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Sample records for suspected myocardial ischemia

  1. Myocardial Ischemia

    MedlinePlus

    ... typically on the left side of the body (angina pectoris). Other signs and symptoms — which might be experienced ... ed. Philadelphia, Pa.: Saunders Elsevier; 2014. Podrid PJ. Angina pectoris: Chest pain caused by myocardial ischemia. www.uptodate. ...

  2. Diagnostic and Prognostic Value of Lead aVR During Exercise Testing in Patients Suspected of Having Myocardial Ischemia.

    PubMed

    Wagener, Max; Abächerli, Roger; Honegger, Ursina; Schaerli, Nicolas; Prêtre, Gil; Twerenbold, Raphael; Puelacher, Christian; Sunier, Germaine; Reddiess, Philipp; Rubini Gimenez, Maria; Wildi, Karin; Boeddinghaus, Jasper; Nestelberger, Thomas; Badertscher, Patrick; Sabti, Zaid; Schmid, Ramun; Leber, Remo; Widmer, Dayana Flores; Shrestha, Samyut; Strebel, Ivo; Wild, Damian; Osswald, Stefan; Zellweger, Michael; Mueller, Christian; Reichlin, Tobias

    2017-01-05

    We aimed to assess the diagnostic and prognostic value of ST-segment deviation in aVR, a lead often ignored in clinical practice, during exercise testing and to compare it to the most widely used criterion of ST-segment depression in V5. We enrolled 1,596 patients with suspected myocardial ischemia referred for nuclear perfusion imaging undergoing bicycle stress testing. ST-segment amplitudes in leads aVR and V5 were automatically measured. The presence of inducible myocardial ischemia was the diagnostic end point and adjudicated based on nuclear perfusion imaging and coronary angiography. Major adverse cardiac events (MACE) during 2 years of follow-up including death, acute myocardial infarction, and coronary revascularization were the prognostic end point. Exercise-induced myocardial ischemia was detected in 470 patients (29%). Median ST amplitudes for leads aVR and V5 differed significantly among patients with and without ischemia (p <0.01). The diagnostic accuracy of ST changes for myocardial ischemia as quantified by the area under the receiver operating characteristic curve was highest 2 minutes into recovery and similar in aVR and V5 (0.62, 95% confidence interval CI 0.60 to 0.65 vs 0.60, 95% confidence interval 0.58 to 0.63, p = 0.08 for comparison). In multivariate analysis, ST changes in lead aVR, but not lead V5, contributed independent diagnostic information on top of clinical parameters and manual electrocardiographic interpretation. Within 2 years of follow-up, MACE occurred in 33% of patients with ST elevations in aVR and in 16% without (p <0.001). In conclusion, ST elevation in lead aVR during exercise testing indicates inducible myocardial ischemia independently of ST depressions in lead V5 and clinical factors and also predicts MACE during follow-up.

  3. Severe Hypokalemia Masquerading Myocardial Ischemia

    PubMed Central

    Petrov, Daniel Bogdanov; Sardovski, Svetlozar Ivanov; Milanova, Maria Hristova

    2012-01-01

    An advanced degree of body potassium deficit may produce striking changes in the electrocardiogram (ECG). These changes can result in incidental findings on the 12-lead ECG or precipitate potentially life-threatening dysrhythmias. Although usually readily recognized, at times these abnormalities may be confused with myocardial ischemia. The object was to report a case of severe hypokalemia mimicking myocardial ischemia. A 33-year-old, previously healthy man, presented to the Emergency Department (ED) with a progressive weakness and chest discomfort. The electrocardiogram showed a marked ST-segment depression in leads II, III, aVF, V1-V6. The initial diagnosis was non ST-elevation myocardial infarction. Echocardiography was normal and troponin levels were within normal limits. A more detailed history revealed that the patient had an episode of acute gastroenteritis with diarrhea and vomiting. Serum chemistries were notable for a potassium concentration of 1,8 mmol per liter. With aggressive electrolyte correction, the ECG abnormalities reverted as potassium levels normalized. Hypokalemia induced ST-segment depression may simulate myocardial ischemia. The differential diagnosis might be difficult, especially in the cases when ST changes are accompanied with chest discomfort.

  4. Functional tests for myocardial ischemia

    SciTech Connect

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A. )

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references.

  5. [Painless myocardial ischemia in patient with extensive constrictive atherosclerosis of coronary arteries].

    PubMed

    Oshchepkova, E V; Lazareva, N V

    2012-01-01

    We describe in this article a clinical case of a patient with arterial hypertension, painless myocardial ischemia and extensive constrictive atherosclerosis of coronary arteries. Coronary heart disease (painless ischemia) was suspected basing on results of transesophageal electrostimulation coupled with stress echocardiography and was confirmed by coronary angiography. This description is followed by discussion of possibilities of different instrumental methods in diagnostics of painless ischemia, classification of painless ischemia, treatment, and prognosis.

  6. Ethanol-induced myocardial ischemia: close relation between blood acetaldehyde level and myocardial ischemia.

    PubMed

    Ando, H; Abe, H; Hisanou, R

    1993-05-01

    A patient with vasospastic angina who developed myocardial ischemia following ethanol ingestion but not after exercise was described. Myocardial ischemia was evidenced by electrocardiograms (ECGs) and thallium-201 scintigrams. The blood acetaldehyde level after ethanol ingestion was abnormally high. The time course and severity of myocardial ischemia coincided with those of the blood ethanol and acetaldehyde level. Coronary arteriography showed ergonovine maleate-induced coronary vasospasm at the left anterior descending coronary artery. ECG changes similar to those induced by ethanol ingestion were observed at the same time. These findings suggest that the high blood acetaldehyde level might be responsible for the development of coronary vasospasm and myocardial ischemia in this patient.

  7. 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.

  8. Protective approaches against myocardial ischemia reperfusion injury

    PubMed Central

    Li, Xianchi; Liu, Min; Sun, Rongrong; Zeng, Yi; Chen, Shuang; Zhang, Peiying

    2016-01-01

    Myocardial ischemia-reperfusion is the leading cause for the events of cardiovascular disease, and is considered as a major contributor to the morbidity and mortality associated with coronary occlusion. The myocardial damage caused by ischemia-reperfusion injury constitutes the primary pathological manifestation of coronary artery disease. It results from the interaction between the substances that accumulate during ischemia and those that are delivered on reperfusion. The level of this damage can range from a small insult resulting in limited myocardial damage to a large injury culminating in myocyte death. Importantly, major ischemia-reperfusion injury to the heart can result in permanent disability or death. Given the worldwide prevalence of coronary artery disease, developing a strategy to provide cardioprotection against ischemia-reperfusion-induced damage is of great importance. Currently, the treatment of reperfusion injury following ischemia is primarily supportive, since no specific target-oriented therapy has been validated thus far. Nevertheless, therapeutic approaches to protect against myocardial ischemia-reperfusion injury remain an active area of investigation given the detrimental effects of this phenomenon. PMID:28101167

  9. 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

  10. Myocardial Ischemia Caused by Subepicardial Hematoma

    PubMed Central

    Grieshaber, Philippe; Nef, Holger; Böning, Andreas; Niemann, Bernd

    2017-01-01

    Background Bleeding from bypass anastomosis leakage occurs early after coronary artery bypass grafting. Later, once the anastomosis is covered by intima, spontaneous bleeding is unlikely. Case Description A 63-year-old male patient developed a pseudoaneurysm-like, subepicardial late-term bleeding resulting in a hematoma that compromised coronary artery flow by increasing extracoronary pressure. This resulted in severe angina pectoris (Canadian Cardiovascular Society IV) and myocardial ischemia within the affected area. After surgical removal of the hematoma and repair of the anastomosis, the patient's symptoms disappeared and no signs of myocardial ischemia were present. Conclusion Surgical removal is an efficient therapy for subepicardial hematoma inducing myocardial ischemia. PMID:28352501

  11. 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.

  12. Steroid-induced recurrent myocardial ischemia.

    PubMed

    Yildirim, Ufuk; Gulel, Okan; Soylu, Korhan; Yuksel, Serkan; Sahin, Mahmut

    2014-01-01

    We report the case of a female patient under oral prednisolone therapy due to a diagnosis of idiopathic intracranial hypertension with papilledema. Unfortunately, short-term treatment with prednisolone caused an unusual complication in the patient, i.e., recurrent myocardial ischemia. Possible mechanisms leading to this complication were evaluated in the light of current knowledge.

  13. [Myocardial ischemia-reperfusion injury and melatonin].

    PubMed

    Sahna, Engin; Deniz, Esra; Aksulu, Hakki Engin

    2006-06-01

    It is believed that myocardial ischemia-reperfusion injury is related to increased free radical generated and intracellular calcium overload especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger, antioxidant and can inhibit the intracellular calcium overload. In this review, we have summarized the fundamental of cardiac ischemia-reperfusion injury and the effects of melatonin on myocardial damage that related to cardiac ischemia-reperfusion injury. The total antioxidant capacity of human serum is related to melatonin levels. Incidence of sudden cardiac death is high in the morning hours. It has been shown that melatonin levels are significantly low at these times and patients with coronary heart disease have lower than normal individuals. These findings thought that melatonin would be valuable to test in clinical trials for prevention of possible ischemia-reperfusion-induced injury, especially life threatening arrhythmias and infarct size, effecting life quality, associated with thrombolysis, angioplasty, coronary artery spasm or coronary bypass surgery.

  14. Angina pectoris during daily activities and exercise stress testing: The role of inducible myocardial ischemia and psychological distress.

    PubMed

    Sullivan, Mark D; Ciechanowski, Paul S; Russo, Joan E; Spertus, John A; Soine, Laurie A; Jordan-Keith, Kier; Caldwell, James H

    2008-10-31

    Physicians often consider angina pectoris to be synonymous with myocardial ischemia. However, the relationship between angina and myocardial ischemia is highly variable and we have little insight into the sources of this variability. We investigated the relationship of inducible myocardial ischemia on SPECT stress perfusion imaging to angina reported with routine daily activities during the previous four weeks (N=788) and to angina reported during an exercise stress test (N=371) in individuals with confirmed or suspected coronary disease referred for clinical testing. We found that angina experienced during daily life is more strongly and consistently associated with psychological distress and the personal threat associated with angina than with inducible myocardial ischemia. In multivariable models, the presence of any angina during routine activities over the prior month was significantly associated with age, perceived risk of myocardial infarction, and anxiety when compared to those with no reported angina in the past month. Angina during daily life was not significantly associated with inducible myocardial ischemia on stress perfusion imaging in bivariate or multivariable models. In contrast, angina experienced during exercise stress testing was significantly related to image and ECG ischemia, though it was also significantly associated with anxiety. These results suggest that angina frequency over the previous four weeks is more strongly associated with personal threat and psychosocial distress than with inducible myocardial ischemia. These results lend support to angina treatment strategies that aim to reduce threat and distress as well as to reduce myocardial ischemia.

  15. 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.

  16. 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.

  17. Myocardial ischemia reperfusion injury: from basic science to clinical bedside.

    PubMed

    Frank, Anja; Bonney, Megan; Bonney, Stephanie; Weitzel, Lindsay; Koeppen, Michael; Eckle, Tobias

    2012-09-01

    Myocardial ischemia reperfusion injury contributes to adverse cardiovascular outcomes after myocardial ischemia, cardiac surgery or circulatory arrest. Primarily, no blood flow to the heart causes an imbalance between oxygen demand and supply, named ischemia (from the Greek isch, restriction; and haema, blood), resulting in damage or dysfunction of the cardiac tissue. Instinctively, early and fast restoration of blood flow has been established to be the treatment of choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. Unfortunately, restoring blood flow to the ischemic myocardium, named reperfusion, can also induce injury. This phenomenon was therefore termed myocardial ischemia reperfusion injury. Subsequent studies in animal models of acute myocardial infarction suggest that myocardial ischemia reperfusion injury accounts for up to 50% of the final size of a myocardial infarct. Consequently, many researchers aim to understand the underlying molecular mechanism of myocardial ischemia reperfusion injury to find therapeutic strategies ultimately reducing the final infarct size. Despite the identification of numerous therapeutic strategies at the bench, many of them are just in the process of being translated to bedside. The current review discusses the most striking basic science findings made during the past decades that are currently under clinical evaluation, with the ultimate goal to treat patients who are suffering from myocardial ischemia reperfusion-associated tissue injury.

  18. Direct imaging of myocardial ischemia: a potential new paradigm in nuclear cardiovascular imaging.

    PubMed

    Jain, Diwakar; He, Zuo-Xiang

    2008-01-01

    Myocardial perfusion imaging has been in clinical use for over 30 years, serving as an effective, reliable, and relatively simple tool for diagnosis, risk stratification, and long-term follow-up of patients with suspected or known coronary artery disease. However, a unique strength of nuclear imaging is its ability to provide tools for imaging biochemical and metabolic processes and receptor and transporter functions at molecular and cellular levels in intact organisms under a wide variety of physiologic conditions. Despite their high resolution and technical sophistication, other imaging modalities currently do not have this capability. Metabolic imaging techniques using radiolabeled free fatty acid and glucose analogs provide a unique ability to image myocardial ischemia directly in patients with known or suspected coronary artery disease. These techniques can potentially overcome some of the limitations of currently used stress-rest perfusion imaging and also provide a unique opportunity to detect and image an episode of ischemia in the preceding hours even in the absence of other markers of ongoing myocardial ischemia. We describe recent studies using fluorine 18-labeled deoxyglucose and iodine 123 beta-methyl-p-iodophenyl-pentadecanoic acid for imaging myocardial ischemia.

  19. Myocardial ischemia and ventricular fibrillation: pathophysiology and clinical implications.

    PubMed

    Luqman, Nazar; Sung, Ruey J; Wang, Chun-Li; Kuo, Chi-Tai

    2007-07-31

    Ventricular fibrillation (VF) and myocardial ischemia are inseparable. The first clinical manifestation of myocardial ischemia or infarction may be sudden cardiac death in 20-25% of patients. The occurrence of potentially lethal arrhythmia is the end result of a cascade of pathophysiological abnormalities that result from complex interactions between coronary vascular events, myocardial injury, and changes in autonomic tone, metabolic conditions and ionic state of the myocardium. It is also related to the time from the onset of ischemia. Within the first few minutes there is abundant ventricular arrhythmogenesis usually lasting for 30 min. Triggers for ischemic VF occur at the border zone or regionally ischemic heart. The border zone of ischemia is the predominant site of fragmentation. Acute ischemia opens K(ATP) channels and causes acidosis and hypoxia of myocardial cells leading to a large dispersion in repolarization across the border zone. Abnormalities of intracellular Ca2+ handling also occur in the first few minutes of acute myocardial ischemia and may be an important cause of arrhythmias in human coronary artery disease. Substrate on the other hand transforms triggers into VF and serves to maintain it through fragmentation of waves in the ischemic zone. Thrombin levels, stretch, catecholamine, genetic predisposition, etc. are some of these factors. Reentry models described are spiral wave reentry, 3 dimensional rotors, reentry around 'M' cells and figure-of-eight reentry. Continuing efforts to better understand these arrhythmias will help identify patients of myocardial ischemia prone to arrhythmias.

  20. 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.

  1. 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

  2. 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

  3. The economics of cardiac biomarker testing in suspected myocardial infarction.

    PubMed

    Goodacre, Steve; Thokala, Praveen

    2015-03-01

    Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Angina and Mental Stress-Induced Myocardial Ischemia

    PubMed Central

    Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon; Ibeanu, Ijeoma; Raggi, Paolo; Vaccarino, Viola

    2015-01-01

    Objective Mental stress-induced myocardial ischemia is a common phenomenon in patients with coronary artery disease (CAD) and an emerging prognostic factor. Mental stress ischemia is correlated with ambulatory ischemia. However, whether it is related to angina symptoms during daily life has not been examined. Methods We assessed angina-frequency (past month) in 98 post-myocardial infarction (MI) subjects (age 18-60 years) using the Seattle Angina Questionnaire. Patients underwent [99mTc]sestamibi SPECT perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed-difference score (SDS), the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. Results The mean age was 50 years, 50% were female and 60% were non-white. After adjustment for age, sex, smoking, CAD-severity, depressive, anger and anxiety symptoms, each 1-point increase in mental-stress SDS was associated with 1.73-unit increase in the angina-frequency score (95% CI: 0.09-3.37) and 17% higher odds of being in a higher angina-frequency category (OR: 1.17, 95% CI: 1.00-1.38). Depressive symptoms were associated with 12% higher odds of being in a higher angina-frequency category (OR: 1.12, 95% CI: 1.03-1.21). In contrast, exercise/pharmacological stress-induced SDS was not associated with angina-frequency. Conclusion Among young and middle-aged post-MI patients, myocardial ischemia induced by mental stress in the lab, but not by exercise/pharmacological stress, is associated with higher frequency of retrospectively reported angina during the day. Psychosocial stressors related to mental stress ischemia may be important contributory factor to daily angina. PMID:25727240

  9. 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

  10. 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

  11. 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.

  12. Regional Myocardial Blood Flow and Ultrastructure Following Acute Temporary Ischemia.

    DTIC Science & Technology

    1982-01-01

    kidneys of dogs and cats , and suggest some element present in whole blood, but not present in filtered blood may serve to further damage ischemic...minutes of myocardial ischemia in the dog as Krug et al. (66) has reported in the cat . Finally, in this experiment the relationship of inhibited reflow...transient inhibition of flow. One has to wonder if their 6 cats with smaller areas of risk are more like the dogs in this study and may also have had

  13. Coronary vasodilator reserve persists despite tachycardia and myocardial ischemia

    SciTech Connect

    Bristow, J.D.; McFalls, E.O.; Anselone, C.G.; Pantely, G.A. )

    1987-08-01

    During myocardial ischemia, the authors tested whether coronary blood flow measured with radioactive microspheres labeled with {sup 141}Ce, {sup 51}Cr, {sup 103}Ru, and {sup 95}Nb would increase in response to tachycardia thereby employing known coronary flow reserve. The authors instrumented the left anterior descending (LAD) coronary circulation in anesthetized pigs and performed three sets of experiments while coronary pressure was controlled and several heart rate increases were produced. (1) Pacing-induced tachycardia at normal LAD pressure was characterized by increased LAD flow and myocardial oxygen consumption, without production of lactate. (2) Tachycardia at a mean LAD pressure of 38 mmHg was associated with a lower, fixed coronary flow and oxygen consumption. Lactate was produced at all rates and local myocardial function declined progressively. (3) Coronary flow at low LAD pressure doubled during tachycardia when intracoronary adenosine was added. The increase to the subepicardium was >100%, whereas subendocardial flow changed little. There is persistent coronary flow reserve during moderately severe myocardial ischemia, even when metabolic demand is increased by tachycardia. This reserve, however, is predominantly subepicardial.

  14. Neuroprotective Antioxidant STAZN Protects Against Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Ley, James J.; Prado, Ricardo; Wei, Jian Qin; Bishopric, Nanette H.; Becker, David A.; Ginsberg, Myron D.

    2009-01-01

    Background Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion. Methods and Results Physiologically controlled male Sprague-Dawley rats were anesthetized with isoflurane, paralyzed with pancuronium and mechanically ventilated. A guide wire was introduced via the femoral artery and advanced retrogradely via the aorta into the left coronary artery under fluoroscopic guidance. Rats with established coronary ischemia (85 min after occlusion) were given STAZN 3.5 mg/kg or its vehicle 5 minutes before and 2 hours after reperfusion, and were subjected to functional and histopathologic studies at 3 days. Ischemia-associated Q wave amplitude was reduced by 73% in STAZN-treated rats (P=0.01), while infarct-related ejection fraction, fractional shortening and severe regional wall-motion impairments were reduced by 48%, 54% and 37%, respectively, relative to vehicle-treated controls (P=0.05). Total myocardial infarct volume in STAZN-treated rats was correspondingly reduced by 43% (P<0.05), representing a sparing of 14% of the total left ventricular myocardium. Conclusions STAZN, a second-generation azulenyl nitrone with potent neuroprotective efficacy in brain ischemia, is also a rapidly acting and highly effective cardioprotective agent in acute coronary ischemia. Our results suggest the potential for clinical benefit in the setting of acute coronary syndromes. PMID:17936251

  15. Stable angina pectoris: the medical management of symptomatic myocardial ischemia.

    PubMed

    Parker, John D; Parker, John O

    2012-01-01

    Coronary artery disease (CAD) remains an important cause of morbidity and mortality and is a serious public health problem. Over the last 4 decades there have been dramatic advances in the both the prevention and treatment of CAD. The management of CAD was revolutionized by the development of effective surgical and percutaneous revascularization techniques. In this review we discuss the importance of the medical management of symptomatic, stable angina. Medical management approaches to both the treatment and prevention of symptomatic myocardial ischemia are summarized. In Canada, organic nitrates, β-adrenergic blocking agents, and calcium channel antagonists have been available for the therapy of angina for more than 25 years. All 3 classes are of proven benefit in the improvement of symptoms and exercise capacity in patients with stable angina. Although there is no clear first choice within these classes of anti-anginal agents, the presence of prior or concurrent conditions (for example, prior myocardial infarction and/or hypertension) plays an important role in the choice of anti-anginal class in individual patients. For some patients, combinations of different anti-anginal agents can be effective; however it is recommended that this approach be individualized. Although not currently available in Canada, other classes of anti-anginal agents have been developed; their mechanism of action and clinical efficacy is discussed. Patients with stable angina have an excellent prognosis. Patients in this category who obtain relief from symptomatic myocardial ischemia may do well without invasive intervention.

  16. Systolically gated 3D phase contrast MRA of mesenteric arteries in suspected mesenteric ischemia

    SciTech Connect

    Wasser, M.N.; Schultze Kool, L.J.; Roos, A. de

    1996-03-01

    Our goal was to assess the value of MRA for detecting stenoses in the celiac (CA) and superior mesenteric (SMA) arteries in patients suspected of having chronic mesenteric ischemia, using an optimized systolically gated 3D phase contrast technique. In an initial study in 24 patients who underwent conventional angiography of the abdominal vessels for different clinical indications, a 3D phase contrast MRA technique (3D-PCA) was evaluated and optimized to image the CAs and SMAs. Subsequently, a prospective study was performed to assess the value of systolically gated 3D-PCA in evaluation of the mesenteric arteries in 10 patients with signs and symptoms of chronic mesenteric ischemia. Intraarterial digital subtraction angiography and surgical findings were used as the reference standard. In the initial study, systolic gating appeared to be essential in imaging the SMA on 3D-PCA. In 10 patients suspected of mesenteric ischemia, systolically gated 3D-PCA identified significant proximal disease in the two mesenteric vessels in 4 patients. These patients underwent successful reconstruction of their stenotic vessels. Cardiac-gated MRA may become a useful tool in selection of patients suspected of having mesenteric ischemia who may benefit from surgery. 16 refs., 6 figs., 4 tabs.

  17. Constrictive pericarditis causing a positive TI-201 SPECT stress test for myocardial ischemia

    SciTech Connect

    Matthews, R.J.; Lightfoote, J.; Grusd, R.S. )

    1990-08-01

    A case of constritive pericarditis was demonstrated by a positive thallium SPECT stress test for myocardial ischemia. After pericardiectomy, the repeat thallium stress test was normal. The disappearance of the criteria for a positive test suggests that constrictive pericarditis can cause myocardial ischemia, which can be demonstrated by thallium SPECT stress testing.

  18. Silent myocardial ischemia: Current perspectives and future directions

    PubMed Central

    Ahmed, Amany H; Shankar, KJ; Eftekhari, Hossein; Munir, MS; Robertson, Jillian; Brewer, Alan; Stupin, Igor V; Casscells, S Ward

    2007-01-01

    Silent myocardial ischemia (SMI) is increasingly being recognized as part of the spectrum of ischemic heart disease. The spectrum of SMI ranges from asymptomatic coronary artery disease to critical illness necessitating intensive care. Although many diagnostic tools have been used to identify low- and high-risk subgroups, their use is limited by modest sensitivities and specificities. The present review identifies current concepts in the management of SMI in various clinical settings, as well as emerging technologies that may simplify the diagnosis and treatment of this condition. PMID:18651003

  19. [Pharmacological properties of phosphorylacetohydrazides in experimental myocardial ischemia].

    PubMed

    Balashov, V P; Al'miasheva, M I; Tarasova, R I; Rusina, I F; Kul'kova, N P; Kurmysheva, T V; Voskresenskaia, O V

    2007-01-01

    It is shown that 2-chloroethoxy-para-N-dimethylphosphorylacetohydrazide and N-acethylhydrazide-para-dimethylaminophenyl-2-chloroethoxyphosphorylacetic acid reliably reduce ischemia-induced depression of inotropic functions of the left ventricle in cats with experimental myocardial infarction model. The effect of both compounds can be explained by the maintenance of viability of the injured myocardium via a delay of the development of acidosis and the support of oxygen recycling in the ischemized zone. Both compounds show pronounced antiradical properties with a non-standard mechanism of action.

  20. Calpain system and its involvement in myocardial ischemia and reperfusion injury

    PubMed Central

    Neuhof, Christiane; Neuhof, Heinz

    2014-01-01

    Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria. Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia, reperfusion and postischemic structural remodelling. The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains. Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria. Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria. Calpain inhibition can prevent or attenuate myocardial injury during ischemia, reperfusion, and in later stages of myocardial infarction. PMID:25068024

  1. 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

  2. Ablation of cereblon attenuates myocardial ischemia-reperfusion injury.

    PubMed

    Kim, Jooyeon; Lee, Kwang Min; Park, Chul-Seung; Park, Woo Jin

    2014-05-16

    Cereblon (CRBN) was originally identified as a target protein for a mild type of mental retardation in humans. However, recent studies showed that CRBN acts as a negative regulator of AMP-activated protein kinase (AMPK) by binding directly to the AMPK catalytic subunit. Because AMPK is implicated in myocardial ischemia-reperfusion (I-R) injury, we reasoned that CRBN might play a role in the pathology of myocardial I-R through regulation of AMPK activity. To test this hypothesis, wild-type (WT) and crbn knockout (KO) mice were subjected to I-R (complete ligation of the coronary artery for 30 min followed by 24h of reperfusion). We found significantly smaller infarct sizes and less fibrosis in the hearts of KO mice than in those of WT mice. Apoptosis was also significantly reduced in the KO mice compared with that in WT mice, as shown by the reduced numbers of TUNEL-positive cells. In parallel, AMPK activity remained at normal levels in KO mice undergoing I-R, whereas it was significantly reduced in WT mice under the same conditions. In rat neonatal cardiomyocytes, overexpression of CRBN significantly reduced AMPK activity, as demonstrated by reductions in both phosphorylation levels of AMPK and the expression of its downstream target genes. Collectively, these data demonstrate that CRBN plays an important role in myocardial I-R injury through modulation of AMPK activity.

  3. 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.

  4. Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway

    PubMed Central

    Wang, Fang; Qiang, Jiao; Liu, Pan; Zhang, Jun; Xu, Jin-Wen

    2017-01-01

    The protective effects of ilexsaponin A on ischemia-reperfusion-induced myocardial injury were investigated. Myocardial ischemia/reperfusion model was established in male Sprague–Dawley rats. Myocardial injury was evaluated by TTC staining and myocardial marker enzyme leakage. The in vitro protective potential of Ilexsaponin A was assessed on hypoxia/reoxygenation cellular model in neonatal rat cardiomyocytes. Cellular viability and apoptosis were evaluated by MTT and TUNEL assay. Caspase-3, cleaved caspase-3, bax, bcl-2, p-Akt and Akt protein expression levels were detected by western-blot. Ilexsaponin A treatment was able to attenuate the myocardial injury in ischemia/reperfusion model by reducing myocardial infarct size and lower the serum levels of LDH, AST and CK-MB. The in vitro study also showed that ilexsaponin A treatment could increase cellular viability and inhibit apoptosis in hypoxia/reoxygenation cardiomyocytes. Proapoptotic proteins including caspase-3, cleaved caspase-3 and bax were significantly reduced and anti-apoptotic protein bcl-2 was significantly increased by ilexsaponin A treatment in hypoxia/reoxygenation cardiomyocytes. Moreover, Ilexsaponin A treatment was able to increase the expression levels of p-Akt in hypoxia/reoxygenation cellular model and myocardial ischemia/reperfusion animal model. Coupled results from both in vivo and in vitro experiments indicate that Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway. PMID:28182689

  5. 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

  6. Myeloperoxidase Is Not Useful for Detecting Stress Inducible Myocardial Ischemia but May Be Indicative of the Severity of Coronary Artery Disease

    PubMed Central

    Schuhmann, Christoph G.; Hacker, Marcus; Jung, Philip; Krötz, Florian

    2014-01-01

    Background and Objectives Elevated levels of myeloperoxidase (MPO) have been found in patients in different stages of coronary artery disease (CAD). The aim of this study was to assess whether the MPO liberation is increased by stress inducible myocardial ischemia and could be used to improve the diagnostic accuracy of non-invasive evaluation for myocardial ischemia. Subjects and Methods Seventy-six patients with suspected myocardial ischemia who underwent stress myocardial perfusion scintigraphy (MPS) were enrolled. 59 patients with an acute coronary syndrome (ACS) who received a percutaneous coronary intervention along with 12 healthy volunteers were also included in the study. In every subject the MPO plasma levels were assessed by enzyme linked immunosorbent assay. In patients undergoing MPS, the MPO levels were measured serially before and after the stress testing. Results Of the 76 patients undergoing MPS, 38 were diagnosed with a stress inducible myocardial ischemia. The patients with a stress induced ischemia had significantly higher basal MPO levels than those without it (32±3 ng/mL vs. 24±4 ng/mL, p=0.03). However, there was no relevant change in the MPO levels after the stress test compared to the baseline. The patients with ACS showed significantly higher MPO levels than the patients undergoing MPS (131±14 ng/mL vs. 28±2 ng/mL, p<0.01) and the healthy subjects (131±14 ng/mL vs. 26±2 ng/mL, p<0.01). Conclusion Since the MPO plasma levels did not increase after the stress MPS, MPO appears not to be a useful biomarker for detecting a stress inducible myocardial ischemia. Yet, the MPO levels correlate with the different stages of CAD and may hold significance as an indicator for its clinical severity. PMID:24497884

  7. 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.

  8. [The adrenergic mechanisms are involved in the pulmonary hemodynamics changes following experimental myocardial ischemia in rabbits].

    PubMed

    Evlakhov, V I; Poiasov, I Z

    2012-05-01

    In acute experiments in anesthetized rabbits the changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the blockade of alpha-adrenoreceptors by phentolamine or N-cholinoreceptors of autonomic ganglia by hexamethonium. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was elevated not significantly, the cardiac output decreased more than pulmonary artery flow. Following myocardial ischemia after the blockade of alpha-adrenoreceptors the pulmonary artery flow and cardiac output decreased in the same level and the pulmonary vascular resistance was decreased. In these conditions the pulmonary artery pressure decreased more than in control animals, meanwhile the pulmonary artery flow was decreased in the same level as in the last case. Following myocardial ischemia after the blockade of N-cholinoreceptors the pulmonary hemodynamics changes were the same as they were following myocardial ischemia in the control rabbits, the cardiac output decreased more than pulmonary artery flow. The disbalance of the cardiac output and pulmonary artery flow changes in the case of myocardial ischemia was caused by the pulmonary vessel reactions following activations of the humoral adrenergic mechanisms.

  9. 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.

  10. Investigation of ischemia modified albumin, oxidant and antioxidant markers in acute myocardial infarction

    PubMed Central

    Hazini, Ahmet; Işıldak, İbrahim; Alpdağtaş, Saadet; Önül, Abdullah; Şenel, Ünal; Kocaman, Tuba; Dur, Ali; Iraz, Mustafa; Uyarel, Hüseyin

    2015-01-01

    Introduction Acute myocardial infarction (AMI) is still one of the most common causes of death worldwide. In recent years, for diagnosis of myocardial ischemia, a new parameter, called ischemia modified albumin (IMA), which is thought to be more advantageous than common methods, has been researched. Aim In this study, systematic analysis of parameters considered to be related to myocardial ischemia has been performed, comparing between control and myocardial ischemia groups. Material and methods We selected 40 patients with AMI and 25 healthy controls for this study. Ischemia modified albumin levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) antioxidant enzyme activities and non-enzymatic antioxidants such as retinol, α-tocopherol, β-carotene and ascorbic acid levels were investigated in both groups. Glutathione (GSH) and malondialdehyde (MDA) levels, which are indicators of oxidative stress, were compared between patient and control groups. Results Ischemia modified albumin levels were found significantly higher in the AMI diagnosed group when compared with controls. The MDA level was elevated in the patient group, whereas the GSH level was decreased. SOD, GPx and CAT enzyme levels were decreased in the patient group, where it could be presumed that oxidative stress causes the cardiovascular diseases. Conclusions Due to the increased oxidative stress, non-enzymatic and enzymatic antioxidant capacity was affected. Systematic investigation of parameters related to myocardial infarction has been performed, and it is believed that such parameters can contribute to protection and early diagnosis of AMI and understanding the mechanism of development of the disease. PMID:26677379

  11. 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

  12. Myocardial Ischemia Induces SDF-1α Release in Cardiac Surgery Patients.

    PubMed

    Kim, Bong-Sung; Jacobs, Denise; Emontzpohl, Christoph; Goetzenich, Andreas; Soppert, Josefin; Jarchow, Mareike; Schindler, Lisa; Averdunk, Luisa; Kraemer, Sandra; Marx, Gernot; Bernhagen, Jürgen; Pallua, Norbert; Schlemmer, Heinz-Peter; Simons, David; Stoppe, Christian

    2016-06-01

    In the present observational study, we measured serum levels of the chemokine stromal cell-derived factor-1α (SDF-1α) in 100 patients undergoing cardiac surgery with cardiopulmonary bypass at seven distinct time points including preoperative values, myocardial ischemia, reperfusion, and the postoperative course. Myocardial ischemia triggered a marked increase of SDF-1α serum levels whereas cardiac reperfusion had no significant influence. Perioperative SDF-1α serum levels were influenced by patients' characteristics (e.g., age, gender, aspirin intake). In an explorative analysis, we observed an inverse association between SDF-1α serum levels and the incidence of organ dysfunction. In conclusion, time of myocardial ischemia was identified as the key stimulus for a significant upregulation of SDF-1α, indicating its role as a marker of myocardial injury. The inverse association between SDF-1α levels and organ dysfunction association encourages further studies to evaluate its organoprotective properties in cardiac surgery patients.

  13. 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

  14. 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

  15. Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.

    PubMed

    Gorsuch, W Brian; Guikema, Benjamin J; Fritzinger, David C; Vogel, Carl-Wilhelm; Stahl, Gregory L

    2009-12-01

    Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use.

  16. 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

  17. [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.

  18. 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

  19. Tachycardic vs. pharmacologic stress myocardial perfusion imaging: differential implications in multi-vessel ischemia

    PubMed Central

    Nguyen, Thanh H; Horowitz, John D; Unger, Steven A

    2012-01-01

    Background In patients unable to exercise, potential methods of induction of reversible myocardial ischemia include physiological heart rate acceleration via pacing or dobutamine infusion and asymmetric coronary vasodilatation using dipyridamole. Although their bases for induction of ischemia are widely disparate, no direct comparison of these techniques has previously been reported. Methods We performed a randomised, paired comparison of dipyridamole and pacing myocardial perfusion imaging (MPI) in 28 patients in whom exercise stress imaging was precluded, comparing the detection, localisation and quantitation of ischemia. Results Reversible myocardial ischemia was detected in 21 patients, concordantly in 13 (p = 0.042). There was a high degree of concordance (p < 0.0001) regarding locations of sites of ischemia. While there was a good correlation (r = 0.74, p < 0.0001) between size of total ischemic zones with dipyridamole and pacing, the magnitude of ischemia tended to be greater with dipyridamole (mean percentage of left ventricular myocardium ± SD, 9.4 ± 11.0% vs. 7.0 ± 9.0%, p = 0.091). Furthermore, this difference resulted from accentuation of the primary ischemic zone with dipyridamole in patients with multi-vessel ischemia (mean ± SD, 28.1 ± 21.1% vs. 18.7 ± 16.1%, p = 0.046). Conclusions Despite major differences in mechanism(s) of induction of ischemia, dipyridamole and pacing produce similar results regarding detection, localisation and severity of ischemia. However, dipyridamole accentuates ischemia in primary (vs. secondary) ischemic zones, consistent with known induction of coronary “steal". This should be taken into account in interpretation of scan results. PMID:22254212

  20. 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.

  1. Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection

    SciTech Connect

    Carrio, I.; Berna, L.; Ballester, M.; Estorch, M.; Obrador, D.; Cladellas, M.; Abadal, L.; Ginjaume, M.

    1988-12-01

    Indium-111 antimyosin scans were used to assess myocardial damage in patients with suspected myocarditis and cardiac transplant rejection. The calculation of a myocardium to lung ratio (AM index) to quantify antimyosin uptake was performed. AM index in normal subjects (n = 8) at 48 hr postinjection was 1.46 +/- 0.04. In patients with suspected myocarditis (16 studies in 13 patients), AM index was 2.0 +/- 0.5 (p less than 0.001); suggesting a considerable incidence of ongoing cell damage in this group, despite the small proportion of positive right ventricular endomyocardial biopsy (RVbx) (4/13). In patients studied after cardiac transplantation (37 studies in 17 patients), AM indexes correlated with RVbx. In patients with RVbx proven rejection (n = 14), AM index was 1.87 +/- 0.19 (p less than 0.001). In patients with RVbx showing infiltrates but not myocyte damage (n = 13), AM index was 1.80 +/- 0.27 (p = 0.02). In patients with normal RVbx (n = 10), AM index was 1.56 +/- 0.17 (p = NS versus controls; p = 0.001 versus those with positive RVbx). Calculated AM indexes correlated with graded visual analysis of the scans (r = 0.823; p = 0.001). Antimyosin scans are an appropriate method to assess myocardial damage in patients with suspected myocarditis and cardiac rejection.

  2. Molecular Characterization of Reactive Oxygen Species in Myocardial Ischemia-Reperfusion Injury.

    PubMed

    Zhou, Tingyang; Chuang, Chia-Chen; Zuo, Li

    2015-01-01

    Myocardial ischemia-reperfusion (I/R) injury is experienced by individuals suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. The occlusion of blood flow to the tissue, termed ischemia, can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue can result in further damage. Reactive oxygen species (ROS) have been studied intensively to reveal their role in myocardial I/R injury. Under normal conditions, ROS function as a mediator in many cell signaling pathways. However, stressful environments significantly induce the generation of ROS which causes the level to exceed body's antioxidant defense system. Such altered redox homeostasis is implicated in myocardial I/R injury. Despite the detrimental effects from ROS, low levels of ROS have been shown to exert a protective effect in the ischemic preconditioning. In this review, we will summarize the detrimental role of ROS in myocardial I/R injury, the protective mechanism induced by ROS, and potential treatments for ROS-related myocardial injury.

  3. Myocardial ischemia-reperfusion injury: a neglected therapeutic target

    PubMed Central

    Hausenloy, Derek J.; Yellon, Derek M.

    2013-01-01

    Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI. PMID:23281415

  4. Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and reduces myocardial ischemia-reperfusion injury by up-regulating HIF-1

    PubMed Central

    Yang, Long; Xie, Peng; Wu, Jianjiang; Yu, Jin; Yu, Tian; Wang, Haiying; Wang, Jiang; Xia, Zhengyuan; Zheng, Hong

    2016-01-01

    Background: Sevoflurane postconditioning (SPostC) can exert myocardial protective effects similar to ischemic preconditioning. However, the exact myocardial protection mechanism by SPostC is unclear. Studies indicate that hypoxia-inducible factor-1 (HIF-1) maintains cellular respiration homeostasis by regulating mitochondrial respiratory chain enzyme activity under hypoxic conditions. This study investigated whether SPostC could regulate the expression of myocardial HIF-1α and to improve mitochondrial respiratory function, thereby relieving myocardial ischemia-reperfusion injury in rats. Methods: The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, postconditioning was performed using sevoflurane alone or in combination with the HIF-1α inhibitor 2-methoxyestradiol (2ME2). The changes in hemodynamic parameters, HIF-1α protein expression levels, mitochondrial respiratory function and enzyme activity, mitochondrial reactive oxygen species (ROS) production rates, and mitochondrial ultrastructure were measured or observed. Results: Compared to the ischemia-reperfusion (I/R) group, HIF-1α expression in the SPostC group was significantly up-regulated. Additionally, cardiac function indicators, mitochondrial state 3 respiratory rate, respiratory control ratio (RCR), cytochrome C oxidase (CcO), NADH oxidase (NADHO), and succinate oxidase (SUCO) activities, mitochondrial ROS production rate, and mitochondrial ultrastructure were significantly better than those in the I/R group. However, these advantages were completely reversed by the HIF-1α specific inhibitor 2ME2 (P<0.05). Conclusion: The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1α expression. PMID:27830025

  5. Real time measurement of myocardial oxygen dynamics during cardiac ischemia-reperfusion of rats.

    PubMed

    Lee, Gi-Ja; Kim, Seung Ki; Kang, Sung Wook; Kim, Ok-Kyun; Chae, Su-Jin; Choi, Samjin; Shin, Jae Ho; Park, Hun-Kuk; Chung, Joo-Ho

    2012-11-21

    Because oxygen plays a critical role in the pathophysiology of myocardial injury during subsequent reperfusion, as well as ischemia, the accurate measurement of myocardial oxygen tension is crucial for the assessment of myocardial viability by ischemia-reperfusion (IR) injury. Therefore, we utilized a sol-gel derived electrochemical oxygen microsensor to monitor changes in oxygen tension during myocardial ischemia-reperfusion. We also analyzed differences in oxygen tension recovery in post-ischemic myocardium depending on ischemic time to investigate the correlation between recovery parameters for oxygen tension and the severity of IR injury. An oxygen sensor was built using a xerogel-modified platinum microsensor and a coiled Ag/AgCl reference electrode. Rat hearts were randomly divided into 5 groups: control (0 min ischemia), I-10 (10 min ischemia), I-20 (20 min ischemia), I-30 (30 min ischemia), and I-40 (40 min ischemia) groups (n = 3 per group, respectively). After the induction of ischemia, reperfusion was performed for 60 min. As soon as the ischemia was initiated, oxygen tension rapidly declined to near zero levels. When reperfusion was initiated, the changes in oxygen tension depended on ischemic time. The normalized peak level of oxygen tension during the reperfusion episode was 188 ± 27 in group I-10, 120 ± 24 in group I-20, 12.5 ± 10.6 in group I-30, and 1.24 ± 1.09 in group I-40 (p < 0.001, n = 3, respectively). After 60 min of reperfusion, the normalized restoration level was 129 ± 30 in group I-10, 88 ± 4 in group I-20, 3.40 ± 4.82 in group I-30, and 0.99 ± 0.94 in group I-40 (p < 0.001, n = 3, respectively). The maximum and restoration values of oxygen tension in groups I-30 and I-40 after reperfusion were lower than pre-ischemic values. In particular, oxygen tension in the I-40 group was not recovered at all. These results were also demonstrated by TTC staining. We suggest that these recovery parameters could be utilized as an index of

  6. The contrast of immunohistochemical studies of myocardial fibrinogen and myoglobin in early myocardial ischemia in rats.

    PubMed

    Xiaohong, Zhao; Xiaorui, Chen; Jun, Hu; Qisheng, Qin

    2002-03-01

    In this study, an animal model of early myocardial ischemia (EMI) was established by ligating the left anterior descending coronary artery of rats. The experimental animals were divided into five groups according to different intervals of MI (15, 30min, 1, 2, and 3h) and one control group. Tissues from the apex of the myocardium and the adjacent myocardium were taken for paraffin sections, followed by hematoxylin-eosin and streptavidin-biotin-peroxidase complex (SABC) staining. Results showed that the myoglobin (Mb) depletion and the fibrinogen (Fg) staining increase were detected in the 30min MI group. The wavy-like increasing extension of the size and the intensity of the Mb depletion and the Fg staining intensification from the subendocardial to the subepicardial cells were observed along with the prolongation of the ischemic period. Both changes had similar patterns and sensitivity, except Fg was less reliable than Mb as it is more easily contaminated by blood. After overcoming blood contamination, the SABC-Fg technique will provide a new method for the diagnosis of EMI.

  7. Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

    PubMed Central

    Collins, R.; MacMahon, S.; Flather, M.; Baigent, C.; Remvig, L.; Mortensen, S.; Appleby, P.; Godwin, J.; Yusuf, S.; Peto, R.

    1996-01-01

    OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer

  8. 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.

  9. 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

  10. [Antioxidant and cardioprotective effects of N-tyrosol in myocardial ischemia with reperfusion in rats].

    PubMed

    Smol'iakova, V I; Chernyshova, G A; Plotnikov, M B; Aliev, O I; Krasnov, E A

    2010-01-01

    We demonstrated in experiments on rats with left coronary artery occlusion that intravenous administration of 20 mg/kg n-tyrosol during ischemia limited manifestations of oxidative stress in myocardial tissue during early post reperfusion period: content of diene and triene conjugates lowered 16 and 20%, respectively. This was associated with higher preservation of cardiomyocytes and reduction of the infarction zone.

  11. Relation between the electrocardiographic stress test and degree and location of myocardial ischemia.

    PubMed

    Tavel, M E; Shaar, C

    1999-07-15

    Factors that influence frequency and location of stress-induced electrocardiographic (ECG) ST depression and the development of chest pain are incompletely understood. We studied 331 patients with ischemic myocardial nuclear defects in response to routine clinical treadmill testing with simultaneous ECG recording. Nuclear defects were analyzed for location and extent of myocardium involved. Exercise-induced ischemic ST changes were demonstrated in 59% of patients (196 of 331). Subjects with stress-induced ECG changes and/or chest pain had more extensive nuclear perfusion defects. Diabetic patients were significantly less likely to experience chest pain (24%) versus nondiabetics (41%) during testing (p = 0.04). Larger perfusion defects were associated with greater magnitude, lead distribution, and incidence of ECG changes. The number of ECG lead zones (anterior, lateral, and inferior) responding positively were related to both magnitude of ST depression and severity of ischemia, but not to location of ischemic defects. Regardless of location of ischemia, ST depression occurred with similar frequency. Thus, exercise-induced ECG ST depression remains a valuable indicator of the severity of myocardial ischemia. Greater ST depression involving multiple leads usually signified extensive myocardial ischemia, but provided no information regarding its location. Anginal-type chest pain induced by exercise testing also denoted more extensive ischemia.

  12. Acute myocardial ischemia in adults secondary to missed Kawasaki disease in childhood.

    PubMed

    Rizk, Sherif R Y; El Said, Galal; Daniels, Lori B; Burns, Jane C; El Said, Howaida; Sorour, Khaled A; Gharib, Soliman; Gordon, John B

    2015-02-15

    Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood.

  13. Acute Myocardial Ischemia in Adults Secondary to Missed Kawasaki Disease in Childhood

    PubMed Central

    Rizk, Sherif RY; El Said, Galal; Daniels, Lori B; Burns, Jane C; El Said, Howaida; Sorour, Khaled A; Gharib, Soliman; Gordon, John B

    2015-01-01

    Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions due Kawasaki disease (KD) in childhood. We reviewed a total of 580 angiograms of patients ≤ 40 years of age presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9 %) of whom nine presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n=10), probable (n=29), or equivocal (n=7). Compared to the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults age 40 years or younger undergoing angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be due to missed KD in childhood. PMID:25555655

  14. [Cardiovascular adaptability to acute hypercalcemia in the dog. The role of peroperative myocardial ischemia].

    PubMed

    Dumont, L; Stanley, P; Chartrand, C

    1985-01-01

    Since the hemodynamic consequences of acute hypercalcemia are altered by numerous interferences we have evaluated the role of peroperative myocardial ischemia on the adaptability to rapid calcium increment. Twenty-two dogs served as control and 16 were submitted to 1 hour of myocardial ischemia along with topical myocardial cooling. Each animal was equipped with blood flow transducer positioned around the ascending aorta and with central venous and aortic catheters. During each study 0.90 mEq of calcium was rapidly injected and hemodynamic data were recorded until base-line resetting. This experimental protocol was carried out 3 hours postoperatively and then daily during one month. Base-line hemodynamic data indicated the presence of myocardial failure in the experimental group in the immediate postoperative period only. Rapid calcium administration elicited transient positive inotropic response, widening of the arterial pulse pressure, reflex bradycardia and no evidence of peripheral vasoconstriction. In the early postoperative period (3 hours after surgery) the failing myocardium is more sensitive to the inotropic effect of hypercalcemia. Twenty-four hours after surgery both groups of animals have the same hemodynamic response to this stress; thereafter for both groups this response gradually decreased and finally stabilized by the 6th to 10th day after surgery. Acute hypercalcemia bears hemodynamic consequences that are amplified early after peroperative myocardial ischemia. However in long term this surgical component widely used clinically does not interfered with the cardiovascular adaptability to this pharmacological stress.

  15. 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.

  16. Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers

    ClinicalTrials.gov

    2017-03-02

    Acute Myocardial Infarction (AMI); Acute Coronary Syndrome (ACS); ST Elevation (STEMI) Myocardial Infarction; Ischemic Reperfusion Injury; Non-ST Elevation (NSTEMI) Myocardial Infarction; Angina, Unstable

  17. Clinical characteristics of silent myocardial ischemia diagnosed with adenosine stress 99mTc-tetrofosmin myocardial scintigraphy in Japanese patients with acute cerebral infarction.

    PubMed

    Nomura, Tetsuya; Kusaba, Tetsuro; Kodama, Naotoshi; Terada, Kensuke; Urakabe, Yota; Nishikawa, Susumu; Keira, Natsuya; Matsubara, Hiroaki; Tatsumi, Tetsuya

    2013-01-01

    It is well known that silent myocardial ischemia (SMI) often complicates patients with cerebral infarction and that stroke patients often die of ischemic heart disease. Therefore, it is considered important to treat myocardial ischemia in stroke patients. This study investigated SMI complicating Japanese patients with fresh stroke, using (99m)Tc-tetrofosmin myocardial scintigraphy with pharmacologic stress testing to elucidate their clinical manifestations. This study included 41 patients (26 men, mean age 76.0 ± 10.7 years) with acute cerebral infarction and no history of coronary artery disease. All patients underwent (99m)Tc-tetrofosmin myocardial scintigraphy with intravenous administration of adenosine to diagnose SMI. Of the 41 patients, myocardial ischemia was confirmed in 17 patients (41.5%). Atherosclerotic etiology was the major cause of stroke in the ischemia(+) group and embolic origin was the major cause in the ischemia(-) group. Patients with myocardial ischemia had a higher incidence of diabetes mellitus (52.9 vs 20.8%; P = 0.0323) and more than two conventional cardiovascular risk factors (64.7 vs 25.0%; P = 0.0110) compared with the nonischemic patients. Infarction subtype of atherosclerotic origin was an independent positive predictor of asymptomatic myocardial ischemia in patients with stroke. These findings indicate that the prevalence of asymptomatic myocardial ischemia is relatively high, especially in patients with stroke of atherosclerotic origin. Therefore, it is beneficial for us to narrow the target population who are at the highest risk when screening for SMI in Japanese patients with acute cerebral infarction.

