, 61 +/- 12 years old) with class III to IV angina, having reversible and/or fixed myocardial perfusion defects on single-photon emission computed tomographic perfusion imaging. A dual-isotope protocol was used, consisting of rest and 4-hour redistribution thallium images followed by adenosine technetium-99m sestamibi imaging. Average rest endocardial unipolar voltage (UpV) and local shortening (LS) mapping values were compared with visually derived perfusion scores. There was gradual and proportional reduction in regional UpV and LS in relation to thallium-201 uptake score at rest (p = 0.0001 and p = 0.0002, respectively) and redistribution studies (p = 0.0001 and p = 0.003, respectively). UpV > or = 7.4 mV and LS > or = 5.0% had a sensitivity of 78% and 65%, respectively, with a specificity of 68% and 67% for detecting viable myocardium. UpV values of 12.3 and 5.4 mV had 90% specificity and sensitivity, respectively, to predict viable tissue. UpV, but not LS, values differentiated between normal segments and those with adenosine-induced severe perfusion defects (11.8 +/- 5.3 vs 8.8 +/- 4.1 mV, p = 0.005). Catheter-based left ventricular assessment of electromechanical activity correlates with the degree of single-photon emission computed tomographic perfusion abnormality and can identify myocardial viability with a greater accuracy than myocardial ischemia.

  7. N-Acetylcysteine Restores Sevoflurane Postconditioning Cardioprotection against Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    PubMed Central

    Lin, Jiefu; Wang, Tingting; Li, Yalan; Wang, Mengxia

    2016-01-01

    The effect of sevoflurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four weeks starting at five weeks after streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3 which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC but not N-Acetylcysteine significantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic rats displayed reduction of cardiac p-STAT3, adiponectin deficiency, and increase of FoxO1 and CD36 expression, which may be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36. PMID:26783539

  8. ATP-induced cardioprotection against myocardial ischemia/reperfusion injury is mediated through the RISK pathway

    PubMed Central

    Lian, Zhe-Xun; Wang, Fang; Fu, Jun-Hua; Chen, Zuo-Yuan; Xin, Hui; Yao, Ru-Yong

    2016-01-01

    The aim of the present study was to examine the post-infarct acute effect of adenosine-5′-triphosphate (ATP) on myocardial infarction (MI) size as well as its precise molecular mechanism. Sixty New Zealand white male rabbits were exposed to 40 min of ischemia followed by 180 min of reperfusion. The rabbits were intravenously administered 3 mg/kg of ATP (ATP group) or saline (control group) immediately after reperfusion and maintained throughout the first 30 min. The wortmannin+ATP, PD-98059+ATP, and 5-hydroxydecanoic acid (5-HD) sodium salt+ATP groups were separately injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), and 5-HD (5 mg/kg) 5 min prior to ATP administration. MI size was calculated as the percentage of the risk area in the left ventricle. Myocardial apoptosis was determined using a TUNEL assay. Western blot analysis was performed to examine the levels of protein kinase B (Akt)/p-Akt and extracellular signal-regulated kinase (ERK)/p-ERK in the ischemic myocardium, 180 min after reperfusion. The infarct size was significantly smaller in the ATP group than in the control group (p<0.05). The infarct size-reducing effect of ATP was completely blocked by wortmannin, PD-98059 and 5-HD. Compared with the control group, cardiomyocyte apoptosis was significantly reduced in the ATP group, while this did not occur in the wortmannin+ATP, PD-98059+ATP and 5-HD+ATP groups. Western blot analysis revealed a higher myocardial expression of p-Akt and p-ERK 180 min following reperfusion in the ATP versus the control group. In conclusion, cardioprotection by postischemic ATP administration is mediated through activation of the reperfusion injury salvage kinase (RISK) pathway and opening of the mitochondrial ATP-dependent potassium channels. PMID:27698693

  9. ATP-induced cardioprotection against myocardial ischemia/reperfusion injury is mediated through the RISK pathway

    PubMed Central

    Lian, Zhe-Xun; Wang, Fang; Fu, Jun-Hua; Chen, Zuo-Yuan; Xin, Hui; Yao, Ru-Yong

    2016-01-01

    The aim of the present study was to examine the post-infarct acute effect of adenosine-5′-triphosphate (ATP) on myocardial infarction (MI) size as well as its precise molecular mechanism. Sixty New Zealand white male rabbits were exposed to 40 min of ischemia followed by 180 min of reperfusion. The rabbits were intravenously administered 3 mg/kg of ATP (ATP group) or saline (control group) immediately after reperfusion and maintained throughout the first 30 min. The wortmannin+ATP, PD-98059+ATP, and 5-hydroxydecanoic acid (5-HD) sodium salt+ATP groups were separately injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), and 5-HD (5 mg/kg) 5 min prior to ATP administration. MI size was calculated as the percentage of the risk area in the left ventricle. Myocardial apoptosis was determined using a TUNEL assay. Western blot analysis was performed to examine the levels of protein kinase B (Akt)/p-Akt and extracellular signal-regulated kinase (ERK)/p-ERK in the ischemic myocardium, 180 min after reperfusion. The infarct size was significantly smaller in the ATP group than in the control group (p<0.05). The infarct size-reducing effect of ATP was completely blocked by wortmannin, PD-98059 and 5-HD. Compared with the control group, cardiomyocyte apoptosis was significantly reduced in the ATP group, while this did not occur in the wortmannin+ATP, PD-98059+ATP and 5-HD+ATP groups. Western blot analysis revealed a higher myocardial expression of p-Akt and p-ERK 180 min following reperfusion in the ATP versus the control group. In conclusion, cardioprotection by postischemic ATP administration is mediated through activation of the reperfusion injury salvage kinase (RISK) pathway and opening of the mitochondrial ATP-dependent potassium channels.

  10. Evolution of myocardial ischemia and left ventricular function in patients with angina pectoris without myocardial infarction and total occlusion of the left anterior descending coronary artery and collaterals from other coronary arteries

    SciTech Connect

    Juilliere, Y.; Marie, P.Y.; Danchin, N.; Karcher, G.; Bertrand, A.; Cherrier, F. )

    1991-07-01

    Repeated episodes of myocardial ischemia might lead to progressive impairment of left ventricular (LV) function. This radionuclide study assessed myocardial ischemia and LV function several years after documented coronary occlusion without myocardial infarction. Over 5 years, 24 consecutive patients, who underwent cardiac catheterization for angina pectoris without myocardial infarction, had isolated total occlusion of the left anterior descending coronary artery with well-developed collateral vessels. Five patients were successfully treated by coronary bypass grafting and 3 by coronary angioplasty. Among the 16 medically treated patients, 1 was lost to follow-up and 1 died (extracardiac death). The mean (+/- standard deviation) follow-up (14 patients) was 48 +/- 15 months. At follow-up, 8 patients still had clinical chest pain, 11 received antianginal therapy, 4 patients had no stress ischemia and the other 10 had greater than or equal to 1 sign of stress ischemia. All patients had a normal LV ejection fraction at rest (mean 60 +/- 3%; range 55 to 65%). Collateral circulation preserves LV function at the time of occlusion and, in some cases, prevents the development of myocardial ischemia; in patients with persisting myocardial ischemia after well-collateralized coronary occlusion, LV function is not impaired at long-term follow-up.

  11. RP105 protects against myocardial ischemia-reperfusion injury via suppressing TLR4 signaling pathways in rat model.

    PubMed

    Li, Xinxin; Yang, Jun; Yang, Jian; Dong, Wusong; Li, Song; Wu, Hui; Li, Li

    2016-04-01

    Myocardial ischemia-reperfusion (I/R) injury severely impacts the postoperative survival rate of coronary atherosclerotic heart disease. Radioprotective 105 kDa protein (RP105) is a regulator of Toll-like receptor 4 (TLR4), an inflammatory factor whose functions have been reported in myocardial I/R injury. To investigate the roles of RP105 in mediating myocardial I/R injury, we overexpressed RP105 by injecting its adenovirus vectors, and induced myocardial I/R injury rat model in this study. Myocardial structure injuries of rat hearts were examined by hematoxylin eosin staining, and myocardial infarct area was calculated after Evans blue and triphenyltetrazolium chloride dual staining. Expression changes of TLR4, myeloid differentiation factor 88 (MyD88), and nuclear factor κB (NF-κB) in myocardia were detected by quantitative real-time PCR and Western blot. Amount changes of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay. Results showed that RP105 attenuated myocardial injuries and effectively reduced myocardial infarct area after I/R (P<0.05). RP105 was also proved to significantly inhibit TLR4 and downstream inflammatory factors MyD88, NF-κB, TNF-α and IL-6 (P<0.05), whose expression levels were up-regulated by I/R induction. These results indicated that RP105 could protect against myocardial I/R injury via suppressing inflammatory responses mediated by TLR4 signaling pathways. This study revealed the anti-inflammatory roles of RP105 and its potential in preventing and treating myocardial I/R injury.

  12. Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules

    PubMed Central

    Nagata, Takanobu; Yasukawa, Hideo; Kyogoku, Sachiko; Oba, Toyoharu; Takahashi, Jinya; Nohara, Shoichiro; Minami, Tomoko; Mawatari, Kazutoshi; Sugi, Yusuke; Shimozono, Koutatsu; Pradervand, Sylvain; Hoshijima, Masahiko; Aoki, Hiroki; Fukumoto, Yoshihiro; Imaizumi, Tsutomu

    2015-01-01

    Myocardial ischemia reperfusion injury (IRI) adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT) 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS)-3, an intrinsic negative feedback regulator of the Janus kinase (JAK)-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT–activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO). The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI. PMID:26010537

  13. Activation of histamine H3 receptors inhibits carrier-mediated norepinephrine release in a human model of protracted myocardial ischemia.

    PubMed

    Hatta, E; Yasuda, K; Levi, R

    1997-11-01

    During protracted myocardial ischemia, ATP depletion promotes Na+ accumulation in sympathetic terminals and prevents vesicular storage of norepinephrine (NE). This forces the reversal of the neuronal uptake1 transporter, and NE is massively released (carrier-mediated release). We had shown that histamine H3 receptors (H3Rs) modulate ischemic NE release in animals. We have now used a human model of protracted myocardial ischemia to investigate whether H3Rs may control carrier-mediated NE release. Surgical specimens of human atrium were incubated in anoxic conditions. NE release increased approximately 7-fold within 70 min of anoxia. This release was carrier mediated because it was Ca++ independent and inhibited by the uptake1 inhibitor desipramine. Furthermore, the Na+/H+ exchanger (NHE) inhibitors ethyl-isopropyl-amiloride and HOE 642, and the Na+ channel blocker tetrodotoxin inhibited NE release, whereas the Na+ channel activator aconitine potentiated it. The selective H3R agonist imetit decreased NE release, an effect that was blocked by each of the H3R antagonists thioperamide and clobenpropit. Notably, imetit acted synergistically with ethyl-isopropyl-amiloride, HOE 642 and tetrodotoxin to reduce anoxic NE release. Thus, activation of H3R appears to result in an inhibition of both NHE- and voltage-dependent Na+ channels. Most importantly, endogenous histamine was released from the anoxic human heart, and thioperamide and clobenpropit each alone increased NE release, indicating that H3R become activated in myocardial ischemia. Our findings indicate that H3Rs are likely to mitigate sympathetic overactivity in the ischemic human heart and suggest new therapeutic strategies to alleviate dysfunctions associated with myocardial ischemia.

  14. Can myocardial ischemia be recognized by the exercise electrocardiogram in coronary disease patients with abnormal resting Q waves

    SciTech Connect

    Ahnve, S.; Savvides, M.; Abouantoun, S.; Atwood, J.E.; Froelicher, V.

    1986-05-01

    This study was performed in order to determine whether exercise-induced myocardial ischemia demonstrated by thallium-201 imaging could be detected by ST segment shifts in patients with abnormal Q waves at rest. Fifty-four patients with coronary artery disease and exercise-induced thallium-201 defects were compared to 22 patients with similar Q wave patterns but without thallium-201 exercise defects and to 14 normal subjects. Exercise data were analyzed visually in the 12-lead ECG and for spatial ST vector shifts. Both ST segment depression observed on the 12-lead ECG and spatial criteria were reasonably sensitive and specific for ischemia when the resting ECG showed no Q waves or inferior Q waves (range 69% to 93%). However, when anterior Q waves were present, ST segment shifts could not distinguish patients with ischemia from those with normal perfusion as determined by thallium imaging.

  15. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    SciTech Connect

    Li, Weixin; Wu, Mingchai; Tang, Longguang; Pan, Yong; Liu, Zhiguo; Zeng, Chunlai; Wang, Jingying; Wei, Tiemin; Liang, Guang

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

  16. Redox activation of Ref-1 potentiates cell survival following myocardial ischemia reperfusion injury.

    PubMed

    Gurusamy, Narasimman; Malik, Gautam; Gorbunov, Nikolai V; Das, Dipak K

    2007-08-01

    A recent study showed that cardiac adaptation could potentiate translocation of thioredoxin-1 (Trx-1) into the nucleus, which then interacted with Ref-1, resulting in a survival signal. Here, we present evidence that such adaptation also causes nuclear translocation of Ref-1, which is almost completely inhibited when the hearts were pretreated with antisense Ref-1 that also abolished the cardioprotective adaptive response. Significant amounts of NFkappaB and Nrf2 were found to be associated with Ref-1 when the nuclear extract obtained from the left ventricle was immunoprecipitated with Ref-1. Such Ref-1-NFkappaB and Ref-1-Nrf2 interactions were significantly inhibited with antisense Ref-1. However, immunoprecipitation of nuclear extract with NFkappaB showed that the association of Trx-1 with NFkappaB is increased in the adapted heart, which was again significantly blocked by antisense Ref-1. Nrf2 was also associated with NFkappaB; however, such association appeared to be independent of Ref-1. In contrast, myocardial adaptation to ischemia inhibited the ischemia reperfusion-induced loss of Nrf2 from the nucleus, which was inhibited by antisense Ref-1. The nuclear translocation and activation of Ref-1 appeared to generate a survival signal as evidenced by the increased phosphorylation of Akt that was inhibited with antisense Ref-1. Finally, confocal microscopy confirmed the results of immunoblotting, clearly showing the nuclear translocation of Ref-1 and nuclear 3D colocalization of Ref-1 with NFkappaB in the adapted heart and its inhibition with antisense Ref-1. Our results show that PC potentiates a survival signal through the phosphorylation of Akt by causing nuclear translocation and activation of Ref-1, where significant interaction among NFkappaB and Ref-1, Trx-1, and Nrf2 appears to regulate Ref-1-induced survival signal.

  17. Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

    PubMed

    Steffensen, Lasse Bach; Poulsen, Christian Bo; Shim, Jeong; Bek, Marie; Jacobsen, Kevin; Conover, Cheryl A; Bentzon, Jacob Fog; Oxvig, Claus

    2015-12-01

    The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

  18. Intermedin protects against myocardial ischemia-reperfusion injury in diabetic rats

    PubMed Central

    2013-01-01

    Background Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown. Methods Diabetes was induced by streptozotocin in Sprague–Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation. Results IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 ± 4.84 pmol/L, p < 0.05) and myocardial tissue (9.8 ± 0.60 pmol/L, p < 0.01) compared to pre-MI control values (43.62 ± 3.47 pmol/L and 4.4 ± 0.41). IMD administration to diabetic rats subjected to MI/R decreased oxidative stress product generation, apoptosis, infarct size, and inflammatory cytokine release (p < 0.05 or p < 0.01). Conclusions By reducing oxidative stress, inflammation, and apoptosis, IMD may represent a promising novel therapeutic target mitigating diabetic ischemic heart injury. PMID:23777472

  19. The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury.

    PubMed

    Chen-Scarabelli, Carol; Agrawal, Pratik R; Saravolatz, Louis; Abuniat, Cadigia; Scarabelli, Gabriele; Stephanou, Anastasis; Loomba, Leena; Narula, Jagat; Scarabelli, Tiziano M; Knight, Richard

    2014-12-01

    A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cytoplasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated catabolic cellular 'housekeeping' process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protective mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the variability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic manipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling. PMID:25593583

  20. Total saponins from Aralia taibaiensis protect against myocardial ischemia/reperfusion injury through AMPK pathway

    PubMed Central

    YAN, JIAJIA; DUAN, JIALIN; WU, XIAOXIAO; GUO, CHAO; YIN, YING; ZHU, YANRONG; HU, TIANXIN; WEI, GUO; WEN, AIDONG; XI, MIAOMIAO

    2015-01-01

    It was previously shown that total saponins extracted from Aralia taibaiensis (sAT) have potent antioxidant activities for treating diabetes mellitus and attenuate D-galactose-induced aging. Since diabetes mellitus and aging are closely associated with cardiac dysfunction, particularly ischemic heart disease, sAT may have potential protective activity against myocardial ischemia/reperfusion injury (MI/RI). However, the anti-MI/RI effects of sAT have yet to be examined, and the possible molecular mechanisms remain to be determined. The present study was undertaken to investigate the anti-MI/RI activities of sAT and to elucidate the mechanisms underlying these effects in rats using TUNEL and Hoechst 33258 staining. The results confirmed the cardioprotective effects in vivo and elucidated the potential molecular mechanisms of sAT in vitro. Pretreatment with sAT significantly reduced infarct size, decreased the levels of lactate dehydrogenase and creatine kinase in the serum and blocked apoptosis. In addition, sAT inhibited A/R-induced apoptosis by decreasing DNA strand breaks, caspase-3 activity and cytochrome c release in H9c2 cells. Furthermore, sAT markedly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase and elevated the Bcl2/Bcl-2-associated X protein ratio. These effects were blocked by compound C. The results suggested that sAT pretreatment exerts protective effects on myocardial cells in vitro and in vivo against MI/RI-induced apoptosis by activating AMPK pathway. PMID:26498380

  1. Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs

    PubMed Central

    Stark, Christoffer K.-J.; Tarkia, Miikka; Kentala, Rasmus; Malmberg, Markus; Vähäsilta, Tommi; Savo, Matti; Hynninen, Ville-Veikko; Helenius, Mikko; Ruohonen, Saku; Jalkanen, Juho; Taimen, Pekka; Alastalo, Tero-Pekka; Saraste, Antti; Knuuti, Juhani; Savunen, Timo; Koskenvuo, Juha

    2016-01-01

    The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI. PMID:27199757

  2. Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs.

    PubMed

    Stark, Christoffer K-J; Tarkia, Miikka; Kentala, Rasmus; Malmberg, Markus; Vähäsilta, Tommi; Savo, Matti; Hynninen, Ville-Veikko; Helenius, Mikko; Ruohonen, Saku; Jalkanen, Juho; Taimen, Pekka; Alastalo, Tero-Pekka; Saraste, Antti; Knuuti, Juhani; Savunen, Timo; Koskenvuo, Juha

    2016-01-01

    The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI. PMID:27199757

  3. Diagnosis of Coronary Heart Diseases Using Gene Expression Profiling; Stable Coronary Artery Disease, Cardiac Ischemia with and without Myocardial Necrosis.

    PubMed

    Kazmi, Nabila; Gaunt, Tom R

    2016-01-01

    Cardiovascular disease (including coronary artery disease and myocardial infarction) is one of the leading causes of death in Europe, and is influenced by both environmental and genetic factors. With the recent advances in genomic tools and technologies there is potential to predict and diagnose heart disease using molecular data from analysis of blood cells. We analyzed gene expression data from blood samples taken from normal people (n = 21), non-significant coronary artery disease (n = 93), patients with unstable angina (n = 16), stable coronary artery disease (n = 14) and myocardial infarction (MI; n = 207). We used a feature selection approach to identify a set of gene expression variables which successfully differentiate different cardiovascular diseases. The initial features were discovered by fitting a linear model for each probe set across all arrays of normal individuals and patients with myocardial infarction. Three different feature optimisation algorithms were devised which identified two discriminating sets of genes, one using MI and normal controls (total genes = 6) and another one using MI and unstable angina patients (total genes = 7). In all our classification approaches we used a non-parametric k-nearest neighbour (KNN) classification method (k = 3). The results proved the diagnostic robustness of the final feature sets in discriminating patients with myocardial infarction from healthy controls. Interestingly it also showed efficacy in discriminating myocardial infarction patients from patients with clinical symptoms of cardiac ischemia but no myocardial necrosis or stable coronary artery disease, despite the influence of batch effects and different microarray gene chips and platforms.

  4. Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions.

    PubMed

    Chen, Ouyang; Ye, Zhouheng; Cao, Zhiyong; Manaenko, Anatol; Ning, Ke; Zhai, Xiao; Zhang, Rongjia; Zhang, Ting; Chen, Xiao; Liu, Wenwu; Sun, Xuejun

    2016-01-01

    Myocardial infarction (MI) remains the most frequent cardiovascular disease with high mortality. Recently, methane has been shown protective effects on small intestinal ischemia-reperfusion injury. We hypothesized that methane-rich saline (MS) could protect the myocardium again MI via its anti-oxidative, anti-apoptotic and anti-inflammatory effects. In experiment 1, tetrazolium chloride staining and detection of myocardial enzymes and oxidative and inflammatory parameters were performed at 12h after MI to determine the optimal dose at which intraperitoneal MS exerted the best protective effects on MI. In experiment 2, rats were treated with 10 ml/kg MS. Myocyte apoptosis was detected 72 h after MI, and cardiac function and myocardial remodeling were evaluated 4 weeks after MI. Results showed different dose of MS reduced infarct area, decreased myocardial enzymes, inhibited inflammation and oxidative stress following MI. The optimal dose of MS was 10 mg/kg. Moreover, treatment with 10mg/kg MS for 3 days significantly reduced myocyte apoptosis, improved cardiac function and inhibited myocardial remodeling (reduced anterior wall thickness, attenuated myocyte hypertrophy, and decreased myocardial collagen). MS protects the myocardium of MI rats via its anti-oxidative, anti-inflammatory, anti-apoptotic and anti-remodeling activities. Thus, MS provides a novel and promising strategy for the treatment of ischemic heart diseases. PMID:26585905

  5. Diagnosis of Coronary Heart Diseases Using Gene Expression Profiling; Stable Coronary Artery Disease, Cardiac Ischemia with and without Myocardial Necrosis

    PubMed Central

    Kazmi, Nabila; Gaunt, Tom R.

    2016-01-01

    Cardiovascular disease (including coronary artery disease and myocardial infarction) is one of the leading causes of death in Europe, and is influenced by both environmental and genetic factors. With the recent advances in genomic tools and technologies there is potential to predict and diagnose heart disease using molecular data from analysis of blood cells. We analyzed gene expression data from blood samples taken from normal people (n = 21), non-significant coronary artery disease (n = 93), patients with unstable angina (n = 16), stable coronary artery disease (n = 14) and myocardial infarction (MI; n = 207). We used a feature selection approach to identify a set of gene expression variables which successfully differentiate different cardiovascular diseases. The initial features were discovered by fitting a linear model for each probe set across all arrays of normal individuals and patients with myocardial infarction. Three different feature optimisation algorithms were devised which identified two discriminating sets of genes, one using MI and normal controls (total genes = 6) and another one using MI and unstable angina patients (total genes = 7). In all our classification approaches we used a non-parametric k-nearest neighbour (KNN) classification method (k = 3). The results proved the diagnostic robustness of the final feature sets in discriminating patients with myocardial infarction from healthy controls. Interestingly it also showed efficacy in discriminating myocardial infarction patients from patients with clinical symptoms of cardiac ischemia but no myocardial necrosis or stable coronary artery disease, despite the influence of batch effects and different microarray gene chips and platforms. PMID:26930047

  6. Relation between QT dispersion and adenosine triphosphate stress thallium-201 single-photon emission computed tomographic imaging for detecting myocardial ischemia and scar.

    PubMed

    Teragawa, H; Hirao, H; Muraoka, Y; Yamagata, T; Matsuura, H; Kajiyama, G

    1999-04-15

    It is not known if QT dispersion is useful for detecting coronary artery disease. We investigated whether QT dispersion at baseline and during adenosine triphosphate (ATP) infusion correlate with the imaging patterns obtained from ATP stress thallium-201 single-photon emission computed tomography (ATP-SPECT). QT dispersion was determined in 169 patients who underwent ATP-SPECT from 12-lead electrocardiograms obtained at baseline and 3 minutes after the beginning of ATP infusion. Based on the results of ATP-SPECT, patients were divided into 4 groups: normal (n = 55), ischemia (n = 38), ischemia and scar (n = 42), and scar (n = 34). Baseline QT dispersions (mean +/- SD) in the normal, ischemia, ischemia and scar, and scar groups were 48 +/- 15, 50 +/- 17, 69 +/- 25, and 70 +/- 24 ms, respectively. Baseline QT dispersion was significantly greater in the groups with myocardial scar. QT dispersions during ATP infusion were 43 +/- 16, 63 +/- 20, 76 +/- 20, and 62 +/- 25 ms in the normal, ischemia, ischemia and scar, and scar groups, respectively. QT dispersion increased with ATP infusion in patients with myocardial ischemia. QT dispersion at baseline and during ATP infusion correlated with the ATP-SPECT imaging pattern. These findings suggest that baseline QT dispersion and ATP-induced changes in QT dispersion may help detect the presence of myocardial ischemia and scar. PMID:10215275

  7. Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion

    PubMed Central

    Zou, Ning; Ao, Lihua; Cleveland, Joseph C.; Yang, Xiaoping; Su, Xin; Cai, Guang-Yun; Banerjee, Anirban; Fullerton, David A.; Meng, Xianzhong

    2010-01-01

    Previous studies showed that Toll-like receptor 4 (TLR4) modulates the myocardial inflammatory response to ischemia-reperfusion injury, and we recently found that cytokines link TLR4 to postischemic cardiac dysfunction. Although TLR4 can be activated in cultured cells by endogenous agents including heat shock protein 70, how it is activated during myocardial ischemia-reperfusion is unknown. In the present study, we examined 1) whether heat shock cognate protein 70 (HSC70), which is constitutively expressed in the myocardium, is released during ischemia-reperfusion; 2) whether extracellular HSC70 induces the myocardial inflammatory response and modulates cardiac function; and 3) whether HSC70 exerts these effects via TLR4. We subjected isolated mouse hearts to global ischemia-reperfusion via the Langendorff technique. Immunoblotting and immunostaining detected the release of HSC70 from the myocardium during reperfusion. Treatment with an antibody specific to HSC70 suppressed myocardial cytokine expression and improved cardiac functional recovery after ischemia-reperfusion. Recombinant HSC70 induced NF-κB activation and cytokine expression and depressed myocardial contractility in a TLR4-dependent manner. These effects required the substrate-binding domain of HSC70. Fluorescence resonance energy transfer analysis of isolated macrophages demonstrated that extracellular HSC70 interacts with TLR4. Therefore, this study demonstrates for the first time that 1) the myocardium releases HSC70 during ischemia-reperfusion, 2) extracellular HSC70 contributes to the postischemic myocardial inflammatory response and to cardiac dysfunction, 3) HSC70 exerts these effects through a TLR4-dependent mechanism, and 4) the substrate-binding domain of HSC70 is required to induce these effects. Thus extracellular HSC70 plays a critical role in regulating the myocardial innate immune response and cardiac function after ischemia-reperfusion. PMID:18441202

  8. The effects and mechanism of miR-92a and miR-126 on myocardial apoptosis in mouse ischemia-reperfusion model.

    PubMed

    Jiang, Changhao; Ji, Ningning; Luo, Gaojiang; Ni, Shimao; Zong, Jinbo; Chen, Zhili; Bao, Donglai; Gong, Xinyan; Fu, Ting

    2014-12-01

    Our objective was to explore the effects of miR-92a and miR-126 on myocardial apoptosis in mouse ischemia-reperfusion model and further investigate the underlying mechanisms. Eighteen Kunming mice were selected and randomly divided into sham operation group and ischemia-reperfusion group with nine mice in each group. Cardiac muscle tissue was stained with Evans blue to confirm myocardial infarction and ischemia. Annexin V/PI double staining was used to detect the apoptotic rate of myocardial cells, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) was used to detect the number of apoptotic cells; Western blot was used to detect expression of Caspase 3 to evaluate the apoptosis of mouse myocardial cells; qRT-PCR was used to detect expression of miR-92a and miR-126 in mouse myocardium, and Western blot was used to detect expression of HSP70 in two groups. Evans blue staining results showed that there was a large area of ischemia in myocardium of ischemia-reperfusion mice with marked infarction, suggesting successful establishment of the model. In sham operation group, myocardial cells were mostly normal cells. Annexin V/PI double staining of flow cytometry result showed that the apoptotic rate was 5.9 % in sham operation group and 37.0 % in ischemia-reperfusion group, respectively. Apoptosis detection results showed that apoptotic index (AI) of myocardial cells in ischemia-reperfusion mice was significantly higher than in sham operation group. In addition, qRT-PCR results showed that miR-92a expression in ischemia-reperfusion group was significantly higher than in sham operation group (F = 32.302, P = 0.000), and miR-126 expression in ischemia-reperfusion group was significantly lower than in sham operation group (F = 41.125, P = 0.000). Moreover, HSP70 detected by Western blot showed that HSP expression in ischemia-reperfusion group was significantly lower than in sham operation group. The change of miR-92a was in accordance with AI of

  9. Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function.

    PubMed

    Luo, Tao; Chen, Baihe; Zhao, Zonglei; He, Nvqin; Zeng, Zhi; Wu, Bing; Fukushima, Yasushi; Dai, Meng; Huang, Qiaobing; Xu, Dingli; Bin, Jianping; Kitakaze, Masafumi; Liao, Yulin

    2013-05-01

    There is evidence that H2R blockade improves ischemia/reperfusion (I/R) injury, but the underlying cellular mechanisms remain unclear. Histamine is known to increase vascular permeability and induce apoptosis, and these effects are closely associated with endothelial and mitochondrial dysfunction, respectively. Here, we investigated whether activation of the histamine H2 receptor (H2R) exacerbates myocardial I/R injury by increasing mitochondrial and endothelial permeability. Serum histamine levels were measured in patients with coronary heart disease, while the influence of H2R activation was assessed on mitochondrial and endothelial function in cultured cardiomyocytes or vascular endothelial cells, and myocardial I/R injury in mice. The serum histamine level was more than twofold higher in patients with acute myocardial infarction than in patients with angina or healthy controls. In neonatal rat cardiomyocytes, histamine dose-dependently reduced viability and induced apoptosis. Mitochondrial permeability and the levels of p-ERK1/2, Bax, p-DAPK2, and caspase 3 were increased by H2R agonists. In cultured human umbilical vein endothelial cells (HUVECs), H2R activation increased p-ERK1/2 and p-moesin levels and also enhanced permeability of HUVEC monolayer. All of these effects were abolished by the H2R blocker famotidine or the ERK inhibitor U0126. After I/R injury or permanent ischemia, the infarct size was reduced by famotidine and increased by an H2R agonist in wild-type mice. In H2R KO mice, the infarct size was smaller; myocardial p-ERK1/2, p-DAPK2, and mitochondrial Bax were downregulated. These findings indicate that H2R activation exaggerates myocardial I/R injury by promoting myocardial mitochondrial dysfunction and by increasing cardiac vascular endothelial permeability.

  10. N-11C-Methyl-Dopamine PET Imaging of Sympathetic Nerve Injury in a Swine Model of Acute Myocardial Ischemia: A Comparison with 13N-Ammonia PET

    PubMed Central

    Zhou, Weina; Wang, Xiangcheng; He, Yulin; Nie, Yongzhen; Zhang, Guojian; Wang, Cheng; Wang, Chunmei; Wang, Xuemei

    2016-01-01

    Objective. Using a swine model of acute myocardial ischemia, we sought to validate N-11C-methyl-dopamine (11C-MDA) as an agent capable of imaging cardiac sympathetic nerve injury. Methods. Acute myocardial ischemia was surgically generated in Chinese minipigs. ECG and serum enzyme levels were used to detect the presence of myocardial ischemia. Paired 11C-MDA PET and 13N-ammonia PET scans were performed at baseline, 1 day, and 1, 3, and 6 months after surgery to relate cardiac sympathetic nerve injury to blood perfusion. Results. Seven survived the surgical procedure. The ECG-ST segment was depressed, and levels of the serum enzymes increased. Cardiac uptake of tracer was quantified as the defect volume. Both before and immediately after surgery, the images obtained with 11C-MDA and 13N-ammonia were similar. At 1 to 6 months after surgery, however, 11C-MDA postsurgical left ventricular myocardial defect volume was significantly greater compared to 13N-ammonia. Conclusions. In the Chinese minipig model of acute myocardial ischemia, the extent of the myocardial defect as visualized by 11C-MDA is much greater than would be suggested by blood perfusion images, and the recovery from myocardial sympathetic nerve injury is much slower than the restoration of blood perfusion. 11C-MDA PET may provide additional biological information during recovery from ischemic heart disease. PMID:27034950

  11. Pretreatment with low-dose gadolinium chloride attenuates myocardial ischemia/reperfusion injury in rats

    PubMed Central

    Chen, Min; Zheng, Yuan-yuan; Song, Yun-tao; Xue, Jing-yi; Liang, Zheng-yang; Yan, Xin-xin; Luo, Da-li

    2016-01-01

    Aim: We have shown that low-dose gadolinium chloride (GdCl3) abolishes arachidonic acid (AA)-induced increase of cytoplasmic Ca2+, which is known to play a crucial role in myocardial ischemia/reperfusion (I/R) injury. The present study sought to determine whether low-dose GdCl3 pretreatment protected rat myocardium against I/R injury in vitro and in vivo. Methods: Cultured neonatal rat ventricular myocytes (NRVMs) were treated with GdCl3 or nifedipine, followed by exposure to anoxia/reoxygenation (A/R). Cell apoptosis was detected; the levels of related signaling molecules were assessed. SD rats were intravenously injected with GdCl3 or nifedipine. Thirty min after the administration the rats were subjected to LAD coronary artery ligation followed by reperfusion. Infarction size, the release of serum myocardial injury markers and AA were measured; cell apoptosis and related molecules were assessed. Results: In A/R-treated NRVMs, pretreatment with GdCl3 (2.5, 5, 10 μmol/L) dose-dependently inhibited caspase-3 activation, death receptor-related molecules DR5/Fas/FADD/caspase-8 expression, cytochrome c release, AA release and sustained cytoplasmic Ca2+ increases induced by exogenous AA. In I/R-treated rats, pre-administration of GdCl3 (10 mg/kg) significantly reduced the infarct size, and the serum levels of CK-MB, cardiac troponin-I, LDH and AA. Pre-administration of GdCl3 also significantly decreased the number of apoptotic cells, caspase-3 activity, death receptor-related molecules (DR5/Fas/FADD) expression and cytochrome c release in heart tissues. The positive control drug nifedipine produced comparable cardioprotective effects in vitro and in vivo. Conclusion: Pretreatment with low-dose GdCl3 significantly attenuates I/R-induced myocardial apoptosis in rats by suppressing activation of both death receptor and mitochondria-mediated pathways. PMID:26948086

  12. Comparison of Electric- and Magnetic-Cardiograms Produced by Myocardial Ischemia in Models of the Human Ventricle and Torso

    PubMed Central

    Alday, Erick A. Perez; Ni, Haibo; Zhang, Chen; Colman, Michael A.; Gan, Zizhao; Zhang, Henggui

    2016-01-01

    Myocardial ventricular ischemia arises from a lack of blood supply to the heart, which may cause abnormal repolarization and excitation wave conduction patterns in the tissue, leading to cardiac arrhythmias and even sudden death. Current diagnosis of cardiac ischemia by the 12-lead electrocardiogram (ECG) has limitations as they are insensitive in many cases and may show unnoticeable differences to normal patterns. As the magnetic field provides extra information on cardiac excitation and is more sensitive to tangential currents to the surface of the chest, whereas the electric field is more sensitive to flux currents, it has been hypothesized that the magnetocardiogram (MCG) may provide a complementary method to the ECG in ischemic diagnosis. However, it is unclear yet about the differences in sensitivity regions of body surface ECG and MCG signals to ischemic conditions. The aim of this study was to investigate such differences by using 12-, 36- ECG and 36-MCG computed from multi-scale biophysically detailed computational models of the human ventricles and torso in both control and ischemic conditions. It was shown that ischemia produced changes in the ECG and MCG signals in the QRS complex, T-wave and ST-segment, with greater relative differences seen in the 36-lead ECG and MCG as compared to the 12-leads ECG (34% and 37% vs 26%, respectively). The 36-lead ECG showed more averaged sensitivity than the MCG in the change of T-wave due to ischemia (37% vs 32%, respectively), whereas the MCG showed greater sensitivity than the ECG in the change of the ST-segment (50% vs 40%, respectively). In addition, both MCG and ECG showed regional-dependent changes to ischemia, but with MCG showing a stronger correlation between ischemic region in the heart. In conclusion, MCG shows more sensitivity than ECG in response to ischemia, which may provide an alternative method for the diagnosis of ischemia. PMID:27556808

  13. Comparison of Electric- and Magnetic-Cardiograms Produced by Myocardial Ischemia in Models of the Human Ventricle and Torso.

    PubMed

    Alday, Erick A Perez; Ni, Haibo; Zhang, Chen; Colman, Michael A; Gan, Zizhao; Zhang, Henggui

    2016-01-01

    Myocardial ventricular ischemia arises from a lack of blood supply to the heart, which may cause abnormal repolarization and excitation wave conduction patterns in the tissue, leading to cardiac arrhythmias and even sudden death. Current diagnosis of cardiac ischemia by the 12-lead electrocardiogram (ECG) has limitations as they are insensitive in many cases and may show unnoticeable differences to normal patterns. As the magnetic field provides extra information on cardiac excitation and is more sensitive to tangential currents to the surface of the chest, whereas the electric field is more sensitive to flux currents, it has been hypothesized that the magnetocardiogram (MCG) may provide a complementary method to the ECG in ischemic diagnosis. However, it is unclear yet about the differences in sensitivity regions of body surface ECG and MCG signals to ischemic conditions. The aim of this study was to investigate such differences by using 12-, 36- ECG and 36-MCG computed from multi-scale biophysically detailed computational models of the human ventricles and torso in both control and ischemic conditions. It was shown that ischemia produced changes in the ECG and MCG signals in the QRS complex, T-wave and ST-segment, with greater relative differences seen in the 36-lead ECG and MCG as compared to the 12-leads ECG (34% and 37% vs 26%, respectively). The 36-lead ECG showed more averaged sensitivity than the MCG in the change of T-wave due to ischemia (37% vs 32%, respectively), whereas the MCG showed greater sensitivity than the ECG in the change of the ST-segment (50% vs 40%, respectively). In addition, both MCG and ECG showed regional-dependent changes to ischemia, but with MCG showing a stronger correlation between ischemic region in the heart. In conclusion, MCG shows more sensitivity than ECG in response to ischemia, which may provide an alternative method for the diagnosis of ischemia. PMID:27556808

  14. The Frequency and Significance of Silent Myocardial Ischemia Due to Hyoscine Butylbromide Use in Peripheral Angiography

    SciTech Connect

    Maher, Richard; Phillips-Hughes, Jane; Banning, Adrian; Boardman, Philip

    1999-09-15

    Purpose: Hyoscine-N-butylbromide (HB) is an anticholinergic drug used in digital subtraction angiography of the aortoiliac region because it decreases bowel gas movement artifact. HB also causes an increase in heart rate. We investigated whether this could cause silent myocardial ischemia (SMI) in susceptible patients during peripheral angiography. Methods: Thirty-six patients undergoing peripheral angiography were randomized into two groups, with 17 patients receiving 20 mg HB intraarterially during the angiogram and 19 patients receiving no drug. All patients were fitted with a Holter monitor that recorded the electrocardiogram before, during, and after the angiogram. Heart rate trends and ST segments were then analyzed. Results: Patients given HB had a statistically significant rise in heart rate compared with the control group. Although the difference was not statistically significant, two (12%) patients receiving HB had procedural ST depression compared with none in the control group. Pre- and postprocedural episodes of ST depression were common, occurring in 41% of patients receiving HB and 37% of patients receiving no drug, and were associated with an increase in heart rate. Conclusion: The infrequent episodes of procedural SMI, potentially caused by the positive chronotropic effects of HB, are probably insignificant when compared with the high frequency of SMI episodes occurring outside the procedure.

  15. Crocetin ester improves myocardial ischemia via Rho/ROCK/NF-κB pathway.

    PubMed

    Huang, Zhiheng; Nan, Chen; Wang, Hanqing; Su, Qiang; Xue, Wenda; Chen, Yanyan; Shan, Xin; Duan, Jinao; Chen, Gang; Tao, Weiwei

    2016-09-01

    Crocetin ester (CE) is the active ingredient of Crocus sativus L. stigmas and Gardenia jasminoides Ellis fruit. The main purpose of the present study was to investigate the protective effect of CE on isoproterenol (ISO)-induced acute myocardial ischemia (AMI) through Rho/ROCK/NF-κB pathway and explore its underlying mechanism. Administration of CE (25 and 50mg/kg) could significantly reduce the serum contents of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6). In addition, pretreatment with CE attenuated the contents of creatine kinase (CK), malondialdehyde (MDA) and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD) in serum. Treatment with CE also improved the histopathological alteration and decreased the ST elevation. Furthermore, CE could ameliorate the cardiac expressions of Cu, Zn-superoxide dismutase (SOD1), MDA5, Rho, ROCK, p-IκB and p-NF-κBp65 in ISO-induced rats. It was assumed that CE might be a new therapeutic candidate for the treatment of AMI possibly through the inhibition of Rho/ROCK/NF-κB pathway. PMID:27285672

  16. Metabolomic profiles of myocardial ischemia under treatment with salvianolic acid B

    PubMed Central

    2012-01-01

    Background Radix Salvia miltiorrhiza (Danshen) has been used as a principal herb in treating cardiovascular diseases in Chinese medicine. Salvianolic acid B (SA-B), a water-soluble active component of Danshen, was found to have anti-myocardial ischemia (anti-MI) effect. This study aims to investigate mechanisms of SA-B on MI. Methods Five conventional Western medicines (isosorbide dinitrate, verapamil, propranolol, captopril and trimethazine) with different mechanisms for treating cardiovascular diseases were selected as positive references to compare with SA-B in changing of the metabolomic profiles in MI rats under treatment. Potential mechanisms of SA-B were further investigated in H9C2 cell line. Results The metabolomic profiles between SA-B- and propranolol-treated MI rats were similar, since there was a big overlap between the two groups in the PLS-DA score plot. Finally, it was demonstrated that SA-B exhibited a protective effect on MI mainly by decreasing the concentration of cyclic adenosine monophosphate (cAMP) and Ca2+ and inhibiting protein kinase A (PKA). Conclusion SA-B and propanolol exhibited similar metabolomic profiles, indicating that the two drugs might have a similar mechanism. PMID:22409910

  17. Design and fabrication of nanowire electrodes on a flexible substrate for detection of myocardial ischemia

    NASA Astrophysics Data System (ADS)

    Ramachandran, Vasuda; Yoon, Hargsoon; Varadan, Vijay K.

    2009-03-01

    According to a report by the American Heart Association, there are approximately 3-4 million Americans that may experience silent Myocardial Ischemia (MI). Silent MI is a serious heart condition that can progress to a severe heart attack without any warning and the consequences of such an event can turn fatal quickly. Therefore, there is a strong need for a sensor that can continuously monitor the onset of the condition to prevent high risk individuals from deadly heart attacks. An increase in extracellular potassium levels is the first sign of MI and timely sensing with an implantable potassium sensing biosensor could play a critical role in detecting and expediting care. There are challenges in the development of an implantable potassium sensing electrode one of which includes signal drift. The incorporation of novel nanostructures and smarter materials hold the potential to combat these problems. This paper presents a unique design for an all-solid-state potassium sensing device which offers miniaturization along with enhanced signal transduction. These characteristics are important when it comes to implantable devices and signal drift. Sensor design details along with fabrication processes and sensing results are discussed.

