When preforming surgeries, an obstacle that has to be dealt with is making sure that the patient;s blood doesn’t coagulate (or thicken) when it comes into contact with metal intruments. This is currently dealt with by a drug called heparin, which thins the blood so that it doesn’t have an adverse reaction to the touch of an instrument. Heparin is widely used and is successful…most of the time. It creates negative reactions in three to ten per cent of all patients in which the blood will coagulate and clot up all around an instrument as soon as direct contact is made. The image below shows that when Heparin fails, coagulation occurs and the device used in surgery is covered with blood clots:

At Brigham Young University, BYU, an alternative solution has been found. Dr. Kenneth Solen and Jared Parker, biomedical engineers who have dedicated much time to this problem, believe that a different type of precaution needs to be taken. They suggested that rather than adding something to the blood that may induce an immune reaction, they would like to remove something. There exist specific proteins in the blood that carry a strong electrical charge in order to cause coagulation. One could conclude that to remove these proteins, something with a negative charge must be utilized. Therefore, the research team used a negatively-charged gel to attract and remove these coagulation proteins, while leaving the rest of the neutral and negatively-charged proteins in the blood. In the lab, this was proven to be successful, however human testing has not been conducted yet. Dr. Solen continues to pursue the perfection of this innovation at W.L. Gore.

After Dr. Solen’s anticoagulation method, the device used in surgery remains clear of blood clotting:

I would like to thank Blake Ferguson for sharing this article with me.

-Amy

Drugs are used in numerous medical applications, such as improving the patency of a stent, cancer treatment, and infection control. Although drugs are used to treat an injury or alleviate pain, many of them will have adverse side effects if the drug is administered systemically (throughout the entire body). Once drugs are administered, they are nonlinearly absorbed into the body and result in only acute (short term) effects. For this reason, a method of chronic (long-lasting or long-term) and localized drug delivery would be advantageous to treating the area of interest without causing adverse systemic effect. The two main variables that need to be controlled are drug dosage and timed release of the drug. Many methods, such as polymer blends and biodegradable capsules, have been attempted to gain maximum control of these two factors. However, both variables have been proven to be controlled effectively through light-initiated drug delivery.

At Queen’s University, Belfast in Northern Ireland, Dr. Colin McCoy and his fellow researchers developed medications combined with photosensitive chemicals. When light falls upon the site of the body where the drugs are present, the drugs will slowly begin to release into the body. The drug release stops whenever the light is turned off or not shining directly on the site. The group’s main goal was to create a drug delivery method with minimal side effects for patients. This method also leads to more controlled drug dosage, better time release, and a cheaper drug delivery option for patients.

Although pacemakers are usually associated with the heart, Medtronic has developed a pacemaker attached to two electrodes to induce deep-brain stimulation for minimally conscious coma patients.  Figure 1 shows an x-ray image of the device in a patients head, notice how deep the device must be in order to stimulate the brain sufficiently to wake someone from a coma.  Patients with severe brain injuries often slip into comas for the rest of their lives and are more than often thought of as “gonners”.  This success story from Chicago could change the way modern medicine sees these victims.  The plan is to test the device in 12 more patients and then move on to the wide-spread clinical applications thereafter.

Figure 1

-Amy Shah

Coronary Artery Disease and Coronary Bypass Grafting

Coronary artery disease (CAD) is the leading cause of death for both men and women in the United States. The process of atherosclerosis is the hardening of an artery due to a lipid build up, resulting in functional loss. Fatty deposits, or plaques, may accumulate inside the arterial wall and cause stenosis, or an abnormal narrowing the artery wall. This causes the flow of blood to be reduced or completely stop and the vessel wall to lose its flexibility and ability to handle pulsatile flow. There are several forms of treatment available for CAD depending on the severity of the disease, including lifestyle changes, medicines, angioplasty, and coronary artery bypass grafting (CABG).

