In today’s episode, we are going to talk about the most common vasopressors we use in the ICU. Those being norepinephrine, epinephrine, phenylephrine, vasopressin, and dopamine.
Vasopressors are a powerful class of drugs that induce vasoconstriction, they elevate mean arterial pressure (MAP). Vasopressors differ from inotropes, inotropes increase cardiac contractility. Keep in mind that many drugs have both vasopressor and inotropic effects.
- Vasopressors are a group of medicines that contract (tighten) blood vessels and raise blood pressure.
- They’re used to treat severe low blood pressure, especially in a critical care setting.
- When blood pressure is continuously low it can lead to organ damage and even death.
- Most commonly used on patients who are in shock, undergoing surgery, or during an emergency.
- Alpha 1 adrenergic receptors
- Located primarily in the skin and GU tract and ultimately decrease blood flow to these organs when activated.
- Activation of these receptors will result in vasoconstriction and an increase in peripheral vascular resistance and systemic arterial blood pressure.
- Alpha 2 adrenergic receptors
- Contribute both to control of sympathetic tone and to local and regional blood flow in the peripheral vasculature.
- Sits alongside the more plentiful α1-adrenergic receptor.
- Beta 1 adrenergic receptors
- Located near the SA node, AV node, and cardiac myocytes (make up the heart muscle).
- Activation causes an increased heart rate (chronotropic effect), automaticity, and contractility (inotropic effect).
- Beta 2 adrenergic receptors
- Located in the tissues of the GI tract, bronchi, uterus, pancreas, striated muscle (cardiac), blood vessels, coronary arteries, and hepatic artery.
- Activation causes smooth muscle relaxation, vasodilation and increases perfusion, and increased cardiac contractility.
- Dopamine receptors
- Present throughout the body, dopamine is a precursor to epinephrine and norepinephrine
- Activation causes vasodilation, increased myocardial contraction, and increases cardiac output without changing heart rate
Depending on the size of the extravasation, bring 5 to 10 mg of phentolamine to the bedside. This will need to be reconstituted, and further diluted to 0.5 mg/mL in normal saline. Treatment of the extravasation will involve the nurse administering the phentolamine intradermally around the site of the extravasation.
NEO-SYNEPHRINE hydrochloride produces vasoconstriction that lasts longer than that of epinephrine. Its action on the heart contrasts sharply with that of epinephrine and ephedrine, in that it slows the heart rate and increases the stroke output, producing no disturbance in the rhythm of the pulse. Phenylephrine is a powerful postsynaptic alpha-receptor stimulant with little effect on the beta receptors of the heart.
- Neo causes a rise in systolic and diastolic pressures.
- Reflex bradycardia that can be blocked by atropine.
- Cardiac output is slightly decreased and peripheral resistance is considerably increased. Circulation time is slightly prolonged, and venous pressure is slightly increased.
- Most vascular beds are constricted leading to renal splanchnic, cutaneous, and limb blood flow reduction but coronary blood flow is increased.
- Pulmonary vessels are constricted, and pulmonary arterial pressure is raised.
- Severe hypotension
- Septic shock
- Cardiogenic shock
- Situations where levo causes tachyarrhythmias
The drug is a powerful vasoconstrictor with properties very similar to norepinephrine but almost completely lacking the chronotropic and inotropic actions on the heart that norepinephrine provides.
The majority of norepinephrine effects are going to lead to an activation of the alpha 1, alpha 2, and beta 1 receptors. Levophed functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action)
- Increases heart rate
- Increase BP through an increase in cardiac output and systemic vascular resistance.
- Vasoconstriction of arteries and veins (alpha 1 and alpha 2)
- Increase in heart contractility (beta 1 mediated).
- Increases blood flow to skeletal muscle.
- Reduces blood flow to the gastrointestinal system.
- Inhibits voiding of the bladder and gastrointestinal motility.
- Severe hypotension
- Septic shock
- Cardiogenic shock
Stimulates alpha 1 and 2, and beta 1, and 2 adrenergic receptors. Epinephrine is usually given as a last resort drip or pushed during a code. It has the shortest half-life of all the vasopressors.