  18. Protective effects of p-nitro caffeic acid phenethyl ester on acute myocardial ischemia-reperfusion injury in rats

    PubMed Central

    DU, QIN; HAO, CHUNZHI; GOU, JING; LI, XIAOLI; ZOU, KAILI; HE, XIAOYAN; LI, ZHUBO

    2016-01-01

    Myocardial ischemia-reperfusion (IR) causes widespread cardiomyocyte dysfunction, including apoptosis and necrosis. The present study aimed to investigate the possible cardioprotective effects of p-nitro caffeic acid phenethyl ester (CAPE-NO2) on myocardial IR-induced injury in vivo. To generate a rat model of myocardial IR, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion for 2 h. The rats were administered either the sham treatment (the sham and IR control groups) or the therapeutic agents [the caffeic acid phenethyl ester (CAPE) and CAPE-NO2 groups] 10 min prior to the occlusion. Myocardial IR-induced injury is characterized by: A significant increase in the levels of myocardial enzymes, including creatine kinase, lactate dehydrogenase and aspartate transaminase; a marked increase in intercellular adhesion molecule 1 expression levels, lipid peroxidation products and inflammatory mediators; and a significant decrease in myocardial antioxidants, including catalase, total superoxide dismutase and glutathione peroxidase. In the present study, pretreatment with CAPE-NO2 significantly ameliorated these changes, and decreased the infarct size, as compared with the IR control group (10.32±3.8 vs. 35.65±5.4%). Furthermore, western blotting demonstrated that pretreatment with CAPE-NO2 downregulated the myocardial IR-induced protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), cleaved caspase-3, P38 and the Bax/Bcl-2 ratio. CAPE-NO2 also upregulated the myocardial IR-induced expression levels of Bcl-2, phosphoinositide-3-kinase, phosphorylated Akt and mammalian target of rapamycin. In conclusion, the results of the present study indicated that CAPE-NO2 demonstrated improved cardioprotective effects, as compared with CAPE; therefore, CAPE-NO2 may represent a novel approach to pharmacological cardioprotection. PMID:27073461

  19. Hydrogen sulfide preconditioning protects against myocardial ischemia/reperfusion injury in rats through inhibition of endo/sarcoplasmic reticulum stress

    PubMed Central

    Li, Changyong; Hu, Min; Wang, Yuan; Lu, Huan; Deng, Jing; Yan, Xiaohong

    2015-01-01

    Ischemia reperfusion (I/R) injury is a major cause of myocardial damage. Hydrogen sulfide (H2S), a gaseous signal molecule, has drawn considerable attention for its role in various pathophysiological processes. Multiple lines of evidence reveal the protective effects of H2S in various models of cardiac injury, however, the exact mechanism underlying this protective effect of H2S against myocardial I/R injury is not fully understood. The present study was designed to investigate whether H2S preconditioning attenuates myocardial I/R injury in rats and whether the observed protection is associated with reduced endo/sarcoplasmic reticulum (ER/SR) stress. We found that H2S preconditioning significantly reduced myocardial infarct size, preserved left ventricular function, and inhibited I/R-induced cardiomyocyte apoptosis in vivo. Furthermore, H2S preconditioning significantly attenuated I/R-induced ER/SR stress responses, including the increased expression of glucose-regulated protein 78, C/EBP homologous protein, and activate transcription factor in myocardium. Additionally, we demonstrate that H2S preconditioning attenuates ER/SR stress and inhibits cardiomyocyte apoptosis in an in vitro model of hypoxia/reoxygenation in rat H9c2 cardiac myocytes. In conclusion, these results suggest that H2S-attenuated ER/SR stress plays an important role in its protective effects against I/R-induced myocardial injury. PMID:26339339

  20. Quantitative myocardial perfusion imaging in a porcine ischemia model using a prototype spectral detector CT system

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2016-03-01

    We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR  <  0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR ≈ 0.65, the anterior-to-lateral flow ratio was 0.29  ±  0.01, over-estimating stenosis severity as compared to 0.42  ±  0.01 (p  <  0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50  ±  0.04 falsely indicating an actionable ischemic condition in a healthy

  1. Quantitative myocardial perfusion imaging in a porcine ischemia model using a prototype spectral detector CT system.

    PubMed

    Fahmi, Rachid; Eck, Brendan L; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G; Wilson, David L

    2016-03-21

    We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR < 0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR ≈ 0.65, the anterior-to-lateral flow ratio was 0.29 ± 0.01, over-estimating stenosis severity as compared to 0.42 ± 0.01 (p < 0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50 ± 0.04 falsely indicating an actionable ischemic condition in a healthy territory. This ratio was 1.00 ± 0.08 at 70 ke

  2. Structural basis for phosphorylation and lysine acetylation cross-talk in a kinase motif associated with myocardial ischemia and cardioprotection.

    PubMed

    Parker, Benjamin L; Shepherd, Nicholas E; Trefely, Sophie; Hoffman, Nolan J; White, Melanie Y; Engholm-Keller, Kasper; Hambly, Brett D; Larsen, Martin R; James, David E; Cordwell, Stuart J

    2014-09-12

    Myocardial ischemia and cardioprotection by ischemic pre-conditioning induce signal networks aimed at survival or cell death if the ischemic period is prolonged. These pathways are mediated by protein post-translational modifications that are hypothesized to cross-talk with and regulate each other. Phosphopeptides and lysine-acetylated peptides were quantified in isolated rat hearts subjected to ischemia or ischemic pre-conditioning, with and without splitomicin inhibition of lysine deacetylation. We show lysine acetylation (acetyl-Lys)-dependent activation of AMP-activated protein kinase, AKT, and PKA kinases during ischemia. Phosphorylation and acetyl-Lys sites mapped onto tertiary structures were proximal in >50% of proteins investigated, yet they were mutually exclusive in 50 ischemic pre-conditioning- and/or ischemia-associated peptides containing the KXXS basophilic protein kinase consensus motif. Modifications in this motif were modeled in the C terminus of muscle-type creatine kinase. Acetyl-Lys increased proximal dephosphorylation by 10-fold. Structural analysis of modified muscle-type creatine kinase peptide variants by two-dimensional NMR revealed stabilization via a lysine-phosphate salt bridge, which was disrupted by acetyl-Lys resulting in backbone flexibility and increased phosphatase accessibility.

  3. Role of endogenous opioids on nociceptive threshold in patients with exercise-induced myocardial ischemia.

    PubMed

    Fedele, F; Benedetti, G; Vizza, C D; Agati, L; Penco, M; Barletta, C; Scavo, D; Dagianti, A

    1991-03-01

    To evaluate whether endogenous opioids (EO) play a role in the perception of anginal pain, a randomized double blind clinical trial, using naloxone (N) and placebo (P) and measuring beta-endorphin (beta-ep) plasma levels, was performed. We studied 10 patients with angiographically assessed coronary artery disease (CAD) and stable exercise-induced myocardial ischemia (established by 2 preliminary bicycle ergometric tests) of whom 5 symptomatic (SYM) and 5 asymptomatic (ASYM) and 5 subjects without CAD as a control group (CON). On a third exercise test the beta-ep plasma level (fmol/ml) was measured at rest (SYM 5.4 +/- 2.3 vs ASYM 7.2 +/- 2.3 vs CON 6.8 +/- 2.6, NS), at peak exercise (SYM 4.4 +/- 1.8 vs ASYM 8.0 +/- 4.2 and vs CON 6.2 +/- 2.7, NS) and during recovery (SYM 7.5 +/- 4.2 vs ASYM 7.2 +/- 3.0 vs CON 6.7 +/- 2.5, NS). On 2 subsequent tests patients received N (0.2 mg/kg) or P intravenously and chest pain was evaluated on an analogue scale (score from 1 to 10). After N compared to P we observed: an increased perception of chest pain in SYM (6.8 +/- 1.5 vs 4.2 +/- 1.0; p less than 0.01) without significant changes of the ischemic threshold (total work, heart rate-blood pressure product, ST segment changes, 2D-echocardiographic wall motion abnormalities); no modifications in ASYM and CON.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Effects of different inotropes with antioxidant properties on acute regional myocardial ischemia in isolated rabbit hearts.

    PubMed

    Rump, A F; Schüssler, M; Acar, D; Cordes, A; Ratke, R; Theisohn, M; Rösen, R; Klaus, W; Fricke, U

    1995-05-01

    1. The antiischemic properties of the flavonoids acetylvitexin-rhamnoside (AVR) and luteolin-7-glucoside-(LUT), combining phosphodiesterase (PDE)-inhibitory and antioxidant properties, were studied in comparison to amrinone (AMR) or superoxide dismutase (SOD). The effects of the new dihydropyridine-type calcium-agonist Bay T 5006 were studied in comparison to Bay K 8644. 2. In isolated Langendorff-rabbit hearts perfused at constant pressure, acute regional ischemia (MI) was induced by coronary artery occlusion (CAO) and quantitated from epicardial NADH-fluorescence photography. Drugs were applied either before or after CAO (pre-treatment or treatment) to permit distinguishing the influence of functional and direct cytoprotective actions in the poorly collateralized rabbit hearts. 3. SOD did not affect left ventricular pressure (LVP) or coronary flow (CF) and reduced MI only if applied before CAO. LVP and CF were enhanced by LUT or AMR but not by AVR. MI was reduced to a similar extent in hearts treated with either drug. Cardioprotection by LUT was not improved by starting drug application before CAO. 4. Bay K 8644 reduced LVP and particularly CF, whereas Bay T 5006 did not affect functional parameters. MI was enlarged by Bay K 8644 and remained unaffected by treatment or pretreatment with Bay T 5006. 5. AMR, LUT and AVR possess antiischemic properties related to an improvement of myocardial perfusion. Although oxygen free radicals contribute to ischemic tissue injury, as shown by the cardioprotective effectiveness of SOD, antioxidant properties of the flavonoids LUT and AVR do not seem to be relevant for the antiischemic effects. Our findings also give no evidence for antioxidant properties of dihydropyridines relevant for cardioprotection. PMID:7789735

  5. Plasma Catestatin: A Useful Biomarker for Coronary Collateral Development with Chronic Myocardial Ischemia

    PubMed Central

    Xu, Weixian; Yu, Haiyi; Li, Weihong; Gao, Wei; Guo, Lijun; Wang, Guisong

    2016-01-01

    Backgrounds Catestatin is an endogenous multifunctional neuroendocrinepeptide. Recently, catestatin was discovered as a novel angiogenic cytokine. The study was to investigate the associations between endogenous catestatin and coronary collateral development among the patients with chronic myocardial ischemia. Methods Thirty-eight patients with coronary artery chronic total occlusions (CTO) (CTO group) and 38 patients with normal coronary arteries (normal group) were enrolled in the series. Among the patients with CTO, coronary collateral development was graded according to the Rentrop score method. Rentrop score 0–1 collateral development was regarded as poor collateral group and 2–3 collateral development was regarded as good collateral group. Plasma catestatin level and vascular endothelial growth factor (VEGF) were measured by ELISA kits. Results The plasma catestatin levels in CTO group were significantly higher than that in normal group (1.97±1.01 vs 1.36±0.97ng/ml, p = 0.009). In the CTO group, the patients with good collateral development had significantly higher catestatin and VEGF levels than those with poor collateral development (2.36±0.73 vs 1.61±1.12 ng/ml, p = 0.018; 425.23±140.10 vs 238.48±101.00pg/mL, p<0.001). There is a positive correlation between plasma catestatin levels and Rentrop scores (r = 0.40, p = 0.013) among the patients with CTO. However, there is no correlations between plasma catestatin levels and VEGF (r = -0.06, p = 0.744). In the multiple linear regression models, plasma catestatin level was one of the independent factors of coronary collateral development after adjustment for confounders. Conclusions Plasma catestatin was associated with coronary collateral developments. It may be a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis in patients with CTO. PMID:27304618

  6. Anti-apoptotic potency of TNFR:Fc gene in ischemia/ reperfusion-induced myocardial cell injury.

    PubMed

    Guo, Jun; Zheng, Dong; Li, Hai-Rui; Zhang, Ai-Dong; Li, Zi-Cheng

    2015-04-01

    The aim of the study was to investigate the anti-apoptotic potency of TNFR:Fc gene in ischemia/reperfusion-induced myocardial cell injury and hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes injury. Rats were randomly divided into the following groups (n=8): (1) sham operation group; (2) ischemia-reperfusion (I/R) rats treated with rAAV-EGFP; (3) I/R rats treated with rAAV-TNFR:Fc group. rAAV-EGFP or rAAV-TNFR:Fc was injected intra-myocardial at four sites on the anterior and posterior walls of left ventricle immediately after the construction of I/R-induced AMI model in rats. The effects of TNFR:Fc on apoptosis and cardiacfunction were observed after 72 h of coronary reperfusion. In the in vitro study, apoptosis was analyzed in H9c2 rat cardiomyocytes treated either with nomoxia alone, or hypoxia/reoxygenation in the presence of rAAV-GFP or rAAV-TNFR:Fc. We found that (1) TNFR:Fc gene improved cardiac function (EF, LVESP, LVEDP and dp/dt max) post I/R-induced AMI; (2) TNFR:Fc gene inhibited I/R-induced apoptosis and attenuated the level of TNF-α in serum and cardiac tissue; (3) TNFR:Fc gene prevented apoptosis in hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes associated with inhibition of caspase-3 activation and normalization of ratio of the Bcl-2/Bax. We concluded that TNFR:Fc gene transfection has anti-apoptotic potency in ischemia/reperfusion-induced myocardial cell injury. PMID:25015882

  7. QRS-ST-T triangulation with repolarization shortening as a precursor of sustained ventricular tachycardia during acute myocardial ischemia.

    PubMed

    Batchvarov, Velislav N; Behr, Elijah R

    2015-04-01

    We present segments from a 24-hour 12-lead digital Holter recording in a 48-year-old man demonstrating transient ST elevations in the inferior leads that triggered sustained ventricular tachycardia/ventricular fibrillation (VT/VF) requiring cardioversion. The onset of VT was preceded by a gradual increase in the ST with marked QRS broadening that lacked distinction between the end of the QRS and the beginning of the ST (QRS-ST-T "triangulation"), and shortening of the QT interval not caused by an increased heart rate. This is a relatively rare documentation of the mechanisms immediately triggering sustained ventricular arrhythmias during acute myocardial ischemia obtained with 12-lead ECG.

  8. [Evaluation of the antianginal action of pharmacological substances by the change in the initiation threshold for myocardial ischemia in conscious rabbits].

    PubMed

    Rozonov, Iu B; Morozova, T V

    1984-10-01

    The threshold of the initiation of myocardial ischemia was determined for conscious rabbits with the help of a special preliminary implanted appliance, which made it possible to perform the occlusion and reperfusion of the coronary artery. Nitroglycerin and propranolol were shown to increase the threshold of the initiation of ischemia, while dipyridamole was discovered to reduce it. The method described is offered for evaluation of the drug antianginal effect, since it is adequate and easily reproduced.

  9. Effects of KR-32570, a new sodium hydrogen exchanger inhibitor, on myocardial infarction and arrhythmias induced by ischemia and reperfusion.

    PubMed

    Lee, Byung Ho; Yi, Kyu Yang; Lee, Sunkyung; Lee, Sunghou; Yoo, Sung-eun

    2005-10-31

    The present study was performed to evaluate the cardioprotective effects of [5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl]guanidine (KR-32570) in rat and dog models of coronary artery occlusion and reperfusion. In addition, we sought to clarify the efficacy of KR-32570 on reperfusion-induced fatal ventricular arrhythmia. In anesthetized rats subjected to 45-min coronary occlusion and 90-min reperfusion, KR-32570 (i.v. bolus) dose-dependently reduced myocardial infarct size from 58.0% to 50.7%, 35.3%, 33.5% and 27.0% for 0.03, 0.1, 0.3 and 1.0 mg/kg, respectively (P<0.05). In anesthetized beagle dogs that underwent 1.2-h occlusion followed by 3.0-h reperfusion, KR-32570 (3 mg/kg, i.v. bolus) markedly decreased infarct size from 28.9% in vehicle-treated group to 8.0% (P<0.05), and reduced the reperfusion-induced release in creatine kinase isoenzyme MB, lactate dehydrogenase, Troponin-I and glutamic-oxaloacetic transaminase. KR-32570 dose-dependently decreased the incidence of premature ventricular contraction, ventricular tachycardia or ventricular fibrillation induced by ischemia and reperfusion in rats. Similar results were obtained in dogs with reperfusion-induced arrhythmia. In separate experiments to assess the effects of timing of treatment, KR-32570 given 10 min before or at reperfusion in rat models also significantly reduced the myocardial infarct size (40.9% and 46.1%, respectively) compared with vehicle-treated group. In all studies, KR-32570 caused no significant changes in any hemodynamic profiles. Taken together, these results indicate that KR-32570 significantly reduced the myocardial infarction and incidence of arrhythmias induced by ischemia and reperfusion in rats and dogs, without affecting hemodynamic profiles. Thus, it could be potentially useful in the prevention and treatment of myocardial injuries and lethal ventricular arrhythmias.

  10. Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

    PubMed Central

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2016-01-01

    There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham-operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre-treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang-(1–7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang-(1–7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre-treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA. PMID:27633002

  11. Postoperative myocardial infarction documented by technetium pyrophosphate scan using single-photon emission computed tomography: Significance of intraoperative myocardial ischemia and hemodynamic control

    SciTech Connect

    Cheng, D.C.; Chung, F.; Burns, R.J.; Houston, P.L.; Feindel, C.M. )

    1989-12-01

    The aim of this prospective study was to document postoperative myocardial infarction (PMI) by technetium pyrophosphate scan using single-photon emission computed tomography (TcPPi-SPECT) in 28 patients undergoing elective coronary bypass grafting (CABG). The relationships of intraoperative electrocardiographic myocardial ischemia, hemodynamic responses, and pharmacological requirements to this incidence of PMI were correlated. Radionuclide cardioangiography and TcPPi-SPECT were performed 24 h preoperatively and 48 h postoperatively. A standard high-dose fentanyl anesthetic protocol was used. Twenty-five percent of elective CABG patients were complicated with PMI, as documented by TcPPi-SPECT with an infarcted mass of 38.0 +/- 5.5 g. No significant difference in demographic, preoperative right and left ventricular function, number of coronary vessels grafted, or aortic cross-clamp time was observed between the PMI and non-PMI groups. The distribution of patients using preoperative beta-adrenergic blocking drugs or calcium channel blocking drugs was found to have no correlation with the outcome of PMI. As well, no significant differences in hemodynamic changes or pharmacological requirements were observed in the PMI and non-PMI groups during prebypass or postbypass periods, indicating careful intraoperative control of hemodynamic indices did not prevent the outcome of PMI in these patients. However, the incidence of prebypass ischemia was 39.3% and significantly correlated with the outcome of positive TcPPi-SPECT, denoting a 3.9-fold increased risk of developing PMI. Prebypass ischemic changes in leads II and V5 were shown to correlate with increased CPK-MB release (P less than 0.05) and tends to occur more frequently with lateral myocardial infarction.

  12. Core-shell hybrid liposomal vesicles loaded with panax notoginsenoside: preparation, characterization and protective effects on global cerebral ischemia/reperfusion injury and acute myocardial ischemia in rats

    PubMed Central

    Zhang, Jing; Han, Xizhen; Li, Xiang; Luo, Yun; Zhao, Haiping; Yang, Ming; Ni, Bin; Liao, Zhenggen

    2012-01-01

    Purpose: Novel panax notoginsenoside-loaded core-shell hybrid liposomal vesicles (PNS-HLV) were developed to resolve the restricted bioavailability of PNS and to enhance its protective effects in vivo on oral administration. Methods: Physicochemical characterizations of PNS-HLV included assessment of morphology, particle size and zeta potential, encapsulation efficiency (EE%), stability and in vitro release study. In addition, to evaluate its oral treatment potential, we compared the effect of PNS-HLV on global cerebral ischemia/reperfusion and acute myocardial ischemia injury with those of PNS solution, conventional PNS-loaded nanoparticles, and liposomes. Results: In comparison with PNS solution, conventional PNS-loaded nanoparticles and liposomes, PNS-HLV was stable for at least 12 months at 4°C. Satisfactory improvements in the EE% of notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were shown with the differences in EE% shortened and the greater controlled drug release profiles were exhibited from PNS-HLV. The improvements in the physicochemical properties of HLV contributed to the results that PNS-HLV was able to significantly inhibit the edema of brain and reduce the infarct volume, while it could markedly inhibit H2O2, modified Dixon agar, and serum lactate dehydrogenase, and increase superoxide dismutase (P < 0.05). Conclusion: The results of the present study imply that HLV has promising prospects for improving free drug bioactivity on oral administration. PMID:22915851

  13. Real-Time 12-Lead High-Frequency QRS Electrocardiography for Enhanced Detection of Myocardial Ischemia and Coronary Artery Disease

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Kulecz, Walter B.; DePalma, Jude L.; Feiveson, Alan H.; Wilson, John S.; Rahman, M. Atiar; Bungo, Michael W.

    2004-01-01

    Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

  14. Protective effects of Ping-Lv-Mixture (PLM), a medicinal formula on arrhythmias induced by myocardial ischemia-reperfusion.

    PubMed

    An, Wei; Yang, Jing

    2006-11-01

    Ping-Lv-Mixture (PLM) is a Chinese medicinal formula. The present study aimed to determine the effects of PLM on myocardial ischemia-reperfusion (MI/R) induced arrhythmias in rats. Arrhythmia model was established by occlusion of the left arterial descending coronary artery and thereafter reperfusion. A lead II electrocardiogram was monitored throughout the experiment. The results showed that pretreatment of PLM to MI/R rats significantly reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation. On induction of MI/R, the activities of creatine kinase and lactate dehydrogenase were increased in vehicle group. PLM (0.04-1.00 g/kg) administration prevented the increase of these enzymes. Moreover, a significant increase of myocardium superoxide dismutase and decrease of malondialdehyde contents were observed in rats of PLM groups. On the other hand, the expressions of platelet activating factor (PAF) receptor mRNA was down-regulated in a dose-dependent manner in the PLM-treated groups by RT-PCR. Thus, it can be concluded that pretreatment with PLM inhibited lipid peroxidation in rats through suppressing the expression of PAF receptor, which may contribute to its preventive effect on myocardial ischemia-reperfusion induced arrhythmias.

  15. Comparison of the usefulness of heart rate variability versus exercise stress testing for the detection of myocardial ischemia in patients without known coronary artery disease.

    PubMed

    Goldkorn, Ronen; Naimushin, Alexey; Shlomo, Nir; Dan, Ariella; Oieru, Dan; Moalem, Israel; Rozen, Eli; Gur, Ilan; Levitan, Jacob; Rosenmann, David; Mogilewsky, Yakov; Klempfner, Robert; Goldenberg, Ilan

    2015-06-01

    Heart rate variability (HRV) has been shown to be attenuated in patients with coronary artery disease (CAD) and may, therefore, be possibly used for the early detection of myocardial ischemia. We aimed to evaluate the diagnostic yield of a novel short-term HRV algorithm for the detection of myocardial ischemia in subjects without known CAD. We prospectively enrolled 450 subjects without known CAD who were referred to tertiary medical centers for exercise stress testing (EST) with single-photon emission computed tomography myocardial perfusion imaging (MPI). All subjects underwent 1-hour Holter testing with subsequent HRV analysis before EST with MPI. The diagnostic yield of HRV analysis was compared with EST, using MPI as the gold standard for the noninvasive detection of myocardial ischemia. All subjects had intermediate pretest probability for CAD. Mean age was 62 years, 38% were women, 51% had hypertension, and 25% diabetes mellitus. HRV analysis showed superior sensitivity (77%) compared with standard EST (27%). After multivariate adjustment, HRV was independently associated with an 8.4-fold (p <0.001) increased likelihood for the detection of myocardial ischemia by MPI, whereas EST did not show a statistically significant association with a positive MPI (odds ratio 2.1; p = 0.12). Of subjects who were referred for subsequent coronary angiography, the respective sensitivities of HRV and EST for the detection of significant CAD were 73% versus 26%. Our data suggest that HRV can be used as an important noninvasive technique for the detection of myocardial ischemia in subjects without known CAD, providing superior sensitivity to conventional EST in this population.

  16. Effects of Fluvastatin on Characteristics of Stellate Ganglion Neurons in a Rabbit Model of Myocardial Ischemia

    PubMed Central

    Cheng, Li-Jun; Li, Guang-Ping; Li, Jian; Chen, Yan; Wang, Xing-Hua

    2016-01-01

    Background: Stellate ganglion (SG) plays an important role in cardiovascular diseases. The electrical activity of SG neurons is involved in the regulation of the autonomic nervous system. The aim of this research was to evaluate the effects of fluvastatin on the electrophysiological characteristics of SG neurons in a rabbit model of myocardial ischemia (MI). Methods: The MI model was induced by abdominal subcutaneous injections of isoproterenol in rabbits. Using whole-cell patch clamp technique, we studied the characteristic changes of ion channels and action potentials (APs) in isolated SG neurons in control group (n = 20), MI group (n = 20) and fluvastatin pretreated group (fluvastatin group, n = 20), respectively. The protein expression of sodium channel in SG was determined by immunohistochemical analysis. Results: MI and the intervention of fluvastatin did not have significantly influence on the characteristics of delayed rectifier potassium channel currents. The maximal peak current density of sodium channel currents in SG neurons along with the characteristics of activation curves, inactivation curves, and recovery curves after inactivation were changed in the MI group. The peak current densities of control group, MI group, and fluvastatin group (n = 10 in each group) were −71.77 ± 23.22 pA/pF, −126.75 ± 18.90 pA/pF, and −86.42 ± 28.30 pA/pF, respectively (F = 4.862, P = 0.008). Fluvastatin can decrease the current amplitude which has been increased by MI. Moreover, fluvastatin induced the inactivation curves and post-inactive recovery curves moving to the position of the control group. But the expression of sodium channel-associated protein (Nav1.7) had no significantly statistical difference among the three groups. The percentages of Nav1.7 protein in control group, MI group, and fluvastatin group (n = 5 in each group) were 21.49 ± 7.33%, 28.53 ± 8.26%, and 21.64 ± 2.78%, respectively (F = 1.495, P = 0.275). Moreover, MI reduced the electrical

  17. Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death.

    PubMed

    Sanchez, Gina; Berrios, Daniela; Olmedo, Ivonne; Pezoa, Javier; Riquelme, Jaime A; Montecinos, Luis; Pedrozo, Zully; Donoso, Paulina

    2016-01-01

    Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion.

  18. Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death

    PubMed Central

    Sanchez, Gina; Berrios, Daniela; Olmedo, Ivonne; Pezoa, Javier; Riquelme, Jaime A.; Montecinos, Luis; Pedrozo, Zully; Donoso, Paulina

    2016-01-01

    Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. PMID:27529620

  19. Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death.

    PubMed

    Sanchez, Gina; Berrios, Daniela; Olmedo, Ivonne; Pezoa, Javier; Riquelme, Jaime A; Montecinos, Luis; Pedrozo, Zully; Donoso, Paulina

    2016-01-01

    Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion. PMID:27529620

  20. Increased regional epicardial fat volume associated with reversible myocardial ischemia in patients with suspected coronary artery disease.

    PubMed

    Khawaja, Tuba; Greer, Christine; Thadani, Samir R; Kato, Tomoko S; Bhatia, Ketan; Shimbo, Daichi; Kontak, Andrew; Konkak, Andrew; Bokhari, Sabahat; Einstein, Andrew J; Schulze, P Christian

    2015-04-01

    Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm(3), 156.4 ± 121.9 cm(3), and 96.3 ± 102.1 cm(3), respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm(3); P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm(3); P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease.

  1. Increased Regional Epicardial Fat Volume Associated with Reversible Myocardial Ischemia in Patients with Suspected Coronary Artery Disease

    PubMed Central

    Khawaja, Tuba; Greer, Christine; Thadani, Samir R.; Kato, Tomoko S.; Bhatia, Ketan; Shimbo, Daichi; Konkak, Andrew; Bokhari, Sabahat; Einstein, Andrew J.; Schulze, P. Christian

    2015-01-01

    Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm3, 156.4 ± 121.9 cm3, and 96.3 ± 102.1 cm3, respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm3; P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm3; P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease. PMID:25339129

  2. Vagus nerve stimulation attenuates myocardial ischemia/reperfusion injury by inhibiting the expression of interleukin-17A

    PubMed Central

    YI, CHUNFENG; ZHANG, CHANGJIANG; HU, XIAORONG; LI, YUANHONG; JIANG, HONG; XU, WEIPAN; LU, JIAJIA; LIAO, YUANXI; MA, RUISONG; LI, XUEFEI; WANG, JICHUN

    2016-01-01

    Interleukin (IL)-17A has an important role in myocardial ischemia/reperfusion (I/R) injury, and vagal stimulation (VS) has been demonstrated to exert cardioprotective effects. The present study aimed to investigate the effects of VS on a rat model of myocardial I/R injury, and detected an association between VS and IL-17A. Anesthetized rats underwent VS (2 msec; 10 Hz) or were treated with anti-IL-17A neutralized monoclonal antibodies (mAbs) (200 µg; iv), and subjected to ischemia for 30 min prior to 4 h reperfusion. The following parameters were measured: Infarct size; lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activity levels; tumor necrosis factor (TNF)-α and IL-6 expression levels; and the percentage of terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) positive cells. High mobility group box 1 protein (HMGB1) and IL-17A expression levels were assessed by immunoblotting. Following 4 h reperfusion, VS was able to significantly decrease the infarct size and the activity levels of LDH and CK (P<0.05). Furthermore, VS administration significantly suppressed the increased MDA and decreased SOD activity levels, and significantly reduced caspase-3 activity and the percentage of TUNEL-positive cells (P<0.05). Treatment with anti-IL-17A mAbs demonstrated the same effects as VS. Furthermore, VS was able to significantly inhibit the increased expression levels of TNF-α, IL-6, HMGB1 and IL-17A induced by I/R (P<0.05). The results of the present study suggested that VS may attenuate myocardial I/R injury by reducing the expression of inflammatory cytokines, oxidative stress and the apoptosis of cardiomyocytes. Furthermore, VS may induce cardioprotective effects, which may be associated with the inhibition of IL-17A expression. PMID:26889235

  3. Seabuckthorn Pulp Oil Protects against Myocardial Ischemia-Reperfusion Injury in Rats through Activation of Akt/eNOS.

    PubMed

    Suchal, Kapil; Bhatia, Jagriti; Malik, Salma; Malhotra, Rajiv Kumar; Gamad, Nanda; Goyal, Sameer; Nag, Tapas C; Arya, Dharamvir S; Ojha, Shreesh

    2016-01-01

    Seabuckthorn (SBT) pulp oil obtained from the fruits of seabuckthorn [Hippophae rhamnoides L. (Elaeagnaceae)] has been used traditionally for its medicinal and nutritional properties. However, its role in ischemia-reperfusion (IR) injury of myocardium in rats has not been elucidated so far. The present study reports the cardioprotective effect of SBT pulp oil in IR-induced model of myocardial infarction in rats and underlying mechanism mediating activation of Akt/eNOS signaling pathway. Male albino Wistar rats were orally administered SBT pulp oil (5, 10, and 20 ml/kg/day) or saline for 30 days. On the day 31, ischemia was induced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. SBT pulp oil pretreatment at the dose of 20 ml/kg observed to stabilize cardiac function and myocardial antioxidants such as glutathione, superoxide dismutase, catalase, and inhibited lipid peroxidation evidenced by reduced malondialdehyde levels as compared to IR-control group. SBT pulp oil also improved hemodynamic and contractile function and decreased tumor necrosis factor and activities of myocyte injury marker enzymes; lactate dehydrogenase and creatine kinase-MB. Additionally, a remarkable rise in expression of pAkt-eNOS, Bcl-2 and decline in expression of IKKβ/NF-κB and Bax was observed in the myocardium. The histopathological and ultrastructural salvage of cardiomyocytes further supports the cardioprotective effect of SBT pulp oil. Based on findings, it can be concluded that SBT pulp oil protects against myocardial IR injury mediating favorable modulation of Akt-eNOS and IKKβ/NF-κB expression. PMID:27445803

  4. Strophanthus hispidus attenuates the Ischemia-Reperfusion induced myocardial Infarction and reduces mean arterial pressure in renal artery occlusion

    PubMed Central

    Gundamaraju, Rohit; Vemuri, Ravi Chandra; Singla, Rajeev K; Manikam, Rishya; Rao, A Ranga; Sekaran, Shamala Devi

    2014-01-01

    Background: The myocardium is generally injured in the case of reperfusion injury and arterial damage is caused by hypertension. In reference to these statements, the present study was focused. Cardiac glycosides were said to have protective effects against myocardial infarction and hypertension. Strophanthus hispidus was thus incorporated in the study. Objective: The prime objective of the study was to investigate the protective effects of Strophanthus hispidus against ischemia-reperfusion myocardial Infarction and renal artery occluded hypertension in rats. Materials and Methods: The animal model adopted was surgically-induced myocardial ischemia, performed by means of left anterior descending coronary artery occlusion (LAD) for 30 min followed by reperfusion for another 4 h. Infarct size was assessed by using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride). Hypertension was induced by clamping the renal artery with renal bulldog clamp for 4 h. Results: The study was fruitful by the effect of Strophanthus hispidus on infarction size, which got reduced to 27.2 ± 0.5and 20.0 ± 0.2 by 500 mg/Kg and 1000 mg/Kg ethanolic extracts which was remarkably significant when compared with that of the control group 52.8 ± 4.6. The plant extract did reduce heart rate at various time intervals. There was also a protective effect in the case of mean arterial blood pressure were the 500 mg/Kg and 1000 mg/Kg of the plant extract did reduce the hypertension after 60 minutes was 60.0 ± 4.80 and 50.50 ± 6.80. Conclusion: The results suggest that 500 mg/Kg and 100 mg/Kg ethanolic extract of Strophanthus hispidus was found to possess significant cardiac protective and anti-hypertensive activity. PMID:25298674

  5. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation

    PubMed Central

    Nakano, Yasuhiro; Matoba, Tetsuya; Tokutome, Masaki; Funamoto, Daiki; Katsuki, Shunsuke; Ikeda, Gentaro; Nagaoka, Kazuhiro; Ishikita, Ayako; Nakano, Kaku; Koga, Jun-ichiro; Sunagawa, Kenji; Egashira, Kensuke

    2016-01-01

    Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg−1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg−1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI. PMID:27403534

  6. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation

    NASA Astrophysics Data System (ADS)

    Nakano, Yasuhiro; Matoba, Tetsuya; Tokutome, Masaki; Funamoto, Daiki; Katsuki, Shunsuke; Ikeda, Gentaro; Nagaoka, Kazuhiro; Ishikita, Ayako; Nakano, Kaku; Koga, Jun-Ichiro; Sunagawa, Kenji; Egashira, Kensuke

    2016-07-01

    Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg‑1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg‑1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.

  7. Timing and duration of myocardial ischemia on Holter monitoring following percutaneous coronary intervention and their association with clinical outcomes (a PROTECT-TIMI 30 Substudy Analysis).

    PubMed

    Gibson, C Michael; Pride, Yuri B; Buros, Jacqueline L; Ciaglo, Lauren N; Morrow, David A; Scirica, Benjamin M; Stone, Peter H

    2009-07-01

    In patients with unstable angina, evidence of myocardial ischemia on Holter monitoring is associated with an adverse prognosis. However, the association of duration and timing of ischemia on Holter monitoring with outcomes after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTEACSs) has not been systematically evaluated. PROTECT-TIMI 30 randomized 857 patients with NSTEACSs undergoing PCI to eptifibatide plus a heparin product or bivalirudin monotherapy. Patients underwent continuous Holter monitoring following PCI, and the association between ischemia and clinical outcomes was evaluated retrospectively. Forty-three patients (5.0%) had ischemia on Holter after PCI. Any ischemia was associated with a significant increase in the incidence of death or myocardial infarction (MI) within 48 hours (32.6% vs 6.1%, odds ratio 7.5, 95% confidence interval 3.70 to 15.10, p <0.001). In patients who developed ischemia, there was a 1.44-fold increase in the odds for death or MI for every 30 minutes of ischemia (95% confidence interval 1.12 to 1.84, p = 0.004). Duration of ischemic events was related to their timing, such that ischemic events that occurred within the first 4 hours after PCI (median duration 141 minutes, interquartile range 36 to 227.5) were significantly longer than events occurring 4 to 24 hours after PCI (median duration 32.8 minutes, interquartile range 17.5 to 118, p = 0.041). In conclusion, early ischemia after PCI for NSTEACS is of longer duration, and longer duration of ischemia recognized by Holter monitoring is associated with an increased incidence of death or MI. Holter monitoring may be a useful surrogate end point in clinical trials.

  8. Effects of remote ischemic preconditioning and myocardial ischemia on microRNA-1 expression in the rat heart in vivo.

    PubMed

    Brandenburger, Timo; Grievink, Hilbert; Heinen, Nicole; Barthel, Franziska; Huhn, Ragnar; Stachuletz, Friederike; Kohns, Malte; Pannen, Benedikt; Bauer, Inge

    2014-09-01

    Remote ischemic preconditioning (RIPC) is an easily applicable method for protecting the heart against a subsequent ischemia and reperfusion (I/R) injury. However, the exact molecular mechanisms underlying RIPC are unknown. We examined the involvement of microRNAs (miRNAs) and in particular the expression of miRNA-1 (miR-1) in RIPC and myocardial ischemia. Remote ischemic preconditioning was conducted by four cycles of 5-min bilateral hind-limb ischemia in male Wistar rats. Cardiac ischemia was induced by ligation of the left anterior descending coronary artery for 35 min followed by 2 or 6 h of reperfusion. MicroRNA expression was analyzed by Taqman miRNA arrays and quantitative polymerase chain reaction assays. Luciferase assays were performed to validate the miR-1 target gene brain-derived neurotrophic factor (BDNF). Brain-derived neurotrophic factor mRNA and protein levels were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Remote ischemic preconditioning led to a differential expression of miRNAs. The most abundant cardiac miRNA, miR-1, was downregulated by RIPC without following ischemia as well as after I/R and RIPC followed by I/R after 2 h of reperfusion. After 6 h of reperfusion, RIPC led to an upregulation of miR-1, whereas ischemia had no effect on miR-1 expression. Luciferase assays confirmed the interaction of miR-1 with BDNF, a protein that has been shown to exert cardioprotective effects. Brain-derived neurotrophic factor protein levels in rat hearts measured by enzyme-linked immunosorbent assay were not significantly altered after 2 or 6 h of reperfusion in all intervention groups. Remote ischemic preconditioning leads to changes in the expression levels of the most abundant cardiac miRNA, miR-1. MicroRNA 1 levels did not correlate with protein levels of BDNF, a known miR-1 target, in vivo. Further studies are needed to explore the biological significance of changes in miR-1 expression levels and the

  9. Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia

    SciTech Connect

    Schuler, G.; Schlierf, G.; Wirth, A.; Mautner, H.P.; Scheurlen, H.; Thumm, M.; Roth, H.; Schwarz, F.; Kohlmeier, M.; Mehmel, H.C.

    1988-01-01

    The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 (69 to 304) mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and ''usual medical care'' was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress.

  10. Glucagon-like peptide-1 (7-36) but not (9-36) augments cardiac output during myocardial ischemia via a Frank-Starling mechanism.

    PubMed

    Goodwill, Adam G; Tune, Johnathan D; Noblet, Jillian N; Conteh, Abass M; Sassoon, Daniel; Casalini, Eli D; Mather, Kieren J

    2014-01-01

    This study examined the cardiovascular effects of GLP-1 (7-36) or (9-36) on myocardial oxygen consumption, function and systemic hemodynamics in vivo during normal perfusion and during acute, regional myocardial ischemia. Lean Ossabaw swine received systemic infusions of saline vehicle or GLP-1 (7-36 or 9-36) at 1.5, 3.0, and 10.0 pmol/kg/min in sequence for 30 min at each dose, followed by ligation of the left circumflex artery during continued infusion at 10.0 pmol/kg/min. Systemic GLP-1 (9-36) had no effect on coronary flow, blood pressure, heart rate or indices of cardiac function before or during regional myocardial ischemia. Systemic GLP-1 (7-36) exerted no cardiometabolic or hemodynamic effects prior to ischemia. During ischemia, GLP-1 (7-36) increased cardiac output by approximately 2 L/min relative to vehicle-controls (p = 0.003). This response was not diminished by treatment with the non-depolarizing ganglionic blocker hexamethonium. Left ventricular pressure-volume loops measured during steady-state conditions with graded occlusion of the inferior vena cava to assess load-independent contractility revealed that GLP-1 (7-36) produced marked increases in end-diastolic volume (74 ± 1 to 92 ± 5 ml; p = 0.03) and volume axis intercept (8 ± 2 to 26 ± 8; p = 0.05), without any change in the slope of the end-systolic pressure-volume relationship vs. vehicle during regional ischemia. GLP-1 (9-36) produced no changes in any of these parameters compared to vehicle. These findings indicate that short-term systemic treatment with GLP-1 (7-36) but not GLP-1 (9-36) significantly augments cardiac output during regional myocardial ischemia, via increases in ventricular preload without changes in cardiac inotropy.

  11. Isoflurane Favorably Modulates Guanosine Triphosphate Cyclohydrolase-1 and Endothelial Nitric Oxide Synthase during Myocardial Ischemia and Reperfusion Injury in Rats

    PubMed Central

    Baotic, Ines; Weihrauch, Dorothee; Procknow, Jesse; Vasquez-Vivar, Jeanette; Ge, Zhi-Dong; Sudhakaran, Shaan; Warltier, David C.; Kersten, Judy R.

    2015-01-01

    Background We investigated the hypothesis that isoflurane modulates NO synthesis and protection against myocardial infarction through time-dependent changes in expression of key NO regulatory proteins, guanosine triphosphate cyclohydrolase (GTPCH) -1, the rate-limiting enzyme involved in the biosynthesis of tetrahydrobiopterin and endothelial nitric oxide synthase (eNOS). Methods Myocardial infarct size, NO production (ozone-mediated chemiluminescence), GTPCH-1 and eNOS expression (real-time reverse transcriptase polymerase chain reaction and western blotting), were measured in male Wistar rats with or without APC (1.0 minimum alveolar concentration isoflurane for 30 min) and in the presence or absence of an inhibitor of GTPCH-1, 2,4-diamino-6-hydroxypyrimidine. Results NO−2 production (158±16 and 150±13 pmol/mg protein at baseline in control and APC groups, respectively) was significantly (P<0.05) increased 1.5±0.1 and 1.4±0.1 fold by APC (n=4) at 60 and 90 min of reperfusion, concomitantly, with increased expression of GTPCH-1 (1.3±0.3 fold; n=5) and eNOS (1.3±0.2 fold; n=5). In contrast, total NO (NO−2 and NO−3) was decreased after reperfusion in control experiments. Myocardial infarct size was decreased [43±2% of the area at risk for infarction; n=6] by APC as compared to control experiments (57±1%; n=6). 2, 4-Diamino-6-hydroxypyrimidine decreased total NO production at baseline (221±25 and 175±31 pmol/mg protein at baseline in control and APC groups, respectively), abolished isoflurane-induced increases in NO at reperfusion, and prevented reductions of myocardial infarct size by APC (60±2%; n=6). Conclusions APC favorably modulated a NO biosynthetic pathway by upregulating GTPCH-1 and eNOS, and this action contributed to protection of myocardium against ischemia and reperfusion injury. PMID:26192027

  12. Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression.

    PubMed

    Bouma, Wobbe; Noma, Mio; Kanemoto, Shinya; Matsubara, Muneaki; Leshnower, Bradley G; Hinmon, Robin; Gorman, Joseph H; Gorman, Robert C

    2010-05-01

    The female sex has been associated with improved myocardial salvage after ischemia and reperfusion (I/R). Estrogen, specifically 17beta-estradiol, has been demonstrated to mediate this phenomenon by limiting cardiomyocyte apoptosis. We sought to quantitatively assess the effect of sex, ovarian hormone loss, and I/R on myocardial Bax, Bcl-2, and apoptosis repressor with caspase recruitment domain (ARC) expression. Male (n = 48), female (n = 26), and oophorectomized female (n = 20) rabbits underwent 30 min of regional ischemia and 3 h of reperfusion. The myocardial area at risk and infarct size were determined using a double-staining technique and planimetry. In situ oligo ligation was used to assess apoptotic cell death. Western blot analysis was used to determine proapoptotic (Bax) and antiapoptotic (Bcl-2 and ARC) protein levels in all three ischemic groups and, additionally, in three nonischemic groups. Infarct size (43.7 +/- 3.2%) and apoptotic cell death (0.51 +/- 0.10%) were significantly attenuated in females compared with males (56.4 +/- 1.6%, P < 0.01, and 4.29 +/- 0.95%, P < 0.01) and oophorectomized females (55.7 +/- 3.4%, P < 0.05, and 4.36 +/- 0.51%, P < 0.01). Females expressed significantly higher baseline ARC levels (3.62 +/- 0.29) compared with males (1.78 +/- 0.18, P < 0.01) and oophorectomized females (1.08 +/- 0.26, P < 0.01). Males expressed a significantly higher baseline Bax-to-Bcl-2 ratio (4.32 +/- 0.99) compared with females (0.65 +/- 0.13, P < 0.01) and oophorectomized females (0.42 +/- 0.10, P < 0.01). I/R significantly reduced Bax-to-Bcl-2 ratios in males. In all other groups, ARC levels and Bax-to-Bcl-2 ratios did not significantly change. These results support the conclusion that in females, endogenous estrogen limits I/R-induced cardiomyocyte apoptosis by producing a baseline antiapoptotic profile, which is associated with estrogen-dependent high constitutive myocardial ARC expression.

  13. Reverse and pseudo redistribution of thallium-201 in healed myocardial infarction and normal and negative thallium-201 washout in ischemia due to background oversubtraction

    SciTech Connect

    Lear, J.L.; Raff, U.; Jain, R.

