- History of CPR
- Sex After Heart Disease: When Is It Safe to Get Back in the Saddle?
- The College Conversation: Essays That Worked
- How Viagra puts a brake on a master growth regulator to treat heart disease
- Surprising Body Cues That Could Be a Heart Concern
- Direct (but Surprising) Signs of Heart Problems
- Johns Hopkins Study Suggests Intermittent Fasting for a Longer, Healthier Life
History of CPR
The Bellows Method
The Bellows Method1 first used by Swiss physician Paracelsus.
In Alloa, Scotland, local surgeon William Tossach uses mouth-to-mouth breaths to revive a suffocated coal-pit miner. Dr. Tossach documents the success 12 years later, in what may be the first clinical description of mouth-to-mouth resuscitation in medical literature.
The Academie des Sciences in Paris officially recommends mouth-to-mouth resuscitation for reviving victims of drowning.2
London physicians William Hawes and Thomas Cogan found the Society for the Recovery of Persons Apparently Drowned (later to become The Royal Humane Society) to assist victims of sudden and unexpected death.
Experimenting with animals, Danish veterinarian Peter Abildgaard discovers that after rendering a chicken lifeless by shocking it, countershocks to the chest could restore a heartbeat.3
The Royal Humane Society expresses its preference for using bellows rather than mouth-to-mouth ventilation to artificially inflate the lungs.4
The Hall and Silvester methods become the most commonly used forms of artificial respiration until the early 20th century.5
The Hall Method
London physician Marshall Hall introduces his simple resuscitation technique: alternately repositioning the patient from face up to side. He updates the approach by adding pressure on the thorax.6
Henry Silvester, another London physician, creates the chest-pressure arm-lift method: raise the patient’s arms up to expand the chest, then cross the arms over the chest to apply expiratory pressure.7
The Silvester Method
German physiologist Moritz Schiff’s research on animals in Florence, Italy8 reveals that massaging the heart during surgery can restore circulation.
In Germany, Rudolph Boehm shows that external compressions of the heart provide adequate circulation in cats.9
After using external compressions to restart the hearts of 2 young human patients, German surgeon Dr. Friedrich Maass becomes the first to advocate chest compressions, rather than ventilation alone, to help with circulation.10 But the technique doesn’t take hold, and for the next half century, open-heart massage is the standard.
In Cleveland, Ohio, Dr. George Crile’s research confirms that external chest compressions restore circulation in dogs.11
Dr. Crile reports successful closed-chest cardiac massage in 1 human case.12 But once again, the noninvasive technique doesn’t gain traction, and patients continue to receive open-heart massage.
Six cardiologists meet in Chicago and form the American Heart Association (AHA) as a professional society for physicians. Nearly a century later, the AHA will be the world leader in CPR and emergency cardiovascular care (ECC) training and education.
Early meeting of the AHA
Researchers at Johns Hopkins University, led by electrical engineer William Kouwenhoven, PhD, accidentally rediscover external compressions when they find that pressure on a dog’s sternum provides adequate circulation to the brain to keep the animal alive until defibrillation can restart its heart. Their results are confirmed in more than 100 dogs.13
A canine patient in Kouwenhoven’s lab, revived by the team’s experimental combo: external chest compressions and defibrillation.
In Cleveland, Ohio, cardiothoracic surgeon Dr. Claude Beck performs the first successful use of an electric defibrillator on an exposed human heart.14
Original AHA logo
The AHA begins publishing Circulation, a scientific journal that informs doctors, researchers, and others about cardiovascular breakthroughs.
American physician and respiratory researcher Dr. James Elam becomes the first person to prove that expired air is sufficient to maintain adequate oxygenation.15
Dr. Elam and Dr. Peter Safar prove that mouth-to-mouth resuscitation is an effective lifesaving method. Drs. Elam, Safar, and Archer Gordon play leading roles in promoting rescue breathing to professional healthcare providers and the public a.16
For the first time in human medicine, an external defibrillator successfully restores a steady rhythm to a quivering heart. Harvard cardiologist Dr. Paul Zoll leads the study with funding from the AHA.