  18. The production of hydrogen sulfide limits myocardial ischemia and reperfusion injury and contributes to the cardioprotective effects of preconditioning with endotoxin, but not ischemia in the rat.

    PubMed

    Sivarajah, A; McDonald, M C; Thiemermann, C

    2006-08-01

    We investigated whether (endogenous) hydrogen sulfide (H2S) protects the heart against myocardial ischemia and reperfusion injury. Furthermore, we investigated whether endogenous H2S is involved in the protection afforded by (1) ischemic preconditioning and (2) the second window of protection caused by endotoxin. The involvement of one of the potential (end) effectors of the cardioprotection afforded by H2S was investigated using the mitochondrial KATP channel blocker, 5-hydroxydecanoate (5-HD; 5 mg/kg). Animals were subjected to 25 min regional myocardial ischemia followed by reperfusion (2 h) and were pretreated with the H2S donor, sodium hydrosulfide (3 mg/kg i.v.). Animals were also subjected to shorter periods of myocardial ischemia (15 min) and reperfusion (2 h) and pretreated with an irreversible inhibitor of cystathionine-gamma-lyase, dl-propargylglycine (PAG; 50 mg/kg i.v.). Animals were also pretreated with PAG (50 mg/kg) and subjected to either (1) ischemic preconditioning or (2) endotoxin (1 mg/kg i.p.) 16 h before myocardial ischemia. Myocardial infarct size was determined by p-nitroblue tetrazolium staining. Administration of sodium hydrosulfide significantly reduced myocardial infarct size, and this effect was abolished by 5-HD. Administration of PAG (50 mg/kg) or 5-HD significantly increased infarct size caused by 15 min of myocardial ischemia. The delayed cardioprotection afforded by endotoxin was abolished by 5-HD or PAG. In contrast, PAG (50 mg/kg) did not affect the cardioprotective effects of ischemic preconditioning. These findings suggest that (1) endogenous H2S is produced by myocardial ischemia in sufficient amounts to limit myocardial injury and (2) the synthesis or formation of H2S by cystathionine-gamma-lyase may contribute to the second window of protection caused by endotoxin.

  19. Protective Effects of L-Malate against Myocardial Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Ding, Shiao; Yang, Yang; Mei, Ju

    2016-01-01

    Objective. To investigate the protective effects of L-malate against myocardial ischemia/reperfusion (I/R) injury in rats. Methods. Male Sprague-Dawley rats were randomly assigned to the following groups: sham (sham), an ischemia/reperfusion (I/R) model group (model), an DMF pretreated group (DMF), and 5 L-malate pretreated groups (15, 60, 120, 240, or 480 mg/kg, gavage) before inducing myocardial ischemia. Plasma LDH, cTn-I, TNF-α, hs-CRP, SOD, and GSH-PX were measured 3 h later I/R. Areas of myocardial infarction were measured; hemodynamic parameters during I/R were recorded. Hearts were harvested and Western blot was used to quantify Nrf2, Keap1, HO-1, and NQO-1 expression in the myocardium. Results. L-malate significantly reduced LDH and cTn-I release, reduced myocardial infarct size, inhibited expression of inflammatory cytokines, and partially preserved heart function, as well as increasing antioxidant activity after myocardial I/R injury. Western blot confirmed that L-malate reduced Kelch-like ECH-associated protein 1 in ischemic myocardial tissue, upregulated expression of Nrf2 and Nrf2 nuclear translocation, and increased expression of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1, which are major targets of Nrf2. Conclusions. L-malate may protect against myocardial I/R injury in rats and this may be associated with activation of the Nrf2/Keap1 antioxidant pathway. PMID:26941825

  20. The influence of hypertonic mannitol on regional myocardial blood flow during acute and chronic myocardial ischemia in anesthetized and awake intact dogs.

    PubMed Central

    Willerson, J T; Watson, J T; Hutton, I; Fixler, D E; Curry, G C; Templeton, G H

    1975-01-01

    The influence of hypertonic mannitol on regional myocardial blood flow and ventricular performance was studied during acute myocardial ischemia in awake, unsedated and in anesthesized dogs and after myocardial infarction in awake unsedated dogs. Regional myocardial blood flow was measured with radioactive microspheres. Generalized increases in regional myocardial blood flow occurred after mannitol in all of the different animal models studied. The increases in coronary blood flow after mannitol were just as impressive in the nonischemic regions as in the ischemic portion of the left ventricle in all of the different models that were examined in this study. Improvement in regional myocardial blood flow to the ischemic area of the left ventricle after mannitol was associated with a reduction in ST segment elevation during acute myocardial ischemia in anesthetized dogs. The increases in regional myocardial flow after mannitol were also associated with increases in contractility, but the increases in flow appeared to be more impressive than the changes in contractility. The data obtained demonstrate that mannitol increases regional coronary blood flow to both ischemic and nonischemic myocardium in both anesthetized and awake, unsedated, intact dogs with acute and chronic myocardial ischemia and that mannitol reduces ST segment elevation during acute myocardial ischemia in anesthetized dogs. Thus the results suggest that under these circumstances the increases in regional myocardial blood flow after mannitol are of physiological importance in reducing the extent of myocardial injury. Since coronary blood flow increased to nonischemic regions the increases in regional myocardial flow demonstrated in this study after mannitol cannot be entirely explained by the mechanism of reduction in ischemic cell swelling. PMID:1123427

  1. Impact of acute propranolol administration on dobutamine-induced myocardial ischemia as evaluated by myocardial perfusion imaging and echocardiography.

    PubMed

    Shehata, A R; Gillam, L D; Mascitelli, V A; Herman, S D; Ahlberg, A W; White, M P; Chen, C; Waters, D D; Heller, G V

    1997-08-01

    Beta-blocker therapy may delay or completely prevent myocardial ischemia during exercise testing, as assessed by ST-segment shifts, myocardial perfusion defects, or echocardiographic wall motion abnormalities. However, the impact of beta-blocker therapy on these end points during dobutamine stress testing has not been well established. The purpose of this study was to determine the impact of propranolol on dobutamine stress testing with ST-segment monitoring, technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging, and echocardiography. In 17 patients with known reversible perfusion defects, dobutamine stress tests with and without propranolol were performed in randomized order and on separate days, following discontinuation of oral beta blockers and calcium antagonists. Propronolol was administered intravenously to a cumulative dose of 8 mg or to a maximum heart rate reduction of 25% and dobutamine was infused in graded doses in 3 minute stages until a standard clinical end point or the maximum dose of 40 microg/kg/min was achieved. The dobutamine stress test after propranolol was associated with a lower maximum heart rate (83 +/- 18 vs 125 +/- 17, p <0.001) and rate pressure product (14,169 +/- 4,248 vs 19,894 +/- 3,985, p <0.001) despite a higher infusion dose. The SPECT myocardial ischemia score was also lower (6.9 +/- 5.8 vs 10.1 +/- 7.1, p = 0.047) and fewer echocardiographic segments were abnormal (3.4 +/- 3.0 vs 4.6 +/- 3.4, p = 0.042). In 4 of 17 patients, reversible perfusion defects and echocardiographic wall motion abnormalities were detected during the control but not during the propranolol test. Thus, during dobutamine stress testing, beta-blocker therapy attenuates, and in some cases eliminates, evidence of myocardial ischemia.

  2. Effects of rosuvastatin and pitavastatin on ischemia-induced myocardial stunning in dogs.

    PubMed

    Satoh, Kumi; Takaguri, Akira; Itagaki, Mai; Kano, Seiichiro; Ichihara, Kazuo

    2008-04-01

    Incomplete recovery of myocardial contraction after reperfusion following brief ischemia is called the "stunning phenomenon" in an animal experiment. A hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) does not affect this phenomenon, but lipophilic statins further reduce the contraction during reperfusion. The effects of novel hydrophilic rosuvastatin and lipophilic pitavastatin on myocardial stunning in dogs were examined. In a preliminary experiment in vitro, pitavastatin reduced L6 cell viability at 10(-6) M and higher, whereas rosuvastatin and pravastatin up to 10(-5) M did not show such effects. An empty capsule or a capsule filled with rosuvastatin (2 mg/kg per day) or pitavastatin (0.4 mg/kg per day) was orally administered to dogs. After 3 weeks, both statins lowered the serum cholesterol level to the same extent. Under pentobarbital anesthesia, dogs were subjected to 15-min ischemia followed by 120-min reperfusion. Ischemia arrested the myocardial contraction in the ischemic area, and reperfusion recovered it but incompletely, showing the stunning phenomenon. Rosuvastatin did not modify the stunning phenomenon, while pitavastatin further deteriorated the myocardial contraction during reperfusion.

  3. Evaluation of TRPM (transient receptor potential melastatin) genes expressions in myocardial ischemia and reperfusion.

    PubMed

    Demir, Tuncer; Yumrutas, Onder; Cengiz, Beyhan; Demiryurek, Seniz; Unverdi, Hatice; Kaplan, Davut Sinan; Bayraktar, Recep; Ozkul, Nadide; Bagcı, Cahit

    2014-05-01

    In the present study, the expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, and TRPM8 genes were evaluated in heart tissues after ischemia/reperfusion (IR). For this study, 30 albino male Wistar rats were equally divided into three groups as follows: Group 1: control group (n:10), Group II: ischemia group (ischemia for 60 min) (n:10) and Group III: IR (reperfusion 48 h after ischemia for 60 min and reperfusion for 48 h). The expression levels of the TRPM genes were analyzed by semi-quantitative reverse transcriptase-PCR. When compared to the ischemia control, the expression levels of TRPM2, TRPM4, and TRPM6 did not change, whereas that of TRPM7 increased. However, TRPM1, TRPM3, TRPM5, and TRPM8 were not expressed in heart tissue. Histopathological analysis of the myocardial tissues showed that the structures that were most damaged were those exposed to IR. The findings showed that there is a positive relationship between TRPM7 expression and myocardial IR injury.

  4. Nonuniform loss of regional flow reserve during myocardial ischemia in dogs.

    PubMed

    Coggins, D L; Flynn, A E; Austin, R E; Aldea, G S; Muehrcke, D; Goto, M; Hoffman, J I

    1990-08-01

    To determine whether coronary vasodilator reserve that persists during myocardial ischemia is present in all left ventricular regions, we measured regional blood flow in 192 left ventricular pieces (mean weight, 201 mg) in each of eight dogs by using radioactive microspheres while perfusing the left main coronary artery at 70, 50, 40, and 30 mm Hg. Flows were measured before and during adenosine infusion to determine flow reserve. Perfusion at 40 and 30 mm Hg produced ischemia in all dogs. At 70 mm Hg, 100% of left ventricular regions had significant flow reserve, compared with 92%, 55%, and 8% during perfusion at 50, 40, and 30 mm Hg, respectively. A greater amount of flow reserve and a greater number of regions responded to adenosine in the subepicardium than in the subendocardium at 50, 40, and 30 mm Hg. We conclude that coronary flow reserve persists in only a subset of left ventricular regions during ischemia and that the number of regions with persistent flow reserve decreases with perfusion pressure. These findings may best be explained by a model in which regional ischemia is a maximal coronary vasodilator and persistent pharmacological vasodilator reserve seen when global markers indicate ischemia simply reflects persistent endogenous flow reserve in myocardial regions not yet ischemic.

  5. 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

  6. c-Cbl Inhibition Improves Cardiac function and Survival in Response to Myocardial Ischemia

    PubMed Central

    Rafiq, Khadija; Kolpakov, Mikhail A; Seqqat, Rachid; Guo, Jianfen; Guo, Xinji; Qi, Zhao; Yu, Daohai; Mohapatra, Bhopal; Zutshi, Neha; An, Wei; Band, Hamid; Sanjay, Archana; Houser, Steven R; Sabri, Abdelkarim

    2014-01-01

    Background The proto-oncogene Casitas b-lineage lymphoma (c-Cbl) is an adaptor protein with an intrinsic E3 ubiquitin ligase activity that targets receptor and non-receptor tyrosine kinases, resulting in their ubiquitination and down-regulation. However, the function of c-Cbl in the control of cardiac function is currently unknown. In this study, we examined the role of c-Cbl in myocyte death and cardiac function after myocardial ischemia. Methods and Results We show increased c-Cbl expression in human ischemic and dilated cardiomyopathy hearts and in response to pathological stress stimuli in mice. c-Cbl deficient mice demonstrated a more robust functional recovery after myocardial ischemia reperfusion injury, as well as significantly reduced myocyte apoptosis and improved cardiac function. Ubiquitination and downregulation of key survival c-Cbl targets, epidermal growth factor receptors and focal adhesion kinase, were significantly reduced in c-Cbl knockout mice. Inhibition of c-Cbl expression or its ubiquitin ligase activity in cardiac myocytes offered protection against H2O2 stress. Interestingly, c-Cbl deletion reduced the risk of death and increased cardiac functional recovery after chronic myocardial ischemia. This beneficial effect of c-Cbl deletion was associated with enhanced neoangiogenesis and increased expression of vascular endothelial growth factor (VEGF)-a and VEGF receptor type 2 in the infarcted region. Conclusions c-Cbl activation promotes myocyte apoptosis, inhibits angiogenesis and causes adverse cardiac remodeling after myocardial infarction. These findings point to c-Cbl as a potential therapeutic target for the maintenance of cardiac function and remodeling after myocardial ischemia. PMID:24583314

  7. 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

    2016-07-29

    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.

  8. 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

  9. Functional, Cellular, and Molecular Characterization of the Angiogenic Response to Chronic Myocardial Ischemia in Diabetes

    PubMed Central

    Boodhwani, Munir; Sodha, Neel R.; Mieno, Shigetoshi; Xu, Shu-Hua; Feng, Jun; Ramlawi, Basel; Clements, Richard T.; Sellke, Frank W.

    2009-01-01

    Background Ischemic heart disease is the most common cause of mortality in diabetic patients. Although therapeutic angiogenesis is an attractive option for these patients, they appear to have reduced collateral formation in response to myocardial ischemia. The aims of this study were to establish a large animal model of diabetes and chronic myocardial ischemia, evaluate the effects of diabetes on the angiogenic response, and elucidate the molecular pathways involved. Methods and Results Diabetes was induced in male Yucatan miniswine using a pancreatic β-cell specific toxin, alloxan (150 mg/kg; n=8). Age-matched swine served as controls (n=8). Eight weeks after induction, chronic ischemia was induced by ameroid constrictor placement around the circumflex coronary artery. Myocardial perfusion and function were assessed at 3 and 7 weeks after ameroid placement using isotope-labeled microspheres. Endothelial cell density and myocardial expression of angiogenic mediators was evaluated. Diabetic animals exhibited significant endothelial dysfunction. Collateral dependent perfusion and LV function were significantly impaired in diabetic animals. Diabetic animals also demonstrated reduced endothelial cell density (173±14 versus 234±23 cells/hpf, P=0.03). Expression of VEGF, Ang-1, and Tie-2 was reduced, whereas antiangiogenic proteins, angiostatin (4.4±0.9-fold increase, P<0.001), and endostatin (2.9±0.4-fold increase, P=0.03) were significantly elevated in the diabetic myocardium. Conclusions Diabetes results in a profound impairment in the myocardial angiogenic response to chronic ischemia. Pro-and antiangiogenic mediators identified in this study offer novel targets for the modulation of the angiogenic response in diabetes. PMID:17846323

  10. Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress

    PubMed Central

    Wu, Shao-ze; Tao, Lu-yuan; Wang, Jiao-ni; Xu, Zhi-qiang; Wang, Jie; Xue, Yang-jing; Huang, Kai-yu; Lin, Jia-feng; Li, Lei

    2017-01-01

    The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart. Our results indicate that amifostine pretreatment has a protective effect against myocardial I/R injury via scavenging ROS. PMID:28392886

  11. Arginase as a target for treatment of myocardial ischemia-reperfusion injury.

    PubMed

    Tratsiakovich, Yahor; Yang, Jiangning; Gonon, Adrian Thomas; Sjöquist, Per-Ove; Pernow, John

    2013-11-15

    Two distinct enzymes of arginase (1 and 2) are critically regulating nitric oxide (NO) bioavailability by competing with NO synthase for their common substrate l-arginine. Increased expression and activity of arginase is observed in atherosclerosis and myocardial ischemia-reperfusion (I/R). Several studies have demonstrated a key pathophysiological role of increased activity of arginase during I/R. Pharmacological inhibition of arginase results in restoration of NO availability and salvage of myocardium during I/R. Arginase inhibition might be a promising therapeutic strategy for the limitation of myocardial injury in acute myocardial infarction. Current understanding of the role of arginase and efficacy of arginase inhibition during myocardial I/R is reviewed in the present article.

  12. Pericardial mesothelioma presenting as a suspected ST-elevation myocardial infarction.

    PubMed

    Barroso, Ana Sofia; Leite, Sérgio; Friões, Fernando; Vasconcelos, Mariana; Azevedo, Daniela; Baldaia, Helena; Amorim, Mário Jorge; Dias, Paula

    2017-03-23

    Primary cardiac and pericardial tumors are rare entities with an autopsy frequency of 0.001-0.03%. Metastases to the heart and pericardium are much more common than primary tumors. Malignant pericardial mesotheliomas account for up to 50% of primary pericardial tumors. We report the case of a 75-year-old woman with hypertension, dyslipidemia and atrial fibrillation who went to the emergency department due to nonspecific thoracic discomfort of over six hours duration associated with syncope. Physical examination revealed a low-amplitude arrhythmic pulse, no heart murmurs and no signs of pulmonary congestion. The ECG revealed atrial fibrillation with ST-segment elevation in V2-V6, I and aVL. The patient was transferred for emergent coronary angiography, which revealed a long stenosis in the mid-distal portion of the left anterior descending artery. The echocardiogram showed a large pericardial effusion with diffuse thickening of the myocardium. Due to worsening hemodynamics, cardiac rupture was suspected and the patient underwent urgent sternotomy and pericardiotomy with drainage of a large quantity of hematic fluid. The surgeons then identified a large, unresectable tumor occupying the distal half of the anterior portion of the heart. This is, to our knowledge, the first case report of primary pericardial mesothelioma presenting with suspected ST-elevation myocardial infarction. In this case, direct observation of the tumor led to biopsy and the final diagnosis. These are highly malignant tumors and when diagnosed are usually already at an advanced stage.

  13. Dictionary-driven Ischemia Detection from Cardiac Phase-Resolved Myocardial BOLD MRI at Rest

    PubMed Central

    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) w.r.t. 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. PMID:26292338

  14. Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Herzog, Christine; Schmitz, Martina; Levkau, Bodo; Herrgott, Ilka; Mersmann, Jan; Larmann, Jan; Johanning, Kai; Winterhalter, Michael; Chun, Jerold; Müller, Frank Ulrich; Echtermeyer, Frank; Hildebrand, Reinhard; Theilmeier, Gregor

    2010-01-01

    HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P3 was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P3-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P3 receptor. PMID:21274265

  15. Transient mitral regurgitation: An adjunctive sign of myocardial ischemia during dipyridamole-thallium imaging

    SciTech Connect

    Lette, J.; Gagnon, A.; Lapointe, J.; Cerino, M.

    1989-07-01

    A patient developed transient exacerbation of a mitral insufficiency murmur and a reversible posterior wall perfusion defect during dipyridamole-thallium imaging. Coronary angiography showed significant stenoses of both the right and the circumflex coronary arteries that supply the posterior papillary muscle. Cardiac auscultation for transient mitral incompetence, a sign of reversible papillary muscle dysfunction, is a simple and practical adjunctive test for myocardial ischemia during dipyridamole-thallium imaging. It may confirm that an isolated reversible posterior wall myocardial perfusion defect is truly ischemic in nature as opposed to an artifact resulting from attenuation by the diaphragm.

  16. Prevalence and Clinical Characteristics of Mental Stress–Induced Myocardial Ischemia in Patients With Coronary Heart Disease

    PubMed Central

    Jiang, Wei; Samad, Zainab; Boyle, Stephen; Becker, Richard C.; Williams, Redford; Kuhn, Cynthia; Ortel, Thomas L.; Rogers, Joseph; Kuchibhatla, Maragatha; O’Connor, Christopher; Velazquez, Eric J.

    2014-01-01

    Objectives The goal of this study was to evaluate the prevalence and clinical characteristics of mental stress–induced myocardial ischemia. Background Mental stress–induced myocardial ischemia is prevalent and a risk factor for poor prognosis in patients with coronary heart disease, but past studies mainly studied patients with exercise-induced myocardial ischemia. Methods Eligible patients with clinically stable coronary heart disease, regardless of exercise stress testing status, underwent a battery of 3 mental stress tests followed by a treadmill test. Stress-induced ischemia, assessed by echocardiography and electrocardiography, was defined as: 1) development or worsening of regional wall motion abnormality; 2) left ventricular ejection fraction reduction ≥8%; and/or 3) horizontal or downsloping ST-segment depression ≥1 mm in 2 or more leads lasting for ≥3 consecutive beats during at least 1 mental test or during the exercise test. Results Mental stress–induced ischemia occurred in 43.45%, whereas exercise-induced ischemia occurred in 33.79% (p = 0.002) of the study population (N = 310). Women (odds ratio [OR]: 1.88), patients who were not married (OR: 1.99), and patients who lived alone (OR: 2.24) were more likely to have mental stress–induced ischemia (all p < 0.05). Multivariate analysis showed that compared with married men or men living with someone, unmarried men (OR: 2.57) and married women (OR: 3.18), or living alone (male OR: 2.25 and female OR: 2.72, respectively) had higher risk for mental stress-induced ischemia (all p < 0.05). Conclusions Mental stress-induced ischemia is more common than exercise-induced ischemia in patients with clinically stable coronary heart disease. Women, unmarried men, and individuals living alone are at higher risk for mental stress-induced ischemia. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847) PMID:23410543

  17. Increased myocardial ischemia during nitrate therapy: caused by multiple coronary artery-left ventricle fistulae?

    PubMed

    Heper, Gulumser; Kose, Sedat

    2005-01-01

    We present the case of a 54-year-old man who had crescendo angina during nitrate therapy. Selective coronary angiograms showed no atherosclerotic lesions, but did show plexuses of intramural vessels that connected the distal thirds of the left and right coronary systems with the left ventricle. The cause of our patient's increased myocardial ischemia during nitrate therapy may have been the coronary "steal" phenomenon.

  18. Intra-QRS Spectral Changes Accompany ST Segment Changes During Episodes of Myocardial Ischemia

    PubMed Central

    Gramatikov, Boris; Iyer, Vivek

    2014-01-01

    Background Coronary artery disease and myocardial ischemia cause substantial morbidity and mortality. While ischemia is traditionally diagnosed on the 12-lead electrocardiogram (ECG) by shifts in the ST segment, electrical changes are also produced within the QRS complex during depolarization of ischemic ventricular tissue, though these are often of small amplitude and can be missed in traditional ECG analysis. We explore the utility of an easily implemented spectral analysis method for detecting intra-QRS changes during episodes of myocardial ischemia, using Holter recordings from the European ST-T database. Methods Time-frequency distributions of QRS complexes from each recording were computed using the continuous wavelet transform. Indices corresponding to frequency content of four overlapping frequency bands were computed: F1 (24–35 Hz), F2 (30–45 Hz), F3 (40–60 Hz), and F4 (50–80 Hz). Values of these indices were compared during annotated episodes of ST change and during a baseline during the recording. Results Marked changes in intra-QRS frequency content were identified during ischemia, grouped by ECG lead analyzed. In lead III, a pronounced and statistically significant increase in the highest frequency sub-bands (F3 and F4) was consistently observed. Analysis of anterior precordial leads also showed significant increases in F4. Conclusions Intra-QRS time-frequency analysis using the continuous wavelet transform can identify a spectral signature corresponding to myocardial ischemia in the range 24–80 Hz. Intra-QRS spectral analysis has the potential for many clinical applications. PMID:25266140

  19. 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

  20. Exercise-induced silent myocardial ischemia in patients with vasospastic angina

    SciTech Connect

    Aoki, M.; Koyanagi, S.; Sakai, K.; Irie, T.; Takeshita, A.; Nakamura, M.; Nakagaki, O. )

    1990-03-01

    To clarify the incidence and clinical characteristics of exercise-induced myocardial ischemia in patients with vasospastic angina, we performed exercise thallium computed tomography in 25 patients who had no significant coronary artery stenosis greater than 70%. Coronary artery spasm was documented by coronary angiography in all patients. Eleven patients (44%) developed exercise-induced perfusion defects, but only four of them had anginal pain (36%). Diltiazem (90 mg, administered orally) prevented the development of exercise-induced perfusion defects in all patients. Multivessel coronary spasm was documented by coronary angiography in 11 patients, and nine of them (82%) showed exercise-induced perfusion defects (p less than 0.05). From this study it can be concluded: (1) Exercise-induced myocardial ischemia was demonstrated in 44% of patients who had vasospastic angina without fixed coronary stenosis, and 64% of them were asymptomatic. (2) Patients with multivessel spasm had a greater prevalence of exercise-induced myocardial ischemia than those with single-vessel spasm.

  1. Protective effect of lidocaine during regional myocardial ischemia: an altered pathophysiologic response assessed by NADH fluorescence

    SciTech Connect

    Baron, D.W.; Walls, J.T.; Anderson, R.E.; Harrison, C.E. Jr.

    1982-07-01

    Studies were undertaken to determine the effects of lidocaine on ischemic myocardium, which was induced by coronary artery constriction in open-chested dogs. A real-time epicardial fluorescent technique to detect in vivo-reduced nicotinamide adenine dinucleotide (NADH) during 60 seconds of ischemia was used. Blood flow of ischemic myocardium was measured by using radioactive microspheres of 9 +/- 1 micrometers (mean +/- SE) and was compared with that of normal myocardium, shown by injection of alpha-zurine blue dye. Lidocaine effectively reduced peak NADH fluorescence by 18.6%, from 93.9 +/- 7.2 to 76.4 +/-4.1 mV (p less than 0.005). Lidocaine delayed the onset of fluorescence (2.2 +/- 0.2 versus 1.3 +/- 0.1 s p less than 0.002) and facilitated the recovery from ischemia (38.4 +/- 2.9 versus 54.8 +/- 2.9 s p less than 0.001). Increase in NADH concentration during ischemia correlated (r.0.76, p less than 0.006) with ischemic fluorescence. These findings were independent of altered hemodynamics or change in myocardial blood flow. Results indicate that lidocaine provides myocardial cellular protection during transient ischemia; there is an altered NADH fluorescent response to coronary artery occlusion.

  2. Incomplete Relaxation between Beats after Myocardial Hypoxia and Ischemia

    PubMed Central

    Weisfeldt, Myron L.; Armstrong, Paul; Scully, Hugh E.; Sanders, Charles A.; Daggett, Willard M.

    1974-01-01

    Recovery from hypoxia has been shown to prolong cardiac muscle contraction, particularly the relaxation phase. The present studies were designed to examine whether incomplete relaxation between beats can result from this prolongation of contraction and relaxation in isolated muscle after hypoxia and in the canine heart after both hypoxia and acute ischemia. The relationship between heart rate and the extent of incomplete relaxation is emphasized in view of the known enhancement of the velocity of contraction caused by increasing heart rate. The extent of incomplete relaxation during 10-s periods of pacing at increasing rates was examined before and after hypoxia in isometric cat right ventricular papillary muscle (12-120 beats/min) and in the canine isovolumic left ventricle (120-180 beats/min). Incomplete relaxation was quantified by measuring the difference between the lowest diastolic tension or pressure during pacing and the true resting tension or pressure determined by interruption of pacing at each rate. In eight cat papillary muscles (29°C), there was significantly greater incomplete relaxation 5 min after hypoxia at rates of 96 and 120 beats/min (P < 0.02 vs. before hypoxia). In seven canine isovolumic left ventricles, recovery from hypoxia and higher heart rates also resulted in incomplete relaxation. Incomplete relaxation before hypoxia at a rate of 180 beats/min was 0.8±0.5 cm H2O and at 5 min of recovery from hypoxia was 12.6±3.5 cm H2O (P < 0.01). 12 hearts were subjected to a 1.5-3-min period of acute ischemia and fibrillation. There was significant incomplete relaxation at a rate of 140 beats/min for 5 min after defibrillation and reperfusion. These data indicate that incomplete relaxation is an important determinant of diastolic hemodynamics during recovery from ischemia or hypoxia. The extent of incomplete relaxation appears to be a function of the rate of normalization of the velocity of relaxation and tension development after ischemia or

  3. Ginsenoside Rg3 Improves Cardiac Function after Myocardial Ischemia/Reperfusion via Attenuating Apoptosis and Inflammation

    PubMed Central

    Zhang, Li-ping; Jiang, Yi-chuan; Yu, Xiao-feng; Xu, Hua-li; Li, Min

    2016-01-01

    Objectives. Ginsenoside Rg3 is one of the ginsenosides which are the main constituents isolated from Panax ginseng. Previous study demonstrated that ginsenoside Rg3 had a protective effect against myocardial ischemia/reperfusion- (I/R-) induced injury. Objective. This study was designed to evaluate the effect of ginsenoside Rg3 on cardiac function impairment induced by myocardial I/R in rats. Methods. Sprague-Dawley rats were subjected to myocardial I/R. Echocardiographic and hemodynamic parameters and histopathological examination were carried out. The expressions of P53, Bcl-2, Bax, and cleaved caspase-3 and the levels of TNF-α and IL-1β in the left ventricles were measured. Results. Ginsenoside Rg3 increased a left ventricular fractional shortening and left ventricular ejection fraction. Treatment with ginsenoside Rg3 also alleviated increases of left ventricular end diastolic pressure and decreases of left ventricular systolic pressure and ±dp/dt in myocardial I/R-rats. Ginsenoside Rg3 decreased apoptosis cells through inhibiting the activation of caspase-3. Ginsenoside Rg3 also caused significant reductions of the contents of TNF-α and IL-1β in left ventricles of myocardial I/R-rats. Conclusion. The findings suggested that ginsenoside Rg3 possessed the effect of improving myocardial I/R-induced cardiac function impairment and that the mechanism of pharmacological action of ginsenoside Rg3 was related to its properties of antiapoptosis and anti-inflammation. PMID:28105061

  4. 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

  5. Chest pain with myocardial ischemia in a child: should we think about coronary slow flow phenomenon?

    PubMed

    Kocabaş, Abdullah; Kardelen, Fırat; Akçurin, Gayaz; Ertuğ, Halil

    2013-10-01

    The coronary slow flow phenomenon (CSFP) is an angiographic finding characterized by delayed opacification of epicardial coronary arteries in the absence of stenotic lesion. Herein, we present a 13-year-old boy with recurrent chest pain who was diagnosed with acute ST-segment elevation myocardial infarction associated with CSFP, which has not been reported previously in the pediatric age group. Coronary angiography revealed only the presence of slow flow in the left anterior descending (LAD) coronary artery. Myocardial perfusion scintigraphy revealed a reversible perfusion defect in the LAD territory, which regressed partially at rest and showed complete improvement after dipyridamole infusion. All the symptoms, electrocardiogram abnormalities and cardiac markers returned to normal after dipyridamole treatment during the follow-up. We conclude that CSFP should be kept in mind in the differential diagnosis of chest pain with myocardial ischemia in the pediatric age group.

  6. Effects and Mechanisms of Chinese Herbal Medicine in Ameliorating Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Liu, Qing; Li, Jiqiang; Wang, Jing; Li, Jianping; Janicki, Joseph S.

    2013-01-01

    Myocardial ischemia-reperfusion (MIR) injury is a major contributor to the morbidity and mortality associated with coronary artery disease, which accounts for approximately 450,000 deaths a year in the United States alone. Chinese herbal medicine, especially combined herbal formulations, has been widely used in traditional Chinese medicine for the treatment of myocardial infarction for hundreds of years. While the efficacy of Chinese herbal medicine is well documented, the underlying molecular mechanisms remain elusive. In this review, we highlight recent studies which are focused on elucidating the cellular and molecular mechanisms using extracted compounds, single herbs, or herbal formulations in experimental settings. These studies represent recent efforts to bridge the gap between the enigma of ancient Chinese herbal medicine and the concepts of modern cell and molecular biology in the treatment of myocardial infarction. PMID:24288571

  7. Impaired contractile recovery after low-flow myocardial ischemia in a porcine model of metabolic syndrome.

    PubMed

    Huang, Janice V; Lu, Li; Ye, Shuyu; Bergman, Bryan C; Sparagna, Genevieve C; Sarraf, Mohammad; Reusch, Jane E B; Greyson, Clifford R; Schwartz, Gregory G

    2013-03-15

    Clinical metabolic syndrome conveys a poor prognosis in patients with acute coronary syndrome, not fully accounted for by the extent of coronary atherosclerosis. To explain this observation, we determined whether postischemic myocardial contractile and metabolic function are impaired in a porcine dietary model of metabolic syndrome without atherosclerosis. Micropigs (n = 28) were assigned to a control diet (low fat, no added sugars) or an intervention diet (high saturated fat and simple sugars, no added cholesterol) for 7 mo. The intervention diet produced obesity, hypertension, dyslipidemia, and impaired glucose tolerance, but not atherosclerosis. Under open-chest, anesthetized conditions, pigs underwent 45 min of low-flow myocardial ischemia and 120 min of reperfusion. In both diet groups, contractile function was similar at baseline and declined similarly during ischemia. However, after 120 min of reperfusion, regional work recovered to 21 ± 12% of baseline in metabolic syndrome pigs compared with 61 ± 13% in control pigs (P = 0.01). Ischemia-reperfusion caused a progressive decline in mechanical/metabolic efficiency (regional work/O2 consumption) in metabolic syndrome hearts, but not in control hearts. Metabolic syndrome hearts demonstrated altered fatty acyl composition of cardiolipin and increased Akt phosphorylation in both ischemic and nonischemic regions, suggesting tonic activation. Metabolic syndrome hearts used more fatty acid than control hearts (P = 0.03). When fatty acid availability was restricted by prior insulin exposure, differences between groups in postischemic contractile recovery and mechanical/metabolic efficiency were eliminated. In conclusion, pigs with characteristics of metabolic syndrome demonstrate impaired contractile and metabolic recovery after low-flow myocardial ischemia. Contributory mechanisms may include remodeling of cardiolipin, abnormal activation of Akt, and excessive utilization of fatty acid substrates.

  8. 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.

  9. Impaired contractile recovery after low-flow myocardial ischemia in a porcine model of metabolic syndrome

    PubMed Central

    Huang, Janice V.; Lu, Li; Ye, Shuyu; Bergman, Bryan C.; Sparagna, Genevieve C.; Sarraf, Mohammad; Reusch, Jane E. B.; Greyson, Clifford R.

    2013-01-01

    Clinical metabolic syndrome conveys a poor prognosis in patients with acute coronary syndrome, not fully accounted for by the extent of coronary atherosclerosis. To explain this observation, we determined whether postischemic myocardial contractile and metabolic function are impaired in a porcine dietary model of metabolic syndrome without atherosclerosis. Micropigs (n = 28) were assigned to a control diet (low fat, no added sugars) or an intervention diet (high saturated fat and simple sugars, no added cholesterol) for 7 mo. The intervention diet produced obesity, hypertension, dyslipidemia, and impaired glucose tolerance, but not atherosclerosis. Under open-chest, anesthetized conditions, pigs underwent 45 min of low-flow myocardial ischemia and 120 min of reperfusion. In both diet groups, contractile function was similar at baseline and declined similarly during ischemia. However, after 120 min of reperfusion, regional work recovered to 21 ± 12% of baseline in metabolic syndrome pigs compared with 61 ± 13% in control pigs (P = 0.01). Ischemia-reperfusion caused a progressive decline in mechanical/metabolic efficiency (regional work/O2 consumption) in metabolic syndrome hearts, but not in control hearts. Metabolic syndrome hearts demonstrated altered fatty acyl composition of cardiolipin and increased Akt phosphorylation in both ischemic and nonischemic regions, suggesting tonic activation. Metabolic syndrome hearts used more fatty acid than control hearts (P = 0.03). When fatty acid availability was restricted by prior insulin exposure, differences between groups in postischemic contractile recovery and mechanical/metabolic efficiency were eliminated. In conclusion, pigs with characteristics of metabolic syndrome demonstrate impaired contractile and metabolic recovery after low-flow myocardial ischemia. Contributory mechanisms may include remodeling of cardiolipin, abnormal activation of Akt, and excessive utilization of fatty acid substrates. PMID:23335793

  10. Prevalence of Ischemia on Myocardial Perfusion Scintigraphy of Pre- and Postmenopausal Women

    PubMed Central

    dos Santos, Daniel Augusto Message; Navarro, Wendy Yasdin Sierraalta; Alexandre, Leonardo Machado; Cestari, Priscila Feitosa; Smanio, Paola Emanuela Poggio

    2013-01-01

    Background In postmenopausal women, the presence of risk factors for coronary artery disease (CAD) increases. However, the difference in prevalence of ischemia between pre- and postmenopausal women with multiple risk factors for CAD has not been well established. Objectives To compare the prevalence of ischemia on Tc99m-sestamibi myocardial perfusion scintigraphy (MPS) in pre-and postmenopausal women, and to evaluate whether menopause can be considered an independent risk predictor of ischemia in women with multiple risk factors for CAD. Methods This study retrospectively assessed 500 MPS of pre- and postmenopausal women with multiple risk factors for CAD. Statistical analysis was performed by using Fisher exact test and univariate and multivariate analysis, a p value ≤ 0.05 being considered significant. Results Postmenopausal women represented 55.9% of the sample; 83.3% were hypertensive; 28.9%, diabetic; 32.1%, smokers; 25%, obese; 61.2% had high cholesterol levels; and 34.3% had known CAD. Postmenopausal women were more often hypertensive, diabetic and dyslipidemic, and had lower functional capacity on exercise testing (p = < 0.005). The presence of ischemia on MPS did not significantly differ between the pre- and postmenopausal groups (p = 0.395). The only variable associated with ischemia on MPS was known CAD (p = 0.004). Conclusion The results suggest that, in women with multiple risk factors for CAD, menopause was not an independent predictor of ischemia on MPS. Those data support the idea that the investigation of ischemia via MPS in women with multiple risk factors for CAD should begin prior to menopause. PMID:24217403

  11. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury.

    PubMed

    Kawaguchi, Masanori; Takahashi, Masafumi; Hata, Takeki; Kashima, Yuichiro; Usui, Fumitake; Morimoto, Hajime; Izawa, Atsushi; Takahashi, Yasuko; Masumoto, Junya; Koyama, Jun; Hongo, Minoru; Noda, Tetsuo; Nakayama, Jun; Sagara, Junji; Taniguchi, Shun'ichiro; Ikeda, Uichi

    2011-02-15

    Background- Inflammation plays a key role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury; however, the mechanism by which myocardial I/R induces inflammation remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple-protein complex called the inflammasome. Therefore, we hypothesized that the inflammasome is an initial sensor for danger signal(s) in myocardial I/R injury. Methods and Results- We demonstrate that inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, is crucially involved in the initial inflammatory response after myocardial I/R injury. We found that inflammasomes are formed by I/R and that its subsequent activation of inflammasomes leads to interleukin-1β production, resulting in inflammatory responses such as inflammatory cell infiltration and cytokine expression in the heart. In mice deficient for apoptosis-associated speck-like adaptor protein and caspase-1, these inflammatory responses and subsequent injuries, including infarct development and myocardial fibrosis and dysfunction, were markedly diminished. Bone marrow transplantation experiments with apoptosis-associated speck-like adaptor protein-deficient mice revealed that inflammasome activation in bone marrow cells and myocardial resident cells such as cardiomyocytes or cardiac fibroblasts plays an important role in myocardial I/R injury. In vitro experiments revealed that hypoxia/reoxygenation stimulated inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, and that hypoxia/reoxygenation-induced activation was mediated through reactive oxygen species production and potassium efflux. Conclusions- Our results demonstrate the molecular basis for the initial inflammatory response after I/R and suggest that the inflammasome is a potential novel therapeutic target for preventing myocardial I/R injury.

  12. 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.

  13. Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion.

    PubMed

    Okere, Isidore C; McElfresh, Tracy A; Brunengraber, Daniel Z; Martini, Wenjun; Sterk, Joseph P; Huang, Hazel; Chandler, Margaret P; Brunengraber, Henri; Stanley, William C

    2006-01-01

    In the normal heart, there is loss of citric acid cycle (CAC) intermediates that is matched by the entry of intermediates from outside the cycle, a process termed anaplerosis. Previous in vitro studies suggest that supplementation with anaplerotic substrates improves cardiac function during myocardial ischemia and/or reperfusion. The present investigation assessed whether treatment with the anaplerotic medium-chain fatty acid heptanoate improves contractile function during ischemia and reperfusion. The left anterior descending coronary artery of anesthetized pigs was subjected to 60 min of 60% flow reduction and 30 min of reperfusion. Three treatment groups were studied: saline control, heptanoate (0.4 mM), or hexanoate as a negative control (0.4 mM). Treatment was initiated after 30 min of ischemia and continued through reperfusion. Myocardial CAC intermediate content was not affected by ischemia-reperfusion; however, treatment with heptanoate resulted in a more than twofold increase in fumarate and malate, with no change in citrate and succinate, while treatment with hexanoate did not increase fumarate or malate but increased succinate by 1.8-fold. There were no differences among groups in lactate exchange, glucose oxidation, oxygen consumption, and contractile power. In conclusion, despite a significant increase in the content of carbon-4 CAC intermediates, treatment with heptanoate did not result in improved mechanical function of the heart in this model of reversible ischemia-reperfusion. This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion.

  14. 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.

  15. Leukocyte CD11a expression and granulocyte activation during experimental myocardial ischemia and long lasting reperfusion

    PubMed Central

    Lantos, János; Grama, László; Orosz, Tamás; Temes, Gyula; Rőth, Elizabeth

    2001-01-01

    BACKGROUND: Myocardial ischemia and reperfusion are accompanied by leukocyte activation and expression of surface adhesion molecules, which induce pathological interactions between endothelial cells and circulating neutrophils, leading to tissue damage. While the dynamics of these processes have been well defined during acute reperfusion, there is very little information regarding long lasting reperfusion. OBJECTIVES: To investigate neutrophil granulocyte (PMN) activation and the CD11a expression of leukocytes during myocardial ischemia and reperfusion for four weeks. ANIMALS AND METHODS: The left anterior descending coronary artery was occluded for 1 h in six dogs, followed by reperfusion for four weeks. Peripheral blood samples were collected before the operation, at the end of ischemia, at 5 and 60 min of reperfusion, and on postoperative days 1, 2, 3, 7, 14, 21 and 28. Sham operation on four dogs served as control. Leukocyte expression of CD11a was measured by flow cytometry. Superoxide radical production of isolated PMNs was determined spectrophotometrically. RESULTS: Granulocyte CD11a expression increased while the superoxide radical-producing capacity decreased significantly by the third postoperative day. Sham operation produced similar alterations in these parameters during the first postoperative week. From the second postoperative week, however, granulocyte radical production and adhesion molecule expression were higher in the ischemic animals. CONCLUSIONS: The exhaustion of PMN radical production and maximal CD11a expression during the first postoperative week are probably due to the surgical trauma caused by thoracotomy, but increased granulocyte function during later reperfusion indicates prolonged healing of injured myocardium. PMID:20428266

  16. 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

  17. Cardioprotective Effect of Electroacupuncture Pretreatment on Myocardial Ischemia/Reperfusion Injury via Antiapoptotic Signaling

    PubMed Central

    Lu, Sheng-feng; Huang, Yan; Wang, Ning; Shen, Wei-xing; Fu, Shu-ping; Li, Qian; Yu, Mei-ling; Liu, Wan-xin; Chen, Xia; Jing, Xin-yue; Zhu, Bing-mei

    2016-01-01

    Objectives. Our previous study has used RNA-seq technology to show that apoptotic molecules were involved in the myocardial protection of electroacupuncture pretreatment (EAP) on the ischemia/reperfusion (I/R) animal model. Therefore, this study was designed to investigate how EAP protects myocardium against myocardial I/R injury through antiapoptotic mechanism. Methods. By using rats with myocardial I/R, we ligated the left anterior descending artery (LAD) for 30 minutes followed by 4 hr of reperfusion after EAP at the Neiguan (PC6) acupoint for 12 days; we employed arrhythmia scores, serum myocardial enzymes, and cardiac troponin T (cTnT) to evaluate the cardioprotective effect. Heart tissues were harvested for western blot analyses for the expressions of pro- and antiapoptotic signaling molecules. Results. Our preliminary findings showed that EAP increased the survival of the animals along with declined arrhythmia scores and decreased CK, LDH, CK-Mb, and cTnT levels. Further analyses with the heart tissues detected reduced myocardial fiber damage, decreased number of apoptotic cells and the protein expressions of Cyt c and cleaved caspase 3, and the elevated level of Endo G and AIF after EAP intervention. At the same time, the protein expressions of antiapoptotic molecules, including Xiap, BclxL, and Bcl2, were obviously increased. Conclusions. The present study suggested that EAP protected the myocardium from I/R injury at least partially through the activation of endogenous antiapoptotic signaling. PMID:27313648

  18. Ischemia/Reperfusion Injury following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists

    PubMed Central

    Neri, Margherita; Pascale, Natascha; Pomara, Cristoforo

    2017-01-01

    Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Reperfusion strategies are the current standard therapy for AMI. However, they may result in paradoxical cardiomyocyte dysfunction, known as ischemic reperfusion injury (IRI). Different forms of IRI are recognized, of which only the first two are reversible: reperfusion-induced arrhythmias, myocardial stunning, microvascular obstruction, and lethal myocardial reperfusion injury. Sudden death is the most common pattern for ischemia-induced lethal ventricular arrhythmias during AMI. The exact mechanisms of IRI are not fully known. Molecular, cellular, and tissue alterations such as cell death, inflammation, neurohumoral activation, and oxidative stress are considered to be of paramount importance in IRI. However, comprehension of the exact pathophysiological mechanisms remains a challenge for clinicians. Furthermore, myocardial IRI is a critical issue also for forensic pathologists since sudden death may occur despite timely reperfusion following AMI, that is one of the most frequently litigated areas of cardiology practice. In this paper we explore the literature regarding the pathophysiology of myocardial IRI, focusing on the possible role of the calpain system, oxidative-nitrosative stress, and matrix metalloproteinases and aiming to foster knowledge of IRI pathophysiology also in terms of medicolegal understanding of sudden deaths following AMI. PMID:28286377

  19. 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.

  20. 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.

  1. Dang Gui Bu Xue Tang ameliorates coronary artery ligation-induced myocardial ischemia in rats.

    PubMed

    Chunhua, Ma; Hongyan, Long; Weina, Zhu; Xiaoli, He; Yajie, Zhang; Jie, Ruan

    2017-01-28

    Dang The present study was designed to investigate cardioprotective effects of Dang Gui Bu Xue Tang (DGBUT) on coronary artery ligation-induced myocardial ischemia. Myocardial ischemia (MI) model was induced in SD rats by surgical ligation of the left anterior descending coronary artery. ST segment elevation of Electrocardiograph (ECG) infarct size, levels of lactate dehydrogenase (LDH), creatine kinase (CK), glutathione (GSH) and catalase (CAT), catalase (SOD), malondialdehyde (MDA), and inflammatory cytokines and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun NH2 terminal kinases (JNK), nuclear factor (NF)-κBp65, inhibitory kappa B (IκB) α, IκB kinase (IKK) α and IKKβ were evaluated in rats treated with or without DGBUT. DGBUT treatment significantly reduced the elevation of the ST segment of ECG, the myocardial infarct size of MI. The level of LDH, CK and MDA were suppressed, the contents of SOD, GSH and CAT were enhanced with DGBUT. The elevated concentration of inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 in MI rats were effectively reversed by the DGBUT administration. Also, highly expressed p-JNK, p-ERK, p-p38, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ in MI rats were restored respectively by DGBUT treatment. The protective effect of DGBUT against MI injury might be associated with MAPK/NF-кB pathway.

  2. Metabonomic analysis of Allium macrostemon Bunge as a treatment for acute myocardial ischemia in rats.

    PubMed

    Li, Fang; Xu, Qian; Zheng, Ting; Huang, Fang; Han, Lintao

    2014-01-01

    Myocardial ischemia (MI) refers to a pathological state of the heart caused by reduced cardiac blood perfusion, which leads to a decreased oxygen supply in the heart and an abnormal myocardial energy metabolism. Acute myocardial ischemia (AMI) has posed a significant health risk for humans. Allium macrostemon Bunge (AMB), a popular traditional Chinese medicine, is used for MI treatment. The therapeutic effects of AMB were assessed and the detailed mechanisms of AMB for AMI treatment were investigated. We characterized the metabonomic variations in rats from the sham surgery, AMI, and AMB-pretreated AMI groups through a combination of nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analysis. Thirty-five metabolites including carbohydrates, a range of amino acids, and organic acids were detected. The (1)H NMR spectra of the rat serum were analyzed using the principal component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA). Results showed that AMI induced some physiological changes in rats and also led to metabolic disorders related to glycolysis promotion, amino acid metabolism disruption, and other metabolite metabolism perturbation. AMB pretreatment reduced the AMI injury and maintained metabolic balance, possibly by limiting the change in energy metabolism and regulating amino acid metabolism. These findings provide a comprehensive insight on the metabolic response of AMI rats to AMB pretreatment and are important for the use of AMB for AMI therapy.

  3. Rho-Kinase Activation in Leukocytes Plays a Pivotal Role in Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Kitano, Katsunori; Usui, Soichiro; Ootsuji, Hiroshi; Takashima, Shin-ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Nomura, Ayano; Kaneko, Shuichi; Takamura, Masayuki

    2014-01-01

    The Rho/Rho-kinase pathway plays an important role in many cardiovascular diseases such as hypertension, atherosclerosis, heart failure, and myocardial infarction. Although previous studies have shown that Rho-kinase inhibitors reduce ischemia/reperfusion (I/R) injury and cytokine production, the role of Rho-kinase in leukocytes during I/R injury is not well understood. Mice were subjected to 30-min ischemia and reperfusion. Rho-kinase activity was significantly greater in leukocytes subjected to myocardial I/R compared to the sham-operated mice. Administration of fasudil, a Rho-kinase inhibitor, significantly reduced the I/R-induced expression of the proinflammatory cytokines interleukin (IL)-6, C-C motif chemoattractant ligand 2 (CCL2), and tumor necrosis factor (TNF)-α, in leukocytes, compared with saline as the vehicle. Furthermore, fasudil decreased I/R-induced myocardial infarction/area at risk (IA) and I/R-induced leukocyte infiltration in the myocardium. Interestingly, IA in fasudil-administered mice with leukocyte depletion was similar to that in fasudil-administered mice. I/R also resulted in remarkable increases in the mRNA expression levels of the proinflammatory cytokines TNF-α, IL-6, and CCL2 in the heart. Inhibition of Rho-kinase activation in leukocytes has an important role in fasudil-induced cardioprotective effects. Hence, inhibition of Rho-kinase may be an additional therapeutic intervention for the treatment of acute coronary syndrome. PMID:24638037

  4. Increased Pericardial Fat Volume Measured From Noncontrast CT Predicts Myocardial Ischemia by SPECT

    PubMed Central

    Tamarappoo, Balaji; Dey, Damini; Shmilovich, Haim; Nakazato, Ryo; Gransar, Heidi; Cheng, Victor Y.; Friedman, John D.; Hayes, Sean W.; Thomson, Louise EJ; Slomka, Piotr J.; Rozanski, Alan; Berman, Daniel S.