    1988-09-15

    While the interpolative background subtraction used in quantitative planar thallium scanning can significantly overestimate the background overlying the heart, the effects of background oversubtraction on quantitative analysis have not been well defined. A mathematical model that relates myocardial washout determined using interpolative background subtraction to true myocardial washout is presented. The model was validated using phantoms and applied to myocardial and pulmonary thallium kinetic data in 100 patients, 85 with and 15 without coronary artery disease. The model showed that when using interpolative background subtraction, measured washout equals true washout in normally perfused myocardium; however, depending on the relation between myocardial and pulmonary thallium clearance, myocardial washout in ischemic regions and areas of infarction can be substantially over- or underestimated. Based on generally accepted quantitative criteria, this incorrect washout determination can at times lead to misdiagnosis of infarction as ischemia and ischemia as normally perfused tissue. It can also cause both ''reverse redistribution'' and ''pseudo redistribution'' of thallium in myocardial infarction in the absence of a physiologic basis.

  14. Alpha-tocopherol acetate significantly suppressed the increase in heart interstitial 8-hydroxydeoxyguanosine following myocardial ischemia and reperfusion in anesthetized rats.

    PubMed

    Yang, C S; Chen, W Y; Tsai, P J; Kuo, J S

    1999-07-01

    The effect of alpha-tocopherol acetate, an aqueous form of alpha-tocopherol, on the increase in heart interstitial 8-hydroxydeoxyguanosine (8-OH-dG) levels following myocardial ischemia/reperfusion was investigated. A microdialysis probe was implanted in the left ventricular interstitial space of anesthetized rat hearts. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Levels of 8-OH-dG in microdialysates were analyzed via an on-line high-performance liquid chromatography system equipped with an electrochemical detector. The 8-OH-dG levels significantly increased (maximum 3.6-fold of increase relative to basal value) during the 60-min reperfusion stage following a 20 min ischemia. Administration of alpha-tocopherol acetate (20 mg/kg, intravenous, bolus) at 3 min prior to onset of reperfusion, significantly suppressed the reperfusion-induced increase in 8-OH-dG levels. These results suggested that one of the possible protective effect of alpha-tocopherol acetate was to reduce oxidative DNA damage during in myocardial ischemia and reperfusion.

  15. Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1

    PubMed Central

    Yu, Liming; Li, Qing; Yu, Bo; Yang, Yang; Jin, Zhenxiao; Duan, Weixun; Zhao, Guolong; Zhai, Mengen; Liu, Lijun; Yi, Dinghua; Chen, Min; Yu, Shiqiang

    2016-01-01

    Berberine (BBR) exerts potential protective effect against myocardial ischemia/reperfusion (MI/R) injury. Activation of silent information regulator 1 (SIRT1) signaling attenuates MI/R injury by reducing oxidative damage and inflammation response. This study investigated the antioxidative and anti-inflammatory effects of BBR treatment in MI/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with BBR in the absence or presence of the SIRT1 inhibitor sirtinol (Stnl) and then subjected to MI/R injury. BBR conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Stnl attenuated these effects by inhibiting SIRT1 signaling. BBR treatment also reduced myocardium superoxide generation, gp91phox expression, malondialdehyde (MDA) level, and cardiac inflammatory markers and increased myocardium superoxide dismutase (SOD) level. However, these effects were also inhibited by Stnl. Consistently, BBR conferred similar antioxidative and anti-inflammatory effects against simulated ischemia reperfusion injury in cultured H9C2 cardiomyocytes. SIRT1 siRNA administration also abolished these effects. In summary, our results demonstrate that BBR significantly improves post-MI/R cardiac function recovery and reduces infarct size against MI/R injury possibly due to its strong antioxidative and anti-inflammatory activity. Additionally, SIRT1 signaling plays a key role in this process. PMID:26788242

  16. Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion.

    PubMed

    Mourmoura, Evangelia; Leguen, Marie; Dubouchaud, Hervé; Couturier, Karine; Vitiello, Damien; Lafond, Jean-Luc; Richardson, Melanie; Leverve, Xavier; Demaison, Luc

    2011-09-01

    Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10- or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H(2)O(2) release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H(2)O(2) when they oxidize FADH(2)-linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration of the coronary perfusion was explained by an increased mitochondrial ROS release related to the

  17. Copper and iron are mobilized following myocardial ischemia: possible predictive criteria for tissue injury.

    PubMed Central

    Chevion, M; Jiang, Y; Har-El, R; Berenshtein, E; Uretzky, G; Kitrossky, N

    1993-01-01

    Direct evidence for substantial mobilization of copper in the coronary flow immediately following prolonged, but not short, cardiac ischemia is presented. In the first coronary flow fraction (CFF) of reperfusion (0.15 ml), after 35 min of ischemia, the level of copper (as well as of iron) was 8- to 9-fold higher than the preischemic value. The levels in subsequent CFFs decreased and reached the preischemic value, indicating that both metals appear in a burst at the resumption of coronary flow. When the first CFF was used in a reaction mixture containing ascorbate and salicylate, the latter underwent chemical hydroxylation and was converted to its dihydroxybenzoate derivatives. Likewise, this CFF promoted the ascorbate-driven DNA degradation. Subsequent 150 CFFs were serially collected and demonstrated low activities. Following 18 min of ischemia, the copper level in the first CFF of reperfusion was only 15% over the preischemic value. In contrast, the mobilization of iron into coronary flow was significant but markedly lower than after 35 min. The levels of copper and the redox activity of the first CFF correlated well with the degree of loss of cardiac function, after 18 and 35 min of ischemia, respectively. After 18 min of ischemia, cardiac function was about 50% and the damage is considered reversible, whereas after 35 min the functional loss exceeded 80% and is considered irreversible. These results are in accord with the causative role that copper and iron can play in heart injury following ischemia, by virtue of their capacity to catalyze the production of hydroxyl radicals, and could lead to the development of new modalities for intervention in tissue injury. Images PMID:8430081

  18. Cardioprotective Effects of Genistin in Rat Myocardial Ischemia-Reperfusion Injury Studies by Regulation of P2X7/NF-κB Pathway

    PubMed Central

    Gu, Meng; Zheng, Ai-bin; Jin, Jing; Cui, Yue; Zhang, Ning; Che, Zhi-ping; Wang, Yan; Zhan, Jie; Tu, Wen-juan

    2016-01-01

    The present study aimed to assess the effects and mechanisms of genistin in the rat model of myocardial ischemia reperfusion injury. The rat hearts were exposed to the left anterior descending coronary artery (LAD) ligation for 30 min followed by 1 h of reperfusion. In the rat of myocardial ischemia/reperfusion (MI/R), it was found that genistin pretreatment reduced myocardial infarct size, improved the heart rate, and decreased creatine kinase (CK) and lactate dehydrogenase (LDH) levels in coronary flow. This pretreatment also increased catalase (CAT), superoxide dismutase (SOD) activities but decreased glutathione (GSH), malondialdehyde (MDA) levels. Furthermore, we determined that genistin can ameliorate the impaired mitochondrial morphology and oxidation system; interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) levels were also recovered. Besides, related-proteins of nuclear factor kappa-B (NF-κB) signal pathway activated by P2X7 were investigated to determine the molecular mechanism of genistin and their expressions were measured by western blot. These results presented here demonstrated that genistin enhanced the protective effect on the rats with myocardial ischemia reperfusion injury. Therefore, the cardioprotective effects of genistin may rely on its antioxidant and anti-inflammatory activities via suppression of P2X7/NF-κB pathways. PMID:27087823

  19. Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors

    PubMed Central

    2014-01-01

    Background Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion. Methods & Results 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury. Conclusions Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress. PMID

  20. Amelioration of ischemia/reperfusion-induced myocardial infarction by the 2-alkynyladenosine derivative 2-octynyladenosine (YT-146).

    PubMed

    Sasamori, Jun; Aihara, Kazuyuki; Yoneyama, Fumiya; Sato, Isamu; Kogi, Kentaro; Takeo, Satoshi

    2006-04-01

    The present study was aimed at determining whether the novel adenosine A2-agonist YT-146 may have cardioprotective effects against ischemia-reperfusion injury. Anesthetized open-chest dogs underwent 90-min occlusion of the left anterior descending artery and subsequent 300-min reperfusion. The animals were randomly assigned to receive vehicle, 3, or 10 microg/kg YT-146 or ischemic preconditioning (4 episodes of 5 min occlusion followed by 5 min of reperfusion). Blood pressure, heart rate, and regional myocardial blood flow throughout the experiment were measured, as was the myocardial infarct size after reperfusion. The infarct size of the vehicle-treated dog was 56.2% +/- 2.7% (n = 5), whereas that of 3 or 10 microg/kg YT-146-treated dog was smaller (ie, 29.5% +/- 8.7% or 20.2% +/- 7.0%, respectively; n = 5). The infarct size of the dog treated with 10 microg/kg YT-146 was reduced to a degree similar to that of the ischemic preconditioning (19.2% +/- 6.3%, n = 5). YT-146 at both doses elicited a dose-dependent increase in acute hyperemic coronary flow immediately after reperfusion. The cardioprotective effect may be attributed to the limitation of the infarct size, probably via A2-receptor-mediated coronary artery dilatation during the early period of reperfusion.

  1. Observations on plasma ANP levels during short-term transient myocardial ischemia produced by PTCA in patients with LAD stenosis.

    PubMed

    Gasser, R; Luha, O; Dusleag, J; Eber, B; Rotman, R; Klein, W; Fueger, G R

    1993-04-01

    Ten patients with coronary artery disease and stable angina (mean age fifty-seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature.

  2. Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling

    PubMed Central

    Han, Dan; Wei, Jie; Zhang, Rui; Ma, Wenhuan; Shen, Chen; Feng, Yidong; Xia, Nian; Xu, Dan; Cai, Dongcheng; Li, Yunman; Fang, Weirong

    2016-01-01

    Hyperlipidemia aggravates myocardial ischemia/reperfusion (MI/R) injury through stimulating excessive inflammatory response. Therefore, blockade of inflammatory signal is a potential therapeutic management for MI/R complicated with hyperlipidemia. Hydroxysafflor yellow A (HSYA, a monomer extracted from Carthamus tinctorius L.), was studied in this article to address that the regulation of inflammatory signal would alleviate MI/R combined with hyperlipidemia injury. High-fat diet induced hyperlipidemia worsened MI/R mediated heart injury (elevation of infarct size, CK-MB and LDH activity), activated TLR4 over-expression in hearts, released inflammatory cytokines (LPS, TNF-α and IL-1β) excessively. HSYA administration suppressed the over-expression of TLR4 and alleviated heart damage caused by MI/R complicated with hyperlipidemia. Furthermore, HSYA had little influence on MI/R injury in TLR4-knockout mice, which indicated that HSYA protected MI/R through TLR4 inhibition. In vitro, hypoxia/reoxygenation (H/R) coexisting with LPS model in neonatal rat ventricular myocytes (NRVMs) induced serious damage compared with H/R injury to NRVMs. HSYA decreased excessive secretion of inflammatory cytokines, down-regulated over-expression of TLR4 and NF-κB in H/R + LPS injured NRVMs. In conclusion, HSYA alleviated myocardial inflammatory injury through suppressing TLR4, offering an alternative medication for MI/R associated with hyperlipidemia. PMID:27731393

  3. Upregulated ATF6 contributes to chronic intermittent hypoxia-afforded protection against myocardial ischemia/reperfusion injury

    PubMed Central

    JIA, WEIKUN; JIAN, ZHAO; LI, JINGWEI; LUO, LIN; ZHAO, LIANG; ZHOU, YANG; TANG, FUQIN; XIAO, YINGBIN

    2016-01-01

    In the present study, we investigated the role of activating transcription factor 6 (ATF6) in the mechanism by which chronic intermittent hypoxia (CIH) increases tolerance to myocardial ischemia/reperfusion (I/R). Experiments were conducted using a rat model of I/R injury in vivo and isolated Langendorff-perfused rat hearts ex vivo. The role of Akt in this process was also investigated in vitro using rat myoblast H9c2 cells. Cell viability was measured using a cell counting kit-8 assay. Lactate dehydrogenase (LDH) and creatine kinase cardiac isoenzyme activity were also measured as markers of cellular damage. ATF6, Akt and phosphorylated (p)-Akt expression was analyzed by western blot analysis. RNA interference (RNAi) was used to suppress ATF6 expression. We noted that ATF6 expression in the ventricular myocardium was significantly increased in rats exposed to CIH. Furthermore, we noted that CIH preserved cardiac function after I/R in vivo and improved post-ischemic recovery of myocardial performance in isolated rat hearts. ATF6 and p-Akt expression was upregulated in cultured H9c2 cells exposed to chronic mild hypoxia compared with those cultured under normoxic conditions. Chronic mild hypoxia attenuated subsequent simulated I/R injury in H9c2 cells (48 h), as evidenced by increased cell viability and decreased LDH activity. By contrast, decreased cell viability and increased LDH activity were observed in siRNA-ATF6-transfected H9c2 cells, with a concomitant reduction in p-Akt levels. These results indicated that ATF6 upregulation is involved in the mechanism by which CIH attenuates myocardial I/R injury, possibly through upregulation of p-Akt, which is a key regulator of cardiomyocyte survival. PMID:27035093

  4. The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway

    PubMed Central

    Liu, Zhenling; Chen, Ji-Mei; Huang, Huanlei; Kuznicki, Michelle; Zheng, Shaoyi; Sun, Wanqing; Quan, Nanhu; Wang, Lin; Yang, Hui; Guo, Hui-Ming; Li, Ji; Zhuang, Jian; Zhu, Ping

    2016-01-01

    Introduction Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. Methods The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p < 0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p < 0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in

  5. Upregulation of microRNA-22 contributes to myocardial ischemia-reperfusion injury by interfering with the mitochondrial function.

    PubMed

    Du, Jian-Kui; Cong, Bin-Hai; Yu, Qing; Wang, He; Wang, Long; Wang, Chang-Nan; Tang, Xiao-Lu; Lu, Jian-Qiang; Zhu, Xiao-Yan; Ni, Xin

    2016-07-01

    Mitochondrial oxidative damage is critically involved in cardiac ischemia reperfusion (I/R) injury. MicroRNA-22 (miR-22) has been predicted to potentially target sirtuin-1 (Sirt1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), both of which are known to provide protection against mitochondrial oxidative injury. The present study aims to investigate whether miR-22 is involved in the regulation of cardiac I/R injury by regulation of mitochondrial function. We found that miR-22 level was significantly increased in rat hearts subjected to I/R injury, as compared with the sham group. Intra-myocardial injection of 20 ug miR-22 inhibitor reduced I/R injury as evidenced by significant decreases in cardiac infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels and the number of apoptotic cardiomyocytes. H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R) insult exhibited an increase in miR-22 expression, which was blocked by reactive oxygen species (ROS) scavenger and p53 inhibitor. In addition, miR-22 inhibitor attenuated, whereas miR-22 mimic aggravated H/R-induced injury in H9c2 cardiomyocytes. MiR-22 inhibitor per se had no significant effect on cardiac mitochondrial function. Mitochondria from rat receiving miR-22 inhibitor 48h before ischemia were found to have a significantly less mitochondrial superoxide production and greater mitochondrial membrane potential and ATP production as compared with rat receiving miR control. In H9c2 cardiomyocyte, it was found that miR-22 mimic aggravated, whilst miR-22 inhibitor significantly attenuated H/R-induced mitochondrial damage. By using real time PCR, western blot and dual-luciferase reporter gene analyses, we identified Sirt1 and PGC1α as miR-22 targets in cardiomyocytes. It was found that silencing of Sirt1 abolished the protective effect of miR-22 inhibitor against H/R-induced mitochondrial dysfunction and cell injury in cardiomyocytes. Taken together, our

  6. Assesment of Myocardial Ischemia by Combination of Tissue Synchronisation Imaging and Dobutamine Stress Echocardiography

    PubMed Central

    Aksakal, Enbiya; Gurlertop, Yekta; Simsek, Ziya; Gundogdu, Fuat; Sevimli, Serdar; Bakirci, Eftal Murat; Karakelleoglu, Sule

    2013-01-01

    Background and Objectives Dobutamine stress echocardiography (DSE) is an important non-invasive imaging method for evaluating ischemia. However, wall motion interpretation can be impaired by the experience level of the interpreter and the subjectivity of the visual assessment. In our study we aimed to combine DSE and tissue syncronisation imaging to increase sensitivity for detecting ischemia. Subjects and Methods 50 patients with indications for DSE were included in the study. In 25 patients we found DSE positive for ischemia and in the other 25 patients we found it to be negative. The negative group was accepted as the control group. There was no significant difference in terms of risk factors and echocardiographic parameters between the two groups, except for wall motion scores. In both groups, left ventricular dyssychrony was accepted as the difference between time to peak systolic velocity (Ts) in the reciprocal four couple of non-apical segments at rest and during peak stress. Timings were corrected for heart rate. We compared the differences of the dyssynchronisation value at rest and during peak stress to determine the distinctions within the groups and between the groups of DSE positive and negative patients. Results We found that stress and ischemia did not create any significant difference over the left intraventricular dyssynchrony with DSE, although at the segmenter level it prolonged the time to peak systolic velocity (p<0.05). These alterations did not show any significant difference between positive and negative DSE groups. Conclusion As a result, this segmenter dyssynchrony and the time to peak systolic velocity, which is corrected for heart rate, did not enhance any new value over DSE for detecting ischemia. PMID:23882287

  7. 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

  8. Caffeoylquinic Acid Derivatives Extract of Erigeron multiradiatus Alleviated Acute Myocardial Ischemia Reperfusion Injury in Rats through Inhibiting NF-KappaB and JNK Activations

    PubMed Central

    Liu, Yuan; Ren, Xuecong; Wang, Kaishun; Zhang, Hao

    2016-01-01

    Erigeron multiradiatus (Lindl.) Benth. has been used in Tibet folk medicine to treat various inflammatory diseases. The aim of this study was to investigate antimyocardial ischemia and reperfusion (I/R) injury effect of caffeoylquinic acids derivatives of E. multiradiatus (AE) in vivo and to explain underling mechanism. AE was prepared using the whole plant of E. multiradiatus and contents of 6 caffeoylquinic acids determined through HPLC analysis. Myocardial I/R was induced by left anterior descending coronary artery occlusion for 30 minutes followed by 24 hours of reperfusion in rats. AE administration (10, 20, and 40 mg/kg) inhibited I/R-induced injury as indicated by decreasing myocardial infarct size, reducing of CK and LDH activities, and preventing ST-segment depression in dose-dependent manner. AE decreased cardiac tissue levels of proinflammatory factors TNF-α and IL-6 and attenuated leukocytes infiltration. AE was further demonstrated to significantly inhibit I-κB degradation, nuclear translocation of p-65 and phosphorylation of JNK. Our results suggested that cardioprotective effect of AE could be due to suppressing myocardial inflammatory response and blocking NF-κB and JNK activation pathway. Thus, caffeoylquinic acids might be the active compounds in E. multiradiatus on myocardial ischemia and be a potential natural drug for treating myocardial I/R injury. PMID:27516722

  9. Caffeoylquinic Acid Derivatives Extract of Erigeron multiradiatus Alleviated Acute Myocardial Ischemia Reperfusion Injury in Rats through Inhibiting NF-KappaB and JNK Activations.

    PubMed

    Zhang, Zhifeng; Liu, Yuan; Ren, Xuecong; Zhou, Hua; Wang, Kaishun; Zhang, Hao; Luo, Pei

    2016-01-01

    Erigeron multiradiatus (Lindl.) Benth. has been used in Tibet folk medicine to treat various inflammatory diseases. The aim of this study was to investigate antimyocardial ischemia and reperfusion (I/R) injury effect of caffeoylquinic acids derivatives of E. multiradiatus (AE) in vivo and to explain underling mechanism. AE was prepared using the whole plant of E. multiradiatus and contents of 6 caffeoylquinic acids determined through HPLC analysis. Myocardial I/R was induced by left anterior descending coronary artery occlusion for 30 minutes followed by 24 hours of reperfusion in rats. AE administration (10, 20, and 40 mg/kg) inhibited I/R-induced injury as indicated by decreasing myocardial infarct size, reducing of CK and LDH activities, and preventing ST-segment depression in dose-dependent manner. AE decreased cardiac tissue levels of proinflammatory factors TNF-α and IL-6 and attenuated leukocytes infiltration. AE was further demonstrated to significantly inhibit I-κB degradation, nuclear translocation of p-65 and phosphorylation of JNK. Our results suggested that cardioprotective effect of AE could be due to suppressing myocardial inflammatory response and blocking NF-κB and JNK activation pathway. Thus, caffeoylquinic acids might be the active compounds in E. multiradiatus on myocardial ischemia and be a potential natural drug for treating myocardial I/R injury. PMID:27516722

  10. A myocardial ischemia- and reperfusion-induced injury is mediated by reactive oxygen species released from blood platelets.

    PubMed

    Seligmann, Christian; Prechtl, Gerald; Kusus-Seligmann, Magda; Daniel, Werner G

    2013-01-01

    In recent experimental studies, blood platelets have been found to exhibit some cardiodepressive effects in ischemic and reperfused guinea pig hearts independent of thrombus formation. These effects seemed to be mediated by reactive oxygen species (ROS). However, the source of these ROS - platelets or heart - remained still unknown. Isolated, buffer-perfused and pressure-volume work performing guinea pig hearts were exposed to a low-flow ischemia (1 ml/min) of 30 min duration and reperfused at a constant flow of 5 ml/min. Human thrombocytes were administered as 1 min bolus (20 000 thrombocytes/µl perfusion buffer) in the 15th min of ischemia or in the 1st or 5th min of reperfusion in the presence of thrombin (0.3 U/ml perfusion buffer). Recovery of external heart work (REHW) was expressed as ratio between postischemic and preischemic EHW in percent. Intracoronary platelet retention (RET) was quantified as percent of platelets applied. In a second set of experiments, thrombocytes were incubated with 10 µM of the irreversible NADPH oxidase blocker diphenyliodonium chloride and washed twice, thereafter, and administered according to the same protocol as described above. Hearts exposed to ischemia and reperfusion in the presence of thrombin but without application of platelets served as controls. Controls without application of platelets did not reveal a severe compromisation of myocardial function (REHW 85.5 ± 1%). However, addition of platelets during ischemia or in the 1st or 5th min of reperfusion led to a significant reduction of REHW as compared with controls (REHW 62.4 ± 6, 53.9 ± 3, 40.5 ± 3, respectively). Application of platelets pretreated with diphenyliodonium chloride did not reveal any cardiodepressive effects being significantly different from controls without platelet application. Moreover, treatment of platelets with diphenyliodonium chloride did not significantly decrease intracoronary platelet retention. In conclusion, these results demonstrate

  11. HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism.

    PubMed

    Kong, Qiuyue; Dai, Leyang; Wang, Yana; Zhang, Xiaojin; Li, Chuanfu; Jiang, Surong; Li, Yuehua; Ding, Zhengnian; Liu, Li

    2016-01-01

    Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. HSPA12B is an endothelial-cell-specifically expressed heat shock protein. However, the roles of HSPA12B in acute myocardial I/R injury is unknown. Here we reported that myocardial I/R upregulated HSPA12B expression in ventricular tissues, and endothelial overexpression of HSPA12B in transgenic mice (Tg) limited infarct size, attenuated cardiac dysfunction and improved cardiomyocyte survival compared with their wild type littermates. These improvements were accompanied with the diminished myocardial no-reflow phenomenon, decreased microvascular leakage, and better maintained endothelial tight junctions. The I/R-evoked neutrophil infiltration was also suppressed in Tg hearts compared with its wild type (WT) littermates. Moreover, Tg hearts exhibited the enhanced activation of PI3K/Akt//mTOR signaling following I/R challenge. However, pharmacological inhibition of PI3K abolished the HSPA12B-induced cardioprotection against myocardial I/R injury. The data demonstrate for the first time that the endothelial HSPA12B protected hearts against myocardial I/R injury. This cardioprotective action of HSPA12B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. Our study suggests that targeting endothelial HSPA12B could be an alternative approach for the management of patients with myocardial I/R injury. PMID:27644317

  12. HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism

    PubMed Central

    Kong, Qiuyue; Dai, Leyang; Wang, Yana; Zhang, Xiaojin; Li, Chuanfu; Jiang, Surong; Li, Yuehua; Ding, Zhengnian; Liu, Li

    2016-01-01

    Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. HSPA12B is an endothelial-cell-specifically expressed heat shock protein. However, the roles of HSPA12B in acute myocardial I/R injury is unknown. Here we reported that myocardial I/R upregulated HSPA12B expression in ventricular tissues, and endothelial overexpression of HSPA12B in transgenic mice (Tg) limited infarct size, attenuated cardiac dysfunction and improved cardiomyocyte survival compared with their wild type littermates. These improvements were accompanied with the diminished myocardial no-reflow phenomenon, decreased microvascular leakage, and better maintained endothelial tight junctions. The I/R-evoked neutrophil infiltration was also suppressed in Tg hearts compared with its wild type (WT) littermates. Moreover, Tg hearts exhibited the enhanced activation of PI3K/Akt//mTOR signaling following I/R challenge. However, pharmacological inhibition of PI3K abolished the HSPA12B-induced cardioprotection against myocardial I/R injury. The data demonstrate for the first time that the endothelial HSPA12B protected hearts against myocardial I/R injury. This cardioprotective action of HSPA12B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. Our study suggests that targeting endothelial HSPA12B could be an alternative approach for the management of patients with myocardial I/R injury. PMID:27644317

  13. Three-year follow-up of patients with silent ischemia in the subacute phase of myocardial infarction after thrombolysis and early coronary intervention.

    PubMed

    Lotze, U; Ozbek, C; Gerk, U; Kaufmann, H; Sen, S; Figulla, H R

    1999-10-31

    In order to assess the prognostic value of silent myocardial ischemia in acute myocardial infarction after thrombolysis and early coronary angiography (14-48 h after start of thrombolysis) including percutaneous transluminal coronary angioplasty, if indicated, 126 patients underwent 24 h-Holter-monitoring in the early postinfarction period. The 24 h-Holter-recording was initiated directly after early coronary intervention (40+/-11 h after onset of symptoms). Of the 126 patients initially eligible for the study 29 had to be excluded from further analysis for clinical or methodical reasons. Of the remaining 97 patients, 10 (10%) had silent ischemia (group A) and 87/97 (90%) patients showed no significant ST-segment alterations. Both groups did not significantly differ from each other with regard to baseline clinical characteristics, severity of coronary artery disease and frequency of successful percutaneous transluminal coronary angioplasty. The left ventricular ejection fraction showed a trend towards lower values in patients with than in those without silent ischemia (47+/-15% vs. 55+/-13%, p=0.07). When both silent ischemia and left ventricular ejection fraction <40% were present, a subset of patients at high risk for cardiac death could be identified (specificity: 98%, positive predictive accuracy: 75%). By Kaplan-Meier analysis, significantly more cardiac deaths occurred in group A than in group B (30% vs. 6%, p<0.01) during the three-year follow-up (950+/-392 days) after acute myocardial infarction. Regarding the cardiac events during long-term follow-up (emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, non-fatal reinfarction, and cardiac death) there was no significant difference between both groups (30% vs. 18%, NS). In conclusion, Holter monitor-detected silent ischemia in the subacute phase of myocardial infarction after thrombolysis followed by early delayed coronary intervention occurs in 10% of the patients

  14. Diurnal variation in myocardial ischemia/reperfusion tolerance; mediation by the circadian clock within the cardiomyocyte

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in cardiovascular physiology (e.g. blood pressure and heart rate) and pathophysiology (e.g. myocardial infarction (MI)) exist. Humans exhibit a marked increase in MI frequency during the early hours of the morning. However, MIs occurring during the evening are more likely to result...

  15. Oxidative Stress-Related Biomarkers in Essential Hypertension and Ischemia-Reperfusion Myocardial Damage

    PubMed Central

    Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

    2013-01-01

    Cardiovascular diseases are a leading cause of mortality and morbidity worldwide, with hypertension being a major risk factor. Numerous studies support the contribution of reactive oxygen and nitrogen species in the pathogenesis of hypertension, as well as other pathologies associated with ischemia/reperfusion. However, the validation of oxidative stress-related biomarkers in these settings is still lacking and novel association of these biomarkers and other biomarkers such as endothelial progenitor cells, endothelial microparticles, and ischemia modified albumin, is just emerging. Oxidative stress has been suggested as a pathogenic factor and therapeutic target in early stages of essential hypertension. Systolic and diastolic blood pressure correlated positively with plasma F2-isoprostane levels and negatively with total antioxidant capacity of plasma in hypertensive and normotensive patients. Cardiac surgery with extracorporeal circulation causes an ischemia/reperfusion event associated with increased lipid peroxidation and protein carbonylation, two biomarkers associated with oxidative damage of cardiac tissue. An enhancement of the antioxidant defense system should contribute to ameliorating functional and structural abnormalities derived from this metabolic impairment. However, data have to be validated with the analysis of the appropriate oxidative stress and/or nitrosative stress biomarkers. PMID:24347798

  16. Prevalence and predictors of ischemia and outcomes in outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging.

    PubMed

    Bourque, Jamieson M; Patel, Chetan A; Ali, Mohamed M; Perez, Margarita; Watson, Denny D; Beller, George A

    2013-05-01

    Background- The prevalence of ischemia and its prediction of events are unclear in outpatients with diabetes mellitus in the modern era of intensive medical management. We sought to identify the prevalence of ischemia, subsequent cardiac events, and impact of sex, stress type, and symptom status on these findings in a cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging (MPI). Methods and Results- The study cohort included 575 consecutive outpatients with diabetes mellitus who underwent quantitative, gated single-photon emission computed tomography MPI. Clinical information, stress MPI variables, and cardiac events were prospectively collected and analyzed. The study population was at intermediate risk of coronary artery disease or had known coronary artery disease (40.3%); 29% of patients were asymptomatic at the time of stress testing. Scintigraphic ischemia and significant (≥10%) left ventricular ischemia were present in 126 patients (21.9%) and 29 patients (5.0%), respectively, and <1% of patients had early revascularization. The risk of ischemia was increased >2-fold by male sex (P<0.001), but was not impacted by pharmacological stress (P=0.15) or presence of symptoms (P=0.89). During a median 4.4 years follow-up, the rate of cardiac death/nonfatal myocardial infarction was moderate at 2.6%/y (cardiac death 0.8%/y) in the total cohort, but was 5.7%/y in those with ischemia (P<0.001). Pharmacological stress predicted a higher cardiac event rate (P<0.001) but symptoms did not (P=0.55). Conclusions- This cohort of stable outpatients with diabetes mellitus referred for single-photon emission computed tomography had low rates of significant ischemia and early revascularization; an initially low cardiac event rate increased after 2 years. Independent predictors of cardiac death/nonfatal myocardial infarction were known coronary artery disease, pharmacological stress, and MPI

  17. ST-segment changes in high-resolution body surface potential maps measured during exercise to assess myocardial ischemia: a pilot study

    PubMed Central

    Zaczek, Rajmund; Zavala-Fernandez, Heriberto; Janusek, Dariusz; Kobylecka, Małgorzata; Królicki, Leszek; Opolski, Grzegorz; Maniewski, Roman

    2014-01-01

    Introduction The aim of the study was to assess myocardial ischemia by analysis of ST-segment changes in high-resolution body surface potential maps (HR-BSPM) measured at rest and during an exercise stress test. Material and methods The study was carried out on a group of 28 patients with stable coronary artery disease and 15 healthy volunteers. The HR-BSPM were measured at rest and during the exercise stress test on a supine ergometer. The workload was increased in stages by 25 W every 2 min, beginning at 50 W. The maps of ST-segment depression (ST60) were calculated from time averaged recordings at rest and at maximal workload. Results The efficiency in detection of myocardial ischemia was higher for HR-BSPM than for standard 12-lead electrocardiography (ECG) when both methods were evaluated by outcomes of coronarography. The sensitivity of HR-BSPM was 82.4% while for the standard 12-lead ECG exercise stress test it was 58.8%. For some patients significant changes in the ST segment were observed at stress HR-BSPM but were not visible in standard 12-lead ECG recorded under the same conditions. Conclusions Obtained high values of sensitivity and specificity in myocardial ischemia detection suggest that maps of ST60 calculated from HR-BSPM can improve detection of patients with ischemic heart disease in comparison to the standard electrocardiographic exercise stress test examinations. PMID:25624843

  18. High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats.

    PubMed

    Liu, Jian; Lloyd, Steven G

    2013-04-01

    Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats

  19. Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion.

    PubMed

    Liu, Jian; Wang, Peipei; Douglas, Samuel L; Tate, Joshua M; Sham, Simon; Lloyd, Steven G

    2016-07-01

    High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.

  20. Experimental Study on the Effect of Intravenous Stem Cell Therapy on Intestinal Ischemia Reperfusion Induced Myocardial Injury

    PubMed Central

    Embaby, Azza; Metwally, Hala Gabr

    2013-01-01

    Background and Objectives: The myocyte death that follows intestinal ischemia reperfusion (I/R) injury is a major factor contributing to high mortality and morbidity in ischemic heart disease. The purpose of stem cell (SC) therapy for myocardial infarction is to improve clinical outcomes. The present study aimed at investigating the possible therapeutic effect of intravenous human cord blood mesenchymal stem cells (HCBMSCs) on intestinal ischemia reperfusion induced cardiac muscle injury in albino rat. Methods and Results: Thirty male albino rats were divided equally into control (Sham-operated) group, I/R group where rats were exposed to superior mesenteric artery ligation for 1 hour followed by 1 hour reperfusion. In SC therapy group, the rats were injected with HCBMSCs into the tail vein. The rats were sacrificed four weeks following therapy. Cardiac muscle sections were exposed to histological, histochemical, immunohistochemical and morphometric studies. In I/R group, multiple fibers exhibited deeply acidophilic sarcoplasm with lost striations and multiple fibroblasts appeared among the muscle fibers. In SC therapy group, few fibers appeared with deeply acidophilic sarcoplasm and lost striations. Mean area of muscle fibers with deeply acidophilic sarcoplasm and mean area% of fibroblasts were significantly decreased compared to I/R group. Prussion blue and CD105 positive cells were found in SC therapy group among the muscle fibers, inside and near blood vessels. Conclusions: Intestinal I/R induced cardiac muscle degenerative changes. These changes were ameliorated following HCBMSC therapy. A reciprocal relation was recorded between the extent of regeneration and the existence of undifferentiated mesenchymal stem cells. PMID:24386556

  1. Contrast agents and cardiac MR imaging of myocardial ischemia: from bench to bedside.

    PubMed

    Croisille, Pierre; Revel, Didier; Saeed, Maythem

    2006-09-01

    This review paper presents, in the first part, the different classes of contrast media that are already used or are in development for cardiac magnetic resonance imaging. A classification of the different types of contrast media is proposed based on the distribution of the compounds in the body, their type of relaxivity and their potential affinity to particular molecules. In the second part, the different uses of the extracellular type of T1-enhancing contrast agent for myocardial imaging is covered from the detection of stable coronary artery disease to the detection and characterization of chronic infarction. A particular emphasis is placed on the clinical use of gadolinium-chelates, which are the universally used type of MRI contrast agent in the clinical routine. Both approaches, first-pass magnetic resonance imaging (FP-MRI) as well as delayed-enhanced magnetic resonance imaging (DE-MRI), are covered in the different situations of acute and chronic myocardial infarction. PMID:16633792

  2. Apelinergic system in endothelial cells and its role in angiogenesis in myocardial ischemia.

    PubMed

    Novakova, Vera; Sandhu, Gurpreet S; Dragomir-Daescu, Dan; Klabusay, Martin

    2016-01-01

    Apelin is a peptide known to have a vital role in cardiovascular diseases. It has been proven to induce proliferation and tube formation in endothelial cells, stabilise contacts between endothelial cells, and mediate pericyte recruitment. Since apelin level is reduced early after myocardial infarction, a supportive therapy with apelin is being investigated for its beneficial effect on blood vessel formation. It is becoming apparent, however, that the final effect of apelin often depends on stimuli the cell receives and the cross-talk with other molecules inside the cell. Hence, understanding the apelin pathway potentially can help us to improve angiogenic therapy. This review summarises recent knowledge regarding molecules involved in apelin signalling while focusing on their roles in angiogenesis within the ischemic environment after myocardial infarction.

  3. [Myocardial ischemia during exertion. Correlations between blood levels of thromboxane B2 and changes in coronary flow and resistance].

    PubMed

    De Servi, S; Vidale, E; Mussini, A; Cafiso, A; Gavazzi, A; Falcone, C; Bramucci, E; Angoli, L; Ferrario, M; Ghio, S

    1985-01-01

    Platelet activation, with the subsequent generation of Thromboxane (Tx) A2, has been implied as a possible cause of resting as well as exercise induced myocardial ischemia. To verify the latter hypothesis, we measured the exercise release of TxB2, the stable metabolite of TxA2, in 9 patients with exertional angina and left anterior descending coronary artery disease. Three of the patients also suffered from angina at rest, due to coronary vasospasm. The great cardiac vein flow, venous efflux from the myocardial territory supplied by the left anterior descending, was determined by the thermodilution technique in the basal conditions, at peak exercise when angina and/or significant ST changes occurred, and 20 min after exercise. Simultaneous blood samples were drawn from the great cardiac vein and a peripheral artery for TxB2 measurements. Regional coronary resistances were calculated as the ratio of mean arterial pressure and coronary flow. At peak exercise the great cardiac vein flow increased and regional coronary resistances decreased in all patients, except in one who showed exercise induced coronary spasm. An increase in TxB2 release was found in 3 patients, a decrease in 3, while the remaining 3 patients did not show significant changes. After exercise the great cardiac vein flow and regional coronary resistances returned to control values in all, whereas both great cardiac vein and arterial TxB2 levels were increased in 6 patients. Our data show that no apparent relation exists between exercise-induced changes in coronary resistances and generation of TxB2.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. High-fat, low-carbohydrate diet promotes arrhythmic death and increases myocardial ischemia-reperfusion injury in rats

    PubMed Central

    Liu, Jian; Wang, Peipei; Zou, Luyun; Qu, Jing; Litovsky, Silvio; Umeda, Patrick; Zhou, Lufang; Chatham, John; Marsh, Susan A.; Dell'Italia, Louis J.

    2014-01-01

    High-fat, low-carbohydrate diets (HFLCD) are often eaten by humans for a variety of reasons, but the effects of such diets on the heart are incompletely understood. We evaluated the impact of HFLCD on myocardial ischemia/reperfusion (I/R) using an in vivo model of left anterior descending coronary artery ligation. Sprague-Dawley rats (300 g) were fed HFLCD (60% calories fat, 30% protein, 10% carbohydrate) or control (CONT; 16% fat, 19% protein, 65% carbohydrate) diet for 2 wk and then underwent open chest I/R. At baseline (preischemia), diet did not affect left ventricular (LV) systolic and diastolic function. Oil red O staining revealed presence of lipid in the heart with HFLCD but not in CONT. Following I/R, recovery of LV function was decreased in HFLCD. HFLCD hearts exhibited decreased ATP synthase and increased uncoupling protein-3 gene and protein expression. HFLCD downregulated mitochondrial fusion proteins and upregulated fission proteins and store-operated Ca2+ channel proteins. HFLCD led to increased death during I/R; 6 of 22 CONT rats and 16 of 26 HFLCD rats died due to ventricular arrhythmias and hemodynamic shock. In surviving rats, HFLCD led to larger infarct size. We concluded that in vivo HFLCD does not affect nonischemic LV function but leads to greater myocardial injury during I/R, with increased risk of death by pump failure and ventricular arrhythmias, which might be associated with altered cardiac energetics, mitochondrial fission/fusion dynamics, and store-operated Ca2+ channel expression. PMID:24929857

  5. Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers

    SciTech Connect

    Fleg, J.L.; Gerstenblith, G.; Zonderman, A.B.; Becker, L.C.; Weisfeldt, M.L.; Costa, P.T. Jr.; Lakatta, E.G. )

    1990-02-01

    Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.

  6. High-fat, low-carbohydrate diet promotes arrhythmic death and increases myocardial ischemia-reperfusion injury in rats.

    PubMed

    Liu, Jian; Wang, Peipei; Zou, Luyun; Qu, Jing; Litovsky, Silvio; Umeda, Patrick; Zhou, Lufang; Chatham, John; Marsh, Susan A; Dell'Italia, Louis J; Lloyd, Steven G

    2014-08-15

    High-fat, low-carbohydrate diets (HFLCD) are often eaten by humans for a variety of reasons, but the effects of such diets on the heart are incompletely understood. We evaluated the impact of HFLCD on myocardial ischemia/reperfusion (I/R) using an in vivo model of left anterior descending coronary artery ligation. Sprague-Dawley rats (300 g) were fed HFLCD (60% calories fat, 30% protein, 10% carbohydrate) or control (CONT; 16% fat, 19% protein, 65% carbohydrate) diet for 2 wk and then underwent open chest I/R. At baseline (preischemia), diet did not affect left ventricular (LV) systolic and diastolic function. Oil red O staining revealed presence of lipid in the heart with HFLCD but not in CONT. Following I/R, recovery of LV function was decreased in HFLCD. HFLCD hearts exhibited decreased ATP synthase and increased uncoupling protein-3 gene and protein expression. HFLCD downregulated mitochondrial fusion proteins and upregulated fission proteins and store-operated Ca(2+) channel proteins. HFLCD led to increased death during I/R; 6 of 22 CONT rats and 16 of 26 HFLCD rats died due to ventricular arrhythmias and hemodynamic shock. In surviving rats, HFLCD led to larger infarct size. We concluded that in vivo HFLCD does not affect nonischemic LV function but leads to greater myocardial injury during I/R, with increased risk of death by pump failure and ventricular arrhythmias, which might be associated with altered cardiac energetics, mitochondrial fission/fusion dynamics, and store-operated Ca(2+) channel expression.

  7. [Progress of researches on mechanisms of acupuncture therapy underlying improving myocardial ischemia and the future approach for in-depth study on its mechanisms from epigenetics].

    PubMed

    He, Su-Yun; Lu, Sheng-Feng; Zhu, Bing-Mei

    2014-02-01

    As an important content of alternative and complementary medicine, acupuncture therapy has been proved to be effective in relieving myocardial ischemia (MI). Authors of the present paper review recent progress of researches on acupuncture therapy in resisting MI from 1) improving cardiovascular function and promoting angiogenesis, and 2) protecting myocardial cells from further injury and reducing cellular apoptosis at different pathological stages of MI. Moreover, the authors discuss the characteristics of epigenetic regulation in the process of MI and cardiac repair including the methylating of DNA, modification of histone, remodeling of the chromatin, and micro-RNA expression, mediating cellular apoptosis, regeneration of myocardial blood vessels, etc. The authors hold that future studies on the underlying mechanisms of acupuncture therapy in the prevention and treatment of MI from epigenetics may be a new approach and a new direction.

  8. Developmental Programming Resulting from Maternal Obesity: Effects on Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Calvert, John W.; Lefer, David J.; Gundewar, Susheel; Poston, Lucilla; Coetzee, William A.

    2010-01-01

    A comprehensive number of epidemiological and animal studies suggest that prenatal and early life events are important determinants for disorders later in life. Among them, prenatal stress (i.e. stress experienced by the pregnant mother with impact on the fetal ontogeny) has clear programming effects on the cardiovascular system. A fetus developing under adverse conditions becomes an adult who is susceptible to disease, which may include hypertension, insulin resistance, altered blood lipid levels and cardiovascular disease. Recent evidence demonstrates that maternal programming can occur in the absence of other adverse environmental factors. Obesity, which is becoming a problem of large proportions in Western countries, is a possible cause of programming. With over 30% of the US population currently obese, many mothers currently suffer from obesity during their child-bearing years (in fact, these conditions are often aggravated during pregnancy). One of the targets of programming is the cardiovascular system and reported consequences include hypertension, endothelial dysfunction and vascular abnormalities. The overall goal of our studies was to investigate the susceptibility of the heart to ischemia/reperfusion in an animal model of maternal obesity. Our data demonstrate that normal (non-mutant) offspring from obese Agouti mouse dams had an increased susceptibility to ischemia/reperfusion injury. These data may provide insights into the long-term cardiovascular consequences of programming. PMID:19395658

  9. Meta-analysis of trials on mortality after percutaneous coronary intervention compared with medical therapy in patients with stable coronary heart disease and objective evidence of myocardial ischemia.

    PubMed

    Gada, Hemal; Kirtane, Ajay J; Kereiakes, Dean J; Bangalore, Sripal; Moses, Jeffrey W; Généreux, Philippe; Mehran, Roxana; Dangas, George D; Leon, Martin B; Stone, Gregg W

    2015-05-01

    Outcomes of percutaneous coronary intervention (PCI) versus medical therapy (MT) in the management of stable ischemic heart disease (SIHD) remain controversial, with some but not all studies showing improved results in patients with ischemia. We sought to elucidate whether PCI improves mortality compared to MT in patients with objective evidence of ischemia (assessed using noninvasive imaging or its invasive equivalent). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PCI to MT in patients with SIHD. To maintain a high degree of specificity for ischemia, studies were only included if ischemia was defined on the basis of noninvasive stress imaging or abnormal fractional flow reserve. The primary outcome was all-cause mortality. We identified 3 RCTs (Effects of Percutaneous Coronary Interventions in Silent Ischemia After Myocardial Infarction II, Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2, and a substudy of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial) enrolling a total of 1,557 patients followed for an average of 3.0 years. When compared with MT in this population of patients with objective ischemia, PCI was associated with lower mortality (hazard ratio 0.52, 95% confidence interval 0.30 to 0.92, p=0.02). There was no evidence of study heterogeneity or bias among included trials. In this meta-analysis of published RCTs, PCI was shown to have a mortality benefit over MT in patients with SIHD and objective assessment of ischemia using noninvasive imaging or its invasive equivalent. In conclusion, this study provides insight into the management of a higher-risk SIHD population that is the focus of the ongoing International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial.

