The motivation behind writing this article is that the U.S. FDA, for the first time, has approved an artificial pancreas. Artificial body parts which: see for us (intraocular lenses); allow our blood to flow in our hearts in a desired direction without backflow (artificial heart valves); pump our blood for us on the order of 7 liters per minute; and control the glucose level within our systemic circulation (which also controls how much glucose is within our cells). Startingly, we have approximately 1 trillion cells per kilogram of body mass. We have a lot of cells to take care of, given the average person weighs approximately 70 kg.
Biomedical engineering is transformative, to say the least. This article will briefly discuss discuss artificial lenses for eyes (intraocular lenses), artificial heart valves, hearts, and pancreata (pancreases).
Introacular lenses
Intraocular lenses used to be manufactured using poly(methyl methacrylate) or PMMA. PMMA was the material of choice because of the serendipitous observation made by “British ophthalmologist Sir Harold Ridley observed that Royal Air Force pilots who sustained eye injuries during World War II involving PMMA windshield material did not show any rejection or foreign body reaction. Deducing that the transparent material was inert and useful for implantation in the eye, Ridley designed and implanted the first intraocular lens in a human eye.” (-wikipedia).
Artificial heart valves
An artificial heart valve is a device implanted in the heart of a patient with valvular heart disease. When one of the four heart valvesmalfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires open-heart surgery. Heart valvesare integral to the normal physiological functioning of the humanheart. Natural heart valves induce unidirectional blood flow through the valve structure from one chamber of the heart to another. Natural heart valves become dysfunctional for a variety of pathological causes, some of which may require complete surgical replacement of the natural heart valve with an artificial valve. (-wikipedia)
Middle: Starr-Edwards Valve
Bottom: Smeloff-Cutter Valve
Artificial hearts
An artificial heart is a device that replaces the heart. Artificial hearts are typically used to bridge the time to heart transplantation, or to permanently replace the heart in case heart transplantation is impossible. Although other similar inventions preceded it from the late 1940s, the first artificial heart to be successfully implanted in a human was the Jarvik-7 in 1982, designed by a team including Willem Johan Kolff and Robert Jarvik.
An artificial heart is distinct from a ventricular assist device (VAD) designed to support a failing heart. It is also distinct from a cardiopulmonary bypass machine, which is an external device used to provide the functions of both the heart and lungs and are used only for a few hours at a time, most commonly during cardiac surgery.
Origins of artificial hearts
A synthetic replacement for the heart remains a long-sought “holy grail” of modern medicine. The obvious benefit of a functional artificial heart would be to lower the need for heart transplants, because the demand for organs always greatly exceeds supply (rather necessary for transplants are normally unfit for transfer).
Although the heart is conceptually a pump, it embodies subtleties that defy straightforward emulation with synthetic materials and power supplies. Consequences of these issues include severe foreign-body rejection and external batteries that limit mobility. These complications limited the lifespan of early human recipients to hours or days.
Early development of artificial hearts
The first artificial heart was made by the Soviet scientist Vladimir Demikhov in 1937. It was transplanted to a dog.
On 2 July 1952, 41-year-old Henry Opitek, suffering from shortness of breath, made medical history at Harper University Hospital at Wayne State University in Michigan. The Dodrill-GMR heart machine, considered to be the first operational mechanical heart, was successfully used while performing heart surgery.[1][2] Ongoing research was done on young male cows at Hershey Medical Center, Animal Research Facility in Hershey, PA during the 1970’s.
Forest Dewey Dodrill, working closely with Matthew Dudley, used the machine in 1952 to bypass Henry Opitek’s left ventricle for 50 minutes while he opened the patient’s left atrium and worked to repair the mitral valve. In Dodrill’s post-operative report, he notes, “To our knowledge, this is the first instance of survival of a patient when a mechanicaly heart mechanism was used to take over the complete body function of maintaining the blood supply of the body while the heart was open and operated on.”[3]
A heart–lung machine was first used in 1953 during a successful open heart surgery. John Heysham Gibbon, the inventor of the machine, performed the operation and developed the heart–lung substitute himself.
Following these advances, scientific interest for the development of a solution for heart disease developed in numerous research groups worldwide.
First U.S. FDA Approved Artificial Pancreas (Medtronic)
This is a brief overview of information related to FDA’s approval to market this product. See the links below to the Summary of Safety and Effectiveness Data (SSED) and product labeling for more complete information on this product, its indications for use, and the basis for the FDA’s approval.
Product Name: The 670G System
PMA Applicant: Medtronic MiniMed, Inc.