- Relaxation of the smooth muscle of the bronchial tree
- (increasing myocardial oxygen consumption)
- Increased heart rate and contractility (beta 1)
- Vasoconstriction in most arteries and veins (alpha 1 and 2)
- Low concentrations cause vasodilation of muscle and liver vasculature (Beta 2)
- High concentrations cause vasoconstriction (alpha mediated)
- Cardiac output is increased but with a small change in MAP due to a decrease in systemic vascular resistance (Beta 2 mediated)
- Increase in myocardial oxygen consumption
- Anaphylactic shock
- Cardiogenic shock
- Cardiac arrest
- Inotropic support
Vasopressin doesn’t act on the same receptors as the prior pressors. Vasopressin is a peptide hormone that acts on 2 major sites, V1 which is the blood vessels and V2 are the kidneys.
- V1 is responsible for the constriction of blood vessels through an increase in systemic vascular resistance leading to an increase in MAP
- V2 is responsible for regulating extracellular fluid volume. Activation causes fluid reabsorption leading to an increase in blood volume causing an increase in MAP.
Dopamine is a precursor of norepinephrine and stimulates norepinephrine release. At low doses, dopamine stimulates the heart and decreases systemic vascular resistance. At high doses, dopamine’s vasodilation effect becomes vasoconstriction as lower affinity α-receptors bind to the dopamine. Dopamine also binds to D1 receptors in the kidney, producing vasodilation.
- Stimulates both adrenergic and dopaminergic receptors.
- Lower doses
- Mainly dopaminergic stimulating producing renal and mesenteric vasodilation.
- Higher doses
- Both dopaminergic and beta1-adrenergic stimulating and produce cardiac stimulation and renal vasodilation.
- Larger doses
- Stimulate alpha-adrenergic receptors causing vasoconstriction
- Hemodynamic support
- Acute heart failure and cardiogenic shock
- Acute renal failure
In this episode, we will be talking about 7 lifestyle changes for 2021 to boost your immune system and overall improve your wellbeing. This episode couldn’t have been in a better time, with a global pandemic and the start of the new year.
As you kick off 2021, reflect on the past year and set goals for yourself. I think the lockdown was a great teacher for many, whether it’s about your health or career. The key for 2021 success will require a mindset shift, not empty New Years promises. Don’t waste this upcoming year with stagnation, take this new chapter as a way to grow and develop yourself as a person.
Since we are in a global pandemic and the government nor the masks won’t save us from illness, it’s time to do our part in society and strengthen our immune health. There are several dietary and lifestyle changes to incorporate which may strengthen your body’s natural defenses and help you fight harmful pathogens, or disease-causing microbes.
1. Getting enough sleep
What happens if you don’t sleep enough? Not getting quality sleep can weaken your immune system, lower your sex drive, make it harder to think straight, ages your skin, and leads to weight gain. Lack of sleep is literally making us fat, sick, inflamed, and imbalanced.
In fact, according to the CDC, more than one-third of Americans don’t get enough sleep. If you find yourself in the one-third category, it’s time to realize that the first thing you should do is prioritize sleep. We’d all love to be the sleepless hustler who works like a maniac, pushes hard at the gym, goes out on weekends, and always feels great on only five hours of sleep.
Newsflash: This person doesn’t exist, and if you know someone like this, they’re heading for burnout. Your brain does allow you to feel sleepy sometimes, but trying to block that feeling with caffeine will short-circuit a lot of important warning signs of sleep deprivation.
- Depressed mood
- Difficulty learning new concepts
- Inability to concentrate
- Lack of motivation
- Reduced sex drive
In a study in 164 healthy adults, those who slept fewer than 6 hours each night were more likely to catch a cold than those who slept 6 hours or more each night. Short sleep duration = susceptibility to infectious illness. The participants tracked sleep using wrist actigraphy for 7 consecutive days and then were quarantined and administered nasal drops containing the rhinovirus and monitored over 5 days.
Sleep deprivation may decrease the production of protein cytokines and antibodies. How much sleep do you need to bolster your immune system? The optimal amount of sleep for most adults is seven to eight hours of good sleep each night. Teenagers need nine to 10 hours of sleep. School-aged children may need 10 or more hours of sleep.
Sleep and vaccines
Studies have clearly shown that sleep improves the effects of vaccines, demonstrating sleep’s benefits for adaptive immunity.
Vaccines work by introducing a weakened or deactivated antigen to the body, triggering an immune response. In this way, immunizations effectively teach the immune system9 to recognize and attack that antigen.
Sleep is an important factor that helps determine the effectiveness of vaccines. Studies of vaccines for hepatitis and swine flu (H1N1) have found that when people don’t sleep the night after receiving a vaccine, the body’s immune response is weaker. In some cases, this reduces the vaccine’s protection and may even require a second dose of the vaccine.
