Research

The Extracorporeal Life Support Laboratory investigates novel physiological applications of core and related extracorporeal life support and bio-artificial organ technologies developed by
Laboratory Director and Professor Emeritus Robert Bartlett, MD. We have modified extracorporeal membrane oxygenation (ECMO) systems for a number of clinical scenarios, from multiple types of acute organ failure and extreme prematurity to organ resuscitation, perfusion and culture to expand the much-needed supply of donor organs.

The ECLS Research Laboratory is a highly collaborative and multidisciplinary consortium of many principal investigators – currently 14. In addition to conducting research related to life support, each also maintains a busy clinical practice in surgical specialties that include cardiac, thoracic, pediatric, orthopedic, transplant and trauma. Other specialties represented include emergency medicine and
nephrology, as well as biomedical engineering and chemistry. All lab investigators share a common motivation and mission: to better understand and to apply ECLS core technology to an important clinical problem. We conduct basic science, translational and pre-clinical and clinical research — from concept to bench to bedside and back again.

Current Research Projects:

• Extracorporeal Circulation Without Anticoagulation: The goal of this project is to develop and evaluate non-thrombogenic surface coatings.
  • Dr. Bartlett (Principal Investigator), Dr. Meyerhoff (Co-Investigator)
• Resuscitating Organs for Transplantation (DCD): The goal of this project is to develop methodologies for resuscitation and transplantation of organs from donors that have experienced uncontrolled cardiac death.
  • Dr. Rojas, Dr. Punch, Dr. Bartlett (Co-Investigators)
• Organ Perfusion and Culture: This project explores the idea of culturing and maintaining transplanted organs after an extended period of time away from the donor, therefore increasing the number of potential transplant recipients.
  • Dr. Rojas (Principal Investigator), Dr. Bartlett, Dr. Punch, Dr. Haft, Dr. Owens, Dr. Lynch, Dr. Ozer (Co-Investigators)
• Development of an Artificial Placenta: This project explores the development of a respiratory support device for premature infants with respiratory failure using arteriovenous extracorporeal life support (AV-ECLS).
  • Dr. Mychaliska (Principal Investigator), Dr. Hirschl, Dr. Bartlett, Dr. Rojas (Co-Investigators)
• Development of an Implantable Pediatric Artificial Lung: The goal of the proposed research is to develop implantable artificial lung technology for children that can serve as a bridge to recovery or transplantation.
  • Dr. Hirschl (Principal Investigator), Dr. Bartlett, Dr. Rojas, Dr. Potkay (Co-Investigator)

With many research initiatives underway, the ECLS laboratory has developed processes for basic science and clinical investigations, device development and assessment. As part of our approach, we continuously look at each component of our core ECLS technologies and ask ourselves how we can further minimize complications, improve outcomes and benefit additional critically ill patients.

We take a similar approach to all projects in the lab, which currently include:

• Development of an artificial placenta
• Use of ECMO technology and new techniques following cardiac arrest to improve survival and minimize complications
• Development of a fully implantable pediatric artificial lung
• Development of a wearable artificial lung to provide ambulatory respiratory support to adults with chronic lung disease
• Development of an ex-vivo lung perfusion system to give clinicians more time to assess organ viability for transplant and to enable longer transit times to suitable recipients
• Development of systems and techniques to resuscitate, maintain and heal organs for transplantation after uncontrolled cardiac death
• Development of ECMO components that replicate natural vasculature, prevent clotting and minimize use of anticoagulants and therefore complications. These include nonthrombogenic surfaces for artificial organs and NO releasing cannulae.
• Understanding mechanisms underlying complications of cardiopulmonary bypass, such as clotting and the no-reflow phenomenon
• Finding new ways for ECLS technologies to make a difference for patients lies at the heart of our work.

Our lab has made many discoveries over the years, building on previous work and collaboration. Examples of important results include:

• Dr. Bartlett's early work modifying heart-lung bypass so that it could support, at first, infants and now adults for more than just a few hours. Today, more than 60,000 critically ill patients have been supported by ECMO, one for as long as 650 days, an unprecedented achievement.
• Dr. Bartlett also co-developed the spirometer, in wide use in hospitals worldwide.
• Continual improvements over the years by many investigators of related ECLS technologies, including oxygenators, pump systems and catheters
• Development of a smart device to regulate and control a wearable artificial lung to support ambulatory adults with chronic lung disease
• Resuscitation of organs — lungs, kidneys, livers, limbs and hearts — after significant periods of cardiac death, including another unprecedented achievement: prolonged preservation of ovine hearts for 72 hours with successful subsequent transplants into healthy animals
• Respiratory support with room-air breathing for more than 10 days, with high long-term survival rates, using our artificial placenta in an ovine model

From the start, work in the ECLS Research Laboratory has had remarkable clinical impact. More than 60,000 patients globally have undergone ECMO support. Although the work began in infants with acute needs, it has since been successfully applied to acute-care pediatric and adult patients. The ECMO support model is now used earlier in the care process to prolong life, improve quality of life and serve as a bridge to transplant in many patients. This and related technologies have changed, and will continue to change, how we care for our sickest patients.

Investigators in our lab, including Dr. Robert Neumar of Emergency Medicine, have developed a strategy, extracorporeal cardiopulmonary resuscitation (ECPR), for patients suffering out-of-hospital cardiac arrest. This work has led to a research model as well as training for paramedics and emergency medicine physicians. Novel sensors developed by Dr. Mark Meyerhoff of the Department of Chemistry are used in nearly every hospital in the United States to monitor gases during heart-lung bypass. Dr. Meyerhoff also is working to develop and characterize nitric oxide-eluting materials with antithrombotic and antibacterial properties for use in ECLS components and related systems to further minimize complications and improve outcomes.

Using ECLS technology, orthopedic surgeons at U-M were the first in the world to perfuse human limbs for 24 hours, thereby improving the availability and viability of organs available for transplant. This is especially relevant for the increased number of veterans who have suffered blast injuries. Improving the condition of limbs for transplant leads to better outcomes for patients with devastating upper extremity injuries. The clinical relevance and impact of our work will continue in the same spirit of innovation as we invest heavily in training the many student- and medical-resident researchers who work in the ECLS Research Laboratory.

We continue to work toward our vision of an organ bank to serve as a repository for many types of healthy, functioning organs ready for transplant into patients who need them. Prolonged perfusion, of more than 12 hours, also opens up new options for investigators who need viable systems with which to study immunoregulation, genetic modification and other complex and important questions related to organ function and transplantation. We hope to extend this work one day, too, to treating diseased organs out of the body and re-implanting them to cure, for example, cancer or diabetes or chronic kidney disease. The potential to save additional critically ill patients continually encourages our investigators to push the envelope and innovate.

Broad and deep collaborations define the many research initiatives in the ECLS Laboratory. We work closely with many units across the U-M Medical School, College of Engineering and College
of Literature, Science, and the Arts as well as with a number of industry partners. Current collaborators include:

• U-M Frankel Cardiovascular Center
• U-M Department of Emergency Medicine
• U-M Department of Pathology and its blood bank
• U-M Unit for Laboratory Animal Medicine
• U-M Proteomic and metabolomics core facilities
• Multiple investigators in the U-M Department of Biomedical Engineering and core 3D printing facilities
• Industry partners include companies such as MC3, Medarray, Breonics Inc., Innovative BioTherapies, Terumo, XVIVO and Medtronic.