CABG is the preferred treatment for patients with multiple areas of coronary artery narrowing or blockage and also for patients with higher percentages of stenosis, this relation can be seen in figure 1 above. Patients typically have 1 to 5 bypasses within one surgical procedure. This form of treatment is the most common type of surgery in the United States, with about 500,000 surgeries per year. Typically, the patient’s saphenous vein from the leg, internal mammary artery (IMA), or the radial artery from the arm is used. Figure 2 shows the location of the saphenous vein and IMA. These vessels are removed and grafted onto the hardened artery to revascularize the affected area.

Figure 2

Advantages and Disadvantages of the Current Gold Standard

The current gold standard for the CABG procedure is the use of autologous (from self) saphenous vein and IMA because of their resemblance to the native coronary artery and their relatively high patency rates. It was not until recently that the radial artery has been widely studied as another source for this procedure. The five and ten year artery patency rates for these have all shown to be greater than 70% and 50%, respectively. These rates vary depending on the blood vessel used for the procedure.

Even with the success this procedure has had, there are several disadvantages that may lead to complications. Removing an autologous vein for the procedure may cause donor site morbidity, which can lead to problems such as groin infection near the site of the saphenous vein removal. In addition, there is only a limited supply of donor vessels for this procedure. Up to 30% of patients undergoing lower limb bypass do not have a suitable vein. This can be problematic for patients who need multiple CABGs or have had previous procedures. There is also a greater risk with the use of multiple vessels. For example, there are more incidents of deep sternal wound infection when both IMAs are used for this procedure, especially for patients with obesity and diabetes.

Existing Vascular Grafts and Improvements

Although living autologous vessels seem to be the ideal conduits for CABG, there are several factors, as discussed above, which have prompted efforts to develop a more suitable donor vessel. The ideal blood vessel substitute should mimic the characteristics of a native blood vessel, including its composition, structure, function, and mechanical properties. It should be durable enough to endure the mechanical stresses, as well as the threat of biodegradation and infection within the body after implantation. The vessel should be made up of materials that promote cell-specific interactions and needs to be able to have similar viscoelastic properties as a normal artery to avoid a compliance mismatch. It should be flexible in order to maintain its contour, yet rigid enough to prevent kinking. The materials used, especially on its luminal surface, must be nonthrombogenic to prevent blood clotting in the vascular graft. It is favorable that the vessel is easily and quickly manufactured, and should be readily available in multiple lengths and sizes.

However, no existing conduit possesses all the properties and qualities of the ideal arterial vascular graft listed above. Current alternatives to autologous vascular grafts are prosthetic conduits based on expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (Dacron ®). Their patency at 5 years is 40% to 50%, which is acceptable but relatively low. Tissue engineering has proven to be successful in wound management, burns, and cartilage repair; therefore their has been a growing interest in designing biological blood vessels as an alternative to autologous vascular grafts and current prosthetic conduits. However, previously proposed and designed tissue engineered vascular grafts were not durable, were prone to early thrombosis, and had poor patency rates. This means that a new vascular graft with all the above mentioned qualities is yet to be manufactured, but is a hopeful potential cure for the future.

Everyone knows that science has been booming at an insanely quick rate for the past decade. The world has erupted with stem cells, tissue engineering, cures for diabetes and Alzheimer’s Disease all in the past ten years! But what about the next ten years? MSNBC predicts that stem cells will be the norm, tissue engineering will be a replacement for most major surgeries with the remaining surgeries to be preformed by robots, and cures to widespread diseases will be perfected. If you’re not very fond of reading, watch this video The Year 2017 and get a glipse of what is to come (the video will play after a 30 second commercial).

There’s so much going on in the world of science, unfortunately I can not cover it all. Here’s the latest buzz going around in the field.

Reversing Alzheimer’s Disease
Alzheimer’s Disease has gotten SO much buzz this week! It’s on CNN.com, Medical News Today UK, Google News, and the list goes on…
The interesting thing about this “cure” is the possibility of reversing memory loss through mental stimulation by a specific drug treatment. MIT has conducted extensive research on patients with neurodegenerative disorders and shown that the memories aren’t lost, they are just inaccessible. Further research may lead to endless possibilities for not only Alzheimer’s patients, but patients with dementia or any type of neurological damage.