The United States military adopts the mouth-to-mouth resuscitation method to revive unresponsive victims.
Dr. Safar performs mouth-to-mouth resuscitation in Baltimore, 1957.
A Hopkins Closed Chest Defibrillator
After several years of research on closed-chest defibrillation, Dr. Kouwenhoven’s team at John’s Hopkins, which includes James Jude, MD, and Guy Knickerbocker, PhD, unveils its prototype of the first portable external defibrillator (on a wheeled cart): the 200-lb Hopkins Closed Chest Defibrillator.17
(l to r) Doctors Jude, Kouwenhoven, and Knickerbocker
Resuscitation pioneers Drs. Kouwenhoven, Safar, and Jude combine mouth-to-mouth breathing with chest compressions to create cardiopulmonary resuscitation, the lifesaving actions we now call CPR.
The AHA starts a program to acquaint physicians with closed-chest cardiac resuscitation, which becomes the forerunner of CPR training for the general public.
The life-size training manikin (a collaborative effort by Drs. Safar, Elam, and Gordon and Norwegian toymaker Åsmund Lærdal) goes on to teach CPR skills to more than 400 million people—and counting—worldwide.18
Resusci Anne through the ages: 1960-2018
Cardiologist Dr. Leonard Scherlis establishes the AHA’s CPR Committee. That same year, the AHA formally endorses CPR.
The National Research Council of the National Academy of Sciences convenes an ad hoc conference on cardiopulmonary resuscitation. The conference is the direct result of requests from the American National Red Cross and other agencies to establish standardized training and performance standards for CPR.
Dr. Leonard Cobb
In Seattle, University of Washington cardiologist Dr. Leonard Cobb launches Medic II, the world’s first mass citizen training in CPR.19 During its first 2 years, the program helps train more than 100,000 people.
Second National Conference on CPR and ECC
The AHA publishes the first Advanced Cardiovascular Life Support (ACLS) Textbook.
A program to provide telephone instructions for performing CPR begins in King County, Washington. The program trains emergency dispatchers to give callers CPR instructions while EMT personnel are in route to the scene. Fast forward to the 21st century: Dispatcher-assisted telephone CPR is standard in dispatch centers across the United States.
The AHA convenes a national conference on pediatric resuscitation to develop CPR and ECC guidelines for pediatric and neonatal patients.
Fourth National Conference on CPR and ECC
In co-sponsorship with The American Academy of Pediatrics, the AHA introduces the first pediatric courses: pediatric BLS, pediatric advanced life support (PALS), and neonatal resuscitation.
Public access defibrillation programs provide training and resources, including AEDs, to the public so that they can help resuscitate victims of cardiac arrest.
Fifth National Conference on CPR and ECC
Founding of the International Committee on Resuscitation (ILCOR)
The first task force on first aid is appointed. This year also sees the first International Conference on Guidelines for CPR and ECC.
The AHA and ILCOR release a statement about AED use in children, stating that for children ages 1 year to 8 years who have no signs of circulation, it is appropriate to use an AED.
The AHA develops the Family & Friends® CPR Anytime® kit, an innovative product that enables anyone to learn the core skills of CPR in just 20 minutes. The kit provides everything needed to learn basic CPR, AED skills, and choking relief anywhere, from a family room at home to a setting for instructing large groups.
The 2005 International Consensus on CPR and ECC Science With Treatment Recommendations (CoSTR) Conference leads to the AHA publishing the 2005 AHA Guidelines for CPR and ECC. The Guidelines recommend a new compression-to-ventilation ratio of 30:2 as well as changes to AED usage.
The AHA releases new recommendations that say bystanders can skip mouth-to-mouth resuscitation and use Hands-Only CPR to help an adult who suddenly collapses.20 In Hands-Only CPR, bystanders dial 9-1-1 and provide high-quality chest compressions by pushing hard and fast in the center of the victim’s chest.
