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  1. Article ; Online: Swine Model of Myocardial Infarction Induced by Ischemia-Reperfusion and Embolization.

    Mazurek, Renata / Bikou, Olympia / Ishikawa, Kiyotake

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2803, Page(s) 189–203

    Abstract: Acute myocardial infarction continues to account for a growing burden of heart failure worldwide. Despite existing therapies, new approaches for reducing the extent of damage and better managing heart failure progression are urgently needed. Preclinical ... ...

    Abstract Acute myocardial infarction continues to account for a growing burden of heart failure worldwide. Despite existing therapies, new approaches for reducing the extent of damage and better managing heart failure progression are urgently needed. Preclinical large animal models are a critical step in the translation of scientific discoveries toward clinical trials and therapeutic application. In this chapter, we detail methods to induce swine models of myocardial infarction through catheter-mediated approaches involving either temporary (ischemia-reperfusion) or permanent (thrombus injection or embolic coil) occlusions. These techniques are relatively low in invasiveness, while infarct size with corresponding cardiac dysfunction can be controlled by adjusting the location of coronary occlusion. We also describe methods for cardiac angiography and echocardiography in pigs. This is the second edition of a previously published chapter with modifications.
    MeSH term(s) Animals ; Myocardial Infarction/therapy ; Myocardial Infarction/pathology ; Disease Models, Animal ; Swine ; Myocardial Reperfusion Injury/therapy ; Myocardial Reperfusion Injury/etiology ; Myocardial Reperfusion Injury/pathology ; Echocardiography/methods ; Coronary Angiography/methods ; Embolism/etiology ; Embolism/therapy ; Embolism/pathology
    Language English
    Publishing date 2024-04-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3846-0_14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: ELISpot Assay for Gene Therapy in Large Animal Studies.

    Mazurek, Renata / Ishikawa, Kiyotake

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2573, Page(s) 323–332

    Abstract: Formation of neutralizing antibodies and cellular immune response with repeat adeno-associated virus (AAV) gene therapy dosing are critical concerns in translational, large animal studies. The enzyme-linked immunospot/immunosorbent spot (ELISpot) assay ... ...

    Abstract Formation of neutralizing antibodies and cellular immune response with repeat adeno-associated virus (AAV) gene therapy dosing are critical concerns in translational, large animal studies. The enzyme-linked immunospot/immunosorbent spot (ELISpot) assay introduced a way to track B- and/or T-cell response to therapy over time at a protein level. We describe the protocol for this assay looking at relative interferon (IFN)-γ secretion in pre- and post-AAV injections in a pig model.
    MeSH term(s) Animals ; Enzyme-Linked Immunospot Assay/methods ; Genetic Therapy ; Immunity, Cellular ; Interferon-gamma/metabolism ; Swine ; T-Lymphocytes
    Chemical Substances Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2707-5_25
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  3. Article ; Online: Swine Model of Coronary Artery Dissection.

    Leonard, Kyra / Mavropoulos, Spyros A / Mazurek, Renata / Ishikawa, Kiyotake

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2803, Page(s) 219–226

    Abstract: Coronary artery dissection (CAD) is the intimal tearing of the coronary arterial wall and can be iatrogenic, spontaneous, or traumatic in origin. CAD is a rare but challenging condition that can cause significant hemodynamic compromise. Management ... ...

    Abstract Coronary artery dissection (CAD) is the intimal tearing of the coronary arterial wall and can be iatrogenic, spontaneous, or traumatic in origin. CAD is a rare but challenging condition that can cause significant hemodynamic compromise. Management strategies for CAD, such as the use of mechanical circulatory support devices, are available in the clinical setting. However, the incidence, etiology, and optimal management of CAD are not well-defined, emphasizing the need for adequate animal models in preclinical studies. Large animal models provide the human-like conditions necessary for testing and development of potential treatment strategies. In this chapter, we describe a method for the creation of a CAD swine model.
    MeSH term(s) Animals ; Swine ; Disease Models, Animal ; Coronary Vessels/pathology ; Aortic Dissection ; Humans ; Coronary Vessel Anomalies ; Vascular Diseases/etiology ; Vascular Diseases/pathology ; Vascular Diseases/therapy ; Vascular Diseases/congenital ; Coronary Artery Disease/pathology
    Language English
    Publishing date 2024-04-27
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3846-0_16
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Barriers in Heart Failure Gene Therapy and Approaches to Overcome Them.