    2010-01-01

    OBJECTIVES We evaluated the association between pericardial fat and myocardial ischemia for risk stratification. BACK GROUND Pericardial fat volume (PFV) and thoracic fat volume (TFV) measured from noncontrast computed tomography (CT) performed for calculating coronary calcium score (CCS) are associated with increased CCS and risk for major adverse cardiovascular events. METHODS From a cohort of 1,777 consecutive patients without previously known coronary artery disease (CAD) with noncontrast CT performed within 6 months of single photon emission computed tomography (SPECT), we compared 73 patients with ischemia by SPECT (cases) with 146 patients with normal SPECT (controls) matched by age, gender, CCS category, and symptoms and risk factors for CAD. TFV was automatically measured. Pericardial contours were manually defined within which fat voxels were automatically identified to compute PFV. Computer-assisted visual interpretation of SPECT was performed using standard 17-segment and 5-point score model; perfusion defect was quantified as summed stress score (SSS) and summed rest score (SRS). Ischemia was defined by: SSS – SRS ≥4. Independent relationships of PFV and TFV to ischemia were examined. RESULTS Cases had higher mean PFV (99.1 ± 42.9 cm3 vs. 80.1 ± 31.8 cm3, p = 0.0003) and TFV (196.1 ± 82.7 cm3 vs. 160.8 ± 72.1 cm3, p = 0.001) and higher frequencies of PFV >125 cm3 (22% vs. 8%, p = 0.004) and TFV >200 cm3 (40% vs. 19%, p = 0.001) than controls. After adjustment for CCS, PFV and TFV remained the strongest predictors of ischemia (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.53 to 5.52, p = 0.001 for each doubling of PFV; OR: 2.64, 95% CI: 1.48 to 4.72, p = 0.001 for TFV. Receiver operating characteristic analysis showed that prediction of ischemia, as indicated by receiver-operator characteristic area under the curve, improved significantly when PFV or TFV was added to CCS (0.75 vs. 0.68, p = 0.04 for both). CONCLUSIONS Pericardial fat

  5. Ischemia-induced alterations in myocardial (Na+ + K+)-ATPase and cardiac glycoside binding.

    PubMed Central

    Beller, G A; Conroy, J; Smith, T W

    1976-01-01

    The effects of ischemia on the canine myocardial (Na+ + K+)-ATPase complex were examined in terms of alterations in cardiac glycoside binding and enzymatic activity. Ability of the myocardial cell to bind tritiated ouabain in vivo was assessed after 1, 2, and 6 h of coronary occlusion followed by 45 min of reperfusion, and correlated with measurements of in vitro (Na+ + K+)-ATPase activity and in vitro [3H]ouabain binding after similar periods of ischemia. Regional blood flow alterations during occlusion and reperfusion were simultaneously determined utilizing 15 mum radioactive microspheres to determine the degree to which altered binding of ouabain might be flow related. Anterior wall infarction was produced in 34 dogs by snaring of confluent branches of the left coronary system. Epicardial electrograms delineated ischemic and border zone areas. Coronary reperfusion after 2 and 6 h of occlusion was associated with impaired reflow of blood and markedly impaired uptake of [3H]ouabain in ischemic myocardium. In both groups, in vivo [3H]ouabain binding by ischemic tissue was reduced out of proportion to the reduction in flow. Despite near-complete restoration of flow in seven dogs occluded for 1 h and reperfused, [3H]ouabain remained significantly reduced to 58 +/- 9% of nonischemic uptake in subendocardial layers of the central zone of ischemia. Thus, when coronary flow was restored to areas of myocardium rendered acutely ischemia for 1 or more hours, ischemic zones demonstrated progressively diminished ability to bind ouabain. To determine whether ischemia-induced alteration in myocardial (Na+ + K+)-ATPase might underlie these changes, (Na+ + K+)-ATPase activity and [3H]ouabain binding were measured in microsomal fractions from ischemic myocardium after 1, 2, and 6 h of coronary occlusion. In animals occluded for 6 h, (Na+ + K+)-ATPase activity was significantly reduced by 40% in epicardial and by 35% in endocardial layers compared with nonischemic myocardium

  6. The role of PPAR in myocardial response to ischemia in normal and diseased heart.

    PubMed

    Ravingerova, Tana; Adameova, Adriana; Carnicka, Slavka; Nemcekova, Martina; Kelly, Tara; Matejikova, Jana; Galatou, Eleftheria; Barlaka, Eleftheria; Lazou, Antigone

    2011-12-01

    Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors, belong to the nuclear hormone receptor superfamily regulating expression of genes involved in different aspects of lipid metabolism, inflammation and cardiac energy production. Activation of PPAR-α isoform by its natural ligands, fatty acids (FA) and eicosanoids, promotes mitochondrial FA oxidation as the primary ATP-generating pathway. On the other hand, PPAR-γ regulates lipid anabolism or storage, while, until recently, the function of PPAR-β/δ has been less explored. Under conditions associated with acute or chronic oxygen deprivation, PPAR-α modulates expression of genes that determine substrate switch (FA vs. glucose) aimed at maintenance of basic cardiac function. Although PPAR-α and PPAR-γ synthetic agonists, hypolipidemic and antidiabetic drugs, have been reported to protect the heart against ischemia/reperfusion injury, it is still a matter of debate whether PPAR activation plays a beneficial or detrimental role in myocardial response to ischemia, in particular, in pathological conditions. This article reviews some findings demonstrating the impact of PPAR activation on cardiac resistance to ischemia in normal and pathologically altered heart. Specifically, it addresses the issue of susceptibility to ischemia in the diabetic myocardium, with particular regards to the role of PPAR. Finally, involvement of PPAR in the mechanisms of lipid-independent cardioprotective effects of some hypolipidemic drugs is also discussed.

  7. [Effectiveness of various dopamine doses in acute myocardial ischemia complicated by cardiogenic shock (an experimental study)].

    PubMed

    Kipshidze, N N; Korotkov, A A; Marsagishvili, L A; Prigolashvili, T Sh; Bokhua, M R

    1981-06-01

    The effect of various doses of dopamine on the values of cardiac contractile and hemodynamic function under conditions of acute two-hour ischemia complicated by cardiogenic shock was studied in 27 experiments on dogs. In a dose of 5 microgram/kg/min dopamine caused an optimum increase in cardiac productive capacity, reduction of peripheral resistance, adequate increase in coronary circulation and decrease in ST segment depression on the ECG. Infusion of 10 microgram/kg/min dopamine usually caused myocardial hyperfunction with an increase in total peripheral resistance and cardiac performance. Maximum dopamine doses (10 microgram/kg/min and more) were effective in the areactive form of cardiogenic shock. In longterm dopamine infusion it is necessary to establish continuous control over the hemodynamic parameters and the ECG to prevent aggravation of ischemia and for stage-by-stage reduction of the drug concentration and determination of the minimum maintenance dose.

  8. [Efficiency of mildronate in rats of different age with experimental-induced myocardial ischemia].

    PubMed

    Kukes, V G; Zhernakova, N I; Gorbach, T V; Romashchenko, O V; Rumbesht, V V

    2013-01-01

    Under experimental myocardial ischemia in rats of 10 months treatment with mildronate resulted in essential changes in metabolism of cardiomyocites. This includes stimulation of aerobic and anaerobic ways of power supply of heart cells: activation of glycolysis, oxidative phosphorylation and oxidative pyruvate decarboxylation with restoration of adenosine triphosphate pool to intact rats level in myocardium, serum and erythrocytes with signs of stabilization of cardiomyocytes membranes and essential decrease of tissue hypoxia. Introduction of mildronate to old rats (24 months) with an experimental myocardium ischemia was accompanied by lesser expressed changes of metabolism: activation of glycolysis and oxidative pyruvate decarboxylation without stimulation of Crebs' cycle enzymes. This became sufficient for restoration of adenosine triphosphate pool in myocardium without change of its quantity in serum and erythrocytes with signs of stabilization of cardiomyocytes membranes and moderate reduction of tissue hypoxia degree.

  9. 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

  10. 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

  11. 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.

  12. N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy

    PubMed Central

    Wang, Sheng; Yan, Fuxia; Wang, Tingting; He, Yi

    2017-01-01

    Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day) for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of 15-F2t-Isoprostane were increased and that autophagy was evidenced as increases in ratio of LC3 II/I and protein P62 and AMPK and mTOR expressions were significantly increased in diabetic compared to nondiabetic rats, concomitant with increased postischemic myocardial infarct size and CK-MB release but decreased Akt and eNOS activation. Diabetes was also associated with increased postischemic apoptotic cell death manifested as increases in TUNEL positive cells, cleaved-caspase-3, and ratio of Bax/Bcl-2 protein expression. NAC significantly attenuated I/RI-induced increases in oxidative stress and cardiac apoptosis, prevented postischemic autophagy formation in diabetes, and reduced postischemic myocardial infarction (all p < 0.05). Conclusions. NAC confers cardioprotection against diabetic heart I/RI primarily through inhibiting excessive autophagy which might be a major mechanism why diabetic hearts are less tolerant to I/RI. PMID:28265179

  13. Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia.

    PubMed

    Guo, Jiahua; Yong, Yonghong; Aa, Jiye; Cao, Bei; Sun, Runbin; Yu, Xiaoyi; Huang, Jingqiu; Yang, Na; Yan, Lulu; Li, Xinxin; Cao, Jing; Aa, Nan; Yang, Zhijian; Kong, Xiangqing; Wang, Liansheng; Zhu, Xuanxuan; Ma, Xiaohui; Guo, Zhixin; Zhou, Shuiping; Sun, He; Wang, Guangji

    2016-12-01

    The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic.

  14. Plasma nociceptin/orphanin FQ levels rise after spontaneous episodes of angina, but not during induced myocardial ischemia.

    PubMed

    Fontana, Fiorella; Bernardi, Pasquale; Pizzi, Carmine; Spampinato, Santi; Bedini, Andrea; Pich, Emilio Merlo

    2009-09-01

    The aim of our study was to evaluate the effects of repeated episodes of angina and induced myocardial ischemia on plasma nociceptin/orphanin FQ (N/OFQ) levels. Patients with unstable angina (23 with new onset severe angina or accelerated angina and 18 with subacute angina at rest) who had had repeated spontaneous episodes of chest pain in the last week before the study underwent myocardial perfusion single-photon emission computed tomography using adenosine infusion. Twenty subjects without clinical symptoms of angina matched for age, sex and cardiac risk factors served as a control group. N/OFQ levels were significantly (P<0.01) higher in the patients (15.2+/-2.1 pg/ml) than in the control group (8.5+/-2.6 pg/ml). Blood pressure and heart rate did not significantly differ. All patients showed transient adenosine infusion myocardial ischemia that did not induce chest pain or significantly modify plasma N/OFQ levels or hemodynamic parameters. Our findings show that unstable angina is associated with a significant increase in circulating N/OFQ levels unrelated to intervening transient myocardial ischemia or hemodynamic changes. This increase is probably related to the chest pain repeatedly occurring in the course of coronary artery disease, but absent during transient adenosine-induced myocardial ischemia.

  15. Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia

    PubMed Central

    Guo, Jiahua; Yong, Yonghong; Aa, Jiye; Cao, Bei; Sun, Runbin; Yu, Xiaoyi; Huang, Jingqiu; Yang, Na; Yan, Lulu; Li, Xinxin; Cao, Jing; Aa, Nan; Yang, Zhijian; Kong, Xiangqing; Wang, Liansheng; Zhu, Xuanxuan; Ma, Xiaohui; Guo, Zhixin; Zhou, Shuiping; Sun, He; Wang, Guangji

    2016-01-01

    The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic. PMID:27905409

  16. 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

  17. Regional myocardial downregulation of the inhibitory guanosine triphosphate-binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of chronic episodic myocardial ischemia.

    PubMed Central

    Hammond, H K; Roth, D A; McKirnan, M D; Ping, P

    1993-01-01

    Regional myocardial ischemia is associated with increased levels of adenosine and norepinephrine, factors that may alter activation of the beta-adrenergic receptor (beta AR)-G protein-adenylyl cyclase pathway in the heart. We have used the ameroid constrictor model to determine whether alterations in myocardial signal transduction through the beta AR-G protein-adenylyl cyclase pathway occur in the setting of chronic episodes of reversible ischemia. Pigs were instrumented with ameroid occluders placed around the left circumflex coronary artery. 5 wk later, after ameroid closure, flow and function were normal in the ischemic bed, but flow (P = 0.001) and function (P < 0.03) were abnormal when metabolic demands were increased. The ischemic bed showed a reduction in myocardial beta AR number (P < 0.005). Despite regional downregulation of myocardial beta AR number, adenylyl cyclase activity was similar in the ischemic and control beds. Quantitative immunoblotting showed that the cardiac inhibitory GTP-binding protein, Gi alpha 2, was decreased in the ischemic bed (P = 0.02). In contrast, the cardiac stimulatory GTP-binding protein, Gs alpha, was increased in endocardial sections from the ischemic bed (P = < 0.05). Decreased Gi alpha 2 content was associated with decreased inhibition of adenylyl cyclase. Reduced Gi alpha 2 content, in conjunction with increased Gs alpha content in the endocardium, may provide a means by which adrenergic activation is maintained in the setting of chronic episodic myocardial ischemia. Images PMID:8254020

  18. A METHOD OF CORONARY RETROPERFUSION FOR THE TREATMENT OF ACUTE MYOCARDIAL ISCHEMIA.

    PubMed

    Feola, Mario; Wiener, Leslie

    1978-09-01

    A method of retrograde perfusion of the myocardium has been developed in dogs. It consists of a double lumen balloon-tipped catheter inserted transvenously into the coronary sinus, with one lumen connected to a roller pump, the other to a helium counterpulsing pump. Oxygenated heparinized blood is obtained from the femoral artery and pumped continuously into the coronary sinus at a pressure of 50-75 mm Hg. The balloon is inflated during diastole, sealing the coronary sinus and promoting retrograde flow, and is deflated during systole, allowing blood drainage into the right atrium and preventing venous congestion. Thirteen anesthetized open-chest dogs were subjected to 15 minutes of proximal LAD artery occlusion and 30 minutes of diastolic coronary sinus perfusion (DCSP). The area of ischemia was mapped by means of platinum electrodes capable of simultaneously measuring myocardial tissue oxygen tension M(p)O(2)) and electrograms. Reduction of M(p)O(2) with simultaneous elevation of the ST segment on the corresponding electrogram was considered an indication of ischemia. Diastolic coronary sinus perfusion improved myocardial oxygen tension in the ischemic myocardium, reduced ST segment elevation, and tended to restore arterial blood pressure. Histologically, there was no intramyocardial hemorrhage.

  19. 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.

  20. In Silico Investigation into Cellular Mechanisms of Cardiac Alternans in Myocardial Ischemia

    PubMed Central

    Liu, Jiaqi; Zhao, Xiaopeng

    2016-01-01

    Myocardial ischemia is associated with pathophysiological conditions such as hyperkalemia, acidosis, and hypoxia. These physiological disorders may lead to changes on the functions of ionic channels, which in turn form the basis for cardiac alternans. In this paper, we investigated the roles of hyperkalemia and calcium handling components played in the genesis of alternans in ischemia at the cellular level by using computational simulations. The results show that hyperkalemic reduced cell excitability and delayed recovery from inactivation of depolarization currents. The inactivation time constant τf of L-type calcium current (ICaL) increased obviously in hyperkalemia. One cycle length was not enough for ICaL to recover completely. Alternans developed as a result of ICaL responding to stimulation every other beat. Sarcoplasmic reticulum calcium-ATPase (SERCA2a) function decreased in ischemia. This change resulted in intracellular Ca (Cai) alternans of small magnitude. A strong Na+-Ca2+ exchange current (INCX) increased the magnitude of Cai alternans, leading to APD alternans through excitation-contraction coupling. Some alternated repolarization currents contributed to this repolarization alternans. PMID:28070211

  1. Niacin-bound chromium enhances myocardial protection from ischemia-reperfusion injury.

    PubMed

    Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Juhasz, Bela; Zhan, Lijun; Cordis, Gerald; Altaf, Elham; Bagchi, Manashi; Bagchi, Debasis; Maulik, Nilanjana

    2006-08-01

    A novel niacin-bound, chromium-based energy formula (EF; InterHealth Nutraceuticals, Benicia, CA) has been developed in conjunction with D-ribose, caffeine, ashwagandha extract (containing 5% withanolides), and selected amino acids. We have assessed the efficacy of oral administration of EF (40 mg x kg body wt(-1) x day(-1)) in male and female rats over a period of 90 consecutive days on the cardiovascular and pathophysiological functions in an isolated rat heart model. After 30, 60, and 90 days of treatment with EF, the hearts of male and female rats were subjected to 30 min of global ischemia followed by 2 h of reperfusion and were measured for myocardial ATP, creatine phosphate (CP), phosphorylated AMP kinase (p-AMPK), and heat shock proteins. Myocardial ATP and CP levels were increased in both male and female rats after EF treatment compared with the controls. Western blot analyses were performed to quantify the expression of stress-related proteins such as heat shock proteins (HSP-70, -32, and -25) and are found to be increased in both male and female rats after EF treatment. The p-AMPK level, which is a sensor for the energy state in various cell types, was also found to be increased after treatment with EF in both male and female rats. Aortic flow, maximum first derivative of developed pressure, left ventricular developed pressure, and infarct size were observed after ischemia-reperfusion and found to be significantly improved in EF-treated rats compared with control animals. Thus EF demonstrated long-term safety as well as exhibiting significant cardioprotective ability during ischemia and reperfusion injury by increased energy production, improved cardiac function, and reduced infarct size.

  2. 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

  3. A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury

    PubMed Central

    Totzeck, Matthias; Hendgen-Cotta, Ulrike B.; French, Brent A.; Rassaf, Tienush

    2016-01-01

    Although urgently needed in clinical practice, a cardioprotective therapeutic approach against myocardial ischemia/ reperfusion injury remains to be established. Remote ischemic preconditioning (rIPC) and ischemic preconditioning (IPC) represent promising tools comprising three entities: the generation of a protective signal, the transfer of the signal to the target organ, and the response to the transferred signal resulting in cardioprotection. However, in light of recent scientific advances, many controversies arise regarding the efficacy of the underlying signaling. We here show methods for the generation of the signaling cascade by rIPC as well as IPC in a mouse model for in vivo myocardial ischemia/ reperfusion injury using highly reproducible approaches. This is accomplished by taking advantage of easily applicable preconditioning strategies compatible with the clinical setting. We describe methods for using laser Doppler perfusion imaging to monitor the cessation and recovery of perfusion in real time. The effects of preconditioning on cardiac function can also be assessed using ultrasound or magnetic resonance imaging approaches. On a cellular level, we confirm how tissue injury can be monitored using histological assessment of infarct size in conjunction with immunohistochemistry to assess both aspects in a single specimen. Finally, we outline, how the rIPC-associated signaling can be transferred to the target cell via conservation of the signal in the humoral (blood) compartment. This compilation of experimental protocols including a conditioning regimen comparable to the clinical setting should proof useful to both beginners and experts in the field of myocardial infarction, supplying information for the detailed procedures as well as troubleshooting guides. PMID:28066791

  4. Myocardial ischemia, reperfusion, and infarction in chronically instrumented, intact, conscious, and unrestrained mice

    PubMed Central

    Lujan, Heidi L.; Janbaih, Hussein; Feng, Han-Zhong; Jin, Jian-Ping

    2012-01-01

    In the United States alone, the National Heart, Lung, and Blood Institute (NHLBI) has invested several hundred million dollars in pursuit of myocardial infarct-sparing therapies. However, due largely to methodological limitations, this investment has not produced any notable clinical application or cardioprotective therapy. Among the major methodological limitations is the reliance on animal models that do not mimic the clinical situation. In this context, the limited use of conscious animal models is of major concern. In fact, whenever possible, studies of cardiovascular physiology and pathophysiology should be conducted in conscious, complex models to avoid the complications associated with the use of anesthesia and surgical trauma. The mouse has significant advantages over other experimental models for the investigation of infarct-sparing therapies. The mouse is inexpensive, has a high throughput, and presents the ability of one to create genetically modified models. However, successful infarct-sparing therapies in anesthetized mice or isolated mouse hearts may not be successful in more complex models, including conscious mice. Accordingly, a conscious mouse model of myocardial ischemia and reperfusion has the potential to be of major importance for advancing the concepts and methods that drive the development of infarct-sparing therapies. Therefore, we describe, for the first time, the use of an intact, conscious, and unrestrained mouse model of myocardial ischemia-reperfusion and infarction. The conscious mouse model permits occlusion and reperfusion of the left anterior descending coronary artery in an intact, complex model free of the confounding influences of anesthetics and surgical trauma. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research. PMID:22538514

  5. Myocardial Ischemia During Mental Stress: Role of Coronary Artery Disease Burden and Vasomotion

    PubMed Central

    Ramadan, Ronnie; Sheps, David; Esteves, Fabio; Maziar Zafari, A.; Douglas Bremner, J.; Vaccarino, Viola; Quyyumi, Arshed A.

    2013-01-01

    Background Mental stress–induced myocardial ischemia (MSIMI) is associated with adverse prognosis in patients with coronary artery disease (CAD), yet the mechanisms underlying this phenomenon remain unclear. We hypothesized that compared with exercise/pharmacological stress–induced myocardial ischemia (PSIMI) that is secondary to the atherosclerotic burden of CAD, MSIMI is primarily due to vasomotor changes. Methods and Results Patients with angiographically documented CAD underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and following both mental and physical stress testing, performed on separate days. The severity and extent of CAD were quantified using the Gensini and Sullivan scores. Peripheral arterial tonometry (Itamar Inc) was used to assess the digital microvascular tone during mental stress as a ratio of pulse wave amplitude during speech compared with baseline. Measurements were made in a discovery sample (n=225) and verified in a replication sample (n=159). In the pooled (n=384) sample, CAD severity and extent scores were not significantly different between those with and without MSIMI, whereas they were greater in those with compared with those without PSIMI (P<0.04 for all). The peripheral arterial tonometry ratio was lower in those with compared with those without MSIMI (0.55±0.36 versus 0.76±0.52, P=0.009). In a multivariable analysis, the peripheral arterial tonometry ratio was the only independent predictor of MSIMI (P=0.009), whereas angiographic severity and extent of CAD independently predicted PSIMI. Conclusions The degree of digital microvascular constriction, and not the angiographic burden of CAD, is associated with MSIMI. Varying causes of MSIMI compared with PSIMI may require different therapeutic interventions that require further study. PMID:24145741

  6. Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with suspected coronary artery disease

    SciTech Connect

    Ladenheim, M.L.; Pollock, B.H.; Rozanski, A.; Berman, D.S.; Staniloff, H.M.; Forrester, J.S.; Diamond, G.A.

    1986-03-01

    The ability of exercise-induced myocardial hypoperfusion on thallium scintigraphy to predict coronary events was assessed in 1,689 patients with symptoms suggestive of coronary artery disease but without prior myocardial infarction or coronary artery bypass surgery. A total of 74 patients had a coronary event in the year after testing (12 cardiac deaths, 20 nonfatal infarctions and 42 referrals for bypass surgery more than 60 days after testing). Stepwise logistic regression identified only three independent predictors: the number of myocardial regions with reversible hypoperfusion (an index of the extent of hypoperfusion), the maximal magnitude of hypoperfusion (an index of the severity of hypoperfusion) and the achieved heart rate (an index of exercise performance). Both extent and severity were exponentially correlated with event rate (r greater than 0.97 and p less than 0.01 for each), whereas achieved heart rate was linearly correlated with event rate (r = 0.79 and p less than 0.05). On the basis of these data, a prognostic model was defined that employs extent and severity as stress-dependent orthogonal variables. Using this model, the predicted coronary event rate ranged over two orders of magnitude--from a low of 0.4% in patients able to exercise adequately without developing severe and extensive hypoperfusion at a low heart rate (less than 85% of their maximal predicted heart rate). Extent and severity of myocardial hypoperfusion, therefore, are important independent variables of prognosis in patients with suspected coronary artery disease.

  7. Blockage of transient receptor potential vanilloid 4 alleviates myocardial ischemia/reperfusion injury in mice

    PubMed Central

    Dong, Qian; Li, Jing; Wu, Qiong-feng; Zhao, Ning; Qian, Cheng; Ding, Dan; Wang, Bin-bin; Chen, Lei; Guo, Ke-Fang; Fu, Dehao; Han, Bing; Liao, Yu-Hua; Du, Yi-Mei

    2017-01-01

    Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24–72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion. Importantly, the therapeutic window for HC-067047 lasts for at least 12 h following reperfusion. Furthermore, treatment with HC-067047 reduced apoptosis, as evidenced by the decrease in TUNEL-positive myocytes, Bax/Bcl-2 ratio, and caspase-3 activation. Meanwhile, treatment with HC-067047 attenuated the decrease in the activation of reperfusion injury salvage kinase (RISK) pathway (phosphorylation of Akt, ERK1/2, and GSK-3β), while the activation of survival activating factor enhancement (SAFE) pathway (phosphorylation of STAT3) remained unchanged. In addition, the anti-apoptotic effects of HC-067047 were abolished by the RISK pathway inhibitors. We conclude that blockade of TRPV4 reduces apoptosis via the activation of RISK pathway, and therefore might be a promising strategy to prevent myocardial I/R injury. PMID:28205608

  8. Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory.

    PubMed

    Evonuk, Kirsten S; Prabhu, Sumanth D; Young, Martin E; DeSilva, Tara M

    2017-03-01

    The incidence of cognitive impairment in cardiovascular disease (CVD) patients has increased, adversely impacting quality of life and imposing a significant economic burden. Brain imaging of CVD patients has detected changes in the hippocampus, a brain region critical for normal learning and memory. However, it is not clear whether adverse cardiac events or other associated co-morbidities impair cognition. Here, using a murine model of acute myocardial ischemia/reperfusion (I/R), where the coronary artery was occluded for 30min followed by reperfusion, we tested the hypothesis that acute myocardial infarction triggers impairment in cognitive function. Two months following cardiac I/R, behavioral assessments specific for hippocampal cognitive function were performed. Mice subjected to cardiac I/R performed worse in the fear-conditioning paradigm as well as the object location memory behavioral test compared to sham-operated mice. Reactive gliosis was apparent in the hippocampal subregions CA1, CA3, and dentate gyrus 72h post-cardiac I/R as compared with sham, which was sustained two months post-cardiac I/R. Consistent with the inflammatory response, the abundance of doublecortin positive newborn neurons was decreased in the dentate gyrus 72h and 2months post-cardiac I/R as compared with sham. Therefore, we conclude that following acute myocardial infarction, rapid inflammatory responses negatively affect neurogenesis, which may underlie long-term changes in learning and memory.

  9. 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

  10. 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

  11. Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against ischemia-reperfusion injury-induced myocardial infarction.

    PubMed

    Chakraborty, Manodeep; Kamath, Jagadish Vasudev

    2014-07-01

    Globally, the rate of development of myocardial diseases and hypertension is very common, which is responsible for incremental morbidity and mortality statistics. Treatment of ischemic hypertensive patients with diuretics such as hydrochlorothiazide (HCTZ) can precipitate myocardial infarction due to hypokalemia. This study was undertaken to evaluate the pharmacodynamic interaction of green tea extract (GTE) with HCTZ against ischemia-reperfusion induced myocardial toxicity. Wistar albino rats of either sex were taken and pretreated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of GTE for 30 days. Standard, high and low dose of interactive groups received HCTZ (10 mg/kg, p.o.) for last 7 days. Ischemia-reperfusion injury was induced by modified Lagendorff apparatus, and the effect of different treatments was evaluated by percentage recovery in terms of heart rate and developed tension, serum biomarkers, and heart tissue antioxidant levels. Prophylactic treatment groups, such as high and low dose of GTE and their interactive groups with HCTZ, exhibited significant percentage recovery in terms of heart rate and developed tension. Apart from that, significant increase in superoxide dismutase and catalase, decrease in thiobarbituric acid reactive species in heart tissue, as well as significant decrease in serum lactate dehydrogenase, creatinine phosphokinase-MB and N-acetylcysteine levels have also been documented. The present findings clearly suggest that GTE dose-dependently reduces myocardial toxicity due to ischemia, and combination with HCTZ can reduce the associated side-effects and exhibits myocardial protection.

  12. Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    PubMed Central

    Jeddi, Sajad; Khalifi, Saeedeh; Ghanbari, Mahboubeh; Bageripour, Fatemeh; Ghasemi, Asghar

    2016-01-01

    Background Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. Objective We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Method Rats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx). Results Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Conclusion Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart. PMID:27849257

  13. All-Trans Retinoic Acid Ameliorates Myocardial Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis.

    PubMed

    Zhu, Zhengbin; Zhu, Jinzhou; Zhao, Xiaoran; Yang, Ke; Lu, Lin; Zhang, Fengru; Shen, Weifeng; Zhang, Ruiyan

    2015-01-01

    Myocardial ischemia/reperfusion (I/R) injury interferes with the restoration of blood flow to ischemic myocardium. Oxidative stress-elicited apoptosis has been reported to contribute to I/R injury. All-trans retinoic acid (ATRA) has anti-apoptotic activity as previously reported. Here, we investigated the effects and the mechanism of action of ATRA on myocardial I/R injury both in vivo and in vitro. In vivo, ATRA reduced the size of the infarcted area (17.81±1.05% vs. 24.41±1.03%, P<0.05) and rescued cardiac function loss (ejection fraction 46.42±6.76% vs. 37.18±4.63%, P<0.05) after I/R injury. Flow-cytometric analysis and TUNEL assay demonstrated that the protective role of ATRA on myocardial I/R injury was related to its anti-apoptotic effects. The anti-apoptotic effects of ATRA were associated with partial inhibition of reactive oxygen species (ROS) production and significantly less phosphorylation of mitogen-activated protein kinases (MAPKs) including p38, JNK, and ERK. Western blot analysis also revealed that ATRA pre-treatment increased a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression (0.65 ± 0.20 vs. 0.41±0.02 in vivo) and reduced the level of receptor for advanced glycation end-products (RAGE) (0.38 ± 0.17 vs. 0.52 ± 0.11 in vivo). Concomitantly, the protective role of ATRA on I/R injury was not observed in RAGE-KO mice. The current results indicated that ATRA could prevent myocardial injury and reduced cardiomyocyte apoptosis after I/R effectively. One possible mechanism underlying these effects is that ATRA could increase ADAM10 expression and thus cleave RAGE, which is the main receptor up-stream of MAPKs in myocardial I/R injury, resulting in the down-regulation of MAPK signaling and protective role on myocardial I/R injury.

  14. 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

  15. Risk factors for silent myocardial ischemia in patients with well-controlled essential hypertension.

    PubMed

    Rendina, Domenico; Ippolito, Renato; De Filippo, Gianpaolo; Muscariello, Riccardo; De Palma, Daniela; De Bonis, Silvana; Schiano di Cola, Michele; Benvenuto, Domenico; Galderisi, Maurizio; Strazzullo, Pasquale; Galletti, Ferruccio

    2017-03-01

    Silent myocardial ischemia (SMI) is frequently observed in patients with essential hypertension (EH). The major risk factor for SMI is uncontrolled blood pressure (BP), but SMI is also observed in patients with well-controlled BP. To evaluate the prevalence of SMI and the factors associated with SMI in EH patients with well-controlled BP. The medical records of 859 EH patients who underwent simultaneous 24-h ambulatory blood pressure monitoring (ABPM) and 24-h ambulatory electrocardiogram recording (AECG) were retrospectively evaluated. Each SMI episode was characterized by: (a) ST segment depression ≥0.5 mm; (b) duration of ST segment depression >60 s; and (c) reversibility of the ST segment depression. Overall 126 EH patients (14.7 %) had at least one episode of SMI. The SMI events were more frequent among patients with poorly controlled compared to those with well-controlled BP [86/479 (17.95 %) vs. 40/380 (10.52 %), p < 0.01]. Among EH patients with well-controlled BP, current and past smoking as well as the presence of an additional metabolic syndrome (MetS) constitutive element (obesity, impaired fasting glucose level or dyslipidemia) were significantly associated with the occurrence of SMI. In all EH patients with well-controlled BP and AECG evidence of SMI, there were one or more coronary artery stenotic lesions greater than 50 % found at coronary angiography. In EH patients who are current smokers, or have one or more additional components of a MetS there is markedly reduced benefit associated with good BP control with regard to the occurrence of myocardial ischemia: in this patient category, an AECG may help detect this condition.

  16. Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus.

    PubMed

    Wang, Ying; Qi, Xiuru; Wang, Chunliang; Zhao, Danning; Wang, Hongjie; Zhang, Jianxin

    2017-01-01

    The current study aimed to examine the effects of propofol on myocardial ischemia-reperfusion injury (MIRI) in rats with type-2 diabetes mellitus (T2DM) and to assess the role of inflammatory mediators. Fifty healthy male adult Sprague-Dawley rats were randomly divided into the sham, ischemia-reperfusion (IR), IR plus low, middle and high-dose (6, 12 and 24 mg/kg/h, intravenous) propofol groups. The rats of all the groups were fed a high-sugar and high-fat diet for 8 weeks and streptozotocin (30 mg/kg, intraperitoneally) was used to establish the T2DM model. Apart from the sham group rats, MIRI was induced by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. Heart rate (HR), left ventricular systolic pressure (LVSP), and the rate of left ventricular pressure increase in early systole (± dp/dtmax) were recorded. Levels of cardiac troponin T (cTnT), nitric oxide (NO), endothelin-1 (ET-1), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured. Myocardial lesions were observed under light microscopy and scanning electron microscopy. Compared with levels prior to arterial occlusion, HR, LVSP, and ± dp/dtmax were significantly reduced (P<0.05) following occlusion for 30 min and reperfusion for 2 h. The administration of propofol ameliorated the cardiac function of rats as reflected by the increase in HR, LVSP and ± dp/dtmax. In addition, the administration of propofol increased the serum NO concentration, and reduced ET-1 and cTnT levels, as well as levels of inflammatory mediators including IL-1β, IL-6 and TNF-α. Thus, propofol exerts protective effects against MIRI in T2DM rats by increasing NO and reducing ET-1 and the inflammatory mediators.

  17. Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus

    PubMed Central

    Wang, Ying; Qi, Xiuru; Wang, Chunliang; Zhao, Danning; Wang, Hongjie; Zhang, Jianxin

    2017-01-01

    The current study aimed to examine the effects of propofol on myocardial ischemia-reperfusion injury (MIRI) in rats with type-2 diabetes mellitus (T2DM) and to assess the role of inflammatory mediators. Fifty healthy male adult Sprague-Dawley rats were randomly divided into the sham, ischemia-reperfusion (IR), IR plus low, middle and high-dose (6, 12 and 24 mg/kg/h, intravenous) propofol groups. The rats of all the groups were fed a high-sugar and high-fat diet for 8 weeks and streptozotocin (30 mg/kg, intraperitoneally) was used to establish the T2DM model. Apart from the sham group rats, MIRI was induced by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. Heart rate (HR), left ventricular systolic pressure (LVSP), and the rate of left ventricular pressure increase in early systole (± dp/dtmax) were recorded. Levels of cardiac troponin T (cTnT), nitric oxide (NO), endothelin-1 (ET-1), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured. Myocardial lesions were observed under light microscopy and scanning electron microscopy. Compared with levels prior to arterial occlusion, HR, LVSP, and ± dp/dtmax were significantly reduced (P<0.05) following occlusion for 30 min and reperfusion for 2 h. The administration of propofol ameliorated the cardiac function of rats as reflected by the increase in HR, LVSP and ± dp/dtmax. In addition, the administration of propofol increased the serum NO concentration, and reduced ET-1 and cTnT levels, as well as levels of inflammatory mediators including IL-1β, IL-6 and TNF-α. Thus, propofol exerts protective effects against MIRI in T2DM rats by increasing NO and reducing ET-1 and the inflammatory mediators. PMID:28123710

  18. Beat-to-beat QT interval variability associated with acute myocardial ischemia.

    PubMed

    Murabayashi, Taizo; Fetics, Barry; Kass, David; Nevo, Erez; Gramatikov, Boris; Berger, Ronald D

    2002-01-01

    Beat-to-beat QT interval variability (QTV) quantifies lability in ventricular repolarization. We hypothesized that myocardial ischemia destabilizes ventricular repolarization and increases QTV. We analyzed 2-hour 2-lead digitized electrocardiogram records of 68 patients in the European ST-T Database. All patients had ischemic episodes during the 2-hour record, annotated by the developers of the database. We determined the normalized QTV (QTVnorm), QT variability index (QTVI), and normalized heart rate variability (HRVnorm) for each 5-minute epoch by automated analysis. QTVnorm was greater during ischemic episodes than during nonischemic episodes (1.41 +/- 0.77 vs. 0.88 +/- 0.23, P <.0001). There was no significant difference in HRVnorm between ischemic and nonischemic episodes (1.22 +/- 0.63 vs. 0.94 +/- 0.18, not significant). The QTVI was higher during ischemic episodes than during nonischemic episodes (0.14 +/- 0.31 vs. -0.051 +/- 0.12, P <.0001). Acute ischemia is associated with labile ventricular repolarization, which manifests as enhanced beat-to-beat QT interval variability. The association between ischemic repolarization liability and arrhythmic risk deserves further study.

  19. 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

  20. 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.

  1. Activity exerted by a testosterone derivative on myocardial injury using an ischemia/reperfusion model.

    PubMed

    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.

  2. Improvement of pacing induced regional myocardial ischemia by Solcoseryl in conscious dogs with coronary stenosis.

    PubMed

    Shimada, T; Sasayama, S; Takahashi, M; Osakada, G; Kawai, C

    1984-02-01

    The effects of Solcoseryl on regional myocardial function were studied in 5 conscious dogs with partial coronary constriction, in which temporary ischemia was induced by rapid cardiac pacing. During the coronary artery constriction, the percent shortening of the ischemic segment decreased by 9%. When the heart rate was increased by pacing, the percent shortening of the ischemic segments was further reduced by 57%. On cessation of cardiac pacing, the early potentiation of dP/dt and of control segment shortening became evident and was followed by exponential decay in the subsequent several beats. In the ischemic segment, the percent shortening was significantly improved in the first post-pacing beat but was more severely depressed at five seconds. Thirty minutes after administration of Solcoseryl, the cardiac pacing was repeated in the same manner but the pacing-induced hypokinesia of the ischemic segment were less marked, the percent shortening being at an average of 9.1% during control pacing and 12.7% during the second pacing after Solcoseryl (p less than 0.05). Postpacing deterioration of the ischemic segment shortening was also significantly improved from 9.8 to 11.8% at 5 seconds (p less than 0.05). These findings indicate that Solcoseryl exerts protective effects on the ischemic myocardium by promoting a rapid recovery from ischemia, probably due to the improvement of oxygen utility through activated cellular respiration.

  3. Biphasic modulation of the mitochondrial electron transport chain in myocardial ischemia and reperfusion.

    PubMed

    Lee, Hsin-Ling; Chen, Chwen-Lih; Yeh, Steve T; Zweier, Jay L; Chen, Yeong-Renn

    2012-04-01

    Mitochondrial electron transport chain (ETC) is the major source of reactive oxygen species during myocardial ischemia-reperfusion (I/R) injury. Ischemic defect and reperfusion-induced injury to ETC are critical in the disease pathogenesis of postischemic heart. The properties of ETC were investigated in an isolated heart model of global I/R. Rat hearts were subjected to ischemia for 30 min followed by reperfusion for 1 h. Studies of mitochondrial function indicated a biphasic modulation of electron transfer activity (ETA) and ETC protein expression during I/R. Analysis of ETAs in the isolated mitochondria indicated that complexes I, II, III, and IV activities were diminished after 30 min of ischemia but increased upon restoration of flow. Immunoblotting analysis and ultrastructural analysis with transmission electron microscopy further revealed marked downregulation of ETC in the ischemic heart and then upregulation of ETC upon reperfusion. No significant difference in the mRNA expression level of ETC was detected between ischemic and postischemic hearts. However, reperfusion-induced ETC biosynthesis in myocardium can be inhibited by cycloheximide, indicating the involvement of translational control. Immunoblotting analysis of tissue homogenates revealed a similar profile in peroxisome proliferator-activated receptor-γ coactivator-1α expression, suggesting its essential role as an upstream regulator in controlling ETC biosynthesis during I/R. Significant impairment caused by ischemic and postischemic injury was observed in the complexes I- III. Analysis of NADH ferricyanide reductase activity indicated that injury of flavoprotein subcomplex accounts for 50% decline of intact complex I activity from ischemic heart. Taken together, our findings provide a new insight into the molecular mechanism of I/R-induced mitochondrial dysfunction.

  4. The cardioprotective effects of citric Acid and L-malic Acid on myocardial ischemia/reperfusion injury.

    PubMed

    Tang, Xilan; Liu, Jianxun; Dong, Wei; Li, Peng; Li, Lei; Lin, Chengren; Zheng, Yongqiu; Hou, Jincai; Li, Dan

    2013-01-01

    Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components of Fructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation. In vitro experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient of Fructus Choerospondiatis responsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease.

  5. Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury In Vivo and In Vitro

    PubMed Central

    Fan, Huaying; Yang, Liu; Fu, Fenghua; Xu, Hui; Meng, Qinggang; Zhu, Haibo; Teng, Lirong; Yang, Mingyan; Zhang, Leiming; Zhang, Ziliang; Liu, Ke

    2012-01-01

    Salvianolic acid A (SAA), one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2)-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2), and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application. PMID:21789047

  6. Apelin/APJ System: A Novel Therapeutic Target for Myocardial Ischemia/Reperfusion Injury.

    PubMed

    Chen, Zhe; Wu, Di; Li, Lanfang; Chen, Linxi

    2016-12-01

    Apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Recently, researches indicate that the apelin/APJ system involves in myocardial ischemia-reperfusion injury (MIRI), which is a common pathophysiological process in patients with heart diseases and therapies. The reperfusion induces the expression of apelin and APJ receptor, which play an important role in cardioprotection of MIRI. The apelin/APJ system alleviates MIRI mainly by decreasing mitochondrial reactive oxygen species and delaying the opening of mitochondrial permeability transition pores, which induce the initiation of mitophagy. Besides, the apelin/APJ system prevents mitochondrial oxygen damage and lipid peroxidation through nitric oxide formation. The apelin/APJ system also improves MIRI through other pathways, including promoting metabolic and functional recovery, significantly increasing myocardial capillary density and arteriole formation, inhibiting endoplasmic reticulum stress-induced cell apoptosis, and maintaining integrity of cell membranes. In this review, we discuss how the mechanisms of the apelin/APJ system reverse MIRI in detail and elaborate on APJ agonists, which may be used for therapy of MIRI.

  7. Polymeric electrospun scaffolds: neuregulin encapsulation and biocompatibility studies in a model of myocardial ischemia.

    PubMed

    Simón-Yarza, Teresa; Rossi, Angela; Heffels, Karl-Heinz; Prósper, Felipe; Groll, Jürgen; Blanco-Prieto, Maria J

    2015-05-01

    Cardiovascular disease represents one of the major health challenges in modern times and is the number one cause of death globally. Thus, numerous studies are under way to identify effective cell- and/or growth factor (GF)-based therapies for repairing damaged cardiac tissue. In this regard, improving the engraftment or survival of regenerative cells and prolonging GF exposure have become fundamental goals in advancing these therapeutic approaches. Biomaterials have emerged as innovative scaffolds for the delivery of both cells and proteins in tissue engineering applications. In the present study, electrospinning was used to generate smooth homogenous polymeric fibers, which consisted of a poly(lactic-co-glycolic acid) (PLGA)/NCO-sP(EO-stat-PO) polymer blend encapsulating the cardioactive GF, Neuregulin-1 (Nrg). We evaluated the biocompatibility and degradation of this Nrg-containing biomaterial in a rat model of myocardial ischemia. Histological analysis revealed the presence of an initial acute inflammatory response after implantation, which was followed by a chronic inflammatory phase, characterized by the presence of giant cells. Notably, the scaffold remained in the heart after 3 months. Furthermore, an increase in the M2:M1 macrophage ratio following implantation suggested the induction of constructive tissue remodeling. Taken together, the combination of Nrg-encapsulating scaffolds with cells capable of inducing cardiac regeneration could represent an ambitious and promising therapeutic strategy for repairing diseased or damaged myocardial tissue.

  8. Reduction of myocardial ischemia reperfusion injury with regular consumption of grapes.

    PubMed

    Cui, Jianhua; Cordis, Gerald A; Tosaki, Arpad; Maulik, Nilanjana; Das, Dipak K

    2002-05-01

    Recently several polyphenolic antioxidants derived from grape seeds and skins have been implicated in cardioprotection. This study was undertaken to determine if the grapes were equally cardioprotective. Sprague Dawley male rats were given (orally) standardized grape extract (SGE) for a period of three weeks. Time-matched control experiments were performed by feeding the animals 45 microg/100 of glucose plus 45 microg/100 g fructose per day for three weeks. After 30 days, rats were sacrificed, hearts excised and perfused via working-mode. Hearts were made ischemic for 30 min followed by two hours of reperfusion. At 100 mg/kg and at 200 mg/kg, SGE provided significant cardioprotection as evidenced by improved post-ischemic ventricular recovery and reduced amount of myocardial infarction. No cardioprotection was apparent when rats were given grape samples at a dose of 50 mg/100 g/day. In vitro studies demonstrated that the SGE could directly scavenge superoxide and hydroxyl radicals which are formed in the ischemic reperfused myocardium. The results demonstrate that the heats of the rats fed SGE reduced myocardial ischemia reperfusion injury by functioning as in vivo antioxidant.

  9. Study of baicalin on sympathoexcitation induced by myocardial ischemia via P2X3 receptor in superior cervical ganglia.

    PubMed

    Zhang, Jun; Liu, Shuangmei; Xu, Baohua; Li, Guodong; Li, Guilin; Huang, An; Wu, Bing; Peng, Lichao; Song, Miaomiao; Xie, Qiuyu; Lin, Weijian; Xie, Wei; Wen, Shiyao; Zhang, Zhedong; Xu, Xiaoling; Liang, Shangdong

    2015-05-01

    After the myocardial ischemia, injured myocardial tissues released large quantity of ATP, which activated P2X3 receptor in superior cervical ganglia and made the SCG postganglionic neurons excited. Excitatory of sympathetic postganglionic efferent neurons increased the blood pressure and heart rates, which aggravated the myocardial ischemic injury. Baicalin has anti-inflammatory and anti-oxidant properties. Our study showed that baicalin reduced the incremental concentration of serum CK-MB, cTn-T, epinephrine and ATP, decreased the up-regulated expression levels of P2X3 mRNA and protein in SCG after MI, and then inhibited the sympathetic excitatory activity triggered by MI injury. These results indicated that baicalin acted on P2X3 receptor was involved in the transmission of sympathetic excitation after the myocardial ischemic injury. Baicalin might decrease sympathetic activity via inhibiting P2X3 receptor in rat SCG to protect the myocardium.

  10. The nuclear melatonin receptor RORα is a novel endogenous defender against myocardial ischemia/reperfusion injury.

    PubMed

    He, Ben; Zhao, Yichao; Xu, Longwei; Gao, Lingchen; Su, Yuanyuan; Lin, Nan; Pu, Jun

    2016-04-01

    Circadian rhythm disruption or decrease in levels of circadian hormones such as melatonin increases ischemic heart disease risk. The nuclear melatonin receptors RORs are pivotally involved in circadian rhythm regulation and melatonin effects mediation. However, the functional roles of RORs in the heart have never been investigated and were therefore the subject of this study on myocardial ischemia/reperfusion (MI/R) injury pathogenesis. RORα and RORγ subtypes were detected in the adult mouse heart, and RORα but not RORγ was downregulated after MI/R. To determine the pathological consequence of MI/R-induced reduction of RORα, we subjected RORα-deficient staggerer mice and wild-type (WT) littermates to MI/R injury, resulting in significantly increased myocardial infarct size, myocardial apoptosis and exacerbated contractile dysfunction in the former. Mechanistically, RORα deficiency promoted MI/R-induced endoplasmic reticulum stress, mitochondrial impairments, and autophagy dysfunction. Moreover, RORα deficiency augmented MI/R-induced oxidative/nitrative stress. Given the emerging evidence of RORα as an essential melatonin effects mediator, we further investigated the RORα roles in melatonin-exerted cardioprotection, in particular against MI/R injury, which was significantly attenuated in RORα-deficient mice, but negligibly affected by cardiac-specific silencing of RORγ. Finally, to determine cell type-specific effects of RORα, we generated mice with cardiomyocyte-specific RORα overexpression and they were less vulnerable to MI/R injury. In summary, our study provides the first direct evidence that the nuclear melatonin receptor RORα is a novel endogenous protective receptor against MI/R injury and an important mediator of melatonin-exerted cardioprotection; melatonin-RORα axis signaling thus appears important in protection against ischemic heart injury.

  11. SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.

    PubMed

    Yang, Yang; Duan, Weixun; Lin, Yan; Yi, Wei; Liang, Zhenxing; Yan, Juanjuan; Wang, Ning; Deng, Chao; Zhang, Song; Li, Yue; Chen, Wensheng; Yu, Shiqiang; Yi, Dinghua; Jin, Zhenxiao

    2013-12-01

    Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling.

  12. Radiographic evaluation of the patient with chest pain of suspected myocardial origin

    SciTech Connect

    Green, C.E.; Satler, L.F.; Elliott, L.P.

    1984-11-01

    The evaluation of the patient with suspected angina pectoris is discussed and an approach presented which makes use of radiologic tests in conjunction with exercise testing to quickly and efficiently determine the likelihood and severity of coronary artery disease. The relative merits and limitations of chest radiography, cardiac fluoroscopy, nuclear medicine, and coronary arteriography are discussed.

  13. 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.

  14. The Prognostic Significance of Resting Regional Left Ventricular Function in Patients With Varying Degrees of Myocardial Ischemia

    PubMed Central

    Kilcullen, Niamh M.; Uthamalingam, Shanmugan; Gurm, Gagandeep S; Gregory, Shawn A.; Picard, Michael H.

