Ultrasound-Targeted Therapy for Acute Myocardial Infarction

Summary

Principal Investigator: Sanjiv Kaul
Abstract: DESCRIPTION (provided by applicant): Acute myocardial infarction is one of the leading causes of death in the developed world and is fast becoming a leading cause of death even in the developing world. If a patient has access to a hospital with interventionalists on 24 hr a day call, the chances of opening an infarct-related artery (IRA) within 90-120 minutes of the onset of chest pain is 85%. Most patients, even in the US, do not have access to such facilities and if they arrive at a regional hospital are likely to receive thrombolytic therapy that has a success rate of 60% in opening the infarct-related artery. If some other non-invasive and easily applied treatment could enhance the success of thrombolytics alone and bring it closer to the 85% that can be achieved with percutaneous coronary interventions, it could have a major public health impact. The overall aim of this proposal is to develop novel ultrasound device technologies for microbubble-ultrasound mediated treatment of acute myocardial infarction. The specific aims of this proposal are to develop an integrated in vivo therapy-imaging system to: 1. Determine the optimal ultrasound parameters that cause successful thrombolysis in vivo using a vascular shunt model in baboons. 2. Develop therapy probe(s) that can deliver appropriate ultrasound energy to the thrombus in order to dissolve it and reduce microthromboembolism after reperfusion. 3. Integrate the therapy probe(s) with a 4D ultrasound imaging system that can image microbubbles in vivo and gate ultrasound pulses to automatically dissolve the thrombus. 4. Determine the mechanisms of myocardial microcirculation during acute coronary occlusion and prevent microthromboembolism after reperfusion by treating the myocardium with ultrasound. This proposal is for a Biomedical Research Parternership that involves the leaders in the country in their specific fields. Steve Hanson, PhD (OHSU) is an expert on thrombosis and has used innovative baboon models to study thrombolysis. Thomas Porter, MD (University of Nebraska) is a pioneer in the use of microbubbles and ultrasound for arterial thrombus dissolution. Robert Siegel, MD (Cedars-Sinai, UCLA) has described the novel findings of direct myocardial protection by ultrasound during acute coronary occlusion that is independent of its effect on the thrombus. Sanjiv Kaul, MD, (OHSU) has pioneered the field of MCE and has developed sophisticated techniques to assess the microcirculation, including measurement of no reflow, quantifying regional myocardial perfusion, and molecular imaging. Pierre Khuri-Yakub (Stanford) is a leader in transducer technology, and GE is a world leader in ultrasound systems. Xubo Song (OHSU) is an authority on deterministic tracking algorithms that can assist in delivery of ultrasound to the correct target in a beating heart.
Funding Period: 2010-08-15 - 2014-06-30
more information: NIH RePORT