Embryonic Stem Cells
When this embryonic stem cell revolution began over eight years ago, people didn’t expect such a large moral argument to arise from what considered a future medical miracle. This article presents a different view of embryonic stem cells that many people may not be used to reading: The View From the Hill.

Cloning
A new country is now on the brink of medical research: Victoria, Australia. A measure to use embryos to create and clone stem cells has been passed and an exciting project is now underway! Embryonic stem cells are clonogenic, which means that they can give rise to a colony of genetifcally identical cells (clones) that have the same properties of the original cell. Imagine the possibilities.

There’s so much going on in the world of science, unfortunately I can not cover it all. Here’s the latest buzz going around in the field.

Alzheimer’s Disease Cure on the Way
Purdue University has discovered the first step in a cascade of events leading to amyloid plaque formation in the brain. This is the beginning of finding a cure to Alzheimer’s Disease. A vital enzyme, called memapsin 2, was discovered to be what seems like the cause of plaque formation in the brain. Further research into this area delves into creating a memapsin 2 inhibitor protein to block the function of the enzyme before it causes plaque to build up.

Immune System Activation
Scientists at the University of Michigan have discovered a bacteria that inserts itself into the body and evokes a strong immune response. These bacteria attach onto receptors on the surface of immune cells and hyperactivate them. Think of the possibilities for victims with weak immune systems and post-traumatic surgery patients!

Dr. Heart Robot
HeartLander, a 20 millimeter long robot, has been invented to deliver drugs to the heart in a minimally invasive manner. Surgeons can monitor this robot’s crawling motion across a beating heart with an X-ray video and control its movement by using a joystick. Scientists are continuously developing this robot to become more eclectic so that they may be able to utilize it for the treatment of a plethora of heart conditions.

There’s so much going on in the world of science, unfortunately I can not cover it all. Here’s the latest buzz going around in the field.

Stem Cells
Scientists in the UK have developed an artificial heart valve grown from stem cells. Artificial heart valves are usually made from bovine materials, plastic, or metal alloys, however immune rejection of foreign materials in the body becomes a huge problem that can lead to heart disorders. These stem cell heart valves have the potential to prevent risk of endocarditis and stenosis because they act just like natural heart valves.

Nanotechnology
Purdue’s Brick nanotechnology center is utilizing nanopore channels to distinguish specific sequences of DNA. They created channels with diameters between ten and twenty nanometers in silicone and attached a single strand of DNA to each channel. As liquid containing DNA translocates through the nanopores due to a generated voltage difference across the channel, they can differentiate between certain DNA molecules.

Nicotine and Memory
Nicotine has the ability to cross the blood-brain barrier and activates reward pathways in the brain that trigger feelings of euphoria and satisfaction; this is what makes it so addictive. Dutch scientists have taken advantage of this powerful property of nicotine and discovered how it affects memory in the brain. Nicotine influences neural wiring to enhance memory by strengthening the connections between neurons when the brain is accessing memory.

-Amy Shah

Blood, an essential component of life that delivers nutrients and oxygen throughout the body, constitutes about 7.5% of a human’s body weight (average adult blood volume = 5.5 L). According to Taber’s Cyclopedic Medical Dictionary, blood is composed of about 43% cells (erythrocytes, leukocytes, thrombocytes) and 57% plasma (ions, proteins, hormones, lipids, and water). Blood is a Casson fluid (due to its particulate suspensions), therefore as its viscosity increases (as in the aorta), more pressure is needed to maintain constant aortic blood flow (30 cm/sec) in order to deliver blood throughout the entire circulatory system in 60 seconds.

Artificial blood is a saline-based blood substitute designed for trauma victims that suffer from massive blood loss or low Hb levels. Research in attempt to create the perfect blood substitute has been going on for over 50 years. Most artificial bloods today are cell free to avoid blood type cross-matching, immunosuppressive effects, and viral or bacterial contamination. Artificial blood is superior to natural blood because it can be readily available (due to a longer shelf life), can transport more Hb (due to cell-free solution), and it can act like a Newtonian fluid at high shear rates due to its lower viscosity. The majority of artificial blood substitutes created have side effects of hypertension, short biological half-life, and increased bilirubin levels. Although there are side effects, several companies are in Phase II and III trails and there is hope for a successful artificial blood substitute in the near future. (Cohn 2003).