    2013-01-01

    Background Our aim was to determine whether regional left ventricular (LV) function on a resting transthoracic echo (TTE) provides prognostic information in patients with varying degrees of ischemia on myocardial perfusion imaging. Methods Between 2004 - 2009, we identified 503 patients (mean age 69 (SD 11); 79% male) with reversible ischemia on a myocardial SPECT scan who had a TTE within 30 days. We evaluated the rate of subsequent revascularization and death for all patients. Results Following the SPECT scan and TTE, 246/503(49%) patients underwent revascularization, 64/503 (13%) patients died, 369 (73%) patients had a normal left ventricular ejection fraction (LVEF), 242 (48%) patients had a resting wall motion abnormality (WMA), 21/261 (8%) with no WMA died compared to 43/242 (18%) in patients with a WMA. In patients with a WMA (n = 242) there was no significant difference in mortality when comparing patients with small (< 6 segments) and large (> 6 segments) WMA (P = 0.44). In patients with moderate/severe ischemia, the presence of a resting WMA was associated with a higher mortality rate (18% v 7%; P = 0.005). In a multivariable model, LVEF (< 50%) was associated with a hazard ratio of 2.2 (P = 0.002, 95% CI 1.34 - 3.68) however, WMA and number of abnormal segments did not reach statistical significance. Conclusion A resting wall motion abnormality in patients with moderate/severe ischemia is associated with a higher mortality compared to patients with mild ischemia on myocardial perfusion imaging. Regional left ventricular dysfunction unlike LVEF was not an independent predictor of mortality.

  15. Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways

    PubMed Central

    Tullio, Francesca; Femminò, Saveria; Nigro, Debora; Chiazza, Fausto; Collotta, Debora; Cocco, Mattia; Bertinaria, Massimo; Aragno, Manuela

    2016-01-01

    Although the nucleotide-binding oligomerization domain- (NOD-) like receptor pyrin domain containing 3 (NLRP3) inflammasome has been recently detected in the heart, its role in cardiac ischemia/reperfusion (IR) is still controversial. Here, we investigate whether a pharmacological modulation of NLRP3 inflammasome exerted protective effects in an ex vivo model of IR injury. Isolated hearts from male Wistar rats (5-6 months old) underwent ischemia (30 min) followed by reperfusion (20 or 60 min) with and without pretreatment with the recently synthetized NLRP3 inflammasome inhibitor INF4E (50 μM, 20 min before ischemia). INF4E exerted protection against myocardial IR, shown by a significant reduction in infarct size and lactate dehydrogenase release and improvement in postischemic left ventricular pressure. The formation of the NLRP3 inflammasome complex was induced by myocardial IR and attenuated by INF4E in a time-dependent way. Interestingly, the hearts of the INF4E-pretreated animals displayed a marked improvement of the protective RISK pathway and this effect was associated increase in expression of markers of mitochondrial oxidative phosphorylation. Our results demonstrate for the first time that INF4E protected against the IR-induced myocardial injury and dysfunction, by a mechanism that involves inhibition of the NLRP3 inflammasome, resulting in the activation of the prosurvival RISK pathway and improvement in mitochondrial function. PMID:28053692

  16. 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

  17. Protective Effects of Co-Administration of Gallic Acid and Cyclosporine on Rat Myocardial Morphology Against Ischemia/Reperfusion

    PubMed Central

    Dianat, Mahin; Sadeghi, Najmeh; Badavi, Mohammad; Panahi, Marziyeh; Taheri Moghadam, Mahin

    2014-01-01

    Background: Irreversible myocardial ischemic injury begins 20 minutes after the onset of coronary occlusion. Then the infarcted cells show signs of necrosis and death. Objectives: This study investigated the effects of co-administration of Gallic acid (antioxidant) with cyclosporine (mitochondrial permeability transition pore [mPTP] inhibitor) on myocardial morphology of rats during ischemia and reperfusion. Materials and Methods: Fifty-four male Wistar rats (250-300 g), were randomly divided into 9 groups: sham, control (Ca received saline, 1 mL/kg, Cb: perfused with cyclosporine CsA 0.2 µM), 3 groups pretreated with Gallic acid in saline (G1a:7.5, G2a:15, and G3a: 30 mg/kg/day, and gavage daily for 10 days, n = 6), and the other three groups were pretreated with Gallic acid then perfused using CsA, (G1b:7.5, G2b:15, and G3b: 30 mg/kg/day) at the first 13 minutes of reperfusion period. After 10 days pretreatment, the rat hearts were isolated and transferred to Langendorff apparatus and exposed to 30 minutes ischemia following 60 minutes reperfusion. Afterward, the hearts were preserved in 10% formalin for histological studies at the end of the experiment. Finally, hematoxylin and eosin and Masson’s trichrome staining techniques were used for evaluating the changes in myocardial architecture, degradation of myofibers, and collagen integrity. The differences were analyzed using Pearson test. Results: Cell degenerative changes, pyknotic nuclei, contraction bands, edema, and loosening of collagen in between muscle fibers were observed during ischemia-reperfusion. Myocardial architecture and cellular morphology were recovered in co-administration groups, especially in (Gallic acid 15 mg/kg + CsA, P < 0.001). Conclusions: The results suggest the important role of the antioxidant system potentiation in the prevention of myocardial damage. PMID:25625048

  18. Calpain Inhibition Improves Collateral Dependent Perfusion in a Hypercholesterolemic Swine Model of Chronic Myocardial Ischemia

    PubMed Central

    Sabe, Ashraf A.; Potz, Brittany A.; Elmadhun, Nassrene Y.; Liu, Yuhong; Feng, Jun; Abid, M. Ruhul; Abbott, Jinnette D; Senger, Donald R; Sellke, Frank W.

    2015-01-01

    Background Calpain over-expression is implicated in aberrant angiogenesis. We hypothesized that calpain inhibition (CI, MDL28170) would improve collateral perfusion in a swine model with hypercholesterolemia and chronic myocardial ischemia. Methods and Results Yorkshire swine fed a high cholesterol diet for 4 weeks underwent surgical placement of an ameroid constrictor to their left circumflex coronary artery. Three weeks later, animals received either: no drug, high cholesterol control group (HCC; n= 8); low dose CI (0.12 mg/kg; LCI, n= 9); or high dose CI (0.25 mg/kg; HCI, n= 8). The heart was harvested after 5 weeks. There was a trend toward increased right to left collateral vessels on angiography with HCI. Myocardial perfusion in ischemic myocardium significantly improved with HCI at rest and with demand pacing (p = 0.016 and 0.011). Endothelium-dependent microvessel relaxation was significantly improved with LCI (p = 0.001). There was a significant increase in capillary density, with LCI and HCI (p= 0.01 and 0.01), and arteriolar density with LCI (p= 0.001). CI significantly increased several proangiogenic proteins including VEGF (p= 0.02), VEGFR1 (p= 0.003), VEGFR2 (p= 0.003) and talin, a microvascular structural protein (p= 0.0002). There was a slight increase in proteins implicated in endothelial-dependent (NO Mediated) relaxation including ERK, p-ERK and iNOS with CI. Conclusions In the setting of hypercholesterolemia, CI improved perfusion, with a trend toward increased collateralization on angiography and increased capillary and arteriolar densities in ischemic myocardium. CI also improved endothelium-dependent microvessel relaxation and increased expression of proteins implicated in angiogenesis and vasodilatation. PMID:26478238

  19. Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion

    PubMed Central

    Vreeswijk-Baudoin, Inge; Groot, Hilde E.; van de Kolk, Kees W. A.; de Boer, Rudolf A.; Mateo Leach, Irene; Vliegenthart, Rozemarijn; Sillje, Herman H. W.; van der Harst, Pim

    2016-01-01

    Background Interleukin-6 (IL-6) levels are upregulated in myocardial infarction. Recent data suggest a causal role of the IL-6 receptor (IL-6R) in coronary heart disease. We evaluated if IL-6R blockade by a monoclonal antibody (MR16-1) prevents the heart from adverse left ventricular remodeling in a mouse model of ischemia-reperfusion (I/R). Methods CJ57/BL6 mice underwent I/R injury (left coronary artery ligation for 45 minutes) or sham surgery, and thereafter received MR16-1 (2mg/mouse) 5 minutes before reperfusion and 0.5mg/mouse weekly during four weeks, or control IgG treatment. Cardiac Magnetic Resonance Imaging (CMR) and hemodynamic measurements were performed to determine cardiac function after four weeks. Results I/R caused left ventricular dilatation and a decrease in left ventricular ejection fraction (LVEF). However, LVEF was significantly lower in the MR16-1 treatment group compared to the IgG group (28±4% vs. 35±6%, p = 0.02; sham 45±6% vs. 43±4%, respectively; p = NS). Cardiac relaxation (assessed by dP/dT) was not significantly different between the MR16-1 and IgG groups. Also, no differences were observed in histological myocardial fibrosis, infarct size and myocyte hypertrophy between the groups. Conclusion Blockade of the IL-6R receptor by the monoclonal MR16-1 antibody for four weeks started directly after I/R injury did not prevent the process of cardiac remodeling in mice, but rather associated with a deterioration in the process of adverse cardiac remodeling. PMID:27936014

  20. 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

  1. Lysophosphatidic Acid Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury in the Immature Hearts of Rats

    PubMed Central

    Chen, Haibo; Liu, Si; Liu, Xuewen; Yang, Jinjing; Wang, Fang; Cong, Xiangfeng; Chen, Xi

    2017-01-01

    The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1–LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury. The results showed that in Langendorff-perfused immature rat hearts (2 weeks), compared to I/R group, LPA pretreatment significantly enhanced the cardiac function, attenuated myocardial infarct size and CK-MB release, decreased myocardial apoptosis and increased the expression of pro-survival signaling molecules. All these effects could be abolished by Ki16425, an antagonist to LPA1 and LPA3. Similarly, LPA pretreatment protected H9C2 from hypoxia-reoxygenation (H/R) induced apoptosis and necrosis in vitro. The mechanisms underlying the anti-apoptosis effects were related to activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (AKT) signaling pathways as well as phosphorylation of the downstream effector of AKT, glycogen synthase kinase 3 beta (GSK3β), through LPA1 and/or LPA3. What's more, we found that LPA preconditioning increased glucose uptake of H9C2 subjected to H/R by the activation of AMP-Activated Protein Kinase (AMPK) but not the translocation of GLUT4. In conclusion, our study indicates that LPA is a potent survival factor for immature hearts against I/R injuries and has the potential therapeutic function as a cardioplegia additive for infantile cardiac surgery. PMID:28377726

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

    PubMed Central

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

    2014-01-01

    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

  3. Cardioprotection by a novel recombinant serine protease inhibitor in myocardial ischemia and reperfusion injury.

    PubMed

    Murohara, T; Guo, J P; Lefer, A M

    1995-09-01

    Polymorphonuclear neutrophils (PMN) play an important role in myocardial ischemia/reperfusion (MI/R) injury; however, the role of neutrophilic proteases is less understood. The effects of a novel serine protease inhibitor (serpin), LEX032, were investigated in a murine model of MI (20 min) and R (24 hr) injury in vivo. LEX032 is a recombinant human alpha 1-antichymotrypsin in which six amino acid residues were replaced around the active center with those of alpha-1 protease inhibitor. LEX032 has the ability to inhibit both neutrophil elastase and cathepsin G, two major neutral serine proteases in neutrophils, as well as superoxide generation. LEX032 (25 or 50 mg/kg) administered i.v. 1 min before reperfusion significantly attenuated myocardial necrotic injury evaluated by cardiac creatine kinase loss compared to MI/R rats receiving only vehicle (P < .001). Moreover, cardiac myeloperoxidase activity, an index of PMN accumulation, in the ischemic myocardium was significantly attenuated by LEX032 as compared with rats receiving vehicle (P < .001). LEX032 also moderately attenuated leukotriene B4-stimulated PMN adherence to rat superior mesenteric artery endothelium and markedly diminished superoxide radical release from LTB4-stimulated PMN in vitro. In a glycogen-induced rat peritonitis model, LEX032 (50 mg/kg) significantly attenuated PMN transmigration into the peritoneal cavity in vivo. In conclusion, the recombinant serine protease inhibitor, LEX032, appears to be an effective agent for attenuating MI/R injury by inhibiting neutrophil-accumulation into the ischemic-reperfused myocardium and by inactivating cytotoxic metabolites (proteases and superoxide radical) released from neutrophils.

  4. Relationship between myocardial metabolites and contractile abnormalities during graded regional ischemia. Phosphorus-31 nuclear magnetic resonance studies of porcine myocardium in vivo.

    PubMed Central

    Schaefer, S; Schwartz, G G; Gober, J R; Wong, A K; Camacho, S A; Massie, B; Weiner, M W

    1990-01-01

    The mechanisms responsible for changes in myocardial contractility during regional ischemia are unknown. Since changes in high-energy phosphates during ischemia are sensitive to reductions in myocardial blood flow, it was hypothesized that myocardial function under steady-state conditions of graded regional ischemia is closely related to changes in myocardial high-energy phosphates. Therefore, phosphorus-31 nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional subendocardial blood flow, high-energy phosphates, pH, and myocardial segment shortening were made during various degrees of regional ischemia in which subendocardial blood flow was reduced by 16-94%. During mild reductions in myocardial blood flow (subendocardial blood flow = 83% of nonischemic myocardium), only the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), Pi, and [H+] were significantly changed from control. PCr, ATP, and PCr/ATP were not significantly reduced from control with mild reductions in blood flow. Changes in myocardial segment shortening were most closely associated with changes in PCr/Pi (r = 0.94). Pi and [H+] were negatively correlated with segment shortening (r = -0.64 and -0.58, respectively) and increased over twofold when blood flow was reduced by 62%. Thus, these data demonstrate that PCr/Pi is sensitive to reductions in myocardial blood flow and closely correlates with changes in myocardial function. These data are also consistent with a role for Pi or H+ as inhibitors of myocardial contractility during ischemia. Images PMID:2312722

  5. In vivo gene transfection with heat shock protein 70 enhances myocardial tolerance to ischemia-reperfusion injury in rat.

    PubMed Central

    Suzuki, K; Sawa, Y; Kaneda, Y; Ichikawa, H; Shirakura, R; Matsuda, H

    1997-01-01

    Heat shock protein 70 (HSP70) has been reported to be involved in the myocardial self-preservation system. To obtain the evidence that HSP70 plays a direct role in the protection from myocardial ischemia-reperfusion injury, rat hearts were transfected with human HSP70 gene by intracoronary infusion of hemagglutinating virus of Japan (HVJ)-liposome containing human HSP70 gene. The control hearts were infused with HVJ-liposome without the HSP70 gene. The hearts from whole-body heat-stressed or nontreated rats were also examined. Western blot and immunohistochemical analysis showed that apparent overexpression of HSP70 occurred in the gene transfected hearts and that gene transfection might be more effective for HSP70 induction than heat stress. In Langendorff perfusion, better functional recovery as well as less creatine phosphokinase leakage after ischemia were obtained in the gene transfected hearts with HSP70 than in the control or nontreated hearts. Furthermore, the gene transfected hearts showed better functional recovery than the heat-stressed hearts. These results indicated that overexpressed HSP70 plays a protective role in myocardial injury, suggesting the possibility that gene transfection with HSP70 may become a novel method for myocardial protection through enforcing the self-preservation systems. PMID:9120008

  6. Effect of Escitalopram on Mental Stress-Induced Myocardial Ischemia: The Results of the REMIT Trial

    PubMed Central

    Jiang, Wei; Velazquez, Eric J.; Kuchibhatla, Maragatha; Samad, Zainab; Boyle, Stephen H.; Kuhn, Cynthia; Becker, Richard C.; Ortel, Thomas L.; Williams, Redford B.; Rogers, Joseph G.; O’Connor, Christopher

    2015-01-01

    Importance Mental-stress-induced myocardial ischemia (MSIMI) is an intermediate surrogate endpoint representing the pathophysiological link between psychosocial risk factors and adverse outcomes of coronary heart disease (CHD). However, pharmacological interventions aimed at reducing MSIMI have not been well studied. Objective To examine the effects of 6 weeks of escitalopram treatment vs. placebo on MSIMI and other psychological stress-related biophysiological and emotional parameters. Design, Setting, and Participants The REMIT study is a randomized, double-blind, placebo-controlled trial of patients with clinically stable CHD and laboratory MSIMI. Enrollment occurred from 7/24/2007–8/24/2011 at a tertiary medical center. Interventions Eligible participants were randomized 1:1 to receive escitalopram (dose began at 5 mg with titration to 20 mg/day in 3 weeks) or placebo over 6 weeks. Main Outcome Measure Occurrence of MSIMI, defined as (1) development or worsening of regional wall motion abnormality; (2) left ventricular ejection fraction reduction ≥8%; and/or (3) horizontal or downsloping ST-segment depression ≥1mm in ≥2 leads lasting for ≥3 consecutive beats during ≥1 of 3 mental tasks. Results 127 participants were randomized to escitalopram (n=64) or placebo (n=63); 112 (96.1%) completed endpoint assessments (n=56 in each arm). At the end of 6 weeks, more patients taking escitalopram (34.2% [95% CI, 25.4 to 43.0]) had absence of MSIMI during the 3 mental stressors compared with patients taking placebo (17.5% [95% CI, 10.4 to 24.5]) based on unadjusted multiple imputation model for intention-to-treat analysis. A significant difference favoring escitalopram was observed (OR=2.62 [95% CI, 1.06 to 6.44]). Rates of exercise-induced ischemia were slightly lower at 6 weeks in the escitalopram group (45.8% [95% CI, 36.6 to 55.0]) than in patients receiving placebo (52.5% [95% CI, 43.3 to 61.7]), compared with baseline escitalopram (49.2% [95% CI, 39.9 to

  7. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II.

    PubMed

    Ibarra-Lara, Luz; Sánchez-Aguilar, María; Sánchez-Mendoza, Alicia; Del Valle-Mondragón, Leonardo; Soria-Castro, Elizabeth; Carreón-Torres, Elizabeth; Díaz-Díaz, Eulises; Vázquez-Meza, Héctor; Guarner-Lans, Verónica; Rubio-Ruiz, María Esther

    2016-12-28

    Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.

  8. 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

  9. 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

  10. Chronic Exercise Downregulates Myocardial Myoglobin and Attenuates Nitrite Reductase Capacity During Ischemia-Reperfusion

    PubMed Central

    Nicholson, Chad K.; Lambert, Jonathan P.; Chow, Chi-Wing; Lefer, David J.; Calvert, John W.

    2013-01-01

    Background The infarct sparing effects of exercise are evident following both long-term and short-term training regimens. Here we compared the infarct-lowering effects of nitrite therapy, voluntary exercise, and the combination of both following myocardial ischemia-reperfusion (MI/R) injury. We also compared the degree to which each strategy increased cardiac nitrite levels, as well as the effects of each strategy on the nitrite reductase activity of the heart. Methods and Results Mice subjected to voluntary wheel running (VE) for 4 weeks displayed an 18% reduction in infarct size when compared to sedentary mice, whereas mice administered nitrite therapy (25 mg/L in drinking water) showed a 53% decrease. However, the combination of VE and nitrite exhibited no further protection than VE alone. Although the VE and nitrite therapy mice showed similar nitrite levels in the heart, cardiac nitrite reductase activity was significantly reduced in the VE mice. Additionally, the cardiac protein expression of myoglobin, a known nitrite reductase, was also reduced after VE. Further studies revealed that cardiac NFAT activity was lower after VE due to a decrease in calcineurin activity and an increase in GSK3β activity. Conclusion These data suggest that VE downregulates cardiac myoglobin levels by inhibiting calcineurin/NFAT signaling. Additionally, these results suggest that the modest infarct sparing effects of VE are the result of a decrease in the hearts ability to reduce nitrite to nitric oxide during MI/R. PMID:23962643

  11. 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.

  12. [Application of fuzzy reasoning to myocardial ischemia judgment based on electrocardiogram ST-T complex].

    PubMed

    Song, Jinzhong; Yan, Hong; Liu, Guizhi; Kuang, Hong

    2012-02-01

    Electrocardiogram (ECG) is a convenient, economic, and non-invasive detecting tool in myocardial ischemia (MI). Its clinical appearance is mainly exhibited by ST-T complex change. MI events are usually instantaneous and asymptomatic in some cases, which cannot be forecasted to have a precautionary measure in time by doctors. The automatic detection of MI by computer and a cued warning of danger in real time play an important role in diagnosing heart disease. With the help of the medical staff, some quantitative approbatory indicators, such as ST-segment deviation, the amplitude of T-wave peak and the rate of ST and heart rate (HR), were combined to judge MI using fuzzy reasoning. After MIT-BIH database and the long-term ST database (LTST) verification, sensitivity and positive predictive values reached 75% and 78% respectively, and specificity and negative predictive values were 85% and 87% respectively. In addition, the proposed method was close to human way of thinking and understanding, and easy to apply in clinical detection and engineering fields.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Comparison of dipyridamole-echocardiography with dipyridamole-thallium scintigraphy for the diagnosis of myocardial ischemia

    SciTech Connect

    Perin, E.C.; Moore, W.; Blume, M.; Hernandez, G.; Dhekne, R.; DeCastro, C.M. )

    1991-06-01

    After an intravenous infusion of dipyridamole (0.56 mg/kg), the authors performed both echocardiography and thallium scintigraphy in 63 patients who were referred for known or suspected coronary artery disease. Of those patients, 25 returned for coronary arteriography within 1 month after the tests, thus forming the study group for this report. Sensitivity for detection of coronary artery disease, when analyzed region-by-region, was 80% for thallium scintigraphy and 57% for echocardiography, whereas specificity was 85% and 98%, respectively. When evaluating individual patients for the presence or absence of ischemia, they found a sensitivity of 95% for scintigraphy and 58% for echocardiography; corresponding specificities were 50% and 100%. By using arteriography as the gold standard for comparison, it appears that thallium scintigraphy has a significantly higher sensitivity but lower specificity for the detection of coronary artery disease than does echocardiography. Echocardiography may, however, be a useful adjunct to thallium scintigraphy in the evaluation of patients with coronary artery disease.

  18. [The Internet as a solution facilitating the identification of patients with a suspected acute myocardial infarct].

    PubMed

    Fernandes, A; Fiúza, M; Dias, E; Carôla, B; Dionísio, I; Correia, L C; Pinto, F J; Lopes, M G

    1999-03-01

    The current steps for diagnosing heart disease are very time consuming, delaying the correct identification of the problem, therefore, delaying the right treatment. In this study we have developed an experimental method using e-mail in order to identify patients with "rule out myocardial" condition and reduce the time lag for thrombolysis or coronary angioplasty in this clinical setting. Three different locations linked to the Internet by ISDN lines were used. Each line was connected with a computer. A pager and a dedicated phone line were also used. The following steps were performed for each situation: filling out of a questionnaire, ECG recording, questionnaire mailing and ECG by e-mail as attachment, pager warning that an urgent cardiology consultation was requested, including the doctor and patient's phone number, time to open the message and reply by e-mail, phone call for additional comments. A total of 24 attempts of interactive communication were performed. In 22 of those, an answer was obtained in less than 30 minutes. Two failures were recorded. One was due to a delay in the pager message, which did not arrive within the first hour; the second was due to a computer break down. This report shows that it is possible to establish a fast communication between the out patient clinic and the hospital (less than 30 minutes in most cases) at a very low cost and in a simple manner.

  19. Ischemia

    NASA Astrophysics Data System (ADS)

    Byeon, Suk Ho; Kim, Min; Kwon, Oh Woong

    "Ischemia" implies a tissue damage derived from perfusion insufficiency, not just an inadequate blood supply. Mild thickening and increased reflectivity of inner retina and prominent inner part of synaptic portion of outer plexiform layer are "acute retinal ischemic changes" visible on OCT. Over time, retina becomes thinner, especially in the inner portion. Choroidal perfusion supplies the outer portion of retina; thus, choroidal ischemia causes predominant change in the corresponding tissue.

  20. Puerarin alleviates aggravated sympathoexcitatory response induced by myocardial ischemia via regulating P2X3 receptor in rat superior cervical ganglia.

    PubMed

    Liu, Shuangmei; Yu, Shicheng; Xu, Changshui; Peng, Lichao; Xu, Hong; Zhang, Chunping; Li, Guilin; Gao, Yun; Fan, Bo; Zhu, Qicheng; Zheng, Chaoran; Wu, Bing; Song, Miaomiao; Wu, Qin; Liang, Shangdong

    2014-05-01

    Myocardial ischemia elicits a sympathoexcitatory response characterized by increase in blood pressure and sympathetic nerve activity. Puerarin, a major active ingredient extracted from the traditional Chinese plant medicine Ge-gen, has been widely used in treatment of myocardial and cerebral ischemia. However, little is known about the mechanism. Our study was aimed to explore the effect of puerarin on sympathoexcitatory response induced by myocardial ischemic injury and possible relationship with P2X3 receptor. Our results showed that puerarin alleviated systolic blood pressure and heart rate, and decreased the up-regulated of P2X3 mRNA and protein in SCG of myocardial ischemic rats. The amplitude of ATP-activated currents of SCG neurons was much larger in myocardial ischemic group than that in control group. Puerarin reduced ATP-activated currents in myocardial ischemic group and control group, and the inhibiting effects of puerarin in myocardial ischemic group were stronger than those in control group. Puerarin also significantly inhibited ATP-activated currents in HEK293 cells transfected with P2X3 receptor. These results suggest that puerarin can depress up-sympathoexcitatory response induced by myocardial ischemia via acting on P2X3 receptor in rat SCG to protect myocardium.

  1. MiR-146b protects cardiomyocytes injury in myocardial ischemia/reperfusion by targeting Smad4

    PubMed Central

    Di, Yun-Feng; Li, De-Cai; Shen, Yan-Qing; Wang, Chun-Lei; Zhang, Da-Yong; Shang, An-Quan; Hu, Teng

    2017-01-01

    MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, have been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia-/reperfusion-induced cardiac injury. In the present study, we report on the role of miR-146b in myocardial I/R injury and the underlying cardio-protective mechanism. Antagomir-146b was used to explore the effects of miR-146b on cardiac ischemia/reperfusion injury (30 min ischemia followed by 180 min reperfusion). As predicted, miR-146b overexpression significantly reduced the infarct size and cardiomyocytes apoptosis and release of creatine kinase and lactate dehydrogenase. In addition, miR-146b attenuated H9c2 cell apoptosis. Furthermore, Smad4 was predicted and verified as a potential miR-146b target using bioinformatics and luciferase assay. In summary, this study demonstrated that miR-146b plays a critical protective role in cardiac ischemic injury and may provide a new therapeutic approach for the treatment of myocardial I/R injury.

  2. Activation of Poly(ADP-Ribose) Polymerase by Myocardial Ischemia and Coronary Reperfusion in Human Circulating Leukocytes

    PubMed Central

    Tóth-Zsámboki, Emese; Horváth, Eszter; Vargova, Katarina; Pankotai, Eszter; Murthy, Kanneganti; Zsengellér, Zsuzsanna; Bárány, Tamás; Pék, Tamás; Fekete, Katalin; Kiss, Róbert Gábor; Préda, István; Lacza, Zsombor; Gerö, Domokos; Szabó, Csaba

    2006-01-01

    Reactive free radical and oxidant production leads to DNA damage during myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose) polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized that PARP is activated in circulating leukocytes in patients with myocardial infarction and reperfusion during primary percutaneous coronary intervention (PCI). In 15 patients with ST segment elevation acute myocardial infarction, before and after primary PCI and 24 and 96 h later, we determined serum hydrogen peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2′-deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of apoptosis-inducing factor (AIF) in circulating leukocytes. Plasma 8OHdG levels and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly, poly(ADP-ribose) content of the leukocytes increased in cells isolated just after PCI, indicating immediate PARP activation triggered by reperfusion of the myocardium. In contrast, serum hydrogen peroxide concentrations and the translocation of AIF gradually increased over time and were most pronounced at 96 h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which leads to PARP activation in circulating leukocytes. Translocation of AIF and lipid peroxidation occurs at a later stage. These results represent the first direct demonstration of PARP activation in human myocardial infarction. Future work is required to test whether pharmacological inhibition of PARP may offer myocardial protection during primary PCI. PMID:17225870

  3. Activation of NOD1 by DAP contributes to myocardial ischemia/reperfusion injury via multiple signaling pathways.

    PubMed

    Yang, Hui; Li, Nan; Song, Li-Na; Wang, Lei; Tian, Cui; Tang, Chao-Shu; Du, Jie; Li, Hui-Hua; Yu, Xiao-Hong; Wang, Hong-Xia

    2015-04-01

    NOD1 is a member of nucleotide-binding oligomerization domain-like receptors family that participates in many inflammatory processes. Previous studies demonstrated that NOD1 plays an important role in inflammatory cardiovascular diseases. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. The present study investigate whether NOD1 is involved in the pathogenesis of mouse myocardial I/R injury and the underlying mechanisms. Administration of NOD1 ligand (DAP) significantly enhanced myocardial I/R injury, as demonstrated by increased infarct size, the number of TUNEL-positive nuclei, caspase-3 activity, the infiltration of Mac-2- and IL-6-positive cells as compared with untreated heart or cardiomyocytes after I/R injury. In contrast, knockdown of NOD1 by siRNA markedly attenuated mimetic I/R induced cardiomyocyte apoptosis in vitro, indicating that NOD1 enhanced myocardial I/R injury partially through direct heart effects. These effects were partially associated with activation of JNK, p38 MAPK and NF-κB signaling pathways. Taken together, these results provide the first evidence that activation of intracellular sensor NOD1 enhances myocardial I/R injury and may provide novel therapeutic target for ameliorating the ischemic heart diseases.

  4. Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes.

    PubMed

    Tóth-Zsámboki, Emese; Horváth, Eszter; Vargova, Katarina; Pankotai, Eszter; Murthy, Kanneganti; Zsengellér, Zsuzsanna; Bárány, Tamás; Pék, Tamás; Fekete, Katalin; Kiss, Róbert Gábor; Préda, István; Lacza, Zsombor; Gerö, Domokos; Szabó, Csaba

    2006-01-01

    Reactive free radical and oxidant production leads to DNA damage during myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose) polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized that PARP is activated in circulating leukocytes in patients with myocardial infarction and reperfusion during primary percutaneous coronary intervention (PCI). In 15 patients with ST segment elevation acute myocardial infarction, before and after primary PCI and 24 and 96 h later, we determined serum hydrogen peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of apoptosis-inducing factor (AIF) in circulating leukocytes. Plasma 8OHdG levels and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly, poly(ADP-ribose) content of the leukocytes increased in cells isolated just after PCI, indicating immediate PARP activation triggered by reperfusion of the myocardium. In contrast, serum hydrogen peroxide concentrations and the translocation of AIF gradually increased over time and were most pronounced at 96 h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which leads to PARP activation in circulating leukocytes. Translocation of AIF and lipid peroxidation occurs at a later stage. These results represent the first direct demonstration of PARP activation in human myocardial infarction. Future work is required to test whether pharmacological inhibition of PARP may offer myocardial protection during primary PCI.

  5. Effect of cerebrolysin on oxidative stress-induced apoptosis in an experimental rat model of myocardial ischemia.

    PubMed

    Boshra, V; Atwa, A

    2016-09-01

    Apoptosis plays a role in the process of tissue damage after myocardial infarction (MI). This study was designed to investigate the possible effect of cerebrolysin against apoptosis triggered by oxidative cell stress in myocardial ischemia induced by isoproterenol in rat. Rats were pretreated with cerebrolysin 5 mL/kg intraperitoneally for 7 days and intoxicated with isoproterenol (ISO, 85 mg/kg, sc) on the last 2 days. Hearts were excised and stained to detect the infarction size. Serum levels of cardiotoxicity indices as creatine kinase isoenzyme (CK-MB) and troponin I (cTnI) as well as the cardiac oxidative stress parameters as thiobarbituric acid reactive substances and superoxide dismutase were estimated. The expression of prodeath gene p53 and antideath gene Bcl-2 was also assessed from the excised heart tissues. Leakage of cardiac enzymes, elevated oxidative stress markers, and apoptotic indices confirmed the MI occurring as a consequence of isoproterenol-induced ischemia. Cerebrolysin pretreatment caused significant attenuation of the oxidative stress-induced apoptosis in the ischemic myocardial tissue. These findings provided an evidence that cerebrolysin could protect rat myocardium against ischemic insult that was attributed to its antioxidant as well as its anti-apoptotic properties.

  6. Adora2b Signaling on Bone Marrow Derived Cells Dampens Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Koeppen, Michael; Harter, Patrick N.; Bonney, Stephanie; Bonney, Megan; Reithel, Susan; Zachskorn, Cornelia; Mittelbronn, Michel; Eckle, Tobias

    2012-01-01

    Background Cardiac ischemia-reperfusion injury (I/R) represents a major cause of cardiac tissue injury. Adenosine signaling dampens inflammation during cardiac I/R. Here, we investigated the role of the adenosine A2b-receptor (Adora2b) on inflammatory cells during cardiac I/R. Methods To study Adora2b signaling on inflammatory cells, we transplanted wild-type (WT) bone marrow (BM) into Adora2b−/− mice or Adora2b−/− BM into WT mice. To study the role of polymorphonuclear leukocytes (PMNs), neutrophil-depleted WT mice were treated with an Adora2b agonist. Following treatments, mice were exposed to 60 min of myocardial ischemia and 120 min of reperfusion. Infarct sizes and Troponin-I levels were determined by triphenyltetrazolium chloride staining and ELISA, respectively. Results Transplantation of WT-BM into Adora2b−/− mice decreased infarct sizes by 19 ± 4% and Troponin-I by 87.5 ± 25.3 ng/ml (mean ± SD, n = 6). Transplantation of Adora2b−/− BM into WT mice increased infarct sizes by 20 ±3% and Troponin-I levels by 69.7 ± 17.9 ng/ml (mean ± SD, n = 6). Studies on the reperfused myocardium revealed PMNs as dominant cell type. PMN-depletion or Adora2b agonist treatment reduced infarct sizes by 30 ± 11% or 26 ± 13% (mean ± SD, n = 4), however the combination of both did not reveal further cardioprotection. Cytokine profiling showed significantly higher cardiac tumor-necrosis-factor-α levels in Adora2b−/− compared to WT mice (39.3 ± 5.3 vs. 7.5 ± 1.0 pg/mg protein, mean ± SD, n = 4). Pharmacological studies on human activated PMNs revealed an Adora2b dependent tumor-necrosis-factor-α release. Conclusion Adora2b signaling on BM-derived cells such as PMNs represents an endogenous cardioprotective mechanism during cardiac I/R. Our findings suggest that Adora2b agonist treatment during cardiac I/R reduces tumor-necrosis-factor-α release of PMNs, thereby dampening tissue injury. PMID:22531331

  7. 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

  8. 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

  9. Structural Basis for Phosphorylation and Lysine Acetylation Cross-talk in a Kinase Motif Associated with Myocardial Ischemia and Cardioprotection*

    PubMed Central

    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.

    2014-01-01

    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. PMID:25008320

  10. 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

  11. Bnip3 functions as a mitochondrial sensor of oxidative stress during myocardial ischemia and reperfusion.

    PubMed

    Kubli, Dieter A; Quinsay, Melissa N; Huang, Chengqun; Lee, Youngil; Gustafsson, Asa B

    2008-11-01

    Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) is a member of the Bcl-2 homology domain 3-only subfamily of proapoptotic Bcl-2 proteins and is associated with cell death in the myocardium. In this study, we investigated the potential mechanism(s) by which Bnip3 activity is regulated. We found that Bnip3 forms a DTT-sensitive homodimer that increased after myocardial ischemia-reperfusion (I/R). The presence of the antioxidant N-acetylcysteine reduced I/R-induced homodimerization of Bnip3. Overexpression of Bnip3 in cells revealed that most of exogenous Bnip3 exists as a DTT-sensitive homodimer that correlated with increased cell death. In contrast, endogenous Bnip3 existed mainly as a monomer under normal conditions in the heart. Screening of the Bnip3 protein sequence revealed a single conserved cysteine residue at position 64. Mutation of this cysteine to alanine (Bnip3C64A) or deletion of the NH2-terminus (amino acids 1-64) resulted in reduced cell death activity of Bnip3. Moreover, mutation of a histidine residue in the COOH-terminal transmembrane domain to alanine (Bnip3H173A) almost completely inhibited the cell death activity of Bnip3. Bnip3C64A had a reduced ability to interact with Bnip3, whereas Bnip3H173A was completely unable to interact with Bnip3, suggesting that homodimerization is important for Bnip3 function. A consequence of I/R is the production of reactive oxygen species and oxidation of proteins, which promotes the formation of disulfide bonds between proteins. Thus, these experiments suggest that Bnip3 functions as a redox sensor where increased oxidative stress induces homodimerization and activation of Bnip3 via cooperation of the NH2-terminal cysteine residue and the COOH-terminal transmembrane domain.

  12. Painless myocardial ischemia is associated with mortality in patients with chronic kidney disease

    PubMed Central

    Wetmore, James B.; Broce, Mike; Malas, Amer; Almehmi, Ammar

    2015-01-01

    Background Painless myocardial ischemia (PMI) is associated with poor outcomes in the general population. We hypothesized that presence of PMI is inversely related to level of kidney function and is associated with impaired survival in CKD. Methods A total of 356 patients who underwent percutaneous coronary intervention were assessed for PMI, defined as the absence of chest pain in response to balloon dilation of the affected vessel. Cox proportional hazards analysis was used to calculate 10-year all-cause mortality. Results There was an increase in PMI occurrence by strata of estimated glomerular filtration rate (eGFR), whereby PMI was present in only 20.6% of individuals with eGFR ≥ 90 ml/min/1.73m2 but was found in 50.0% of individuals with eGFR < 30 ml/min/1.73m2 (P = 0.004 for trend). Classification of individuals as having either CKD or PMI showed significant differences in adjusted mortality between groups (P < 0.001 for trend), with individuals having both CKD and PMI demonstrating the highest 10-year mortality. Compared to individuals with neither CKD nor PMI, individuals with CKD and no PMI had a hazard ratio (HR) for mortality of 1.64 (95% confidence intervals 1.03 – 2.63, P = 0.038), while individuals with both PMI and CKD had a HR of 2.08 (1.30 – 3.33, P = 0.002). Conclusion PMI is common in CKD population, is inversely related to the level of eGFR, and confers substantially increased risk in CKD. These findings may partially explain the high mortality traditionally attributed to cardiovascular disease in CKD patients. PMID:23466572

  13. Conditional deletion of cardiomyocyte peroxisome proliferator-activated receptor γ enhances myocardial ischemia-reperfusion injury in mice.

    PubMed

    Hobson, Michael J; Hake, Paul W; O'Connor, Michael; Schulte, Christine; Moore, Victoria; James, Jeanne M; Piraino, Giovanna; Zingarelli, Basilia

    2014-01-01

    The nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of the inflammatory response to an array of biologic insults. We have previously demonstrated that PPARγ ligands reduce myocardial ischemia-reperfusion injury in rodents. In the current study, we directly determined the role of cardiomyocyte PPARγ in ischemia-reperfusion injury, using a model of conditional cardiomyocyte-specific deletion of PPARγ in vivo. In mice, α-myosin heavy chain-restricted Cre-mediated PPARγ deficiency was induced by tamoxifen treatment (30 mg/kg intraperitoneally) for 4 days (PPARγ mice), whereas controls included mice treated with the oil diluent vehicle (PPARγ mice). Western blot and histochemical analyses confirmed that expression of PPARγ protein was abolished in cardiomyocytes of mice treated with tamoxifen, but not with vehicle. After tamoxifen or vehicle treatment, animals were subjected to 30-min ligation of the left anterior descending coronary artery followed by 2-h reperfusion. In PPARγ mice, myocardial ischemia and reperfusion induced extensive myocardial damage, which was associated with elevated tissue activity of myeloperoxidase, indicating infiltration of neutrophils, and elevated plasma levels of troponin I when compared with PPARγ mice. Upon echocardiographic analysis, PPARγ mice also demonstrated ventricular dilatation and systolic dysfunction. Plasma levels of the proinflammatory cytokines interleukin 1β and interleukin 6 were higher in PPARγ mice when compared with PPARγ mice. These pathological events in PPARγ mice were associated with enhanced nuclear factor κB DNA binding in the infarcted hearts. Thus, our data suggest that cardiomyocyte PPARγ is a crucial protective receptor and may prevent reperfusion injury by modulating mechanisms of inflammation.

  14. Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: a role for ER stress?

    PubMed

    Cook, Alexandra R; Bardswell, Sonya C; Pretheshan, Subashini; Dighe, Kushal; Kanaganayagam, Gajen S; Jabr, Rita I; Merkle, Sabine; Marber, Michael S; Engelhardt, Stefan; Avkiran, Metin

    2009-02-01

    Sarcolemmal Na(+)/H(+) exchanger (NHE) activity, which is provided by the NHE isoform 1 (NHE1), has been implicated in ischemia/reperfusion-induced myocardial injury in animal models and humans, on the basis of studies with pharmacological NHE1 inhibitors. We generated a transgenic (TG) mouse model with cardiac-specific over-expression of NHE1 to determine whether this would be sufficient to increase myocardial susceptibility to ischemia/reperfusion-induced injury. TG mouse hearts exhibited increased sarcolemmal NHE activity and normal morphology and function. Surprisingly, they also showed reduced susceptibility to ischemia/reperfusion-induced injury, as reflected by improved functional recovery and smaller infarcts. Such protection was sustained in the presence of NHE1 inhibition with zoniporide, indicating a mechanism that is independent of sarcolemmal NHE activity. Immunoblot analysis revealed accumulation of immature NHE1 protein as well as marked upregulation of both cytoprotective (78/94 kDa glucose-regulated proteins, calreticulin, protein disulfide isomerase) and pro-apoptotic (C/EBP homologous protein) components of the endoplasmic reticulum (ER) stress response in TG myocardium. With increasing age, NHE1 TG mice exhibited increased myocyte apoptosis, developed left ventricular contractile dysfunction, underwent cardiac remodelling and died prematurely. Our findings indicate that: (1) Cardiac-specific NHE1 over-expression induces the ER stress response in mouse myocardium, which may afford protection against ischemia/reperfusion-induced injury despite increased NHE activity; (2) Ageing NHE1 TG mice exhibit myocyte apoptosis, cardiac remodelling and failure, likely as a result of sustained ER stress; (3) The pluripotent effects of the ER stress response may confound studies that are based on the chronic over-expression of complex proteins in myocardium.

  15. Relationships between the lung-heart ratio assessed from post-exercise thallium-201 myocardial tomograms, myocardial ischemia and the extent of coronary artery disease

    SciTech Connect

    Ilmer, B.; Reijs, A.E.; Reiber, J.H.; Bakker, W.; Fioretti, P. )

    1990-01-01

    Uptake of thallium (Tl)-201 in the lungs has been proposed as a measure of left ventricular dysfunction. In this study we were interested in pursuing two goals: (1) to assess possible relationships between the post-exercise Tl-201 lung-heart (LH)-ratio determined from the anterior view during SPECT-acquisition, myocardial ischemia and the extent of coronary artery disease; and (2) to explore the effects of coronary revascularisation procedures on the LH-ratio. The study group consisted of 145 patients with early and late postexercise Tl-201 tomograms, including 32 PTCA-patients with pre- and post-PTCA studies and 20 patients who underwent coronary artery bypass surgery (CABG) with corresponding pre- and post-CABG studies. Ischemia was defined as evoked angina during the exercise test in combination with greater than or equal to 1 mm horizontal or downsloping ST-depression on the ECG. The severity of coronary obstructions was assessed from coronary angiograms with a PC-based digital caliper technique; a stenosis was defined to be significant when its severity exceeded 50% diameter stenosis. The LH-ratio was defined by the ratio of the mean pulmonary counts and the mean myocardial counts assessed from corresponding regions of interest (ROI's) positioned over the left lung and the heart, respectively in the anterior view of a tomographic data acquisition procedure. Our results made clear that the LH-ratio was not significantly different between patients with and without ischemia during exercise, and between patients with single vs. multiple vessel disease.

  16. Evaluation of Silent Myocardial Ischemia with Single-Photon Emission Computed Tomography/Computed Tomography in Asymptomatic Subjects with Diabetes and Pre-Diabetes

    PubMed Central

    Özdemir, Elif; Burçak Polat, Şefika; Yıldırım, Nilüfer; Türkölmez, Şeyda; Ersoy, Reyhan; Durmaz, Tahir; Keleş, Telat; Bozkurt, Engin; Çakır, Bekir

    2016-01-01

    Objective: The aim of this study was to disclose the prevalence of myocardial ischemia, as detected by adenosine stress myocardial perfusion imaging (MPI) with hybrid single-photon emission computed tomography/computed tomography (SPECT/CT), in asymptomatic diabetic and pre-diabetic patients and to find out whether ischemia predicted the occurrence of adverse cardiac/cerebrovascular events (ACCE) at follow-up. Methods: Forty-three diabetic and thirty-five pre-diabetic asymptomatic patients without any history of coronary artery disease, underwent MPI and were followed-up for a 12.8±2.2 (8-19) months for the occurrence of ACCE. Baseline variables that would predict the presence of ischemia and the value of ischemia on MPI for predicting the occurrence of ACCE at follow-up were evaluated by logistic regression analysis. Results: Ischemia was detected in ten (23.3%) of the diabetic and in four (11.4%) of the pre-diabetic patients. The presence of diabetes was the only independent predictor of myocardial ischemia [odds ratio (OR): 12.31, 95% confidence interval (CI): 1.83-82.66; p<0.01]. During 12.8±2.2 (8-19) months of follow-up, ACCE was observed in five out of 78 (6.4%) patients. Patients with ischemia were significantly more likely to have ACCE during follow-up as compared to those with normal MPI scans (event rates: 21.4% vs. 3.1%, OR: 8.455 95% CI: 1.264-56.562, p=0.038). Conclusion: Myocardial ischemia as detected by adenosine stress SPECT/CT in a population of asymptomatic patients with diabetes mellitus or pre-diabetes appeared to predict the occurrence of ACCE at follow-up. PMID:27277323

  17. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model.

    PubMed

    Kang, Pin-Fang; Wu, Wen-Juan; Tang, Yang; Xuan, Ling; Guan, Su-Dong; Tang, Bi; Zhang, Heng; Gao, Qin; Wang, Hong-Ju

    2016-01-01

    The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2) when diabetes mellitus (DM) rat heart was subjected to ischemia/reperfusion (I/R) intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH); cardiomyocyte in high glucose (HG) condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker), atractyloside (mitoPTP opener), and wortmannin (PI3K inhibitor) groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.

  18. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model

    PubMed Central

    Kang, Pin-Fang; Wu, Wen-Juan; Tang, Yang; Xuan, Ling; Guan, Su-Dong; Tang, Bi; Zhang, Heng

    2016-01-01

    The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2) when diabetes mellitus (DM) rat heart was subjected to ischemia/reperfusion (I/R) intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH); cardiomyocyte in high glucose (HG) condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker), atractyloside (mitoPTP opener), and wortmannin (PI3K inhibitor) groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening. PMID:27829984

  19. 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.

  20. The association of depressed angiogenic factors with reduced capillary density in the Rhesus monkey model of myocardial ischemia.

    PubMed

    Zhang, Wenjing; Zhao, Xinmei; Xiao, Ying; Chen, Jianmin; Han, Pengfei; Zhang, Jingyao; Fu, Haiying; James Kang, Y

    2016-07-13

    Depressed capillary density is associated with myocardial ischemic infarction, in which hypoxia-inducible factor 1α (HIF-1α) is increased. The present study was undertaken to examine changes in the angiogenic factors whose expression is regulated by HIF-1 and their relation to the depressed capillary density in the Rhesus monkey model of myocardial ischemic infarction. Male Rhesus monkeys 2-3 years old were subjected to myocardial ischemia by permanent ligation of left anterior descending (LAD) artery leading to the development of myocardial infarction. Eight weeks after LAD ligation, copper concentrations, myocardial histological changes and capillary density were examined, along with Western blot and immunohistochemical analysis of angiogenic factors and detection of HIF-1 activity. Capillary density was significantly decreased but the concentrations of HIF-1α and HIF-1β were significantly increased in the infarct area. However, the levels of mRNA and protein for VEGF and VEGFR1 were significantly decreased. Other HIF-1 regulated angiogenic factors, including Tie-2, Ang-1 and FGF-1, were also significantly depressed, but vascular destabilizing factor Ang-2 was significantly increased. Copper concentrations were depressed in the infarct area. Copper-independent HIF-1 activity was increased shown by the elevated mRNA level of IGF-2, a HIF-1 target gene. Removal of copper by a copper chelator, tetraethylenepentamine, from primary cultures of neonatal rat cardiomyocytes also suppressed the expression of HIF-1 regulated VEGF and BNIP3, but not IGF-2. The data suggest that under ischemic conditions, copper loss suppressed the expression of critical angiogenic genes regulated by HIF-1, but did not affect copper-independent HIF-1 activation of gene expression. This copper-dependent dysregulation of angiogenic gene expression would contribute to the pathogenesis of myocardial ischemic infarction.

  1. 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

  2. Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury

    PubMed Central

    RONG, REN; XIJUN, XIAO

    2015-01-01

    Erythropoietin (EPO), a glycoprotein originally known for its important role in the stimulation of erythropoiesis, has recently been shown to have significant protective effects in animal models of kidney and intestinal ischemia-reperfusion injury (IRI). However, the mechanism underlying these protective effects remains unclear. The aim of the current study was to evaluate the effects of EPO on myocardial IRI and to investigate the mechanism underlying these effects. A total of 18 male Sprague Dawley rats were randomly divided into three groups, namely the sham, IRI-saline and IRI-EPO groups. Rats in the IRI-EPO group were administered 5,000 U/kg EPO intraperitoneally 24 h prior to the induction of IRI. IRI was induced by ligating the left descending coronary artery for 30 min, followed by reperfusion for 3 h. Pathological changes in the myocardial tissue were observed and scored. The levels of the proinflammatory cytokines, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, were evaluated in the serum and myocardial tissue. Furthermore, the effects of EPO on phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling and EPO receptor (EPOR) phosphorylation were measured. Pathological changes in the myocardial tissue, increased expression levels of TNF-α, IL-6 and IL-1β in the myocardium, and increased serum levels of these mediators, as a result of IRI, were significantly decreased by EPO pretreatment. The effects of EPO were found to be associated with the activation of PI3K/Akt signaling, which suppressed the inflammatory responses, following the initiation of EPOR activation by EPO. Therefore, EPO pretreatment was demonstrated to decrease myocardial IRI, which was associated with activation of EPOR, subsequently increasing PI3K/Akt signaling to inhibit the production and release of inflammatory mediators. Thus, the results of the present study indicated that EPO may be useful for preventing myocardial IRI. PMID:26622330

  3. 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

  4. Prevalence and risk factors accounting for true silent myocardial ischemia: a pilot case-control study comparing type 2 diabetic with non-diabetic control subjects

    PubMed Central

    2011-01-01

    Background Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, the need to screen asymptomatic diabetic patients for CAD assumes increasing importante. The aims of the study were to assess prospectively the prevalence and risk factor predictors of true silent myocardial ischemia (myocardial perfusion defects in the absence of both angina and ST-segment depression) in asymptomatic type 2 diabetic patients. Methods Stress myocardial perfusion gated SPECT (Single Photon Emission Computed Tomography) was carried out in 41 type 2 diabetic patients without history of cardiovascular disease (CVD) and 41 nondiabetic patients matched by age and gender. Results There were no significant differences between the two groups regarding either the classic CVD risk factors or left ventricular function. True silent ischemia was detected in 21.9% of diabetic patients but only in 2.4% of controls (p < 0.01). The presence of myocardial perfusion defects was independently associated with male gender and the presence of diabetic retinopathy (DR). The probability of having myocardial perfusion defects in an asymptomatic diabetic patient with DR in comparison with diabetic patients without DR was 11.7 [IC95%: 3.7-37]. Conclusions True silent myocardial ischemia is a high prevalent condition in asymptomatic type 2 diabetic patients. Male gender and the presence of DR are the risk factors related to its development. PMID:21255408

  5. 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.