After the 2010 International CoSTR Conference, the AHA publishes the 2010 AHA Guidelines for CPR and ECC. 2010 also marks the 50th anniversary of CPR.
The AHA's Hands-Only Mobile Tour hits the road to teach Hands-Only CPR across the country.
AHA's Hands-Only CPR mobile tour visits southern Maine.
The AHA installs an interactive CPR kiosk at Dallas-Ft. Worth airport. It features a practice manikin, video, and touch screen that give performance feedback as passengers between flights learn to perform hands-only CPR. Within 5 years, there will be more than 30 CPR kiosks in cities across the country.
The Institute of Medicine releases its report Strategies to Improve Cardiac Arrest Survival: A Time to Act (2015). After the 2015 International CoSTR Conference, the AHA publishes the 2015 AHA Guidelines Update for CPR and ECC.
The AHA begins its continuous evidence evaluation process for the Guidelines for CPR and ECC and, later that year, releases the 2017 Focused Update.
In June, the AHA publishes “Resuscitation Education Science: Educational Strategies to Improve Outcomes from Cardiac Arrest” in the journal Circulation.
This statement, which is applicable to all resuscitation training programs (not exclusive to AHA), examines best practices in education and applies them to resuscitation.
By implementing the statement’s guidance, training programs and resuscitation instructors will help raise the standard of care and increase survival from cardiac arrest.
Return to 1700s
1 Image 1530-1800s, Europe, The Bellows Method, first used by Swiss physician Paracelsus. Reprinted by permission from Chicago’s Museum of Science and Industry.
2 Baker AB. Artificial Respiration, The History of An Idea. Medical History. 1971;15(4):336-351. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1034194/pdf/medhist00129-0028.pdf
3 Cakulev I, Efimov IR, Waldo AL. Cardioversion: Past, Present, and Future. Circulation. 2009; 120:1623-1632. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782563/ ; Driscol TE, Ratnoff OD, Nygaard OF. The remarkable Dr. Abildgaard and countershock. The bicentennial of his electrical experiments on animals. Ann Intern Med. 1975;83(6):878-82 https://www.ncbi.nlm.nih.gov/pubmed/1106286
4 Trubuhovich RV. History of mouth-to-mouth rescue breathing. Part 2: the 18th century. Crit Care Resusc. 2006;8(2):157-71. https://www.ncbi.nlm.nih.gov/pubmed/16749887
Return to 1800s
5 Baskett TF. The Holger Nielsen method of artificial respiration. Resuscitation. 2007;74:403-405. https://www.resuscitationjournal.com/article/S0300-9572(07)00168-2/abstract
6 Baskett TF. Silvester’s technique of artificial respiration. Resuscitation.2007;74:8-10. https://www.resuscitationjournal.com/article/S0300-9572(07)00019-6/abstract
Photo courtesy of Laerdal Medical Corporation. 1856-Marshall Hall Method. Chest elevated, a victim is pulled up on his side momentarily, then rolled back. Pressure on back expelled air.
7 Baskett TF. Silvester’s technique of artificial respiration. Resuscitation. 2007;74:8-10. https://www.resuscitationjournal.com/article/S0300-9572(07)00019-6/abstract
Photo courtesy of Laerdal Medical Corporation. 1861-Silvester Method Victim on back, arms over head. Arms moved forward, folded on chest and pressed. Tongue held, keeping air passage open.