If you’re having trouble sleeping, try limiting screen time for an hour before bed, as the blue light emitted from your phone, TV, and computer may disrupt your circadian rhythm or your body’s natural wake-sleep cycle. Other sleep hygiene tips can be darkening, using a sleep mask, and going to bed at the same time every night.
2. Stay hydrated
Hydration doesn’t necessarily protect you from germs and viruses, but preventing dehydration is important to your overall health.
Our immune system is highly dependent on the nutrients in our bloodstream, and our bloodstream is made mostly of water! If we don’t have enough water, we cannot properly transport nutrients to each organ system. Staying well-hydrated is also very important for detoxification pathways, increasing lymphatic draining, and making sure we are clearing out any foreign invaders and other waste materials. Dehydration can contribute to muscle tension, headaches, low serotonin production, and digestive issues.
The easy rule of thumb for how much water to drink is a minimum of half of your body weight in ounces of water. This means, if you weigh 150 pounds, you need to drink at least 75 ounces of water daily. If you drink a cup of coffee – drink an additional 1 cup of water.
3. Eat more whole plant foods
An astounding 70 to 80 percent of your immune system resides in your gut. The immune system is separated from the 100 trillion microbes of your gut microbiome by a single layer of cells a fraction of the width of a strand of hair. The two are in constant communication.
A strong microbiome empowers the neighboring immune cells for optimal function. The foods that are highest in fiber are whole plant foods, including vegetables, fruits, whole grains, legumes, nuts, and seeds. Instead of focusing on a single micronutrient, like vitamin C, it’s important to eat a wide variety, since they contain different vitamins, minerals, antioxidants, and phytochemicals that work in synergy.
These whole foods also contain antioxidants that decrease inflammation by combatting unstable compounds called free radicals, which can cause inflammation when they build up in your body at high levels. Chronic inflammation is linked to numerous health conditions, including heart disease, Alzheimer’s, and certain cancers.
4. Exercise more
Improvements in immunity due to the regular exercise of moderate intensity may be due to reductions in inflammation, maintenance of thymic mass, alterations in the composition of “older” and “younger” immune cells, enhanced immunosurveillance, and/or the improvement of psychological stress. Indeed, exercise is a powerful behavioral intervention that has the potential to improve immune
We do not know exactly if or how exercise increases your immunity to certain illnesses. There are several theories. However, none of these theories have been proven. Some of these theories are:
- Physical activity may help flush bacteria out of the lungs and airways. This may reduce your chance of getting a cold, flu, or other illness.
- Exercise causes a change in antibodies and white blood cells (WBC). WBCs are the body’s immune system cells that fight disease. These antibodies or WBCs circulate more rapidly, so they could detect illnesses earlier than they might have before. However, no one knows whether these changes help prevent infections.
- The brief rise in body temperature during and right after exercise may prevent bacteria from growing. This temperature rise may help the body fight infection better. (This is similar to what happens when you have a fever.)
- Exercise slows down the release of stress hormones. Some stress increases the chance of illness. Lower stress hormones may protect against illness.
5. Limit added sugars
Many experts say that sugar is one of the most harmful substances we can ingest. Take a look at western culture, where obesity and diabetes are on the rise. According to the American Heart Association, the limit for added sugar should be no more than six teaspoons of sugar for women and nine teaspoons for men (One teaspoon is 5g). In the United States, the average person consumes more than 126 grams of sugar per day!
Sucrose is the scientific name for sugar. Sucrose is naturally made by plants, through photosynthesis. The sucrose molecule is made up of two parts: glucose and fructose. fructose is not needed. Fructose can only be metabolized in the liver; any excess is converted into fat, which is then stored in the liver. A prevalent form of fructose is high fructose corn syrup.
A big impact at that – immune function decreases for hours after sugar is consumed. A research study was done by Loma Linda University in which participants were fed different forms of sugar found that the effectiveness of white blood cells (our immune cells that fight infection) decreased up to 50% after 1-2 hours of eating sugar, lasting up to five hours!
6. Eating more fermented foods or taking a probiotic supplement
Fermentation is an ancient technique of preserving food. Fermented foods are rich in beneficial probiotics and have been associated with a range of health benefits — from better digestion to stronger immunity. These foods include yogurt, sauerkraut, kimchi, and kefir. Research suggests that a flourishing network of gut bacteria can help your immune cells differentiate between normal, healthy cells and harmful invader organisms.
A systematic review provides evidence from a number of good-quality Respiratory tract infections that probiotics reduce the duration of illness in otherwise healthy children and adults.