  10. Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography

    SciTech Connect

    Mahmarian, J.J.; Pratt, C.M.; Cocanougher, M.K.; Verani, M.S. )

    1990-10-01

    The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia. The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia.

  11. Nitrative Thioredoxin Inactivation as a Cause of Enhanced Myocardial Ischemia/Reperfusion Injury in the Aging Heart

    PubMed Central

    Zhang, Hangxiang; Tao, Ling; Jiao, Xiangying; Gao, Erhe; Lopez, Bernard L.; Christopher, Theodore A.; Koch, Walter; Ma, Xin L.

    2007-01-01

    Objective Several recent studies have demonstrated that thioredoxin (Trx) is an important anti-apoptotic/cytoprotective molecule. The present study was designed to determine whether Trx activity is altered in the aging heart in a way that may contribute to increased susceptibility to myocardial ischemia/reperfusion (MI/R). Methods and Results Compared to young animals, MI/R-induced cardiomyocyte apoptosis and infarct size were increased in aging animals (P<0.01). Trx activity was decreased in the aging heart before MI/R, and this difference was further amplified after MI/R. Trx expression was moderately increased and Trx nitration, a post-translational modification that inhibits Trx activity, was increased in the aging heart. Moreover, Trx-ASK1 complex formation was reduced and activity of p38 MAPK was increased. Treatment with FP15 (a peroxynitrite decomposition catalyst) reduced Trx nitration, increased Trx activity, restored Trx-ASK1 interaction, reduced P38 MAPK activity, attenuated caspase 3 activation and reduced infarct size in aging animals (p<0.01). Conclusions Our results demonstrated that Trx activity is decreased in the aging heart by post-translational nitrative modification. Interventions that restore Trx activity in the aging heart may be novel therapies to attenuate MI/R injury in aging patients. PMID:17561092

  12. Relation between electrocardiographic and scintigraphic location of myocardial ischemia during exercise in one-vessel coronary artery disease

    SciTech Connect

    Fox, R.M.; Hakki, A.H.; Iskandrian, A.S.

    1984-06-01

    The purpose of this study was to determine the usefulness of exercise electrocardiography in predicting the site of myocardial ischemia. Fifty-two patients were studied who had angiographically documented 1-vessel coronary artery disease (CAD) and exercise-induced reversible thallium-201 perfusion defects. The patients were divided into 2 groups: group I (28 patients) had left anterior descending CAD and group II (24 patients) had left circumflex or right CAD. There were no significant differences between the 2 groups in severity of coronary stenosis, heart rate and systolic blood pressure during exercise. The size of the perfusion defect was larger in group I than II (28 +/- 12% vs 19 +/- 10%, p less than 0.02). There was no significant difference between the 2 groups in the frequency of ST depression in the anterior, inferior or lateral electrocardiographic leads. ST depression occurred in 16 patients (57%) in group I and 11 patients (46%) in group II (difference not significant). The sensitivity of the exercise electrocardiogram was 52% using 12 leads, 50% using 3 leads (V3, V5 and aVF) and 50% using V5 alone (difference not significant). Thus, the site of ST depression during exercise is not a good predictor of the site of exercise-induced perfusion defect or anatomic site of CAD. The use of 12 leads does not improve the sensitivity of exercise electrocardiography in patients with CAD.

  13. Functional benefits of PLGA particulates carrying VEGF and CoQ10 in an animal of myocardial ischemia.

    PubMed

    Simón-Yarza, Teresa; Tamayo, Esther; Benavides, Carolina; Lana, Hugo; Formiga, Fabio R; Grama, Charitra N; Ortiz-de-Solorzano, Carlos; Kumar, M N V Ravi; Prosper, Felipe; Blanco-Prieto, Maria J

    2013-10-01

    Myocardial ischemia (MI) remains one of the leading causes of death worldwide. Angiogenic therapy with the vascular endothelial growth factor (VEGF) is a promising strategy to overcome hypoxia and its consequences. However, from the clinical data it is clear that fulfillment of the potential of VEGF warrants a better delivery strategy. On the other hand, the compelling evidences of the role of oxidative stress in diseases like MI encourage the use of antioxidant agents. Coenzyme Q10 (CoQ10) due to its role in the electron transport chain in the mitochondria seems to be a good candidate to manage MI but is associated with poor biopharmaceutical properties seeking better delivery approaches. The female Sprague Dawley rats were induced MI and were followed up with VEGF microparticles intramyocardially and CoQ10 nanoparticles orally or their combination with appropriate controls. Cardiac function was assessed by measuring ejection fraction before and after three months of therapy. Results demonstrate significant improvement in the ejection fraction after three months with both treatment forms individually; however the combination therapy failed to offer any synergism. In conclusion, VEGF microparticles and CoQ10 nanoparticles can be considered as promising strategies for managing MI.

  14. Soy Isoflavone Protects Myocardial Ischemia/Reperfusion Injury through Increasing Endothelial Nitric Oxide Synthase and Decreasing Oxidative Stress in Ovariectomized Rats

    PubMed Central

    Tang, Yan; Li, Shuangyue; Zhang, Ping; Zhu, Jinbiao; Meng, Guoliang; Xie, Liping; Yu, Ying; Ji, Yong; Han, Yi

    2016-01-01

    There is a special role for estrogens in preventing and curing cardiovascular disease in women. Soy isoflavone (SI), a soy-derived phytoestrogen, has similar chemical structure to endogenous estrogen-estradiol. We investigate to elucidate the protective mechanism of SI on myocardial ischemia/reperfusion (MI/R) injury. Female SD rats underwent bilateral ovariectomy. One week later, rats were randomly divided into several groups, sham ovariectomy (control group), ovariectomy with MI/R, or ovariectomy with sham MI/R. Other ovariectomy rats were given different doses of SI or 17β-estradiol (E2). Four weeks later, they were exposed to 30 minutes of left coronary artery occlusion followed by 6 or 24 hours of reperfusion. SI administration significantly reduced myocardial infarct size and improved left ventricle function and restored endothelium-dependent relaxation function of thoracic aortas after MI/R in ovariectomized rats. SI also decreased serum creatine kinase and lactate dehydrogenase activity, reduced plasma malonaldehyde, and attenuated oxidative stress in the myocardium. Meanwhile, SI increased phosphatidylinositol 3 kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) signal pathway. SI failed to decrease infarct size of hearts with I/R in ovariectomized rats if PI3K was inhibited. Overall, these results indicated that SI protects myocardial ischemia/reperfusion injury in ovariectomized rats through increasing PI3K/Akt/eNOS signal pathway and decreasing oxidative stress. PMID:27057277

  15. A case of chronic hepatitis C patient of myocardial ischemia accompanied with interstitial pneumonia induced by pegylated interferon alpha-2a

    PubMed Central

    Qu, Caihong; Zheng, Zhenda; Liu, Weimin; Jiao, Ju; Zhu, Jieming

    2014-01-01

    After 3 months of combination treatment using interferon α-2a and Ribavirin, a case of 59-year-old female patient with chronic viral hepatitis C demonstrated symptoms such as headache, dizziness accompanied by nausea, vomiting, dry cough, breathing difficulty, and shortness of breath. Dynamic electrocardiogram showed occasional atrial premature beats, paroxysmal tachycardia, and abnormal ST-T (T wave inversion and prolongation of the QT interval). Ambulatory blood pressure indicated that mean blood pressure was elevated than before. Myocardial radionuclide scan showed focal myocardial ischemia in left ventricular inferior wall. Pulmonary function tests showed that pulmonary diffusion function was decreased, indicating the possibility of interstitial pneumonia. The patient had no history of coronary heart disease or chest X-ray abnormalities before medication, but had hypertensive medical history for 8 years with good blood pressure control. After withdrawal of antiviral drugs, symptoms such as dry cough, breathing difficulty and T wave inversion were gradually relieved. This case indicated that myocardial ischemia and pulmonary lesions were associated with the application of pegylated interferon α-2a. PMID:25197402

  16. Toward modeling of regional myocardial ischemia and infarction: generation of realistic coronary arterial tree for the heart model of the XCAT phantom

    NASA Astrophysics Data System (ADS)

    Fung, George S. K.; Segars, W. Paul; Veress, Alexander I.; Gullberg, Grant T.; Tsui, Benjamin M. W.

    2009-02-01

    A realistic 3D coronary arterial tree (CAT) has been developed for the heart model of the computer generated 3D XCAT phantom. The CAT allows generation of a realistic model of the location, size and shape of the associated regional ischemia or infarction for a given coronary arterial stenosis or occlusion. This in turn can be used in medical imaging applications. An iterative rule-based generation method that systematically utilized anatomic, morphometric and physiologic knowledge was used to construct a detailed realistic 3D model of the CAT in the XCAT phantom. The anatomic details of the myocardial surfaces and large coronary arterial vessel segments were first extracted from cardiac CT images of a normal patient with right coronary dominance. Morphometric information derived from porcine data from the literature, after being adjusted by scaling laws, provided statistically nominal diameters, lengths, and connectivity probabilities of the generated coronary arterial segments in modeling the CAT of an average human. The largest six orders of the CAT were generated based on the physiologic constraints defined in the coronary generation algorithms. When combined with the heart model of the XCAT phantom, the realistic CAT provides a unique simulation tool for the generation of realistic regional myocardial ischemia and infraction. Together with the existing heart model, the new CAT provides an important improvement over the current 3D XCAT phantom in providing a more realistic model of the normal heart and the potential to simulate myocardial diseases in evaluation of medical imaging instrumentation, image reconstruction, and data processing methods.

  17. Acute myocardial ischemia: magnetic resonance contrast enhancement with gadolinium-DTPA. [Dogs

    SciTech Connect

    McNamara, M.T.; Higgins, C.B.; Ehman, R.L.; Revel, D.; Sievers, R.; Brasch, R.C.

    1984-10-01

    Gadolinium-DTPA (Gd-DTPA) was used to improve the diagnostic utility of magnetic resonance (MR) in detecting early ischemia, before the onset of infarction. Following one minute of left anterior descending coronary artery occlusion, 9 dogs were intraveneously injected with either 0.5 mM/kg of Gd-DTPA (6 dogs) or normal saline (3 dogs). There was no visible difference in intensity or alterations in magnetic relaxation times between normal and ischemic myocardium in the control (saline-injected) animals. The Gd-DTPA-injected dogs had a well-defined segment of high intensity representing the ischemic myocardium in the anterior wall of the left ventricle. Both T1 and T2 were significantly shortened in the normal myocardium of the Gd-DTPA animals, but relatively greater T2 relaxation rate enhancement resulted in reduced intensity of normal myocardium, thus increasing contrast with ischemic myocardium. It is concluded that Gd-DTPA has the potential to expand the sensitivity and diagnostic utility of MR in the study of occlusive coronary artery disease.

  18. Study of T-wave morphology parameters based on Principal Components Analysis during acute myocardial ischemia

    NASA Astrophysics Data System (ADS)

    Baglivo, Fabricio Hugo; Arini, Pedro David

    2011-12-01

    Electrocardiographic repolarization abnormalities can be detected by Principal Components Analysis of the T-wave. In this work we studied the efect of signal averaging on the mean value and reproducibility of the ratio of the 2nd to the 1st eigenvalue of T-wave (T21W) and the absolute and relative T-wave residuum (TrelWR and TabsWR) in the ECG during ischemia induced by Percutaneous Coronary Intervention. Also, the intra-subject and inter-subject variability of T-wave parameters have been analyzed. Results showed that TrelWR and TabsWR evaluated from the average of 10 complexes had lower values and higher reproducibility than those obtained from 1 complex. On the other hand T21W calculated from 10 complexes did not show statistical diferences versus the T21W calculated on single beats. The results of this study corroborate that, with a signal averaging technique, the 2nd and the 1st eigenvalue are not afected by noise while the 4th to 8th eigenvalues are so much afected by this, suggesting the use of the signal averaged technique before calculation of absolute and relative T-wave residuum. Finally, we have shown that T-wave morphology parameters present high intra-subject stability.

  19. High Concordance Between Mental Stress–Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients: Hemodynamic and Biomarker Correlates

    PubMed Central

    Wawrzyniak, Andrew J.; Dilsizian, Vasken; Krantz, David S.; Harris, Kristie M.; Smith, Mark F.; Shankovich, Anthony; Whittaker, Kerry S.; Rodriguez, Gabriel A.; Gottdiener, John; Li, Shuying; Kop, Willem; Gottlieb, Stephen S.

    2016-01-01

    Mental stress can trigger myocardial ischemia, but the prevalence of mental stress–induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress–induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced left-ventricular function using SPECT to precisely quantify segment-level myocardial perfusion. Methods Thirty-four coronary artery disease patients (mean age ± SD, 62 ± 10 y) with CHF longer than 3 mo and ejection fraction less than 40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtraction of serial sevens. The presence and extent of myocardial ischemia was quantified using the conventional 17-segment model. Results Sixty-eight percent of patients had 1 ischemic segment or more during mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion with mental stress and adenosine were highly correlated. No significant differences were found between any 2 time points for B-type natriuretic peptide, tumor necrosis factor-α, IL-1b, troponin, vascular endothelin growth factor, IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after stress. Left-ventricular end diastolic dimension was 179 ± 65 mL at rest and increased to 217 ± 71 after mental stress and 229 ± 86 after adenosine (P < 0.01 for both). Resting end systolic volume was 129 ± 60 mL at rest and increased to 158 ± 66 after mental stress (P < 0.05) and 171 ± 87 after adenosine (P < 0.07), with no significant differences between adenosine and mental stress. Ejection fraction was 30 ± 12 at baseline, 29 ± 11 with mental stress, and 28 ± 10 with adenosine (P = not significant). Conclusion There was high concordance between ischemic perfusion defects induced

  20. Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

    PubMed

    Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

    2016-05-15

    Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function.

  1. Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

    PubMed

    Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

    2016-05-15

    Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. PMID:27055755

  2. Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

    PubMed Central

    Hanawa, Kenichiro; Ito, Kenta; Aizawa, Kentaro; Shindo, Tomohiko; Nishimiya, Kensuke; Hasebe, Yuhi; Tuburaya, Ryuji; Hasegawa, Hideyuki; Yasuda, Satoshi; Kanai, Hiroshi; Shimokawa, Hiroaki

    2014-01-01

    Background Although a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD. Methods and Results We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05), but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group. Conclusions These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD. PMID:25111309

  3. Dynamic CT myocardial perfusion imaging: detection of ischemia in a porcine model with FFR verification

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    Dynamic cardiac CT perfusion (CTP) is a high resolution, non-invasive technique for assessing myocardial blood ow (MBF), which in concert with coronary CT angiography enable CT to provide a unique, comprehensive, fast analysis of both coronary anatomy and functional ow. We assessed perfusion in a porcine model with and without coronary occlusion. To induce occlusion, each animal underwent left anterior descending (LAD) stent implantation and angioplasty balloon insertion. Normal ow condition was obtained with balloon completely de ated. Partial occlusion was induced by balloon in ation against the stent with FFR used to assess the extent of occlusion. Prospective ECG-triggered partial scan images were acquired at end systole (45% R-R) using a multi-detector CT (MDCT) scanner. Images were reconstructed using FBP and a hybrid iterative reconstruction (iDose4, Philips Healthcare). Processing included: beam hardening (BH) correction, registration of image volumes using 3D cubic B-spline normalized mutual-information, and spatio-temporal bilateral ltering to reduce partial scan artifacts and noise variation. Absolute blood ow was calculated with a deconvolutionbased approach using singular value decomposition (SVD). Arterial input function was estimated from the left ventricle (LV) cavity. Regions of interest (ROIs) were identi ed in healthy and ischemic myocardium and compared in normal and occluded conditions. Under-perfusion was detected in the correct LAD territory and ow reduction agreed well with FFR measurements. Flow was reduced, on average, in LAD territories by 54%.

  4. Metabolomic profiling reveals distinct patterns of myocardial substrate utilization in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia-reperfusion

    PubMed Central

    Turer, Aslan T.; Stevens, Robert D.; Bain, James R.; Muehlbauer, Michael J.; van der Westhuizen, Johannes; Mathew, Joseph P.; Schwinn, Debra A.; Glower, Donald D.; Newgard, Christopher B.; Podgoreanu, Mihai V.

    2009-01-01

    Background Human myocardial metabolism has been incompletely characterized in the setting of surgical cardioplegic arrest and ischemia/reperfusion. Furthermore, the effect of pre-existing ventricular state on ischemia-induced metabolic derangements has not been established. Methods and Results We applied a mass spectrometry-based platform to profile 63 intermediary metabolites in serial paired peripheral arterial and coronary sinus blood effluents obtained from 37 patients undergoing cardiac surgery, stratified by presence of coronary artery disease (CAD) and left ventricular dysfunction (LVD). The myocardium was a net user of a number of fuel substrates before ischemia, with significant differences between patients with or without CAD. Following reperfusion, there were significantly lower extraction ratios of most substrates and significant release of two specific acylcarnitine species, acetyl-carnitine and 3-hydroxybutyryl-carnitine. These changes were especially evident in patients with impaired ventricular function, who exhibited profound limitations in extraction of all forms of metabolic fuels. Principal component analysis highlighted several metabolic groupings as potentially important in post-operative clinical course. Conclusions The pre-existing ventricular state is associated with significant differences in myocardial fuel uptake at baseline and following I/R. The dysfunctional ventricle is associated with global suppression of metabolic fuel uptake, and limited myocardial metabolic reserve and flexibility following global I/R stress associated with cardiac surgery. Altered metabolic profiles following I/R are associated with post-operative hemodynamic course, and suggest a role for perioperative metabolic monitoring and targeted optimization in cardiac surgical patients. PMID:19307475

  5. The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone isolated from Millettia pulchra on myocardial ischemia in vitro and in vivo.

    PubMed

    Jian, Jie; Qing, Feizhang; Zhang, Shijun; Huang, Jianchun; Huang, Renbin

    2012-08-01

    The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone isolated from the roots of Millettia pulchra (Benth.) Kurz var. Laxior (Dunn) Z. Wei on rat myocardial ischemia has been investigated. An in vitro cardiocyte apoptosis model and an in vivo myocardial ischemia model were used to elucidate the mechanism of 17-methoxyl-7-hydroxy-benzene-furanchalcone. In contrast to hydrogen peroxide (H2O2, 100 µmol/L), 17-methoxyl-7-hydroxy-benzene-furanchalcone in vitro (255 and 510 µmol/L) increased the quantity of total superoxide dismutase and the protein expression of B cell lymphoma/leukemia-2, while it inhibited cardiocyte apoptosis, the release of malondialdehyde and tumor necrosis factor α, and protein expression of nuclear factor κ Bp65 and Bcl-2-associated X protein. Furthermore, pretreatment with MHBFC in vivo (10 and 20 mg/kg) decreased heart rate, systolic pressure, diastolic pressure, average pressure, left ventricular systolic pressure, the largest upstroke velocity of the left ventricular pressure (+ dp/dtmax), total antioxidative capability, myoglobin isoenzyme of creatine kinase, and inducible nitric oxide synthase, while it increased endothelial nitric oxide synthase, ATPases, left ventricular diastolic pressure, left ventricular end-diastolic pressure, the largest descendent velocity of the left ventricular pressure (-dp/dtmax) and the interval from the beginning of left ventricular contraction to +dp/dtmax (t - dp/dtmax), all in a dose-dependent manner. Our present results suggest that 17-methoxyl-7-hydroxy-benzene-furanchalcone is an attractive antimyocardial ischemia agent mostly because of its negative heart rate and negative inotropic effects, the reduction in myocardial oxidative damage, and the modulating expression of genes associated with apoptosis, which improves diastolic function. PMID:22700048

  6. Myocardial ischemia caused by paroxysmal supraventricular tachycardia in a patient with anomalous origin of right coronary artery arising from left sinus of valsalva.

    PubMed

    Song, Sang Hee; Suh, Seong Eun; Jin, Sun Mi; Moon, Jie Hye; Cho, Yun Kyung; Lim, Sang Wook

    2013-02-01

    Anomalous origin of a coronary artery is rare and does not generally lead to myocardial infarction and paroxysmal supraventricular tachycardia (PSVT). We report an uncommon case of anomalous origin of the right coronary artery (RCA) originating from the left sinus of Valsalva with PSVT and myocardial ischemia. A 58-year-old man presented with PSVT. After arrhythmia subsided, electrocardiogram showed ST and T wave abnormalities, and transient cardiac enzymes were found to be elevated. Coronary CT angiography confirmed that there was anomalous origin of the RCA originating from the left sinus of Valsalva and no intracoronary stenotic lesion. He was managed with conservative treatment, having no symptoms on clinical follow-up for 4 years.

  7. Intake of hot water-extracted apple protects against myocardial injury by inhibiting apoptosis in an ischemia/reperfusion rat model.

    PubMed

    Kim, Mi Young; Lim, Sun Ha; Lee, Jongwon

    2014-11-01

    Intakes of apple and its products are shown to reduce the risk of coronary heart disease by delaying occlusion of coronary arteries. In our previous study, we showed that apple pectin protected against myocardial injury by prohibiting apoptotic cascades in a rat model of ischemia/reperfusion. Thus, we hypothesized that water-extracted apple, into which apple pectin was released from the cell wall, might exhibit the same efficacy as apple pectin. To test this hypothesis, we fed rats either cold water- (400 mg kg(-1) d(-1)) or hot water-extracted apples (HWEA; 40, 100, and 400 mg kg(-1) d(-1)). Three days later, the rats were subjected to myocardial injuries by ligating the left anterior descending coronary artery (30 minutes), and subsequently, the heart (3 hours) reperfused by releasing the ligation. Only the rats that were supplemented with HWEA (400 mg kg(-1) d(-1)) showed significant reductions in infarct size, which was 28.5% smaller than that of the control group. This infarct size reduction could be partly attributed to the prevention of steps leading to apoptosis. These steps are manifested by a higher Bcl-2/Bax ratio, lower procaspase-3 conversion to caspase-3, and inhibition of DNA nick generation, which reflects the extent of apoptosis. The findings indicate that HWEA supplementation reduces myocardial injury by inhibiting apoptosis under ischemia/reperfusion conditions. In conclusion, this study suggests that apple intake, specifically boiled apple, might reduce the risk of coronary heart disease by inhibiting postocclusion steps, such as myocardial injury after artery occlusion, as well as preocclusion steps, such as atherosclerotic plaque formation. PMID:25304826

  8. Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway

    PubMed Central

    He, Fei; Xu, Bang-long; Chen, Cai; Jia, Hong-jing; Wu, Ji-xiong; Wang, Xiao-chen; Sheng, Jian-long; Huang, Li; Cheng, Jing

    2016-01-01

    Aim: The dried tuber root of Ophiopogon japonicus has been used in the traditional Chinese medicine for treatment of myocardial ischemia and thrombosis. In this study we investigated the effects of methylophiopogonanone A (MO-A), a major homoisoflavonoid in Ophiopogon japonicus, on myocardial ischemia/reperfusion (I/R) injury. Methods: Mice were pretreated with MO-A (10 mg·kg-1·d-1, po) for 2 weeks and then subjected to transient occlusion of the left anterior descending coronary artery. Cardiac function was evaluated, and the infarct size and apoptosis index were assessed. The mechanisms underlying the cardio-protection of MO-A were analyzed in H9C2 rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The cell viability and apoptosis were evaluated; apoptotic and relevant signaling proteins were analyzed. NO levels in the culture medium were assessed. Results: In I/R mice, pretreatment with MO-A significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function. In H9C2 cells subjected to H/R, pretreatment with MO-A (10 μmol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production. Furthermore, pretreatment with MO-A markedly increased the activation of PI3K/Akt/eNOS pathway in H9C2 cells subjected to H/R, and the protective effects of MO-A were abolished in the presence of the PI3K inhibitor wortmannin (100 nmol/L). Conclusion: MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway. PMID:27063216

  9. Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

    PubMed Central

    Issan, Yossi; Kornowski, Ran; Aravot, Dan; Shainberg, Asher; Laniado-Schwartzman, Michal; Sodhi, Komal; Abraham, Nader G.; Hochhauser, Edith

    2014-01-01

    Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by

  10. Comparison of Support-Vector Machine and Sparse Representation Using a Modified Rule-Based Method for Automated Myocardial Ischemia Detection

    PubMed Central

    Tseng, Yi-Li; Lin, Keng-Sheng; Jaw, Fu-Shan

    2016-01-01

    An automatic method is presented for detecting myocardial ischemia, which can be considered as the early symptom of acute coronary events. Myocardial ischemia commonly manifests as ST- and T-wave changes on ECG signals. The methods in this study are proposed to detect abnormal ECG beats using knowledge-based features and classification methods. A novel classification method, sparse representation-based classification (SRC), is involved to improve the performance of the existing algorithms. A comparison was made between two classification methods, SRC and support-vector machine (SVM), using rule-based vectors as input feature space. The two methods are proposed with quantitative evaluation to validate their performances. The results of SRC method encompassed with rule-based features demonstrate higher sensitivity than that of SVM. However, the specificity and precision are a trade-off. Moreover, SRC method is less dependent on the selection of rule-based features and can achieve high performance using fewer features. The overall performances of the two methods proposed in this study are better than the previous methods. PMID:26925158

  11. A New Biomarkers Feature Pattern Consisting of TNF- α , IL-10, and IL-8 for Blood Stasis Syndrome with Myocardial Ischemia.

    PubMed

    Guo, Shuzhen; Chen, Jianxin; Chuo, Wenjing; Liu, Lei; Feng, Xuanchao; Lian, Hongjian; Zheng, Lei; Wang, Yong; Xie, Hua; Luo, Liangtao; Zheng, Chenglong; Fu, Bangze; Wang, Wei

    2013-01-01

    Objective. To explore new diagnostic patterns for syndromes to overcome the insufficiency of obtainable macrocharacteristics and specific biomarkers. Methods. Chinese miniswines were subjected to Ameroid constrictor, placed around the proximal left anterior descending branch. On the 4th week, macrocharacteristics, coronary angiography, echocardiography, and hemorheology indices were detected for diagnosis. IL-1, IL-6, IL-8, IL-10, TNF- α , and hsCRP in serum were detected, and Decision Tree was built. Results. According to current official-issued standard, model animals matched the diagnosis of blood stasis syndrome with myocardial ischemia based on findings, including >90% occlusion, attenuated left ventricular segmental motion, dark red or purple tongues, and higher blood viscosity. Significant decrease of IL-10 and increase of TNF- α were found in model animals. However, in the Decision Tree, besides IL-10 and TNF- α , IL-8 helped to increase the accuracy of classification to 86%. Conclusions. The Decision Tree building with TNF- α , IL-10, and IL-8 is helpful for the diagnosis of blood stasis syndrome in myocardial ischemia animals. What is more is that our data set up a new path to the differentiation of syndrome by feature patterns consisting of multiple biomarkers not only for animals but also for patients. We believe that it will contribute to the standardization and international application of syndromes. PMID:24371451

  12. A New Biomarkers Feature Pattern Consisting of TNF-α, IL-10, and IL-8 for Blood Stasis Syndrome with Myocardial Ischemia

    PubMed Central

    Chen, Jianxin; Chuo, Wenjing; Liu, Lei; Lian, Hongjian; Zheng, Lei; Wang, Yong; Xie, Hua; Luo, Liangtao; Zheng, Chenglong; Fu, Bangze; Wang, Wei

    2013-01-01

    Objective. To explore new diagnostic patterns for syndromes to overcome the insufficiency of obtainable macrocharacteristics and specific biomarkers. Methods. Chinese miniswines were subjected to Ameroid constrictor, placed around the proximal left anterior descending branch. On the 4th week, macrocharacteristics, coronary angiography, echocardiography, and hemorheology indices were detected for diagnosis. IL-1, IL-6, IL-8, IL-10, TNF-α, and hsCRP in serum were detected, and Decision Tree was built. Results. According to current official-issued standard, model animals matched the diagnosis of blood stasis syndrome with myocardial ischemia based on findings, including >90% occlusion, attenuated left ventricular segmental motion, dark red or purple tongues, and higher blood viscosity. Significant decrease of IL-10 and increase of TNF-α were found in model animals. However, in the Decision Tree, besides IL-10 and TNF-α, IL-8 helped to increase the accuracy of classification to 86%. Conclusions. The Decision Tree building with TNF-α, IL-10, and IL-8 is helpful for the diagnosis of blood stasis syndrome in myocardial ischemia animals. What is more is that our data set up a new path to the differentiation of syndrome by feature patterns consisting of multiple biomarkers not only for animals but also for patients. We believe that it will contribute to the standardization and international application of syndromes. PMID:24371451

  13. Comparative analysis of the diagnostic and prognostic value of exercise ECG and thallium-201 scintigraphic markers of myocardial ischemia in asymptomatic and symptomatic patients

    SciTech Connect

    Gibson, R.S. )

    1989-08-01

    A considerable amount of data now exists that indicates that exercise ECG--due to its suboptimal sensitivity and specificity--has limited diagnostic and prognostic value in asymptomatic subjects, patients with chest pain of unclear etiology or those with chronic stable angina pectoris, and in patients recovering from acute myocardial infarction. Because of this and the well-recognized advantages of thallium-201 scintigraphy, there appears to be a strong rationale for recommending exercise perfusion imaging, rather than exercise ECG alone, as the preferred method for detecting CAD and staging its severity. This recommendation seems justified given the fact that (1) thallium-201 scintigraphy is far more sensitive and specific in detecting myocardial ischemia than exercise testing; (2) unlike stress ECG, thallium-201 scintigraphy can localize ischemia to a specific area of areas subtended by a specific coronary artery; and (3) thallium-201 scintigraphy has been shown to be more reliable to risk stratification of individual patients than exercise testing alone. The more optimal prognostic efficiency of thallium-201 scintigraphy is due, in part, to the fact that the error rate in falsely classifying patients as low-risk is substantially and significantly smaller with thallium-201 scintigraphy than with stress ECG. 52 references.

  14. Breathing Maneuvers as a Vasoactive Stimulus for Detecting Inducible Myocardial Ischemia – An Experimental Cardiovascular Magnetic Resonance Study

    PubMed Central

    Fischer, Kady; Guensch, Dominik P; Shie, Nancy; Lebel, Julie; Friedrich, Matthias G

    2016-01-01

    Background Breathing maneuvers can elicit a similar vascular response as vasodilatory agents like adenosine; yet, their potential diagnostic utility in the presence of coronary artery stenosis is unknown. The objective of the study is to investigate if breathing maneuvers can non-invasively detect inducible ischemia in an experimental animal model when the myocardium is imaged with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR). Methods and Findings In 11 anesthetised swine with experimentally induced significant stenosis (fractional flow reserve <0.75) of the left anterior descending coronary artery (LAD) and 9 control animals, OS-CMR at 3T was performed during two different breathing maneuvers, a long breath-hold; and a combined maneuver of 60s of hyperventilation followed by a long breath-hold. The resulting change of myocardial oxygenation was compared to the invasive measurements of coronary blood flow, blood gases, and oxygen extraction. In control animals, all breathing maneuvers could significantly alter coronary blood flow as hyperventilation decreased coronary blood flow by 34±23%. A long breath-hold alone led to an increase of 97±88%, while the increase was 346±327% (p<0.001), when the long breath-hold was performed after hyperventilation. In stenosis animals, the coronary blood flow response was attenuated after both hyperventilation and the following breath-hold. This was matched by the observed oxygenation response as breath-holds following hyperventilation consistently yielded a significant difference in the signal of the MRI images between the perfusion territory of the stenosis LAD and remote myocardium. There was no difference between the coronary territories during the other breathing maneuvers or in the control group at any point. Conclusion In an experimental animal model, the response to a combined breathing maneuver of hyperventilation with subsequent breath-holding is blunted in myocardium subject to significant coronary

  15. ZFP580, a Novel Zinc-Finger Transcription Factor, Is Involved in Cardioprotection of Intermittent High-Altitude Hypoxia against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Zhang, Wen-cheng; Wang, Tian-hui; Mai, Xia; Liu, Hong-tao; Xu, Rui-cheng

    2014-01-01

    Background ZFP580 is a novel C2H2 type zinc-finger transcription factor recently identified by our laboratory. We previously showed that ZFP580 may be involved in cell survival and growth. The aim of this study was to elucidate whether ZFP580 is involved in the cardioprotective effects of intermittent high-altitude (IHA) hypoxia against myocardial ischemia-reperfusion (I/R) injury. Methods and Results After rats were subjected to myocardial ischemia for 30 min followed by reperfusion, ZFP580 expression in the left ventricle was measured. ZFP580 protein expression was found to be up-regulated within 1 h and decreased at 2 h after reperfusion. Comparing normoxic and IHA hypoxia-adapted rats (5000 m, 6 h day−1, 6 weeks) following I/R injury (30 min ischemia and 2 h reperfusion), we found that adaptation to IHA hypoxia attenuated infarct size and plasma leakage of lactate dehydrogenase and creatine kinase-MB. In addition, ZFP580 expression in the myocardium was up-regulated by IHA hypoxia. Consistent with this result, ZFP580 expression was found to be significantly increased in cultured H9c2 myocardial cells in the hypoxic preconditioning group compared with those in the control group following simulated I/R injury (3 h simulated ischemic hypoxia and 2 h reoxygenation). To determine the role of ZFP580 in apoptosis, lentivirus-mediated gene transfection was performed in H9c2 cells 72 h prior to simulated I/R exposure. The results showed that ZFP580 overexpression significantly inhibited I/R-induced apoptosis and caspase-3 activation. H9c2 cells were pretreated with or without PD98059, an inhibitor of ERK1/2 phosphorylation, and Western blot results showed that PD98059 (10 µM) markedly suppressed I/R-induced up-regulation of ZFP580 expression. Conclusions Our findings demonstrate that the cardioprotective effect of IHA hypoxia against I/R injury is mediated via ZFP580, a downstream target of ERK1/2 signaling with anti-apoptotic roles in myocardial cells. PMID:24722354

  16. ECG-Based Detection of Early Myocardial Ischemia in a Computational Model: Impact of Additional Electrodes, Optimal Placement, and a New Feature for ST Deviation

    PubMed Central

    Loewe, Axel; Schulze, Walther H. W.; Jiang, Yuan; Wilhelms, Mathias; Luik, Armin; Dössel, Olaf; Seemann, Gunnar

    2015-01-01

    In case of chest pain, immediate diagnosis of myocardial ischemia is required to respond with an appropriate treatment. The diagnostic capability of the electrocardiogram (ECG), however, is strongly limited for ischemic events that do not lead to ST elevation. This computational study investigates the potential of different electrode setups in detecting early ischemia at 10 minutes after onset: standard 3-channel and 12-lead ECG as well as body surface potential maps (BSPMs). Further, it was assessed if an additional ECG electrode with optimized position or the right-sided Wilson leads can improve sensitivity of the standard 12-lead ECG. To this end, a simulation study was performed for 765 different locations and sizes of ischemia in the left ventricle. Improvements by adding a single, subject specifically optimized electrode were similar to those of the BSPM: 2–11% increased detection rate depending on the desired specificity. Adding right-sided Wilson leads had negligible effect. Absence of ST deviation could not be related to specific locations of the ischemic region or its transmurality. As alternative to the ST time integral as a feature of ST deviation, the K point deviation was introduced: the baseline deviation at the minimum of the ST-segment envelope signal, which increased 12-lead detection rate by 7% for a reasonable threshold. PMID:26587538

  17. ECG-Based Detection of Early Myocardial Ischemia in a Computational Model: Impact of Additional Electrodes, Optimal Placement, and a New Feature for ST Deviation.

    PubMed

    Loewe, Axel; Schulze, Walther H W; Jiang, Yuan; Wilhelms, Mathias; Luik, Armin; Dössel, Olaf; Seemann, Gunnar

    2015-01-01

    In case of chest pain, immediate diagnosis of myocardial ischemia is required to respond with an appropriate treatment. The diagnostic capability of the electrocardiogram (ECG), however, is strongly limited for ischemic events that do not lead to ST elevation. This computational study investigates the potential of different electrode setups in detecting early ischemia at 10 minutes after onset: standard 3-channel and 12-lead ECG as well as body surface potential maps (BSPMs). Further, it was assessed if an additional ECG electrode with optimized position or the right-sided Wilson leads can improve sensitivity of the standard 12-lead ECG. To this end, a simulation study was performed for 765 different locations and sizes of ischemia in the left ventricle. Improvements by adding a single, subject specifically optimized electrode were similar to those of the BSPM: 2-11% increased detection rate depending on the desired specificity. Adding right-sided Wilson leads had negligible effect. Absence of ST deviation could not be related to specific locations of the ischemic region or its transmurality. As alternative to the ST time integral as a feature of ST deviation, the K point deviation was introduced: the baseline deviation at the minimum of the ST-segment envelope signal, which increased 12-lead detection rate by 7% for a reasonable threshold.

  18. Protection against Myocardial Ischemia-Reperfusion Injury at Onset of Type 2 Diabetes in Zucker Diabetic Fatty Rats Is Associated with Altered Glucose Oxidation

    PubMed Central

    Povlsen, Jonas Agerlund; Løfgren, Bo; Dalgas, Christian; Birkler, Rune Isak Dupont; Johannsen, Mogens; Støttrup, Nicolaj Brejnholt; Bøtker, Hans Erik

    2013-01-01

    Background Inhibition of glucose oxidation during initial reperfusion confers protection against ischemia-reperfusion (IR) injury in the heart. Mitochondrial metabolism is altered with progression of type 2 diabetes (T2DM). We hypothesized that the metabolic alterations present at onset of T2DM induce cardioprotection by metabolic shutdown during IR, and that chronic alterations seen in late T2DM cause increased IR injury. Methods Isolated perfused hearts from 6 (prediabetic), 12 (onset of T2DM) and 24 (late T2DM) weeks old male Zucker diabetic fatty rats (ZDF) and their age-matched heterozygote controls were subjected to 40 min ischemia/120 min reperfusion. IR injury was assessed by TTC-staining. Myocardial glucose metabolism was evaluated by glucose tracer kinetics (glucose uptake-, glycolysis- and glucose oxidation rates), myocardial microdialysis (metabolomics) and tissue glycogen measurements. Results T2DM altered the development in sensitivity towards IR injury compared to controls. At late diabetes ZDF hearts suffered increased damage, while injury was decreased at onset of T2DM. Coincident with cardioprotection, oxidation of exogenous glucose was decreased during the initial and normalized after 5 minutes of reperfusion. Metabolomic analysis of citric acid cycle intermediates demonstrated that cardioprotection was associated with a reversible shutdown of mitochondrial glucose metabolism during ischemia and early reperfusion at onset of but not at late type 2 diabetes. Conclusions The metabolic alterations of type 2 diabetes are associated with protection against IR injury at onset but detrimental effects in late diabetes mellitus consistent with progressive dysfunction of glucose oxidation. These findings may explain the variable efficacy of cardioprotective interventions in individuals with type 2 diabetes. PMID:23704975

  19. Dissecting the Effects of Ischemia and Reperfusion on the Coronary Microcirculation in a Rat Model of Acute Myocardial Infarction

    PubMed Central

    Hollander, Maurits R.; de Waard, Guus A.; Konijnenberg, Lara S. F.; Meijer-van Putten, Rosalie M. E.; van den Brom, Charissa E.; Paauw, Nanne; de Vries, Helga E.; van de Ven, Peter M.; Aman, Jurjan; Van Nieuw-Amerongen, Geerten P.; Hordijk, Peter L.; Niessen, Hans W. M.; Horrevoets, Anton J. G.; Van Royen, Niels

    2016-01-01

    Background Microvascular injury (MVI) after coronary ischemia-reperfusion is associated with high morbidity and mortality. Both ischemia and reperfusion are involved in MVI, but to what degree these phases contribute is unknown. Understanding the etiology is essential for the development of new potential therapies. Methods and Findings Rats were divided into 3 groups receiving either 30 minutes ischemia, 90 minutes ischemia or 30 minutes ischemia followed by 60 minutes reperfusion. Subsequently hearts were ex-vivo perfused in a Langendorff-model. Fluorescence and electron microscopy was used for analysis of capillary density, vascular permeability and ultrastructure. Most MVI was observed after 30 minutes ischemia followed by 60 minutes reperfusion. In comparison to the 30’ and 90’ ischemia group, wall thickness decreased (207.0±74 vs 407.8±75 and 407.5±71, p = 0.02). Endothelial nuclei in the 30’-60’ group showed irreversible damage and decreased chromatin density variation (50.5±9.4, 35.4±7.1 and 23.7±3.8, p = 0.03). Cell junction density was lowest in the 30’-60’ group (0.15±0.02 vs 2.5±0.6 and 1.8±0.7, p<0.01). Microsphere extravasation was increased in both the 90’ ischemia and 30’-60’ group. Conclusions Ischemia alone for 90 minutes induces mild morphological changes to the coronary microcirculation, with increased vascular permeability. Ischemia for 30 minutes, followed by 60 minutes of reperfusion, induces massive MVI. This shows the direct consequences of reperfusion on the coronary microcirculation. These data imply that a therapeutic window exists to protect the microcirculation directly upon coronary revascularization. PMID:27391645

  20. Inhibition of cytochrome c release by 10-N-nonyl acridine orange, a cardiolipin-specific dye, during myocardial ischemia-reperfusion in the rat.

    PubMed

    Zhang, Guo-Xing; Kimura, Shoji; Murao, Koji; Obata, Koji; Matsuyoshi, Hiroko; Takaki, Miyako

    2010-02-01

    The release of cytochrome c from the mitochondria to the cytosol is a critical step for downstream caspase-mediated apoptotic signal transduction in ischemia-reperfusion (I/R)-induced myocardial tissue injury. 10-N-nonyl acridine orange (NAO), a cardiolipin-specific dye, has been shown to inhibit Bid-mediated cytochrome c release from isolated mitochondria in vitro; however, the possible protective effects of NAO and the mechanisms underlying the protection from myocardial I/R-induced tissue injury in a rat model are unknown. Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion. All rats received either vehicle or NAO (100 microg/kg iv) 10 min before the occlusion. The infarct size in the heart at 24 h after reperfusion was significantly reduced in NAO-treated rats compared with vehicle-treated rats. NAO treatment significantly reduced the cytosolic cytochrome c contents and caspase-9 activity in the ischemic region but did not affect caspase-8 activity. Furthermore, NAO treatment markedly suppressed the translocation of truncated Bid, a proapoptotic Bcl-2 family member, to the mitochondrial fraction. NAO also suppressed the mitochondrial swelling and oxygen uptake stimulated by calcium overload. The results suggest that NAO possesses protective effects against myocardial I/R injury, which may be due to the suppression of cytochrome c release through blockade of truncated Bid translocation to mitochondria and inhibition of the opening of mitochondrial permeability transition pores.

  1. Effects of KR-33028, a novel Na+/H+ exchanger-1 inhibitor, on ischemia and reperfusion-induced myocardial infarction in rats and dogs.

    PubMed

    Oh, Kwang-Seok; Seo, Ho Won; Yi, Kyu Yang; Lee, Sunkyung; Yoo, Sung-eun; Lee, Byung Ho

    2007-06-01

    The present study was performed to evaluate the cardioprotective effects of KR-33028, a novel Na+/H+ exchanger subtype 1 (NHE-1) inhibitor, in rat and dog models of coronary artery occlusion and reperfusion. In anesthetized rats subjected to a 45-min coronary occlusion and a 90-min reperfusion, KR-33028 at 5 min before occlusion (i.v. bolus) dose-dependently reduced myocardial infarct size from 58.0% to 46.6%, 40.3%, 39.7%, 33.1%, and 27.8% for 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg respectively (P < 0.05). In anesthetized beagle dogs that underwent a 1.0-h occlusion followed by a 3.0-h reperfusion, KR-33028 (3 mg/kg, i.v. bolus) markedly decreased infarct size from 45.6% in vehicle-treated group to 16.4% (P < 0.05), and reduced the reperfusion-induced release in creatine kinase myocardial band isoenzyme (MB), lactate dehydrogenase, troponin-I, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase. In separate experiments to assess the effects of timing of treatment, KR-33028 (1 mg/kg, i.v. bolus) given 10 min before or at reperfusion in rat models also significantly reduced the myocardial infarct size (46.3% and 44.1% respectively) compared with vehicle-treated group. In all studies, KR-33028 caused no significant changes in any hemodynamic profiles. In an isolated rat heart model of hypothermic cardioplegia, KR-33028 (30 mum), which was added to the heart preservation solution (histidin-tryptophan-ketoglutarate) during hypothermic cardioplegic arrest, significantly improved the recovery of left ventricular developed pressure, heart rate and dP/dt(max) after reperfusion. Taken together, these results indicate that KR-33028 significantly reduced the myocardial infarction induced by ischemia and reperfusion in rats and dogs, without affecting hemodynamic profiles.