8 Vallejo-Manzur F, Varon J, Fromm Jr R, Baskett P. Moritz Schiff and the history of open-chest cardiac massage. Resuscitation. 2002;53:3-5. https://www.resuscitationjournal.com/article/S0300-9572(02)00028-X/abstract
9 Hurt R. Modern cardiopulmonary resuscitation—not so new after all. JR Soc Med. 2005;98(7):327-331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1168923/
10 Taw Jr. R. Dr. Friedrich Maass: 100th Anniversary of “New” CPR. Clin Cardiol. 1991;14:1000-1002. https://acilci.net/wp-content/uploads/2013/08/Dr.-Friedrich-Maass-100th-Anniversary-of-New-CPR.pdf
Return to 1900 to 1940s
11 Crile G. Blood Pressure in Surgery: an experimental and clinical research. Cartwright prize essay for 1903. https://archive.org/stream/b21510842/b21510842_djvu.txt
12 Hurt R. Modern cardiopulmonary resuscitation—not so new after all. J R Soc Med. 2005;98(7):327-331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1168923/
13-14 Beaudouin D. W.B. Kouwenhoven: Reviving the Body Electric. Johns Hopkins Engineering. 2002(Fall):27-32. https://engineering.jhu.edu/include/content/pdf/engmag02/27_32.pdf
Return to 1950s
15 Sands RP, Bacon DR. An Inventive Mind: The Career of James O. Elam, MD (1918-1995). Anesthesiology. 1998;88:1107-1112. http://anesthesiology.pubs.asahq.org/Article.aspx?articleid=1947621
Image Dr. Safar performs mouth-to-mouth resuscitation in Baltimore, 1957. Reprinted by permission from the Safar Center for Resuscitation Research.
16 Sands RP, Bacon DR. An Inventive Mind: The Career of James O. Elam, MD (1918-1995). Anesthesiology. 1998; 88:1107-1112. http://anesthesiology.pubs.asahq.org/Article.aspx?articleid=1947621
17 Beaudouin D. W.B. Kouwenhoven: Reviving the Body Electric. Johns Hopkins Engineering. 2002(Fall):27-32. https://engineering.jhu.edu/include/content/pdf/engmag02/27_32.pdf
Image A Hopkins Closed Chest Defibrillator. Photo courtesy of Johns Hopkins Magazine.
Image (l to r)Dr. James Jude, William Kouwenhoven, and Guy Knickerbocker. Reprinted by permission from the Veterinary Emergency and Critical Care Society.
Return to 1960s
18 Tjomsland, Nina. Saving more lives – together. The vision for 2020. 2015. Laerdal Medical Corporation.
Three variations of Resuscitation Anne manikin heads. Photo courtesy of Laerdal Medical Corporation.
Return to 1970s
19 History. Medic One Foundation website. https://www.mediconefoundation.org/who-we-are/history/
Dr. Leonard Cobb. Photo courtesy of the Medic One Foundation.
Return to 2000s
20 History of the American Heart Association. American Heart Association website. https://www.heart.org/en/about-us/history-of-the-american-heart-association
Sex After Heart Disease: When Is It Safe to Get Back in the Saddle?
From the WebMD Archives
You've been treated for heart disease. You've followed your doctor's orders to a T. Now she says you're ready to get back to normal life. But does that include sex?
You know that clichéd yet haunting scene. Someone's having a fine time in bed. Then he clutches his heart and slumps over — and then it's, well, over. But here's the truth: You're more ly to have a heart attack while arguing with your mate than during sex, says Richard A. Stein, MD. He's a cardiologist at New York University School of Medicine in New York.
The media helps feed the idea that having sex after heart disease is risky. “The story goes back a long time,” Stein says. “The mythology is that at the time of sex, the time of orgasm, you have enormous cardiovascular effort and you put yourself at sudden risk of heart attack.”
But sex is really no harder on the body than climbing a few flights of stairs or briskly walking four or five blocks.
In fact, lots of people get the green light for sex within a week after they leave treatment, says Erin Michos, MD. She's an associate professor of medicine at Johns Hopkins University in Baltimore.
“Patients with heart disease that are stable are generally at very low risk,” she says.
Still, the subject makes many people afraid. But if you replace your fears with these tips, you can be snuggling again quicker than you think.
Get a Stress Test. This is sometimes called a treadmill test. You'll work out on a piece of equipment such as a treadmill or stationary bike while your doctor measures how well your heart keeps up with your body. There are several benefits to this:
- You'll see firsthand what you can do, and you'll feel more confident.
- If your spouse or partner goes along, they'll see your progress and feel more at ease about your physical health and strength.