Not to mention many fermented foods are rich in vitamin C, iron, and zinc — all of which are proven to contribute to a stronger immune system.
7. Manage your stress levels
Managing your stress levels and anxiety is key to your immune system. Evidence is tracing the pathways of the mind-body connection. For example, chronic feelings of loneliness can help to predict health status – may be because lonely people have more psychological stress or experience it more intensely and that stress, in turn, tamps down immunity.
Short-term stress can enhance the acquisition and/or expression of immunoprotective (wound healing, vaccination, anti-infectious agent, anti-tumor) or immuno-pathological (pro-inflammatory, autoimmune) responses.
In contrast, chronic stress can suppress protective immune responses and/or exacerbate pathological immune responses.
Activities that may help you manage your stress include meditation, exercise, journaling, and yoga.
These healthy lifestyle practices can lessen the intensity and duration of your symptoms when you do catch a bug. Getting sick and getting better is part of a healthy life. The more you can build up that memory of different viruses, the more likely your sickness is to be uneventful.
In this episode, we are going to cover self-care, burnout, and mental health.
Aleksandra Zubek is currently in a clinical psychology counseling internship. We discuss Mental health, self-care, depression, and burnout during COVID.
- 1 in 5 U.S. adults experience mental illness each year
- 1 in 20 U.S. adults experience serious mental illness each year
- 1 in 6 U.S. youth aged 6-17 experience a mental health disorder each year
- 50% of all lifetime mental illness begins by age 14, and 75% by age 24
- Suicide is the 2nd leading cause of death among people aged 10-34
These are some of the questions we answer with Aleks.
- What is burnout?
- What is self-care?
- Why do you think people see it as selfish? Is it selfish?
- Because if your cup isn’t full then you can’t give more than that.
- How can we promote our self-care during covid? What can people do?
- Ever thought about what you do for yourself that makes you feel good?
- Whether it’s going to do a face mask, reading a fun novel, or going on a 10-minute walk.
- How can someone figure out what makes them feel good? Let’s take for example someone with depression that just can’t find something to be happy about, how can they find that spark or how can we help them find it?
- Drug overdoses have been on a rise in 2020, where can it stem from?
- How can we promote self-healing? In the sense how can we get past trauma?
- How to approach Different types of trauma?
- Traumatic grief
- Annual prevalence among U.S. adults, by condition, top 3. Can we touch upon each? What they are, symptoms, whos at risk, how it develops, best approaches?
- Anxiety Disorders: 19.1% (estimated 48 million people)
- Major Depressive Episode: 7.8% (19.4 million people)
- Posttraumatic Stress Disorder: 3.6% (estimated 9 million people)
In this episode, we’re going to talk about the ICU. Specifically why we prefer ICU and why nurses like working in the ICU. The main reasons are; patient ratios, makes us more marketable, more critical thinking, and being there for the patient in their most vulnerable point. We’ll also touch base on some good qualities of ICU nurses.
Why do we prefer ICU?
Every year, intensive care units (ICUs) in the United States admit over 5.7 million patients. The ICU is a unit reserved for some of the most vulnerable patients, those who are critically ill and need close supervision in case their condition rapidly takes a turn for the worse. Some ICUs specialize in certain areas such as pediatric, cardiac, or trauma, but many serve a general-purpose. Occupational, respiratory, and physical therapists, dieticians, doctors, and nurses all collaborate in these units in pursuit of successful patient recovery.
ICU patients are often intubated, ventilated, and have multiple IV drips at a time. They must know the ins and outs of a lot more equipment than nurses who practice in a lower-stakes environment. They must also chart a lot more to keep up with intensive monitoring, assessments, and equipment.
Critical care nurses monitor their patients 24/7. Their patients need a high level of constant care, so there should always be a nurse to watch over patients. As such, ICU nurses often only work with one to two patients at any given time.
Having 2 patients sounds like a walk in the park but these patients are very critical with a change in condition within seconds. There are even 1-1 patients that are really sick usually requiring CRRT, ECMO, IABP, and special catheters.
Usually pays more/ more marketable
Some facilities offer more pay to their ICU nurses or specialized units. This is because these units tend to take care of a certain population and often require more critical thinking and hands-on work.
ICU nurses tend to be more marketable because ICU is the highest tier in a hospital setting. ICU nurses can float to other parts of the hospital like med-Surg, tele, stepdown, etc. It’s expected that you should know more during a critical patient situation than other nurses.