  2. Myocardial ischemia due to a type IV dual LAD with the long LAD arising from the right sinus of valsalva: a case report and literature review.

    PubMed

    Gao, Xiangyu; Li, Hongwei; Chen, Hui

    2015-01-01

    We herein report the case of a 60-year-old man who presented with chest discomfort. Coronary angiography demonstrated that the short left anterior descending artery (LAD) arose from the left main coronary artery and the long LAD from the right coronary sinus of Valsalva, which was confirmed by 64-slice multidetector computed tomography coronary angiography. Single-photon emission computed tomography revealed a significant, almost irreversible degree of hypoperfusion in the anterior wall of the left ventricle, thus indicating that the short LAD was associated with myocardial ischemia and severe atherosclerotic lesions. Therefore, SPECT showed that the myocardium was largely necrotic, and we did not perform angioplasty for the short LAD. PMID:26466699

  3. The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades.

    PubMed

    Elshazly, Shimaa M; Abd El Motteleb, Dalia M; Nassar, Noha N

    2013-09-01

    Myocardial ischemia induces 5-lipoxygenase (LOX) translocation and leukotriene production in the heart. Leukotrienes increase inflammatory responses aggravating, thereby, ischemia-reperfusion (I/R) injury. This study aimed to investigate whether the selective 5-LOX inhibitor 11-keto-β-boswellic acid (11-keto BA), in three different dose levels, exert a protective effect on myocardial I/R injury in an in vivo rat heart model. Sixty male Wister rats were used in this study and divided into five equal groups (n=12): GP1, sham-operated receiving normal saline; Gp 2, rats were subjected to 45 min left anterior descending coronary artery ligation followed by 4 h reperfusion to serve as I/R group. Gps 3-5 received 11-keto BA in doses 250, 500, 1,000 mg/kg, respectively, via an oral gavage for 7 days then were exposed to I/R. I/R injury induced a significant elevation in myeloperoxidase activity and gene expression of intracellular adhesion molecules, cyclooxygenase-2, 5-lipooxygenasae, nuclear factor kappa-beta, tumor necrosis factor alpha, nuclear factor (erythroid-derived 2)-like 2, and hemeoxygenease-1 consequently with reduction in glutathione peroxidase in heart tissues. Furthermore, immunohistochemical examination of the heart tissues showed positive immuostaining for both 3-nitrotyrosine and caspase-3 with DNA-ladder formation in all diseased rats. 11-keto BA in three dose levels exerted dose dependent cardioprotective effect manifested by dose-dependent reduction in serum lactate dehydrogenase and infract size through mechanisms related to enhancement of antioxidant capacity and prevention of inflammatory cascades.

  4. Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair: a randomized, placebo-controlled, clinical trial.

    PubMed

    Gögenur, Ismail; Kücükakin, Bülent; Panduro Jensen, Leif; Reiter, Russel J; Rosenberg, Jacob

    2014-08-01

    The aim was to examine the effect of perioperative melatonin treatment on clinical cardiac morbidity and markers of myocardial ischemia in patients undergoing elective surgery for abdominal aortic aneurism. Reperfusion injury results in increased cardiac morbidity in patients undergoing surgery for abdominal aortic aneurisms (AAA). A randomized, placebo-controlled, clinical trial including patients undergoing surgery for AAA was performed. The patients received by infusion over a 2-hr period either, 50 mg melatonin or placebo intra-operatively, and 10 mg melatonin or placebo orally, the first three nights after surgery. Postoperative cardiac morbidity was registered, and blood samples for analysis of troponin-I (TpI) were collected preoperatively, and at 5 min, 6, 24, 48, 72, and 96 hr after clamp removal/recirculation of the first leg. Continuous measurement of ST-segment depression was performed by Holter monitoring. A total of 26 patients received melatonin, while 24 received placebo. A significant reduction in cardiac morbidity was seen in the melatonin-treated patients compared with those given placebo [4% versus 29% (P = 0.02)]. Five patients (19%) who received melatonin had increased TpI levels in the postoperative period compared with 12 patients (50%) who were given placebo (P = 0.036). The median number of ST-segment deviations was less in the melatonin-treated patients compared with the placebo group [median 1 (range 0-4) versus 6 (range 0-13) (P = 0.01)], but no differences were found in the duration of ST-segment deviations. Melatonin treatment in the perioperative period decreased clinical cardiac morbidity as well as the occurrence of myocardial ischemia after abdominal aortic aneurism repair. PMID:24708480

  5. Gastrodin Pretreatment Impact on Sarcoplasmic Reticulum Calcium Transport ATPase (SERCA) and Calcium Phosphate (PLB) Expression in Rats with Myocardial Ischemia Reperfusion

    PubMed Central

    Li, Yufen; Wang, Xiaomei; Lou, Changli

    2016-01-01

    Background Calcium overload, inflammation, and apoptosis play important roles in myocardial ischemia-reperfusion injury (MIRI). Gastrodin pretreatment can alleviate MIRI. This study observed sarcoplasmic reticulum calcium transport ATPase (Ca2+-ATPase, SERCA) and calcium phosphate (PLB) protein expression in the ventricular remodeling process after myocardial infarction to explore the effect of gastrodin pretreatment on MIRI. Material/Methods Healthy 7-week-old male SD rats were randomly divided into a sham group (A), a model group (B), and gastrodin pretreatment groups C, D, and E (100, 200, and 400 mg/kg, respectively) with 20 in each group. Anterior descending coronary artery ligation method was used to establish a rat MIRI model with 30-min ischemia and 120-min reperfusion. Cardiac electrophysiological activity was recorded. Serum IL-6 and IL10 levels were determined by ELISA. SERCA activity was tested by colorimetric phosphorus method. SERCA, PLB, and pSer-PLB protein expression were detected by Western blot. Results Compared with the sham group, IL-6 and IL-10 levels were elevated, SERCA2a expression was downregulated, and PLB protein was elevated in the model group (P<0.05). pSer16-PLB showed no significant difference among groups, and the ratio of pSer16-PLB/PLB obviously decreased (P<0.05). IL-6 level gradually declined and IL-10 increased in the gastrodin group following concentration elevation. SERCA 2a expression rose in the gastrodin group in a dose-dependent manner (P<0.05). Elevated PLB protein expression showed no significant difference, while pSer16-PLB protein increased (P<0.05), leading to elevated pSer16 PLB/PLB ratio (P<0.05). Conclusions Gastrodin pretreatment alleviates MIRI and inflammation injury by regulating SERCA and PLB expression to decrease calcium overload. PMID:27641420

  6. Gastrodin Pretreatment Impact on Sarcoplasmic Reticulum Calcium Transport ATPase (SERCA) and Calcium Phosphate (PLB) Expression in Rats with Myocardial Ischemia Reperfusion.

    PubMed

    Li, Yufen; Wang, Xiaomei; Lou, Changli

    2016-01-01

    BACKGROUND Calcium overload, inflammation, and apoptosis play important roles in myocardial ischemia-reperfusion injury (MIRI). Gastrodin pretreatment can alleviate MIRI. This study observed sarcoplasmic reticulum calcium transport ATPase (Ca2+-ATPase, SERCA) and calcium phosphate (PLB) protein expression in the ventricular remodeling process after myocardial infarction to explore the effect of gastrodin pretreatment on MIRI. MATERIAL AND METHODS Healthy 7-week-old male SD rats were randomly divided into a sham group (A), a model group (B), and gastrodin pretreatment groups C, D, and E (100, 200, and 400 mg/kg, respectively) with 20 in each group. Anterior descending coronary artery ligation method was used to establish a rat MIRI model with 30-min ischemia and 120-min reperfusion. Cardiac electrophysiological activity was recorded. Serum IL-6 and IL10 levels were determined by ELISA. SERCA activity was tested by colorimetric phosphorus method. SERCA, PLB, and pSer-PLB protein expression were detected by Western blot. RESULTS Compared with the sham group, IL-6 and IL-10 levels were elevated, SERCA2a expression was downregulated, and PLB protein was elevated in the model group (P<0.05). pSer16-PLB showed no significant difference among groups, and the ratio of pSer16-PLB/PLB obviously decreased (P<0.05). IL-6 level gradually declined and IL-10 increased in the gastrodin group following concentration elevation. SERCA 2a expression rose in the gastrodin group in a dose-dependent manner (P<0.05). Elevated PLB protein expression showed no significant difference, while pSer16-PLB protein increased (P<0.05), leading to elevated pSer16 PLB/PLB ratio (P<0.05). CONCLUSIONS Gastrodin pretreatment alleviates MIRI and inflammation injury by regulating SERCA and PLB expression to decrease calcium overload. PMID:27641420

  7. The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II.

    PubMed

    Kravchuk, Ekaterina; Grineva, Elena; Bairamov, Alekber; Galagudza, Michael; Vlasov, Timur

    2011-01-01

    In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM). Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P < .01), indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s) may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation.

  8. The Effect of Metformin on the Myocardial Tolerance to Ischemia-Reperfusion Injury in the Rat Model of Diabetes Mellitus Type II

    PubMed Central

    Kravchuk, Ekaterina; Grineva, Elena; Bairamov, Alekber; Galagudza, Michael; Vlasov, Timur

    2011-01-01

    In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM). Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P < .01), indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s) may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation. PMID:21754920

  9. Comparison of myocardial ischemia during intense mental stress using flight simulation in airline pilots with coronary artery disease to that produced with conventional mental and treadmill exercise stress testing.

    PubMed

    Doorey, Andrew; Denenberg, Barry; Sagar, Vidya; Hanna, Tracy; Newman, Jack; Stone, Peter H

    2011-09-01

    Mental stress increases cardiovascular morbidity and mortality. Although laboratory mental stress often causes less myocardial ischemia than exercise stress (ES), it is unclear whether mental stress is intrinsically different or differences are due to less hemodynamic stress with mental stress. We sought to evaluate the hemodynamic and ischemic response to intense realistic mental stress created by modern flight simulators and compare this response to that of exercise treadmill testing and conventional laboratory mental stress (CMS) testing in pilots with coronary disease. Sixteen airline pilots with angiographically documented coronary disease and documented myocardial ischemia during ES were studied using maximal treadmill ES, CMS, and aviation mental stress (AMS) testing. AMS testing was done in a sophisticated simulator using multiple system failures as stressors. Treadmill ES testing resulted in the highest heart rate, but AMS caused a higher blood pressure response than CMS. Maximal rate-pressure product was not significantly different between ES and AMS (25,646 vs 23,347, p = 0.08), although these were higher than CMS (16,336, p <0.0001). Despite similar hemodynamic stress induced by ES and AMS, AMS resulted in significantly less ST-segment depression and nuclear ischemia than ES. Differences in induction of ischemia by mental stress compared to ES do not appear to be due to the creation of less hemodynamic stress. In conclusion, even with equivalent hemodynamic stress, intense realistic mental stress induced by flight simulators results in significantly less myocardial ischemia than ES as measured by ST-segment depression and nuclear ischemia.

  10. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.

    PubMed

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-11-12

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  11. Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats

    PubMed Central

    Lu, Xin; Bi, Yan-Wen; Chen, Ke-Biao

    2015-01-01

    OBJECTIVES: Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning. METHODS: Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF–1α mRNA expression, miR-21 expression and miR-210 expression were measured. RESULTS: Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF–1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. CONCLUSION: The results indicate that 1 the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; 2 chronic treatment with Olmesartan down-regulates HIF–1α, miR-21 and miR-210 expression and

  12. Can areas of myocardial ischemia be localized by the exercise electrocardiogram. A correlative study with thallium-201 scintigraphy

    SciTech Connect

    Abouantoun, S.; Ahnve, S.; Savvides, M.; Witztum, K.; Jensen, D.; Froelicher, V.

    1984-10-01

    In order to determine whether areas of ischemia identified by thallium-201 scintigraphy could be localized by exercise ECG, we studied 54 patients with stable coronary heart disease. All 54 patients had exercise-induced thallium-201 scintigraphic defects. Their exercise ECG test results were compared to their thallium-201 images and also to 14 low-risk normal subjects. Exercise data were analyzed for spatial ST vector shifts, using a computer program in order to most accurately classify ST segment depression and elevation. Thallium-201 ischemic defects detected in our patients included areas in the septum and the inferior, lateral, and anterior walls. Twenty-six of these 54 patients also had coronary angiography for classification and comparison as having either localized or generalized disease. None of the scintigraphic ischemic sites or angiographic diseased areas could be specifically identified by exercise-induced ST vector shifts. Therefore, the surface exercise ECG has limitations in localizing ischemia to specific areas of the myocardium.

  13. Assessment of the (/sup 18/F) fluorodeoxyglucose kinetic model in calculations of myocardial glucose metabolism during ischemia. [Rabbits

    SciTech Connect

    Marshall, R.C.; Huang, S.C.; Nash, W.W.; Phelps, M.E.

    1983-11-01

    The lumped constant - a term in the operational equation of the Sokoloff tracer kinetic model for deoxyglucose that accounts for the difference in transport and phosphorylation between glucose and its analog, deoxyglucose - could potentially vary from normal to ischemic conditions in the heart. To test the stability of the lumped constant during ischemia, the authors evaluated the ratio of the extraction fraction for (F-18)-fluorodeoxyglucose (FDG) to that for glucose(a measure of the lumped constant if there is no significant dephosphorylation of FDG-6-PO/sub 4/) and the rate constant for dephosphorylation of FDG-6-/sub 4/(k/sub 4/) in the isolated, arterially perfused interventricular septum of the rabbit during moderate and severe demand-induced and reduced-flow ischemias. The lumped constant and k/sub 4/* in each of the four ischemic experimental conditions were found not to be significantly different from the value obtained from the nonischemic controls.

  14. Combined 1,25-Dihydroxy-vitamin D and Resveratrol: A Novel Therapeutic Approach to Ameliorate Ischemia Reperfusion-Induced Myocardial Injury.

    PubMed

    Safari, Fatemeh; Zarei, Farideh; Shekarforoush, Shahnaz; Fekri, Asefeh; Klishadi, Mohsen Sharifi; Hekmatimoghaddam, Seyedhossein

    2015-01-01

    The aim of this study was to assess the effect of combined 1,25-dihydroxyvitamin D (1,25 D) and resveratrol on cardiac arrhythmias, infarct size, and transcription of catalase, thioredoxin-1 and B-cell lymphoma 2 (Bcl-2), following myocardial ischemia-reperfusion (IR) in male rats. Ligation of coronary artery was performed in rats (n = 6 per group) without any treatment (IR group), pretreated with 0.1 μg/kg/day of 1,25 D (1,25 D + IR), 1 mg/kg/day of resveratrol (Res + IR) or a combination (1,25 D + Res + IR) for 14 days. Arrhythmias were analyzed according to the Lambeth conventions, and infarct size was measured by 2,3,5-triphenyl-2H-tetrazolium chloride staining. Expression of prosurvival genes was evaluated by real-time polymerase chain reaction. In the 1,25 D + Res + IR group the mean infarct size was 17.6 ± 3.5 %, which was significantly less than that in the IR, 1,25 D + IR, and Res + IR groups (p < 0.001). Although the single therapy of either 1,25 D or resveratrol did not change the incidence of arrhythmias significantly, a reduction in the number of ventricular ectopic beats was noted in group 1,25 D + Res + IR (179.19 ± 58.87, p < 0.001 vs IR; p < 0.05 vs Res + IR; p < 0.01 vs Vit D + IR). Combination of 1,25 D and resveratrol increased transcription of catalase by 119 ± 37 % (p < 0.001 vs IR, p < 0.01 vs Res + IR, p < 0.001 vs 1,25 D + IR). Our study showed that combination of a non-hypotensive dose of 1,25 D and resveratrol can be a novel and effective strategy for protecting against ischemia. PMID:26780396

  15. Effects of dexmedetomidine postconditioning on myocardial ischemia and the role of the PI3K/Akt-dependent signaling pathway in reperfusion injury

    PubMed Central

    CHENG, XIANG YANG; GU, XIAO YU; GAO, QIN; ZONG, QIAO FENG; LI, XIAO HONG; ZHANG, YE

    2016-01-01

    The present study aimed to determine whether post-ischemic treatment with dexmedetomidine (DEX) protected the heart against acute myocardial ischemia/reperfusion (I/R)-induced injury in rats. The phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)-dependent signaling pathway was also investigated. Male Sprague Dawley rats (n=64) were subjected to ligation of the left anterior descending artery (LAD), which produced ischemia for 25 min, followed by reperfusion. Following LAD ligation, rats were treated with DEX (5, 10 and 20 µg/kg) or underwent post-ischemic conditioning, which included three cycles of ischemic insult. In order to determine the role of the PI3K/Akt signaling pathway, wortmannin (Wort), a PI3K inhibitor, was used to treat a group of rats that had also been treated with DEX (20 µg/kg). Post-reperfusion, lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzymes (CK-MB), superoxide dismutase (SOD) and malondialdehyde (MDA) serum levels were measured using an ultraviolet spectrophotometer. The protein expression levels of phosphorylated (p)-Akt, Ser9-p-glycogen synthase kinase-3β (p-GSK-3β) and cleaved caspase-3 were detected in heart tissue by western blotting. The mRNA expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected using reverse transcription-polymerase chain reaction. At the end of the experiment, the hearts were removed and perfused in an isolated perfusion heart apparatus with Evans blue (1%) in order to determine the non-ischemic areas. The risk and infarct areas of the heart were not dyed. As expected, I/R induced myocardial infarction, as determined by the increased serum levels of cTnI, CK-MB and MDA, and the decreased levels of SOD. Post-ischemic treatment with DEX increased the expression levels of p-Akt and p-GSK-3β, whereas caspase-3 expression was reduced following DEX treatment compared with in the I/R group. Compared with the I/R group, the ratio of Bcl

  16. Contrast echocardiography in acute myocardial ischemia. III. An in vivo comparison of the extent of abnormal wall motion with the area at risk for necrosis.

    PubMed

    Kaul, S; Pandian, N G; Gillam, L D; Newell, J B; Okada, R D; Weyman, A E

    1986-02-01

    To define the in vivo relation between abnormal wall motion and the area at risk for necrosis after acute coronary occlusion, 11 open chest dogs were studied. Five dogs underwent left anterior descending coronary artery occlusion and six underwent left circumflex artery occlusion. Area at risk was defined at five short-axis levels (mitral valve, chordal, high and low papillary muscle and apex) using myocardial contrast echocardiography. Wall motion was measured in the cycles preceding injection of contrast medium. Two observers used two different methods to measure wall motion. In method A, end-diastolic to end-systolic fractional radial change for each of 32 endocardial targets was determined. The extent of abnormal wall motion was then calculated using three definitions of wall motion abnormality: akinesia/dyskinesia, fractional inward endocardial excursion of less than 10%, and fractional inward endocardial excursion of less than 20%. In method B, the information from the entire systolic contraction sequence was analyzed and correlated with a normal contraction pattern. The best linear correlation between area at risk (AR) and abnormal wall motion (AWM) was achieved using method B and expressed by the following linear regression: AWM = 0.92 AR + 3.0 (r = 0.92, p less than 0.0001, SEE = 1.7%). Of the three definitions of abnormality used in method A, the best correlation was achieved between area at risk and less than 10% inward endocardial excursion and was expressed by the following polynomial regression: AWM = -0.01 AR2 + 1.5 AR -0.14 (r = 0.92, p less than 0.001, SEE = 1.7%). These data demonstrate that there is a definite relation between area at risk and abnormal wall motion but that this relation varies depending on the method used to analyze wall motion. However, wall motion during acute ischemia is also influenced by the loading conditions of the heart. Because these may vary in a manner that is independent of the ischemic process, measurement of both

  17. MicroRNA-128 inhibition attenuates myocardial ischemia/reperfusion injury-induced cardiomyocyte apoptosis by the targeted activation of peroxisome proliferator-activated receptor gamma

    PubMed Central

    ZENG, XIAO CONG; LI, LANG; WEN, HONG; BI, QI

    2016-01-01

    The aim of the present study was to investigate the effects of microRNA (miR)-128 inhibition on the targeted activation of peroxisome proliferator-activated receptor gamma (PPARG) and on cardiomyocyte apoptosis induced by myocardial ischemia/reperfusion (I/R) injury. In vitro, the expression of PPARG was detected by reverse transcription-quantitative polymerase chain reaction and western blotting in neonatal rat ventricular myocytes (NRVMs) and HEK293 cells transfected with the mimics or inhibitors of miR-128 or control RNA. Luciferase reporter assays were used to identify whether PPARG is a direct target of miR-128. In vivo, miR-128 was knocked down via ear vein injection of antagomir-128 in a rabbit myocardial I/R injury model. Western blotting investigated the activation of Akt [phosphorylated (p)-Akt] and the expression of total-Akt, PPARG and myeloid leukemia cell differentiation protein-1 (Mcl-1) in the myocardium. Cardiomyocyte apoptosis was examined with transmission electron microscropy and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. PPARG mRNA and protein were downregulated in NRVMs transfected with miR-128 mimics, but upregulated by antagomir-128 compared with control. This indicates that PPARG is a direct miR-128 target. Activation of Akt (p-Akt), Mcl-1 and PPARG expression in the myocardium were increased by miR-128 inhibition. Furthermore, miR-128 antagomirs significantly reduced apoptosis in hearts subjected to I/R injury, which was blocked by the PPARG inhibitor GW9662. In conclusion, miR-128 inhibition attenuated I/R injury-induced cardiomyocyte apoptosis by the targeted activation of PPARG signaling. PMID:27150726

  18. The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone on NF-κB and the inflammatory response during myocardial ischemia reperfusion injury in rats.

    PubMed

    Liang, Xingmei; Huang, Jianchun; Lin, Xing; Qin, Feizhang; Wen, Qingwei; Chen, Chunxia; Li, Yingxin; Ge, Wenyi; Huang, Renbin

    2014-01-01

    The aim of this study was to investigate the effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) on nuclear factor-kappa-binding (NF-κB) and the inflammatory response in rats with myocardial ischemia reperfusion injury (MI/RI). Sprague-Dawley rats were randomly divided into 7 groups, and the rat MI/RI model was established by the ligation of the left anterior descending for 30 minutes followed by ligation release for 1 hour. Areas of myocardial infarction were measured using Evans blue-2,3,5-Triphenyltetrazolium chloride (TTC) staining. Levels of malondialdehyde, glutathione peroxidase, and total superoxide dismutase were assessed. Release of interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) was measured by means of an enzyme-linked immunosorbent assay. NF-κBp65 and intercellular adhesion molecule-1 protein expression and caspase-3 and adenine nucleotide translocator-1 messenger RNA expression were evaluated by immunohistochemistry and reverse transcription polymerase chain reaction, respectively. Pretreatment with MHBFC decreased the infarction areas, the malondialdehyde, IL-1β and IL-6 levels, the expression of caspase-3, NF-κBp65, and intercellular adhesion molecule-1. Further, MHBFC increased total superoxide dismutase and glutathione peroxidase activities, the release of IL-10, and the expression of adenine nucleotide translocator-1 messenger RNA compared with the results of the model group. The experiment showed that MHBFC protected the heart against MI/RI possibly by reducing lipid peroxidation damage while inhibiting the activity of NF-κBp65 and the inflammatory response. PMID:24126566

  19. Effects of nitroglycerin and propranolol on the distribution of transmural myocardial blood flow during ischemia in the absence of hemodynamic changes in the unanesthetized dog.

    PubMed

    Swain, J L; Parker, J P; McHale, P A; Greenfield, J C

    1979-05-01

    Chronically instrumented awake dogs were used to study the effects of nitroglycerin and propranolol on the transmural distribution of myocardial blood flow during transient ischemia. Studies were carried out 7-14 d after implantation of an electromagnetic flowmeter probe and balloon occluder on the left circumflex coronary artery, placement of epicardial minor axis sonar crystals, and implantation of left atrial, left ventricular, and aortic catheters. The occluder was inflated to completely interrupt flow for 10 s followed by partial release to reestablish flow at 60% of the preocclusion level. During this partial release, which served as the control for the study, regional myocardial blood flow was measured with 7- to 10-mum radioactive microspheres. After control measurements, seven dogs were given nitroglycerin (0.4 mg i.v.) and eight dogs propranolol (0.2 mg/kg i.v.). 5 min later the occlusion and partial release sequence was repeated, and regional myocardial blood flow was measured when heart rate, aortic and left ventricular end-diastolic pressure, and minor axis diameter were unchanged from control values.The data values were selected so that total flow to the ischemic region during partial release after nitroglycerin or propranolol administration was not significantly different from flow during the control partial release. After nitroglycerin administration, endocardial flow (endo) in the ischemic region increased from 0.46+/-0.07 to 0.59+/-0.06 ml/min per g (P < 0.006); epicardial flow (epi) decreased from 0.78+/-0.09 to 0.70+/-0.08 ml/min per g (P < 0.04). The endo:epi ratio increased from 0.65+/-0.07 to 0.92+/-0.10 (P < 0.05). In contrast, administration of propranolol produced no significant change in transmural flow (endo, 0.42+/-0.02 and 0.46+/-0.03 ml/min per g; epi, 0.71+/-0.06 and 0.70+/-0.07 ml/min per g) or in the endo:epi ratio (0.60+/-0.03, 0.66+/-0.06) in the ischemic region. Nitroglycerin and propranolol produce different effects on the

  20. Maladaptive Modulations of NLRP3 Inflammasome and Cardioprotective Pathways Are Involved in Diet-Induced Exacerbation of Myocardial Ischemia/Reperfusion Injury in Mice

    PubMed Central

    Penna, Claudia; Nigro, Debora; Chiazza, Fausto; Fracasso, Veronica; Tullio, Francesca; Aragno, Manuela

    2016-01-01

    Excessive fatty acids and sugars intake is known to affect the development of cardiovascular diseases, including myocardial infarction. However, the underlying mechanisms are ill defined. Here we investigated the balance between prosurvival and detrimental pathways within the heart of C57Bl/6 male mice fed a standard diet (SD) or a high-fat high-fructose diet (HFHF) for 12 weeks and exposed to cardiac ex vivo ischemia/reperfusion (IR) injury. Dietary manipulation evokes a maladaptive response in heart mice, as demonstrated by the shift of myosin heavy chain isoform content from α to β, the increased expression of the Nlrp3 inflammasome and markers of oxidative metabolism, and the downregulation of the hypoxia inducible factor- (HIF-)2α and members of the Reperfusion Injury Salvage Kinases (RISK) pathway. When exposed to IR, HFHF mice hearts showed greater infarct size and lactic dehydrogenase release in comparison with SD mice. These effects were associated with an exacerbated overexpression of Nlrp3 inflammasome, resulting in marked caspase-1 activation and a compromised activation of the cardioprotective RISK/HIF-2α pathways. The common mechanisms of damage here reported lead to a better understanding of the cross-talk among prosurvival and detrimental pathways leading to the development of cardiovascular disorders associated with metabolic diseases. PMID:26788246

  1. HIF-1α may provide only short-term protection against ischemia-reperfusion injury in Sprague-Dawley myocardial cultures

    PubMed Central

    WANG, SIYANG; SHAO, XIN; LI, XIAOXUE; SU, XIAOJUAN; HUO, YONGXU; YANG, CHUNLEI

    2016-01-01

    Hypoxia-inducible factor-1 (HIF-1α) exerts an important role in protecting against cardiac tissue damage, for example, following ischemia-reperfusion (I/R), although the time frame during which it acts has yet to be fully elucidated. In the present study, a culture model of myocardial cells from Sprague-Dawley rats was used to examine the expression levels of HIF-1α and various downstream effectors at different times following I/R. The levels of HIF-1α were manipulated by overexpressing HIF-1α prior to I/R. HIF-1α levels peaked at 6 h following I/R, subsequently decreasing to low levels. The levels of downstream effectors peaked at 48 h, and decreased almost to pre-I/R levels by 72 h. These results suggest that HIF-1α and its downstream targets offer only short-term protection following I/R. These results may have implications for the treatment of I/R-associated injury in a variety of clinical contexts. PMID:27073667

  2. Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201

    SciTech Connect

    Sinusas, A.J.; Watson, D.D.; Cannon, J.M. Jr.; Beller, G.A. )

    1989-12-01

    The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two-dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations.

  3. [Sudden cardiac death: the possible role of latent myocardial ischemia in the mechanisms of its formation and development].

    PubMed

    Bobrov, V O; Bilonozhko, O H; Stepanenko, A P; Zotov, S Iu; Mymrenko, S M; Zinchenko, Iu V; Osos, I P; Verezhnykova, H P; Dolzhenko, M M; Lohvynenko, A O

    2000-01-01

    An analysis was performed of comprehensive (non-invasive and invasive) observations of IHD patients presenting with atherosclerotic lesions of coronary arteries of the heart and atypical clinical picture of the condition. A possibility was shown of a significant obstruction of arteries of the heart in atypical localization of pain and in those patients who had not derived much benefit from nitroglycerin during the development of ischemia and measures instituted against it. Inadequate reaction to nitroglycerin may be explained by specificities of changes in the vegetative nervous system, by the hemodynamics reaction, and, in the first place, by a propensity for developing tachycardia under physical loading, emotional stress, and after ingestion of nitroglycerin. PMID:10878965

  4. Screening β1AR inhibitors by cell membrane chromatography and offline UPLC/MS method for protecting myocardial ischemia.

    PubMed

    Yue, Yuan; Dou, Lili; Wang, Xin; Xue, Hui; Song, Yanhong; Li, Xiaoni

    2015-11-10

    A high expression β1AR/cell membrane chromatography (β1AR-CMC) and offline UPLC/MS method has been developed for screening active ingredients from Coptis chinensis. In this study, the fractions retained by CMC column were separated and identified by UPLC/MS system. Using metoprolol as a positive control drug, coptisine from C. chinensis was identified as the active component which could inhibit β1AR. Compared with the control group: coptisine could attenuate the infarct size and release malondialdehyde (MDA) while increasing superoxide dismutase (SOD) activity, suggesting a role in reducing myocardial injury. In vitro, coptisine could decrease apoptosis, showing their protective effects upon cardiomyocytes. This β1AR-CMC-offline-UPLC/MS method can be applied for screening active components acting on β1AR from traditional Chinese medicines. PMID:26263062

  5. Ambient Fine Particulate Matter Exposure and Myocardial Ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI) Study

    PubMed Central

    Zhang, Zhu-ming; Whitsel, Eric A.; Quibrera, P. Miguel; Smith, Richard L.; Liao, Duanping; Anderson, Garnet L.; Prineas, Ronald J.

    2009-01-01

    Background Ambient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated. Methods We studied the association between PM and ischemia among 57,908 Women’s Health Initiative clinical trial participants from 1999–2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency’s monitor data to estimate concentrations of PM < 2.5 μm (PM2.5) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration ≥ 120 msec. Results Overall, 6% of the remaining 55,529 women (52–90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from −14 to 349 μV). PM2.5 (mean ± SD) averaged over lag0–2 was 14 ± 7 μg/m3. In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-μg/m3 increase in lag0–2 PM2.5 was associated with a 4% [95% confidence interval (CI), −3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of −2 μV (95% CI, −5 to 0 μV) in lead V3. Conclusions Short-term PM2.5 exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST–T abnormalities and decreases in T amplitude. PMID:19479017

  6. Interaction of MIF Family Proteins in Myocardial Ischemia/Reperfusion Damage and Their Influence on Clinical Outcome of Cardiac Surgery Patients

    PubMed Central

    Rex, Steffen; Goetzenich, Andreas; Kraemer, Sandra; Emontzpohl, Christoph; Soppert, Josefin; Averdunk, Luisa; Sun, Yu; Rossaint, Rolf; Lue, Hongqi; Huang, Caleb; Song, Yan; Pantouris, Georgios; Lolis, Elias; Leng, Lin; Schulte, Wibke; Bucala, Richard; Weber, Christian

    2015-01-01

    Abstract Aims: Cardiac surgery involves myocardial ischemia/reperfusion (I/R) with potentially deleterious consequences. Macrophage migration inhibitory factor (MIF) is a stress-regulating chemokine-like cytokine that protects against I/R damage, but functional links with its homolog, d-dopachrome tautomerase (MIF-2), and the circulating soluble receptor CD74 (sCD74) are unknown. In this study, we investigate the role of MIF, MIF-2, sCD74, and MIF genotypes in patients scheduled for elective single or complex surgical procedures such as coronary artery bypass grafting or valve replacement. Results: MIF and MIF-2 levels significantly increased intraoperatively, whereas measured sCD74 decreased correspondingly. Circulating sCD74/MIF complexes were detectable in 50% of patients and enhanced MIF antioxidant activity. Intraoperative MIF levels were independently associated with a reduced risk for the development of atrial fibrillation (AF) (odds ratio 0.99 [0.98–1.00]; p=0.007). Circulating levels of MIF-2, but not MIF, were associated with an increased frequency of organ dysfunction and predicted the occurrence of AF (area under the curve [AUC]=0.663; p=0.041) and pneumonia (AUC=0.708; p=0.040). Patients with a high-expression MIF genotype exhibited a reduced incidence of organ dysfunction compared with patients with low-expression MIF genotypes (3 vs. 25; p=0.042). Innovation: The current study comprehensively highlights the kinetics and clinical relevance of MIF family proteins and the MIF genotype in cardiac surgery patients. Conclusion: Our findings suggest that increased MIF levels during cardiac surgery feature organ-protective properties during myocardial I/R, while the soluble MIF receptor, sCD74, may enhance MIF antioxidant activity. In contrast, high MIF-2 levels are predictive of the development of organ dysfunction. Importantly, we provide first evidence for a gene–phenotype relationship between variant MIF alleles and clinical outcome in cardiac

  7. [Elective coronary angioplasty in recurrent ischemia after successful fibrinolysis in myocardial infarction. Comparison with results of angioplasty in the acute phase].

    PubMed

    Castillo, J A; Iñíguez, A; Macaya, C

    1992-01-01

    To assess the initial and long-term results of 149 percutaneous transluminal coronary angioplasty (PTCA) procedures performed within 1 month of an acute myocardial infarction (AMI), 83 of them because of recurrent ischemia (post-infarction angina) after thrombolytic therapy with initial reperfusion success in the AMI (100 lesions attempted) (group I) and 66 PTCAs (69 lesions) performed during the acute phase of the AMI (group II). Mean age was 56 +/- 14 and 127 (85%) patients were male. Although successful dilation was obtained in 151 (89%) of the 169 attempted lesions, (96[96%] in group I vs 55[78%] in group II), clinical success was obtained in only 123 (82%) (76[92%] vs 64[77%] in both groups, respectively). Late occlusion occurred in 14 (9%) of the 151 lesions successfully dilated (6[6%] and 8[15%], respectively) and reinfarction was documented in 7 (5%) patients (5[5%] and 2[3%]). One patient in group I underwent coronary bypass surgery. There were 4 (3%) hospital deaths (1[1%] and 3[4%]) in group I and II, respectively). Event-free (no occurrence of death, AMI, coronary surgery, repeat PTCA or angina recurrence) survival rate was 76%, 73% and 67% in group I versus 62%, 57% and 40% in group II, at 1, 2 and 4 years respectively. During follow-up, 1 (1%) patient of the group I and 4 of the group II died. At last follow-up, 63 (78%) of the 81 patients alive vs 33 (67%) of the 59 patients in the group I and II respectively remained asymptomatic. In conclusion, in our experience elective PTCA performed in the subacute phase after an AMI provides better initial and long-term outcome than that performed in the acute phase. Therefore, the procedure would be delayed whenever possible.

  8. The interleukin-1β-511 T>C (rs16944) gene polymorphism is associated with risk of developing silent myocardial ischemia in diabetic patients.

    PubMed

    Vargas-Alarcón, Gilberto; Cruz-López, Miguel; Valladares, Adán; Álvarez-León, Edith; Juárez-Cedillo, Teresa; Pérez-Méndez, Óscar; de-la-Peña, Jorge Escobedo; Escobedo, Galileo; Fragoso, Jose Manuel

    2015-11-01

    Silent myocardial ischemia (SMI) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. Considering the prominent role of IL-1β, IL-1F10 and IL-1RN as regulators of the inflammatory process and vascular physiology, the aim of the present study was to analyze whether IL-1β, IL-1F10 and IL-1RN single nucleotide polymorphisms (SNPs) are associated with SMI. One polymorphism was associated with risk of SMI. Under co-dominant, recessive and additive models, the IL-1β-511 T>C polymorphism was associated with increased risk of SMI when compared to healthy controls (OR=4.68, 95%CI=2.21-9.92, pCCo-dom=0.0048; OR=3.97, 95%CI=1.97-7.99, pCRec=0.0024; OR=2.02, 95%CI=1.41-2.90, pCAdd=0.0024, respectively). All models were adjusted for gender, age and smoking. Linkage disequilibrium analysis showed four haplotypes (CTCC, CCTC, CCCT and CTCC) with increased frequency in SMI patients when compared to healthy controls (OR=2.53, 95%CI=1.47-4.36, pC=0.0009, OR=2.34, 95%CI=1.15-4.74, pC=0.02, OR=2.44, 95%CI=1.14-5.18, pC=0.02, OR=5.11, 95%CI=1.37-19.05, pC=0.01, respectively). In summary, our data suggest that the IL-1β-511 T>C polymorphism plays an important role in the development of SMI in diabetic patients. In addition, in our study was possible to distinguish one protective and four risk haplotypes for development of SMI.

  9. Use of bio-informatics assessment schema (BIAS) to improve diagnosis and prognosis of myocardial perfusion data: results from the NHLBI-sponsored women’s ischemia syndrome evaluation (WISE)

    PubMed Central

    Pohost, Gerald M.; Bairey Merz, C. Noel; Shaw, Leslee J.; Sopko, George; Rogers, William J.; Sharaf, Barry L.; Pepine, Carl J.; Thompson, Diane V.; Rayarao, Geetha; Tauxe, Lindsey; Kelsey, Sheryl F.; Biederman, Robert W. W.

    2016-01-01

    Background We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bio-informatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia. For each patient, the BIAS model value is used to set an appropriate threshold for the detection of ischemia. Methods Women (n=130), with symptoms and signs of suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two different modalities: gated SPECT and MR. To determine perfusion status, MR data were evaluated qualitatively (MRIQL) and semi-quantitatively (MRISQ) while SPECT data were evaluated using conventional clinical criteria. Evaluators were masked to results of the alternate modality. These MPI status readings were designated “original”. Two regression models designated “BIAS” models were generated to model MPI status obtained with one modality (e.g., MRI) compared with a second modality (e.g., SPECT), but importantly, the BIAS models did not include the primary Original MPI reading of the predicting modality. Instead, the BIAS models included auxiliary measurements like left ventricular chamber volumes and myocardial wall thickness. For each modality, the BIAS model was used to set a progressive threshold for interpretation of MPI status. Women were then followed for 38±14 months for the development of a first major adverse cardiovascular event [MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for heart failure]. Original and BIAS-augmented perfusion status were compared in their ability to detect coronary artery

  10. Rotigaptide (ZP123) prevents spontaneous ventricular arrhythmias and reduces infarct size during myocardial ischemia/reperfusion injury in open-chest dogs.

    PubMed

    Hennan, James K; Swillo, Robert E; Morgan, Gwen A; Keith, James C; Schaub, Robert G; Smith, Robert P; Feldman, Hal S; Haugan, Ketil; Kantrowitz, Joel; Wang, Phil J; Abu-Qare, Aqel; Butera, John; Larsen, Bjarne D; Crandall, David L

    2006-04-01

    The antiarrhythmic and cardioprotective effect of increasing gap junction intercellular communication during ischemia/reperfusion injury has not been studied. The antiarrhythmic peptide rotigaptide (previously ZP123), which maintains gap junction intercellular communication, was tested in dogs subjected to a 60-min coronary artery occlusion and 4 h of reperfusion. Rotigaptide was administered i.v. 10 min before reperfusion as a bolus + i.v. infusion at doses of 1 ng/kg bolus + 10 ng/kg/h infusion (n = 6), 10 ng/kg bolus + 100 ng/kg/h infusion (n = 5), 100 ng/kg bolus + 1000 ng/kg/h infusion (n = 8), 1000 ng/kg bolus + 10 mug/kg/h infusion (n = 6), and vehicle control (n = 5). Premature ventricular complexes (PVCs) were quantified during reperfusion. A series of four or more consecutive PVCs was defined as ventricular tachycardia (VT). The total incidence of VT was reduced significantly with the two highest doses of rotigaptide (20.3 +/- 10.9 and 4.3 +/- 4.1 events; p < 0.05) compared with controls (48.7 +/- 6.0). Total PVCs were reduced significantly from 25.1 +/- 4.2% in control animals to 11.0 +/- 4.4 and 1.7 +/- 1.3% after the two highest doses of rotigaptide. Infarct size, expressed as a percentage of the left ventricle, was reduced significantly from 13.2 +/- 1.9 in controls to 7.1 +/- 1.0 (p < 0.05) at the highest dose of rotigaptide. Ultrastructural evaluation revealed no differences in myocardial injury in the infarct area, area at risk, border zone, or normal zone in vehicle and rotigaptide-treated animals. However, rotigaptide did increase the presence of gap junctions in the area at risk (p = 0.022, Fisher's exact test). Rotigaptide had no effect on heart rate, blood pressure, heart rate-corrected QT interval, or left ventricular end-diastolic pressure. In conclusion, these results demonstrate that rotigaptide is a potent antiarrhythmic compound with cardioprotective effects and desirable safety.

  11. Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway.

    PubMed

    Katare, Rajesh G; Kakinuma, Yoshihiko; Arikawa, Mikihiko; Yamasaki, Fumiyasu; Sato, Takayuki

    2009-03-01

    Chronic heart failure (CHF) is the major cause of death in the developed countries. Calorie restriction is known to improve the recovery in these patients; however, the exact mechanism behind this protective effect is unknown. Here we demonstrate the activation of cell survival PI3kinase/Akt and VEGF pathway as the mechanism behind the protection induced by intermittent fasting in a rat model of established chronic myocardial ischemia (MI). Chronic MI was induced in rats by occlusion of the left coronary artery. Two weeks later, the rats were randomly assigned to a normal feeding group (MI-NF) and an alternate-day feeding group (MI-IF). After 6 weeks of observation, we evaluated the effect of intermittent fasting on cellular and ventricular remodeling and long-term survival after CHF. Compared with the normally fed group, intermittent fasting markedly improved the survival of rats with CHF (88.5% versus 23% survival, P<0.05). The heart weight body weight ratio was significantly less in the MI-IF group compared to the MI-NF group (3.4+/-0.17 versus 3.9+/-0.18, P<0.05). Isolated heart perfusion studies exhibited well preserved cardiac functions in the MI-IF group compared to the MI-NF group (P<0.05). Molecular studies revealed the upregulation of angiogenic factors such asHIF-1-alpha (3010+/-350% versus 650+/-151%), BDNF (523+/-32% versus 110+/-12%), and VEGF (450+/-21% versus 170+/-30%) in the fasted hearts. Immunohistochemical studies confirmed increased capillary density (P<0.001) in the border area of the ischemic myocardium and synthesis VEGF by cardiomyocytes. Moreover fasting also upregulated the expression of other anti-apoptotic factors such as Akt and Bcl-2 and reduced the TUNEL positive apoptotic nuclei in the border zone. Chronic intermittent fasting markedly improves the long-term survival after CHF by activation through its pro-angiogenic, anti-apoptotic and anti-remodeling effects.

  12. Synergistic cardioprotective effects of Danshensu and hydroxysafflor yellow A against myocardial ischemia-reperfusion injury are mediated through the Akt/Nrf2/HO-1 pathway

    PubMed Central

    HU, TIANXIN; WEI, GUO; XI, MIAOMIAO; YAN, JIAJIA; WU, XIAOXIAO; WANG, YANHUA; ZHU, YANRONG; WANG, CHAO; WEN, AIDONG

    2016-01-01

    In clinical practice, the traditional Chinese medicinal herbs, Radix Salvia Miltiorrhiza and Carthamus tinctorius L., are usually prescribed in combination due to their significant cardioprotective effects. However, the mechanisms responsible for these combined effects remain unknown. Thus, in this study, we investigated the mechanisms responsible for the combined effects of Danshensu (DSS) and hydroxysafflor yellow A (HSYA) by establishing a rat model of myocardial ischemia/reperfusion (MI/R), as well as a model of hypoxia/reoxygenation (H/R) using H9c2 cells. The combination index (CI) was calculated using the median-effect method. DSS and HSYA in combination led to a CI value of <1 as regards infarct size in vivo and cell viability in vitro. The rats with MI/R injury that were treated with DSS and/or HSYA were found to have significantly lower levels of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) and malondialdehyde (MDA), and a lower expressoin of 8-hydroxydeoxyguanosine (8-OHdG), and markedly enhanced superoxide dismutase (SOD) activity. Our in vitro experiments revealed that the cells treated with DSS and/or HSYA had a reduced lactate dehydrogenase (LDH) activity and a decreased percentage of cell apoptosis (increased Bcl-2/Bax ratio, decreased expression of cleaved caspase-3). DSS and HSYA increased the expression of heme oxygenase-1 (HO-1), the phosphorylation of Akt and the trans-location of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the Akt inhibitor, LY294002, partially hampered the expression of Nrf2 and HO-1. The HO-1 inhibitor, zinc protoporphyrin IX (ZnPP-IX), did not decrease the expression of p-Akt and Nrf2, although it abolished the anti-apoptotic and antioxidant effects of DSS and HSYA. The findings of our study thus demonstrate that DSS and HSYA confer synergistic cardioprotective effects through the Akt/Nrf2/HO-1 signaling pathway, to certain extent, by enhancing the antioxidant defense system and exerting

  13. Synergistic cardioprotective effects of Danshensu and hydroxysafflor yellow A against myocardial ischemia-reperfusion injury are mediated through the Akt/Nrf2/HO-1 pathway.