Research Grants

Detail Information

Research Grants30

  1. Blood Pressure Regulation: Novel Roles for the Kidney
    Pablo A Ortiz; Fiscal Year: 2013
    ..Thus it will accelerate acquisition of knowledge of the novel mechanisms by which the kidney regulates blood pressure, and may provide new targets for anti-hypertensive drugs. ..
  2. Interactive Signaling Modules in Vascular Inflammation
    Linda H Shapiro; Fiscal Year: 2013
    ..abstract_text> ..
  3. Prognostic Utility of Absolute Coronary Microvascular Function by PET/CT
    Sharmila Dorbala; Fiscal Year: 2013
    ..The purpose of this study is to find out If microcirculatory abnormalities can predict risk of future adverse outcomes from heart disease. (End of Abstract) ..
  4. Elafin Therapy for Lung Diseases
    Marlene Rabinovitch; Fiscal Year: 2013
    ..The Administrative Core facilitates exchange of information and postdoctoral training in Lung Translational Medicine, and facilitates our strategy to move elafin into clinical trial in the next cycle. ..
  5. Novel Therapies for Muco-Obstructive Lung Diseases
    RICHARD CHARLES BOUCHER; Fiscal Year: 2013
    ..abstract_text> ..
  6. Safety of Allogeneic Cardiosphere-Derived Cells for Acute Myocardial Infarction
    Rachel Ruckdeschel Smith; Fiscal Year: 2013
    ..CAP-1002 developed successfully for all MI patients would offer both a cardioprotective and regenerative therapy, to be administered as needed. ..
  7. Chymase-Mediated MMP Activation in Ishemia Reperfusion Injury
    LOUIS JOSEPH DELL'ITALIA; Fiscal Year: 2013
    ....
  8. INTEGRATED MECHANISMS OF CARDIAC MALADAPTATION
    R John Solaro; Fiscal Year: 2013
    ..Studies proposed here offer the potential for novel diagnostic procedures early in the progression of the disorders, and targets for novel therapies. (End of Abstract) ..
  9. Non-invasive detection of heart transplant rejection with MRI
    NEIL RANJAN CHATTERJEE; Fiscal Year: 2013
    ..In the proposed work, we will develop these new sequences in healthy volunteers, validate them, and then apply them to the intended population of transplant recipients. ..
  10. Therapeutic Protein C Activator for Myocardial Ischemia
    NORAH VERBOUT; Fiscal Year: 2013
    ..Reaching our milestones will prompt the initiation of formal product development towards an IND for the emergency treatment of suspected and/or verified myocardial ischemia. ..
  11. Surgical Revascularization's Impact on Mitochondria in Hibernating Myocardium
    ROSEMARY FRANCES KELLY; Fiscal Year: 2013
    ..By performing a surgical operation to resupply blood to the heart, our research will test whether these adaptations to ischemia are reversible and allow the heart to return to normal function, or if the adaptations are permanent. ..
  12. Heart Vascular Function and Thyroid Hormone Receptors
    Wolfgang H Dillmann; Fiscal Year: 2013
    ..These findings may lead to clinical translation in future approaches. ..
  13. Mechanisms of Atherogenesis in Insulin Resistance
    IRA A TABAS; Fiscal Year: 2013
    ..End of Abstract) ..
  14. Neutralizing Antibody &AAV FIX Gene Therapy
    Richard J Samulski; Fiscal Year: 2013
    ..The long-term objective of this PPG is to advance basic understanding of vector-cell-animal model interactions for safe gene delivery. ..
  15. Effect of Mitral Regurgitation on Ischemic LV Remodeling
    Robert A Levine; Fiscal Year: 2013
    ..The work will focus on the central impact of MR repair on LV function as the key determinant of prognosis, and on increasing our mechanistic understanding to identify new therapeutic targets. ..
  16. Phase II Clinical Trial to Evaluate the Benefits of Postconditioning in STEMI
    Jay H Traverse; Fiscal Year: 2013
    ..Our clinical trial will investigate if the modification of reperfusion using a technique called Postconditioning will reduce the size of a myocardial infarction and improve LV function as measured by cardiac MRI at 3 and 12months. ..
  17. Immune-Based Interventions Against Infectious Diseases
    Alan L Rothman; Fiscal Year: 2013
    ..3. Recruit promising junior investigators and provide mentoring by established NIH-funded researchers. 4. Support a multidisciplinary research program led by junior investigators in translational infectious diseases immunology. ..
  18. Surgery to Prevent Postinfarction Ventricular Remodeling
    Robert C Gorman; Fiscal Year: 2013
    ..The affect of novel early and late therapies on the remodeling process will also be assessed. ..
  19. GENE THERAPY FOR LONG-TERM MYOCARDIAL PROTECTION
    Victor J Dzau; Fiscal Year: 2013
    ..Public Health Relevance: This proposal is to study the mechanisms responsible for 2-catenin and ROR3t-regulated T cell apoptosis. ..
  20. Cellular S-nitrosothiol signaling in respiratory biology
    Lisa Palmer; Fiscal Year: 2013
    ..This program will make extensive use of intramural and extramural collaborations, as well as Program Core facilities, to make good use of our institutional strengths in S-nitrosothiol biology. ..