More thinking and fixing, less touchy-feely
A lot happens in the ICU. The majority of our patients are intubated sedated. What that means is they can’t talk. It does have its positives and negatives. When you have an intubated and sedated patient they run on your clock, patient care wise. You do your hourly rounding and plan out when you’re going to do what task. There isn’t the time or opportunity for the patient to refuse, no playing cat and mouse with their bath or dinner. You have more control.
There is a lot of emotion in the ICU just not the touchy-feely stuff you commonly find on other units. A lot of the emotion comes from being the middle man; patient to family, patient to MD. Another part is during death or a crashing patient. Unfortunately, the ICU sees a lot of death and disgruntled family dynamics.
Being there for people in their worst situation
There’s something about the ICU patients being at their most vulnerable and at the brink of death that draws nurses to it. There are 2 options for a patient in the ICU, death or transfer. Our role in the ICU is to stabilize, treat, and repeat. There are days in the ICU where every patient looks like they are fighting a losing battle with death and as hard as those are we are with that patient through it all. Even though we can’t always talk to our patients the energy is in the rooms and that draws people.
The worst situations bring out the best in us, which doesn’t only apply to life outside the scrubs but also to ICU nursing. As crazy as it sounds critically ill patients stimulate our minds and are a learning opportunity.
Good Qualities of an ICU nurse
- Critical thinking
- Physical abilities
- Time management
Covid-19 cases are steadily rising in the US and there is an aim for another lockdown. Evidence is showing that a more positive outlook on life and feeling happy in general is being associated with less memory decline. The benefits of caffeine have been debated for years, most recently caffeine intake is being linked with long-term memory benefits. Organ-on-chip has the potential to transform the way we do research on human cells with the potential of benefiting reperfusion therapy.
As of 11/15 – Cases: 54,817,231 Deaths: 1,324,461
US: 11,366,503 Deaths: 251,836 Recovered: 6,935,630
- Texas – 1,093,645
- California – 1,033,687
- Florida – 885,201
- New York – 597,394
- Illinois – 573,616
Positivity Is Associated With Less Memory Decline: Evidence From a 9-Year Longitudinal Study
A new study finds that people who feel enthusiastic and cheerful — what psychologists call ‘positive affect’ — are less likely to experience memory decline as they age. This result adds to a growing body of research on the positive effect’s role in healthy aging.
Unfortunately, we wish some memorization could last a lifetime, but emotional factors can negatively impact our ability to remember information throughout life.
A team of researchers analyzed data from 991 middle-aged and older U.S. adults who participated in a national study conducted at three time periods: between 1995 and 1996, 2004 and 2006, and 2013 and 2014.
In each assessment, participants reported on a range of positive emotions they had experienced during the past 30 days. In the final two assessments, participants also completed tests of memory performance. These tests consisted of recalling words immediately after their presentation and again 15 minutes later.
Results revealed that positive affect was associated with less memory decline across 9 years when analyses controlled for age, gender, education, depression, negative affect, and extraversion (state of primarily obtaining gratification from outside oneself.)
What’s interesting is as people get older, they experience fewer negative emotions. Older adults are more emotionally gratifying memory distortion for past choices. This is a broad statement but the positivity effect in older adults’ memories seems to be due to their greater focus on emotion regulation secondary to cognitive control mechanisms that enhance positive and diminish negative information.
80% of the population consumes some type of caffeine, in the US it’s at about 90%.
Caffeine is a natural stimulant most commonly found in tea, coffee, and cacao plants.
It works by stimulating the brain and central nervous system, helping you stay alert and prevent the onset of tiredness.
Caffeine vs adenosine
To understand the function of caffeine one has to grasp the concept of another neurotransmitter called adenosine.
Most people initially drink caffeine in the form of a beverage. It’s absorbed in the small intestines within an hour and becomes available throughout the blood and most parts of the body, including your brain. The mean half-life of caffeine is about 5 hrs.
As it starts entering your brain, it starts competing with adenosine.
How adenosine makes you feel sleepy
There are many different receptors in your brain, different ones have different effects. The one we’re interested in is the A1 receptor. Adenosine locks with the A1 receptor, it promotes muscle relaxation and sleepiness, which is why people get tired as the day progresses.
Furthermore, adenosine can bind to the A2A receptor. This binding interferes with the release of mood-improving neurotransmitters, such as dopamine. Adenosine itself is produced primarily from physical work and intensive brain use. That is why over the course of the day your body accumulates adenosine.
The caffeine in your brain is competing with adenosine and preventing it from binding to A1 receptors. This is why it promotes wakefulness.