    PubMed

    Hu, Tianxin; Wei, Guo; Xi, Miaomiao; Yan, Jiajia; Wu, Xiaoxiao; Wang, Yanhua; Zhu, Yanrong; Wang, Chao; Wen, Aidong

    2016-07-01

    In clinical practice, the traditional Chinese medicinal herbs, Radix Salvia Miltiorrhiza and Carthamus tinctorius L., are usually prescribed in combination due to their significant cardioprotective effects. However, the mechanisms responsible for these combined effects remain unknown. Thus, in this study, we investigated the mechanisms responsible for the combined effects of Danshensu (DSS) and hydroxysafflor yellow A (HSYA) by establishing a rat model of myocardial ischemia/reperfusion (MI/R), as well as a model of hypoxia/reoxygenation (H/R) using H9c2 cells. The combination index (CI) was calculated using the median-effect method. DSS and HSYA in combination led to a CI value of <1 as regards infarct size in vivo and cell viability in vitro. The rats with MI/R injury that were treated with DSS and/or HSYA were found to have significantly lower levels of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) and malondialdehyde (MDA), and a lower expressoin of 8-hydroxydeoxyguanosine (8-OHdG), and markedly enhanced superoxide dismutase (SOD) activity. Our in vitro experiments revealed that the cells treated with DSS and/or HSYA had a reduced lactate dehydrogenase (LDH) activity and a decreased percentage of cell apoptosis (increased Bcl-2/Bax ratio, decreased expression of cleaved caspase-3). DSS and HSYA increased the expression of heme oxygenase-1 (HO-1), the phosphorylation of Akt and the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the Akt inhibitor, LY294002, partially hampered the expression of Nrf2 and HO-1. The HO-1 inhibitor, zinc protoporphyrin IX (ZnPP‑IX), did not decrease the expression of p-Akt and Nrf2, although it abolished the anti-apoptotic and antioxidant effects of DSS and HSYA. The findings of our study thus demonstrate that DSS and HSYA confer synergistic cardioprotective effects through the Akt/Nrf2/HO-1 signaling pathway, to certain extent, by enhancing the antioxidant

  14. A computational and functional study elicits the ameliorating effect of the Chinese herbal formula Huo Luo Xiao Ling Dan on experimental ischemia-induced myocardial injury in rats via inhibition of apoptosis.

    PubMed

    Han, Xiang-Dong; Zhou, Zhi-Wei; Yang, Wei; Ye, Hang-Cheng; Xu, Ying-Zi; Huang, Yun-Feng; Zhang, Tong; Zhou, Shu-Feng

    2015-01-01

    Ischemic heart disease (IHD) is the leading cause of death worldwide and remains a major life-threatening factor in humans. Apoptosis has been implicated in the pathogenesis of IHD. The Chinese herbal formula Huo Luo Xiao Ling Dan (HLXLD), one of the commonly used Chinese herbal formulas, consists of Salviae miltiorrhizae, Angelica sinensis, Gummi olibanum, and Commiphora myrrha, with a wide spectrum of pharmacological activity. However, the mechanism of action and molecular targets of HLXLD in the treatment of IHD are unclear. This study aimed to computationally predict the molecular interactions between the major active components of HLXLD and key regulators of apoptosis and then examine the effect of HLXLD on coronary artery ligation-induced acute myocardial ischemia in rats. The molecular interactions between the major active components of HLXLD, including ferulic acid, ligustilide, succinic acid, vanillic acid, tanshinone IIA, tanshinone IIB, danshensu, salvianolic acid A, salvianolic acid C, protocatechuic aldehyde, and β-boswellic acid and human protein molecules including B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 antagonist/killer 1 (Bak1), B cell lymphoma 2 (Bcl-2), procaspase 3, and caspase 9 with regard to hydrogen bond formation, charge interaction, and π-π stacking using Discovery Studio(®) program 3.1. The 12 HLXLD components were predicted by ADMET (absorption, distribution, metabolism, excretion and toxicity) Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate

  15. Regulation of Heat Shock Proteins 27 and 70, p-Akt/p-eNOS and MAPKs by Naringin Dampens Myocardial Injury and Dysfunction In Vivo after Ischemia/Reperfusion

    PubMed Central

    Rani, Neha; Bharti, Saurabh; Manchanda, Mansi; Nag, T. C.; Ray, Ruma; Chauhan, S. S.; Kumari, Santosh; Arya, Dharamvir Singh

    2013-01-01

    Naringin has antioxidant properties that could improve redox-sensitive myocardial ischemia reperfusion (IR) injury. This study was designed to investigate whether naringin restores the myocardial damage and dysfunction in vivo after IR and the mechanisms underlying its cardioprotective effects. Naringin (20–80 mg/kg/day, p.o.) or saline were administered to rats for 14 days and the myocardial IR injury was induced on 15th day by occluding the left anterior descending coronary artery for 45 min and subsequent reperfusion for 60 min. Post-IR rats exhibited pronounced cardiac dysfunction as evidenced by significantly decreased mean arterial pressure, heart rate, +LVdP/dtmax (inotropic state), -LVdP/dtmax (lusitropic state) and increased left ventricular end diastolic pressure as compared to sham group, which was improved by naringin. Further, on histopathological and ultrastructural assessments myocardium and myocytes appeared more normal in structure and the infarct size was reduced significantly in naringin 40 and 80 mg/kg/day group. This amelioration of post-IR-associated cardiac injury by naringin was accompanied by increased nitric oxide (NO) bioavailability, decreased NO inactivation to nitrotyrosine, amplified protein expressions of Hsp27, Hsp70, β-catenin and increased p-eNOS/eNOS, p-Akt/Akt, and p-ERK/ERK ratio. In addition, IR-induced TNF-α/IKK-β/NF-κB upregulation and JNK phosphorylation were significantly attenuated by naringin. Moreover, western blotting and immunohistochemistry analysis of apoptotic signaling pathway further established naringin cardioprotective potential as it upregulated Bcl-2 expression and downregulated Bax and Caspase-3 expression with reduced TUNEL positivity. Naringin also normalized the cardiac injury markers (lactate dehydrogenase and creatine kinase-MB), endogenous antioxidant activities (superoxide dismutase, reduced glutathione and glutathione peroxidase) and lipid peroxidation levels. Thus, naringin restored IR injury

  16. PET imaging of in vivo caspase-3/7 activity following myocardial ischemia-reperfusion injury with the radiolabeled isatin sulfonamide analogue [18F]WC-4-116

    PubMed Central

    Thukkani, Arun K; Shoghi, Kooresh I; Zhou, Dong; Xu, Jinbin; Chu, Wenhua; Novak, Eric; Chen, Delphine L; Gropler, Robert J; Mach, Robert H

    2016-01-01

    The utility of [18F]WC-4-116, a PET tracer for imaging caspase-3 activation, was evaluated in an animal model of myocardial apoptosis. [18F]WC-4-116 was injected into rats at 3 hours after a 30 min period of ischemia induced by temporary occlusion of the left anterior descending coronary artery in Sprague-Dawley rats. [18F]WC-4-116 uptake was quantified by 1) autoradiography, 2) microPET imaging studies, and 3) post-PET biodistribution studies. MicroPET imaging also assessed uptake of the non-caspase-3-targeted tracer [18F]ICMT-18 at 3 hours postischemia. Enzyme assays and Western blotting assessed caspase-3 activation in both at-risk and not-at-risk regions. Caspase-3 enzyme activity increased in the at-risk but not in the not-at-risk myocardium. Quantitative autoradiographic analysis of [18F]WC-4-116 demonstrated nearly 2-fold higher uptake in the ischemia-reperfusion (IR) versus sham animals. [18F]WC-4-116 microPET imaging studies demonstrated that the IR animals was similarly elevated in relation to sham. [18F]ICMT-18 uptake did not increase in at-risk myocardium despite evidence of caspase-3 activation. Biodistribution studies with [18F]WC-4-116 confirmed the microPET findings. These data indicate that the caspase-3-PET tracer [18F]WC-4-116 can noninvasively image in vivo caspase activity during myocardial apoptosis and may be useful for clinical imaging in humans. PMID:27186438

  17. YiXin-Shu, a ShengMai-San-based traditional Chinese medicine formula, attenuates myocardial ischemia/reperfusion injury by suppressing mitochondrial mediated apoptosis and upregulating liver-X-receptor α

    PubMed Central

    Zhao, Yichao; Xu, Longwei; Qiao, Zhiqing; Gao, Lingchen; Ding, Song; Ying, Xiaoying; Su, Yuanyuan; Lin, Nan; He, Ben; Pu, Jun

    2016-01-01

    Positive evidence from clinical trials has fueled growing acceptance of traditional Chinese medicine (TCM) for the treatment of cardiac diseases; however, little is known about the underlying mechanisms. Here, we investigated the nature and underlying mechanisms of the effects of YiXin-Shu (YXS), an antioxidant-enriched TCM formula, on myocardial ischemia/reperfusion (MI/R) injury. YXS pretreatment significantly reduced infarct size and improved viable myocardium metabolism and cardiac function in hypercholesterolemic mice. Mechanistically, YXS attenuated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway (as reflected by inhibition of mitochondrial swelling, cytochrome c release and caspase-9 activity, and normalization of Bcl-2 and Bax levels) without altering the death receptor and endoplasmic reticulum-stress death pathways. Moreover, YXS reduced oxidative/nitrative stress (as reflected by decreased superoxide and nitrotyrosine content and normalized pro- and anti-oxidant enzyme levels). Interestingly, YXS upregulated endogenous nuclear receptors including LXRα, PPARα, PPARβ and ERα, and in-vivo knockdown of cardiac-specific LXRα significantly blunted the cardio-protective effects of YXS. Collectively, these data show that YXS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and oxidative stress and by upregulating LXRα, thereby providing a rationale for future clinical trials and clinical applications. PMID:26964694

  18. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model

    PubMed Central

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-ichiro; Egashira, Kensuke

    2016-01-01

    Background There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Methods and Results Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. Conclusions NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic

  19. A computational and functional study elicits the ameliorating effect of the Chinese herbal formula Huo Luo Xiao Ling Dan on experimental ischemia-induced myocardial injury in rats via inhibition of apoptosis

    PubMed Central

    Han, Xiang-Dong; Zhou, Zhi-Wei; Yang, Wei; Ye, Hang-Cheng; Xu, Ying-Zi; Huang, Yun-Feng; Zhang, Tong; Zhou, Shu-Feng

    2015-01-01

    Ischemic heart disease (IHD) is the leading cause of death worldwide and remains a major life-threatening factor in humans. Apoptosis has been implicated in the pathogenesis of IHD. The Chinese herbal formula Huo Luo Xiao Ling Dan (HLXLD), one of the commonly used Chinese herbal formulas, consists of Salviae miltiorrhizae, Angelica sinensis, Gummi olibanum, and Commiphora myrrha, with a wide spectrum of pharmacological activity. However, the mechanism of action and molecular targets of HLXLD in the treatment of IHD are unclear. This study aimed to computationally predict the molecular interactions between the major active components of HLXLD and key regulators of apoptosis and then examine the effect of HLXLD on coronary artery ligation-induced acute myocardial ischemia in rats. The molecular interactions between the major active components of HLXLD, including ferulic acid, ligustilide, succinic acid, vanillic acid, tanshinone IIA, tanshinone IIB, danshensu, salvianolic acid A, salvianolic acid C, protocatechuic aldehyde, and β-boswellic acid and human protein molecules including B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 antagonist/killer 1 (Bak1), B cell lymphoma 2 (Bcl-2), procaspase 3, and caspase 9 with regard to hydrogen bond formation, charge interaction, and π-π stacking using Discovery Studio® program 3.1. The 12 HLXLD components were predicted by ADMET (absorption, distribution, metabolism, excretion and toxicity) Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate of

  20. Extent of myocardial ischemia during coronary occlusion in single vessel disease. A comparison between patients with exercise-induced angina and patients with recurrent angina at rest.

    PubMed

    Figueras, Jaume; Missorici, Mario; Gil, Carlos Pena; Cortadellas, Josefa; Angel, Joan

    2008-07-21

    Patients with exercise angina >2 months (n:13) showed significantly lower SigmaST elevation during 120 s balloon coronary occlusion than those with =<2 months (n:7), or those with angina at rest <=2 days (n:8) but similar to patients with angina at rest >2 days (n:7). These results underscore the importance of the kind and duration of angina in limiting the extent of ischemia during coronary occlusion.

  1. Modulation of coronary flow rate and cardiac contractility by the divalent cation ionophore A23187 and inhibitors of the cyclooxygenase and 5-lipoxygenase pathways: development of heterogeneous patterns of myocardial ischemia.

    PubMed

    Björnsson, O G; Kobayashi, K; Williamson, J R

    1988-02-01

    In the present studies, we demonstrate in buffer-perfused isolated working guinea pig hearts that indometacin reduces coronary flow rate in a dose-dependent manner (max 56.7 +/- 5.5%, SEM, n = 6, of control at 5 x 10(-6) mol/l of indometacin, P less than 0.01), and that this leads to a development of heterogeneous patterns of myocardial ischemia (elevated myocardial levels of reduced pyridine nucleotide, NADH) and depressed cardiac work (64.7 +/- 11.7%, SEM, of control at 5 x 10(-6) mol/l of indometacin, P less than 0.05). The effect of indometacin on coronary flow rate and consequently on myocardial tissue oxygenation was completely prevented by the preferential 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) (1 x 10(-6) mol/l), or the sulfidopeptide leukotriene receptor antagonist FPL 55712 (2 x 10(-5) mol/l), indicating that the isolated working guinea pig heart, even when deprived of blood, is able to produce vasoactive sulfidopeptide leukotrienes at significant levels. At higher concentrations of indometacin (5 x 10(-5) mol/l, 1 x 10(-4) mol/l), coronary flow rate returned to initial levels while cardiac work became further depressed despite normoxic levels of NADH. These data support that indometacin also has a direct suppressive effect on the myocardium independent of its coronary vascular effect. This conclusion is supported by the observation that addition of sodium arachidonate (6 x 10(-5) mol/l) completely inhibited the vascular effect of indometacin, but not the depressive effect on the myocardium. The divalent cation ionophore A23187 (6 x 10(-6) mol/l) had a strong positive chronotropic effect on the heart and a biphasic effect on coronary flow rate. After a brief period of increased coronary flow rate, presumably due to coronary vasodilatation, the ionophore caused a sustained reduction in coronary flow, and this was accompanied by high myocardial levels of NADH fluorescence of characteristically heterogeneous pattern. This is presumably

  2. Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome.

    PubMed

    Donner, Daniel G; Elliott, Grace E; Beck, Belinda R; Bulmer, Andrew C; Lam, Alfred K; Headrick, John P; Du Toit, Eugene F

    2016-01-01

    The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS.

  3. Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome.

    PubMed

    Donner, Daniel G; Elliott, Grace E; Beck, Belinda R; Bulmer, Andrew C; Lam, Alfred K; Headrick, John P; Du Toit, Eugene F

    2016-01-01

    The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. PMID:26584015

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

    PubMed Central

    Najafi, Moslem

    2013-01-01

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

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

    PubMed Central

    Najafi, Moslem

    2013-01-01

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

  6. Huangzhi Oral Liquid Prevents Arrhythmias by Upregulating Caspase-3 and Apoptosis Network Proteins in Myocardial Ischemia-Reperfusion Injury in Rats

    PubMed Central

    Ran, Xu; Sun, Xue Gang; Wang, Ming; An, Hui; Huang, Guo Qiang; Zhao, Xiao Shan; Zhou, Feng Hua; Yang, Yun Gao; Miao, Can Ming

    2015-01-01

    To study the effect of Huangzhi oral liquid (HZOL) on I/R after 2 h and 4 h and determine its regulatory function on caspase-3 and protein networks. 70 SD male rats were randomly divided into seven groups and established myocardial I/R injury model by ligating the left anterior descending coronary artery. Myocardial infarction model was defined by TTC staining and color of the heart. The levels of CK-MB, CTnI, C-RPL, SOD, and MDA were tested at 2 h and 4 h after reperfusion. HE staining and ultramicrostructural were used to observe the pathological changes. The apoptotic index (AI) of cardiomyocyte was marked by TUNEL. The expression levels of caspase-3, p53, fas, Bcl-2, and Bax were tested by immunohistochemistry and western blot. HZOL corrected arrhythmia, improved the pathologic abnormalities, decreased CK-MB, CTnI, C-RPL, MDA, AI, caspase-3, p53, fas, and Bax, and increased SOD ans Bcl-2 with different times of myocardial reperfusion; this result was similar to the ISMOC (P > 0.05). HZOL could inhibit arrhythmia at 2 and 4 h after I/R and ameliorate cardiac function, which was more significant at 4 h after reperfusion. This result may be related to decreased expression of caspase-3, p53, and fas and increased Bcl-2/Bax ratio. PMID:26074995

  7. Mesenteric ischemia.

    PubMed

    Bobadilla, Joseph L

    2013-08-01

    This article reviews the presentation, diagnosis, evaluation, and treatment of the various forms of mesenteric ischemia, including acute and chronic ischemia. In addition, nonocclusive mesenteric ischemia and median arcuate ligament compressive syndrome are covered. The goals are to provide a structured and evidence-based framework for the evaluation and management of patients with these intestinal ischemia syndromes. Special attention is given to avoiding typical pitfalls in the diagnostic and treatment pathways. Operative techniques are also briefly discussed, including an evidence-based review of newer endovascular techniques.

  8. Cardiac Magnetic Resonance Myocardial Perfusion Reserve Index Is Reduced in Women With Coronary Microvascular Dysfunction: A National Heart, Lung and Blood Institute-Sponsored Study From the Women's Ischemia Syndrome Evaluation (WISE)

    PubMed Central

    Thomson, Louise E.J.; Wei, Janet; Agarwal, Megha; Haft-Baradaran, Afsaneh; Shufelt, Chrisandra; Mehta, Puja K.; Gill, Edward; Johnson, B. Delia; Kenkre, Tanya; Handberg, Eileen; Li, Debiao; Sharif, Behzad; Berman, Daniel S.; Petersen, John; Pepine, Carl J.; Bairey Merz, C. Noel

    2015-01-01

    Background Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). While traditional noninvasive stress imaging is often normal in CMD, cardiac magnetic resonance imaging (CMRI) may be able to detect CMD in this population. Methods and Results Vasodilator stress CMRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression and sensitivity/specificity. Symptomatic women had lower mean pharmacologic stress MPRI compared to reference subjects (1.71±0.43 vs. 2.23±0.37, p<0.0001). Lower MPRI was predictive of one or more abnormal CRT variables (OR = 0.78 [0.70, 0.88], p<0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%. Conclusions Noninvasive CMRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the non-invasive identification and management of CMD patients. PMID:25801710

  9. Prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: a prospective natural history study

    SciTech Connect

    Gibson, R.S.; Beller, G.A.; Gheorghiade, M.; Nygaard, T.W.; Watson, D.D.; Huey, B.L.; Sayre, S.L.; Kaiser, D.L.

    1986-06-01

    Despite having smaller infarct size and better left ventricular function, patients with non-Q wave myocardial infarction (NQMI) appear to have an unexpectedly high long-term mortality that is ultimately comparable to that of patients with Q-wave myocardial infarction (QMI). Patients with NQMI may lose their initial prognostic advantage because there is more viable tissue in the perfusion zone of the infarct-related vessel, rendering myocardium more prone to reinfarction. We tested this hypothesis in a prospective study of 241 consecutive patients 65 years of age or younger with acute uncomplicated myocardial infarction confirmed by creatine kinase levels (MB fraction). All patients received customary care and none underwent thrombolytic therapy or emergency angioplasty. Predischarge coronary angiography, radionuclide ventriculography, 24 hr Holter monitoring, and quantitative thallium-201 scintigraphy during treadmill exercise were performed 10 +/- 3 days after infarction. Infarcts were designated as QMI (n = 154) or NQMI (n = 87) by accepted criteria applied to serial electrocardiograms obtained on days 1, 2, 3, and 10. The baseline Norris coronary prognostic index, angiographic jeopardy scores, and prevalence of Lown grade ventricular arrhythmias were similar between groups despite evidence for less necrosis with NQMI vs QMI, reflected by lower peak creatine kinase levels (520 vs 1334 IU/liter; p = .0001, 4 hr sampling), higher resting left ventricular ejection fraction (53% vs 46%; p = .0001), fewer akinetic or dyskinetic segments (1.2 vs 2.4; p = .0001), and fewer persistent /sup 201/Tl defects in the infarct zone. Patients with NQMI also had more patent infarct-related vessels and a shorter time from onset of infarction to peak creatine kinase level.

  10. Evaluation of ischemia and myocardial viability in patients with coronary artery disease (CAD) with iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP)

    SciTech Connect

    Kropp, J.; Joergens, M.; Glaenzer, K.P.; Luederitz, B.; Biersack, H.J.; Knapp, F.F. Jr.

    1993-10-01

    Twenty patients with coronary artery disease (CAD) controlled by coronary arteriography (CA) and biplane left ventricular cineventriculography (LVCV) were investigated with the 15- (p[I-123]iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue. During maximal symptom limited exercise 5 mCi (200 MBq) of BMIPP were injected followed by two SPECT studies within three hours. After another 30 min, with the patient at rest a third SPECT was performed after reinjection of 3 mCi (100 MBq) BMIPP. Visual inspection of the short and long axis slices and quantitative comparison of the short axis slices of the tomograms were performed to grade BMIPP uptake and refill and detect turnover abnormalities. These were addressed either as scar or as ischemia and compared to CA and a graded score of regional wall motion by LVCV which provided values for sensitivity (SE) and specificity (SP) to detect CAD. Fifteen infarctions had corresponded clinical, angiographic and scintigraphic findings in 93%.

  11. Alpha lipoic acid protects the heart against myocardial post ischemia-reperfusion arrhythmias via KATP channel activation in isolated rat hearts.

    PubMed

    Dudek, Magdalena; Knutelska, Joanna; Bednarski, Marek; Nowiński, Leszek; Zygmunt, Małgorzata; Bilska-Wilkosz, Anna; Iciek, Małgorzata; Otto, Monika; Żytka, Iwona; Sapa, Jacek; Włodek, Lidia; Filipek, Barbara

    2014-06-01

    The cardiovascular effects of alpha lipoic acid were evaluated in isolated rat hearts exposed to ischemia-reperfusion injury in vitro. Alpha-lipoic acid raised the level of sulfane sulfur playing an important role in the release of hydrogen sulfide. H2S was shown to prevent the post-reperfusion arrhythmias and to protect the cardiomyocytes from death caused by hypoxia. The activation of potassium ATP-sensitive channels (K(ATP) channels) is one of the most important mechanisms of action of hydrogen sulfide in the cardiovascular system. The aim of this study was to investigate whether alpha lipoic acid can prevent the occurrence of post-reperfusion arrhythmias in vitro using a Langendorff model of ischemia-reperfusion in rats affecting the K(ATP) channels. Alpha lipoic acid significantly improved post-reperfusion cardiac function (reducing incidence of arrhythmias), especially in a dose of 10(-7)M. These cardiovascular effects of this compound on the measured parameters were reversed by glibenclamide, a selective K(ATP) blocker. Alpha lipoic acid increased the level of sulfane sulfur in the hearts. This may suggest that the positive effects caused by alpha lipoic acid in the cardiovascular system are not only related to its strong antioxidant activity, and the influence on the activity of such enzymes as aldehyde dehydrogenase 2, as previously suggested, but this compound can affect K(ATP) channels. It is possible that this indirect effect of alpha lipoic acid is connected with changes in the release of sulfane sulfur and hydrogen sulfide.

  12. Cardioprotective Effects of Total Flavonoids Extracted from Xinjiang Sprig Rosa rugosa against Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated Rat Heart.

    PubMed

    Hou, Xuejiao; Han, Jichun; Yuan, Changsheng; Ren, Huanhuan; Zhang, Ya; Zhang, Tao; Xu, Lixia; Zheng, Qiusheng; Chen, Wen

    2016-01-01

    This study evaluated the antioxidative and cardioprotective effects of total flavonoids extracted from Xinjiang sprig Rosa rugosa on ischemia/reperfusion (I/R) injury using an isolated Langendorff rat heart model. The possible mechanism of Xinjiang sprig rose total flavonoid (XSRTF) against I/R injury was also studied. XSRTF (5, 10, and 20 µg/mL) dissolved in Krebs-Henseleit buffer was administered to isolated rat heart. The XSRTF showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide anion radicals in vitro. XSRTF pretreatment improved the heart rate, increased LVDP, and decreased CK and LDH levels in coronary flow. This pretreatment also increased SOD activity and GSH/GSSG ratio but decreased MDA, TNF-α, and CRP levels and IL-8 and IL-6 activities. The infarct size and cell apoptosis in the hearts from the XSRTF-treated group were lower than those in the hearts from the I/R group. Therefore, the cardioprotective effects of XSRTF may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities.

  13. A randomized, double-blind comparison of 10 and 20 mg lercanidipine in patients with stable effort angina: effects on myocardial ischemia and heart rate variability.

    PubMed

    Acanfora, Domenico; Trojano, Luigi; Gheorghiade, Mihai; Picone, Costantino; Papa, Antimo; Furgi, Giuseppe; Giuliano, Franca; Maestri, Roberto; Rengo, Franco

    2002-01-01

    We evaluated the anti-ischemic action and the effects on autonomic function of lercanidipine, a long-acting dihydropyridine calcium antagonist, in 25 patients with stable effort angina in a randomized, double-blind, parallel trial. After a 2-week placebo run-in period, patients entered a 2-week treatment period with 10 or 20 mg of lercanidipine once daily. During the placebo run-in period and at the study end, the patients underwent clinical examination, electrocardiography, exercise tests, 24-hour Holter electrocardiography for long-term heart rate variability evaluation, and short-term spectral analysis of heart rate and systolic blood pressure variability and plasma epinephrine and norepinephrine levels at rest and during tilting. Results showed that time to onset of ST segment depression > or =1 mm was significantly increased by both drug doses. No significant change was recorded in the average hourly heart rate after treatment with both 10 and 20 mg of lercanidipine. During the 24-hour recordings, no significant change was observed in low-frequency power, high-frequency power, or low frequency/high frequency. In the standing position, there was a significant increase in plasma norepinephrine and epinephrine concentration in both groups, and no change in the supine position after 10 and 20 mg of lercanidipine. When considering short-term heart rate variability, no significant difference was observed in either treatment group in low frequency, high frequency, or their ratio on electrocardiographic R-R spectra. The blood pressure spectral component was also unchanged. In conclusion, lercanidipine is effective in reducing ischemia in patients with stable effort angina. Moreover, lercanidipine does not cause adrenergic activation, which is the main mechanism hypothesized to explain the negative effect on cardiovascular mortality assigned to short-acting dihydropyridine calcium antagonists.

  14. Hydrogen Sulfide Attenuates the Recruitment of CD11b+Gr-1+ Myeloid Cells and Regulates Bax/Bcl-2 Signaling in Myocardial Ischemia Injury

    PubMed Central

    Zhang, Youen; Li, Hua; Zhao, Gang; Sun, Aijun; Zong, Nobel C.; Li, Zhaofeng; Zhu, Hongming; Zou, Yunzeng; Yang, Xiangdong; Ge, Junbo

    2014-01-01

    Hydrogen sulfide, an endogenous signaling molecule, plays an important role in the physiology and pathophysiology of the cardiovascular system. Using a mouse model of myocardial infarction, we investigated the anti-inflammatory and anti-apoptotic effects of the H2S donor sodium hydrosulfide (NaHS). The results demonstrated that the administration of NaHS improved survival, preserved left ventricular function, limited infarct size, and improved H2S levels in cardiac tissue to attenuate the recruitment of CD11b+Gr-1+ myeloid cells and to regulate the Bax/Bcl-2 pathway. Furthermore, the cardioprotective effects of NaHS were enhanced by inhibiting the migration of CD11b+Gr-1+ myeloid cells from the spleen into the blood and by attenuating post-infarction inflammation. These observations suggest that the novel mechanism underlying the cardioprotective function of H2S is secondary to a combination of attenuation the recruitment of CD11b+Gr-1+ myeloid cells and regulation of the Bax/Bcl-2 apoptotic signaling. PMID:24758901

  15. The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated 82Rb PET myocardial perfusion imaging

    PubMed Central

    Van Tosh, Andrew; Votaw, John R.; Reichek, Nathaniel; Palestro, Christopher J.; Nichols, Kenneth J.

    2014-01-01

    Background Gated rubidium-82 (82Rb) positron emission tomography (PET) imaging studies are acquired both at rest and during pharmacologic stress. Stress-induced ischemic left ventricular dysfunction (LVD) can produce a significant decrease in left ventricular ejection fraction (LVEF) from rest to stress. We determined the prevalence on PET of stress LVD with reduced ejection fraction (EF) and its association with absolute global and regional coronary flow reserve (CFR), and with relative perfusion defect summed difference score (SDS). Methods and Results We studied 205 patients with known or suspected coronary disease (120 M, 75 F, age 69 ± 13 years) who had clinically indicated rest/regadenoson stress 82Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and 17-segment regional CFR values were computed from first-pass flow data using a 2-compartment model and factor analysis applied to auto-generated time-activity curves. Rest and stress LVEF and SDS were quantified from gated equilibrium myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was defined as a change in LVEF of ≤−5% from rest to stress. A subgroup of 109 patients also had coronary angiography. Stress LVD developed in 32 patients (16%), with mean EF change of −10 ± 5%, vs +6 ± 7% for patients without LVD (P < .0001). EF was similar at rest in patients with and without stress LVD (57 ± 18% vs 56 ± 16%, P = .63), but lower during stress for patients with LVD (47 ± 20% vs 61 ± 16%, P = .0001). CFR was significantly lower in patients with LVD (1.61 ± 0.67 vs 2.21 ± 1.03, Wilcoxon P = .002), and correlated significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = −0.13, P = .07). The single variable most strongly associated with high risk of CAD (i.e., left main stenosis ≥50%, LAD % stenosis ≥70%, and/or 3-vessel disease) was stress EF (χ2 = 17.3, P < .0001). There was a higher prevalence of patients with territorial CFR

  16. A case of acute myocardial infarction due to coronary spasm in the myocardial bridge.

    PubMed

    Fujibayashi, Daisuke; Morino, Yoshihiro; Ikari, Yuji

    2008-07-01

    A 68-year-old Japanese man with acute inferior myocardial infarction underwent emergent coronary angiography which showed a myocardial bridge, but no coronary stenosis, at the infarctrelated artery. A spasm provocation test using intracoronary acetylcholine revealed a total occlusion due to severe spasm at the site of the myocardial bridge. Thus, the myocardial ischemia in this case was caused by the coronary spasm, but not by the limited flow due to the myocardial bridge. Although a beta-blocker is usually the appropriate drug, it should be avoided for coronary spasm. The spasm provocation test is useful to determine the type of medication needed for treatment.

  17. Risk stratification after myocardial infarction. Clinical overview

    SciTech Connect

    O'Rourke, R.A. )

    1991-09-01

    Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification.

  18. Acute myocardial infarction in rats.

    PubMed

    Wu, Yewen; Yin, Xing; Wijaya, Cori; Huang, Ming-He; McConnell, Bradley K

    2011-01-01

    With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial

  19. Physiology and pharmacology of myocardial preconditioning.

    PubMed

    Raphael, Jacob

    2010-03-01

    Perioperative myocardial ischemia and infarction are not only major sources of morbidity and mortality in patients undergoing surgery but also important causes of prolonged hospital stay and resource utilization. Ischemic and pharmacological preconditioning and postconditioning have been known for more than two decades to provide protection against myocardial ischemia and reperfusion and limit myocardial infarct size in many experimental animal models, as well as in clinical studies (1-3). This paper will review the physiology and pharmacology of ischemic and drug-induced preconditioning and postconditioning of the myocardium with special emphasis on the mechanisms by which volatile anesthetics provide myocardial protection. Insights gained from animal and clinical studies will be presented and reviewed and recommendations for the use of perioperative anesthetics and medications will be given.

  20. Prognostic value of radionuclide exercise testing after myocardial infarction

    SciTech Connect

    Schocken, D.D.

    1984-08-01

    Abnormal systolic ventricular function and persistent ischemia are sensitive indicators of poor prognosis following myocardial infarction. The use of exercise improves the utility of both radionuclide ventriculography and myocardial perfusion scintigraphy in the identification of postinfarction patients at high risk of subsequent cardiac events. 51 references.

  1. Clinical Application and Research Advances of CT Myocardial Perfusion Imaging.

    PubMed

    2016-06-10

    Computed tomography (CT)-based myocardial perfusion imaging (CTP)has been widely recognized as a one-station solution for the imaging of myocardial ischemia-related diseases. This article reviews the clinical scanning protocols,analytical methods,and research advances of CTP in recent years and briefly discusses its limitations and future development. PMID:27469926

  2. [Amaurosis fugax in inferior wall myocardial infarction with ST segment elevation].

    PubMed

    Hrycek, Eugeniusz; Bońkowski, Michał; Nowakowski, Przemysław; Żurakowski, Aleksander; Buszman, Paweł

    2016-01-01

    The patient, a fifty nine year old male, was admitted to the ward with symptoms of inferior wall myocardial infarction with ST segment elevation combined with intermittent right side sight loss. Despite typical resting stenocardial chest pain, ST segment elevation in ECG, transient symptoms of acute heart failure and slightly elevated myocardial necrosis biomarkers, coronarography did not reveal obvious source of myocardial ischemia. Moreover, echocardiography did not confirm decreased ejection fraction. However further research confirmed critical stenosis of the left internal carotid artery and chronic occlusion of the right internal carotid artery. Several questions were raised during diagnostic process including: the cause of cardiac ischemia and the cause of cerebral ischemia. Clinical data analysis and available literature allowed authors to exclude cerebral ischemia as a source of ECG ischemic changes and to establish transient myocardial ischemia causing circulatory decompensation amplified by carotid arteries atherosclerosis as the source of neurological symptoms. PMID:27487548

  3. Spontaneous changes in /sup 201/Tl myocardial perfusion imaging after myocardial infarction

    SciTech Connect

    Buda, A.J.; Dubbin, J.D.; MacDonald, I.L.; Strauss, H.D.; Orr, S.A.; Meindok, H.

    1982-12-01

    To examine regional myocardial perfusion after myocardial infarction, 26 patients underwent exercise electrocardiographic testing with /sup 201/Tl myocardial perfusion imaging 3 weeks and 3 months after infarction. At 3 weeks, 9 of 26 patients (35%) had myocardial ischemia by exercise electrocardiographic testing, whereas 18 of 26 (69%) had ischemia by /sup 201/Tl imaging. The /sup 201/Tl scintigrams were scored by dividing each image, in 3 views, into 5 segments, using a 5-point scoring scheme. The exercise /sup 201/Tl score was 44.3 +/- 1.2 and increased to 47.3 +/- 1.2 in the redistribution study (p less than 0.001). Three months after infarction, although there was a significantly greater rate-pressure product which would predict a larger ischemic defect and a decrease in the stress /sup 201/Tl score, the stress score was improved (48.3 +/- 1.1, p less than 0.001). The redistribution score was similar, that is, 48.9 +/- 1.0. The improvement in /sup 201/Tl myocardial perfusion was associated with a loss of stress-induced ischemia in 8 patients (30%). These results indicate that spontaneous improvements in /sup 201/Tl myocardial perfusion imaging may occur after myocardial infarction.

  4. Predictive Modeling of Cardiac Ischemia

    NASA Technical Reports Server (NTRS)

    Anderson, Gary T.

    1996-01-01

    The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

  5. Estimation of jeopardized left ventricular myocardium in symptomatic and silent ischemia as determined by iodine-123 phenylpentadecanoic acid rotational tomography

    SciTech Connect

    Kahn, J.K.; Pippin, J.J.; Akers, M.S.; Corbett, J.R.

    1989-03-01

    Whether patients with silent myocardial ischemia have a lesser mass of ischemic myocardium than patients with symptomatic ischemia is controversial. Forty-five patients with angiographic coronary artery disease (greater than or equal to 70% luminal diameter narrowing) were studied. All patients had ischemic patterns of myocardial uptake and clearance of the long-chain fatty acid perfusion/metabolic imaging agent iodine-123 phenylpentadecanoic acid after maximal exercise. Single-photon emission computed tomography was performed and 25 myocardial segments were analyzed using circumferential activity profile curves. The 21 patients with silent treadmill ischemia exercised longer than the 24 patients with painful treadmill ischemia (430 +/- 137 vs 337 +/- 96 seconds, p less than 0.01) and to a higher heart rate (138 +/- 21 vs 125 +/- 18 beats/min, p less than 0.05). Patients with treadmill silent ischemia had the same number of abnormally perfused myocardial segments as patients with painful treadmill ischemia (8.6 +/- 4.5 vs 6.5 +/- 4.1 segments, difference not significant) and the same number of reversibly ischemic myocardial segments (4.0 +/- 1.4 vs 4.2 +/- 3.0 segments, difference not significant). The angiographic severity and extent of coronary artery disease were similar in the 2 groups. Thus, in this selected group of patients, those with silent treadmill ischemia appear to have at least as great an extent of ischemic myocardium as patients with painful exertional ischemia.

  6. Myocardial diseases of animals.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1986-01-01

    seen less frequently; and, in contrast to man, coronary artery disease and myocardial ischemia are rather infrequent in animals. The present review shows clearly that the spectrum of myocardial diseases in animals is enlarging and that many newly recognized diseases are emerging and assuming considerable importance. For example, various heritable cardiomyopathies have recently been described in the KK mouse, cattle, and rats. Increasingly recognized myocardial diseases include cardiomyopathies in cats, dogs, and birds; anthracycline cardiotoxicity; furazolidone cardiotoxicity; ionophore cardiotoxicity; myocardial damage associated with central nervous system injuries; myocardial hypertrophy in Images Figure 1 Figure 2 Figure 45 Figure 46 Figure 47 Figure 48 Figure 61 Figure 62 Figure 63 Figure 64 Figure 79 Figure 75 Figure 76 Figure 77 Figure 78 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22 Figure 23 Figure 24 Figure 25 Figure 26 Figure 27 Figure 28 Figure 29 & 30 Figure 31 Figure 32 Figure 33 Figure 34 Figure 35 Figure 36 Figure 37 Figure 38 Figure 39 Figure 40 Figure 41 Figure 42 Figure 43 Figure 44 Figure 49 Figure 50 Figure 51 Figure 52 Figure 53 Figure 54 Figure 55 Figure 56 Figure 57 Figure 58 Figure 59 Figure 60 Figure 65 Figure 66 Figure 67 Figure 68 Figure 69 Figure 70 Figure 71 & 72 Figure 73 & 74 PMID:3524254

  7. Myocardial Bridging

    PubMed Central

    Yuan, Shi-Min

    2016-01-01

    Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results. PMID:27074276

  8. Biochemical Markers of Myocardial Damage

    PubMed Central

    2016-01-01

    Heart diseases, especially coronary artery diseases (CAD), are the leading causes of morbidity and mortality in developed countries. Effective therapy is available to ensure patient survival and to prevent long term sequelae after an acute ischemic event caused by CAD, but appropriate therapy requires rapid and accurate diagnosis. Research into the pathology of CAD have demonstrated the usefulness of measuring concentrations of chemicals released from the injured cardiac muscle can aid the diagnosis of diseases caused by myocardial ischemia. Since the mid-1950s successively better biochemical markers have been described in research publications and applied for the clinical diagnosis of acute ischemic myocardial injury. Aspartate aminotransferase of the 1950s was replaced by other cytosolic enzymes such as lactate dehydrogenase, creatine kinase and their isoenzymes that exhibited better cardiac specificity. With the availability of immunoassays, other muscle proteins, that had no enzymatic activity, were also added to the diagnostic arsenal but their limited tissue specificity and sensitivity lead to suboptimal diagnostic performance. After the discovery that cardiac troponins I and T have the desired specificity, they have replaced the cytosolic enzymes in the role of diagnosing myocardial ischemia and infarction. The use of the troponins provided new knowledge that led to revision and redefinition of ischemic myocardial injury as well as the introduction of biochemicals for estimation of the probability of future ischemic myocardial events. These markers, known as cardiac risk markers, evolved from the diagnostic markers such as CK-MB or troponins, but markers of inflammation also belong to these groups of diagnostic chemicals. This review article presents a brief summary of the most significant developments in the field of biochemical markers of cardiac injury and summarizes the most recent significant recommendations regarding the use of the cardiac markers in

  9. Biochemical Markers of Myocardial Damage.

    PubMed

    Bodor, Geza S

    2016-04-01

    Heart diseases, especially coronary artery diseases (CAD), are the leading causes of morbidity and mortality in developed countries. Effective therapy is available to ensure patient survival and to prevent long term sequelae after an acute ischemic event caused by CAD, but appropriate therapy requires rapid and accurate diagnosis. Research into the pathology of CAD have demonstrated the usefulness of measuring concentrations of chemicals released from the injured cardiac muscle can aid the diagnosis of diseases caused by myocardial ischemia. Since the mid-1950s successively better biochemical markers have been described in research publications and applied for the clinical diagnosis of acute ischemic myocardial injury. Aspartate aminotransferase of the 1950s was replaced by other cytosolic enzymes such as lactate dehydrogenase, creatine kinase and their isoenzymes that exhibited better cardiac specificity. With the availability of immunoassays, other muscle proteins, that had no enzymatic activity, were also added to the diagnostic arsenal but their limited tissue specificity and sensitivity lead to suboptimal diagnostic performance. After the discovery that cardiac troponins I and T have the desired specificity, they have replaced the cytosolic enzymes in the role of diagnosing myocardial ischemia and infarction. The use of the troponins provided new knowledge that led to revision and redefinition of ischemic myocardial injury as well as the introduction of biochemicals for estimation of the probability of future ischemic myocardial events. These markers, known as cardiac risk markers, evolved from the diagnostic markers such as CK-MB or troponins, but markers of inflammation also belong to these groups of diagnostic chemicals. This review article presents a brief summary of the most significant developments in the field of biochemical markers of cardiac injury and summarizes the most recent significant recommendations regarding the use of the cardiac markers in

  10. Myocardial infarction caused by myocardial bridging in a male adolescent athlete.

    PubMed

    Zhu, Cheng-Gang; Liu, Jun; Liu, Wei-Dong; Xu, Yan-Lu; Wu, Na-Qiong; Guo, Yuan-Lin; Tang, Yi-Da; Jiang, Li-Xin; Li, Jian-Jun

    2012-02-01

    Myocardial bridging is a common congenital abnormality of a coronary artery, and is usually thought to be a benign anatomical variant. Although rare, previous studies have reported that patients with myocardial bridging may suffer from myocardial ischemia, myocardial infarction (MI), arrhythmias and even sudden death. Here we report the case of an 18-year-old adolescent athlete with myocardial bridging resulting in MI. Coronary angiography revealed 80% luminal narrowing by systolic compression in the proximal and mid segments of the left anterior descending coronary artery, which returned to normal during diastole. We considered that heavy sports might be a potential trigger for his MI attack. Therefore, special attention should be paid to this kind of athlete, especially if adolescent.

  11. Radionuclide imaging of myocardial perfusion and viability in assessment of acute myocardial infarction

    SciTech Connect

    Berman, D.S.; Kiat, H.; Maddahi, J.; Shah, P.K.

    1989-07-18

    Technical advances in radionuclide imaging have important implications for the management of patients with acute myocardial infarction. Single-photon emission computerized tomography with thallium 201 (TI-201) offers greater accuracy than planar imaging in detecting, localizing and sizing myocardial perfusion defects. Use of single-photon emission computerized tomography with TI-201 should allow for a more accurate assessment of prognosis after myocardial infarction. A new radiopharmaceutical, technetium 99-m methoxyisobutyl isonitrile, provides a number of advantages over TI-201, including higher quality images, lack of redistribution, and the ability to assess first-pass ventricular function. Applications of TI-201 and technetium 99-m methoxyisobutyl isonitrile include assessment of arterial patency and myocardial salvage immediately after thrombolytic therapy, detection of resting ischemia after thrombolytic therapy, targeting of subsets of patients for further intervention, and predischarge assessment to predict the future course of patients after an acute myocardial infarction.