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

    PubMed

    An, Wei; Yang, Jing

    2006-11-03

    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.

  7. Ion-sensitive field effect transistors for pH and potassium ion concentration sensing: towards detection of myocardial ischemia

    NASA Astrophysics Data System (ADS)

    Rai, Pratyush; Jung, Soyoun; Ji, Taeksoo; Varadan, Vijay K.

    2008-03-01

    Ion Sensitive Field Effect Transistors (ISFETs) for sensing change in ionic concentration in biological systems can be used for detecting critical conditions like Myocardial Ischemia. Having the ability to yield steady signal characteristics can be used to observe the ionic concentration gradients which mark the onset of ischemia. Two ionic concentrations, pH and [K +], have been considered as the indicator for Myocardial Ischemia in this study. The ISFETs in this study have an organic semi-conductor film as the electronically active component. Poly-3 hexylthiophene was chosen for its compatibility to the solution processing, which is a simple and economical method of thin film fabrication. The gate electrode, which regulates the current in the active layer, has been employed as the sensor element. The devices under study here were fabricated on a flexible substrate PEN. The pH sensor was designed with the Tantalum Oxide gate dielectric as the ion selective component. The charge accumulated on the surface of the metal oxide acts as the source of the effecter electric field. The device was tested for pH values between 6.5 and 7.5, which comprises the variation observed during ischemic attack. The potassium ion sensor has got a floating gate electrode which is functionalized to be selective to potassium ion. The device was tested for potassium ion concentration between 5 and 25 mM, which constitutes the variation in extra cellular potassium ion concentration during ischemic attack. The device incorporated a monolayer of Valinomycin, a potassium specific ionophore, on top of the gate electrode.

  8. Targeting TRAF3IP2 by Genetic and Interventional Approaches Inhibits Ischemia/Reperfusion-induced Myocardial Injury and Adverse Remodeling.

    PubMed

    Erikson, John M; Valente, Anthony J; Mummidi, Srinivas; Kandikattu, Hemanth Kumar; DeMarco, Vincent G; Bender, Shawn B; Fay, William P; Siebenlist, Ulrich; Chandrasekar, Bysani

    2017-02-10

    Re-establishing blood supply is the primary goal for reducing myocardial injury in subjects with ischemic heart disease. Paradoxically, reperfusion results in nitroxidative stress and a marked inflammatory response in the heart. TRAF3IP2 (TRAF3 Interacting Protein 2; previously known as CIKS or Act1) is an oxidative stress-responsive cytoplasmic adapter molecule that is an upstream regulator of both IκB kinase (IKK) and c-Jun N-terminal kinase (JNK), and an important mediator of autoimmune and inflammatory responses. Here we investigated the role of TRAF3IP2 in ischemia/reperfusion (I/R)-induced nitroxidative stress, inflammation, myocardial dysfunction, injury, and adverse remodeling. Our data show that I/R up-regulates TRAF3IP2 expression in the heart, and its gene deletion, in a conditional cardiomyocyte-specific manner, significantly attenuates I/R-induced nitroxidative stress, IKK/NF-κB and JNK/AP-1 activation, inflammatory cytokine, chemokine, and adhesion molecule expression, immune cell infiltration, myocardial injury, and contractile dysfunction. Furthermore, Traf3ip2 gene deletion blunts adverse remodeling 12 weeks post-I/R, as evidenced by reduced hypertrophy, fibrosis, and contractile dysfunction. Supporting the genetic approach, an interventional approach using ultrasound-targeted microbubble destruction-mediated delivery of phosphorothioated TRAF3IP2 antisense oligonucleotides into the LV in a clinically relevant time frame significantly inhibits TRAF3IP2 expression and myocardial injury in wild type mice post-I/R. Furthermore, ameliorating myocardial damage by targeting TRAF3IP2 appears to be more effective to inhibiting its downstream signaling intermediates NF-κB and JNK. Therefore, TRAF3IP2 could be a potential therapeutic target in ischemic heart disease.

  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. 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.

  11. 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

  12. 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.

  13. Prognosis in the thrombolysis in myocardial ischemia III registry according to the Braunwald unstable angina pectoris classification.

    PubMed

    Scirica, Benjamin M; Cannon, Christopher P; McCabe, Carolyn H; Murphy, Sabina A; Anderson, H Vernon; Rogers, William J; Stone, Peter H; Braunwald, Eugene

    2002-10-15

    The unstable angina pectoris (UAP) classification proposed by Braunwald in 1989, although often used, has never been validated in a large, prospective multicenter study in which all subgroups of patients were included. Patients with UAP or non-ST-elevation myocardial infarction (NSTEMI) were enrolled in the Thrombolysis In Myocardial Ischemia III Registry and classified according to the Braunwald classification for UAP. Clinical end points were compared at 6 weeks and 1 year. Of 3,318 patients, those with primary UAP had lower rates of recurrent myocardial infarction (MI) or death when compared with patients with secondary UAP and post-MI UAP at 6 weeks (4.1% vs 6.4% vs 13.4%, respectively; p <0.001) and 1 year (9.7% vs 16.7% vs 19.7%; p <0.001). Recurrent ischemia at 6 weeks followed the same gradient (13.2% vs 18.5% vs 20.8%; p <0.001). Patients with secondary UAP had similar extent of disease at angiography as primary UAP. Patients with nonresting UAP had lower rates of death or MI than patients with UAP at rest (3.0% vs 5.6%, p = 0.011 at 6 weeks, and 8.2% vs 12.5%, p = 0.004 at 1 year). Patients with ST-segment deviation and those who had received prior antianginal medical treatment also had worse outcomes. Thus, the Braunwald classification of UAP predicts prognosis with secondary UAP, post-MI UAP, and patients with pain at rest who have a higher risk for death or recurrent cardiac events. Given their high risk for adverse events, patients with secondary UAP should be treated aggressively.

  14. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    PubMed Central

    2010-01-01

    Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability. PMID:20875134

  15. 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

  16. Protective role of intracellular zinc in myocardial ischemia/reperfusion is associated with preservation of protein kinase C isoforms.

    PubMed

    Karagulova, Gulnura; Yue, Yuankun; Moreyra, Abel; Boutjdir, Mohamed; Korichneva, Irina

    2007-05-01

    The recent discovery of zinc signals and their essential role in the redox signaling network implies that zinc homeostasis and the function of zinc-containing proteins are probably altered as a result of oxidative stress, suggesting new targets for pharmacological intervention. We hypothesized that the level of intracellular labile zinc is changed in hearts subjected to ischemia/reperfusion (I/R) and investigated whether the maintenance of myocardial zinc status protected heart functions. Using fluorescent imaging, we demonstrated decreased levels of labile zinc in the I/R hearts. Phorbol 12-myristate 13-acetate, a known trigger of zinc release, liberated zinc ions in control hearts but failed to produce any increase in zinc levels in the I/R rat hearts. Adding the zinc ionophore pyrithione at reperfusion improved myocardial recovery up to 100% and reduced the incidence of arrhythmias more than 2-fold. This effect was dose-dependent, and high concentrations of zinc were toxic. Adding membrane-impermeable zinc chloride was ineffective. Hearts from rats receiving zinc pyrithione supplements in their diet fully recovered from I/R. The recovery was associated with the prevention of degradation of the two protein kinase C isoforms, delta and epsilon, during I/R. In conclusion, our results suggest a protective role of intracellular zinc in myocardial recovery from oxidative stress imposed by I/R. The data support the potential clinical use of zinc ionophores in the settings of acute redox stress in the heart.

  17. Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B.

    PubMed

    Yang, Lei; Zhang, Yan; Zhu, Mengmeng; Zhang, Qiong; Wang, Xiaoling; Wang, Yanjiao; Zhang, Jincai; Li, Jing; Yang, Liang; Liu, Jie; Liu, Fei; Yang, Yinan; Kang, Licheng; Shen, Yanna; Qi, Zhi

    2016-12-01

    The objective was to examine the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (IR) injury and whether the mechanism was related to vascular endothelial growth factor B (VEGF-B) signaling pathway. Rat hearts were isolated for Langendorff perfusion test and H9c2 cells were used for in vitro assessments. RSV treatment significantly improved left ventricular function, inhibited CK-MB release, and reduced infarct size in comparison with IR group ex vivo. RSV treatment markedly decreased cell death and apoptosis of H9c2 cells during IR. We found that RSV was responsible for the up-regulation of VEGF-B mRNA and protein level, which caused the activation of Akt and the inhibition of GSK3β. Additionally, RSV prevented the generation of reactive oxygen species (ROS) by up-regulating the expression of MnSOD either in vitro or ex vivo. We also found that the inhibition of VEGF-B abolished the cardioprotective effect of RSV, increased apoptosis, and led to the down-regulation of phosphorylated Akt, GSK3β, and MnSOD in H9c2 cells. These results demonstrated that RSV was able to attenuate myocardial IR injury via promotion of VEGF-B/antioxidant signaling pathway. Therefore, the up-regulation of VEGF-B can be a promising modality for clinical myocardial IR injury therapy.

  18. 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.

  19. [The comparative efficacy of emoxipine and sodium oxybutyrate in experimental myocardial ischemia].

    PubMed

    Afanas'ev, S A; Alekseeva, E D; Bardamova, I B; Bogomaz, S A

    1994-01-01

    The efficacy of emoxypine (2-ethyl-6-methyl-3-hydroxypyridine chlorohydrate) versus sodium hydroxybutyrate in total and local ischemia followed by reperfusion was studied in the experiments on rat isolated hearts. Emoxypine in a dose of 1 nM in total ischemia was shown to have a protective action, by decreasing reperfusion contracture. In local ischemia, emoxypine, unlike sodium hydroxybutyrate, did not favour greater restoration of the amplitude of isolated heart contractions, but restored coronary flow and stabilized contraction frequency better than did sodium hydroxybutyrate.

  20. Dynamic myocardial perfusion in a porcine balloon-induced ischemia model using a prototype spectral detector CT

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    Myocardial CT perfusion (CTP) imaging is an application that should greatly benefit from spectral CT through the significant reduction of beam hardening (BH) artifacts using mono-energetic (monoE) image reconstructions. We used a prototype spectral detector CT (SDCT) scanner (Philips Healthcare) and developed advanced processing tools (registration, segmentation, and deconvolution-based flow estimation) for quantitative myocardial CTP in a porcine ischemia model with different degrees of coronary occlusion using a balloon catheter. The occlusion severity was adjusted with fractional flow reserve (FFR) measurements. The SDCT scanner is a single source, dual-layer detector system, which allows simultaneous acquisitions of low and high energy projections, hence enabling accurate projection-based material decomposition and effective reduction of BH-artifacts. In addition, the SDCT scanner eliminates partial scan artifacts with fast (0.27s), full gantry rotation acquisitions. We acquired CTP data under different hemodynamic conditions and reconstructed conventional 120kVp images and projection-based monoenergetic (monoE) images for energies ranging from 55keV-to-120keV. We computed and compared myocardial blood flow (MBF) between different reconstructions. With balloon completely deflated (FFR=1), we compared the mean attenuation in a myocardial region of interest before iodine arrival and at peak iodine enhancement in the left ventricle (LV), and we found that monoE images at 70keV effectively minimized the difference in attenuation, due to BH, to less than 1 HU compared to 14 HU with conventional 120kVp images. Flow maps under baseline condition (FFR=1) were more uniform throughout the myocardial wall at 70keV, whereas with 120kVp data about 12% reduction in blood flow was noticed on BH-hypoattenuated areas compared to other myocardial regions. We compared MBF maps at different keVs under an ischemic condition (FFR < 0.7), and we found that flow

  1. 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.

  2. Cardiac Per2 Functions as Novel Link between Fatty Acid Metabolism and Myocardial Inflammation during Ischemia and Reperfusion Injury of the Heart

    PubMed Central

    Bonney, Stephanie; Kominsky, Doug; Brodsky, Kelley; Eltzschig, Holger; Walker, Lori; Eckle, Tobias

    2013-01-01

    Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In contrast to Clock−/−, Per2−/− mice have larger infarct sizes with deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we measured lactate during reperfusion in Per1−/−, Per2−/− or wildtype mice. As lactate measurements in whole blood indicated an exclusive role of Per2 in controlling lactate production during myocardial ischemia, we next performed gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2−/− mice. Surprisingly, high-throughput gene array analysis revealed dominantly lipid metabolism as the differentially regulated pathway in wildtype mice when compared to Per2−/−. In all ischemia-reperfusion protocols used, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2−/− mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated ‘Per2-genes’. Subsequent studies on inflammatory markers showed increasing IL-6 or TNFα levels during reperfusion in Per2−/− mice. In summary, these studies reveal an important role of cardiac Per2 for fatty acid metabolism and inflammation during myocardial ischemia and reperfusion, respectively. PMID:23977055

  3. 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.

  4. MicroRNAs regulate mitochondrial apoptotic pathway in myocardial ischemia-reperfusion-injury.

    PubMed

    Makhdoumi, Pouran; Roohbakhsh, Ali; Karimi, Gholamreza

    2016-12-01

    MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene regulators. They are involved in the pathogenesis of different disorders including heart diseases. MiRNAs contribute to ischemia/reperfusion injury (I/RI) by altering numerous key signaling elements. Together with alterations in the various potential signaling pathways, modification in miRNA expression has been suggested as a part of the response network following ischemia/reperfusion (I/R). In addition, cardiac mitochondrial homeostasis is closely associated with cardiac function and impairment of mitochondrial activity occurred after ischemia/reperfusion injury. MiRNAs play a key role in the regulation of mitochondrial apoptotic pathway and signaling proteins. In this review, we summarize the knowledge currently available regarding the molecular mechanisms of miRNA-regulated mitochondrial functions during ischemia/reperfusion injury. This regulation occurs in different stages of mitochondrial apoptosis pathway.

  5. Myocardial ischemia during cardiopulmonary bypass. The hazards of ventricular fibrillation in the presence of a critical coronary stenosis.

    PubMed

    Ciardullo, R C; Schaff, H V; Flaherty, J T; Gott, V L

    1977-05-01

    The effect of a critical coronary artery stenosis on myocardial blood flow and metabolism in the fibrillating heart was assessed by placing 10 dogs on cardiopulmonary bypass, venting the ventricle, inducing ventricular fibrillation, and applying critical stenosis to the left anterior descending coronary artery (LAD). Endocardial and epicardial blood flows were measured by the radioactive microsphere technique prior to the application of the stenosis and after one hour and 2 hours of fibrillation. Intramyocardial oxygen tension (PO2) and carbon dioxide tension (PCO2) were continuously monitored in the LAD-supplied myocardium by a mass spectrometer probe inserted at midmyocardial depth. Selective arterial-coronary venous lactate differences were determined at control, one hour, and 2 hours. At the end of the 2 hour period, vital dye injection defined the distribution of the LAD. Endocardial flow to the myocardium of the stenosed LAD was reduced by 50 per cent after one hour and by 70 per cent after 2 hours (p less than 0.05). Epicardial flow fell 40 per cent after one hour and 50 per cent after 2 hours (p less than 0.05). Endocardial and epicardial flow in the distribution of the unstenosed circumflex coronary artery remained unchanged. Changes in myocardial PO2 and PCO2 in the LAD-supplied myocardium indicated the development of severe ischemia in all 10 dogs and suggested myocardial infarction in 5. There was a conversion from lactate extraction to lactate production during the 2 hour period of ventricular fibrillation. From this study, it is concluded that the myocardium distal to a critical stenosis suffers a progressive reduction in flow during ventricular fibrillation which does not occur in regions supplied by unstenosed coronary arteries. Thus prolonged fibrillation in the presence of a flow-limiting coronary stenosis may play a role in the pathogenesis of myocardial infarction during coronary bypass surgery.

  6. Carbon monoxide increases inducible NOS expression that mediates CO-induced myocardial damage during ischemia-reperfusion.

    PubMed

    Meyer, Grégory; André, Lucas; Kleindienst, Adrien; Singh, François; Tanguy, Stéphane; Richard, Sylvain; Obert, Philippe; Boucher, François; Jover, Bernard; Cazorla, Olivier; Reboul, Cyril

    2015-04-01

    We investigated the role of inducible nitric oxide (NO) synthase (iNOS) on ischemic myocardial damage in rats exposed to daily low nontoxic levels of carbon monoxide (CO). CO is a ubiquitous environmental pollutant that impacts on mortality and morbidity from cardiovascular diseases. We have previously shown that CO exposure aggravates myocardial ischemia-reperfusion (I/R) injury partly because of increased oxidative stress. Nevertheless, cellular mechanisms underlying cardiac CO toxicity remain hypothetical. Wistar rats were exposed to simulated urban CO pollution for 4 wk. First, the effects of CO exposure on NO production and NO synthase (NOS) expression were evaluated. Myocardial I/R was performed on isolated perfused hearts in the presence or absence of S-methyl-isothiourea (1 μM), a NOS inhibitor highly specific for iNOS. Finally, Ca(2+) handling was evaluated in isolated myocytes before and after an anoxia-reoxygenation performed with or without S-methyl-isothiourea or N-acetylcystein (20 μM), a nonspecific antioxidant. Our main results revealed that 1) CO exposure altered the pattern of NOS expression, which is characterized by increased neuronal NOS and iNOS expression; 2) cardiac NO production increased in CO rats because of its overexpression of iNOS; and 3) the use of a specific inhibitor of iNOS reduced myocardial hypersensitivity to I/R (infarct size, 29 vs. 51% of risk zone) in CO rat hearts. These last results are explained by the deleterious effects of NO and reactive oxygen species overproduction by iNOS on diastolic Ca(2+) overload and myofilaments Ca(2+) sensitivity. In conclusion, this study highlights the involvement of iNOS overexpression in the pathogenesis of simulated urban CO air pollution exposure.

  7. Changes of endothelin-1 and big endothelin-1 levels and action potential duration during myocardial ischemia-reperfusion in dogs with and without ventricular fibrillation.

    PubMed

    Vágó, Hajnalka; Soós, Pál; Zima, Endre; Gellér, László; Keltai, Katalin; Róka, Attila; Kékesi, Violetta; Juhász-Nagy, Alexander; Merkely, Béla

    2004-11-01

    Myocardial ischemia-reperfusion is associated with increased production of endothelin-1 (ET-1). Moreover, exogenous ET-1 has arrhythmogenic properties. Our aim was to investigate the correlation between endogenous ET-1, big ET-1 levels and epicardial monophasic action potential duration during myocardial ischemia-reperfusion in anesthetized dogs. Thirty-minute myocardial ischemia was followed by a 90-minute reperfusion period in 18 mongrel dogs. The total incidence of ventricular fibrillation (VF) during ischemia and reperfusion was 11.1% and 33.3%, respectively. During ischemia, the monophasic action potential duration at 90% repolarization (MAPD90) decreased significantly (control versus ischemia, 30 minutes, 224.7 +/- 7.1 ms versus 173.8 +/- 7.6 ms; P < 0.05), while during reperfusion a significant prolongation of MAPD90 was observed (ischemia, 30 minutes versus reperfusion, 30 minutes, 173.8 +/- 7.6 ms versus 249.7 +/- 9.9 ms, P < 0.05). During reperfusion ET-1 and big ET-1 levels increased significantly in the coronary sinus and femoral artery (control versus reperfusion, 90 minutes: coronary sinus ET-1, 15.1 +/- 1.4 fmol/mL versus 22.3 +/- 1.1 fmol/mL; big ET-1, 14.7 +/- 1.9 fmol/mL versus 27.4 +/- 2.3 fmol/mL; P < 0.05). The ET-1 concentration increased to a higher level during ischemia in dogs with VF compared with dogs surviving ischemia-reperfusion (non-VF versus VF: control, 15.1 +/- 1.3 versus 15.2 +/- 1.3; ischemia, 30 minutes, 17.6 +/- 1.2 fmol/mL versus 22 +/- 1.6 fmol/mL; P < 0.05), demonstrating a trend of correlation between endothelin levels and development of VF (P = 0.07). ET-1 and big ET-1 levels increased during reperfusion and in the VF group during ischemia; however, there was no correlation between endothelin levels and MAPD90.

  8. Complementary Prognostic Values of Stress Myocardial Perfusion and Late Gadolinium Enhancement Imaging by Cardiac Magnetic Resonance in Patients with Known or Suspected Coronary Artery Disease

    PubMed Central

    Steel, Kevin; Broderick, Ryan; Gandla, Vijay; Larose, Eric; Resnic, Frederick; Jerosch-Herold, Michael; Brown, Kenneth A.; Kwong, Raymond Y.

    2009-01-01

    BACKGROUND Recent studies have demonstrated the significant prognostic value of stress CMR myocardial perfusion imaging (CMRMPI). Apart from characterizing reversible perfusion defect (RevPD) from flow-limiting coronary stenosis, CMR late enhancement imaging (LGE) is currently the most sensitive method in detecting subendocardial infarction (MI). We therefore tested the hypothesis that, characterization of these 2 processes from coronary artery disease (CAD) by CMR can provide complementary prognostic values. Methods and Results We performed CMRMPI followed by LGE imaging on 254 patients referred with symptoms of myocardial ischemia. At a median follow up of 17 months, 49 cardiac events (MACE) occurred including 12 cardiac deaths, 16 acute myocardial infarction (MI), and 21 cardiac hospitalizations. RevPD and LGE both maintained a > 3-fold association with cardiac death or acute MI (Death/MI) when adjusted to each other and to the effects of patient age and gender (adjusted HR 3.31, P=0.02 and 3.43, P=0.01, respectively). In patients without a history of MI who had negative RevPD, LGE presence was associated with >11-fold hazards increase to Death/MI. Patients with neither RevPD nor LGE had a 98.1% negative annual event rate for Death/MI. For association with MACE, RevPD was the strongest multivariable variable in the best overall model (HR 10.92, P<0.0001). Conclusions CMR imaging provides robust risk-stratification of patients who presents with symptoms of ischemia. Characterization of RevPD and LGE by CMR provides strong and complementary prognostic implication towards cardiac death or acute MI. PMID:19770399

  9. Electrocardiologic and related methods of non-invasive detection and risk stratification in myocardial ischemia: state of the art and perspectives

    PubMed Central

    Huebner, Thomas; Goernig, Matthias; Schuepbach, Michael; Sanz, Ernst; Pilgram, Roland; Seeck, Andrea; Voss, Andreas

    2010-01-01

    Background: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia. Objectives: To present and review the state of the art in and new approaches to electrocardiologic methods for non-invasive detection and risk stratification in coronary artery disease (CAD) and myocardial ischemia; secondarily, to explore the future perspectives of these methods. Methods: In follow-up to the Expert Discussion at the 2008 Workshop on "Biosignal Analysis" of the German Society of Biomedical Engineering in Potsdam, Germany, we comprehensively searched the pertinent literature and databases and compiled the results into this review. Then, we categorized the state-of-the-art methods and selected new approaches based on their applications in detection and risk stratification of myocardial ischemia. Finally, we compared the pros and cons of the methods and explored their future potentials for cardiology. Results: Resting ECG, particularly suited for detecting ST-elevation myocardial infarctions, and exercise ECG, for the diagnosis of stable CAD, are state-of-the-art methods. New exercise-free methods for detecting stable CAD include cardiogoniometry (CGM); methods for detecting acute coronary syndrome without ST elevation are Body Surface Potential Mapping, functional imaging and CGM. Heart rate variability and blood pressure variability analyses, microvolt T-wave alternans and signal-averaged ECG mainly serve in detecting and stratifying the risk for lethal arrythmias in patients with myocardial ischemia or previous myocardial infarctions. Telemedicine and ambient

  10. 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.

  11. Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury

    PubMed Central

    Hao, Jia; Ahn, Hee-Yul

    2012-01-01

    Akt/protein kinase B is a well-known cell survival factor and activated by many stimuli including mechanical stretching. Therefore, we evaluated the cardioprotective effect of a brief mechanical stretching of rat hearts and determined whether activation of Akt through phosphatidylinositol 3-kinase (PI3K) is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning reduced infarct size and improved post-ischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3β, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3β inhibitors) before ischemia induction mimicked the protective effects of SIC on rat heart. Gadolinium (Gd3+), a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of Akt and GSK-3β. Furthermore, SIC was abrogated by wortmannin and Gd3+. In vivo stretching induced by an aorto-caval shunt increased Akt phosphorylation and reduced myocardial infarction; these effects were diminished by wortmannin and Gd3+ pretreatment. Our results showed that mechanical stretching can provide cardioprotection against ischemia-reperfusion injury. Additionally, the activation of Akt, which might be regulated by SACs and the PI3K pathway, plays an important role in SIC. PMID:23000580

  12. T-Wave Alternans Is Linked to Microvascular Obstruction and to Recurrent Coronary Ischemia After Myocardial Infarction.

    PubMed

    Floré, V; Claus, P; Vos, M A; Vandenberk, B; Van Soest, S; Sipido, K R; Adriaenssens, T; Bogaert, J; Desmet, W; Willems, R

    2015-11-01

    The purpose of this study is to investigate the relationship between T-wave alternans (TWA), infarct size and microvascular obstruction (MVO) and recurrent cardiac morbidity after ST elevation myocardial infarction (STEMI). One hundred six patients underwent TWA testing 1-12 months and 57 patients underwent cardiac magnetic resonance imaging (MRI) in the first 2-4 days after STEMI. During follow-up (3.5 ± 0.5 years), death (n = 2), ventricular tachycardia (n = 3), supraventricular tachycardia (n = 4), heart failure (n = 3) and recurrent coronary ischemia (n = 25) were observed. After multivariate analysis, positive TWA (HR2.59, CI1.10-6.11, p0.024) and larger MVO (HR1.08, CI1.01-1.16, p0.034) were associated with recurrent angina or ACS. Presence of MVO was correlated with TWA (Spearman rho 0.404, p0.002) and the impairment of LVEF (-0.524, p < 0.001). Patients after STEMI remain at a high risk of symptoms of coronary ischemia. The presence of MVO and TWA 1-12 months after STEMI is related to each other and to recurrent angina or ACS.

  13. Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury.

    PubMed

    Kim, Chan-Hyung; Hao, Jia; Ahn, Hee-Yul; Kim, Si Wook

    2012-09-01

    Akt/protein kinase B is a well-known cell survival factor and activated by many stimuli including mechanical stretching. Therefore, we evaluated the cardioprotective effect of a brief mechanical stretching of rat hearts and determined whether activation of Akt through phosphatidylinositol 3-kinase(PI3K) is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning reduced infarct size and improved postischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3β, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3β inhibitors) before ischemia induction mimicked the protective effects of SIC on rat heart. Gadolinium (Gd3(+)), a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of Akt and GSK-3β. Furthermore, SIC was abrogated by wortmannin and Gd3(+). In vivo stretching induced by an aorto-caval shunt increased Akt phosphorylation and reduced myocardial infarction; these effects were diminished by wortmannin and Gd3(+) pretreatment. Our results showed that mechanical stretching can provide cardioprotection against ischemia-reperfusion injury. Additionally, the activation of Akt, which might be regulated by SACs and the PI3K pathway, plays an important role in SIC.

  14. The impact of ischemia-reperfusion injury on the effectiveness of primary angioplasty in ST-segment elevation myocardial infarction

    PubMed Central

    Grygier, Marek; Lesiak, Maciej; Grajek, Stefan

    2013-01-01

    The most effective method of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PCI), assisted by aspiration thrombectomy and administration of antiplatelet agents and anticoagulants. However, effective restoration of blood flow in the infarct-related artery may paradoxically result in further damage to the heart muscle. This phenomenon, called ischemia-reperfusion injury (IRI), can significantly reduce the beneficial effects of reperfusion therapy. The rapid restoration of blood flow to the previously ischemic area causes a number of pathophysiological mechanisms leading to increased necrosis of myocytes still viable at the end of the ischemic period. It has been postulated that there are several strategies that can reduce damage to the heart muscle. Attempts to translate the results of experimental trials has been disappointing. More recently, however, some of the clinical benefits of ischemic postconditioning in which reperfusion in patients with STEMI who are undergoing PCI is interrupted with short episodes of ischemia were demonstrated. This renewed the interest in the reperfusion phase as a target for cardioprotective therapy. Research in this field has also been reinforced by the discovery of new potential targets for treatment that protects against IRI, such as the kinase pathway to protect against damage (reperfusion injury salvage kinases – RISK) and mitochondrial permeability transition pore. It seems that these findings will help to develop strategies that will improve the efficiency of mechanical reperfusion and may translate into long-term clinical effects. PMID:24570732

  15. Physical training of the patients with coronary heart disease: noninvasive strategies for the evaluation of its effects on the oxygentransport system and myocardial ischemia.

    PubMed

    Doba, N; Shukuya, M; Yoshida, H; Inagaki, M; Inaji, J; Hinohara, S

    1990-11-01

    To clarify the central effects of physical training on patients with coronary heart disease, 81 subjects were selected for the present study. Evaluations of the oxygen transport system function were performed according to the definition proposed by Bruce and others in terms of FAI (functional aerobic impairment), LVI (left ventricular impairment) or MRI (myocardial reserve impairment), CRI (chronotropic reserve impairment) and PCI (peripheral circulatory impairment). Remarkable improvement in left ventricular impairment was found in those patients with single vessel disease or those who experienced disappearance of chest pain after the completion of the program. In another series of study on myocardial perfusion performed on 11 patients with coronary heart disease, improvement in ischemia was also demonstrated in 7 of 8 patients who revealed redistribution pattern in 201TL exercise stress images specifying myocardial ischemia. In conclusion, exercise training could induce improvements not only the left ventricular functions characterized by increased maximal pressure rate product and maximal heart rate, but also in myocardial ischemia. Further studies are needed to specify its effects, since natural progression or regression of the disease process itself may influence the results.

  16. Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats.

    PubMed

    Chiu, Po Yee; Ko, Kam Ming

    2004-11-01

    Schisandrin B (Sch B) is a hepato- and cardioprotective ingredient isolated from the fruit of Schisandra chinensis, a traditional Chinese herb clinically used to treat viral and chemical hepatitis. In order to investigate whether the induction of heat shock protein (Hsp)25 and Hsp70 expression plays a role in the cardioprotection afforded by Sch B pre-treatment against ischemia-reperfusion (I-R) injury, the time-course of myocardial Hsp25 and Hsp70 expression was examined in Sch B-pre-treated rats. Sch B pre-treatment (1.2 mmol/kg) produced time-dependent increases in Hsp25 and Hsp70 expression in rat hearts, with the maximum enhancement observable at 48 and 72 h post-dosing, respectively. Buthionine sulfoximine/phorone treatment, while abolishing the beneficial effect of Sch B on mitochondrial glutathione redox status, did not completely abrogate the cardioprotection against I-R injury. Heat shock treatment could increase myocardial Hsp25 and Hsp70 expression and protect against I-R injury under the present experimental conditions. The results indicate that the induction of Hsp25 and Hsp70 expression contributes at least partly to the cardioprotection afforded by Sch B pre-treatment against I-R injury.

  17. 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

  18. Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury.

    PubMed

    Liu, Baoshan; Wang, Jiali; Li, Minghua; Yuan, Qiuhuan; Xue, Mengyang; Xu, Feng; Chen, Yuguo

    2016-12-27

    Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection.

  19. Glycyrrhiza glabra protects from myocardial ischemia-reperfusion injury by improving hemodynamic, biochemical, histopathological and ventricular function.

    PubMed

    Ojha, Shreesh; Golechha, Mahaveer; Kumari, Santosh; Bhatia, Jagriti; Arya, Dharamvir S

    2013-01-01

    Present study evaluated the cardioprotective effect of Glycyrrhiza glabra against ischemia-reperfusion injury (I-R) induced by ligation of left anterior descending coronary artery (LADCA) in rats. Ligation of LADCA for 45 min followed by 60 min of reperfusion has induced significant (p<0.05) heart dysfunction evidenced by significant (p<0.05) decrease in mean arterial pressure (MAP), heart rate (HR), contractility; (+)LVdP/dtmax and relaxation; (-)LVdP/dtmax along with increased left ventricular end diastolic pressure (LVEDP). Ligation induced I-R injury also significantly (p<0.05) decreased myocyte injury enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) as well as antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Furthermore, I-R injury also induced lipid peroxidation evidenced by significant (p<0.05) increase in malondialdehyde (MDA) formation and histological perturbations concomitant to depletion of glutathione (GSH) from heart. However, pretreatment with G. glabra significantly (p<0.05) prevented the depletion of the antioxidant enzymes; SOD, CAT, GSH-Px and myocyte injury marker enzymes; CK-MB isoenzyme and LDH. Pretreatment with G. glabra also prevented GSH depletion and inhibited lipid peroxidation in heart. In addition to improving biochemical indices of myocardial function, G. glabra also significantly (p<0.05) reinstated MAP, HR, (±)LVdP/dtmax and attenuated abrupt rise in LVEDP. Histopathological preservation evidenced by reduced infiltration of cells and myonecrosis depicted the myocardial salvaging effect of G. glabra. Taken together, results of the present study clearly suggest the cardioprotective potential of G. glabra against myocardial infarction by amelioration of oxidative stress and favorable modulation of cardiac function.

  20. Effect of Salvia miltiorrhiza and ligustrazine injection on myocardial ischemia/reperfusion and hypoxia/reoxygenation injury

    PubMed Central

    Huang, Wendong; Yang, Yongfei; Zeng, Zhi; Su, Meiling; Gao, Qi; Zhu, Banghao

    2016-01-01

    Salvia miltiorrhiza and ligustrazine are traditional Chinese medicines that have been used in combination for treatment of cardiovascular disease, including coronary heart disease, cardiac angina and atherosclerosis in Asia, in particular, China. The present study aimed to determine the effect of S. miltiorrhiza and ligustrazine injection (SLI) on myocardial ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries via the Akt serine/threonine kinase (Akt)-endothelial nitric oxide synthase (eNOS) signaling pathway. Male Sprague-Dawley rats were randomly assigned into six groups: i) Sham group; ii) I/R group; iii) Low-SLI group (6.8 mg/kg/day, i.p.); iv) Medium-SLI group (20.4 mg/kg/day, i.p.); v) High-SLI group (61.2 mg/kg/day, i.p.); vi) verapamil group (6 mg/kg/day, i.p.). Prior to surgery, the aforementioned groups were pretreated with a homologous drug once per day for 3 days. The effect of SLI following 35 min coronary artery occlusion and 2 h reperfusion was evaluated by determining infarct size, hemodynamics, biochemical values and histological observations. Additionally, cell viability, caspase-3 expression, B cell leukemia/lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio, phosphorylated (p-)Akt and p-eNOS were also investigated following 2 h simulated ischemia and 2 h simulated reperfusion in H9C2 cardiomyocyte cells. Pretreatment with SLI significantly improved cardiac function in a dose-dependent manner and reduced myocardial infarct size, creatine kinase, lactate dehydrogenase and malondialdehyde levels in blood serum. Additionally, myocardial histopathology changes in the rat model were also alleviated in SLI treatment groups. The present in vitro study revealed that treatment with SLI reduced the apoptotic rate of H9C2 cells by inhibiting the activation of caspase-3 and increasing the Bcl-2/Bax ratio. The effect of SLI was associated with increased phosphorylation of the survival kinase Akt at Ser473 and its downstream target e

  1. 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

  2. Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway.

    PubMed

    Cui, Yuan-Chen; Pan, Chun-Shui; Yan, Li; Li, Lin; Hu, Bai-He; Chang, Xin; Liu, Yu-Ying; Fan, Jing-Yu; Sun, Kai; -Li, Quan; Han, Jing-Yan

    2017-03-22

    Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury. In addition, the binding affinity of RhoA to Rb1 was detected using surface plasmon resonance (SPR). Results showed that Rb1 treatment at 5 mg/kg/h protected all the cardiac injuries induced by I/R, including damaged myocardial structure, decrease in myocardial blood flow, impaired heart function and microcirculation, cardiomyocyte apoptosis, myocardial infarction and release of myocardial cTnI. Rb1 also inhibited the activation of RhoA signaling pathway and restored the production of ATP during cardiac I/R. Moreover, SPR assay showed that Rb1 was able to bind to RhoA in a dose-dependent manner. These results indicate that Rb1 may prevent I/R-induced cardiac injury by regulation of RhoA signaling pathway, and may serve as a potential regime to improve percutaneous coronary intervention outcome.

  3. Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway

    PubMed Central

    Cui, Yuan-Chen; Pan, Chun-Shui; Yan, Li; Li, Lin; Hu, Bai-He; Chang, Xin; Liu, Yu-Ying; Fan, Jing-Yu; Sun, Kai; -Li, Quan; Han, Jing-Yan

    2017-01-01

    Cardiac ischemia and reperfusion (I/R) injury remains a challenge for clinicians. Ginsenoside Rb1 (Rb1) has been reported to have the ability to attenuate I/R injury, but its effect on energy metabolism during cardiac I/R and the underlying mechanism remain unknown. In this study, we detected the effect of Rb1 on rat myocardial blood flow, myocardial infarct size, cardiac function, velocity of venule red blood cell, myocardial structure and apoptosis, energy metabolism and change in RhoA signaling pathway during cardiac I/R injury. In addition, the binding affinity of RhoA to Rb1 was detected using surface plasmon resonance (SPR). Results showed that Rb1 treatment at 5 mg/kg/h protected all the cardiac injuries induced by I/R, including damaged myocardial structure, decrease in myocardial blood flow, impaired heart function and microcirculation, cardiomyocyte apoptosis, myocardial infarction and release of myocardial cTnI. Rb1 also inhibited the activation of RhoA signaling pathway and restored the production of ATP during cardiac I/R. Moreover, SPR assay showed that Rb1 was able to bind to RhoA in a dose-dependent manner. These results indicate that Rb1 may prevent I/R-induced cardiac injury by regulation of RhoA signaling pathway, and may serve as a potential regime to improve percutaneous coronary intervention outcome. PMID:28327605

  4. 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...

  5. Cardioprotective effects of lixisenatide in rat myocardial ischemia-reperfusion injury studies

    PubMed Central

    2013-01-01

    Background Lixisenatide is a glucagon-like peptide-1 analog which stimulates insulin secretion and inhibits glucagon secretion and gastric emptying. We investigated cardioprotective effects of lixisenatide in rodent models reflecting the clinical situation. Methods The acute cardiac effects of lixisenatide were investigated in isolated rat hearts subjected to brief ischemia and reperfusion. Effects of chronic treatment with lixisenatide on cardiac function were assessed in a modified rat heart failure model after only transient coronary occlusion followed by long-term reperfusion. Freshly isolated cardiomyocytes were used to investigate cell-type specific mechanisms of lixisenatide action. Results In the acute setting of ischemia-reperfusion, lixisenatide reduced the infarct-size/area at risk by 36% ratio without changes on coronary flow, left-ventricular pressure and heart rate. Treatment with lixisenatide for 10 weeks, starting after cardiac ischemia and reperfusion, improved left ventricular end-diastolic pressure and relaxation time and prevented lung congestion in comparison to placebo. No anti-fibrotic effect was observed. Gene expression analysis revealed a change in remodeling genes comparable to the ACE inhibitor ramipril. In isolated cardiomyocytes lixisenatide reduced apoptosis and increased fractional shortening. Glucagon-like peptide-1 receptor (GLP1R) mRNA expression could not be detected in rat heart samples or isolated cardiomyocytes. Surprisingly, cardiomyocytes isolated from GLP-1 receptor knockout mice still responded to lixisenatide. Conclusions In rodent models, lixisenatide reduced in an acute setting infarct-size and improved cardiac function when administered long-term after ischemia-reperfusion injury. GLP-1 receptor independent mechanisms contribute to the described cardioprotective effect of lixisenatide. Based in part on these preclinical findings patients with cardiac dysfunction are currently being recruited for a randomized, double

  6. Mechanistic investigation of extracellular K+ accumulation during acute myocardial ischemia: a simulation study.

    PubMed

    Rodríguez, B; Ferrero, J M; Trénor, B

    2002-08-01

    In this study, we have used computer simulations to study the mechanisms of extracellular K+ accumulation during acute ischemia. A modified version of the Luo-Rudy phase II action potential model was used to simulate the electrical behavior of one ventricular myocyte during 14 min of simulated ischemia. Our results show the following: 1) only the integrated effect of activation of ATP-dependent K+ current, an ischemic Na+ inward current, and inhibition of Na(+)-K(+) pump activity in the absence of coronary flow replicates the biphasic time course of extracellular K+ concentration observed during acute ischemia; 2) the time to onset of the plateau phase and the plateau level value are determined by the rate of stimulation and by the rate of alteration of the three mechanisms. However, acidosis and reduction of extracellular volume produce only a slight anticipation of the plateau phase; and 3) cellular K+ loss is mainly due to an increase of K+ efflux via the time-independent K+ current and ATP-dependent K+ current rather than to a decrease of K+ influx.

  7. Prognostic value of dobutamine stress myocardial perfusion echocardiography in patients with known or suspected coronary artery disease and normal left ventricular function

    PubMed Central

    Mattoso, Angele A. A.; Tsutsui, Jeane M.; Kowatsch, Ingrid; Cruz, Vitória Y. L.; Sbano, João C. N.; Ribeiro, Henrique B.; Kalil Filho, Roberto; Porter, Thomas R.; Mathias, Wilson

    2017-01-01

    Objective We sought to determine the prognostic value of qualitative and quantitative analysis obtained by real-time myocardial perfusion echocardiography (RTMPE) in patients with known or suspected coronary artery disease (CAD). Background Quantification of myocardial blood flow reserve (MBFR) in patients with CAD using RTMPE has been demonstrated to further improve accuracy over the analysis of wall motion (WM) and qualitative analysis of myocardial perfusion (QMP). Methods From March 2003 to December 2008, we prospectively studied 168 patients with normal left ventricular function (LVF) who underwent dobutamine stress RTMPE. The replenishment velocity reserve (β) and MBFR were derived from RTMPE. Acute coronary events were: cardiac death, myocardial infarction and unstable angina with need for urgent coronary revascularization. Results During a median follow-up of 34 months (5 days to 6.9 years), 17 acute coronary events occurred. Abnormal β reserve in ≥2 coronary territories was the only independent predictor of events hazard ratio (HR) = 21, 95% CI = 4.5–99; p<0.001). Both, abnormal β reserve and MBFR added significant incremental value in predicting events over qualitative analysis of WM and MP (χ2 = 6.6 and χ2 = 24.6, respectively; p = 0.001 and χ2 = 6.6 and χ2 = 15.5, respectively; p = 0.012, respectively). When coronary angiographic data was added to the multivariate analysis model, β reserve remained the only predictor of events with HR of 21.0 (95% CI = 4.5–99); p<0.001. Conclusion Quantitative dobutamine stress RTMPE provides incremental prognostic information over clinical variables, qualitative analysis of WM and MP, and coronary angiography in predicting acute coronary events. PMID:28234978

  8. Role of systemic arterial pressure, heart rate, and derived variables in prediction of severity of myocardial ischemia during acute coronary occlusion in anesthetized dogs.

    PubMed

    Moore, P G; Reitan, J A; Kien, N D; White, D A; Safwat, A M

    1992-09-01

    The present study examined the postulate that the quotient of mean systemic arterial pressure and heart rate predicts the severity of myocardial ischemia during occlusion of the left anterior descending coronary artery. Studies were performed in open-chest fentanyl-anesthetized dogs before and during halothane (n = 8) or isoflurane (n = 8) anesthesia. The pressure-rate quotient (PRQ) decreased significantly in both groups during incremental increases in halothane or isoflurane to 68% and 57% of control values at 0.5 MAC and to 41% and 38% at 1.5 MAC for halothane and isoflurane, respectively. Myocardial lactate production was unchanged from the ischemic region, and no correlation between the PRQ and myocardial lactate production was observed. In contrast, heart rate correlated significantly (r = 0.376; P less than 0.05) with lactate production. The product of systolic systemic arterial pressure and heart rate (rate-pressure product) correlated with blood flow (r = 0.493; P less than 0.001) and with oxygen consumption (r = 0.571; P less than 0.001) in the normal myocardium. A weak correlation (r = 0.330; P less than 0.05) of rate-pressure product with myocardial lactate production from the ischemic region was observed. There were no correlations between the PRQ and myocardial lactate production from the ischemic region or indices of blood flow distribution (i.e., inner/outer ratio in the ischemic region or ischemic/normal ratio). The relationship of hemodynamic variables to measurements of regional myocardial metabolism was independent of background anesthetic agent of depth of anesthesia. The current data suggest that heart rate changes are weakly predictive of severity of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. 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

  10. Loss of quality adjusted days as a trial endpoint: effect of early thrombolytic treatment in suspected myocardial infarction. Grampion Region Early Anistreplase Trial (GREAT).

    PubMed Central

    Rawles, J; Light, J

    1993-01-01

    STUDY OBJECTIVES--(1) To measure the quality of life and the loss of quality adjusted days (QADS) after suspected acute myocardial infarction in patients who received thrombolytic treatment either at home or in hospital. (2) To compare the loss of QADS as a trial endpoint with the conventional endpoints of mortality and Q-wave infarction. DESIGN--Randomised double blind parallel group trial of anistreplase (30 U given intravenously) and placebo given either at home or in hospital. SETTING--Rural practices in Grampian admitting patients to teaching hospitals in Aberdeen. PATIENTS--A total of 311 patients with suspected acute myocardial infarction and no contraindications to thrombolytic treatment seen at home within four hours of the onset of symptoms. MEASUREMENTS AND MAIN RESULTS--Loss of quality adjusted days (QADS) in the first 100 days after suspected myocardial infarction (365 QADS = 1 QALY) was the main outcome measure. Compared with later administration in hospital, anistreplase at home resulted in a relative reduction of mortality of 49% (95% confidence interval 3.95%, 2p = 0.04), and a relative reduction of 26% in the proportion of survivors with infarction who had Q-waves (95% CI 7.44%, 2p = 0.007). During the 100 day follow up, the median loss of QADS was 25 for all patients. This loss was significantly greater in those who died than in survivors (65 v 18, 2p < 0.001), and in survivors with infarction than in survivors without infarction (26 v 13, 2p < 0.01). However, there was no significant difference in loss of QADS in those with infarction with or without Q-waves (29 v 21, NS), and the median loss of QADS was not significantly different in those who had thrombolytic treatment at home or in hospital (median difference 0, 95% CI -5, +4 QADS). CONCLUSIONS--Loss of QADS had two serious limitations as an outcome measure: it was less sensitive than mortality and it failed to reflect physiological benefit. Palliative treatment with no physiological effect

  11. [UCP2 and UCP3 gene expression, heart function and oxygen cost of myocardial work changes during aging and ischemia-reperfusion].

    PubMed

    Hoshovs'ka, Iu V; Lisovyĭ, O O; Shymans'ka, T V; Sahach, V F

    2009-01-01

    To examine the effects of ischemia/reperfusion on UCPs genes expression, heart function and oxygen cost of myocardial work, hearts of adult (6 mo) and old (24 mo) rats were perfused by Langendorf preparation and subjected to 20 min ischemia followed by 40 min reperfusion. Mitochondrial permeability transition due to ischemic stimuli was evaluated by release of mitochondrial factor (lambda 250 nm) which was previously shown as a marker of MPTP opening. Expression of UCPs was detected by reverse transcriptional polymerase chain reaction. Mitochondrial membrane potential (deltaphi(m)) and oxygen consumption in isolated heart mitochondria of adult and old rats were measured. It was shown that impaired function of aging rat hearts was accompanied with an increased oxygen cost of myocardial work and lower mitochondrial membrane potential compared with adult rats. Reperfusion disturbances of cardiodynamic, contractile activity of myocardium and noneffective oxygen utilization in early period of reperfusion were less intensive in aged hearts than in adult ones. Therefore, the levels of mRNA of UCP2 in aging hearts were higher and mRNA levels of UCP3 were tended to increase. At the same time ischemia/reperfusion increased the expression of UCP2 and UCP3 in adult myocardium: mRNA levels of UCPs were significantly higher that those in control, whereas there was no such effect in aging hearts. It is concluded that uncoupling proteins are implicated in the age-depended heart dysfunction and development of the pathological mechanisms during ischemia-reperfusion.

  12. Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway.

    PubMed

    Pei, Luo; Shaozhen, Hou; Gengting, Dong; Tingbo, Chen; Liang, Liu; Hua, Zhou

    2013-01-01

    Mechanisms for Panax ginseng's cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardized Panax ginseng extract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE's effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability of Panax ginseng to protect the heart from myocardial I/R injury.

  13. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

    PubMed Central

    Wu, Yang; Leng, Yan; Meng, Qingtao; Xue, Rui; Zhao, Bo; Zhan, Liying

    2017-01-01

    Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim. PMID:28191472

  14. Cardiogenic Shock From Global Myocardial Ischemia Induced by Simultaneous Multivessel Coronary Spasm

    PubMed Central

    Ahn, Jihye; Kim, Bo-sung; Park, Hyekyong; Park, Kyungil

    2012-01-01

    Coronary artery spasm is an uncommon, but well recognized, etiology for acute myocardial infarction. However, cardiogenic shock with myocardial infarction resulting from simultaneous multiple coronary artery spasm has been rarely reported, and not in Korea. Recently, we experienced such a case in a 50-year-old Korean man without previous diagnosis of variant angina. The patient, hospitalized for blood sugar control, developed severe chest pain accompanying ST-segment elevation in multiple leads. The patient immediately received cardiac catheterization because of cardiogenic shock. Coronary angiogram revealed the severe and simultaneous spasm of three major epicardial arteries, which was promptly relieved by an intracoronary administration of isosorbide dinitrate. This case highlights the need to rule out the potential mechanism of coronary spasm even in the most severe episodes of acute coronary syndrome. PMID:22787475

  15. 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.

  16. Protective effect of butin against ischemia/reperfusion-induced myocardial injury in diabetic mice: involvement of the AMPK/GSK-3β/Nrf2 signaling pathway

    PubMed Central

    Duan, Jialin; Guan, Yue; Mu, Fei; Guo, Chao; Zhang, Enhu; Yin, Ying; Wei, Guo; Zhu, Yanrong; Cui, Jia; Cao, Jinyi; Weng, Yan; Wang, Yanhua; Xi, Miaomiao; Wen, Aidong

    2017-01-01

    Hyperglycemia-induced reactive oxygen species (ROS) generation contributes to development of diabetic cardiomyopathy (DCM). This study was designed to determine the effect of an antioxidant butin (BUT) on ischemia/reperfusion-induced myocardial injury in diabetic mice. Myocardial ischemia/reperfusion (MI/R) was induced in C57/BL6J diabetes mice. Infarct size and cardiac function were detected. For in vitro study, H9c2 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Proteins levels were investigated by Western blotting. In diabetes MI/R model, BUT significantly alleviated myocardial infarction and improved heart function, together with prevented diabetes-induced cardiac oxidative damage. The expression of Nrf2, AMPK, AKT and GSK-3β were significantly increased by BUT. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the BUT’s prevention of I/R-induced myocardial injury. Inhibition of AMPK and AKT signaling by relative inhibitor or specific siRNA decreased the level of BUT-induced Nrf2 expression, and diminished the protective effects of BUT. The interplay relationship between GSK-3β and Nrf2 was also verified with relative overexpression and inhibitors. Our findings indicated that BUT protected against I/R-induced ROS-mediated apoptosis by upregulating the AMPK/Akt/GSK-3β pathway, which further activated Nrf2-regulated antioxidant enzymes in diabetic cardiomyocytes exposed to I/R. PMID:28128361

  17. Detection of myocardial ischemia by vessel-specific leads derived from the 12-lead electrocardiogram and its subsets.