Blood pressure (BP) is defined by Taber’s Cyclopedic Medical Dictionary as the amount of tension applied to the walls of arteries due to the strength of the heart’s contraction. Average BP is 120/80 mmHg (systolic/diastolic) and hypertension (high BP) is considered BP over 140/90 mmHg, which can be caused by many factors including rapid heart beat and vasoconstriction. Some things that affect BP are heart contraction, blood volume, blood velocity, diameter of blood vessels, and change in elastance of blood vessels. MAP is the mean (average) arterial pressure of blood traveling through all the arteries during one cardiac cycle and can be defined as: MAP = [(2xdiastolic) + systolic] / 3. The minimum MAP required to perfuse coronary arteries, brain, and kidneys is 60 mmHg and the average MAP is about 93.3 mmHg (McAuley).

Nitric Oxide (NO), also known as endothelium-derived relaxing factor, plays a key role in blood flow regulation and oxygen delivery to body parts. It is manufactured in endothelial cells (embedded in blood vessels) in response to increased shear stress and it’s biosynthesized from oxygen, L-arginine, and nitric oxide synthase. The function of NO is to signal the surrounding smooth muscle to relax, dilate, and create more rapid blood flow, some NO is binds to iron sites on Hb to avoid hyperdilation (Allen 2006, Downer 2001).

Baxter Healthcare created an artificial blood in the 1990s and ran phase III trials in 1998. Their artificial blood was a diaspirin cross-linked hemoglobin (DCLHb) cell-free fluid intended to treat severe traumatic hemorrhage shock. Baxter designed the substitute to be cell-free to allow quicker transport of O₂ throughout the circulatory system and to avoid blood-type matching. Extracellular Hb is proven to be two to three times more efficient in delivering O₂ than RBC-bound Hb because the naked molecules are closer to the vessel walls. Baxter’s diaspirin cross-linked design is mandatory because Hb doesn’t have enough pressure on its own to release O₂ from its iron binding sites. Allosteric mutations were preformed to alter the active site structure of the human Hb tetramere to raise the pressure on the Hb (to p50 of RBCs) and decrease it’s affinity for O₂ (Bloomfeild et al. 2004).

Baxter’s phase III testing involved randomized patients which demonstrated hemorrhaging and tissue hypoxia, of which half received 1 L of 10% DCLHb and half received a control of 1 L of normal saline intravenously. The patients were all monitored for up to 28 days following infusion. Logrank analysis after the testing period demonstrated 46% mortality in the DCLHb group, which was significantly higher than the 17% mortality of the saline group. Although the results were largely inconclusive, the majority of the individuals in the DCLHb group died due to respiratory distress and/or multiple organ failure (Baxter Healthcare Corporation 1998). Baxter’s DCLHb failed because NO had an increased affinity for naked Hb due to the absence of membrane protection by an RBC. This lead to increased rates of NO scavenging and an insufficient amount of NO available for smooth muscle, causing blood vessels to hyperactively contract without dilation. Contraction causes decreased blood flow through vessels and the body tries to counteract that by increasing blood pressure, but this eventually leads to hypertension (Bloomfield et al. 2004, Downer 2001).