  12. Ischemia and reperfusion—from mechanism to translation

    PubMed Central

    Eltzschig, Holger K; Eckle, Tobias

    2013-01-01

    Ischemia and reperfusion–elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion–associated tissue inflammation and organ dysfunction. PMID:22064429

  13. Metabolic Adaptation to Muscle Ischemia

    NASA Technical Reports Server (NTRS)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  14. Ceramide is involved in triggering of cardiomyocyte apoptosis induced by ischemia and reperfusion.

    PubMed Central

    Bielawska, A. E.; Shapiro, J. P.; Jiang, L.; Melkonyan, H. S.; Piot, C.; Wolfe, C. L.; Tomei, L. D.; Hannun, Y. A.; Umansky, S. R.

    1997-01-01

    Involvement of ceramide signaling in the initiation of apoptosis induction in myocardial cells by in vitro and in vivo ischemia and reperfusion was analyzed. Synthetic cell permeable C2-ceramide induced apoptotic death of rat neonatal cardiomyocytes in vitro. In vitro ischemia (oxygen/serum/glucose deprivation) led to a progressive accumulation of ceramide in cardiomyocytes. After 16 hours of simulated in vitro reperfusion (readdition of oxygen, serum and glucose), the level of ceramide in surviving cells was found to have returned to baseline, whereas, levels in nonadherent dead cells remained high. In the rat heart left coronary artery occlusion model, ischemia with the subsequent reperfusion, but not ischemia alone, induced apoptosis in myocardial cells as demonstrated by DNA electrophoresis and measurement of soluble chromatin degradation products. The content of ceramide in ischemic area was elevated to 155% baseline levels at 30 minutes, and to 330% after 210 minutes of ischemia. Ischemia (30 minutes) followed by reperfusion (180 minutes) increased the ceramide level to 250% in the ischemic area. The combination of results obtained in both in vitro and animal models demonstrate for the first time that ceramide signaling can be involved in ischemia/reperfusion death of myocardial cells. Images Figure 2 Figure 4 PMID:9358751

  15. Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction.

    PubMed

    Hofmann, Ulrich; Frantz, Stefan

    2015-01-16

    A large body of evidence produced during decades of research indicates that myocardial injury activates innate immunity. On the one hand, innate immunity both aggravates ischemic injury and impedes remodeling after myocardial infarction (MI). On the other hand, innate immunity activation contributes to myocardial healing, as exemplified by monocytes' central role in the formation of a stable scar and protection against intraventricular thrombi after acute infarction. Although innate leukocytes can recognize a wide array of self-antigens via pattern recognition receptors, adaptive immunity activation requires highly specific cooperation between antigen-presenting cells and distinct antigen-specific receptors on lymphocytes. We have only recently begun to examine lymphocyte activation's relationship to adaptive immunity and significance in the context of ischemic myocardial injury. There is some experimental evidence that CD4(+) T-cells contribute to ischemia-reperfusion injury. Several studies have shown that CD4(+) T-cells, especially CD4(+) T-regulatory cells, improve wound healing after MI, whereas depleting B-cells is beneficial post MI. That T-cell activation after MI is induced by T-cell receptor signaling implicates autoantigens that have not yet been identified in this context. Also, the significance of lymphocytes in humans post MI remains unclear, primarily as a result of methodology. This review summarizes current experimental evidence of lymphocytes' activation, functional role, and crosstalk with innate leukocytes in myocardial ischemia-reperfusion injury, wound healing, and remodeling after myocardial infarction.

  16. Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO.

    PubMed

    Di Paola, Rosanna; Cordaro, Marika; Crupi, Rosalia; Siracusa, Rosalba; Campolo, Michela; Bruschetta, Giuseppe; Fusco, Roberta; Pugliatti, Pietro; Esposito, Emanuela; Cuzzocrea, Salvatore

    2016-08-01

    Myocardial infarction is the leading cause of death, occurs after prolonged ischemia of the coronary arteries. Restore blood flow is the first intervention help against heart attack. However, reperfusion of the arteries leads to ischemia/reperfusion injury (I/R). The fatty acid amide palmitoylethanolamide (PEA) is an endogenous compound widely present in living organisms, with analgesic and anti-inflammatory properties. The present study evaluated the effect of ultramicronized palmitoylethanolamide (PEA-um) treatment on the inflammatory process associated with myocardial I/R. Myocardial ischemia reperfusion injury was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. PEA-um, was administered (10 mg/kg) 15 min after ischemia and 1 h after reperfusion. In this study, we demonstrated that PEA-um treatment reduces myocardial tissue injury, neutrophil infiltration, adhesion molecules (ICAM-1, P-selectin) expression, proinflammatory cytokines (TNF-α, IL-1β) production, nitrotyrosine and PAR formation, nuclear factor kB expression, and apoptosis (Fas-L, Bcl-2) activation. In addition to study whether the protective effect of PEA-um on myocardial ischemia reperfusion injury is also related to the activation of PPAR-α, in a separate set of experiments it has been performed myocardial I/R in PPARα mice. Genetic ablation of peroxisome proliferator activated receptor (PPAR)-α in PPAR-αKO mice exacerbated Myocardial ischemia reperfusion injury when compared with PPAR-αWT mice. PEA-um induced cardioprotection in PPAR-α wild-type mice, but the same effect cannot be observed in PPAR-αKO mice. Our results have clearly shown a modulation of the inflammatory process, associated with myocardial ischemia reperfusion injury, following administration of PEA-um. PMID:26844976

  17. Trauma induced myocardial infarction.

    PubMed

    Lolay, Georges A; Abdel-Latif, Ahmed K

    2016-01-15

    Chest Trauma in athletes is a common health problem. However, myocardial infarction secondary to coronary dissection in the setting of blunt chest trauma is extremely rare. We report a case of acute inferior wall myocardial infarction following blunt chest trauma. A 32-year-old male with no relevant medical problems was transferred to our medical center for retrosternal chest pain after being elbowed in the chest during a soccer game. Few seconds later, he started experiencing sharp retrosternal chest pain that was severe to that point where he called the emergency medical service. Upon arrival to the trauma department patient was still complaining of chest pain. ECG demonstrated ST segment elevation in the inferior leads with reciprocal changes in the lateral leads all consistent with active ischemia. After rolling out aortic dissection, patient was loaded with ASA, ticagerlor, heparin and was emergently taken to the cardiac catheterization lab. Coronary angiography demonstrated 100% thrombotic occlusion in the distal right coronary artery with TIMI 0 flow distally. After thrombus aspiration, a focal dissection was noted on the angiogram that was successfully stented. Two days after admission patient was discharged home. Echocardiography prior to discharge showed inferior wall akinesis, normal right ventricular systolic function and normal overall ejection fraction.

  18. Myocardial Bridge

    MedlinePlus

    ... artery. See also on this site: Ask a Texas Heart Institute Doctor: Search "myocardial bridge" Updated August ... comments. Terms of Use and Privacy Policy © Copyright Texas Heart Institute All rights reserved.

  19. Myocardial stunning in hypertrophic cardiomyopathy: recovery predicted by single photon emission computed tomographic thallium-201 scintigraphy

    SciTech Connect

    Fine, D.G.; Clements, I.P.; Callahan, M.J.

    1989-05-01

    A young woman with hypertrophic cardiomyopathy confirmed by echocardiography and cardiac catheterization presented with chest pain and features of a large left ventricular aneurysm. The initial diagnosis was myocardial ischemia with either an evolving or an ancient myocardial infarction. Subsequently, verapamil therapy was associated with complete resolution of the extensive left ventricular wall motion abnormalities, normalization of left ventricular ejection fraction and a minimal myocardial infarction. Normal thallium uptake on single photon emission computed tomographic scintigraphy early in the hospital course predicted myocardial viability in the region of the aneurysm. Thus, orally administered verapamil may reverse spontaneous extensive myocardial ischemia in hypertrophic cardiomyopathy and possibly limit the extent of myocardial infarction in such circumstances.

  20. Acute mesenteric ischemia.

    PubMed

    Sise, Michael J

    2014-02-01

    Acute mesenteric ischemia is uncommon and always occurs in the setting of preexisting comorbidities. Mortality rates remain high. The 4 major types of acute mesenteric ischemia are acute superior mesenteric artery thromboembolic occlusion, mesenteric arterial thrombosis, mesenteric venous thrombosis, and nonocclusive mesenteric ischemia, including ischemic colitis. Delays in diagnosis are common and associated with high rates of morbidity and mortality. Prompt diagnosis requires attention to history and physical examination, a high index of suspicion, and early contract CT scanning. Selective use of nonoperative therapy has an important role in nonocclusive mesenteric ischemia of the small bowel and colon.

  1. Cardioplegia and myocardial preservation during cardiopulmonary bypass.

    PubMed

    Engelman, R M; Levitsky, S; O'Donoghue, M J; Auvil, J

    1978-09-01

    A standard experimental protocol was developed to explore the role of hypothermia and potassium cardioplegia in myocardial preservation during 120 minutes of ischemic arrest followed by 30 minutes of reperfusion. Seven different experimental groups of six animals each were evaluated using an in-vivo pig heart preparation. Hypothermic arrest without cardioplegia and cardioplegic arrest at normothermia were each compared to hypothermic cardioplegia. In addition, the use of an asanguineous hypothermic coronary perfusate without cardioplegia was compared to both multidose cardioplegia and single-dose cardioplegia followed by the same asanguineous perfusate. The parameters measured included: myocardial contractility and compliance, myocardial blood flow, endocardial/epicardial blood flow ratio, and electron microscopic studies. Myocardial preservation was inadequate with hypothermic arrest alone (without cardioplegia; and with cardioplegia at normothermia. In both experimental groups, myocardial contractility and compliance were so depressed that the) could not be accurately measured following ischemia and reperfusion while coronary blood flow remained significantly elevated. Preservation was improved but still inadequate following myocardial washout with a normokalemic or hypokalemic perfusate and following single dose cardioplegia plus myocardial washout. In the latter four groups, contractility ranged from 42 to 78% of control, and there was a decrease in compliance of 16 to 78%. Adequate preservation was found only after hypothermia and multidose potassium (35 mEq/L) cardioplegia. In this group, contractility was 129 +/- 13% of control and compliance increased by 21 +/- 24% compared to that of the control.

  2. Myocardial ischemic conditioning: Physiological aspects and clinical applications in cardiac surgery.

    PubMed

    Bousselmi, Radhouane; Lebbi, Mohamed Anis; Ferjani, Mustapha

    2014-04-01

    Ischemia-reperfusion is a major determinant of myocardial impairment in patients undergoing cardiac surgery. The main goal of research in cardioprotection is to develop effective techniques to avoid ischemia-reperfusion lesions. Myocardial ischemic conditioning is a powerful endogenous cardioprotective phenomenon. First described in animals in 1986, myocardial ischemic conditioning consists of applying increased tolerance of the myocardium to sustained ischemia by exposing it to brief episodes of ischemia-reperfusion. Several studies have sought to demonstrate its effective cardioprotective action in humans and to understand its underlying mechanisms. Myocardial ischemic conditioning has two forms: ischemic preconditioning (IPC) when the conditioning stimulus is applied before the index ischemia and ischemic postconditioning when the conditioning stimulus is applied after it. The cardioprotective action of ischemic conditioning was reproduced by applying the ischemia-reperfusion stimulus to organs remote from the heart. This non-invasive manner of applying ischemic conditioning has led to its application in clinical settings. Clinical trials for the different forms of ischemic conditioning were mainly developed in cardiac surgery. Many studies suggest that this phenomenon can represent an interesting adjuvant to classical cardioprotection during on-pump cardiac surgery. Ischemic conditioning was also tested in interventional cardiology with interesting results. Finally, advances made in the understanding of mechanisms that underlie the cardioprotective action of ischemic conditioning have paved the way to a new form of myocardial conditioning which is pharmacological conditioning.

  3. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs

    SciTech Connect

    Schelbert, H.R.; Phelps, M.E.

    1980-06-01

    While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (/sup 13/N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique.

  4. Spontaneous colonic ischemia in a patient with Riley-Day syndrome.

    PubMed

    Applegate, K E; Sargent, S K

    1995-01-01

    Familial dysautonomia, or Riley-Day syndrome, is a hereditary disturbance in the autonomic and peripheral sensory nervous systems, first described by Riley, Day, and colleagues in 1949 [1, 2]. Previous reports of myocardial infarction and avascular necrosis in bone suggest that these patients are at risk for ischemia at certain organ sites [3, 4]. We report a case of spontaneous colonic ischemia and stricture which resulted in colocutaneous fistula formation and eventual colonic resection in a child with Riley-Day syndrome.

  5. 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

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

    PubMed Central

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

    2014-01-01

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

  7. Recovery from myocardial stunning is faster with desflurane compared with propofol in chronically instrumented dogs.

    PubMed

    Meissner, A; Weber, T P; Van Aken, H; Zbieranek, K; Rolf, N

    2000-12-01

    Volatile anesthetics exert a protective role in myocardial ischemia. An increase in sympathetic tone might exert deleterious effects on the ischemic myocardium. The use of the volatile anesthetic desflurane in myocardial ischemia is controversial because of its sympathetic activation. We compared propofol and desflurane on myocardial stunning in chronically instrumented dogs. Mongrel dogs (n = 8) were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure, rate of rise of left ventricular pressure, and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed the induction of reversible LAD-ischemia. Two experiments were performed in a cross-over fashion on separate days: 1) Induction of 10 min of LAD-ischemia during desflurane anesthesia and 2) Induction of 10 min of LAD-ischemia during propofol anesthesia. Both anesthetics were discontinued immediately after completion of ischemia. WTF was measured at predetermined time points until complete recovery from ischemic dysfunction occurred. Both anesthetics caused a significant decrease of WTF in the LAD-perfused myocardium. LAD-ischemia led to a further significant decrease of LAD-WTF in both groups. During the first 3 h of reperfusion, WTF was significantly larger in the desflurane group. Mean arterial pressure and heart rate were greater during ischemia and the first 10 min of reperfusion in the desflurane group compared with the propofol group. Recovery from myocardial stunning in dogs was faster when desflurane was used at the time of ischemia as compared with propofol anesthesia. The mechanism for this difference is unclear, but sympathetic activation by desflurane was not a limiting factor for ischemic tolerance in chronically instrumented dogs. PMID:11093975

  8. Physical Stress Echocardiography: Prediction of Mortality and Cardiac Events in Patients with Exercise Test showing Ischemia

    PubMed Central

    de Araujo, Ana Carla Pereira; Santos, Bruno F. de Oliveira; Calasans, Flavia Ricci; Pinto, Ibraim M. Francisco; de Oliveira, Daniel Pio; Melo, Luiza Dantas; Andrade, Stephanie Macedo; Tavares, Irlaneide da Silva; Sousa, Antonio Carlos Sobral; Oliveira, Joselina Luzia Menezes

    2014-01-01

    Background Studies have demonstrated the diagnostic accuracy and prognostic value of physical stress echocardiography in coronary artery disease. However, the prediction of mortality and major cardiac events in patients with exercise test positive for myocardial ischemia is limited. Objective To evaluate the effectiveness of physical stress echocardiography in the prediction of mortality and major cardiac events in patients with exercise test positive for myocardial ischemia. Methods This is a retrospective cohort in which 866 consecutive patients with exercise test positive for myocardial ischemia, and who underwent physical stress echocardiography were studied. Patients were divided into two groups: with physical stress echocardiography negative (G1) or positive (G2) for myocardial ischemia. The endpoints analyzed were all‑cause mortality and major cardiac events, defined as cardiac death and non-fatal acute myocardial infarction. Results G2 comprised 205 patients (23.7%). During the mean 85.6 ± 15.0-month follow-up, there were 26 deaths, of which six were cardiac deaths, and 25 non-fatal myocardial infarction cases. The independent predictors of mortality were: age, diabetes mellitus, and positive physical stress echocardiography (hazard ratio: 2.69; 95% confidence interval: 1.20 – 6.01; p = 0.016). The independent predictors of major cardiac events were: age, previous coronary artery disease, positive physical stress echocardiography (hazard ratio: 2.75; 95% confidence interval: 1.15 – 6.53; p = 0.022) and absence of a 10% increase in ejection fraction. All-cause mortality and the incidence of major cardiac events were significantly higher in G2 (p < 0. 001 and p = 0.001, respectively). Conclusion Physical stress echocardiography provides additional prognostic information in patients with exercise test positive for myocardial ischemia. PMID:25352460

  9. Pediatric myocardial protection: an overview.

    PubMed

    Allen, B S; Barth, M J; Ilbawi, M N

    2001-01-01

    This article describes the experimental infrastructure and subsequent successful clinical application of a comprehensive bypass and cardioplegic strategy that limits intraoperative injury and improves postoperative outcomes in pediatric patients. The infant heart is at high risk of damage from poor protection because of preoperative hypertrophy, cyanosis, and ischemia. The background factors of vulnerability to damage caused by cyanosis and ischemia are discussed, together with studies of the infrastructure of strategies to use normoxia versus hyperoxia as bypass starts, white blood cell filtration, warm induction and reperfusion with substrate enhancements, multidose blood cardioplegia, and an integrated approach to allow ischemia only when vision is needed in pediatric surgeries. Data on cardioplegic management, including reducing calcium, increasing magnesium, and reducing perfusion pressure are shown, as used during this technique. These principles were applied to a consecutive series of 567 patients at the Heart Institute for Children and University of Illinois hospital over a 2-year period. Included also were 72 patients with hypoplastic left heart over a 4-year period with this myocardial management strategy. Application of these concepts may improve the safety of protection in infant hearts. PMID:11309728

  10. Novel adjunctive treatments of myocardial infarction

    PubMed Central

    Schmidt, Michael Rahbek; Pryds, Kasper; Bøtker, Hans Erik

    2014-01-01

    Myocardial infarction is a major cause of death and disability worldwide and myocardial infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome, but reperfusion may induce further myocardial damage itself. Development of adjunctive therapies to limit myocardial reperfusion injury beyond opening of the coronary artery gains increasing attention. A vast number of experimental studies have shown cardioprotective effects of ischemic and pharmacological conditioning, but despite decades of research, the translation into clinical effects has been challenging. Recently published clinical studies, however, prompt optimism as novel techniques allow for improved clinical applicability. Cyclosporine A, the GLP-1 analogue exenatide and rapid cooling by endovascular infusion of cold saline all reduce infarct size and may confer clinical benefit for patients admitted with acute myocardial infarcts. Equally promising, three follow-up studies of the effect of remote ischemic conditioning (RIC) show clinical prognostic benefit in patients undergoing coronary surgery and percutaneous coronary intervention. The discovery that RIC can be performed noninvasively using a blood pressure cuff on the upper arm to induce brief episodes of limb ischemia and reperfusion has facilitated the translation of RIC into the clinical arena. This review focus on novel advances in adjunctive therapies in relation to acute and elective coronary procedures. PMID:24976915

  11. The Utility of Cardiopulmonary Exercise Testing in the Assessment of Suspected Microvascular Ischemia

    PubMed Central

    Chaudhry, Sundeep; Arena, Ross; Wasserman, Karlman; Hansen, James E.; Lewis, Gregory D.; Myers, Jonathan; Belardinelli, Romualdo; LaBudde, Brian; Menasco, Nicholas; Boden, William E.

    2010-01-01

    Evidence demonstrating the potential value of cardiopulmonary exercise testing (CPET) to accurately detect myocardial ischemia secondary to macro-vascular disease is beginning to emerge. Despite distinct mechanisms mediating ischemia in micro-vascular and macrovascular coronary artery disease (CAD), the net physiologic effect of exercise-induced left ventricular (LV) dysfunction is common to both. The abnormal physiologic response to CPET may, therefore, be similar in patients with macro- and micro-vascular ischemia. The following case report describes the CPET abnormalities in a patient with suspected microvascular CAD and the subsequent improvement in LV function following three weeks of medical therapy with the anti-ischemic drug ranolazine. PMID:19233492

  12. [Risk assessment and measuring the need for revascularization on the basis of residual ischemia by means of dobutamine stress echocardiography in the early phase of the first myocardial infarction].

    PubMed

    Nyúzó, B; Pálinkás, A; Szabó, E; Ungi, I; Szécsi, J

    1999-08-29

    The aim of this study is to present a modern method which can be used in the early phase of myocardial infarction. Its results show that with the detection of residual ischaemia, valuable information can be gained concerning the progression of the disease and the claim to revascularisation. During the first week (2-7 days), the authors performed risk assessing dobutamine stress echocardiography in 52 nonselected acute patients with first myocardial infarction. Patients with negative results were regarded as low risk cases 35/52 (67.3%), while those with positive results were regarded as high risk cases 17/52 (32.7%). The number of the serious postinfarction hard events was 22/52 (42.3%) during the one-year following period. In the case of the positive group, during mainly the first three months the occurrence of such events was found to be extremely high: 16/17 (94.1%), while in the case of the negative group it was only 6/35 (17.1%). On the basis of the test results it can be stated that coronarography was performed in 14/17 (82.4%) vs. 3/35 (8.6%) of the cases, and revascularisation in 10/17 (58.8%) vs. 1/35 (2.9%) of the cases. In 2/17 (11.8%) vs. 3/35 (8.6%) of the cases, the patients suffered from acute coronary syndrome and the mortality rate was 2/17 (11.8%) vs. 1/35 (2.9%). The sensitivity value was 79.1%, the specificity value 90.6%, and the positive and negative predictive values 86.3% and 85.3%. There was no such significant complication detected which could be attributable to the examination. On the basis of the results and corresponding to the data in special literature, the authors found the dobutamine stress test a good and safe prognostical method even some days after the infarction. With the help of this method the high and low risk groups of patients can be separated early, and at the same time the claim to revascularisation in the first three months can be measured too.

  13. Myocardial perfusion imaging study of CO(2)-induced panic attack.

    PubMed

    Soares-Filho, Gastão L F; Machado, Sergio; Arias-Carrión, Oscar; Santulli, Gaetano; Mesquita, Claudio T; Cosci, Fiammetta; Silva, Adriana C; Nardi, Antonio E

    2014-01-15

    Chest pain is often seen alongside with panic attacks. Moreover, panic disorder has been suggested as a risk factor for cardiovascular disease and even a trigger for acute coronary syndrome. Patients with coronary artery disease may have myocardial ischemia in response to mental stress, in which panic attack is a strong component, by an increase in coronary vasomotor tone or sympathetic hyperactivity setting off an increase in myocardial oxygen consumption. Indeed, coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. These findings correlating panic disorder with coronary artery disease lead us to raise questions about the favorable prognosis of chest pain in panic attack. To investigate whether myocardial ischemia is the genesis of chest pain in panic attacks, we developed a myocardial perfusion study through research by myocardial scintigraphy in patients with panic attacks induced in the laboratory by inhalation of 35% carbon dioxide. In conclusion, from the data obtained, some hypotheses are discussed from the viewpoint of endothelial dysfunction and microvascular disease present in mental stress response. PMID:24188891

  14. Role of myocardial perfusion imaging in evaluating thrombolytic therapy for acute myocardial infarction

    SciTech Connect

    Beller, G.A.

    1987-03-01

    Myocardial thallium-201 scintigraphy is being increasingly employed as a method for assessing the efficacy of coronary reperfusion in acute myocardial infarction. New thallium uptake after intracoronary tracer administration after successful recanalization indicates that nutrient blood flow has been successfully restored. One may also presume that some myocardial salvage occurred if thallium administered in this manner is transported intracellularly by myocytes with intact sarcolemmal membranes. However, if one injects thallium by way of the intracoronary route immediately after reperfusion, the initial uptake of thallium in reperfused myocardium may predominantly represent hyperemic flow and regional thallium counts measured may not be proportional to the mass of viable myocytes. When thallium is injected intravenously during the occlusion phase the degree of redistribution after thrombolysis is proportional to the degree of flow restoration and myocardial viability. When thallium is injected for the first time intravenously immediately after reperfusion, an overestimation of myocardial salvage may occur because of excess thallium uptake in the infarct zone consequent to significant hyperemia. Another approach to myocardial thallium scintigraphy in patients undergoing thrombolytic therapy is to administer two separate intravenous injections before and 24 hours or later after treatment. Finally, patients with acute myocardial infarction who receive intravenous thrombolytic therapy are candidates for predischarge exercise thallium-201 scintigraphy for risk stratification and detection of residual ischemia.

  15. Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

    PubMed Central

    Kezic, Aleksandra; Spasojevic, Ivan; Lezaic, Visnja; Bajcetic, Milica

    2016-01-01

    Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury. PMID:27313826

  16. Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury.

    PubMed

    Kezic, Aleksandra; Spasojevic, Ivan; Lezaic, Visnja; Bajcetic, Milica

    2016-01-01

    Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury. PMID:27313826

  17. Induction and Assessment of Ischemia-reperfusion Injury in Langendorff-perfused Rat Hearts

    PubMed Central

    Herr, Daniel J.; Aune, Sverre E.; Menick, Donald R.

    2015-01-01

    The biochemical events surrounding ischemia reperfusion injury in the acute setting are of great importance to furthering novel treatment options for myocardial infarction and cardiac complications of thoracic surgery. The ability of certain drugs to precondition the myocardium against ischemia reperfusion injury has led to multiple clinical trials, with little success. The isolated heart model allows acute observation of the functional effects of ischemia reperfusion injury in real time, including the effects of various pharmacological interventions administered at any time-point before or within the ischemia-reperfusion injury window. Since brief periods of ischemia can precondition the heart against ischemic injury, in situ aortic cannulation is performed to allow for functional assessment of non-preconditioned myocardium. A saline filled balloon is placed into the left ventricle to allow for real-time measurement of pressure generation. Ischemic injury is simulated by the cessation of perfusion buffer flow, followed by reperfusion. The duration of both ischemia and reperfusion can be modulated to examine biochemical events at any given time-point. Although the Langendorff isolated heart model does not allow for the consideration of systemic events affecting ischemia and reperfusion, it is an excellent model for the examination of acute functional and biochemical events within the window of ischemia reperfusion injury as well as the effect of pharmacological intervention on cardiac pre- and postconditioning. The goal of this protocol is to demonstrate how to perform in situ aortic cannulation and heart excision followed by ischemia/reperfusion injury in the Langendorff model. PMID:26274877

  18. Evaluation of activity of an estrogen-derivative as cardioprotector drug using an ischemia-reperfusion injury model

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Marcela, Rosas-Nexticapa; Eduardo, Pool-Gómez; Maria, Lopéz-Ramos; Fernanda, Rodriguez-Hurtado; Marissa, Chan-Salvador

    2015-01-01

    Myocardial ischemia/reperfusion injury is a serious problem involved in cardiovascular diseases. There data which indicate that some steroids induce cardioprotective effects on myocardial ischemia-reperfusion injury; however their activity and the molecular mechanism involved on myocardial ischemia-reperfusion injury are very confusing. Therefore, in this study some estrogen derivatives (compound 3 to 7) were synthesized with the objective of evaluating its activity on myocardial ischemia/reperfusion injury using an isolated heart model. Additionally, molecular mechanism involved in the activity exerted by the compounds 3 to 7 on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in absence or presence of following compounds; prazosin, metoprolol, indomethacin and nifedipine. The results showed that 7 reduce infarct size compared with the estrone and other estrogen derivatives (compounds 3, 4, 5, and 6). Other results showed that 7 significantly increase the perfusion pressure and coronary resistance in isolated heart in comparison with estrone, 3, 4, 5, and 6. Finally, other data indicate that 7 increased the left ventricular pressure in a dose-dependent manner; however, this phenomenon was significantly inhibited by nifedipine. In conclusion, all these data suggest that 7 exert a cardioprotective effect through calcium channels activation and consequently induce changes in the left ventricular pressure levels. This phenomenon results in decrease of myocardial necrosis after ischemia and reperfusion. PMID:26550116

  19. The Relationship Between Some Complete Blood Count Parameters and Myocardial Perfusion: A Scintigraphic Approach

    PubMed Central

    Ozdemir, Semra; Barutcu, Ahmet; Gazi, Emine; Tan, Yusuf Ziya; Turkon, Hakan

    2015-01-01

    Recent studies have shown that there is a relationship between some inflammatory and biochemical markers derived from complete blood count (CBC) such as neutrophil/lymphocyte (N/L) ratio, platelet/lymphocyte (P/L) ratio, platelet distribution width (PDW), red blood cell distribution width (RDW), and coronary artery disease (CAD). The aim of this study was to determine N/L ratio, P/L ratio, PDW values, and RDW values, which are associated with myocardial perfusion in patients diagnosed with CAD. This study included 262 patients (149 with myocardial ischemia/infarction and 113 with normal myocardial perfusion) undergoing myocardial perfusion scintigraphy (MPS) with CBC within 90 days of MPS. Myocardial perfusion parameters such as summed stress score and summed difference score (SDS) were compared with N/L ratio, P/L ratio, PDW values, and RDW values. Neutrophil counts and N/L ratios were significantly higher in patients diagnosed with myocardial ischemia and/or infarct. However, there was no statistically significant relationship between myocardial perfusion abnormalities and P/L ratio, PDW values, and RDW values. This study showed that N/L ratio is related to myocardial ischemia/infarction and correlated to left ventricular ejection fraction (LVEF). PMID:26420991

  20. Echocardiographic assessment of myocardial strain.

    PubMed

    Gorcsan, John; Tanaka, Hidekazu

    2011-09-27

    Echocardiographic strain imaging, also known as deformation imaging, has been developed as a means to objectively quantify regional myocardial function. First introduced as post-processing of tissue Doppler imaging velocity converted to strain and strain rate, strain imaging has more recently also been derived from digital speckle tracking analysis. Strain imaging has been used to gain greater understanding into the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, and the effects of valvular disease on myocardial function, and to advance our understanding of diastolic function. Strain imaging has also been used to quantify abnormalities in the timing of mechanical activation for heart failure patients undergoing cardiac resynchronization pacing therapy. Further advances, such as 3-dimensional speckle tracking strain imaging, have emerged to provide even greater insight. Strain imaging has become established as a robust research tool and has great potential to play many roles in routine clinical practice to advance the care of the cardiovascular patient. This perspective reviews the physiology of myocardial strain, the technical features of strain imaging using tissue Doppler imaging and speckle tracking, their strengths and weaknesses, and the state-of-the-art present and potential future clinical applications.

  1. Regulation of the proteasome by ATP: implications for ischemic myocardial injury and donor heart preservation.

    PubMed

    Majetschak, Matthias

    2013-08-01

    Several lines of evidence suggest that proteasomes are involved in multiple aspects of myocardial physiology and pathology, including myocardial ischemia-reperfusion injury. It is well established that the 26S proteasome is an ATP-dependent enzyme and that ischemic heart disease is associated with changes in the ATP content of the cardiomyocyte. A functional link between the 26S proteasome, myocardial ATP concentrations, and ischemic cardiac injury, however, has been suggested only recently. This review discusses the currently available data on the pathophysiological role of the cardiac proteasome during ischemia and reperfusion in the context of the cellular ATP content. Depletion of the myocardial ATP content during ischemia appears to activate the 26S proteasome via direct regulatory effects of ATP on 26S proteasome stability and activity. This implies pathological degradation of target proteins by the proteasome and could provide a pathophysiological basis for beneficial effects of proteasome inhibitors in various models of myocardial ischemia. In contrast to that in the ischemic heart, reduced and impaired proteasome activity is detectable in the postischemic heart. The paradoxical findings that proteasome inhibitors showed beneficial effects when administered during reperfusion in some studies could be explained by their anti-inflammatory and immune suppressive actions, leading to reduction of leukocyte-mediated myocardial reperfusion injury. The direct regulatory effects of ATP on the 26S proteasome have implications for the understanding of the contribution of the 26S proteasome to the pathophysiology of the ischemic heart and its possible role as a therapeutic target.

  2. Cardioprotection against experimental myocardial ischemic injury using cornin

    PubMed Central

    Xu, Y.; Xu, Y.; Luan, H.; Jiang, Y.; Tian, X.; Zhang, S.

    2016-01-01

    Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt. PMID:26871971

  3. Cardioprotection against experimental myocardial ischemic injury using cornin.

    PubMed

    Xu, Y; Xu, Y; Luan, H; Jiang, Y; Tian, X; Zhang, S

    2016-02-01

    Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

  4. Myocardial perfusion SPECT in a case of retropulmonary looping of left coronary artery in a baby after arterial switch surgery

    PubMed Central

    Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga

    2014-01-01

    Pediatric myocardial perfusion imaging (MPI) is not a routine investigation in an Indian setting due to under referrals and logistic problems. However, MPI is a frequently performed and established modality of investigation in adults for the identification of myocardial ischemia and viability. We report myocardial perfusion scintigraphy in a case of retropulmonary looping of left coronary artery in a baby after arterial switch surgery. Adenosine stress MPI revealed a large infarct involving anterior segment with moderate reversible ischemia of the lateral left ventricular segment. Coronary angiogram later confirmed left main coronary artery ostial occlusion with retrograde collateral supply from dilated right coronary artery. PMID:24761067

  5. Myocardial perfusion imaging with dual energy CT.

    PubMed

    Jin, Kwang Nam; De Cecco, Carlo N; Caruso, Damiano; Tesche, Christian; Spandorfer, Adam; Varga-Szemes, Akos; Schoepf, U Joseph

    2016-10-01

    Dual-energy CT (DECT) enables simultaneous use of two different tube voltages, thus different x-ray absorption characteristics are acquired in the same anatomic location with two different X-ray spectra. The various DECT techniques allow material decomposition and mapping of the iodine distribution within the myocardium. Static dual-energy myocardial perfusion imaging (sCTMPI) using pharmacological stress agents demonstrate myocardial ischemia by single snapshot images of myocardial iodine distribution. sCTMPI gives incremental values to coronary artery stenosis detected on coronary CT angiography (CCTA) by showing consequent reversible or fixed myocardial perfusion defects. The comprehensive acquisition of CCTA and sCTMPI offers extensive morphological and functional evaluation of coronary artery disease. Recent studies have revealed that dual-energy sCTMPI shows promising diagnostic accuracy for the detection of hemodynamically significant coronary artery disease compared to single-photon emission computed tomography, invasive coronary angiography, and cardiac MRI. The aim of this review is to present currently available DECT techniques for static myocardial perfusion imaging and recent clinical applications and ongoing investigations.

  6. Release of nucleosides from canine and human hearts as an index of prior ischemia.

    PubMed

    Fox, A C; Reed, G E; Meilman, H; Silk, B B

    1979-01-01

    During ischemia, myocardial adenosine triphosphate is degraded to adenosine, inosine and hypoxanthine. These nucleosides are released into coronary venous blood and may provide an index of ischemia; adenosine may also participate in the autoregulation of coronary flow. In dogs, the temporal relations between reactive hyperemic flow and nucleoside concentrations in regional venous blood were correlated after brief occlusions of a segmental coronary artery. Reactive hyperemia and adenosine release peaked together in 10 seconds, persisted for 10 to 30 seconds and then decreased in a pattern consistent with the hypothesis that they are related. During initial reflow after 45 seconds of ischemia, mean concentrations of adenosine, inosine and hypoxanthine increased, respectively, to 52, 67 and 114 nmol/100 ml plasma; after 5 minutes of ischemia, the respective levels increased to 58, 1,570 and 1,134 nmol and fell quickly. In nine patients there was a similar release of nucleosides into coronary sinus blood during reperfusion after 59 to 80 minutes of ischemic arrest during cardiac surgery. With initial reflow, adenosine, inosine and hypoxanthine levels reached 65, 655 and 917 nmol/100 ml of blood, respectively. Inosine and hypoxanthine concentrations remained high for 5 to 10 minutes after cardiac beating resumed, often when production of lactate had decreased. The results indicate that postischemic release of nucleosides reaches significant levels in man as well as animals, is parallel with the duration of ischemia, is temporary and may be a useful supplement to measurement of lactate as an index of prior myocardial ischemia. PMID:758770

  7. Long-term follow-up of patients with silent ischemia during exercise radionuclide angiography

    SciTech Connect

    Breitenbuecher, A.P.; Pfisterer, M.; Hoffmann, A.; Burckhardt, D. )

    1990-04-01

    A retrospective 5 year follow-up study was performed in 140 patients with unequivocal ischemia during exercise radionuclide angiography (greater than or equal to 10% decrease in left ventricular ejection fraction or greater than or equal to 5% decrease in ejection fraction together with a distinct regional wall motion abnormality). In 84 patients (60%), ischemia during radionuclide angiography was silent (silent ischemia group), whereas 56 patients experienced angina during the test (symptomatic group). Work load and antianginal medication were similar in both groups. Critical cardiac events (unstable angina, myocardial infarction, cardiac death) occurred in 27% of patients in the silent ischemia group and 16% of those in the symptomatic group (p = NS); however, myocardial infarction or death was more frequent in patients with silent ischemia (22% versus 9%; p less than 0.05). If there was additional exercise-induced ST segment depression, the rate of critical events was further increased (p less than 0.05). The difference in critical cardiac events seemed to be influenced by the higher incidence of revascularization procedures in symptomatic patients, whereas medical therapy had no similar effect. Thus, these findings suggest that patients with documented severe ischemia should undergo left heart catheterization and revascularization irrespective of symptoms to improve their prognosis.

  8. The mechanism of myocardial reperfusion injury in neonates.

    PubMed

    Otani, H; Engelman, R M; Rousou, J A; Breyer, R H; Lemeshow, S; Das, D K

    1987-11-01

    Oxygen free radicals and phospholipid degradation have been implicated in the pathogenesis of ischemia and reperfusion injury. The present study examines the involvement of such mechanisms in myocardial reperfusion injury in neonatal hearts. The isolated neonatal pig hearts from two different age groups, 0 to 2 days old (newborn) and 7 to 9 days old (week-old), were subjected to 60 min of normothermic global ischemia followed by 60 min of reperfusion. Although myocardial ischemia reduced superoxide dismutase, catalase, and glutathione peroxidase activities in both age groups, superoxide dismutase and catalase activities remained significantly lower in the newborn pig heart during ischemia and reperfusion. Oxidized glutathione release from the neonatal pig hearts was at minimum levels before ischemia, but it increased 10-fold at the onset of reperfusion and was significantly higher in the newborn heart. This indicates that generation of oxygen free radicals was enhanced in the newborn compared with that in the week-old heart. The increase in phospholipase A2 activity and decrease in acyl CoA synthetase and lysophosphatidylcholine acyl transferase activities during ischemia and reperfusion were associated with comparable loss of membrane phospholipids and accumulation of lysophosphatidylcholine and free fatty acids in both age groups, except that oleic acid content was significantly higher in the newborn heart during reperfusion. Myocardial damage appears to be potentiated in the newborn heart during reperfusion, as evidenced by higher release of creatine kinase and a lower content of high-energy phosphates. These results indicate that oxygen free radicals may play a crucial role in the occurrence of reperfusion injury in immature hearts. PMID:3665015

  9. Thoracic epidural anesthesia improves functional recovery from myocardial stunning in conscious dogs.

    PubMed

    Rolf, N; Van de Velde, M; Wouters, P F; Möllhoff, T; Weber, T P; Van Aken, H K

    1996-11-01

    The effects of thoracic epidural anesthesia (TEA) on the contractile performance of ischemic and postischemic myocardium have not been well investigated. The purpose of this investigation was to examine the effects of TEA on severity and duration of myocardial stunning in an experimental model for sublethal acute myocardial ischemia. Seven dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic and left ventricular pressure (LVP), LV dP/dtmax' and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed induction of reversible LAD ischemia. TEA was performed with lidocaine 4 mg/kg through a chronically implanted epidural catheter at the second thoracic level. Regional myocardial blood flow was determined with colored microspheres. Two experiments were performed in a cross-over design on separate days: Experiment 1, induction of 10 min of LAD ischemia without TEA; and Experiment 2, induction of 10 min of LAD ischemia with TEA. WTF was measured at baseline (BL) and predetermined time points until complete recovery from ischemic dysfunction occurred. LAD ischemia caused a significant decrease of LAD-WTF with (-28% +/- 5.1% versus BL) and without TEA (-15.5% +/- 5.3% versus BL). After 3 h of reperfusion, WTF as percent of BL values was significantly higher with TEA (P < 0.001). BL values of WTF were reached after 24 h with TEA and after more than 48 h without TEA (P < 0.05). There were no significant differences for mean arterial pressure (MAP), heart rate (HR), LVP, LAP, and LVdP/dtmax between the groups during ischemia and reperfusion. In nonischemic myocardium TEA caused an increase of subendocardial blood flow. During ischemia neither the subendocardial/subepicardial nor the occluded/ normal zone blood flow was affected by TEA. TEA attenuates myocardial stunning in conscious dogs. This finding is consistent with data regarding a reduction of infarct size due to TEA. PMID

  10. Neuroprotection after cerebral ischemia

    PubMed Central

    Namura, Shobu; Ooboshi, Hiroaki; Liu, Jialing; Yenari, Midori A.

    2013-01-01

    Cerebral ischemia, a focal or global insufficiency of blood flow to the brain, can arise through multiple mechanisms, including thrombosis and arterial hemorrhage. Ischemia is a major driver of stroke, one of the leading causes of morbidity and mortality worldwide. While the general etiology of cerebral ischemia and stroke has been known for some time, the conditions have only recently been considered treatable. This report describes current research in this field seeking to fully understand the pathomechanisms underlying stroke; to characterize the brain’s intrinsic injury, survival, and repair mechanisms; to identify putative drug targets as well as cell-based therapies; and to optimize the delivery of therapeutic agents to the damaged cerebral tissue. PMID:23488559

  11. Cardioprotective actions of Notch1 against myocardial infarction via LKB1-dependent AMPK signaling pathway.

    PubMed

    Yang, Hui; Sun, Wanqing; Quan, Nanhu; Wang, Lin; Chu, Dongyang; Cates, Courtney; Liu, Quan; Zheng, Yang; Li, Ji

    2016-05-15

    AMP-activated protein kinase (AMPK) signaling pathway plays a pivotal role in intracellular adaptation to energy stress during myocardial ischemia. Notch1 signaling in the adult myocardium is also activated in response to ischemic stress. However, the relationship between Notch1 and AMPK signaling pathways during ischemia remains unclear. We hypothesize that Notch1 as an adaptive signaling pathway protects the heart from ischemic injury via modulating the cardioprotective AMPK signaling pathway. C57BL/6J mice were subjected to an in vivo ligation of left anterior descending coronary artery and the hearts from C57BL/6J mice were subjected to an ex vivo globe ischemia and reperfusion in the Langendorff perfusion system. The Notch1 signaling was activated during myocardial ischemia. A Notch1 γ-secretase inhibitor, dibenzazepine (DBZ), was intraperitoneally injected into mice to inhibit Notch1 signaling pathway by ischemia. The inhibition of Notch1 signaling by DBZ significantly augmented cardiac dysfunctions caused by myocardial infarction. Intriguingly, DBZ treatment also significantly blunted the activation of AMPK signaling pathway. The immunoprecipitation experiments demonstrated that an interaction between Notch1 and liver kinase beta1 (LKB1) modulated AMPK activation during myocardial ischemia. Furthermore, a ligand of Notch1 Jagged1 can significantly reduce cardiac damage caused by ischemia via activation of AMPK signaling pathway and modulation of glucose oxidation and fatty acid oxidation during ischemia and reperfusion. But Jagged1 did not have any cardioprotections on AMPK kinase dead transgenic hearts. Taken together, the results indicate that the cardioprotective effect of Notch1 against ischemic damage is mediated by AMPK signaling via an interaction with upstream LKB1.

  12. Asymptomatic myocardial infarction in Kawasaki disease: Long-term prognosis

    SciTech Connect

    Shiraishi, I.; Onouchi, Z.; Hayano, T.; Hamaoka, K.; Kiyosawa, N. )

    1991-04-01

    Eight patients with Kawasaki disease who had sustained asymptomatic myocardial infarction 8-15 years ago (mean, 13.1 years) were reexamined by various noninvasive cardiac function tests to assess long-term prognosis. At present, electrocardiograms (ECGs) are normal in six patients. However, all eight patients had a prolonged preejection period (PEP) to left ventricular ejection time (LVET) ratio 30 s after amylnitrate (AN) inhalation. Six patients had perfusion defects by exercise thallium-201 myocardial scintigraphy, and two patients developed ST segment depression in treadmill exercise testing. These patients are symptom-free even though their physical activity has not been restricted. Yet they proved to have serious abnormalities suggesting sequelae of myocardial infarction or existing myocardial ischemia. Judging from the results of noninvasive cardiac function tests and recently performed coronary angiography, five of the eight patients require coronary bypass surgery.