    PubMed

    Horácek, B Milan; Mirmoghisi, Maryam; Warren, James W; Wagner, Galen S; Wang, John J

    2008-01-01

    Currently used electrocardiographic criteria for identifying patients with ST-elevation myocardial infarction (STEMI) perform with high specificity but low sensitivity. Our aim was to enhance ischemia-detection ability of conventional STEMI criteria based on 12-lead electrocardiogram (ECG) by adding new criteria using 3 vessel-specific leads (VSLs) derived from 12-lead ECG. Study data consisted of 12-lead ECGs acquired during 99 ischemic episodes caused by balloon inflation in, respectively, left anterior descending coronary artery (LAD; n = 35), right coronary artery (RCA; n = 47), and left circumflex coronary artery (LCx; n = 17). ST deviation was measured at J point in 12 standard leads, and for 3 VSLs, its value was derived from 12-lead ECG by using 8 independent predictor leads or just a pair of precordial leads combined with a pair of limb leads. Mean values of sensitivity (SE) and specificity (SP) of ischemia detection achieved with conventional STEMI vs VSL criteria were then obtained from bootstrap trials. We found that the detection of ischemic state by conventional criteria achieved the mean SE/SP of 60%/96% in the total set of ischemic episodes, 74%/97% in the LAD subgroup, 60%/94% in the RCA subgroup, and 36%/100% in the LCx subgroup. In comparison, the mean SE/SP values of VSLs derived from 8 independent leads of 12-lead ECG were, at 125-microV threshold, 76%(*)/96% in the total set, 91%(*)/97% in the LAD subgroup, 70%/94% in the RCA subgroup, and 71%(*)/100% in the LCx subgroup (with asterisk denoting a statistically significant increase). The mean SE/SP of VSLs derived from some of the 4-predictor lead sets (namely, those including lead V(3)) matched or exceeded values achieved by VSLs derived from 8 predictors; for instance, with predictor leads I, II, V(3), V(6) derived VSLs attained at 125-microV threshold the mean SE/SP of 80%(*)/95% in the total set, 91%(*)/97% in the LAD subgroup, 74%/92% in the RCA subgroup, and 71%(*)/100% in the LCx

  18. [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.

  19. Heart remodeling and ischemia-reperfusion arrhythmias linked to myocardial vitamin d receptors deficiency in obstructive nephropathy are reversed by paricalcitol.

    PubMed

    Diez, Emiliano Raúl; Altamirano, Liliana Berta; García, Isabel Mercedes; Mazzei, Luciana; Prado, Natalia Jorgelina; Fornes, Miguel Walter; Carrión, Fernando Darío Cuello; Zumino, Amira Zulma Ponce; Ferder, León; Manucha, Walter

    2015-03-01

    Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia-reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.

  20. Phosphodiesterase-5 Inhibitor, Tadalafil, Protects against Myocardial Ischemia/Reperfusion through Protein-Kinase G Dependent Generation of Hydrogen Sulfide

    PubMed Central

    Salloum, Fadi N.; Chau, Vinh Q.; Hoke, Nicholas N.; Abbate, Antonio; Varma, Amit; Ockaili, Ramzi A.; Toldo, Stefano; Kukreja, Rakesh C.

    2014-01-01

    Background Tadalafil is a novel long acting inhibitor of phosphodiesterase-5. Since cGMP-dependent protein kinase (PKG) signaling plays a key role in cardioprotection, we hypothesized that PKG activation with tadalafil would limit myocardial ischemia/reperfusion (I/R) injury and dysfunction. Additionally, we contemplated that cardioprotection with tadalafil is mediated by hydrogen sulfide (H2S) signaling in a PKG-dependent fashion. Methods and Results After baseline transthoracic echocardiography (TTE), adult ICR mice were injected i.p. with vehicle (10% DMSO) or tadalafil (1 mg/kg) with or without KT5823 (KT, PKG blocker, 1 mg/kg) or dl-propargylglycine [PAG, Cystathionine-γ-lyase (CSE, H2S-producing enzyme) blocker; 50 mg/kg] 1 h prior to coronary artery ligation for 30 min and reperfusion for 24 h, whereas C57BL-wild type and CSE-knockout mice were treated with either vehicle or tadalafil. After reperfusion, TTE was performed and hearts were collected for infarct size (IS) measurement using TTC staining. Survival was increased with tadalafil (95%) compared with control (65%, P<0.05). Infarct size was reduced with tadalafil (13.2±1.7%) compared to vehicle (40.6±2.5%; P<0.05). KT and PAG abolished tadalafil-induced protection (IS: 39.2±1% and 51.2±2.4%, respectively) similar to genetic deletion of CSE (47.2±5.1%). Moreover, tadalafil preserved fractional shortening (FS: 31±1.5%) compared to control (FS: 22±4.8%, P<0.05). Baseline FS was 44±1.7%. KT and PAG abrogated the preservation of LV function with tadalafil by a decline in FS to 17±1% and 23±3%, respectively. Compared to vehicle, myocardial H2S production was significantly increased with tadalafil and was abolished with KT. Conclusion PKG activation with tadalafil limits myocardial infarction and preserves LV function through H2S signaling. PMID:19752383

  1. Evaluation of nonperfused myocardial ischemia with MRI and an intravascular USPIO contrast agent in an ex vivo pig model.

    PubMed

    Bjerner, T; Ericsson, A; Wikström, G; Johansson, L; Nilsson, S; Ahlström, H; Hemmingsson, A

    2000-12-01

    The ultrasmall superparamagnetic iron oxide (USPIO) preparation NC100150 Injection (Clariscan; Nycomed Imaging, Oslo, Norway) was tested for its ability to delineate nonperfused myocardium under steady-state conditions. An experimental animal model of focal myocardial ischemia induced by ligation of the distal part of the left anterior descending artery was used. The contrast agent was administered in four doses: 0, 4, 8, and 12 mg Fe/kg body weight. Magnetic resonance examination ex vivo, including T1-, T2-, and T2*-weighted sequences, was performed. Nonperfused myocardium was determined by fluorescein. The best delineation of nonperfused myocardium was found with a T1-weighted inversion recovery/turbo spin-echo sequence and doses of 4 and 8 mg Fe/kg body weight, where 95% of the volume was discernible at the dose of 4 mg Fe/kg body weight. The results suggest that steady-state imaging by T1-weighted sequence with the use of NC100150 Injection to delineate nonperfused myocardium is feasible. J. Magn. Reson. Imaging 2000;12:866-872.

  2. 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

  3. Synthesis and biological evaluation of cyclic analogs of L-carnitine as potential agents in the treatment of myocardial ischemia

    SciTech Connect

    Woster, P.M.

    1987-01-01

    The purpose of this research was to synthesize a number of cyclic, rigid analogs of L-carnitine, having a variety of predetermined positional and stereochemical orientations, to be used as probes into the spatial and conformational requirements of the enzyme known as carnitine/acylcarnitine translocase. The ability of these analogs to serve as substrates for this enzyme was to be determined by assessing the degree to which they initiate efflux of {sup 14}C-L-carnitine from isolated heart mitochondria. Toward this end, synthesis of several such analogs was attempted, resulting in the isolation and characterization of 9 cyclic analogs of carnitine, 5 of which are previously unreported. Bioevaluation of these synthetic carnitine analogs was conducted in a previously described assay system. Rat heart mitochondria were isolated by differential centrifugation and prepared for the study by incubation with {sup 14}C-L-carnitine. Efflux of radiolabeled carnitine was then monitored in the presence of the compound being evaluated. This represents the first instance in which non-naturally occurring analogs of L-carnitine have been shown to undergo transport via this mitochondrial translocase, suggesting the possibility that cyclic carnitine analogs may find utility as agents in the treatment of myocardial ischemia.

  4. Effect of Salvianolic Acid b and Paeonol on Blood Lipid Metabolism and Hemorrheology in Myocardial Ischemia Rabbits Induced by Pituitruin

    PubMed Central

    Yang, Qian; Wang, Siwang; Xie, Yanhua; Wang, Jianbo; Li, Hua; Zhou, Xuanxuan; Liu, Wenbo

    2010-01-01

    The purpose of this study was to determine the therapeutic effect of salvianolic acid b and paeonol on coronary disease. The ischemia myocardial animal model is induced by administering pituitrin (20 μg·kg−1) intravenously via the abdominal vein. A combination of salvianolic acid b and paeonol (CSAP) (5, 10 and 15 mg/kg BW) was administrated to experimental rabbits. Biochemical indices were evaluated during six weeks of intervention. We found that the compound of salvianolic acid b and paeonol (5, 10 and 15 mg/kg BW) can markedly and dose-dependently reduce fibrinogen and malonaldehyde levels, increase the HDL level, improve blood viscosity and plasma viscosity in rabbits. In addition, the medicine can still reduce the ratio of NO/ET and the contents of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) in a dose-dependent manner. This study demonstrates that compound of salvianolic acid b and paeonol (5, 10 and 15 mg/kg BW) can improve the blood hemorrheology, decrease oxidative injury and repair the function of blood vessel endothelium, and subsequently prevent the development of Coronary disease. PMID:21152295

  5. [Metabonomic phenotype of "formula corresponding to pattern types" based on "qi and yin deficiency pattern" of myocardial ischemia rat model].

    PubMed

    Yan, Bei; A, Ji-Ye; Hao, Hai-Ping; Wang, Guang-Ji; Liu, Lin-Sheng; Zha, Wei-Bin; Zhang, Ying; Gu, Sheng-Hua

    2011-08-01

    In order to explore the scientific connotation of "Fangzhengduiying (formula corresponding to pattern types)", "Qiyinliangxuzheng (Qi and Yin deficiency pattern)" of myocardial ischemia rat model and GC-TOF/MS based metabonomic method were used for comparing the effects of Sheng-mai injection, Salvia injection and propranolol in the present study. After data processing and pattern recognition, Sheng-mai injection showed better efficacy than the other two drugs in accordance with not only visual observation from PLS-DA scores plots but also the number of abnormal endogenous compounds restored to the normal level. Further studies showed that Sheng-mai injection could normalize the level of plasma endothelin-1, the index related to cardiovascular diseases and sleep disorders, which verified the results of metabonomics. Finally, the regulated metabolites and related metabolic pathways were analyzed, and it was supposed that the effects of Sheng-mai injection involved in the alternation of energy metabolism, lipid metabolism, amino acids metabolism, and so on. These findings provided scientific evidence to Shengmai "Fang" used for "Qi and Yin deficiency pattern" correspondingly, indicating that metabonomics has great potential in traditional Chinese medical research, which provides a novel approach and way to modernization of traditional Chinese medicine.

  6. Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes

    PubMed Central

    Zhao, Dajun

    2017-01-01

    Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD). PMID:28298952

  7. Attenuated NOx responses and myocardial ischemia, a possible risk for structural vascular disease in African men: the SABPA study.

    PubMed

    Uys, A S; Malan, L; van Rooyen, J M; Steyn, H S; Reimann, M; Ziemssen, T

    2014-07-01

    Chronically elevated blood pressure has been associated with impaired NO-mediated vasodilation and structural vascular disease risk. This study aimed to determine whether significant associations exist regarding NO metabolite (NOx) responses, cardiovascular function and structural vascular disease in a cohort of African and Caucasian men. The study included 81 African and 94 Caucasian male teachers stratified via median splits into low and high NOx ethnic groups. Ambulatory blood pressure, electrocardiogram monitoring and ultrasound carotid intima-media thickness (CIMT) images were obtained. Cardiovascular measurements and fasting blood for NOx responses were measured during rest and on challenging the cardiovascular system with the Stroop colour-word conflict test. African men displayed significantly higher resting NOx as well as higher number of 24 h silent ischemic events than their Caucasian counterparts. Low NOx African men displayed enhanced α-adrenergic and ECG ST segment depression acute mental stress responses as well as 24 h silent ischemic events associated with CIMT (adjusted R(2) = 0.47; β = 0.25; confidence interval (CI) = 0.13, 0.41). African men demonstrated a vulnerable cardiovascular profile. Novel findings revealed α-adrenergic-driven blood pressure responses and less NO bioavailability during acute stress. The association between myocardial ischemia and CIMT in this group emphasized their risk for future coronary artery disease and cerebrovascular events.

  8. 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.

  9. Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury by down-regulating the HMGB1-TLR4-MyD88-NF-кB signaling pathway

    PubMed Central

    Zhang, Juan; Meng, Xiao-wen; Ji, Fu-hai

    2017-01-01

    Aims To investigate whether dexmedetomidine (DEX) preconditioning could alleviate the inflammation caused by myocardial ischemia/reperfusion (I/R) injury by reducing HMGB1-TLR4-MyD88-NF-кB signaling. Methods Seventy rats were randomly assigned into five groups: sham group, myocardial I/R group (I/R), DEX+I/R group (DEX), DEX+yohimbine+I/R group (DEX/YOH), and yohimbine+I/R group (YOH). Animals were subjected to 30 min of ischemia induced by occluding the left anterior descending artery followed by 120 min of reperfusion. Myocardial infarct size and histological scores were evaluated. The levels of IL-6 and TNF-α in serum and myocardium were quantified by enzyme-linked immunosorbent assay, and expression of HMGB1, TLR4, MyD88, IκB and NF-κB in the myocardial I/R area were determined with Western blot and immunocytochemistry. Results Myocardial infarct sizes, histological scores, levels of circulating and myocardial IL-6 and TNF-α, the expression of HMGB1, TLR4, MyD88 and NF-κB, and the degradation of IκB were significantly increased in the I/R group compared with the sham group (P<0.01). DEX preconditioning significantly reduced the myocardial infarct size and histological scores (P<0.01 vs. I/R group). Similarly, the serum and myocardial levels of IL-6 and TNF-α, the expression of HMGB1, TLR4, MyD88 and NF-κB, and the degradation of IκB were significantly reduced in the DEX group (P<0.01 vs. I/R group). These effects were partly reversed by yohimbine, a selective α2-adrenergic receptor antagonist, while yohimbine alone had no significant effect on any of the above indicators. Conclusion DEX preconditioning reduces myocardial I/R injury in part by attenuating inflammation, which may be attributed to the downregulation of the HMGB1-TLR4-MyD88-NF-кB signaling pathway mediated by the α2-adrenergic receptor activation. PMID:28222157

  10. Myocardial ischemia-reperfusion enhances transcriptional expression of endothelin-1 and vasoconstrictor ETB receptors via the protein kinase MEK-ERK1/2 signaling pathway in rat

    PubMed Central

    Kruse, Lars Schack; Berchtold, Lukas Adrian; Grell, Anne-Sofie; Warfvinge, Karin; Edvinsson, Lars

    2017-01-01

    Background Coronary artery remodelling and vasospasm is a complication of acute myocardial ischemia and reperfusion. The underlying mechanisms are complex, but the vasoconstrictor peptide endothelin-1 is suggested to have an important role. This study aimed to determine whether the expression of endothelin-1 and its receptors are regulated in the myocardium and in coronary arteries after experimental ischemia-reperfusion. Furthermore, we evaluated whether treatment with a specific MEK1/2 inhibitor, U0126, modified the expression and function of these proteins. Methods and findings Sprague-Dawley rats were randomly divided into three groups: sham-operated, ischemia-reperfusion with vehicle treatment and ischemia-reperfusion with U0126 treatment. Ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes followed by reperfusion. U0126 was administered before ischemia and repeated 6 hours after start of reperfusion. The contractile properties of isolated coronary arteries to endothelin-1 and sarafotoxin 6c were evaluated using wire-myography. The gene expression of endothelin-1 and endothelin receptors were measured using qPCR. Distribution and localization of proteins (pERK1/2, prepro-endothelin-1, endothelin-1, and endothelin ETA and ETB receptors) were analysed by Western blot and immunohistochemistry. We found that pERK1/2 was significantly augmented in the ischemic area 3 hours after ischemia-reperfusion; this correlated with increased ETB receptor and ET-1 gene expressions in ischemic myocardium and in coronary arteries. ETB receptor-mediated vasoconstriction was observed to be increased in coronary arteries 24 hours after ischemia-reperfusion. Treatment with U0126 reduced pERK1/2, expression of ET-1 and ETB receptor, and ETB receptor-mediated vasoconstriction. Conclusions These findings suggest that the MEK-ERK1/2 signaling pathway is important for regulating endothelin-1 and ETB receptors in myocardium and coronary arteries

  11. The impact of screening for asymptomatic myocardial ischemia in individuals with type 2 diabetes.

    PubMed

    Chyun, Deborah A; Katten, Deborah M; Melkus, Gail D; Talley, Sandra; Davey, Janice A; Wackers, Frans J Th

    2006-01-01

    Little is known about factors that contribute to either emotional or behavior outcomes following screening for coronary artery disease (CAD). The purpose of this prospective study was to explore these outcomes, along with potentially contributing factors in individuals enrolled in a screening trial for asymptomatic CAD. Included were 47 subjects with type 2 diabetes. Data were collected at study baseline and 3 and 6 months following entry by self-administered questionnaires and telephone follow-up. Emotional outcomes (quality of life and anxiety) tended to improve in those who underwent more aggressive screening with myocardial perfusion imaging, as well as in those who discussed the results of laboratory tests with their providers. Lower levels of diabetes competence and higher levels of controlled motivation for diet were associated with poorer emotional outcomes. Improvements in CAD risk factor behaviors were not observed.

  12. Comparison of Different Adult Stem Cell Types for Treatment of Myocardial Ischemia

    PubMed Central

    van der Bogt, Koen E.A.; Sheikh, Ahmad Y.; Schrepfer, Sonja; Hoyt, Grant; Cao, Feng; Ransohoff, Katie; Swijnenburg, Rutger-Jan; Pearl, Jeremy; Fischbein, Michael; Contag, Christopher H.; Robbins, Robert C.; Wu, Joseph C.

    2013-01-01

    Introduction A comparative analysis of the efficacy of different cell candidates for the treatment of heart disease remains to be described. This study is designed to evaluate the therapeutic efficacy of 4 cell types in a murine model of myocardial infarction. Methods Bone marrow mononuclear cells (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb) and fibroblasts (Fibro) were isolated from male L2G transgenic mice (FVB background) that constitutively express firefly luciferase (Fluc) and green fluorescence protein (GFP). Cells were characterized by flow cytometry, bioluminescence imaging (BLI), and luminometry. Female FVB mice (n=60) underwent LAD ligation and were randomized into 5 groups to intramyocardially receive one cell type (5 × 105) or PBS as control. Cell survival was measured in vivo by BLI and ex vivo by TaqMan PCR at week 6. Cardiac function was assessed by echocardiography and invasive hemodynamic measurements were made at week 6. Results Fluc expression correlated with the cell number in all groups (r2 >0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and Fibro within 3 weeks after transplantation. By contrast, cardiac signals were still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01). Echocardiography showed significant preservation of fractional shortening in the MN group compared to controls (P<0.05). Measurements of left ventricular end-systolic/diastolic volumes revealed that the least amount of ventricular dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of MN, although there was no evidence of transdifferentiation by donor MN into cardiomyocytes. Conclusion This is the first study to directly compare a variety of cell candidates for myocardial therapy. Compared to MSC, SkMB, and Fibro, our results suggest that MN cells exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function. PMID:18824743

  13. MicroRNAs in myocardial ischemia: identifying new targets and tools for treating heart disease. New frontiers for miR-medicine.

    PubMed

    Sala, V; Bergerone, S; Gatti, S; Gallo, S; Ponzetto, A; Ponzetto, C; Crepaldi, T

    2014-04-01

    MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine.

  14. Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via activating AMPK and PI3K-Akt signaling in diabetic rats.

    PubMed

    Chen, Keke; Li, Guohua; Geng, Fenghao; Zhang, Zhao; Li, Jiani; Yang, Min; Dong, Ling; Gao, Feng

    2014-06-01

    Diabetes increases the risk of cardiovascular diseases. Berberine (BBR), an isoquinoline alkaloid used in Chinese medicine, exerts anti-diabetic effect by lowering blood glucose and regulating lipid metabolism. It has been reported that BBR decreases mortality in patients with chronic congestive heart failure. However, the molecular mechanisms of these beneficial effects are incompletely understood. In the present study, we sought to determine whether BBR exerts cardioprotective effect against ischemia/reperfusion (I/R) injury in diabetic rats and the underlying mechanisms. Male Sprague-Dawley rats were injected with low dose streptozotocin and fed with a high-fat diet for 12 weeks to induce diabetes. The diabetic rats were intragastrically administered with saline or BBR (100, 200 and 400 mg/kg/d) starting from week 9 to 12. At the end of week 12, all rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion. BBR significantly improved the recovery of cardiac systolic/diastolic function and reduced myocardial apoptosis in diabetic rats subjected to myocardial I/R. Furthermore, in cultured neonatal rat cardiomyocytes, BBR (50 μmol/L) reduced hypoxia/reoxygenation-induced myocardial apoptosis, increased Bcl-2/Bax ratio and decreased caspase-3 expression, together with enhanced activation of PI3K-Akt and increased adenosine monophosphate-activated protein kinase (AMPK) and eNOS phosphorylation. Pretreatment with either PI3K/Akt inhibitor wortmannin or AMPK inhibitor Compound C blunted the anti-apoptotic effect of BBR. Our findings demonstrate that BBR exerts anti-apoptotic effect and improves cardiac functional recovery following myocardial I/R via activating AMPK and PI3K-Akt-eNOS signaling in diabetic rats.

  15. 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

  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. Peroxisome proliferator-activated receptor γ (PPARγ) mediates the protective effect of quercetin against myocardial ischemia-reperfusion injury via suppressing the NF-κB pathway

    PubMed Central

    Liu, Xinyu; Yu, Zhangjie; Huang, Xian; Gao, Yi; Wang, Xiuzhi; Gu, Jianmin; Xue, Song

    2016-01-01

    Quercetin plays an important role in myocardial ischemia and reperfusion injury (IRI). However, the underlying mechanism for the protective effect of quercetin is largely unclear. In this study, we explored the protected effects of quercetin against myocardial IRI and its molecular mechanisms. Quercetin, GW9962 (PPARγ antagonist) or PPARγ-siRNA was administered alone or in combination prior to myocardial IRI in mice or to hypoxia and reoxygenation (H/R) treatment in H9C2 cells. Infarct size was evaluated by TTC staining after reperfusion. Myocardial injury was assessed by the serum levels of AST, CK-MB, cardiac troponin T (cTnT) and LDH. Cardiac function was measured by echocardiography. Oxidative stress injury was evaluated by analyses of inducible nitric oxide synthase (iNOS), MDA, SOD and glutathione peroxidase (GSH-PX) levels and by reactive oxygen species (ROS) detection. Myocardium apoptosis was evaluated by TUNEL staining, cleaved caspase-3 and Annexin V/PI detection. Moreover, activation of the NF-κB pathway was reflected by phosphorylation of IκB (p-IκB) and nuclear translocation of NF-κB p65. We reported that pretreatment of quercetin significantly improved cardiac function, diminished myocardial injury and reduced the infarct size. Myocardium oxidative damage and apoptosis were remarkably improved by quercetin treatment in vivo and in vitro. Quercetin also suppressed the activation of the NF-κB pathway induced by myocardial IRI. GW9662 or PPARγ knockdown partially attenuated these cardioprotective effects of quercetin during myocardial IRI. In conclusion, our findings suggest that quercetin ameliorated IRI-induced heart damage via PPARγ activation and the underlying mechanism might involve the inhibition of NF-κB pathway by PPARγ activation. PMID:28077993

  18. Novel transient outward and ultra-rapid delayed rectifier current antagonist, AVE0118, protects against ventricular fibrillation induced by myocardial ischemia.

    PubMed

    Billman, George E; Kukielka, Monica

    2008-04-01

    AVE0118 is a novel drug that blocks the transient outward current (Ito), the ultra rapid component of the delayed rectifier current (IKur), and the acetylcholine dependent potassium channel (IKach). The latter 2 channels are more abundant in atrial tissue. It is possible that AVE0118 could reduce regional differences in repolarization and thereby prevent malignant arrhythmias provoked by ischemia. To test this hypothesis, ventricular fibrillation was induced by a 2-minute occlusion of the left circumflex coronary artery during the last min of exercise in dogs with healed myocardial infarctions (n = 9). On a subsequent day, this exercise plus ischemia test was repeated after pretreatment with AVE0118 (1.0 mg/kg, IV). AVE0118 did not change QTc (Van de Water's correction) interval [245 +/- 6.0 ms (control) versus 242 +/- 2.3 ms (AVE)] and attenuated the dispersion of repolarization as measured by the duration of the descending portion of the T wave (Tpeak - Tend) induced by ischemia [ischemic changes: +11.1 +/- 2.4 ms (no drug) versus +2.2 +/- 3.7 ms (AVE)]. AVE0118 also significantly reduced the incidence of ventricular fibrillation, protecting 7 of 9 animals. Thus, AVE0118 abolished ischemically induced repolarization abnormalities and prevented malignant arrhythmias induced by ischemia without altering QTc interval.

  19. 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%.

  20. Dysferlin Mediates the Cytoprotective Effects of TRAF2 Following Myocardial Ischemia Reperfusion Injury

    PubMed Central

    Tzeng, Huei‐Ping; Evans, Sarah; Gao, Feng; Chambers, Kari; Topkara, Veli K.; Sivasubramanian, Natarajan; Barger, Philip M.; Mann, Douglas L.

    2014-01-01

    Background We have demonstrated that tumor necrosis factor (TNF) receptor‐associated factor 2 (TRAF2), a scaffolding protein common to TNF receptors 1 and 2, confers cytoprotection in the heart. However, the mechanisms for the cytoprotective effects of TRAF2 are not known. Methods/Results Mice with cardiac‐restricted overexpression of low levels of TRAF2 (MHC‐TRAF2LC) and a dominant negative TRAF2 (MHC‐TRAF2DN) were subjected to ischemia (30‐minute) reperfusion (60‐minute) injury (I/R), using a Langendorff apparatus. MHC‐TRAF2LC mice were protected against I/R injury as shown by a significant ≈27% greater left ventricular (LV) developed pressure after I/R, whereas mice with impaired TRAF2 signaling had a significantly ≈38% lower LV developed pressure, a ≈41% greater creatine kinase (CK) release, and ≈52% greater Evans blue dye uptake after I/R, compared to LM. Transcriptional profiling of MHC‐TRAF2LC and MHC‐TRAF2DN mice identified a calcium‐triggered exocytotic membrane repair protein, dysferlin, as a potential cytoprotective gene responsible for the cytoprotective effects of TRAF2. Mice lacking dysferlin had a significant ≈39% lower LV developed pressure, a ≈20% greater CK release, and ≈29% greater Evans blue dye uptake after I/R, compared to wild‐type mice, thus phenocopying the response to tissue injury in the MHC‐TRAF2DN mice. Moreover, breeding MHC‐TRAF2LC onto a dysferlin‐null background significantly attenuated the cytoprotective effects of TRAF2 after I/R injury. Conclusion The study shows that dysferlin, a calcium‐triggered exocytotic membrane repair protein, is required for the cytoprotective effects of TRAF2‐mediated signaling after I/R injury. PMID:24572254

  1. Myocardial ischemia as presenting manifestation of IgG4-related disease: a case-based review.

    PubMed

    Delgado-García, Guillermo; Sánchez-Salazar, Sergio; Rendón-Ramírez, Erick; Castro-Medina, Mario; Sáenz-Ibarra, Bárbara; Barboza-Quintana, Álvaro; Loredo-Alanis, María Azalea; Hernández-Barajas, David; Galarza-Delgado, Dionicio

    2016-11-01

    Coronary involvement in IgG4-related disease (IgG4-RD) has been scarcely reported, and myocardial ischemia as its presenting feature is even rarer. Here, we describe an additional case with novel and relevant observations. The patient was a previously healthy, middle-aged woman who presented to the clinic with new-onset typical angina. One tumefactive lesion encasing the left anterior descending artery was found during her workup. The most common underlying malignancies with secondary cardiac involvement were rationally ruled out. Symptoms persisted despite medical treatment, and she was therefore referred to surgery. Tumor excision was successfully performed, and she received coronary bypass grafting. IgG4-related coronary arteritis with pseudotumor formation was subsequently diagnosed following the comprehensive diagnostic criteria. This condition was clinically classified as active and circulating plasmablasts were found to be increased (5480/mL), even when these were determined 38 days after surgery. A PET/CT revealed an additional hypermetabolic lymph node. She was therefore treated with rituximab as induction therapy (two 1000 mg doses, administered 15 days apart). Three months later, her disease remained clinically inactive. Circulating plasmablasts were repeated and these had dropped to 0/mL. We thereafter review the current and pertinent literature on the topic, emphasizing the previous cases with similar presenting features (n = 7). We lastly suggest that IgG4-RD should be part of the differential diagnosis of any patient with tumefactive lesions surrounding the coronary arteries, since it can initially presented as sudden cardiac death.

  2. 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

  3. Ventricular premature beats on Holter monitoring in patients admitted with chest pain, in whom acute myocardial infarction is not confirmed. The prognostic value and relationship to scars or ischemia on thallium-201 scintigraphy

    SciTech Connect

    Madsen, J.K.; Sorensen, J.N.; Kromann-Andersen, B.; Kjeldgaard, K.M.; Christoffersen, K.; van Duijvendijk, K.; Reiber, J.H.

    1987-05-01

    Ambulatory 24-h Holter monitoring was carried out in 198 patients who had been admitted because of suspected acute myocardial infarction (AMI) due to chest pain, but in whom AMI was not confirmed. During a follow-up period of 12-24 months (median 14 months) 16 cardiac events (i.e., nonfatal AMI or cardiac death) occurred. Ventricular premature beats (VPBs) were found in 65.2% of the patients, complex VPBs in 28.8%. Pairs of VPBs which were seen in 10.0% of the patients were the only important type of VPBs significantly related to an impaired prognosis. Thallium-201 scintigraphy was performed in 144 of the patients. VPBs were significantly related to scar formation (i.e., to permanent defects, but not to ischemia, specifically, to transient defects). It is concluded that ventricular arrhythmias in this patient category indicate presence of chronic ischemic heart disease, and that pairs of VPBs seem to identify patients at risk for cardiac events.

  4. 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

  5. Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury.

    PubMed

    Takaya, Norihide; Katoh, Youichi; Iwabuchi, Kazuhisa; Hayashi, Ichiro; Konishi, Hakuoh; Itoh, Seigo; Okumura, Ko; Ra, Chisei; Nagaoka, Isao; Daida, Hiroyuki

    2005-12-01

    Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor gamma-chain (FcR gamma) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcRgamma. To examine the functional significance of platelet FcR gamma/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcRgamma-deficient (FcRgamma(-/-)) mice that lack GPVI. The infarct size was significantly smaller in FcRgamma(-/-) mice subjected to occlusion and reperfusion of the coronary artery than in control FcR gamma(+/+) mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR gamma(-/-) mice. Platelet Syk was scarcely activated in the FcR gamma(-/-) mice after myocardial ischemia and reperfusion, but significantly activated in the FcR gamma(+/+) mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcRgamma(-/-) mice than in the FcRgamma(+/+) mice. These results suggest that the collagen-induced activation of platelets through the FcR gamma plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRgamma and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.

  6. The effects of oral nafazatrom (= BAY g 6575) on canine coronary artery thrombosis and myocardial ischemia.

    PubMed

    Fiedler, V B

    1983-01-01

    The in-vivo effects of the new antithrombotic compound nafazatrom on experimental thrombosis of the left circumflex coronary artery, on hemodynamics and on ultimate infarct size were studied in pentobarbital-anesthetized, open-chest dogs. Coronary artery thrombosis was induced by low amperage stimulation (150 microA, DC for 6 hr) of the circumflex artery intimal lining. The effects of oral pretreatment of 1%-Tylose suspension as drug diluent and 5 mg/kg nafazatrom plus vehicle were determined. Both agents were administered twice a day before onset of current stimulation. In the drug vehicle group, coronary thrombosis caused severe hemodynamic alterations, e.g. blood pressure and left ventricular pressure decrease, as well as reduction in the LV dP/dtmax associated with increases in end-diastolic filling pressure and heart rate. Time to coronary artery occlusion was delayed by nafazatrom (5.2 +/- 1.1 vs 3.1 +/- 0.4 hr, p less than 0.05). Smaller blood pressure and LV dP/dtmax reductions and minor heart rate and filling pressure increases around the time of thrombus formation suggested cardioprotection with the drug. Smaller R wave changes and S-T segment elevation indicated minor ischemia at the time of occlusive coronary artery occlusion in nafazatrom-treated hearts (24 +/- 0.5 vs 72 +/- 7% ST segment elevation, p less than 0.01). Thrombus wet weight was 18.4 +/- 2.6 mg in the nafazatrom group, but 63.7 +/- 3.1 mg in controls (p less than 0.01). Thus, ultimate infarct size was smaller in nafazatrom-treated hearts as related to left ventricular mass (8.4 +/- 1.4 vs 32.3 +/- 3.1%, p less than 0.02) or to the occluded artery perfusion area at risk for infarction (16 +/- 3.4 vs 53 +/- 6.2%, p less than 0.05). No ex-vivo effect of nafazatrom on collagen-induced platelet aggregation was observed. These results may indicate efficacy of the drug in prevention of acute coronary artery disease as one cause of ischemic jeopardy of the myocardium and/or therapeutic value in

  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.

  8. Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin.

    PubMed

    Yu, Liming; Liang, Hongliang; Dong, Xiaochao; Zhao, Guolong; Jin, Zhenxiao; Zhai, Mengen; Yang, Yang; Chen, Wensheng; Liu, Jincheng; Yi, Wei; Yang, Jian; Yi, Dinghua; Duan, Weixun; Yu, Shiqiang

    2015-10-01

    Diabetes mellitus (DM) increases myocardial oxidative stress and endoplasmic reticulum (ER) stress. Melatonin confers cardioprotective effect by suppressing oxidative damage. However, the effect and mechanism of melatonin on myocardial ischemia-reperfusion (MI/R) injury in type 2 diabetic state are still unknown. In this study, we developed high-fat diet-fed streptozotocin (HFD-STZ) rat, a well-known type 2 diabetic model, to evaluate the effect of melatonin on MI/R injury with a focus on silent information regulator 1 (SIRT1) signaling, oxidative stress, and PERK/eIF2α/ATF4-mediated ER stress. HFD-STZ treated rats were exposed to melatonin treatment in the presence or the absence of sirtinol (a SIRT1 inhibitor) and subjected to MI/R surgery. Compared with nondiabetic animals, type 2 diabetic rats exhibited significantly decreased myocardial SIRT1 signaling, increased apoptosis, enhanced oxidative stress, and ER stress. Additionally, further reduced SIRT1 signaling, aggravated oxidative damage, and ER stress were found in diabetic animals subjected to MI/R surgery. Melatonin markedly reduced MI/R injury by improving cardiac functional recovery and decreasing myocardial apoptosis in type 2 diabetic animals. Melatonin treatment up-regulated SIRT1 expression, reduced oxidative damage, and suppressed PERK/eIF2α/ATF4 signaling. However, these effects were all attenuated by SIRT1 inhibition. Melatonin also protected high glucose/high fat cultured H9C2 cardiomyocytes against simulated ischemia-reperfusion injury-induced ER stress by activating SIRT1 signaling while SIRT1 siRNA blunted this action. Taken together, our study demonstrates that reduced cardiac SIRT1 signaling in type 2 diabetic state aggravates MI/R injury. Melatonin ameliorates reperfusion-induced oxidative stress and ER stress via activation of SIRT1 signaling, thus reducing MI/R damage and improving cardiac function.

  9. Omega-3 Status and the Relationship between Plasma Asymmetric Dimethylarginine and Risk of Myocardial Infarction in Patients with Suspected Coronary Artery Disease

    PubMed Central

    Borgeraas, Heidi; Strand, Elin; Ringdal Pedersen, Eva; Dierkes, Jutta; Ueland, Per Magne; Seifert, Reinhard; Wilberg, Eirik Rebnord; Bohov, Pavol; Berge, Rolf K.; Nilsen, Dennis W. T.; Nygård, Ottar

    2012-01-01

    Background. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. A previous rat study revealed an ADMA lowering effect following treatment with omega-3 polyunsaturated fatty acids (n-3 PUFAs). We sought to examine if an association between plasma ADMA and risk of acute myocardial infarction (AMI) was modified by serum n-3 PUFA status. Methods. The cohort included 1364 patients who underwent coronary angiography for suspected coronary artery disease in 2000-2001. Fatal and nonfatal AMI events were registered until December 31, 2006. Risk associations with AMI were estimated across ADMA quartiles (linear trend) and the upper decile. Results. No association between concentration of any n-3 PUFA and ADMA was observed. Only ADMA levels in upper decile were significantly associated with AMI with a multivariate adjusted hazard ratio (HR) (95% confidence interval) versus the rest of the population of 2.11 (1.34, 3.32). The association was strengthened among patients with below median levels of α-linolenic acid (ALA) (HR 3.12 (1.64, 5.93)), but was only influenced by longer chain n-3 PUFA after additional adjustments for HbA1c, estimated glomerular filtration rate, and hypercholesterolemia. Conclusions. The association of ADMA with risk of AMI is influenced by serum n-3 PUFA and particularly ALA. PMID:23346455

  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. 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.

  12. Inhibition of CD34+ cell migration by matrix metalloproteinase-2 during acute myocardial ischemia, counteracted by ischemic preconditioning

    PubMed Central

    Lukovic, Dominika; Zlabinger, Katrin; Gugerell, Alfred; Spannbauer, Andreas; Pavo, Noemi; Mandic, Ljubica; Weidenauer, Denise T.; Kastl, Stefan; Kaun, Christoph; Posa, Aniko; Sabdyusheva Litschauer, Inna; Winkler, Johannes; Gyöngyösi, Mariann

    2017-01-01

    Background. Mobilization of bone marrow-origin CD34+ cells was investigated 3 days (3d) after acute myocardial infarction (AMI) with/without ischemic preconditioning (IP) in relation to stromal-derived factor-1 (SDF-1α)/ chemokine receptor type 4 (CXCR4) axis, to search for possible mechanisms behind insufficient cardiac repair in the first days post-AMI.  Methods. Closed-chest reperfused AMI was performed by percutaneous balloon occlusion of the mid-left anterior descending (LAD) coronary artery for 90min, followed by reperfusion in pigs. Animals were randomized to receive either IP initiated by 3x5min cycles of re-occlusion/re-flow prior to AMI (n=6) or control AMI (n=12). Blood samples were collected at baseline, 3d post-AMI, and at 1-month follow-up to analyse chemokines and mobilized CD34+ cells. To investigate the effect of acute hypoxia, SDF-1α and matrix metalloproteinase (MMP)-2 in vitro were assessed, and a migration assay of CD34+ cells toward cardiomyocytes was performed.  Results. Reperfused AMI induced significant mobilisation of CD34+ cells (baseline: 260±75 vs. 3d: 668±180; P<0.001) and secretion of MMP-2 (baseline: 291.83±53.40 vs. 3d: 369.64±72.89; P=0.011) into plasma, without affecting the SDF-1α concentration. IP led to the inhibition of MMP-2 (IP: 165.67±47.99 vs. AMI: 369.64±72.89; P=0.004) 3d post-AMI, accompanied by increased release of SDF-1α (baseline: 23.80±12.36 vs. 3d: 45.29±11.31; P=0.05) and CXCR4 (baseline: 0.59±0.16 vs. 3d: 2.06±1.42; P=0.034), with a parallel higher level of mobilisation of CD34+ cells (IP: 881±126 vs. AMI: 668±180; P=0.026), compared to non-conditioned AMI. In vitro, CD34+ cell migration toward cardiomyocytes was enhanced by SDF-1α, which was completely abolished by 90min hypoxia and co-incubation with MMP-2.  Conclusions. Non-conditioned AMI induces MMP-2 release, hampering the ischemia-induced increase in SDF-1α and CXCR4 by cleaving the SDF-1α/CXCR4 axis, with diminished mobilization of

  13. Effects of antagonists for endothelin ET(A) and ET(B) receptors on coronary endothelial and myocardial function after ischemia-reperfusion in anesthetized goats.

    PubMed

    Climent, Belén; Fernández, Nuria; García-Villalón, Angel Luis; Monge, Luis; Sánchez, Ana; Diéguez, Godofredo

    2006-05-01

    To compare the effects of antagonists for endothelin ET(A) and ET(B) receptors on the action of ischemia-reperfusion on endothelial and myocardial function, 30 min of partial or total occlusion followed by 60 min of reperfusion of the left circumflex coronary artery was induced in anesthetized goats treated with intracoronary administration of saline (vehicle), BQ-123 (endothelin ET(A) receptors antagonist) or BQ-788 (endothelin ET(B) receptors antagonist). During reperfusion after partial occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline or BQ-788, and they normalized after BQ-123. In these three groups of animals, the coronary effects of acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) during reperfusion were as under control. During reperfusion after total occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline, and they normalized after BQ-123 or BQ-788. In these three groups of animals, the coronary effects of acetylcholine but not those of sodium nitroprusside during reperfusion were decreased after saline, and they reversed after BQ-123 or BQ-788. Therefore, selective antagonists of endothelin ET(B) and ET(A) receptors may produce similar protection of coronary vasculature and myocardium against reperfusion after severe ischemia. Selective antagonists of endothelin ET(B) receptors, contrarily to those of endothelin ET(A) receptors, may be ineffective to protect coronary vasculature and myocardium against reperfusion after mild ischemia.

  14. Cardio-protective effects of combined l-arginine and insulin: Mechanism and therapeutic actions in myocardial ischemia-reperfusion injury.

    PubMed

    Venardos, Kylie M; Rajapakse, Niwanthi W; Williams, David; Hoe, Louise S; Peart, Jason N; Kaye, David M

    2015-12-15

    Reduced nitric oxide (NO) bioavailability plays a central role in the pathogenesis of myocardial ischemia-reperfusion injury (I-R), and reduced l-arginine transport via cationic amino acid transporter-1 is a key contributor to the reduced NO levels. Insulin can increase NO levels by increasing the transport of its substrate l-arginine but insulin alone exerts minimal cardiac protection in I-R. We hypothesized that combined insulin and l-arginine may provide cardioprotective effects in the setting of myocardial I-R. The effect of supplemental insulin, l-arginine and the combination was examined in cardiomyocytes exposed to hypoxia/reoxygenation and in isolated perfused mouse hearts undergoing ischemia/reperfusion. When compared to controls, cardiomyocytes treated upon reoxygenation with 1nM insulin+1mM l-arginine exhibited significant (all P<0.05) improvements in NO generation and mitochondrial membrane potential, with a concomitant fall in reactive oxygen species production and LDH release. Insulin also increased l-arginine uptake following hypoxia-reoxygenation (P<0.05; n=4-6). In langendorff perfused isolated mouse hearts, combined l-arginine-insulin treatment upon reperfusion significantly (all P<0.05; n=9-11) improved recovery of left ventricular developed pressure, rate pressure product and end diastolic pressure following ischemia, independent of any changes in post-ischemic coronary flow, together with significantly lower LDH release. The observed improvements were greater than l-arginine or insulin treatment alone. In isolated cardiomyocytes (n=3-5), 1nM insulin caused cationic amino acid transporter-1 to redistribute to the cellular membrane from the cytosol and the effects of insulin on l-arginine uptake were partially dependent on the PI3K/Akt pathway. l-arginine-insulin treatment may be a novel strategy to ameliorate I-R injury.

  15. Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine A1-receptors and alpha2-adrenoceptors.

    PubMed

    Imamura, M; Lander, H M; Levi, R

    1996-03-01

    We previously showed that prejunctional histamine H3-receptors downregulate norepinephrine exocytosis, which is markedly enhanced in early myocardial ischemia. In the present study, we investigated whether H3-receptors modulate nonexocytotic norepinephrine release during protracted myocardial ischemia. In this setting, decreased pH(i) in sympathetic nerve endings sequentially leads to a compensatory activation of the Na+-H+ antiporter (NHE), accumulation of intracellular Na+, reversal of the neuronal uptake of norepinephrine, and thus carrier-mediated release of norepinephrine. Accordingly, norepinephrine overflow from isolated guinea pig hearts undergoing 20-minute global ischemia and 45-minute reperfusion was attenuated approximately 80% by desipramine (10 nmol/L) and 70% by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA, 10 micromol/L), inhibitors of norepinephrine uptake and NHE, respectively. The H3-receptor agonist imetit (0.1 micromol/L) decreased carrier-mediated norepinephrine release by approximately 50%. This effect was blocked by the H3-receptor antagonist thioperamide (0.3 micromol/L), indicating that H-receptor activation inhibits carrier-mediated norepinephrine release. At lower concentrations, imetit (10 nmol/L) or EIPA (3 micromol/L) did not inhibit carrier-mediated norepinephrine release. However, a 25% inhibition occurred with imetit (10 nmol/L) and EIPA (3 micromol/L) combined. This synergism suggests an association between H-receptors and NHE. Conceivably, activation of H-receptors may lead to inhibition of NHE. In fact, alpha2-adrenoceptor activation, which is known to stimulate NHE, enhanced norepinephrine release, whereas alpha2-adrenoceptor blockade attenuated it. Furthermore, activation of adenosine A1-receptors markedly attenuated norepinephrine release, whereas their inhibition potentiated it. Because norepinephrine directly correlated with the severity of reperfusion arrhythmia and imetit reduced the incidence of ventricular fibrillation by 50

  16. 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

  17. Different thresholds of myocardial ischemia in ramp and standard bruce protocol exercise tests in patients with positive exercise stress tests and angiographically demonstrated coronary arterial narrowing.

    PubMed

    Noël, Martin; Jobin, Jean; Poirier, Paul; Dagenais, Gilles R; Bogaty, Peter

    2007-04-01

    Gradual instead of abrupt increases in workload favor a more physiologic response in terms of hemodynamic and gas exchange parameters. Therefore, we investigated whether myocardial ischemia is attenuated with a ramp compared with a standard Bruce exercise protocol in patients with coronary artery disease. We compared electrocardiographic ischemic parameters on the standard Bruce protocol treadmill and the individualized ergocycle ramp protocol in 18 men with coronary artery disease and a reproducible ischemic electrocardiographic exercise test. Oxygen consumption (VO2), ischemic threshold (rate-pressure product [RPP]=systolic blood pressure x heart rate at 1-mm ST-segment depression), and maximum ST-segment depression corresponding to the highest RPP common to the 2 tests were determined. Ischemic threshold was higher with the ramp than with the Bruce protocol (23,420+/-5,732 vs 20,018+/-3,542 beats.min/mm Hg, p=0.007). Peak RPP was higher during the ramp than during the Bruce protocol (28,492+/-6,450 vs 25,519+/-6,067 beats.min/mm Hg, respectively, p=0.02) despite similar peak VO2 (25.59+/-5.05 vs 26.39+/-4.65 mlO2.kg-1.min-1, respectively, p=0.6). Maximum ST-segment depression corresponding to the highest RPP common to the 2 tests was less with the ramp than with the Bruce protocol (-1.2+/-0.9 vs -1.9+/-0.7 mm, p=0.003). In conclusion, exercise-induced myocardial ischemia is markedly attenuated on the more gradually increasing workload of the individualized ramp ergocycle compared with the standard Bruce treadmill protocol. This effect is unexplained by energy expenditure (VO2) or myocardial work (RPP) and is consistent with a "warm-up" ischemic mechanism.

  18. Protective Effects of Shen-Yuan-Dan, a Traditional Chinese Medicine, against Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro

    PubMed Central

    Liu, Hongxu; Shang, Juju; Chu, Fuyong; Li, Aiyong; Wu, Bao; Xie, Xinran; Liu, Weihong; Yang, Hongzhi; Tong, Tong

    2013-01-01

    Objectives. The study was to investigate the effects and mechanisms of Shen-Yuan-Dan (SYD) pharmacological postconditioning on myocardial ischemia/reperfusion (I/R) injury. Methods. In the in vivo experiment, myocardial injury markers and histopathology staining were examined. In the in vitro experiment, cell viability and cell apoptosis were, respectively, detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and Hoechst 33342 fluorochrome staining. The protein expressions of Bcl-2 and Bax were determined by immunocytochemistry assay. Results. Both low and high doses of SYD protected myocardium against I/R injury in rat model by reducing lactic dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity and malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activity and attenuating histopathology injury. Meanwhile, in the in vitro experiment, SYD promoted cell viability and inhibited the cardiomyocyte apoptosis. The level of Bcl-2 protein was restored to the normal level by SYD pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by SYD pharmacological postconditioning. These effects of SYD were inhibited by LY294002. Conclusions. The results of this study suggested that SYD pharmacological postconditioning has protective effects against myocardial I/R injury in both in vivo and in vitro models, which are related to activating the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway. PMID:24454518

  19. Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β

    PubMed Central

    Zhou, Mingjie; Ren, Huanhuan; Han, Jichun; Wang, Wenjuan; Zheng, Qiusheng; Wang, Dong

    2015-01-01

    Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats. Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β (GSK-3β), phospho-GSK-3β (P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis. Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and ±dp/dtmax, as well as increased the levels of SOD and P-GSK-3β and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α. Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3β activity in rats with I/R. PMID:26265983

  20. MicroRNA-214 protects against hypoxia/reoxygenation induced cell damage and myocardial ischemia/reperfusion injury via suppression of PTEN and Bim1 expression

    PubMed Central

    Wang, Xiaohui; Ha, Tuanzhu; Hu, Yuanping; Lu, Chen; Liu, Li; Zhang, Xia; Kao, Race; Kalbfleisch, John; Williams, David; Li, Chuanfu

    2016-01-01

    Background Myocardial apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the myocardium from I/R injury. This study investigated the role of miR-214 in hypoxia/reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R injury in vivo. Methods and Results H9C2 cardiomyoblasts were transfected with lentivirus expressing miR-214 (LmiR-214) or lentivirus expressing scrambled miR-control (LmiR-control) respectively, to establish cell lines of LmiR-214 and LmiR-control. The cells were subjected to hypoxia for 4 h followed by reoxygenation for 24 h. Transfection of LmiR-214 suppresses PTEN expression, significantly increases the levels of Akt phosphorylation, markedly attenuates LDH release, and enhances the viability of the cells subjected to H/R. In vivo transfection of mouse hearts with LmiR-214 significantly attenuates I/R induced cardiac dysfunction and reduces I/R-induced myocardial infarct size. LmiR-214 transfection significantly attenuates I/R-induced myocardial apoptosis and caspase-3/7 and caspase-8 activity. Increased expression of miR-214 by transfection of LmiR-214 suppresses PTEN expression, increases the levels of phosphorylated Akt, represses Bim1 expression and induces Bad phosphorylation in the myocardium. In addition, in vitro data shows transfection of miR-214 mimics to H9C2 cells suppresses the expression and translocation of Bim1 from cytosol to mitochondria and induces Bad phosphorylation. Conclusions Our in vitro and in vivo data suggests that miR-214 protects cells from H/R induced damage and attenuates I/R induced myocardial injury. The mechanisms involve activation of PI3K/Akt signaling by targeting PTEN expression, induction of Bad phosphorylation, and suppression of Bim1 expression, resulting in decreases in I/R-induced myocardial apoptosis. PMID:27894079

  1. Myocardial Blood Flow Quantification for Evaluation of Coronary Artery Disease by Positron Emission Tomography, Cardiac Magnetic Resonance Imaging, and Computed Tomography

    PubMed Central

    Waller, Alfonso H.; Blankstein, Ron; Kwong, Raymond Y.; Di Carli, Marcelo F.