    Ravichandran, Anjali J / Romeo, Francisco J / Mazurek, Renata / Ishikawa, Kiyotake

    Heart, lung & circulation

    2023  Volume 32, Issue 7, Page(s) 780–789

    MeSH term(s) Humans ; Genetic Therapy ; Gene Transfer Techniques ; Heart Failure/genetics ; Heart Failure/therapy ; Genetic Vectors ; Transduction, Genetic ; Adenoviridae/genetics
    Language English
    Publishing date 2023-04-11
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2020980-0
    ISSN 1444-2892 ; 1443-9506
    ISSN (online) 1444-2892
    ISSN 1443-9506
    DOI 10.1016/j.hlc.2023.02.011
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4988: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  5. Article ; Online: Cell-Based Determination of Neutralizing Antibodies Against Adeno-Associated Virus in Cardiac Gene Therapy.

    Ravichandran, Anjali J / Mazurek, Renata / Ishikawa, Kiyotake

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2573, Page(s) 293–304

    Abstract: The field of cardiac gene therapy has seen the rising use of adeno-associated viral (AAV) vectors as a promising therapeutic option for cardiac diseases and heart failure. To achieve intended results of AAV delivery, a majority of clinical studies screen ...

    Abstract The field of cardiac gene therapy has seen the rising use of adeno-associated viral (AAV) vectors as a promising therapeutic option for cardiac diseases and heart failure. To achieve intended results of AAV delivery, a majority of clinical studies screen patients for existing neutralizing antibodies that could inhibit the effects of the administered AAV and confound treatment efficacy. The cell-based neutralizing antibody assay offers a method of quantifying and identifying a patient's existing neutralizing antibodies against specific serotypes. Combined with the luciferase assay, the neutralizing antibody assay tests the ability of patient antibodies in the blood to prevent gene transduction of AAV-encoded luciferase gene at ranging serial dilutions. This chapter provides a protocol and experimental techniques to determine the presence of neutralizing antibodies against AAV in the blood.
    MeSH term(s) Antibodies, Neutralizing ; Antibodies, Viral ; Dependovirus/genetics ; Genetic Therapy/methods ; Genetic Vectors/genetics ; Humans ; Serogroup
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2707-5_22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

    Sakata, Tomoki / Mavropoulos, Spyros A / Mazurek, Renata / Romeo, Francisco J / Ravichandran, Anjali J / Marx, Jonas M / Kariya, Taro / Ishikawa, Kiyotake

    The Journal of physiology

    2024  Volume 602, Issue 8, Page(s) 1669–1680

    Abstract: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We ... ...

    Abstract Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicating that the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.
    MeSH term(s) Animals ; Swine ; Diastole/physiology ; Ventricular Function, Left/physiology ; Blood Pressure ; Myocardial Infarction ; Coronary Vessels ; Coronary Circulation/physiology
    Language English
    Publishing date 2024-03-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP285586
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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.65: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Device-Based Approaches Targeting Cardioprotection in Myocardial Infarction: The Expanding Armamentarium of Innovative Strategies.

    Romeo, Francisco José / Mazurek, Renata / Sakata, Tomoki / Mavropoulos, Spyros A / Ishikawa, Kiyotake

    Journal of the American Heart Association

    2022  Volume 11, Issue 23, Page(s) e026474

    Abstract: Coronary reperfusion therapy has played a pivotal role for reducing mortality and heart failure after acute myocardial infarction. Although several adjunctive approaches have been studied for reducing infarct size further, both ischemia-reperfusion ... ...

    Abstract Coronary reperfusion therapy has played a pivotal role for reducing mortality and heart failure after acute myocardial infarction. Although several adjunctive approaches have been studied for reducing infarct size further, both ischemia-reperfusion injury and microvascular obstruction are still major contributors to both early and late clinical events after acute myocardial infarction. The progress in the field of cardioprotection has found several promising proof-of-concept preclinical studies. However, translation from bench to bedside has not been very successful. This comprehensive review discusses the importance of infarct size as a driver of clinical outcomes post-acute myocardial infarction and summarizes recent novel device-based approaches for infarct size reduction. Device-based interventions including mechanical cardiac unloading, myocardial cooling, coronary sinus interventions, supersaturated oxygen therapy, and vagal stimulation are discussed. Many of these approaches can modify ischemic myocardial biology before reperfusion and offer unique opportunities to target ischemia-reperfusion injury.
    MeSH term(s) Humans ; Proof of Concept Study ; Myocardial Infarction/therapy ; Reperfusion Injury
    Language English
    Publishing date 2022-11-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.122.026474
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  8. Article ; Online: Assessing the Effect of Cardiac Gene Therapy Using Catheter-Based Pressure-Volume Measurement in Large Animals.