Caffeine doesn’t actually lock in with the A1 receptor. It’s more like something that gets in the way and occupies the lock, rather than actually unlocking it.
It similarly gets in the way of the A2A receptor, which can help promote the release of dopamine and glutamate, making you feel good after a cup of coffee.
When you first wake up, your body has metabolized away the adenosine molecules. You’re a bit groggy, but you’re waking up.
Effects of Caffeine
- Stimulates your central nervous system, which can make you feel more awake and give you a boost of energy
- Is a diuretic, meaning that it helps your body get rid of extra salt and water by urinating more
- Increases the release of acid in your stomach, sometimes leading to an upset stomach or heartburn
- May interfere with the absorption of calcium in the body
How much Caffeine
- 1 cup of coffee = 100 mg
- 1 cup of tea = 50 mg
- 1 can/ 12 fl oz red bull = 112 mg
- 1 can/ 16fl oz monster = 160 mg
- 1can/ 16 fl oz bang = 300 mg
- This study investigated the within‐person relationship between caffeine intake and sleep duration at home.
- 377 participants (aged 35–85 years) completed a 7‐day diary study.
- Results revealed a significant effect of sleep duration on the change tendency of caffeine use: a shorter sleep duration predicted a stronger tendency to consume caffeine, and this phenomenon was only found in middle-aged adults (aged 35–55 years) not in older adults (aged 55+).
- This study measured the effects of 0, 12.5, 25, 50, and 100 mg caffeine on cognitive performance, mood, and thirst in adults with low and moderate to high habitual caffeine intakes.
- All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat.
- The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers.
- Conclusions: After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood, and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.
- A group of 1875 healthy adults, stratified for age (range 24 – 81 years), sex, and general ability, were screened for the habitual intake of coffee and tea and took part in extensive cognitive testing.
- Multiple regression analysis with control for age, sex, socio‐demographic variables, and substance use showed that habitual caffeine consumption was significantly related to better long‐term memory performance and faster locomotor speed.
- No relationships were found between habitual caffeine consumption and short-term memory, information processing, planning, and attention as measured with the Stroop Test. Moreover, no difference in sensitivity to caffeine intake between different age groups was found, suggesting that caffeine intake did not counteract age-related cognitive decline.
Reviving Cells After a Heart Attack
Researchers have unraveled potential mechanisms behind the healing power of extracellular vesicles and demonstrated their capacity to not only revive cells after a heart attack but keep cells functioning while deprived of oxygen during a heart attack. The researchers demonstrated this functionality in human tissue using a heart-on-a-chip with embedded sensors that continuously tracked the contractions of the tissue.
- Extracellular Vesicles (EVs) are nanometer-sized messengers that travel between cells known as intercellular communication.
- EVs are a promising tool for the next generation of therapies for everything from autoimmune and neurodegenerative disease to cancer and tissue injury.
- EVs derived from stem cells have already been shown to help heart cells recover after a heart attack, but exactly how they help and whether the beneficial effect is specific to EVs derived from stem cells has remained a mystery.
Researchers from Harvard School of Engineering and Applied sciences have unraveled a potential mechanism that demonstrated the potential mechanism behind the healing power of EVs and demonstrated their capacity to not only revive cells after a heart attack but keep cells functioning while deprived of oxygen during a heart attack.
How was this discovered? Researchers used a heart-on-a-chip with embedded sensors that continuously tracked the contractions of the tissue.
The team tested the effect of Endothelial-derived EV’s (EEVs) on human heart tissue using the heart-on-a-chip model. Organ-on-chip platforms mimic the structure and function of native tissue and allow researchers to observe, in real-time, the effects of injuries and treatments in human tissue.
Reperfusion injury mechanism
The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than (or along with) restoration of normal function. The ischemic tissue produces more reactive oxygen species but less nitric oxide following reperfusion and the imbalance results in an inflammatory response.
Findings in the research study
- The researchers simulated a myocardial infarction and reoxygenation on chips that were infused with EEVs and those that were not.
- They found that in tissues treated with EEVs, the cardiomyocytes could better adapt to stress conditions and sustain a higher workload.
- The researchers induced injury by three hours of oxygen restrictions followed by 90 minutes of reoxygenation and then measured the fraction of dead cells and the contractile force of the tissue.
- The heart tissue treated with EEVs had half as many dead cells and had a contractile force four times higher than the untreated tissue after injury.
What will be the future of Exosomal cell therapies?