    2014-01-01

    The noninvasive detection of the presence and functional significance of coronary artery stenosis is important in the diagnosis, risk assessment, and management of patients with known or suspected coronary artery disease. Quantitative assessment of myocardial perfusion can provide an objective and reproducible estimate of myocardial ischemia and risk prediction. Positron emission tomography, cardiac magnetic resonance, and cardiac computed tomography perfusion are modalities capable of measuring myocardial blood flow and coronary flow reserve. In this review, we will discuss the technical aspects of quantitative myocardial perfusion imaging with positron emission tomography, cardiac magnetic resonance imaging and computed tomography, and its emerging clinical applications. PMID:24718671

  2. CDP-choline prevents cardiac arrhythmias and lethality induced by short-term myocardial ischemia-reperfusion injury in the rat: involvement of central muscarinic cholinergic mechanisms.

    PubMed

    Yilmaz, M Sertac; Coskun, Cenk; Yalcin, Murat; Savci, Vahide

    2008-09-01

    In the present study, we aimed to determine whether cytidine-5'-diphosphatecholine (CDP-choline or citicoline) can improve the outcome of short-term myocardial ischemia-reperfusion injury in rats. Ischemia was produced in anesthetized rats by ligature of the left anterior descending coronary artery for 7 min followed by a reperfusion period of 7 min. Reperfusion-induced ventricular tachycardia (VT), ventricular fibrillation (VF), survival rate, and changes in arterial pressure were evaluated. Saline (1 ml/kg), CDP-choline (100, 250,and 500 mg/kg), or lidocaine (5 mg/kg) was intravenously injected in the middle of the ischemic period. Intracerebroventricular (i.c.v.) mecamylamine (50 microg) or atropine sulfate (10 microg) pretreatments were made 10 min before the coronary occlusion period. Pretreatment with intravenous (i.v.) atropine methylnitrate (2 and 5 mg/kg; i.v.) or bilateral vagotomy was performed 5 min before the induction of ischemia. An in vivo microdialysis study was performed in the nucleus ambiguus area (NA); choline and acetylcholine levels were measured in extracellular fluids. In control rats, VT, VF, and lethality were observed in 85%, 60% and 50% of the animals, respectively. Intravenous CDP-choline produced a short-term increase in blood pressure and reduced the incidence of VT, VF, and lethality dose-dependently when injected in the middle of the ischemic period. CDP-choline at doses of 250 and 500 mg/kg completely prevented death. Intracerebroventricular atropine sulfate pretreatment completely abolished the protective effect of CDP-choline, while mecamylamine pretreatment had no effect on the drug. CDP-choline increased the levels of extracellular choline and acetylcholine in the NA area. Bilateral vagotomy completely abolished the protective effect of CDP-choline in the reperfusion period. Moreover, the intravenous pretreatment with atropine methylnitrate produced dose-dependent blockade in the reduction of VT, VF, and mortality rates

  3. Prostaglandin E2 reduces swine myocardial ischemia reperfusion injury via increased endothelial nitric oxide synthase and vascular endothelial growth factor expression levels

    PubMed Central

    Zhou, Ying; Yang, Peng; Li, Aili; Ye, Xiaojun; Ren, Shiyan; Li, Xianlun

    2017-01-01

    Prostaglandin E2 (PGE2) has been demonstrated to attenuate cardiac ischemia-reperfusion (I/R) injury. However, the underlying mechanism of PGE2 in cardiac I/R injury remains unknown. Upregulated expression levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were reported in acute myocardial infarction (AMI), and were demonstrated to diminish I/R injury. In the current study the involvement of VEGF and eNOS in the myocardial protective effect of PGE2 were investigated in a catheter-based porcine model of AMI. Twenty-two Chinese miniature pigs were randomized into sham-surgery (n=6), control (n=8) and PGE2 (n=8) groups. PGE2 (1 µg/kg) was injected from 10 min prior to left anterior descending occlusion up to 1 h after reperfusion in the PGE2 group. Subsequently, the hemodynamic parameters were evaluated. Thioflavin-S and Evans Blue double staining were performed to evaluate the extent of the myocardial reperfusion area (RA) and no-reflow area (NRA). Immunohistochemical and western blot analysis were used to evaluate protein expression levels of VEGF and eNOS. Left ventricular (LV) systolic pressure significantly improved and LV end-diastolic pressure significantly decreased in the PGE2 group when compared with the control group 2 h after occlusion and 3 h after reperfusion (P<0.05, respectively). The RA and NRA were smaller in the PGE2 group than in the control group (P<0.05, respectively). Furthermore, PGE2 treatment increased the myocardial content of VEGF and eNOS when compared with the control group (P<0.05, respectively). Thus, the results of the present study demonstrate the cardio-protective mechanisms of PGE2, which may protect the heart from I/R injury via enhancement of VEGF and eNOS expression levels. PMID:28357071

  4. JNK/PI3K/Akt signaling pathway is involved in myocardial ischemia/reperfusion injury in diabetic rats: effects of salvianolic acid A intervention.

    PubMed

    Chen, Qiuping; Xu, Tongda; Li, Dongye; Pan, Defeng; Wu, Pei; Luo, Yuanyuan; Ma, Yanfeng; Liu, Yang

    2016-01-01

    Recent studies have demonstrated that diabetes impairs the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway, while insulin resistance syndrome has been associated with alterations of this pathway in diabetic rats after ischemia/reperfusion (I/R), and activation of C-jun N-terminal kinase (JNK) is involved. The present study was designed to investigate whether inhibiting JNK activity would partially restore the PI3K/Akt signaling pathway and protect against myocardial I/R injury in diabetic rats, and to explore the effect of intervention with salvianolic acid A (Sal A). The inhibitor of JNK (SP600125) and Sal A were used in type 2 diabetic (T2D) rats, outcome measures included heart hemodynamic data, myocardial infarct size, the release of lactate dehydrogenase (LDH), SERCA2a activity, cardiomyocyte apotosis, expression levels of Bcl-2, Bax and cleaved caspase-3, and the phosphorylation status of Akt and JNK. The p-Akt levels were increased after myocardial I/R in non-diabetic rats, while there was no change in diabetic rats. Pretreatment with the SP600125 and Sal A decreased the p-JNK levels and increased the p-Akt levels in diabetic rats with I/R, and heart hemodynamic data improved, infarct size and LDH release decreased, SERCA2a activity increased, Bax and cleaved caspase-3 expression levels decreased, and the expression of Bcl-2 and the Bcl-2/Bax ratio increased. Our results suggest that the JNK/PI3K/Akt signaling pathway is involved in myocardial I/R injury in diabetic rats and Sal A exerts an anti-apoptotic effect and improves cardiac function following I/R injury through the JNK/PI3K/Akt signaling pathway in this model.

  5. JNK/PI3K/Akt signaling pathway is involved in myocardial ischemia/reperfusion injury in diabetic rats: effects of salvianolic acid A intervention

    PubMed Central

    Chen, Qiuping; Xu, Tongda; Li, Dongye; Pan, Defeng; Wu, Pei; Luo, Yuanyuan; Ma, Yanfeng; Liu, Yang

    2016-01-01

    Recent studies have demonstrated that diabetes impairs the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway, while insulin resistance syndrome has been associated with alterations of this pathway in diabetic rats after ischemia/reperfusion (I/R), and activation of C-jun N-terminal kinase (JNK) is involved. The present study was designed to investigate whether inhibiting JNK activity would partially restore the PI3K/Akt signaling pathway and protect against myocardial I/R injury in diabetic rats, and to explore the effect of intervention with salvianolic acid A (Sal A). The inhibitor of JNK (SP600125) and Sal A were used in type 2 diabetic (T2D) rats, outcome measures included heart hemodynamic data, myocardial infarct size, the release of lactate dehydrogenase (LDH), SERCA2a activity, cardiomyocyte apotosis, expression levels of Bcl-2, Bax and cleaved caspase-3, and the phosphorylation status of Akt and JNK. The p-Akt levels were increased after myocardial I/R in non-diabetic rats, while there was no change in diabetic rats. Pretreatment with the SP600125 and Sal A decreased the p-JNK levels and increased the p-Akt levels in diabetic rats with I/R, and heart hemodynamic data improved, infarct size and LDH release decreased, SERCA2a activity increased, Bax and cleaved caspase-3 expression levels decreased, and the expression of Bcl-2 and the Bcl-2/Bax ratio increased. Our results suggest that the JNK/PI3K/Akt signaling pathway is involved in myocardial I/R injury in diabetic rats and Sal A exerts an anti-apoptotic effect and improves cardiac function following I/R injury through the JNK/PI3K/Akt signaling pathway in this model. PMID:27398138

  6. Sevoflurane post-conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phopshorylated NHE1 levels.

    PubMed

    Cao, Jianfang; Xie, Hong; Sun, Ying; Zhu, Jiang; Ying, Ming; Qiao, Shigang; Shao, Qin; Wu, Haorong; Wang, Chen

    2015-12-01

    The protective effects of sevoflurane post-conditioning against myocardial ischemia/reperfusion (I/R) injury (MIRI) have been previously reported. However, the mechanisms responsible for these protective effects remain elusive. In this study, in order to investigate the molecular mechanisms responsible for the protective effects of sevoflurane post-conditioning on isolated rat hearts subjected to MIRI, Sprague-Dawley rat hearts were randomly divided into the following 6 groups: i) the sham-operated control; ii) 2.5% sevoflurane; iii) ischemia/reperfusion (I/R); iv) 2.5% sevoflurane post-conditioning plus I/R; v) 2.5% sevoflurane post-conditioning + NG-nitro-L-arginine methyl ester (L-NAME) plus I/R; and vi) L-NAME plus I/R. The infarct size was measured using 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Additionally, the myocardial nitric oxide (NO), NO synthase (NOS) and nicotinamide adenine dinucleotide (NAD+) levels were determined. Autophagosomes and apoptosomes in the myocardium were detected by transmission electron microscopy. The levels of Bcl-2, cleaved caspase-3, Beclin-1, microtubule-associated protein light chain 3 (LC3)‑I/II, Na+/H+ exchanger 1 (NHE1) and phosphorylated NHE1 protein were measured by western blot analysis. NHE1 mRNA levels were measured by reverse transcription-quantitative polymerase chain reaction. Compared with the I/R group, 15 min of exposure to 2.5% sevoflurane during early reperfusion significantly decreased the myocardial infarct size, the autophagic vacuole numbers, the NHE1 mRNA and protein expression of cleaved caspase-3, Beclin-1 and LC3-I/II. Post-conditioning with 2.5% sevoflurane also increased the NO and NOS levels and Bcl-2 protein expression (p<0.05 or p<0.01). Notably, the cardioprotective effects of sevoflurane were partly abolished by the NOS inhibitor, L-NAME. The findings of the present study suggest that sevoflurane post-conditioning protects the myocardium against I/R injury and reduces the myocardial

  7. Myocardial viability.

    PubMed Central

    Birnbaum, Y; Kloner, R A

    1996-01-01

    Left ventricular function is a major predictor of outcome in patients with coronary artery disease. Acute ischemia, postischemic dysfunction (stunning), myocardial hibernation, or a combination of these 3 are among the reversible forms of myocardial dysfunction. In myocardial stunning, dysfunction occurs despite normal myocardial perfusion, and function recovers spontaneously over time. In acute ischemia and hibernation, there is regional hypoperfusion. Function improves only after revascularization. Evidence of myocardial viability usually relies on the demonstration of uptake of various metabolic tracers, such as thallium (thallous chloride TI 201) or fludeoxyglucose F 18, by dysfunctional myocardium or by the demonstration of contractile reserve in a dysfunctional region. This can be shown as an augmentation of function during the infusion of various sympathomimetic agents. The response of ventricular segments to increasing doses of dobutamine may indicate the underlying mechanism of dysfunction. Stunned segments that have normal perfusion show dose-dependent augmentation of function. If perfusion is reduced as in hibernating myocardium, however, a biphasic response usually occurs: function improves at low doses of dobutamine, whereas higher doses may induce ischemia and, hence, dysfunction. But in patients with severely impaired perfusion, even low doses may cause ischemia. Myocardial regions with subendocardial infarction or diffuse scarring may also have augmented contractility during catecholamine infusion due to stimulation of the subepicardial layers. In these cases, augmentation of function after revascularization is not expected. Because the underlying mechanism, prognosis, and therapy may differ among these conditions, it is crucial to differentiate among dysfunctional myocardial segments that are nonviable and have no potential to regain function, hibernating or ischemic segments in which recovery of function occurs only after revascularization, and

  8. Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening

    PubMed Central

    2011-01-01

    Background Most guidelines recommend a systematic screening of asymptomatic high risk patients with diabetes for silent ischemia, but the clinical benefit of this strategy has not been demonstrated compared with the simple control of cardiovascular risk factors. We sought to determine whether referring asymptomatic diabetic patients for screening of silent ischemia decreases the risk of cardiovascular events compared with usual care. Methods DYNAMIT was a prospective, randomized, open, blinded end-point multicenter trial run between 2000 and 2005, with a 3.5 year mean follow-up in ambulatory care in 45 French hospitals. The study included 631 male and female with diabetes aged 63.9 ± 5.1 years, with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors, receiving appropriate medical treatment. The patients were randomized centrally to either screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography (N = 316), or follow-up without screening (N = 315). The main study end point was time to death from all causes, non-fatal myocardial infarction, non-fatal stroke, or heart failure requiring hospitalization or emergency service intervention. The results of a meta-analysis of DYNAMIT and DIAD, a similar study, are also presented. Results The study was discontinued prematurely because of difficulties in recruitment and a lower-than expected event rate. Follow-up was complete for 98.9% patients regarding mortality and for 97.5% regarding the main study end point. Silent ischemia detection procedure was positive or uncertain in 68 (21.5%) patients of the screening group. There was no significant difference between the screening and the usual care group for the main outcome (hazard ratio = 1.00 95%CI 0.59 to 1.71). The meta-analysis of these and DIAD results gave similar results, with narrower confidence intervals for each endpoint. Conclusions These results suggest that the

  9. 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

  10. Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning, arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.

    PubMed

    Čarnická, S; Adameová, A; Nemčeková, M; Matejíková, J; Pancza, D; Ravingerová, T

    2011-01-01

    Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 micromol/l) or pravastatin (P, 30 micromol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30-min global ischemia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3 +/- 0.2 in C to 3.0 +/- 0 and 2.7 +/- 0.2 in S and P, respectively, (both P < 0.05), decreased the duration of ventricular tachycardia and suppressed ventricular fibrillation. Likewise, the extent of lethal injury (infarct size) determined by tetrazolium staining and expressed in percentage of risk area, was significantly lower in both treated groups, moreover, the effect of P was more pronounced (27 +/- 2 % and 10 +/- 2 % in S and P groups, respectively, vs. 42 +/- 1 % in C; P < 0.05). In contrast, only S, but not P, was able to improve postischemic recovery of left ventricular developed pressure (LVDP; 48 +/- 12 % of preischemic values vs. 25 +/- 4 % in C and 21 +/ -7 % in P groups; P < 0.05). Our results suggest that differences in water solubility of statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.

  11. Protective effects of Phyllanthus emblica against myocardial ischemia-reperfusion injury: the role of PI3-kinase/glycogen synthase kinase 3β/β-catenin pathway.

    PubMed

    Thirunavukkarasu, Mahesh; Selvaraju, Vaithinathan; Tapias, Leonidas; Sanchez, Juan A; Palesty, J Alexander; Maulik, Nilanjana

    2015-12-01

    Clinical studies of Phyllanthus emblica (P. emblica) have shown that it increases production of nitric oxide, glutathione, and high-density lipoprotein (HDL); decreases low-density lipoprotein (LDL), total cholesterol, triglycerides, and high-sensitivity C-reactive protein (hsCRP); and significantly inhibits platelet aggregation. The following study was designed to examine the effect of P. emblica treatment on myocardial ischemia-reperfusion (I/R) injury and identify the molecular targets and its underlying mechanism(s). Experimental animals were divided into four groups: control sham (CS), P. emblica sham (PS), control I/R (CIR), and P. emblica I/R (PIR). Rats in the P. emblica groups were gavaged with aqueous P. emblica solution (100 mg/kg body weight) for 30 days. After 30 days of gavaging, the I/R group underwent I/R surgery (45-min ischemia) followed by 4 or 30 days of reperfusion. Rats in the sham group underwent surgery without ligation. Left ventricular tissue samples, 4 and 30 days after I/R, were used for Western blot analysis and immunohistochemistry, respectively. Western blot analysis showed upregulation of phosphorylated Akt and GSK3-β and increased nuclear translocation of β-catenin in the PIR group versus CIR. PIR rats also indicated reduced 3-nitrotyrosine and Caspase-3 expression. Increased phosphorylation of endothelial nitric oxide synthase (p-eNOS) and upregulation of anti-apoptotic protein Bcl-2 were found in the PIR group. Echocardiography showed increased ejection fraction and fractional shortening and decreased left ventricular internal diameter in experimental subjects compared to controls. There was decreased fibrosis in P. emblica-treated rats compared to controls. The results of this study indicate that P. emblica is capable of upregulating the PI3K/Akt/GSK3β/β-catenin cardioprotective pathway, thereby preserving cardiac tissue during ischemia-reperfusion injury.

  12. 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.

  13. Antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart.

    PubMed

    Jiang, Jiangtao; Yuan, Xuan; Wang, Ting; Chen, Hongmei; Zhao, Hong; Yan, Xinyan; Wang, Zhiping; Sun, Xiling; Zheng, Qiusheng

    2014-03-01

    This study evaluates antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. (DML). The total flavonoids showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals in vitro. Compared with the ischemia/reperfusion (I/R) group as demonstrated by the use of improved Langendorff retrograde perfusion technology, the total flavonoids (5 μg/mL) pretreatment improved the heart rate and coronary flow, rised left ventricular developed pressure and decreased creatine kinase, lactate dehydrogenase levels in coronary flow. The infarct size/ischemic area at risk of DML-treated hearts was smaller than that of I/R group; the superoxide dismutase activity and glutathione/glutathione disulfide ratio increased and malondialdehyde content reduced obviously (P < 0.01) in total flavonoids treatment groups. In conclusion, the total flavonoids possess obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

  14. Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

    PubMed Central

    Yu, Liming; Gong, Bing; Duan, Weixun; Fan, Chongxi; Zhang, Jian; Li, Zhi; Xue, Xiaodong; Xu, Yinli; Meng, Dandan; Li, Buying; Zhang, Meng; Bin Zhang; Jin, Zhenxiao; Yu, Shiqiang; Yang, Yang; Wang, Huishan

    2017-01-01

    Enhancing mitochondrial biogenesis and reducing mitochondrial oxidative stress have emerged as crucial therapeutic strategies to ameliorate diabetic myocardial ischemia/reperfusion (MI/R) injury. Melatonin has been reported to be a safe and potent cardioprotective agent. However, its role on mitochondrial biogenesis or reactive oxygen species (ROS) production in type 1 diabetic myocardium and the underlying mechanisms remain unknown. We hypothesize that melatonin ameliorates MI/R injury in type 1 diabetic rats by preserving mitochondrial function via AMPK-PGC-1α-SIRT3 signaling pathway. Both our in vivo and in vitro data showed that melatonin reduced MI/R injury by improving cardiac function, enhancing mitochondrial SOD activity, ATP production and oxidative phosphorylation complex (II, III and IV), reducing myocardial apoptosis and mitochondrial MDA, H2O2 generation. Importantly, melatonin also activated AMPK-PGC-1α-SIRT3 signaling and increased SOD2, NRF1 and TFAM expressions. However, these effects were abolished by Compound C (a specific AMPK signaling blocker) administration. Additionally, our cellular experiment showed that SIRT3 siRNA inhibited the cytoprotective effect of melatonin without affecting p-AMPK/AMPK ratio and PGC-1α expression. Taken together, we concluded that melatonin preserves mitochondrial function by reducing mitochondrial oxidative stress and enhancing its biogenesis, thus ameliorating MI/R injury in type 1 diabetic state. AMPK-PGC1α-SIRT3 axis plays an essential role in this process. PMID:28120943

  15. 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.

  16. Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways

    PubMed Central

    Suchal, Kapil; Malik, Salma; Khan, Sana Irfan; Malhotra, Rajiv Kumar; Goyal, Sameer N.; Bhatia, Jagriti; Kumari, Santosh; Ojha, Shreesh; Arya, Dharamvir Singh

    2017-01-01

    Hyperglycemia induced advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) activation is thought to involve in the development of cardiovascular disease in diabetics. Activation of AGE-RAGE axis results in the oxidative stress and inflammation. Mangiferin is found in the bark of mango tree and is known to treat diseases owing to its various biological activities. Thus, this study was designed to evaluate the effect of mangiferin in ischemia-reperfusion (IR) induced myocardial injury in diabetic rats. A single injection of STZ (70 mg/kg; i.p.) was injected to male albino Wistar rats to induce diabetes. After confirmation of diabetes, rats were administered vehicle (2 ml/kg; i.p.) and mangiferin (40 mg/kg; i.p.) for 28 days. On 28th day, left anterior descending coronary artery was ligated for 45 min and then reperfused for 60 min. Mangiferin treatment significantly improved cardiac function, restored antioxidant status, reduced inflammation, apoptosis and maintained myocardial architecture. Furthermore, mangiferin significantly inhibited the activation of AGE-RAGE axis, c-Jun N-terminal kinase (JNK) and p38 and increased the expression of extracellular regulated kinase 1/2 (ERK1/2) in the myocardium. Thus, mangiferin attenuated IR injury in diabetic rats by modulation of AGE-RAGE/MAPK pathways which further prevented oxidative stress, inflammation and apoptosis in the myocardium. PMID:28181586

  17. Cardioprotection by combination of three compounds from ShengMai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission

    PubMed Central

    Li, Fang; Fan, Xiaoxue; Zhang, Yu; Pang, Lizhi; Ma, Xiaonan; Song, Meijia; Kou, Junping; Yu, Boyang

    2016-01-01

    GRS is a drug combination of three active components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai preparations, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study explores the cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury compared with ShengMai preparations and investigates the underlying mechanisms. GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy as Shengmai preparations, as evidenced by decreased myocardium infarct size, ameliorated histological features, the decrease of LDH production and improved cardiac function, and also produced a significant decrease of apoptotic index. Mechanistically, GRS alleviated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway as reflected by inhibition of caspase-3 activity, normalization of Bcl-2/Bax levels and improved mitochondrial function. Moreover, GRS prevented cardiomyocytes mitochondrial fission and upregulated AMPKα phosphorylation. Interestingly, AMPK activation prevented hypoxia and reoxygenation induced mitochondrial fission in cardiomyocytes and GRS actions were significantly attenuated by knockdown of AMPKα. Collectively, these data show that GRS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and modulating AMPK activation-mediated mitochondrial fission, thereby providing a rationale for future clinical applications and potential therapeutic strategy for MI/R injury. PMID:27869201

  18. Technical note: EnVision™ FLEX improves the detectability of depletions of myoglobin and troponin T in forensic cases of myocardial ischemia/infarction.

    PubMed

    Sabatasso, Sara; Pomponio, Catia; Fracasso, Tony

    2017-03-23

    Immunohistochemistry is a well-established technique used in many research laboratories as well as in clinical diagnostics. The method allows to visualize the expression of proteins in biological tissues, as well as to evaluate this expression semi-quantitatively. For diagnosis, an optimal staining, based on a straightforward protocol, is crucial. In many sudden cardiac death cases, immunohistochemistry is the only tool enabling the diagnosis of myocardial ischemia/infarction, thus the diagnosis of the cause of death. Improvements in immunoreactions are actually possible thanks to optimized detection systems. The recently introduced detection system EnVision Flex™ by Dako allows to dramatically improve (in terms of intensity of the signal and practically absence of background) the visualization of antigens in formalin-fixed paraffin-embedded (FFPE) tissue sections. We tested this method for the detection of myoglobin and troponin T in human postmortem cases of myocardial infarction, as the results obtained by using the « classical » ABC (avidin-biotin complex) method have proven to be sub-optimal, thus rendering any interpretation very difficult, if not impossible.

  19. MAPKAPK-2 modulates p38-MAPK localization and small heat shock protein phosphorylation but does not mediate the injury associated with p38-MAPK activation during myocardial ischemia

    PubMed Central

    Gorog, Diana A.; Jabr, Rita I; Tanno, Masaya; Sarafraz, Negin; Clark, James E.; Fisher, Simon G.; Cao, Xou Bin; Bellahcene, Mohamed; Dighe, Kushal; Kabir, Alamgir M. N.; Quinlan, Roy A.; Kato, Kanefusa; Gaestel, Matthias; Marber, Michael S.

    2009-01-01

    MAPKAPK-2 (MK2) is a protein kinase activated downstream of p38-MAPK which phosphorylates the small heat shock proteins HSP27 and αB crystallin and modulates p38-MAPK cellular distribution. p38-MAPK activation is thought to contribute to myocardial ischemic injury; therefore, we investigated MK2 effects on ischemic injury and p38 cellular localization using MK2-deficient mice (KO). Immunoblotting of extracts from Langendorff-perfused hearts subjected to aerobic perfusion or global ischemia or reperfusion showed that the total and phosphorylated p38 levels were significantly lower in MK2−/− compared to MK2+/+ hearts at baseline, but the ratio of phosphorylated/total p38 was similar. These results were confirmed by cellular fractionation and immunoblotting for both cytosolic and nuclear compartments. Furthermore, HSP27 and αB crsytallin phosphorylation were reduced to baseline in MK2−/− hearts. On semiquantitative immunofluorescence laser confocal microscopy of hearts during aerobic perfusion, the mean total p38 fluorescence was significantly higher in the nuclear compared to extranuclear (cytoplasmic, sarcomeric, and sarcolemmal compartments) in MK2+/+ hearts. However, although the increase in phosphorylated p38 fluorescence intensity in all compartments following ischemia in MK2+/+ hearts was lost in MK2−/− hearts, it was basally elevated in nuclei of MK2−/− hearts and was similar to that seen during ischemia in MK2+/+ hearts. Despite these differences, similar infarct volumes were recorded in wild-type MK2+/+ and MK2−/− hearts, which were decreased by the p38 inhibitor SB203580 (1 μM) in both genotypes. In conclusion, p38 MAPK-induced myocardial ischemic injury is not modulated by MK2. However, the absence of MK2 perturbs the cellular distribution of p38. The preserved nuclear distribution of active p38 MAPK in MK2−/− hearts and the conserved response to SB203580 suggests that activation of p38 MAPK may contribute to injury

  20. Aging might augment reactive oxygen species (ROS) formation and affect reactive nitrogen species (RNS) level after myocardial ischemia/reperfusion in both humans and rats.

    PubMed

    Fan, Qian; Chen, Mulei; Fang, Xiangyang; Lau, Wayne Bond; Xue, Lei; Zhao, Lina; Zhang, Hui; Liang, Yan-Hong; Bai, Xi; Niu, Hong-Yu; Ye, Jing; Chen, Qing; Yang, Xinchun; Liu, Miaobing

    2013-08-01

    Previous studies indicate aging results in significantly decreased cardiac function and increased myocardial apoptosis after myocardial ischemia/reperfusion (MI/R) in humans or rats. The underlying mechanisms of aging-exacerbated effects remain unknown. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are known to play vital roles in aging-related MI/R injury. Heretofore, the effects of aging upon ROS and RNS formation were not investigated in humans, which is the focus of the current study. Due to experimental limitations with clinical trials, an additional animal experiment was performed. All enrolled acute myocardial infarction (AMI) patients received percutaneous coronary intervention (PCI) therapy. AMI patients were assigned into two groups: adult (age <65, n = 34) and elderly (age ≥65, n = 45) AMI patients. Blood samples were obtained from all study participants at 24 h and 3 days post-PCI. Plasma/white blood cell (WBC) ROS and RNS markers (malondialdehyde (MDA), myeloperoxidase (MPO), reduced glutathione (GSH), inducible nitric oxide synthase (iNOS) activity, NOx, and nitrotyrosine) were determined. The same markers were determined in rat cardiac tissue after 24 h MI/R. Compared to the adult group, elderly patients manifested increased plasma MDA and MPO and decreased plasma GSH concentrations. No significant differences in plasma NOx or nitrotyrosine concentration existed between adult and elderly patients. Furthermore, WBC iNOS activity in elderly patients was significantly decreased compared to the adult group. The measurement of ROS markers in the rat experiments was consistent and supported human study data. Surprisingly, RNS markers (NOx and nitrotyrosine) in blood and heart tissue increased from young to middle-aged rats but decreased from middle age to old age. Aging augments ROS, which might exacerbate MI/R injury. Additionally, our data support aging-induced changes of RNS levels in humans and rats in vivo.

  1. Sulodexide attenuates myocardial ischemia/reperfusion injury and the deposition of C-reactive protein in areas of infarction without affecting hemostasis.

    PubMed

    Lauver, D Adam; Booth, Erin A; White, Andrew J; Poradosu, Enrique; Lucchesi, Benedict R

    2005-02-01

    Several glycosaminoglycans (GAGs) have been demonstrated to protect the ischemic heart against reperfusion injury, in part, by modulating activation of the complement cascade. The present study assessed the cardioprotective effects of sulodexide (KRX-101), a mixture of GAGs composed of 80% low-molecular mass heparin and 20% dermatan sulfate. KRX-101 differs from other GAGs (e.g., heparin) in that it has limited anticoagulant efficacy and can be administered orally. The experimental protocol was designed to determine whether KRX-101 could protect the ischemic myocardium. Anesthetized New Zealand white rabbits underwent 30 min of coronary artery occlusion. Intravenous doses of KRX-101 (0.5 mg/kg, n = 10) or drug diluent (n = 10) were administered at the end of regional ischemia and at each hour of reperfusion. Infarct size, as a percentage of the area at risk, was calculated for both groups. Myocardial infarct size was 31.3 +/- 4.1% in the vehicle- and 17.3 +/- 3.2% in the KRX-101-treated animals (p < 0.05 versus vehicle). Activated partial thromboplastin times determined at baseline (preischemia) and at each hour of reperfusion (n = 4) were not significantly different between vehicle- and KRX-101-treated groups (p = N.S.). Myocardial injury was further assessed by measuring serum levels of cardiac-specific troponin I. KRX-101 administration significantly reduced (p < 0.05) the serum concentration of troponin I during reperfusion. The results suggest that KRX-101 may be an effective adjunctive agent in myocardial revascularization procedures, without the risk of increased bleeding.

  2. Modulation of Mononuclear Phagocyte Inflammatory Response by Liposome-Encapsulated Voltage Gated Sodium Channel Inhibitor Ameliorates Myocardial Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Ji, Wen-Jie; Zhang, Li; Dong, Yan; Ge, Lan; Lu, Rui-Yi; Sun, Hai-Ying; Guo, Zao-Zeng; Yang, Guo-Hong; Jiang, Tie-Min; Li, Yu-Ming

    2013-01-01

    Background Emerging evidence shows that anti-inflammatory strategies targeting inflammatory monocyte subset could reduce excessive inflammation and improve cardiovascular outcomes. Functional expression of voltage-gated sodium channels (VGSCs) have been demonstrated in monocytes and macrophages. We hypothesized that mononuclear phagocyte VGSCs are a target for monocyte/macrophage phenotypic switch, and liposome mediated inhibition of mononuclear phagocyte VGSC may attenuate myocardial ischemia/reperfusion (I/R) injury and improve post-infarction left ventricular remodeling. Methodology/Principal Findings Thin film dispersion method was used to prepare phenytoin (PHT, a non-selective VGSC inhibitor) entrapped liposomes. Pharmacokinetic study revealed that the distribution and elimination half-life of PHT entrapped liposomes were shorter than those of free PHT, indicating a rapid uptake by mononuclear phagocytes after intravenous injection. In rat peritoneal macrophages, several VGSC α subunits (NaV1.1, NaV1.3, NaV1.4, NaV1.5, NaV1.6, NaV1.7, NaVX, Scn1b, Scn3b and Scn4b) and β subunits were expressed at mRNA level, and PHT could suppress lipopolysaccharide induced M1 polarization (decreased TNF-α and CCL5 expression) and facilitate interleukin-4 induced M2 polarization (increased Arg1 and TGF-β1 expression). In vivo study using rat model of myocardial I/R injury, demonstrated that PHT entrapped liposome could partially suppress I/R injury induced CD43+ inflammatory monocyte expansion, along with decreased infarct size and left ventricular fibrosis. Transthoracic echocardiography and invasive hemodynamic analysis revealed that PHT entrapped liposome treatment could attenuate left ventricular structural and functional remodeling, as shown by increased ejection fraction, reduced end-systolic and end-diastolic volume, as well as an amelioration of left ventricular systolic (+dP/dtmax) and diastolic (-dP/dtmin) functions. Conclusions/Significance Our work for the

  3. Mitochondrially targeted Endonuclease III has a powerful anti-infarct effect in an in vivo rat model of myocardial ischemia/reperfusion

    PubMed Central

    Yang, Xi-Ming; Cui, Lin; White, James; Kuck, Jamie; Ruchko, Mykhaylo V.; Wilson, Glenn L.; Alexeyev, Mikhail; Gillespie, Mark N.; Downey, James M.

    2016-01-01

    Recent reports indicate that elevating DNA glycosylase/AP lyase repair enzyme activity offers marked cytoprotection in cultured cells and a variety of injury models. In this study, we measured the effect of EndoIII, a fusion protein construct that traffics Endonuclease III, a DNA glycosylase/AP lyase, to the mitochondria, on infarct size in a rat model of myocardial ischemia/reperfusion. Open-chest, anesthetized rats were subjected to 30 min of occlusion of a coronary artery followed by 2 h of reperfusion. An intravenous bolus of EndoIII, 8 mg/kg, just prior to reperfusion reduced infarct size from 43.8 ± 1.4 % of the risk zone in control animals to 24.0 ± 1.3 % with no detectable hemodynamic effect. Neither EndoIII’s vehicle nor an enzymatically inactive EndoIII mutant (K120Q) offered any protection. The magnitude of EndoIII’s protection was comparable to that seen with the platelet aggregation inhibitor cangrelor (25.0 ± 1.8 % infarction of risk zone). Because loading with a P2Y12 receptor blocker to inhibit platelets is currently the standard of care for treatment of acute myocardial infarction, we tested whether EndoIII could further reduce infarct size in rats treated with a maximally protective dose of cangrelor. The combination reduced infarct size to 15.1 ± 0.9 % which was significantly smaller than that seen with either cangrelor or EndoIII alone. Protection from cangrelor but not EndoIII was abrogated by pharmacologic blockade of phosphatidylinositol-3 kinase or adenosine receptors indicating differing cellular mechanisms. We hypothesized that EndoIII protected the heart from spreading necrosis by preventing the release of proinflammatory fragments of mitochondrial DNA (mtDNA) into the heart tissue. In support of this hypothesis, an intravenous bolus at reperfusion of deoxyribonuclease I (DNase I) which should degrade any DNA fragments escaping into the extracellular space was as protective as EndoIII. Furthermore, the combination of EndoIII and

  4. Chronic melatonin consumption prevents obesity-related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet-induced obesity.

    PubMed

    Nduhirabandi, Frederic; Du Toit, Eugene F; Blackhurst, Dee; Marais, David; Lochner, Amanda

    2011-03-01

    Obesity, a major risk factor for ischemic heart disease, is associated with increased oxidative stress and reduced antioxidant status. Melatonin, a potent free radical scavenger and antioxidant, has powerful cardioprotective effects in lean animals but its efficacy in obesity is unknown. We investigated the effects of chronic melatonin administration on the development of the metabolic syndrome as well as ischemia-reperfusion injury in a rat model of diet-induced obesity (DIO). Male Wistar rats received a control diet, a control diet with melatonin, a high-calorie diet, or a high-calorie diet with melatonin (DM). Melatonin (4 mg/kg/day) was administered in the drinking water. After 16 wk, biometric and blood metabolic parameters were measured. Hearts were perfused ex vivo for the evaluation of myocardial function, infarct size (IFS) and biochemical changes [activation of PKB/Akt, ERK, p38 MAPK, AMPK, and glucose transporter (GLUT)-4 expression). The high-calorie diet caused increases in body weight (BW), visceral adiposity, serum insulin and triglycerides (TRIG), with no change in glucose levels. Melatonin treatment reduced the BW gain, visceral adiposity, blood TRIG, serum insulin, homeostatic model assessment index and thiobarbituric acid reactive substances in the DIO group. Melatonin reduced IFS in DIO and control groups and increased percentage recovery of functional performance of DIO hearts. During reperfusion, hearts from melatonin-treated rats had increased activation of PKB/Akt, ERK42/44 and reduced p38 MAPK activation. Chronic melatonin treatment prevented the metabolic abnormalities induced by DIO and protected the heart against ischemia-reperfusion injury. These beneficial effects were associated with activation of the reperfusion injury salvage kinases pathway.

  5. An interaction between glucagon-like peptide-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia-reperfusion injury.

    PubMed

    Ihara, Madoka; Asanuma, Hiroshi; Yamazaki, Satoru; Kato, Hisakazu; Asano, Yoshihiro; Shinozaki, Yoshihiro; Mori, Hidezo; Minamino, Tetsuo; Asakura, Masanori; Sugimachi, Masaru; Mochizuki, Naoki; Kitakaze, Masafumi

    2015-05-15

    Dipeptidyl peptidase 4 (DPP4) inhibitors suppress the metabolism of the potent antihyperglycemic hormone glucagon-like peptide-1 (GLP-1). DPP4 was recently shown to provide cardioprotection through a reduction of infarct size, but the mechanism for this remains elusive. Known interactions between DPP4 and adenosine deaminase (ADA) suggest an involvement of adenosine signaling in DPP4 inhibitor-mediated cardioprotection. We tested whether the protective mechanism of the DPP4 inhibitor alogliptin against myocardial ischemia-reperfusion injury involves GLP-1- and/or adenosine-dependent signaling in canine hearts. In anesthetized dogs, the coronary artery was occluded for 90 min followed by reperfusion for 6 h. A 4-day pretreatment with alogliptin reduced the infarct size from 43.1 ± 2.5% to 17.1 ± 5.0% without affecting collateral flow and hemodynamic parameters, indicating a potent antinecrotic effect. Alogliptin also suppressed apoptosis as demonstrated by the following analysis: 1) reduction in the Bax-to-Bcl2 ratio; 2) cytochrome c release, 3) an increase in Bad phosphorylation in the cytosolic fraction; and 4) terminal deoxynucleotidyl transferase dUTP nick end labeling assay. This DPP4 inhibitor did not affect blood ADA activity or adenosine concentrations. In contrast, the nonselective adenosine receptor blocker 8-(p-sulfophenyl)theophylline (8SPT) completely blunted the effect of alogliptin. Alogliptin did not affect Erk1/2 phosphorylation, but it did stimulate phosphorylation of Akt, glycogen synthase kinase-3β, and cAMP response element-binding protein (CREB). Only 8SPT prevented alogliptin-induced CREB phosphorylation. In conclusion, the DPP4 inhibitor alogliptin suppresses ischemia-reperfusion injury via adenosine receptor- and CREB-dependent signaling pathways.

  6. Metabonomic Strategy to the Evaluation of Chinese Medicine Salvia miltiorrhiza and Dalbergia odorifera Interfering Myocardial Ischemia/Reperfusion Injury in Rats.

    PubMed

    Mu, Fei; Duan, Jialin; Bian, Haixu; Zhai, Xiaohu; Shang, Peijin; Lin, Rui; Zhao, Meina; Hu, Dongmei; Yin, Ying; Wen, Aidong; Xi, Miaomiao

    2017-03-07

    Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis. Metabonomics technology was further performed to evaluate the endogenous metabolites profiling systematically. According to the results of pattern recognition analysis, a clear separation of MI/R injury in the Model group and Sham group was achieved and SM-DOO pretreatment group was located much closer to the Sham group than the Model group, which was consistent with results of biochemistry and histopathological assay. Moreover, potential biomarkers were identified to elucidate the drug mechanism of SM-DOO, which may be related with pathways of energy metabolism, especially tricarboxylic acid (TCA) cycle (citric acid) and β-oxidation of fatty acids (3-hydroxybutyric, palmitoleic acid, heptadecanoic acid, and arachidonic acid). Besides, the protein expressions of p-AMPK and p-ACC in the SM-DOO group were significantly elevated, while the levels of carnitine palmitoyl-CoA transferase-1 (CPT-1), p-PDK, and p-PDC were dramatically reduced by SM-DOO. In conclusion, SM-DOO pretreatment could ameliorate MI/R injury by intervening energy metabolism, especially TCA cycle and β-oxidation of fatty acids. This work showed that the metabonomics method combinate with conventional pharmacological methods is a promising tool in the efficacy and mechanism research of traditional

  7. 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

  8. Human Placenta-Derived Multipotent Cells (hPDMCs) Modulate Cardiac Injury: From Bench to Small and Large Animal Myocardial Ischemia Studies.

    PubMed

    Liu, Yuan-Hung; Peng, Kai-Yen; Chiu, Yu-Wei; Ho, Yi-Lwun; Wang, Yao-Horng; Shun, Chia-Tung; Huang, Shih-Yun; Lin, Yi-Shuan; de Vries, Antoine A F; Pijnappels, Daniël A; Lee, Nan-Ting; Yen, B Linju; Yen, Men-Luh

    2015-01-01

    Cardiovascular disease is the leading cause of death globally, and stem cell therapy remains one of the most promising strategies for regeneration or repair of the damaged heart. We report that human placenta-derived multipotent cells (hPDMCs) can modulate cardiac injury in small and large animal models of myocardial ischemia (MI) and elucidate the mechanisms involved. We found that hPDMCs can undergo in vitro cardiomyogenic differentiation when cocultured with mouse neonatal cardiomyocytes. Moreover, hPDMCs exert strong proangiogenic responses in vitro toward human endothelial cells mediated by secretion of hepatocyte growth factor, growth-regulated oncogene-α, and interleukin-8. To test the in vivo relevance of these results, small and large animal models of acute MI were induced in mice and minipigs, respectively, by permanent left anterior descending (LAD) artery ligation, followed by hPDMC or culture medium-only implantation with follow-up for up to 8 weeks. Transplantation of hPDMCs into mouse heart post-acute MI induction improved left ventricular function, with significantly enhanced vascularity in the cell-treated group. Furthermore, in minipigs post-acute MI induction, hPDMC transplantation significantly improved myocardial contractility compared to the control group (p = 0.016) at 8 weeks postinjury. In addition, tissue analysis confirmed that hPDMC transplantation induced increased vascularity, cardiomyogenic differentiation, and antiapoptotic effects. Our findings offer evidence that hPDMCs can modulate cardiac injury in both small and large animal models, possibly through proangiogenesis, cardiomyogenesis, and suppression of cardiomyocyte apoptosis. Our study offers mechanistic insights and preclinical evidence on using hPDMCs as a therapeutic strategy to treat severe cardiovascular diseases.

  9. Antiapoptotic Effect of Recombinant HMGB1 A-box Protein via Regulation of microRNA-21 in Myocardial Ischemia-Reperfusion Injury Model in Rats.

    PubMed

    Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Zhang, Bing; Chen, Hua

    2016-04-01

    The ~80 amino acid A box DNA-binding domain of high mobility group box 1 (HMGB1) protein antagonizes proinflammatory responses during myocardial ischemia reperfusion (I/R) injury. The exact role of microRNA-21 (miR-21) is unknown, but its altered levels are evident in I/R injury. This study examined the roles of HMGB1 A-box and miR-21 in rat myocardial I/R injury model. Sixty Sprague-Dawley rats were randomly divided into six equal groups: (1) Sham; (2) I/R; (3) Ischemic postconditioning (IPost); (4) AntagomiR-21 post-treatment; (5) Recombinant HMGB1 A-box pretreatment; and (6) Recombinant HMGB1 A-box + antagomiR-21 post-treatment. Hemodynamic indexes, arrhythmia scores, ischemic area and infarct size, myocardial injury, and related parameters were studied. Expression of miR-21 was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify apoptosis. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of pressure rise (+dp/dtmax), and decline (-dp/dtmax) showed clear reduction upon treatment with recombinant HMGB1 A-box. Arrhythmia was relieved and infarct area decreased in the group pretreated with recombinant HMGB1 A-box, compared with other groups. Circulating lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels increased in response to irreversible cellular injury, while creatine kinase MB isoenzymes (CK-MB) and superoxide dismutase (SOD) activities were reduced in the I/R group, which was reversed following recombinant HMGB1 A-box treatment. Interestingly, pretreatment with recombinant HMGB1 A-box showed the most dramatic reductions in miR-21 levels, compared with other groups. Significantly reduced apoptotic index (AI) was seen in recombinant HMGB1 A-box pretreatment group and recombinant HMGB1 A-box + antagomiR-21 post-treatment group, with the former showing a more

  10. Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

  11. Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipoprotein-2 subspecies levels in older athletes with silent myocardial ischemia.

    PubMed

    Katzel, L I; Busby-Whitehead, M J; Rogus, E M; Krauss, R M; Goldberg, A P

    1994-02-01

    Healthy older (64 +/- 1 years, mean +/- SEM) athletic (maximal oxygen consumption [VO2max] > 40 mL/kg/min) normocholesterolemic men with no prior history of coronary artery disease (CAD) were recruited for cardiovascular and metabolic studies. Thirty-three percent had asymptomatic exercise-induced ST segment depression on their exercise electrocardiogram (ECG), consistent with silent myocardial ischemia (SI). We hypothesized that abnormalities in high-density lipoprotein (HDL) and postprandial triglyceride (TG) metabolism may increase their risk for CAD. Compared with 12 nonischemic controls of comparable age, percent body fat, and VO2max, the 13 men with SI had decreased fasting HDL cholesterol ([HDL-C] 41 +/- 2 v 50 +/- 2 mg/dL, P < .001) and %HDL2b subspecies levels as measured by gradient gel electrophoresis (22 +/- 2 v 34 +/- 3, P < .001). Fasting plasma TG and low-density lipoprotein cholesterol (LDL-C) levels were the same in both groups. Although plasma glucose levels during an oral glucose tolerance test (OGTT) were similar in both groups, the total insulin area was higher in men with SI (P < .05). After consumption of a standard high-fat meal (680 kcal/m2 body surface area of a formula in which 86% of the calories were derived from fat), postprandial plasma TG, chylomicron-TG, and very-low-density lipoprotein (VLDL)-TG levels and postprandial areas were higher in men with SI (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Variation of plasma levels of endothelin, calcitonin gene-related peptide, nitric oxide, and malondialdehyde in acute myocardial ischemia reperfusion injury in a rabbit model.

    PubMed

    Zhao, Y B; Wang, Y Z; Yue, Y H; Zhao, W C; Feng, G X

    2015-05-25

    We examined the variation in plasma levels of endothelin (ET), calcitonin gene-related peptide (CGRP), nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) activity, in acute myocardial ischemia reperfusion injury in a rabbit model. Seventy rabbits were randomly assigned into 3 groups. Open-chest surgery (OCS) was performed for all rabbits. Group A (N = 20) received sham-surgery, group B (N = 25) was the reperfusion group, and group C (N = 25) was the infarction group. At 12 h after chest clo-sure, plasma ET levels in groups B and C were clearly increased, while CGRP levels were clearly decreased, particularly in group B. At 24 h after chest closure, ET levels were higher than before OCS, while there was no significant difference between groups B and C. ET in group B was decreased, while that in group C was increased at 12 h. No significant difference in CGRP was observed between 12 and 24 h after chest closure. NO levels in groups B and C at 12 h after chest closure were significantly decreased compared to those before OCS. NO levels in group B at 24, 48, and 72 h were significantly lower than those at 12 h, while those of group C were not significantly changed after 12 h. Dynamic monitoring and comparison of plasma levels of ET, CGRP, NO, and MDA as well as SOD activity revealed that appropriate intervention of these factors may reduce reperfusion injury.

  13. Transfusion of Plasma Collected at Late Phase after Preconditioning Reduces Myocardial Infarct Size Induced by Ischemia-reperfusion in Rats In vivo

    PubMed Central

    Zhao, Yang; Zheng, Zhi-Nan; Cheung, Chi-Wai; Zuo, Zhi-Yi; Jin, San-Qing

    2017-01-01

    Background: Plasma transfusion is a common clinical practice. Remote ischemic preconditioning (RIPC) protects organs against ischemia-reperfusion (IR) injury. Whether preconditioned plasma (PP), collected at late phase after RIPC, could protect organs against IR injury in vivo is unknown. This study explored whether transfusion of PP could reduce myocardial infarct size (IS) after IR in rat in vivo. Methods: Eighty Lewis rats were randomized to eight groups (n = 10 for each group). Two groups of plasma donor rats donated plasma at 48 h after transient limb ischemia (PP) or control protocol (nonpreconditioned plasma [NPP]). Six groups of recipient rats received normal saline (NS; NS-IR 1, and NS-IR 24 groups), NPP (NPP-IR 1 and NPP-IR 24 groups), or PP (PP-IR 1 and PP-IR 24 groups) at one or 24 h before myocardial IR. Myocardial IR consisted of 30-min left anterior descending (LAD) coronary artery occlusion and 180-min reperfusion. The area at risk (AAR) and infarct area were determined by double-staining with Evans blue and triphenyltetrazolium chloride. IS was calculated by infarct area divided by AAR. This was a 3 × 2 factorial design study, and factorial analysis was used to evaluate the data. If an interaction between the fluid and transfusion time existed, one-way analysis of variance with Bonferroni correction for multiple comparisons was used to analyze the single effects of fluid type when the transfusion time was fixed. Results: IS in the NPP-IR 1 and PP-IR 1 groups was smaller than in the NS-IR 1 group (F = 6.838, P = 0.005; NPP-IR 1: 57 ± 8% vs. NS-IR1: 68 ± 6%, t = 2.843, P = 0.020; PP-IR 1: 56 ± 8% vs. NS-IR 1: 68 ± 6%, t = 3.102, P = 0.009), but no significant difference was detected between the NPP-IR 1 and PP-IR 1 groups (57 ± 8% vs. 56 ± 8%, t = 0.069, P = 1.000). IS in the NPP-IR 24 and PP-IR 24 groups was smaller than in the NS-IR 24 group (F = 24.796, P < 0.001; NPP-IR 24: 56% ± 7% vs. NS-IR 24: 68 ± 7%, t = 3.102, P = 0.026; PP-IR 24

  14. CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice

    PubMed Central

    Benjamin, Ivor J.; Guo, Yiru; Srinivasan, Sathyanarayanan; Boudina, Sihem; Taylor, Ryan P.; Rajasekaran, Namakkal S.; Gottlieb, Roberta; Wawrousek, Eric F.; Abel, E. Dale; Bolli, Roberto

    2013-01-01

    The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched (~5–9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion × 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 ± 17.9 vs. 59.8 ± 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice (P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges. PMID:17873008

  15. Patients with suspected myocardial infarction: their test request patterns for clinical biochemistry in a British and a Canadian cardiac care unit.