    Sakata, Tomoki / Mazurek, Renata / Mavropoulos, Spyros A / Romeo, Francisco J / Ravichandran, Anjali J / Ishikawa, Kiyotake

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2573, Page(s) 313–321

    Abstract: Gene therapy for heart failure targets various pathways that modulate cardiac function. Its detailed evaluation is crucial for proving the efficacy of cardiac gene therapies. Parameters that can be obtained by noninvasive approaches are generally ... ...

    Abstract Gene therapy for heart failure targets various pathways that modulate cardiac function. Its detailed evaluation is crucial for proving the efficacy of cardiac gene therapies. Parameters that can be obtained by noninvasive approaches are generally influenced by loading conditions of the heart. In contrast, catheter-based left ventricular pressure-volume assessment provides a unique option to minimally invasively assess intrinsic myocardial function in a load-insensitive manner. In this chapter, we describe procedural steps for performing pressure-volume measurements and analysis in a preclinical large animal model.
    MeSH term(s) Animals ; Cardiotonic Agents ; Catheters ; Genetic Therapy ; Heart ; Heart Failure/therapy ; Hemodynamics ; Myocardial Contraction
    Chemical Substances Cardiotonic Agents
    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2707-5_24
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  9. Article ; Online: Negative Impact of Acute Reloading after Mechanical Left Ventricular Unloading.

    Mazurek, Renata / Kariya, Taro / Sakata, Tomoki / Mavropoulos, Spyros A / Ravichandran, Anjali J / Romeo, Francisco J / Yamada, Kelly P / Ishikawa, Kiyotake

    Journal of cardiovascular translational research

    2023  Volume 17, Issue 2, Page(s) 233–241

    Abstract: Mechanical LV unloading for acute myocardial infarction (MI) is a promising supportive therapy to reperfusion. However, no data is available on exit strategy. We evaluated hemodynamic and cellular effects of reloading after Impella-mediated LV unloading ... ...

    Abstract Mechanical LV unloading for acute myocardial infarction (MI) is a promising supportive therapy to reperfusion. However, no data is available on exit strategy. We evaluated hemodynamic and cellular effects of reloading after Impella-mediated LV unloading in Yorkshire pigs. First, we conducted an acute study in normal heart to observe effects of unloading and reloading independent of MI-induced ischemic effects. We then completed an MI study to investigate optimal exit strategy on one-week infarct size, no-reflow area, and LV function with different reloading speeds. Initial studies showed that acute reloading causes an immediate rise in end-diastolic wall stress followed by a significant increase in cardiomyocyte apoptosis. The MI study did not result in any statistically significant findings; however, numerically smaller average infarct size and no-reflow area in the gradual reloading group prompt further examination of reloading approach as an important clinically relevant consideration.
    MeSH term(s) Animals ; Ventricular Function, Left ; Heart-Assist Devices ; Disease Models, Animal ; Myocardial Infarction/physiopathology ; Myocardial Infarction/therapy ; Sus scrofa ; Apoptosis ; Myocytes, Cardiac/pathology ; Myocytes, Cardiac/metabolism ; Time Factors ; Hemodynamics ; No-Reflow Phenomenon/physiopathology ; No-Reflow Phenomenon/etiology ; Recovery of Function ; Myocardium/pathology ; Myocardium/metabolism ; Male
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2422411-X
    ISSN 1937-5395 ; 1937-5387
    ISSN (online) 1937-5395
    ISSN 1937-5387
    DOI 10.1007/s12265-023-10371-z
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  10. Article: Impaired Diastolic Function Predicts Improved Ischemic Myocardial Flow by Mechanical Left Ventricular Unloading in a Swine Model of Ischemic Heart Failure.

    Sakata, Tomoki / Watanabe, Shin / Mazurek, Renata / Mavropoulos, Spyros / Romeo, Francisco / Yamada, Kelly P / Ishikawa, Kiyotake

    Frontiers in cardiovascular medicine

    2022  Volume 8, Page(s) 795322

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-01-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2021.795322
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