Artificial organs: basic science meets critical care

On June 5, 2000, TE had just completed his third year at Indiana University. He was in excellent health and was a gymnast and captain of the IU cheerleading squad. On June 7, 2000, he was in septic shock, comatose, in renal failure, on the mechanical ventilator for severe ARDS, and dying of meningococcal sepsis. With five organ systems failing, TE was referred to the Extracorporeal Life Support Service at the University of Michigan. He was too unstable for conventional transport, so the extracorporeal life support (ECLS) team went to the referral hospital 200 miles away, cannulated his heart through vessels in the neck, established venoarterial cardiopulmonary bypass, and transported him back to the Surgical Intensive Care Unit at University Hospital in Ann Arbor. For the next 20 days, his life was maintained by mechanical devices. In the ICU, he was sustained by more artificial organs (heart, lung, kidneys, and intestine) than native organs, all designed to keep his brain alive and healthy. We will return to TE’s story later. Isador Ravdin was a classic Philadelphia surgeon, a scientist, a teacher, and a man beloved by his students and colleagues. Dr Ravdin had a charismatic and affable personality, a huge clinical practice, and a propensity for bringing basic science research to clinical application. It is this last characteristic that is memorialized in the Ravdin Lecture of the American College of Surgeons. The use of artificial devices to replace the function of vital organs is only about 50 years old. This transition from basic science research to routine clinical application has proceeded so quickly that it is now commonplace, even to the lay public. It is considered routine to have an artificial heart valve, pacemaker, hip joint, or artery; to be on an artificial kidney or mechanical ventilator; or to be completely on IV feedings. Organ replacement makes it possible to provide a bridge to organ recovery or organ transplantation. Millions of people have had their lives extended and improved by artificial organs. Most of the basic research in artificial organs has been done by surgeons. The application of artificial organs is primarily by surgeons, from cardiac surgery to orthopedics to transplantation (Table 1). Hence, this is an appropriate topic for the Ravdin Lecture. For the patient who has a heart operation, a kidney transplant, or a knee prosthesis, there is no thought of basic science. The surgeon, nephrologist, or cardiologist who uses these devices every day understands the basic science but probably is more concerned about the use, safety, and cost of the device than the research that led to its development. But consider the challenge that faced the researchers who developed devices that replace organ function. Substituting for vital organ functions requires not only the basic science of bioengineering, but also a thorough understanding of the basic science related to the native organ itself (Table 2). What has been done seems quite simple in retrospect, but one need only consider the challenge of developing the next generation of artificial organs to see the complexity of the project. Consider, for example, the artificial liver, the artificial spinal cord, and the mechanical reticuloendothelial system, the implantable endocrine organ. In this article, I will focus on the short-term use of artificial organs in intensive care, because it provides the best examples of the application of basic science to this clinical discipline. Admittedly, this is a personalized view of the history and clinical application of those devices in use in ICUs today and a glimpse into the future. Consider first the bioengineering research necessary to replace heart and lunch function. The scientist who first solved this problem was a contemporary of Dr Ravdin, another Philadelphia surgeon, Dr John Gibbon. Dr Gibbon’s clinical incentive was a young woman who died under his care of a massive pulmonary embolism. He recognized that the fatal problem was temporary mechanical obstruction of pulmonary blood flow, and he believed that a mechanical device substituted for heart and lung function for a short time could have solved the problem. Dr Gibbon and his wife, Mali, developed a mechanical heart-lung machine using a roller pump to substitute Presented to the American College of Surgeons as the Ravdin Lecture, October 2002.