    PubMed Central

    Henderson, A R; Gardner, M D

    1986-01-01

    The total number of routine clinical biochemistry tests requested for patients admitted to a coronary care unit with a diagnosis of "query myocardial infarction" were recorded over four to eight months. There were 156 sequential admissions in a British teaching hospital and 163 in a Canadian counterpart; the incidence of confirmed myocardial infarction was 53% and 50%, respectively. The pattern of tests ordered was substantially similar in each unit, unlike the rate of testing. For example, total creatine kinase was requested five times less often per patient in the British hospital than in the Canadian unit in cases of confirmed myocardial infarction (2.17 and 10.17, respectively; p less than 0.0001): the difference was much less, but still significant, when there was no infarction (2.01 and 3.55; p less than 0.0001). This study suggests a significant international difference in the use of clinical biochemistry services between coronary care units. Physicians (clinical and laboratory) need to be more critical of their use of protocols, which may prove wasteful of limited health care resources. PMID:3734118

  16. Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia-Reperfusion Model

    PubMed Central

    Dash, Rajesh; Chung, Jaehoon; Ikeno, Fumiaki; Hahn-Windgassen, Annett; Matsuura, Yuka; Bennett, Mihoko V.; Lyons, Jennifer K.; Teramoto, Tomohiko; Robbins, Robert C.; McConnell, Michael V.; Yeung, Alan C.; Brinton, Todd J.; Harnish, Phillip P.; Yang, Phillip C.

    2011-01-01

    Background Delayed gadolinium (Gd) enhancement MRI (DEMRI) identifies non-viable myocardium, but is non-specific and may overestimate nonviable territory. Manganese (Mn2+)-enhanced MRI (MEMRI) denotes specific Mn2+ uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI will identify viable infarct border zone (BZ) myocardium in vivo. Methods and Results Sixty-minute LAD ischemia-reperfusion injury (IR) was induced in 13 adult swine. Twenty-one days post-IR, 3T cardiac MRI was performed. MEMRI was obtained after injection (0.7 cc/kg) of Mn2+ contrast agent (EVP1001-1, Eagle Vision Pharmaceutical Corp.). DEMRI was then acquired after 0.2mmol/kg Gd injection. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured border zone myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride (TTC) stain and tissue electron microscopy (TEM) to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with TTC (MEMRI: r=0.78; DEMRI: r=0.75; p<0.004). MEMRI infarct volume percentage was significantly lower than DEMRI (14±4%* vs. 23±4%; *p<0.05). BZ MEMRI SNR was intermediate to remote and core infarct SNR (7.5±2.8* vs. 13.2±3.4 and 2.9±1.6; *p<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct (8.4±5.4 vs. 3.3±0.6 and 14.3±6.6; p>0.05). TEM analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement. Conclusions Dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy. PMID:21719779

  17. Type 1 diabetes: Developing the first risk-estimation model for predicting silent myocardial ischemia. The potential role of insulin resistance

    PubMed Central

    Hernández, Cristina; González-Sastre, Montserrat; Rodríguez, Ato-Antonio; Puntí, Jordi; Berlanga, Eugenio; Albert, Lara; Simó, Rafael; Vendrell, Joan; González Clemente, José-Miguel

    2017-01-01

    Objectives The aim of the study was to develop a novel risk estimation model for predicting silent myocardial ischemia (SMI) in patients with type 1 diabetes (T1DM) and no clinical cardiovascular disease, evaluating the potential role of insulin resistance in such a model. Additionally, the accuracy of this model was compared with currently available models for predicting clinical coronary artery disease (CAD) in general and diabetic populations. Research, design and methods Patients with T1DM (35–65years, >10-year duration) and no clinical cardiovascular disease were consecutively evaluated for: 1) clinical and anthropometric data (including classical cardiovascular risk factors), 2) insulin sensitivity (estimate of glucose disposal rate (eGDR)), and 3) SMI diagnosed by stress myocardial perfusion gated SPECTs. Results Eighty-four T1DM patients were evaluated [50.1±9.3 years, 50% men, 36.9% active smokers, T1DM duration: 19.0(15.9–27.5) years and eGDR 7.8(5.5–9.4)mg·kg-1·min-1]. Of these, ten were diagnosed with SMI (11.9%). Multivariate logistic regression models showed that only eGDR (OR = -0.593, p = 0.005) and active smoking (OR = 7.964, p = 0.018) were independently associated with SMI. The AUC of the ROC curve of this risk estimation model for predicting SMI was 0.833 (95%CI:0.692–0.974), higher than those obtained with the use of currently available models for predicting clinical CAD (Framingham Risk Equation: 0.833 vs. 0.688, p = 0.122; UKPDS Risk Engine (0.833 vs. 0.559; p = 0.001) and EDC equation: 0.833 vs. 0.558, p = 0.027). Conclusion This study provides the first ever reported risk-estimation model for predicting SMI in T1DM. The model only includes insulin resistance and active smoking as main predictors of SMI. PMID:28369151

  18. A soluble receptor for advanced glycation end-products inhibits myocardial apoptosis induced by ischemia/reperfusion via the JAK2/STAT3 pathway.

    PubMed

    Jiang, Xue; Guo, Cai-xia; Zeng, Xiang-jun; Li, Hui-hua; Chen, Bu-xing; Du, Feng-he

    2015-08-01

    sRAGE can protect cardiomyocytes from apoptosis induced by ischemia/reperfusion (I/R). However, the signaling mechanisms in cardioprotection by sRAGE are currently unknown. We investigated the cardioprotective effect and potential molecular mechanisms of sRAGE inhibition on apoptosis in the mouse myocardial I/R as an in vivo model and neonatal rat cardiomyocyte subjected to ischemic buffer as an in vitro model. Cardiac function and myocardial infarct size following by I/R were evaluated with echocardiography and Evans blue/2,3,5-triphenyltetrazolium chloride. Apoptosis was detected by TUNEL staining and caspase-3 activity. Expression of the apoptosis-related proteins p53, Bax, Bcl-2, JAK2/p-JAK2, STAT3/p-STAT3, AKT/p-AKT, ERK/p-ERK, STAT5A/p-STAT5A and STAT6/p-STAT6 were detected by western blot analysis in the presence and absence of the JAK2 inhibitor AG 490. sRAGE (100 µg/day) improved the heart function in mice with I/R: the left ventricular ejection fraction and fractional shortening were increased by 42 and 57%, respectively; the infarct size was decreased by 52%, the TUNEL-positive myocytes by 66%, and activity of caspase-3 by 24%, the protein expression of p53 and ratio of Bax to Bcl-2 by 29 and 88%, respectively; protein expression of the p-JAK2, p-STAT3 and p-AKT were increased by 92, 280 and 31%, respectively. sRAGE have no effect on protein expression of p-ERK1/2, p-STAT5A and p-STAT6 following by I/R. sRAGE (900 nmol/L) exhibited anti-apoptotic effects in cardiomyocytes by decreasing TUNEL-positive myocytes by 67% and caspase-3 activity by 20%, p53 protein level and the Bax/Bcl-2 ratio by 58 and 86%, respectively; increasing protein expression of the p-JAK2 and p-STAT3 by 26 and 156%, respectively, p-AKT protein level by 33%. The anti-apoptotic effects of sRAGE following I/R were blocked by JAK2 inhibitor AG 490. The effect of sRAGE reduction on TUNEL-positive myocytes and caspase-3 activity were abolished by PI3K inhibitor LY294002, but not ERK 1

  19. Spooky Suspects

    ERIC Educational Resources Information Center

    Pacifici, Lara

    2011-01-01

    This activity presents an option for covering biology content while engaging students in an investigation that highlights the spirit of Halloween. Students are engaged in the story line and have fun trying to solve the mystery kidnapping by using science skills to examine the evidence and eliminate some ghoulish suspects. (Contains 1 figure.)

  20. One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial).

    PubMed

    Selker, Harry P; Udelson, James E; Massaro, Joseph M; Ruthazer, Robin; D'Agostino, Ralph B; Griffith, John L; Sheehan, Patricia R; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M; Atkins, James M; Aufderheide, Tom P; Sayah, Assaad J; Pirrallo, Ronald G; Levy, Michael K; Richards, Michael E; Braude, Darren A; Doyle, Delanor D; Frascone, Ralph J; Kosiak, Donald J; Leaming, James M; Van Gelder, Carin M; Walter, Gert-Paul; Wayne, Marvin A; Woolard, Robert H; Beshansky, Joni R

    2014-05-15

    The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.

  1. Four Main Active Ingredients Derived from a Traditional Chinese Medicine Guanxin Shutong Capsule Cause Cardioprotection during Myocardial Ischemia Injury Calcium Overload Suppression.

    PubMed

    Liu, Feng; Huang, Zhuang-Zhuang; Sun, Yu-Hong; Li, Ting; Yang, Dong-Hua; Xu, Gang; Su, Ying-Ying; Zhang, Tao

    2017-03-01

    Guanxin Shutong capsule is a traditional Chinese medicine for the treatment of myocardial ischemia (MI). Previous studies have shown that the formula has four main active ingredients (FMAI), protocatechuic acid, cryptotanshinone, borneol, and eugenol. However, the mechanisms of action of these FMAI against MI injury are still not well known. The aim of the present study was to evaluate the protective effects of the FMAI on MI in vitro and in vivo. In vitro, rat neonatal cardiomyocytes were isolated, the cell viability and apoptosis rate were, respectively, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and fluorescence activating cell sorter, and the intracellular calcium concentration ([Ca(2+) ]i ) and CaM and CaMKII δ mRNA as well as protein levels were determined. Meanwhile, their downstream targets of RyR2 and PLB were also measured by western blot. In vivo, a rat model of coronary artery ligation was used to evaluate the cardioprotective effects. Infarct sizes of heart tissues and levels of serum biochemical indicators, including creatine kinase, lactate dehydrogenase, superoxide dismutase, and glutamate oxaloacetic transaminase, were measured. The in vitro results showed that the FMAI inhibited cell apoptosis, reduced [Ca(2+) ]i , decreased the expression of CaM and CaMKII δ, and increased the expression of RyR2 and PLB. In vivo, the FMAI diminished infract size, reduced creatine kinase, lactate dehydrogenase, and aspartate aminotransferase levels, and enhanced superoxide dismutase activity. In conclusion, our data suggest that the FMAI suppressed calcium overload and exerted its protective effect via its antioxidant, antiinflammatory, and anti-apoptosis activities. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Angiotensin-converting enzyme 2 inhibits high-mobility group box 1 and attenuates cardiac dysfunction post-myocardial ischemia

    PubMed Central

    Zhang, Juan; Wang, Lei; Shenoy, Vinayak; Krause, Eric; Oh, S. Paul; Pepine, Carl J; Katovich, Michael J

    2015-01-01

    High-mobility group box 1 (HMGB1) triggers and amplifies inflammation cascade following ischemic injury, and its elevated levels are associated with adverse clinical outcomes in patients with myocardial infarction (MI). Angiotensin-converting enzyme 2 (ACE2), a key member of vasoprotective axis of the renin-angiotensin system (RAS), regulates cardiovascular functions and exerts beneficial effects in cardiovascular disease. However, the association between HMGB1 and ACE2 has not been studied. We hypothesized that overexpression of ACE2 provides cardioprotective effects against MI via inhibiting HMGB1 and inflammation. ACE2 knock-in (KI) mice and littermate wild-type (WT) controls were subjected to either sham or coronary artery ligation surgery to induce MI. Heart function was assessed 4 weeks after surgery using echocardiography and Millar catheterization. Tissues were collected for histology and analysis of the expression of HMGB1, RAS components, and inflammatory cytokines. ACE2 in the heart of the ACE2 KI mice was 58-fold higher than WT controls. ACE2-MI mice exhibited a remarkable preservation of cardiac function and reduction of infarct size in comparison to WT-MI mice. Notably, ACE2 overexpression significantly reduced the MI-induced increase in apoptosis, macrophage infiltration, and HMGB1 and pro-inflammatory cytokine expression (TNF-α and IL-6). Moreover, in an in vitro study, ACE2 activation prevented the hypoxia-induced cell death and upregulation of HMGB1 in adult cardiomyocytes. This protective effect is correlated with downregulation of HMGB1 and downstream pro-inflammatory cascades, which could be useful for the development of novel treatment for ischemic heart disease. PMID:26498282

  3. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction

    PubMed Central

    Twerenbold, Raphael; Jaeger, Cedric; Rubini Gimenez, Maria; Wildi, Karin; Reichlin, Tobias; Nestelberger, Thomas; Boeddinghaus, Jasper; Grimm, Karin; Puelacher, Christian; Moehring, Berit; Pretre, Gil; Schaerli, Nicolas; Campodarve, Isabel; Rentsch, Katharina; Steuer, Stephan; Osswald, Stefan; Mueller, Christian

    2016-01-01

    Aims High-sensitivity cardiac troponin (hs-cTn) assays provide higher diagnostic accuracy for acute myocardial infarction (AMI) when compared with conventional assays, but may result in increased use of unnecessary coronary angiographies due to their increased detection of cardiomyocyte injury in conditions other than AMI. Methods and results We evaluated the impact of the clinical introduction of high-sensitivity cardiac troponin T (hs-cTnT) on the use of coronary angiography, stress testing, and time to discharge in 2544 patients presenting with symptoms suggestive of AMI to the emergency department (ED) within a multicentre study either before (1455 patients) or after (1089 patients) hs-cTnT introduction. Acute myocardial infarction was more often the clinical discharge diagnosis after hs-cTnT introduction (10 vs. 14%, P < 0.001), while unstable angina less often the clinical discharge diagnosis (14 vs. 9%, P = 0.007). The rate of coronary angiography was similar before and after the introduction of hs-cTnT (23 vs. 23%, P = 0.092), as was the percentage of coronary angiographies showing no stenosis (11 vs. 7%, P = 0.361). In contrast, the use of stress testing was substantially reduced from 29 to 19% (P < 0.001). In outpatients, median time to discharge from the ED decreased by 79 min (P < 0.001). Mean total costs decreased by 20% in outpatients after the introduction of hs-cTnT (P = 0.002). Conclusion The clinical introduction of hs-cTn does not lead to an increased or inappropriate use of coronary angiography. Introduction of hs-cTn is associated with an improved rule-out process and thereby reduces the need for stress testing and time to discharge. Clinical Trial Registration Information www.clinicaltrials.gov. Identifier, NCT00470587. PMID:27357358

  4. Effect on treadmill exercise capacity, myocardial ischemia, and left ventricular function as a result of repeated whole-body periodic acceleration with heparin pretreatment in patients with angina pectoris and mild left ventricular dysfunction.

    PubMed

    Miyamoto, Shoichi; Fujita, Masatoshi; Inoko, Moriaki; Oba, Muneo; Hosokawa, Ryohei; Haruna, Tetsuya; Izumi, Toshiaki; Saji, Yoshiaki; Nakane, Eisaku; Abe, Tomomi; Ueyama, Koji; Nohara, Ryuji

    2011-01-15

    Whole-body periodic acceleration (WBPA) has been developed as a passive exercise device capable of improving endothelial function by applying pulsatile shear stress to vascular endothelium. We hypothesized that treatment with WBPA improves exercise capacity, myocardial ischemia, and left ventricular (LV) function because of increased coronary and peripheral vasodilatory reserves in patients with angina. Twenty-six patients with angina who were not indicated for percutaneous coronary intervention and/or coronary artery bypass grafting were randomly assigned to remain sedentary (sedentary group) or undergo 20 sessions of WBPA with the motion platform for 4 weeks (WBPA group) in addition to conventional medical treatment. WBPA was applied at 2 to 3 Hz and approximately ±2.2 m/s² for 45 minutes. We repeated the symptom-limited treadmill exercise test and adenosine sestamibi myocardial scintigraphy. In the WBPA group, the exercise time until 0.1-mV ST-segment depression increased by 53% (p <0.01) and the double product at 0.1-mV ST-segment depression by 23% (p <0.001). Severity score of myocardial scintigraphy during adenosine infusion decreased from 20 ± 10 to 14 ± 8 (p <0.001) and severity score at rest also decreased from 13 ± 10 to 8 ± 10 (p <0.01). On scintigraphic images at rest, LV end-diastolic volume index decreased by 18% (p <0.01) with an augmentation of LV ejection fraction from 50 ± 16% to 55 ± 16% (p <0.01). In contrast, all studied parameters remained unchanged in the sedentary group. In conclusion, treatment with WBPA for patients with angina ameliorates exercise capacity, myocardial ischemia, and LV function.

  5. 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.

  6. 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

  7. 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

  8. Disruption of hypoxia-inducible transcription factor-prolyl hydroxylase domain-1 (PHD-1-/-) attenuates ex vivo myocardial ischemia/reperfusion injury through hypoxia-inducible factor-1α transcription factor and its target genes in mice.

    PubMed

    Adluri, Ram Sudheer; Thirunavukkarasu, Mahesh; Dunna, Nageswara Rao; Zhan, Lijun; Oriowo, Babatunde; Takeda, Kotaro; Sanchez, Juan A; Otani, Hajime; Maulik, Gautam; Fong, Guo-Hua; Maulik, Nilanjana

    2011-10-01

    Hypoxia-inducible transcription factor (HIF)-prolyl hydroxylases domain (PHD-1-3) are oxygen sensors that regulate the stability of the HIFs in an oxygen-dependent manner. Suppression of PHD enzymes leads to stabilization of HIFs and offers a potential treatment option for many ischemic disorders, such as peripheral artery occlusive disease, myocardial infarction, and stroke. Here, we show that homozygous disruption of PHD-1 (PHD-1(-/-)) could facilitate HIF-1α-mediated cardioprotection in ischemia/reperfused (I/R) myocardium. Wild-type (WT) and PHD-1(-/-) mice were randomized into WT time-matched control (TMC), PHD-1(-/-) TMC (PHD1TMC), WT I/R, and PHD-1(-/-) I/R (PHD1IR). Isolated hearts from each group were subjected to 30 min of global ischemia followed by 2 h of reperfusion. TMC hearts were perfused for 2 h 30 min without ischemia. Decreased infarct size (35%±0.6% vs. 49%±0.4%) and apoptotic cardiomyocytes (106±13 vs. 233±21 counts/100 high-power field) were observed in PHD1IR compared to wild-type ischemia/reperfusion (WTIR). Protein expression of HIF-1α was significantly increased in PHD1IR compared to WTIR. mRNA expression of β-catenin (1.9-fold), endothelial nitric oxide synthase (1.9-fold), p65 (1.9-fold), and Bcl-2 (2.7-fold) were upregulated in the PHD1IR compared with WTIR, which was studied by real-time quantitative polymerase chain reaction. Further, gel-shift analysis showed increased DNA binding activity of HIF-1α and nuclear factor-kappaB in PHD1IR compared to WTIR. In addition, nuclear translocation of β-catenin was increased in PHD1IR compared with WTIR. These findings indicated that silencing of PHD-1 attenuates myocardial I/R injury probably by enhancing HIF-1α/β-catenin/endothelial nitric oxide synthase/nuclear factor-kappaB and Bcl-2 signaling pathway.

  9. The evolving concept of physiological ischemia training vs. ischemia preconditioning.

    PubMed

    Ni, Jun; Lu, Hongjian; Lu, Xiao; Jiang, Minghui; Peng, Qingyun; Ren, Caili; Xiang, Jie; Mei, Chengyao; Li, Jianan

    2015-11-01

    Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning.

  10. 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

  11. Evaluation by quantitative 99m-technetium MIBI SPECT and echocardiography of myocardial perfusion and wall motion abnormalities in patients with dobutamine-induced ST-segment elevation.

    PubMed

    Elhendy, A; Geleijnse, M L; Roelandt, J R; van Domburg, R T; Cornel, J H; TenCate, F J; Postma-Tjoa, J; Reijs, A E; el-Said, G M; Fioretti, P M

    1995-09-01

    ST-segment elevation during exercise testing has been attributed to myocardial ischemia and wall motion abnormalities (WMA). However, the functional significance of ST-segment elevation during dobutamine stress testing (DST) has not been evaluated in patients referred for diagnostic evaluation of myocardial ischemia. DST (up to 40 micrograms/kg/min) with simultaneous echocardiography and technetium-99m sestamibi single-photon emission computed tomography (SPECT) was performed in 229 consecutive patients with suspected myocardial ischemia who were unable to perform an adequate exercise test; 127 (55%) had a previous acute myocardial infarction (AMI). ST elevation was defined as > or = 1 mm new or additional J point elevations with a horizontal or upsloping ST segment lasting 80 ms. Reversible perfusion defects on SPECT and new or worsening WMA during stress on echocardiography were considered diagnostic of ischemia. ST elevation occurred in 40 patients (17%) during the test; 34 of them (85%) had previous AMI. All patients with ST-segment elevation had abnormal scintigrams (fixed or reversible defects, or both) and abnormal wall motion (fixed or transient defect, or both) at peak stress. In patients who had ST elevation and no previous AMI (n = 6), ischemia was detected in all by echocardiography and in 5 (83%) by SPECT. In patients with previous AMI, the prevalence of ischemia was not different with or without ST elevation (53% vs 43% by echocardiography and 53% vs 48% by SPECT, respectively). Baseline regional wall motion score in the infarct zone was higher in patients with ST elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. A pilot study on diagnosis of coronary artery disease using computed tomography first-pass myocardial perfusion imaging at rest

    PubMed Central

    Wang, Qi; Qin, Jing; Gai, Lu-yue; Chen, Yun-dai; Dong, Wei; Guan, Zhi-wei; Wang, Zhi-guo; Sun, Zhi-jun; Tian, Jia-he

    2011-01-01

    Background: Although computed tomography coronary angiography (CTCA) can identify coronary stenosis, little data exists on the ability of multislice computed tomography (MSCT) to detect myocardial perfusion defects at rest. Methods: In 33 patients with diagnosed or suspected coronary artery disease (CAD), CTCA using retrospective electrocardiography (ECG) gating at rest and invasive coronary angiography (ICA) was performed. The 2D myocardial images were reconstructed in diastolic and systolic phases using the same raw data for CTCA. CT values of the myocardium were used as an estimate of myocardial enhancement, which were shown by color mapping. Myocardial ischemia was defined as a pattern of transient endocardial hypo-enhancement at systole and normal enhancement at diastole. The results of ICA were taken as the reference standard. Results: When a diameter reduction of more than 50% in ICA was used as diagnostic criteria of CAD, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT first-pass myocardial perfusion imaging (MPI) at rest were 0.85, 0.67, 0.92, and 0.50 per patient, respectively, and 0.58, 0.93, 0.85, and 0.76 per vessel, respectively. Conclusions: CT first-pass MPI at rest could detect CAD patients, which could become a practical and convenient way to detect ischemia, consequently offering the ability for MSCT to act as a “one stop shop” for the diagnosis of CAD. PMID:21634042

  13. Late reperfusion of a totally occluded infarct-related artery increases granulocyte-colony stimulation factor and reduces stroma-derived factor-1alpha blood levels in patients with ongoing ischemia after acute myocardial infarction.

    PubMed

    Kuo, Li-Tang; Chen, Shih-Jen; Cherng, Wen-Jin; Yang, Ning-I; Lee, Chen-Chin; Cheng, Chi-Wen; Verma, Subodh; Wang, Chao-Hung

    2009-07-01

    After acute myocardial infarction (AMI), reopening of a totally occluded infarct-related artery (IRA) at a subacute stage is still controversial in symptom-free patients. However, in patients with persistent ischemic symptoms and inadequate collaterals to the infarct area, recanalization is thought to provide beneficial effects. In addition to augmenting myocardial perfusion, we hypothesized that the benefit of recanalization involves the manipulation of circulating stem cell-mobilizing cytokines. This study included 30 patients with a totally occluded IRA and ongoing ischemic symptoms (the study group) and 30 patients with a partially occluded IRA (the control group). All patients underwent successful angioplasty and/or stenting. Before and immediately after the coronary intervention, blood granulocyte-colony-stimulating factor (G-CSF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and stroma-derived factor-1 (SDF-1alpha) were measured. After recanalization, G-CSF levels significantly increased in the study group compared to the control group (P=0.03). SDF-1alpha levels in the study group decreased relative to the controls (P=0.02). However, no significant changes in VEGF or SCF levels between the two groups were found. In the multivariate analysis, reopening of a totally occluded IRA was independently and significantly associated with changes in G-CSF and SDF-1alpha levels after recanalization. In conclusion, our data suggest that the benefits of late reperfusion of a totally occluded IRA in patients with ongoing myocardial ischemia may involve mechanisms associated with stem cell-mobilizing and plaque-stabilizing cytokines. This study provides the rationale to investigate serial changes in cytokines and the numbers of circulating progenitors after reperfusion in the future.

  14. 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

  15. Effects of resting ischemia assessed by thallium scintigraphy on QRS scoring system for estimating left ventricular function quantified by radionuclide angiography in acute myocardial infarction patients.

    PubMed

    DePace, N L; Hakki, A H; Iskandrian, A S

    1984-06-01

    The purpose of this study was to determine whether resting ischemia limits the usefulness of the QRS scoring system in predicting left ventricular (LV) ejection fraction (EF) in patients with acute infarction. We studied 48 patients after acute infarction by means of 12-lead ECG, thallium-201 scintigraphy, and radionuclide angiography. The thallium-201 scintigrams showed fixed defects in 25 patients, perfusion defects with partial or complete redistribution in the delayed images in 19 patients, and normal images in the remaining four patients. In the 48 patients there was a significant correlation between the QRS score and LVEF (r = -0.67; p less than 0.001). Patients with fixed defects showed a better correlation than patients with resting ischemia (r = -0.77 vs r = -0.60). A QRS score of 3 or less was used to separate patients with LVEF of 40% or greater from those with lower LVEF in patients with fixed defects (p = 0.0005), but this cutoff did not categorize patients with resting ischemia as to LVEF. Thus the presence of rest ischemia in patients with acute infarction may affect the correlation between QRS score and LVEF.

  16. Metabolic adaptation to a disruption in oxygen supply during myocardial ischemia and reperfusion is underpinned by temporal and quantitative changes in the cardiac proteome.

    PubMed

    Li, Xin; Arslan, Fatih; Ren, Yan; Adav, Sunil S; Poh, Kian Keong; Sorokin, Vitaly; Lee, Chuen Neng; de Kleijn, Dominique; Lim, Sai Kiang; Sze, Siu Kwan

    2012-04-06

    Despite decades of intensive research, there is still no effective treatment for ischemia/reperfusion (I/R) injury, an important corollary in the treatment of ischemic disease. I/R injury is initiated when the altered biochemistry of cells after ischemia is no longer compatible with oxygenated microenvironment (or reperfusion). To better understand the molecular basis of this alteration and subsequent incompatibility, we assessed the temporal and quantitative alterations in the cardiac proteome of a mouse cardiac I/R model by an iTRAQ approach at 30 min of ischemia, and at 60 or 120 min reperfusion after the ischemia using sham-operated mouse heart as the baseline control. Of the 509 quantified proteins identified, 121 proteins exhibited significant changes (p-value<0.05) over time and were mostly clustered in eight functional groups: Fatty acid oxidation, Glycolysis, TCA cycle, ETC (electron transport chain), Redox Homeostasis, Glutathione S-transferase, Apoptosis related, and Heat Shock proteins. The first four groups are intimately involved in ATP production and the last four groups are known to be important in cellular antioxidant activity. During ischemia and reperfusion, the short supply of oxygen precipitates a pivotal metabolic switch from aerobic metabolism involving fatty acid oxidation, TCA, and phosphorylation to anaerobic metabolism for ATP production and this, in turn, increases reactive oxygen species (ROS) formation. Therefore the implication of these 8 functional groups suggested that ischemia-reperfusion injury is underpinned in part by proteomic alterations. Reversion of these alterations to preischemia levels took at least 60 min, suggesting a refractory period in which the ischemic cells cannot adjust to the presence of oxygen. Therefore, therapeutics that could compensate for these proteomic alterations during this interim refractory period could alleviate ischemia-reperfusion injury to enhance cellular recovery from an ischemic to a normoxic

  17. 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

  18. 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.

  19. 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

  20. 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

  1. miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Shi, Jing; Bei, Yihua; Kong, Xiangqing; Liu, Xiaojun; Lei, Zhiyong; Xu, Tianzhao; Wang, Hui; Xuan, Qinkao; Chen, Ping; Xu, Jiahong; Che, Lin; Liu, Hui; Zhong, Jiuchang; Sluijter, Joost PG; Li, Xinli; Rosenzweig, Anthony; Xiao, Junjie

    2017-01-01

    Limited microRNAs (miRNAs, miRs) have been reported to be necessary for exercise-induced cardiac growth and essential for protection against pathological cardiac remodeling. Here we determined members of the miR-17-92 cluster and their passenger miRNAs expressions in two distinct murine exercise models and found that miR-17-3p was increased in both. miR-17-3p promoted cardiomyocyte hypertrophy, proliferation, and survival. TIMP-3 was identified as a direct target gene of miR-17-3p whereas PTEN was indirectly inhibited by miR-17-3p. Inhibition of miR-17-3p in vivo attenuated exercise-induced cardiac growth including cardiomyocyte hypertrophy and expression of markers of myocyte proliferation. Importantly, mice injected with miR-17-3p agomir were protected from adverse remodeling after cardiac ischemia/reperfusion injury. Collectively, these data suggest that miR-17-3p contributes to exercise-induced cardiac growth and protects against adverse ventricular remodeling. miR-17-3p may represent a novel therapeutic target to promote functional recovery after cardiac ischemia/reperfusion. PMID:28255358

  2. 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.

  3. 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%.

  4. Safety of dobutamine-atropine stress echocardiography in patients with suspected or proven coronary artery disease.

    PubMed

    Poldermans, D; Fioretti, P M; Boersma, E; Forster, T; van Urk, H; Cornel, J H; Arnese, M; Roelandt, R T

    1994-03-01

    The purpose of this study was to establish the safety of high-dose dobutamine-atropine stress echocardiography in patients with suspected or proven coronary artery disease. Six hundred fifty consecutive examinations were completed. Mean age of patients was 61 years; 300 had a previous myocardial infarction. Heart rate increased from 73 to 129 beats/min during stress testing, blood pressure did not change significantly (from 140/81 to 150/80 mm Hg). Atropine was added to dobutamine in 239 patients when no ischemia was induced with dobutamine alone and the peak heart rate was < 85% of the theoretical maximal heart rate. Atropine was more frequently administered to patients taking beta blockers (77 vs 27%, p < 0.001). New wall motion abnormalities developed in 243 patients (37%). Significant or symptomatic cardiac tachyarrhythmias, or both, developed during 24 examinations: 1 patient developed ventricular fibrillation, 3 patients developed sustained ventricular tachycardia, 12 patients experienced nonsustained ventricular tachycardia (< 10 beats) and 8 patients had paroxysmal atrial fibrillation. Cardiac arrhythmias were more frequent in patients with a history of ventricular arrhythmias (ventricular tachycardia and fibrillation) (odds ratio 9.9, 2.0 to 45) or left ventricular dysfunction at rest (wall motion score > 1.12) (odds ratio 2.9, 1.1-7.6), but not associated with atropine addition. No death or myocardial infarction occurred. The full dose was not given to 13 patients despite absence of signs or markers of ischemia for limiting side effect, yielding an overall feasibility of the stress test of 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. 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.

  6. 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

  7. Myocardial Ischemic Postconditioning Promotes Autophagy against Ischemia Reperfusion Injury via the Activation of the nNOS/AMPK/mTOR Pathway

    PubMed Central

    Hao, Maojuan; Zhu, Suhua; Hu, Liang; Zhu, Hongyi; Wu, Xiaowei; Li, Qingping

    2017-01-01

    Autophagy participates in the progression of many diseases, comprising ischemia/ reperfusion (I/R). It is reported that it is involved in the protective mechanism of ischemic postconditioning (IPostC). According to research, neuronal nitric oxide synthase (nNOS) is also involved in the condition of I/R and IPostC. However, the relationship between nNOS, autophagy and IPostC has not been previously investigated. We hypothesize that IPostC promotes autophagy activity against I/R injury partially through nNOS-mediated pathways. Mouse hearts were subjected to I/R injury through the ligation of the left anterior descending coronary artery. H9c2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro. IPostC, compared with I/R, restored nNOS activity, increased the formation of autophagosome and restored the impaired autophagic flux, thus autophagic activity was raised markedly. IPostC increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and suppressed mammalian target of rapamycin (mTOR), but a selective nNOS inhibitor abolished those effects. Similar effects of IPostC were demonstrated in H9c2 cells in vitro. IPostC decreased infarct size and preserved most of the normal structure. The level of reactive oxygen species (ROS) and cell apoptosis were reduced by IPostC with improved cell viability and mitochondrial membrane potential. However, an autophagy inhibitor suppressed the protective effects. These results suggest that IPostC promoted autophagy against I/R injury at least partially via the activation of nNOS/AMPK/mTOR pathway. PMID:28287478

  8. Assessment of cardiac function using myocardial perfusion imaging technique on SPECT with 99mTc sestamibi

    NASA Astrophysics Data System (ADS)

    Gani, M. R. A.; Nazir, F.; Pawiro, S. A.; Soejoko, D. S.

    2016-03-01

    Suspicion on coronary heart disease can be confirmed by observing the function of left ventricle cardiac muscle with Myocardial Perfusion Imaging techniques. The function perfusion itself is indicated by the uptake of radiopharmaceutical tracer. The 31 patients were studied undergoing the MPI examination on Gatot Soebroto Hospital using 99mTc-sestamibi radiopharmaceutical with stress and rest conditions. Stress was stimulated by physical exercise or pharmacological agent. After two hours, the patient did rest condition on the same day. The difference of uptake percentage between stress and rest conditions will be used to determine the malfunction of perfusion due to ischemic or infarct. Degradation of cardiac function was determined based on the image-based assessment of five segments of left ventricle cardiac. As a result, 8 (25.8%) patients had normal myocardial perfusion and 11 (35.5%) patients suspected for having partial ischemia. Total ischemia occurred to 8 (25.8%) patients with reversible and irreversible ischemia and the remaining 4 (12.9%) patients for partial infarct with characteristic the percentage of perfusion ≤50%. It is concluded that MPI technique of image-based assessment on uptake percentage difference between stress and rest conditions can be employed to predict abnormal perfusion as complementary information to diagnose the cardiac function.

  9. 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.

  10. Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus.

    PubMed

    Lejay, Anne; Fang, Fei; John, Rohan; Van, Julie A D; Barr, Meredith; Thaveau, Fabien; Chakfe, Nabil; Geny, Bernard; Scholey, James W

    2016-02-01

    Ischemia/reperfusion, which is characterized by deficient oxygen supply and subsequent restoration of blood flow, can cause irreversible damages to tissue. Mechanisms contributing to the pathogenesis of ischemia reperfusion injury are complex, multifactorial and highly integrated. Extensive research has focused on increasing organ tolerance to ischemia reperfusion injury, especially through the use of ischemic conditioning strategies. Of morbidities that potentially compromise the protective mechanisms of the heart, diabetes mellitus appears primarily important to study. Diabetes mellitus increases myocardial susceptibility to ischemia reperfusion injury and also modifies myocardial responses to ischemic conditioning strategies by disruption of intracellular signaling responsible for enhancement of resistance to cell death. The purpose of this review is twofold: first, to summarize mechanisms underlying ischemia reperfusion injury and the signal transduction pathways underlying ischemic conditioning cardioprotection; and second, to focus on diabetes mellitus and mechanisms that may be responsible for the lack of effect of ischemic conditioning strategies in diabetes.

  11. Silent Ischemia

    MedlinePlus

    ... Kawasaki Disease Long Q-T Syndrome Marfan Syndrome Metabolic Syndrome Mitral Valve Prolapse Myocardial Bridge Myocarditis Obstructive Sleep Apnea Pericarditis Peripheral Vascular Disease Rheumatic Fever Sick Sinus Syndrome Stroke Sudden Cardiac Arrest ...

  12. 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.

  13. Myocardial Noncompaction Presenting With Myocardial Bridge

    PubMed Central

    Shen, Yuechun; Li, Xinchun; Lu, Dongfeng; Xiao, Aiyi; Li, Jun

    2015-01-01

    Abstract Myocardial noncompaction, namly isolated noncompaction of the left ventricular myocardium (NVM), is a rare congenital disease. It can be either seen in the absence of other cardiac anomalies, or associated with other congenital cardiac defects, mostly stenotic lesions of the left ventricular outflow tract. A myocardial bridge (MB) is thought being associated with coronary heart disease, such as coronary spasm, arrhythmia, and so on. The significance of MB in association with other congenital cardiac conditions is unknown. We report a novel case who was presented NVM and MB. A 34-year-old man complained of chest prickling-like pain and dizzy for 1 year. His blood pressure was 110/70 mm Hg. Echocardiograph revealed increased trabeculations below the level of papillary muscle of left ventricle (LV); deep intertrabecular recesses in the endocardial wall of LV particularly in apex free wall; and LV ejection fraction of 57%. A coronary computerized tomography scan showed that part, 38.9 cm, of left descending artery tunnel was surrounding by cardiac muscles rather than resting on top of the myocardium. The therapeutics interventions included lifestyle cares, agents of anti-ischemia and improvement myocardial cell metabolism. The patient was followed up for 2.6 years, and his general condition was stable. This case indicates that NVM can be developed with MB, and the complete diagnosis of NVM and MB should be made by different image studies. PMID:26356695

  14. 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.

  15. Cordilleran suspect terranes

    USGS Publications Warehouse

    Coney, P.J.; Jones, D.L.; Monger, J.W.H.

    1980-01-01

    Over 70% of the North American Cordillera is made up of 'suspect terranes'. Many of these geological provinces are certainly allochthonous to the North American continent and seem to have been swept from far reaches of the Pacific Ocean before collision and accretion into the Cordilleran margin mostly in Mesozoic to early Cenozoic time. ?? 1980 Nature Publishing Group.

  16. 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.

  17. Regular Alcohol Consumption Mimics Cardiac Preconditioning by Protecting against Ischemia-Reperfusion Injury

    NASA Astrophysics Data System (ADS)

    Miyamae, Masami; Diamond, Ivan; Weiner, Michael W.; Camacho, S. Albert; Figueredo, Vincent M.

    1997-04-01

    Epidemiologic studies indicate that long-term alcohol consumption decreases the incidence of coronary disease and may improve outcome after myocardial infarction. Attenuation of ischemia-reperfusion injury after myocardial infarction improves survival. This study investigates the possibility that alcohol consumption can improve survival after myocardial infarction by reducing ischemia-reperfusion injury. Hearts were isolated from guinea pigs after drinking ethanol for 3-12 weeks and subjected to global ischemia and reperfusion. Hearts from animals drinking ethanol showed improved functional recovery and decreased myocyte damage when compared with controls. Adenosine A1 receptor blockade abolished the protection provided by ethanol consumption. These findings indicate that long-term alcohol consumption reduces myocardial ischemia-reperfusion injury and that adenosine A1 receptors are required for this protective effect of ethanol. This cardioprotective effect of long-term alcohol consumption mimics preconditioning and may, in part, account for the beneficial effect of moderate drinking on cardiac health.

  18. Current technology in assessing painless and painful ischemia

    SciTech Connect

    Selwyn, A.P. )

    1990-09-01

    Recent technologic advances have yielded diverse techniques for studying myocardial ischemia, a useful functional expression of coronary artery disease. These techniques have revealed new characteristics and expanded our understanding of myocardial ischemia. In turn this has led to the establishment of more realistic and discriminating criteria on which to base diagnostic and management decisions. Many of the techniques are noninvasive and can be performed in the cardiologist's office. These include treadmill exercise testing; radioisotope techniques, including ejection fraction studies, stress thallium scintigraphy, and tomographic imaging; and ambulatory monitoring. Other, newer techniques include provocative tests that induce ischemia in patients who cannot exercise. These new noninvasive tests should be used to detect transient ischemia, estimate its severity, and thus record a measure of the patient's risk for adverse coronary events.

  19. [Effect of emoxypine on myocardial electrical instability and homeostasis parameters in patients with acute disturbance of cerebrovascular circulation].

    PubMed

    Stoliarova, V V

    2002-01-01

    The frequency of myocardial ischemia onsets, QT interval dispersion, homeostasis characteristics, and lipid peroxidation parameters were studied in a group of 49 patients with acute disturbance of cerebral circulation (ADCC). The Holter ECG monitoring revealed myocardial ischemia episodes in 42% of patients, and myocardial instability manifested by the QT interval variance in 82% of patients. The control group (30 patients) received standard complex therapy, while the test group (19 patients) additionally received emoxypine. The administration of emoxypine reduced the incidence of myocardial ischemia and positively influenced the QT interval variance and the main parameters of homeostasis.

  20. [Myocardial depression in the burn patient].

    PubMed

    Carrillo-Esper, Raúl; Sánchez-Zúñiga, Martín de Jesús

    2006-01-01

    Myocardial depression and heart failure are frequent complications in critically ill burn patients. The physiopathology is complex and involves the activation of inflammatory pathways, ischemia-reperfusion, oxidative stress and endothelial lesion. Diagnosis should be made early by means of hemodynamic monitoring. Treatment is accomplished by inotropics that act on different pathways of the contractile function and immune response associated with antioxidants and allopurinol.

  1. 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.

  2. 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

  3. Disappearance of myocardial bridging of the left anterior descending coronary artery after inferior myocardial infarction.

    PubMed

    Yıldız, Bekir Serhat; Esin, Fatma; Alihanoğlu, Yusuf Izzettin; Kılıç, Ismail Doğu; Evrengül, Harun

    2014-06-01

    Myocardial bridging (MB) is defined as the intramural course of a major epicardial coronary artery, and is mostly confined to the left ventricle and the left anterior descending coronary artery (LAD). MB 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 MB may suffer from myocardial ischemia, myocardial infarction (MI), arrhythmias, and even sudden death. Therefore, the diagnosis and treatment of MB are both important. Since MB is congenital, its disappearance is unlikely. We here report a very rare case of disappearance of MB after inferior MI.

  4. Myocardial Bridge

    MedlinePlus

    ... Kawasaki Disease Long Q-T Syndrome Marfan Syndrome Metabolic Syndrome Mitral Valve Prolapse Myocarditis Obstructive Sleep Apnea Pericarditis Peripheral Vascular Disease Rheumatic Fever Sick Sinus Syndrome Silent Ischemia Stroke Sudden ...

  5. Mechanisms of cell survival in myocardial hibernation.

    PubMed

    Depre, Christophe; Vatner, Stephen F

    2005-04-01

    Myocardial hibernation represents a condition of regional ventricular dysfunction in patients with chronic coronary artery disease, which reverses gradually after revascularization. The precise mechanism mediating the regional dysfunction is still debated. One hypothesis suggests that chronic hypoperfusion results in a self-protecting downregulation in myocardial function and metabolism to match the decreased oxygen supply. An alternative hypothesis suggests that the myocardium is subject to repetitive episodes of ischemic dysfunction resulting from an imbalance between myocardial metabolic demand and supply that eventually creates a sustained depression of contractility. It is generally agreed that hibernating myocardium is submitted repeatedly to ischemic stress, and therefore one question persists: how do myocytes survive in the setting of chronic ischemia? The hallmark of hibernating myocardium is a maintained viability of the dysfunctional myocardium which relies on an increased uptake of glucose. We propose that, in addition to this metabolic adjustment, there must be molecular switches that confer resistance to ischemia in hibernating myocardium. Such mechanisms include the activation of a genomic program of cell survival as well as autophagy. These protective mechanisms are induced by ischemia and remain activated chronically as long as either sustained or intermittent ischemia persists.

  6. 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.

  7. Assessing the adequacy of myocardial perfusion in man: anatomic and functional techniques

    SciTech Connect

    Miller, S.W.; Boucher, C.A.

    1985-12-01

    The dynamic nature of the coronary vasculature and its stenoses frequently requires more than a subjective anatomic visualization to evaluate potential myocardial ischemia. Although coronary arteriography can assess stenoses of no hemodynamic importance (less than 20 per cent diameter reduction) and lesions that severely impair blood flow (greater than 80 per cent diameter reduction). Most coronary stenoses fall between these two extremes. Quantitative arteriography and radioisotope perfusion studies can improve the accuracy of predicting myocardial ischemia.

  8. 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.

  9. 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.

  10. [Heart failure due to ischemia--the adaptive mechanisms].

    PubMed

    Mitu, M; Mitu, F

    1999-01-01

    Chronic myocardial ischemia is the leading cause of disturbances in myocardial contractility (myocardial infarction) or hemodynamic overload upon the left ventricle. The heart reactions consist in a series of adaptative mechanisms in order to maintain its pump function: Frank-Starling mechanism, myocardial hypertrophy and neurohumoral activation. In heart failure, the cardiac output is maintained by an increase of the preload which enhances the contractility (Frank-Starling law). Myocardial ischemia influences the systolic and diastolic function. The decrease of cardiac output leads to neurohumoral responses which, in the initial stages of cardiac failure are compensatory; along with the progression of the disease, they exert adverse effects. Increased activity of the sympathetic nervous system induces high cardiac rates, chronotropic incompetence. Activation of the renin-angiotensin system held to myocardial and vascular hypertrophy, vasoconstriction, fluid retention. Endothelin is the most powerful vasoconstrictor; its plasmatic concentrations correlate with the severity of the disease. Vasodilator mediators released in cardiac failure are the natriuretic peptide, nitric oxide, dopamine, prostacicline, bradikinin.

  11. 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.

  12. 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.

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

    PubMed

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

    2016-08-01

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

  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. 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.

  16. Regadenoson-stress myocardial CT perfusion and single-photon emission CT: rationale, design, and acquisition methods of a prospective, multicenter, multivendor comparison.

    PubMed

    Cury, Ricardo C; Kitt, Therese M; Feaheny, Kathleen; Akin, Jamie; George, Richard T

    2014-01-01

    Pharmacologic stress myocardial CT perfusion (CTP) has been reported to be a viable imaging modality for detection of myocardial ischemia compared with single-photon emission CT (SPECT) in several single-center studies. However, regadenoson-stress CTP has not previously been compared with SPECT in a multicenter, multivendor study. The rationale and design of a phase 2, randomized, cross-over study of regadenoson-stress myocardial perfusion imaging by CTP compared with SPECT are described herein. The study will be conducted at approximately 25 sites by using 6 different CT scanner models, including 64-, 128-, 256-, and 320-slice systems. Subjects with known/suspected coronary artery disease will be randomly assigned to 1 of 2 imaging procedure sequences; rest and regadenoson-stress SPECT on day 1, then regadenoson-stress CTP and rest CTP/coronary CT angiography (same acquisition) on day 2; or regadenoson-stress CTP and rest CTP/CT angiography on day 1, then rest and regadenoson-stress SPECT on day 2. The prespecified primary analysis examines the agreement rate between CTP and SPECT for detecting or excluding ischemia (≥2 or 0-1 reversible defects, respectively), as assessed by 3 independent blinded readers for each modality. Non-inferiority will be indicated if the lower boundary of the 95% CI for the agreement rate is within 0.15 of 0.78 (the observed agreement rate in the regadenoson pivotal trials). The protocol described herein will support the first evaluation of regadenoson-stress CTP by using multiple scanner types compared with SPECT.

  17. SU-C-201-04: Quantification of Perfusion Heterogeneity Based On Texture Analysis for Fully Automatic Detection of Ischemic Deficits From Myocardial Perfusion Imaging

    SciTech Connect

    Fang, Y; Huang, H; Su, T

    2015-06-15

    Purpose: Texture-based quantification of image heterogeneity has been a popular topic for imaging studies in recent years. As previous studies mainly focus on oncological applications, we report our recent efforts of applying such techniques on cardiac perfusion imaging. A fully automated procedure has been developed to perform texture analysis for measuring the image heterogeneity. Clinical data were used to evaluate the preliminary performance of such methods. Methods: Myocardial perfusion images of Thallium-201 scans were collected from 293 patients with suspected coronary artery disease. Each subject underwent a Tl-201 scan and a percutaneous coronary intervention (PCI) within three months. The PCI Result was used as the gold standard of coronary ischemia of more than 70% stenosis. Each Tl-201 scan was spatially normalized to an image template for fully automatic segmentation of the LV. The segmented voxel intensities were then carried into the texture analysis with our open-source software Chang Gung Image Texture Analysis toolbox (CGITA). To evaluate the clinical performance of the image heterogeneity for detecting the coronary stenosis, receiver operating characteristic (ROC) analysis was used to compute the overall accuracy, sensitivity and specificity as well as the area under curve (AUC). Those indices were compared to those obtained from the commercially available semi-automatic software QPS. Results: With the fully automatic procedure to quantify heterogeneity from Tl-201 scans, we were able to achieve a good discrimination with good accuracy (74%), sensitivity (73%), specificity (77%) and AUC of 0.82. Such performance is similar to those obtained from the semi-automatic QPS software that gives a sensitivity of 71% and specificity of 77%. Conclusion: Based on fully automatic procedures of data processing, our preliminary data indicate that the image heterogeneity of myocardial perfusion imaging can provide useful information for automatic determination

  18. Edema is a sign of early acute myocardial infarction on post-mortem magnetic resonance imaging.

    PubMed

    Ruder, Thomas D; Ebert, Lars C; Khattab, Ahmed A; Rieben, Robert; Thali, Michael J; Kamat, Pranitha

    2013-12-01

    The aim of this study was to investigate if acute myocardial infarction can be detected by post-mortem cardiac magnetic resonance (PMMR) at an earlier stage than by traditional autopsy, i.e., within less than 4 h after onset of ischemia; and if so, to determine the characteristics of PMMR findings in early acute infarcts. Twenty-one ex vivo porcine hearts with acute myocardial infarction underwent T2-weighted cardiac PMMR imaging within 3 h of onset of iatrogenic ischemia. PMMR imaging findings were compared to macroscopic findings. Myocardial edema induced by ischemia and reperfusion was visible on PMMR in all cases. Typical findings of early acute ischemic injury on PMMR consist of a central zone of intermediate signal intensity bordered by a rim of increased signal intensity. Myocardial edema can be detected on cardiac PMMR within the first 3 h after the onset of ischemia