Controlled Reperfusion for Whole Body Ischemic Injury

Summary

Principal Investigator: Gerald Buckberg
Abstract: The long-term objective is to develop a new approach to treat cardiac arrest. Currently, despite early, successful defibrillation in half the patients, the overall mortality rate is 95%. Furthermore, approximately 70% of these few survivors of whole body ischemia develop neurologic injury: we may save the heart, but lose the brain. The causative factors are inadequate treatment of the underlying cause of arrest by insufficient a) delivery of brain flow during CPR, b) restoring of heart blood supply to allow it to recover, and c) correction of the underlying cardiac cause. A novel approach will be taken to 1) promptly use the heart lung machine without opening the chest by an approach through leg vessels to mechanically, and temporarily, take over heart function, 2) change its prime pharmacologically to make a metabolic fuel for recovery, and 3) correct the underlying cause. We will use a relevant surgical model of either deep hypothermic circulatory arrest (DHCA) or lethal normothermic ventricular fibrillation for 10 minutes to cause whole body ischemia. Both insults cause high mortality and brain damage. We will present pilot studies showing complete heart and 100% brain recovery by integrating the specific aims of these three interventions. These results were achieved by use of a standard prime of the CPB circuit, and adding either a sodium hydrogen exchange inhibitor or specially filtering the white blood cells that cause reperfusion damage. We will extend the period of ischemia to two hours and show how this cardiac arrest model (that permits regional brain flow through the carotid arteries) can also be used to treat stroke. If this novel method of management is correct, the scheme of diagnosis and management of this almost always fatal cardiac arrest complex will change markedly.
Funding Period: 2002-09-30 - 2007-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Resuscitation after prolonged cardiac arrest: role of cardiopulmonary bypass and systemic hyperkalemia
    Oliver J Liakopoulos
    Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA
    Ann Thorac Surg 89:1972-9. 2010
  2. pmc Resuscitation after prolonged cardiac arrest: effects of cardiopulmonary bypass and sodium-hydrogen exchange inhibition on myocardial and neurological recovery
    Oliver J Liakopoulos
    Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 40:978-84. 2011
  3. pmc Studies of isolated global brain ischaemia: II. Controlled reperfusion provides complete neurologic recovery following 30 min of warm ischaemia - the importance of perfusion pressure
    Bradley S Allen
    Department of Surgery, University of California, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 41:1147-54. 2012
  4. pmc Studies of isolated global brain ischaemia: III. Influence of pulsatile flow during cerebral perfusion and its link to consistent full neurological recovery with controlled reperfusion following 30 min of global brain ischaemia
    Bradley S Allen
    Department of Surgery, University of California, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 41:1155-63. 2012
  5. pmc Studies of isolated global brain ischaemia: I. A new large animal model of global brain ischaemia and its baseline perfusion studies
    Bradley S Allen
    Department of Surgery, University of California, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 41:1138-46. 2012

Scientific Experts

  • Bradley S Allen
  • Oliver J Liakopoulos
  • Nikola Hristov
  • Gerald D Buckberg
  • Georg Trummer
  • Jonathan Triana
  • J Pablo Villablanca
  • Zhongtuo Tan

Detail Information

Publications5

  1. ncbi Resuscitation after prolonged cardiac arrest: role of cardiopulmonary bypass and systemic hyperkalemia
    Oliver J Liakopoulos
    Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA
    Ann Thorac Surg 89:1972-9. 2010
    ....
  2. pmc Resuscitation after prolonged cardiac arrest: effects of cardiopulmonary bypass and sodium-hydrogen exchange inhibition on myocardial and neurological recovery
    Oliver J Liakopoulos
    Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 40:978-84. 2011
    ....
  3. pmc Studies of isolated global brain ischaemia: II. Controlled reperfusion provides complete neurologic recovery following 30 min of warm ischaemia - the importance of perfusion pressure
    Bradley S Allen
    Department of Surgery, University of California, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 41:1147-54. 2012
    ..This study applies a newly developed isolated model of global brain ischaemia (simulating unwitnessed sudden death) for 30 min to determine if controlled reperfusion permits neurologic recovery...
  4. pmc Studies of isolated global brain ischaemia: III. Influence of pulsatile flow during cerebral perfusion and its link to consistent full neurological recovery with controlled reperfusion following 30 min of global brain ischaemia
    Bradley S Allen
    Department of Surgery, University of California, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 41:1155-63. 2012
    ....
  5. pmc Studies of isolated global brain ischaemia: I. A new large animal model of global brain ischaemia and its baseline perfusion studies
    Bradley S Allen
    Department of Surgery, University of California, Los Angeles, CA, USA
    Eur J Cardiothorac Surg 41:1138-46. 2012
    ..To circumvent this, a new minimally invasive large animal model of isolated global brain ischaemia, together with baseline perfusion studies is described...