Over 20 million transfusion patients worldwide receive a major disease from a contaminated blood donation supply, this increases the need for a safe blood substitute (WHO 2000). Many potential solutions to fix Baxter’s NO scavenging problem are being brainstormed today, such as polyheme, sodium nitrate supplements, and artificial RBCs. The proposed solution in this paper focuses on polyheme to reduce NO scavenging rates, thereby preventing hypertension. Polyheme is chemically altered human Hb that is universally compatible, can be stored for up to 12 months, has extremely low contamination chances due to purification, and rapidly restores lost blood volume and Hb levels. Polyheme is created by purifying human blood, extracting Hb, and polymerizing Hb monomers into polymers that have lower NO affinity than free Hb. These Hb polymers are mixed into a saline solution and called Polyheme blood substitute. Polyheme has about the same P50 (about 32 mmHg) as DCLHb because the crosslinkage in the Hb was altered the same way. The largest difference in Polyheme vs. DCLHb is the decrease in NO affinity due to polymerization. A normal Hb molecule has a diameter of 7 nm, while a Polyheme molecule has a diameter of 9.8 nm, therefore this doesn’t change the viscosity of DCLHb a significant amount (USDHHS 1999). The viscosity of Polyheme is about 1.3 cP, when compared to natural blood (m_bld = 3 cP) one observes a definite increase in volumetric blow flow through the calculations in figure 2. This is a desired effect so that Polyheme can bypass vascular disruptions to provide oxygen to ischemic tissues (Cohn 2003). One 500 mL unit of Polyheme contains 50g of Hb, this is about the same as a normal blood transfusion (Hb concentration in blood = 0.166 m³Hb/m³blood), therefore Polyheme provides a sufficient concentration of Hb to the patient.

-Amy Shah

Sleep apnea is a disorder in which pauses in breathing occur for about 10 to 30 seconds during one’s sleep (American Academy of Family Physicians 2005). An “apnea” is an episode without breath in which one’s body simply skips breathing momentarily. Of the 18 millions Americans that have sleep apnea, 90% don’t even know they have it because they don’t recall waking up hundreds of times during the night due to a break in REM sleep. They feel tired and moody during the day, craving the occasional morning, afternoon, and evening nap; but they often don’t realize that they’re suffering from a disorder. The best means for diagnosis of sleep apnea is an overnight polysomnography that tracks blood pressure (BP), respiration (resp), sympathetic nerve activation (SNA), and body movements (Benedictis 2006).

There are two types of sleep apnea: obstructive and central. Obstructive sleep apnea (OSA) occurs in one out of every five people and is caused by an obstruction in the throat. The obstruction is any physical hindrance in the airway, this can be caused by anything from obesity to enlarged tonsils. People who are more vulnerable to OSA are men, overweight individuals, and individuals over the age of 40. Central sleep apnea (CSA), the main focus of this paper, is caused by an error in the thalamus, the part of the brain that controls involuntary breathing. During CSA, there is no effort by the person’s body to breath; no struggle by respiratory muscles, just stiffness of the body without breathing. Mixed apnea, which is a combination of OSA and CSA, also exists (UMMC 2004, ASAA 2007).

Circadian rhythm sleep, or “normal sleep”, consists of a period of time in which the body is at rest to avoid exhaustion (UMMC 2004). During circadian rhythm sleep, one exhibits tidal breathing in which about 700 mL of air is inhaled and filtered through the lungs for oxygen extraction before exhalation. During circadian rhythm sleep, one’s body should comply with average standards such as an average pulse rate between 60 and 80 beats per minute and average resting blood pressure around 120/80 mmHg. The average respiratory rate for a resting adult is between 12 to 18 breaths per minute; however children take about 20 to 30 breaths per minute (UI Health Care 2005). There are two major respiratory gases: oxygen (O₂) and carbon dioxide (CO₂). The average amount of oxygen in expired breath during tidal breathing is 250 mL of oxygen per breath and for carbon dioxide it is 220 mL of carbon dioxide per breath (George 2007). The average blood pH for a resting adult is 7.35 to 7.45 and red blood cells should be about 33% concentrated with hemoglobin (Hb) (Encyclopedia of Surgery Information 2005).