Address: 18000 Devonshire Street, Northridge, CA, 91325
Approval Date: September 28, 2016
Approval Letter: http://www.accessdata.fda.gov/cdrh_docs/pdf16/P160017a.pdf
What is it? The Medtronic MiniMed 670G System is the first FDA approved hybrid closed loop system that monitors glucose and automatically adjusts the delivery of long acting or basal insulin based on the user’s glucose reading.
How does it work? The Medtronic MiniMed 670G System consists of a continuous glucose monitor (CGM) that measures the user’s glucose levels for up to seven days, an insulin pump that delivers insulin to the user, and a glucose meter used to calibrate the CGM.
The MiniMed 670G System is able to decrease or stop insulin delivery when it detects the user’s glucose is low, or increase the insulin delivery when the system detects the user’s glucose levels are high with no input from the user. The glucose sensor contains a wire that is inserted under the skin on the abdomen and measures glucose values in the tissue fluid. The glucose values are wirelessly sent to the insulin pump, and displayed along with glucose trend information, alerts, and alarms on the pump screen. The insulin pump delivers a prescribed dosage of insulin through an infusion set. The insulin pump can automatically adjust the delivery of insulin using a mathematical equation, or algorithm that incorporates information from the CGM.
The system has two modes; Manual Mode and Auto Mode. While in Manual Mode, the system can be programmed by the user to deliver basal insulin at a preprogrammed constant rate. The system will automatically suspend delivery of insulin if the sensor glucose value falls below or is predicted to fall below a predetermined threshold. The system will also automatically resume delivery of insulin once sensor glucose values rise above or are predicted to rise above a predetermined threshold. While in Auto Mode, the system can automatically adjust basal insulin by continuously increasing, decreasing, or suspending delivery of insulin based on CGM values (different from Manual Mode where basal insulin is delivered at a constant rate). Although Auto Mode can automatically adjust basal insulin delivery without input from the user, the user must still manually deliver insulin therapy during meals.
When is it used? The Medtronic MiniMed 670G system is intended for continuous delivery of basal insulin (at user selectable rates) and administration of insulin boluses (in user selectable amounts) for the management of Type 1 diabetes mellitus in persons fourteen years of age and older. The system requires a prescription.
The CGM component of the MiniMed 670G System is not intended to be used directly for making manual insulin therapy adjustments, but rather to provide an indication of when a glucose measurement should be taken.
What will it accomplish? People with diabetes can use the glucose information from the CGM to help determine patterns in their glucose levels. The MiniMed 670G System can alert users when glucose values are approaching potentially dangerously high (hyperglycemic) and/or dangerously low (hypoglycemic) levels. People with diabetes can use the insulin delivered from the pump to help keep their glucose levels at a safe level. The 670G System provides additional diabetes management assistance by automatically adjusting basal insulin delivery based on changes in glucose levels. When used along with a blood glucose meter to obtain a more accurate reading of actual glucose levels, a continuous glucose monitoring and insulin pump system can also help people with diabetes make long-term adjustments to their treatment plan to keep glucose levels in a safe range.
Data supporting the approval of this device included results of a study with 123 participants with type 1 diabetes. The clinical trial included an initial two-week period where the system’s hybrid closed loop was not used followed by a three-month period during which trial participants used the system’s hybrid closed loop feature as frequently as possible. This clinical trial showed that the device is safe for use in persons fourteen years of age and older with type 1 diabetes
When should it not be used? The MiniMed 670G System should not be used in:
- People who require less than a total insulin dose of 8 units per day because the device requires a minimum of 8 units per day to operate safely
- Children under 7 years of age because most children under the age of 7 require less than 8 units of insulin per day.
- The FDA has not reviewed data to support the safety and effectiveness of the device in children ages 7-14 as these studies are ongoing.
- Anyone unable or unwilling to:
- Perform a minimum of four blood glucose tests per day.
- Maintain contact with their healthcare professional.
- Carry the Medical Emergency Card provided with the system when traveling. The Medical Emergency Card provides critical information about airport security systems, and pump usage on an airplane.
- People whose vision or hearing does not allow recognition of pump signals and alarms.
Patients should always remove their pump, sensor, transmitter, and meter before entering a room that has x-ray, MRI, diathermy, or CT scan equipment. The magnetic fields and radiation in the immediate vicinity of this equipment can make the devices nonfunctional or damage the part of the pump that regulates insulin delivery, possibly resulting in over delivery and severe hypoglycemia.
Patients should not expose their pump to a magnet, such as pump cases that have a magnetic clasp.
Additional information (including warnings, precautions, and adverse events): The Summary of Safety and Effectiveness Data and labeling are available online:
- Approval Letter
- Summary of Safety and Effectiveness Data
- Labeling (Not Yet Available)