  13. Ventricular Arrhythmias and Mortality Associated with Isoflurane and Sevoflurane in a Porcine Model of Myocardial Infarction

    PubMed Central

    Regueiro-Purriños, Marta; Fernández-Vázquez, Felipe; de Prado, Armando Perez; Altónaga, Jose R; Cuellas-Ramón, Carlos; Ajenjo-Silverio, Jose M; Orden, Asuncion; Gonzalo-Orden, Jose M

    2011-01-01

    Ischemia of the myocardium can lead to reversible or irreversible injury depending on the severity and duration of the preceding ischemia. Here we compared sevoflurane and isoflurane with particular reference to their hemodynamic effects and ability to modify the effects of acute severe myocardial ischemia and reperfusion on ventricular arrhythmias and mortality in a porcine model of myocardial infarction. Female Large White pigs were premedicated with ketamine, midazolam, and atropine. Propofol was given intravenously for the anesthetic induction, and anesthesia was maintained with isoflurane or sevoflurane. Endovascular, fluoroscopy-guided, coronary procedures were performed to occlude the midleft anterior descending artery by using a coronary angioplasty balloon. After 75 min, the balloon catheter system was withdrawn and the presence of adequate reperfusion flow was verified. The pigs were followed for 2 mo, and overall mortality rate was calculated. The isoflurane group showed lower arterial pressure throughout the procedure, with the difference reaching statistical significance after induction of myocardial ischemia. The ventricular fibrillation rate was higher in isoflurane group (81.3%) than the sevoflurane group (51.7%; relative risk, 1.57 [1.03 to 2.4]). Overall survival was lower in the isoflurane group (75%) than the sevoflurane group (96.4%). In conclusion, in this porcine model of myocardial ischemia and reperfusion, sevoflurane was associated with higher hemodynamic stability and fewer ventricular arrhythmias and mortality than was isoflurane. PMID:21333167

  14. Reduction of myocardial infarct size with ischemic "conditioning": physiologic and technical considerations.

    PubMed

    Przyklenk, Karin

    2013-10-01

    A wealth of evidence has revealed that the heart can be "conditioned" and rendered less vulnerable to ischemia-reperfusion injury via the upregulation of endogenous protective signaling pathways. Three distinct conditioning strategies have been identified: (1) preconditioning, the phenomenon where brief episodes of myocardial ischemia (too brief to cause cardiomyocyte death) limit necrosis caused by a subsequent sustained ischemic insult; (2) postconditioning, the concept that relief of myocardial ischemia in a staged or stuttered manner attenuates lethal ischemia-reperfusion injury; and (3) remote conditioning, or upregulation of a cardioprotective phenotype initiated by ischemia in a remote organ or tissue and "transported" to the heart. Progress has been made in defining the technical requirements and limitations of each of the 3 ischemic conditioning models (including the timing and severity of the protective stimulus), as well as elucidating the molecular mechanisms (in particular, the receptor-mediated signaling pathways) responsible for conditioning-induced myocardial protection. Moreover, phase III clinical trials are in progress, seeking to capitalize on the protection that can be achieved by postconditioning and remote conditioning, and applying these strategies in patients undergoing cardiac surgery or angioplasty for the treatment of acute myocardial infarction. There is, however, a potentially important caveat to the clinical translation of myocardial conditioning: emerging data suggest that the efficacy of ischemic conditioning is compromised in aging, diabetic, and hypertensive cohorts, the specific populations in which myocardial protection is most relevant. Successful clinical application of myocardial conditioning will therefore require an understanding of the potential confounding consequences of these comorbidities on the "conditioned" phenotype.

  15. Myocardial abscess complicating healed myocardial infarction.

    PubMed Central

    Weisz, S.; Young, D. G.

    1977-01-01

    An isolated myocardial abscess due to Bacteroides fragilis developed in the scar of a myocardial infarction. Fever, chills and signs of pericarditis were the main clinical features. Mild enteritis 1 week prior to the onset of symptoms related to the abscess was the most likely cause of the bacteremia. The diagnosis was established at thoracotomy, performed because of cardiac tamponade. Thirteen other cases of isolated bacterial myocardial abscess accompanying myocardial infarction have been reported, but all the infarctions were recent. Surgical resection for a suspected myocardial abscess should be considered in view of the high mortality, largely from cardiac rupture. Images FIG. 1 PMID:861868

  16. Transluminal coronary angioplasty in the treatment of silent ischemia

    SciTech Connect

    Bergin, P.; Myler, R.K.; Shaw, R.E.; Stertzer, S.H.; Clark, D.A.; Ryan, C.; Murphy, M.C.

    1988-01-01

    Fifty-four asymptomatic patients with positive thallium exercise tests underwent coronary angiography followed by coronary angioplasty (PTCA), as the primary therapy for silent ischemia. The procedure was technically successful in 89% of these patients. Emergency bypass graft surgery was necessary in 2 (3.6%) and q-wave myocardial infarction occurred in 1 (1.8%) of these. All fifty-four patients have been followed for a mean of 35 months since angioplasty. Of the 48 patients with initially successful PTCA, 12 had either clinical restenosis (9/14 or 19%) or a new lesion (3/48 or 6%) during follow-up, which required a repeat PTCA. At the longest follow-up, 46 (85%) had been successfully treated with on or more PTCA procedures. Two patients (3.6%) had sustained late q-wave myocardial infarction and two additional patients reported angina pectoris. There were no deaths. Angioplasty as a primary therapy for silent ischemia appears efficacious, with success and restenosis rates comparable to those in the symptomatic population. Event-free survival is improved, compared with natural history data for patients with silent ischemia from other studies. Prudent risk/benefit analysis may help to define subgroups most likely to benefit from this intervention.

  17. Methods employed for induction and analysis of experimental myocardial infarction in mice.

    PubMed

    Borst, Oliver; Ochmann, Carmen; Schönberger, Tanja; Jacoby, Christoph; Stellos, Konstantinos; Seizer, Peter; Flögel, Ulrich; Lang, Florian; Gawaz, Meinrad

    2011-01-01

    Myocardial ischemia und subsequent reperfusion is followed by a complex sequence of pathophysiological responses involving inflammatory cell infiltration and cytokine release as well as postinfarction wound healing and myocardial tissue remodeling. With the development of gene targeted mice the contribution of individual gene products to the pathophysiology of myocardial ischemia and reperfusion can be defined leading to an increasing interest in the widely-used mouse model of myocardial infarction. This methological paper describes in detail the required equipment, surgical instruments, drugs and additional material, the methods of anesthesia and analgesia, the procedures involved in preparation of the animal, tracheotomy, intubation, thoracotomy, occlusion of the left descending artery, removal of the heart, determination of infarct size, analysis of cardiac functional parameters with echocardiography and magnetic resonance imaging (MRI) as well as determination of the morphological consequences utilizing gelatin zymography, histology and immunohistochemistry. PMID:21865843

  18. Methods employed for induction and analysis of experimental myocardial infarction in mice.

    PubMed

    Borst, Oliver; Ochmann, Carmen; Schönberger, Tanja; Jacoby, Christoph; Stellos, Konstantinos; Seizer, Peter; Flögel, Ulrich; Lang, Florian; Gawaz, Meinrad

    2011-01-01

    Myocardial ischemia und subsequent reperfusion is followed by a complex sequence of pathophysiological responses involving inflammatory cell infiltration and cytokine release as well as postinfarction wound healing and myocardial tissue remodeling. With the development of gene targeted mice the contribution of individual gene products to the pathophysiology of myocardial ischemia and reperfusion can be defined leading to an increasing interest in the widely-used mouse model of myocardial infarction. This methological paper describes in detail the required equipment, surgical instruments, drugs and additional material, the methods of anesthesia and analgesia, the procedures involved in preparation of the animal, tracheotomy, intubation, thoracotomy, occlusion of the left descending artery, removal of the heart, determination of infarct size, analysis of cardiac functional parameters with echocardiography and magnetic resonance imaging (MRI) as well as determination of the morphological consequences utilizing gelatin zymography, histology and immunohistochemistry.

  19. Ischemia detection from morphological QRS angle changes.

    PubMed

    Romero, Daniel; Martínez, Juan Pablo; Laguna, Pablo; Pueyo, Esther

    2016-07-01

    In this paper, an ischemia detector is presented based on the analysis of QRS-derived angles. The detector has been developed by modeling ischemic effects on the QRS angles as a gradual change with a certain transition time and assuming a Laplacian additive modeling error contaminating the angle series. Both standard and non-standard leads were used for analysis. Non-standard leads were obtained by applying the PCA technique over specific lead subsets to represent different potential locations of the ischemic zone. The performance of the proposed detector was tested over a population of 79 patients undergoing percutaneous coronary intervention in one of the major coronary arteries (LAD (n  =  25), RCA (n  =  16) and LCX (n  =  38)). The best detection performance, obtained for standard ECG leads, was achieved in the LAD group with values of sensitivity and specificity of [Formula: see text], [Formula: see text], followed by the RCA group with [Formula: see text], Sp  =  94.4 and the LCX group with [Formula: see text], [Formula: see text], notably outperforming detection based on the ST series in all cases, with the same detector structure. The timing of the detected ischemic events ranged from 30 s up to 150 s (mean  =  66.8 s) following the start of occlusion. We conclude that changes in the QRS angles can be used to detect acute myocardial ischemia. PMID:27243441

  20. Protective Effects of HDL Against Ischemia/Reperfusion Injury

    PubMed Central

    Gomaraschi, Monica; Calabresi, Laura; Franceschini, Guido

    2016-01-01

    Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures. PMID:26834639

  1. Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries.

    PubMed

    Halladin, Natalie Løvland

    2015-04-01

    Ischemia-reperfusion injuries occur when the blood supply to an organ or tissue is temporarily cut-off and then restored. Even though the restoration of blood flow is absolutely essential in preventing tissue death, the reperfusion of oxygenated blood to the oxygen-deprived areas may in itself augment the tissue damage in excess of that produced by the ischemia alone. The process of ischemia-reperfusion is multifactorial and there are several mechanisms involved in the pathogenesis. Ample evidence shows that the injury is in part caused by an excessive generation of reactive oxygen species or free radicals. The free radicals consequently initiate an inflammatory response, which in some cases may affect distant organs, thus causing remote organ injuries. Ischemia-reperfusion injuries are a common complication in many diseases (acute myocardial infarctions, stroke) or surgical settings (transplantations, tourniquet-related surgery) and they have potential detrimental and disabling consequences. The tolerance of ischemia-reperfusion has proven to be time-of-day-dependent and the size of myocardial infarctions has proven to be significantly higher when occurring in the dark-to-light period. This period is characterized by and coincides with a rapid decrease in the plasma levels of the hormone melatonin. Melatonin is the body's most potent antioxidant and is capable of both direct free radical scavenging and indirect optimization of other anti-oxidant enzymes. It also possesses anti-inflammatory properties and is known to inhibit the mitochondrial permeability transition pore during reperfusion. This inhibiting property has been shown to be of great importance in reducing ischemia-reperfusion injuries. Furthermore, melatonin is a relatively non-toxic molecule, which has proven to be safe for use in clinical trials. Thus, there is compelling evidence of melatonin's effect in reducing ischemia-reperfusion injuries in many experimental studies, but the number of human

  2. Matrix metalloproteinases: drug targets for myocardial infarction

    PubMed Central

    Yabluchanskiy, Andriy; Li, Yaojun; Chilton, Robert J.; Lindsey, Merry L.

    2013-01-01

    Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. Rapid advances in the treatment of acute MI have significantly improved short-term outcomes in patient, due in large part to successes in preventing myocardial cell death and limiting infarct area during the time of ischemia and subsequent reperfusion. Matrix metalloproteases (MMPs) play key roles in post-MI cardiac remodeling and in the development of adverse outcomes. This review highlights the importance of MMPs in the injury and remodeling response of the left ventricle and also discusses their potential as therapeutic targets Additional pre-clinical and clinical research is needed to further investigate and understand the cardioprotective effects of MMPs inhibitors. PMID:23316962

  3. The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning

    PubMed Central

    Rezende, Paulo Cury; Rahmi, Rosa Maria

    2016-01-01

    Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning.

  4. The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning

    PubMed Central

    Rezende, Paulo Cury; Rahmi, Rosa Maria

    2016-01-01

    Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning. PMID:27656659

  5. Effect of hydroxy safflower yellow A on myocardial apoptosis after acute myocardial infarction in rats.

    PubMed

    Zhou, M X; Fu, J H; Zhang, Q; Wang, J Q

    2015-04-10

    This study aimed to investigate the effect of hydroxy safflower yellow A (HSYA) on myocardial apoptosis after acute myocardial infarction (AMI) in rats. We randomly divided 170 male Wistar rats into 6 groups (N = 23): normal control, sham, control, SY (90 mg/kg), HSYA high-dose (HSYA-H, 40 mg/kg), and HSYA low-dose groups (HSYA-L, 20 mg/kg). Myocardial ischemic injury was induced by ligating the anterior descending coronary artery, and the degree of myocardial ischemia was evaluated using electrocardiography and nitroblue tetrazolium staining. Bax and Bcl-2 expressions in the ischemic myocardium were determined using immunohistochemical analysis. Peroxisome proliferator-activated receptor-γ (PPAR-γ) expression in the myocardium of rats with AMI was determined using reverse transcription-polymerase chain reaction. Compared to rats in the control group, those in the HYSA-H, HSYA-L, and SY groups showed a decrease in the elevated ST segments and an increase in the infarct size. The rats in the drug-treated groups showed a significantly lower percentage of Bax-positive cells and a significantly higher percentage of Bcl-2-positive cells than those in the control group (P < 0.05). Moreover, mRNA expression of PPAR-γ in the ischemic myocardium of rats in the SY, HSYA-L, and HSYA-H groups was significantly lower than that in the control group (P < 0.05). Thus, HSYA and SY can attenuate myocardial ischemia in rats, possibly by increasing the level of Bcl-2/Bax, and PPAR-γ may be not a necessary link in this process.

  6. Effect of taurine on ischemia-reperfusion injury.

    PubMed

    Schaffer, Stephen W; Jong, Chian Ju; Ito, Takashi; Azuma, Junichi

    2014-01-01

    Taurine is an abundant β-amino acid that regulates several events that dramatically influence the development of ischemia-reperfusion injury. One of these events is the extrusion of taurine and Na+ from the cell via the taurine/Na+ symport. The loss of Na+ during the ischemia-reperfusion insult limits the amount of available Na+ for Na+/Ca2+ exchange, an important process in the development of Ca2+ overload and the activation of the mitochondrial permeability transition, a key process in ischemia-reperfusion mediated cell death. Taurine also prevents excessive generation of reactive oxygen species by the respiratory chain, an event that also limits the activation of the MPT. Because taurine is an osmoregulator, changes in taurine concentration trigger "osmotic preconditioning," a process that activates an Akt-dependent cytoprotective signaling pathway that inhibits MPT pore formation. These effects of taurine have clinical implications, as experimental evidence reveals potential promise of taurine therapy in preventing cardiac damage during bypass surgery, heart transplantation and myocardial infarction. Moreover, severe loss of taurine from the heart during an ischemia-reperfusion insult may increase the risk of ventricular remodeling and development of heart failure. PMID:22936072

  7. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation.

  8. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  9. Oxygen surrounding the heart during ischemic conservation determines the myocardial injury during reperfusion.

    PubMed

    Feng, Yansheng; Bopassa, Jean Chrisostome

    2015-01-01

    There is discrepancy regarding the duration of reperfusion required using 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining to assess myocardial infarction in an isolated, perfused heart model. Several investigators prefer long-term reperfusion (120 minutes) to determine myocardial injury, while others have used a shorter duration (30-40 minutes). We investigated whether oxygen surrounding the myocardium during ischemia plays a critical role in the installation of myocardial infarction during reperfusion. Mice hearts were perfused with a Langendorff apparatus using Krebs Henseleit (KH) buffer oxygenated with 95% O2 plus 5% CO2 at 37°C. Hearts were either immersed in KH or suspended in air during 18 minutes of global ischemia in a normothermic, water-jacketed chamber. Hearts then were reperfused for 40, 60, or 90 minutes. We found that hearts immersed in KH had decreased recovery of function and increased myocardial infarct size, reaching a steady-state level after 40 minutes of reperfusion. In contrast, hearts suspended in air approached steady-state after 90 minutes of reperfusion. Thus, mitochondrial reactive oxygen species (ROS) production was much lower in air-maintained hearts than in KH-immersed hearts. To investigate whether an increase in oxygen surrounding the myocardium during ischemia might cause further damage, we bubbled the KH solution with nitrogen (KH+N2) rather than oxygen (KH+O2). With this alteration, recovery of cardiac function was improved and myocardial infarct size and mitochondrial ROS production were reduced compared with hearts immersed in KH+O2. In conclusion, short-term (40 minutes) reperfusion is sufficient to reach steady-state myocardial infarct size when hearts are immersed in physiologic solution during ischemia; however, a longer duration of reperfusion (90 minutes) is required if hearts are suspended in air. Thus, oxygen surrounding the heart during ischemia determines the extent of myocardium injury during reperfusion

  10. Oxygen surrounding the heart during ischemic conservation determines the myocardial injury during reperfusion.

    PubMed

    Feng, Yansheng; Bopassa, Jean Chrisostome

    2015-01-01

    There is discrepancy regarding the duration of reperfusion required using 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining to assess myocardial infarction in an isolated, perfused heart model. Several investigators prefer long-term reperfusion (120 minutes) to determine myocardial injury, while others have used a shorter duration (30-40 minutes). We investigated whether oxygen surrounding the myocardium during ischemia plays a critical role in the installation of myocardial infarction during reperfusion. Mice hearts were perfused with a Langendorff apparatus using Krebs Henseleit (KH) buffer oxygenated with 95% O2 plus 5% CO2 at 37°C. Hearts were either immersed in KH or suspended in air during 18 minutes of global ischemia in a normothermic, water-jacketed chamber. Hearts then were reperfused for 40, 60, or 90 minutes. We found that hearts immersed in KH had decreased recovery of function and increased myocardial infarct size, reaching a steady-state level after 40 minutes of reperfusion. In contrast, hearts suspended in air approached steady-state after 90 minutes of reperfusion. Thus, mitochondrial reactive oxygen species (ROS) production was much lower in air-maintained hearts than in KH-immersed hearts. To investigate whether an increase in oxygen surrounding the myocardium during ischemia might cause further damage, we bubbled the KH solution with nitrogen (KH+N2) rather than oxygen (KH+O2). With this alteration, recovery of cardiac function was improved and myocardial infarct size and mitochondrial ROS production were reduced compared with hearts immersed in KH+O2. In conclusion, short-term (40 minutes) reperfusion is sufficient to reach steady-state myocardial infarct size when hearts are immersed in physiologic solution during ischemia; however, a longer duration of reperfusion (90 minutes) is required if hearts are suspended in air. Thus, oxygen surrounding the heart during ischemia determines the extent of myocardium injury during reperfusion.

  11. Kappa-opioid receptor antagonism improves recovery from myocardial stunning in chronically instrumented dogs.

    PubMed

    Grosse Hartlage, Maike A; Theisen, Marc M; Monteiro de Oliveira, Nelson P; Van Aken, Hugo; Fobker, Manfred; Weber, Thomas P

    2006-10-01

    We tested the hypothesis that the selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate, left atrial, aortic and left ventricular pressure (LVP), and the maximum rate of LVP increase (LV dP/dt(max)) and decrease (LV dP/dt(max)), coronary blood flow velocity and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography, and beta-endorphin and dynorphin plasma levels by radioimmunoassay. An occluder around the left anterior descending artery (LAD) allowed induction of a reversible LAD-ischemia. Animals underwent two experiments in a randomized crossover fashion on separate days: (a) 10 min LAD-occlusion (control experiment), (b) second ischemic episode 24 h after nor-BNI (2.5 mg/kg IV) (intervention). Dogs receiving nor-BNI showed an increase in wall-thickening fraction, LV dP/dt(max) and LV dP/dt(min) before ischemia and during the whole reperfusion (P < 0.05 versus control experiment). After nor-BNI pretreatment, dynorphin levels increased after induction of ischemia to a peak level of 15.1 +/- 3.6 pg/mL (P < 0.05 versus control experiment). The increase in plasma beta-endorphin during ischemia and early reperfusion was attenuated after nor-BNI. Compared with the control experiment, nor-BNI left global hemodynamics, regional myocardial blood flow, and catecholamine levels unchanged. In conclusion, nor-BNI improves recovery from myocardial stunning after regional myocardial ischemia in chronically instrumented dogs.

  12. Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3.

    PubMed

    Koentges, Christoph; Pfeil, Katharina; Meyer-Steenbuck, Maximilian; Lother, Achim; Hoffmann, Michael M; Odening, Katja E; Hein, Lutz; Bode, Christoph; Bugger, Heiko

    2016-01-01

    Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia-reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (-20%) and rate pressure product (-15%) in SIRT3(-/-) mice. Mitochondrial state 3 respiration (-15%), ATP synthesis (-39%), and ATP/O ratios (-29%) were decreased in hearts of SIRT3(-/-) mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3(-/-) 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3(-/-) 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3(-/-) mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3(-/-) mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.

  13. Digital ischemia in baseball players.

    PubMed

    Sugawara, M; Ogino, T; Minami, A; Ishii, S

    1986-01-01

    Eight baseball players developed digital ischemia as a result of repetitive ball impact. Symptoms and signs were coolness, numbness, cyanosis, paleness, and a positive reaction to the digital Allen's test. Seven of the eight players developed digital ischemia between the ages of 16 and 17. Angiograms of four patients with an occluded index digital artery are presented. Thermograms of four patients with a cool area of the left index finger are also presented. We investigated the incidence of digital ischemia by administration of a questionnaire. The respondents were 578 players belonging to clubs in junior high schools, high schools, and colleges. No digital ischemia was found in 207 junior high school baseball players. The incidence increased in high school (66 of 299) and college (29 of 72). The probability of developing digital ischemia corresponded to the accumulated playing time. Digital ischemia occurred characteristically in the left index finger.

  14. [The effect of decimeter waves on the metabolism of the myocardium and its hormonal regulation in rabbits with experimental ischemia].

    PubMed

    Frenkel', I D; Zubkova, S M; Liubimova, N N; Popov, V I

    1992-01-01

    Biochemical and morphometric methods were employed to study the effect of decimetric waves (460 MHz, 10 and 120 mW/cm2) in cardiac and thyroid exposure on oxygen metabolism, myocardial microcirculation and contractility, thyroid and adrenal hormonal activity, kallikrein-kinin system activity in rabbits with experimental myocardial ischemia. Hypoxia discontinued in all the treatment regimens, but the exposure of the heart (field density 10 mW/sm2) had the additional effect on lipid peroxidation which reduced in the serum and normalized in the myocardium, on myocardial contractility, kallikrein-kinin system and on the adrenal and thyroid hormones.

  15. Myocardial ischemia during intravenous DSA in patients with cardiac disease

    SciTech Connect

    Hesselink, J.R.; Hayman, L.A.; Chung, K.J.; McGinnis, B.D.; Davis, K.R.; Taveras, J.M.

    1984-12-01

    A prospective study was performed for 48 patients who had histories of angina and were referred for digital subtraction angiography (DSA). Cardiac disease was graded according to the American Heart Association (AHA) functional classification system. Each patient received 2-5 injections of 40-ml diatrizoate meglumine and diatrizoate sodium at 15 ml per second in the superior vena cava. Of the 28 patients in functional Classes I or II, 11% had angina and 32% had definite ischemic ECG changes after the DSA injections. Of the patients in functional Class III 63% had angina, and 58% had definite ischemic ECG changes after the injections. These observed cardiac effects following bolus injections of hypertonic ionic contrast media indicate that special precautions are necessary when performing intravenous DSA examinations on this group of high risk patients.

  16. Noninvasive Cardiac Quantum Spectrum Technology Effectively Detects Myocardial Ischemia.

    PubMed

    Li, Ke; Xue, Qiao; Liu, Mohan; Zheng, Xiaoqin; Chen, Rui; Li, Yufeng; Dan, Qing; Fang, Danqun

    2016-01-01

    BACKGROUND A standard resting electrocardiogram (ECG) shows limited sensitivity and specificity for the detection of coronary artery disease (CAD). Several analytic methods exist to enhance the sensitivity and specificity of resting ECG for diagnosis of CAD. We compared a new computer-enhanced, resting ECG analysis device, the cardiac quantum spectrum (CQS) technique, with coronary angiography in the detection of CAD. MATERIAL AND METHODS A consecutive sample of 93 patients with a history of suspected CAD scheduled for coronary angiography was evaluated with CQS before coronary angiography. The sensitivity and specificity of CQS and standard 12-lead ECG for detecting hemodynamically relevant coronary stenosis were compared, using coronary angiography as the reference standard. Kappa analysis was performed to assess the agreement between CQS severity scores and the level of stenosis determined by coronary angiography. RESULTS The CQS system identified 78 of 82 patients with hemodynamically relevant stenosis (sensitivity, 95.1%; specificity, 63.6%; accuracy, 91.4%; positive predictive value, 95.1%; negative predictive value, 63.6%). Sensitivity and accuracy were much higher for CQS analysis than for the standard ECG. The Kappa value, assessing the level of agreement between CQS and coronary angiography, was 0.376 (P<0.001). CONCLUSIONS CQS analysis of resting ECG data detects hemodynamically relevant CAD with high sensitivity and specificity. PMID:27351755

  17. Noninvasive Cardiac Quantum Spectrum Technology Effectively Detects Myocardial Ischemia

    PubMed Central

    Li, Ke; Xue, Qiao; Liu, Mohan; Zheng, Xiaoqin; Chen, Rui; Li, Yufeng; Dan, Qing; Fang, Danqun

    2016-01-01

    Background A standard resting electrocardiogram (ECG) shows limited sensitivity and specificity for the detection of coronary artery disease (CAD). Several analytic methods exist to enhance the sensitivity and specificity of resting ECG for diagnosis of CAD. We compared a new computer-enhanced, resting ECG analysis device, the cardiac quantum spectrum (CQS) technique, with coronary angiography in the detection of CAD. Material/Methods A consecutive sample of 93 patients with a history of suspected CAD scheduled for coronary angiography was evaluated with CQS before coronary angiography. The sensitivity and specificity of CQS and standard 12-lead ECG for detecting hemodynamically relevant coronary stenosis were compared, using coronary angiography as the reference standard. Kappa analysis was performed to assess the agreement between CQS severity scores and the level of stenosis determined by coronary angiography. Results The CQS system identified 78 of 82 patients with hemodynamically relevant stenosis (sensitivity, 95.1%; specificity, 63.6%; accuracy, 91.4%; positive predictive value, 95.1%; negative predictive value, 63.6%). Sensitivity and accuracy were much higher for CQS analysis than for the standard ECG. The Kappa value, assessing the level of agreement between CQS and coronary angiography, was 0.376 (P<0.001). Conclusions CQS analysis of resting ECG data detects hemodynamically relevant CAD with high sensitivity and specificity. PMID:27351755

  18. Diagnosis of early human myocardial ischemic damage with electron probe microanalysis

    SciTech Connect

    Singh, S.; Abraham, J.L.; Raasch, F.; Wolf, P.; Bloor, C.M.

    1983-03-01

    We determined the Na/K x-ray intensity ratio in frozen sections of myocardial tissues obtained at autopsy from patients who died from various causes, using electron probe analysis. We have been able to distinguish between the ischemically injured and normal cells. The method is simple, fast, and dependable even when the duration of ischemia is only 30 minutes.

  19. Targeting Cell Signaling and Apoptotic Pathways by Luteolin: Cardioprotective Role in Rat Cardiomyocytes Following Ischemia/Reperfusion

    PubMed Central

    Xu, Tongda; Li, Dongye; Jiang, Dehua

    2012-01-01

    Myocardial ischemia often results in damaged heart structure and function, which can be restored through ischemia/reperfusion (I/R) in most cases. However, I/R can exacerbate myocardial ischemia reperfusion injury (IRI). Luteolin, a widely distributed flavonoid, a member of a group of naturally occurring polyphenolic compounds found in many fruits, vegetables and medicinal herbs, has been reported to exhibit anti-inflammatory, antioxidant and anti-carcinogenic activities. In recent years, luteolin has been shown to play an important role in the cardioprotection of IRI. However, its role and mechanism in cardioprotection against IRI has not been clearly elucidated with respect to the apoptosis pathway. The purpose of this paper is to review luteolin’s anti-apoptotic role and mechanism following I/R in rats, and indicate luteolin as a potential candidate for preventing and treating cardiovascular diseases. PMID:23235403

  20. Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects

    SciTech Connect

    Brunken, R.; Schwaiger, M.; Grover-McKay, M.; Phelps, M.E.; Tillisch, J.; Schelbert, H.R.

    1987-09-01

    Positron emission tomography with /sup 13/N-ammonia and /sup 18/F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.

  1. The effects of thoracic epidural anesthesia on functional recovery from myocardial stunning in propofol-anesthetized dogs.

    PubMed

    Rolf, N; Meissner, A; Van Aken, H; Weber, T P; Hammel, D; Möllhoff, T

    1997-04-01

    The purpose of this investigation was to examine the effects of thoracic epidural anesthesia (TEA) on myocardial stunning during propofol anesthesia. Six dogs were chronically instrumented for measurement of left atrial, aortic, and left ventricular pressure, maximal rate of increase of left ventricular pressure, and myocardial wall-thickening fraction (WTF). Myocardial blood flow was determined with colored microspheres. Experiments were performed on separate days with 1) 10 min of left anterior descending artery (LAD) ischemia during propofol anesthesia without TEA, and 2) 10 min of LAD ischemia during propofol anesthesia with TEA. WTF was measured as baseline (BL) prior to propofol anesthesia and at predetermined time points until complete recovery from stunning. Propofol anesthesia caused a significant decrease of WTF in the LAD-perfused myocardium (LAD-WTF) compared to BL in awake animals. LAD ischemia led to a further significant decrease of LAD-WTF. There were no significant differences in LAD-WTF between the two experimental conditions at any of the time points measured. TEA did not change subendocardial blood flow in nonischemic myocardium. During ischemia neither the subendocardial/subepicardial nor the occluded/normal zone blood flow ratio were affected by TEA. After myocardial ischemia during propofol anesthesia TEA does not affect functional recovery of stunned myocardium in dogs. PMID:9085946

  2. Myocardial imaging. Coxsackie myocarditis

    SciTech Connect

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  3. Double hazards of ischemia and reperfusion arrhythmias in a patient with variant angina pectoris.

    PubMed

    Xu, Mingzhu; Yang, Xiangjun

    2015-01-01

    Variant angina pectoris, also called Prinzmetal's angina, is a syndrome caused by vasospasms of the coronary arteries. It can lead to myocardial infarction, ventricular arrhythmias, atrioventricular block and even sudden cardiac death. We report the case of a 53 year-old male patient with recurrent episodes of chest pain and arrhythmias in the course of related variant angina pectoris. It is likely that the reperfusion following myocardial ischemia was responsible for the ventricular fibrillation while the ST-segment returned to the baseline. This case showed that potential lethal arrhythmias could arise due to variant angina pectoris. It also indicated that ventricular fibrillation could be self-terminated.

  4. Myocardial injury associated with transcatheter aortic valve implantation (TAVI).

    PubMed

    Kim, Won-Keun; Liebetrau, Christoph; van Linden, Arnaud; Blumenstein, Johannes; Gaede, Luise; Hamm, Christian W; Walther, Thomas; Möllmann, Helge

    2016-05-01

    Transcatheter aortic valve implantation (TAVI) has emerged as an important treatment option for elderly patients with symptomatic aortic stenosis whose risk is too high or prohibitive for conventional surgery. Despite notable progress during the past decade, continuous efforts directed at further improvement of procedural safety and performance are required, especially considering expanding indications for interventional treatment options among lower-risk populations. One issue that needs to be addressed is myocardial damage, which can frequently be observed after TAVI and has been linked to worse prognosis. Yet, knowledge concerning the underlying mechanisms and clinical impact remains scarce, and further investigation in this field is warranted. In this review, we provide a contemporary summary of the types of myocardial injury associated with TAVI, including access-related injury, mechanical trauma and ischemia, the role of myocardial biomarkers, and the impact on left ventricular function, with emphasis on potential mechanisms and clinical implications.

  5. Early-phase myocardial infarction: Evaluation by MR imaging

    SciTech Connect

    Tscholakoff, D.; Higgins, C.B.; McNamara, M.T.; Derugin, N.

    1986-06-01

    In vivo gated magnetic resonance (MR) imaging was performed in 12 dogs immediately after occlusion of the left anterior descending coronary artery and serially up to 5 hours and again between 4 and 14 days. This was done to evaluate the appearance of acute myocardial infarcts and to determine how soon after coronary artery occlusion MR imaging can demonstrate the site of acute myocardial ischemia. In nine dogs with postmortem evidence of myocardial infarction, regional increase of signal intensity of the myocardium was present by 3 hours after coronary occlusion and conformed to the site of myocardial infarct found at autopsy. The signal intensity on T2-weighted images of the infarcted on T2-weighted images of the infarcted myocardium was significantly greater than that of normal myocardium at 3, 4, and 5 hours after occlusion. The T2 (spin-spin) relaxation time was significantly prolonged in the region of myocardial infarct at 3, 4, and 5 hours post-occlusion compared with normal myocardium. Myocardial wall thinning and increased intracavitary flow signal were found in six dogs with comparable pre- and postocclusion images in late systole.

  6. Ischemia causes muscle fatigue

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  7. Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy

    SciTech Connect

    Cannon, R.O. 3d.; Dilsizian, V.; O'Gara, P.T.; Udelson, J.E.; Schenke, W.H.; Quyyumi, A.; Fananapazir, L.; Bonow, R.O. )

    1991-05-01

    Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. Fifty patients with hypertrophic cardiomyopathy underwent exercise {sup 201}Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more {sup 201}Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial {sup 201}Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible {sup 201}Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing compared with four of 13 patients (31%) with normal {sup 201}Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only {sup 201}Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal {sup 201}Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of {sup 201}Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible {sup 201}Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible {sup 201}Tl abnormalities, and 55% had pacing-induced ischemia. Reversible {sup 201}Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium.

  8. Ischemia induced by coronary steal through a patent mammary artery side branch: a role for embolization.

    PubMed

    Moreno, Nuno; da Silva Castro, Alexandra; Pereira, Adriana; Silva, João Carlos; Almeida, Pedro Bernardo; Andrade, Aurora; Maciel, Maria Júlia; Pinto, Paula

    2013-06-01

    Non-occlusion of the internal mammary artery side branches may cause ischemia due to flow diversion after coronary artery bypass grafting. The authors present the case of a 67-year-old man with recurrent angina after undergoing myocardial revascularization with a left internal mammary artery to left anterior descending bypass. He presented with impaired anterior wall myocardial perfusion in the setting of a patent left internal mammary artery side branch. Effective percutaneous treatment was carried out through coil embolization, with improved flow and clinical symptoms, confirmed through ischemia testing. Coronary steal through a patent mammary artery side branch is a controversial phenomenon and this type of intervention should be considered only in carefully selected patients. PMID:23809629

  9. Ischemia induced by coronary steal through a patent mammary artery side branch: a role for embolization.

    PubMed

    Moreno, Nuno; da Silva Castro, Alexandra; Pereira, Adriana; Silva, João Carlos; Almeida, Pedro Bernardo; Andrade, Aurora; Maciel, Maria Júlia; Pinto, Paula

    2013-06-01

    Non-occlusion of the internal mammary artery side branches may cause ischemia due to flow diversion after coronary artery bypass grafting. The authors present the case of a 67-year-old man with recurrent angina after undergoing myocardial revascularization with a left internal mammary artery to left anterior descending bypass. He presented with impaired anterior wall myocardial perfusion in the setting of a patent left internal mammary artery side branch. Effective percutaneous treatment was carried out through coil embolization, with improved flow and clinical symptoms, confirmed through ischemia testing. Coronary steal through a patent mammary artery side branch is a controversial phenomenon and this type of intervention should be considered only in carefully selected patients.

  10. Value of planar 201Tl imaging in risk stratification of patients recovering from acute myocardial infarction

    SciTech Connect

    Gibson, R.S.; Watson, D.D. )

    1991-09-01

    Although exercise ECG testing has been shown to have important prognostic value after acute myocardial infarction, exercise 201Tl scintigraphy offers several potential advantages, including: (1) increased sensitivity for detecting residual myocardial ischemia; (2) the ability to localize ischemia to a specific area or areas subtended by a specific coronary artery; (3) the ability to identify exercise-induced left ventricular dysfunction, which is manifested by increased lung uptake or transient left ventricular dilation; and (4) more reliable risk stratification of individual patients. The more optimal prognostic efficiency of 201Tl scintigraphy partially results from the fact that the error rate in falsely classifying patients as low risk is significantly smaller with 201Tl scintigraphy than with stress ECG. Because of these substantial advantages, there seems to be adequate rationale for recommending exercise perfusion imaging rather than exercise ECG alone as the preferred method for evaluating mortality and morbidity risks after acute myocardial infarction.

  11. Risk stratification in patients with non Q wave myocardial infarction: a role for thallium exercise testing.

    PubMed

    Brophy, J M; Kerouac, M

    1990-12-01

    The ability of maximal exercise thallium testing to stratify patients after non Q wave myocardial infarction was prospectively examined in 20 patients. Patients were enrolled in the study if there was no evidence of residual ischemia nor congestive heart failure during initial hospitalization. The thallium exercise test showed four patients to be at high risk, three of whom had successful revascularization. The remaining 16 patients were considered to be at low risk. There were no re-admissions for unstable angina, no myocardial infarctions and no deaths in the follow-up period (average 15 months). Thus patients with no evidence of early ischemia, no signs of left ventricular failure and a negative maximum thallium exercise test are at low risk following non Q wave myocardial infarction.

  12. Emodin-mediated protection from acute myocardial infarction via inhibition of inflammation and apoptosis in local ischemic myocardium.

    PubMed

    Wu, Yanxia; Tu, Xin; Lin, Guosheng; Xia, Hao; Huang, Hao; Wan, Jing; Cheng, Zhide; Liu, Mengyuan; Chen, Gao; Zhang, Haimou; Fu, Jinrong; Liu, Qian; Liu, Dong-Xu

    2007-10-13

    Acute myocardial infarction (AMI) is associated with inflammation and apoptosis. Emodin plays an anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that emodin protects against myocardial ischemia/reperfusion injury. However, its mechanism underlying its effects remains unknown. In a murine model of AMI, based on ligation of the left coronary artery, administration of emodin reduced myocardial infarct size (MIS) in a dose-dependent manner. Emodin significantly suppressed TNF-alpha expression and NF-kappaB activation in the local myocardial infarction area. Treatment with emodin inhibited myocardial cell apoptosis by inhibiting caspase-3 activation. Therefore, these studies demonstrate that emodin protects against myocardial cell injury via suppression of local inflammation and apoptosis.

  13. Cell Biology of Ischemia/Reperfusion Injury

    PubMed Central

    Kalogeris, Theodore; Baines, Christopher P.; Krenz, Maike; Korthuis, Ronald J.

    2014-01-01

    Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues. PMID:22878108

  14. Limitations of premature ventricular complex morphology in the diagnosis of myocardial infarction

    SciTech Connect

    Wahl, J.M.; Hakki, A.H.; Iskandrian, A.S.; Segal, B.L.

    1986-04-01

    To determine the diagnostic value of Q-waves (greater than or equal to 0.04 seconds duration) in premature ventricular complexes (PVC's) for the presence of myocardial scar, we examined 12-lead electrocardiograms and multiple lead rhythm strips obtained before and after exercise at the time of thallium-201 myocardial imaging in 970 patients. PVC's were found in 233 patients, 112 of whom had fixed thallium-201 perfusion defects indicative of myocardial scar. PVC's occurring during exercise were excluded from the analysis. Twenty-one patients had Q-wave PVC's in one or more electrocardiographic leads. Of those, 14 patients (67%) had myocardial scar in the suggested location. Myocardial scar was more common among patients with Q-wave PVC's than in patients without (67% vs. 36%, p less than 0.01). However, only 6 of 13 patients (46%) with Q-wave PVC's but no diagnostic sinus beats actually had myocardial scar. The remaining seven patients had Q-wave PVC's, no myocardial scar, and no evidence of myocardial ischemia suggested by angina during exercise, exercise electrocardiogram or thallium-201 imaging. We conclude that although Q-wave PVC's indicate the presence of myocardial scar in 67% of patients, they yield little or no additional diagnostic information to that obtained from the sinus beats

  15. Protective effect of ischemic postconditioning against ischemia reperfusion-induced myocardium oxidative injury in IR rats.

    PubMed

    Zhang, Li; Ma, Jiangwei; Liu, Huajin

    2012-03-27

    Brief episodes of myocardial ischemia-reperfusion (IR) employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR)-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA) level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats.

  16. Radionuclide imaging of myocardial infarction using Tc-99m TBI

    SciTech Connect

    Holman, B.L.; Campbell, S.; Kirshenbaum, J.M.; Lister-James, J.; Jones, A.G.; Davison, A.; Antman, E.

    1985-05-01

    The cationic complex Tc-99m t-butylisonitrile (TBI) concentrates in the myocardial tissue of several animal species. Its myocardial distribution is proportional to blood flow both in zones of ischemia and in normal myocardium at rest. Planar, tomographic, and gated myocardial images have been obtained using Tc-99m TBI in the human. The authors investigated the potential application of Tc-99m TBI imaging to detect and localize myocardial infarction. Four subjects without clinical evidence of cardiovascular disease and five patients with ECG evidence of previous myocardial infarction were studied. Tc-99m TBI (10mCi) was injected intravenously with the patient in a resting state with planar imaging in the anterior, 30 and 70 degree LAO projections beginning one hr after injection. The distribution of the tracer was homogeneous throughout the left ventricular wall in the normal subjects. Regional perfusion defects were present in 4/5 of the patients with myocardial infarction. Location of the defects corresponded to the location of the infarct using ECG criteria (2 inferoposterior and 2 anterior). The patient in whom the Tc-99m TBI image appeared normal had sustained a subendocardial myocardial infarct which could not be localized by ECG; the other 4 pts had transmural infarcts. Anterior and 30 degree LAO images were of excellent quality in all cases; there was overlap of the liver on the inferior wall of the left ventricle on the 70 degree LAO views. The authors conclude that accurate perfusion imaging may be possible using Tc-99m TBI in patients with transmural myocardial infarction.

  17. Resveratrol pretreatment protects rat hearts from ischemia/reperfusion injury partly via a NALP3 inflammasome pathway

    PubMed Central

    Dong, Wusong; Yang, Rui; Yang, Jian; Yang, Jun; Ding, Jiawang; Wu, Hui; Zhang, Jing

    2015-01-01

    Inflammatory responses are key players in myocardial ischemia/reperfusion (I/R) injury. Our previous studies showed that resveratrol alleviated I/R injury in myocardial I/R animal models, but whether the NALP3 inflammasome pathway contributes to the mechanisms remains to be elucidated. In this study, we explored the modulation effect of resveratrol on myocardial I/R-induced inflammatory responses in rats. Myocardial I/R rat animal models were induced by occlusion of the left anterior descending coronary arteries (LADs) for 30 min, followed by 2 h of reperfusion. Resveratrol was administered in different doses (2.5, 5, and 10 mg/kg) at the same time as the onset of reperfusion. The serum concentrations of the trinitrotoluene (TnT) and MB isoenzyme creatine kinase (CK-MB) were detected using an automatic biochemical analyzer. Myocardial ultrastructure and morphology were observed with an electron microscope and a light microscope. Myocardial ischemia and infarct sizes were evaluated using Evans blue and tetrazolium chloride (TTC) staining. The NALP3, Caspase1, interleukin 1β (IL-1β) and interleukin 18 (IL-18) mRNA levels were evaluated using RT-PCR. The NALP3 and Caspase1 protein expression levels were detected by western blotting. The IL-1β and IL-18 content in peripheral blood was measured by enzyme-linked immunosorbent assay (ELISA). The myocardial structure in myocardial ischemia reperfusion injury (MI/RI) rats was extensively damaged. After preconditioning with different concentrations of resveratrol (2.5, 5 and 10 mg/kg), the pathology and morphology were significantly improved in a dose-dependent manner. Our results showed that resveratrol treatment significantly reduced the infarct volume and myocardial fibrosis, resulting in myocardial cells that lined up in a more orderly fashion and dose-dependent decreases in TnT and CK-MB levels in the serum of the I/R rats. Resveratrol also significantly modulated mRNA and protein levels by down-regulating NALP3 and

  18. Utility of desmin and a Masson's trichrome method to detect early acute myocardial infarction in autopsy tissues.

    PubMed

    Ouyang, Jie; Guzman, Miguel; Desoto-Lapaix, Fidelina; Pincus, Matthew R; Wieczorek, Rosemary

    2009-09-20

    Detection of early acute myocardial ischemia/infarction prior to neutrophilic infiltration in autopsy myocardium poses a diagnostic dilemma to the surgical pathologist. Morphological changes can be subtle or not identified at all on the hematoxylin and eosin stain. To evaluate the Masson's trichrome stain and immunohistochemical stains, desmin and myoglobin, in detecting acute myocardial ischemia/infarction in autopsy myocardium. We reviewed the autopsy files of the New York Harbor Healthcare System and retrieved 25 cases of early acute myocardial infarction. Three autopsy hearts of non-cardiac related deaths were used as controls. Sections from grossly suspected early acute myocardial infaction areas were stained by a Masson's trichrome stain technique and with desmin by a standard immnunohistochemical method. The ischemic zone surrounding myocardial infarction and the acute infarct itself in 23/25(92%) were detected by desmin depletion, and in all cases with Masson's trichrome color changes. No change in staining for desmin or Masson's trichrome were seen in the three controls. Desmin and Masson's trichrome together are valuable tools when faced with the problem of postmortem detection of early myocardial infarction/ischemia.