Proposed Solution

Apneas disturb circadian rhythm sleep and cause the individual to wake up in the night gasping for air. During an apnea, the individual’s pulse, blood pressure, and respiratory rate decrease and they submit to hypoxia (lower than threshold oxygen levels) and hypercapnia (high carbon dioxide levels) (ASAA 2007). There are several risks to people with sleep apnea, among these are higher risks of car accidents due to drowsiness, stroke due to increased blood viscosity, depression due to lack of sleep and low sexual arousal, heart disease, heart attack, heart failure, kidney failure, seizures, headaches, eye disorders, and memory loss. According to doctors at the University of Maryland Medical Center, people with sleep apnea must be diagnosed and treated to help reduce their chances of these terrible risks (Rice et al. 2006).

After diagnosing a patient with OSA, doctors will recommend a series ideas that will help reduce the amount of apneas a person has. There is positional therapy, dieting, exercising, and surgery. The 20% of the American population with OSA has great chances to permanently correct their disorder by simply losing weight, surgically widening their airway, or surgically moving their jaw forward (Rice et al. 2006, ASAA 2007).

The first thing a doctor will say to their newly diagnosed CSA patient is to avoid alcohol and central nervous system depressants because they worsen CSA by relaxing the muscles and impairing the brain. When looking at CSA, there are many solutions available to relieve it, however none of the devices on the market are a permanent cure for this disorder. In order for a device to help the individual, it must first detect an apnea and then trigger a mechanism to induce breathing without waking them (ASAA 2007, Encyclopedia of Surgery Information 2005).

Some currently patented detection devices are adaptive servo-ventilation devices, snorkels, and sleep apnea detection apparatuses. Our company’s proposed detection device for CSA will be a pulse oximeter, which utilizes infrared light shining through one’s finger to measure the Hb concentration on red blood cells.

A pulse oximeter clips onto the patient’s finger and can be kept on for the whole night. It will sense Hb concentration below 33%, which correlates with hypoxia below 75% O₂ saturation on red blood cells. When O₂ saturation drops below 75%, the photodetector senses an increased amount of infrared light, so the pulse oximeter can trigger the device to induce breathing.

Pulse oximeters are the best detection device because they are comfortable, don’t dry skin out/chaff, are used widely in hospitals, and don’t cause claustrophobia since they are not on the person’s face. For people who move around in their sleep, our company can provide an add-on option to the pulse oximeter that utilizes Bluetooth technology to communicate with the breath induction device rather than a wire. Pulse oximeters are accurate in detecting hypoxia about 80% of the time (AARC 1991, UMMC 2004).

Examples of breath induction devices for CSA patients are continuous positive airway pressure (CPAP), electrical stimulators, and drugs. The most common breath induction device is the CPAP, which delivers a constant flow of air pressure using a nasal mask while the patient is sleeping. Since it is unnecessary to continuously apply pressure to the airway even when the patient is not having an apnea, the R&D department of our company should conduct research to create a positive airway pressure device that administers pressure only when activated by the pulse oximeter (if our company chooses to invest in sleep apnea). CPAP is the most widely used and accepted method for CSA patients because it effectively prevents the patient from having an apnea due to its continuous pressure, thereby providing the patient with smooth respiration throughout the night (Matthews 2003).

On the negative side, the CPAP can cause claustrophobia, dry skin, and discomfort. It is also very large, must be cleaned/maintained meticulously, and cannot be kept in direct sunlight or exposed to excessive amounts of heat. There are several different types of CPAPs like the Auto-CPAP, Smart CPAP, and Goodnight 420E. Our company will use the Auto-CPAP because it is more compact and lightweight than the others, automatically adjusts to altitude changes, and has a display screen that is very user friendly (REMstar 2006).

Our company’s proposed solution consists of a pulse oximeter that detects low Hb/oxygen levels and a CPAP that induces breathing through constant pressure on the airway. This solution works via the feedback loop in figure 5. Although the detection method is wonderful, the breath induction method is already widely in use with many established competitors. Our company should not invest in a sleep apnea device patent because, although the pulse oximeter can cost as low as $80, the CPAP alone is around $800 each at leading companies. A good investment for our company could be not to create a patent, but to have the R&D department create a better CPAP device than leading companies. In conclusion, a patent for a sleep apnea device is not currently a good investment for our company (AARC 1991, Rice 2006, REMstar 2006).

-Amy Shah