- Doctors often prescribe some type of cardio rehab after treatment. This test can double as a fitness check for rehab and for sex.
Be Open With Your Doctor. Most patients don't ask outright when they can start having sex. And many doctors don't freely offer that information. This creates an air of mystery or discomfort that helps no one.
Just because your doctor doesn't bring up sex doesn't means it's off the table. They could have their own hang-ups. For instance, a young doctor counseling an older couple might “see” his parents instead, without being aware of it, Stein says. “The doctors need to be comfortable,” he adds.
A task force is working to help doctors improve their skills when it comes to counseling patients about sex, Michos says. Their guidelines include not only follow-up physicals, but also advice and insights specific to the patient. This could include ideas for sexual positions that might work best for a couple or ways they can be intimate without having intercourse.
Light the Flame at Home. This isn't the best time to get fancy. At first, it's best to avoid having sex in a different place than you're used to. And if you're not married or in a monogamous relationship, try to stick with the same partner. The reason is simple. Being in a strange place or with a new person adds stress.
You should also avoid a heavy meal or alcohol before sex. Both can affect blood flow. Having a couple of drinks, or being anxious, “works against” you, Stein says.
If you think you need drugs to treat erectile dysfunction, ask your doctor. But you also need to be sure not to mix them with nitrate drugs, which are used to treat heart pain. That combo can be deadly.
Relax. Your chances of having a heart attack during sex are small. Some people are more ly than others to have one in the bedroom, Stein says. “In reality, those are the same people who have the heart attack after a fight with the boss or when going to a game and getting riled up.”
But if you have chest pain or find your heart isn't beating regularly, call your doctor right away and get checked out.
Put Sex in Its Place. It's natural. And it's an important quality of life issue for men and women, “a sign of healthy, intimate relationships,” Michos says. Studies show that decreased sexual function is often linked to anxiety and depression.
“When you have sex, the world doesn't move,” Stein says. For a couple who isn't having pain and can handle mild exercise, “sexual activity is absolutely a safe thing to do.”
Richard A. Stein, MD, cardiologist, NYU Langone Medical Center; professor, New York University School of Medicine, New York.
Erin Michos, MD, associate director of preventive cardiology, Ciccarone Center for the Prevention of Heart Disease; associate professor of medicine, Johns Hopkins University, Baltimore.
American Heart Association: “Sex and Heart Disease.”
National Heart, Lung, and Blood Institute: “What to Expect During Stress Testing.”
American Heart Association: “Sex and Heart Attack: Talk with Your Doctor.”
National Institute of Alcohol Abuse and Alcoholism: “Beyond Hangovers: Understanding Alcohol's Impact on Your Health.”
Harvard Health Publications: “Are Erectile Dysfunction Pills Safe for Men With Heart Disease?”
Levine, G. Circulation, published online 2012.
© 2015 WebMD, LLC. All rights reserved.
The College Conversation: Essays That Worked
“If you had to choose one food to eat for the rest of your life, what would it be?”
Having had this question asked of me many a time, I realize that such an inquiry must be considered practically. The correct answer would keep me happily sustained for the rest of my years, whereas the wrong choice could leave me tormented until I wither away from monotony.
If I chose macaroni and cheese, per se, I’d be trapped consuming glutinous pasta, tacky milk-fat, yellow dye No.5, and copious amounts of sodium, forever. But if instead, I call upon my contentment understandings and assess my options accordingly, I may arrive at an indefectible conclusion.
And after much deliberation, I believe that I have come to such a response: potatoes.
These tubers are the perfect sustenance due not only to their nutritional qualities but, most notably, to their remarkable versatility. Potatoes may be prepared in a myriad of dishes.
Creamy mashed-potatoes come first to mind, with their fluffy hills of whipped-bliss gracing one’s tongue so delicately.
The thought of golden tater-tots follows; deep-fried potatoes cooked perfectly so as to create a slow crunch when chewed. Then are characteristic french-fries—shoestring or steak, skin on or off.
Baked-potatoes, latkes, hash-browns, gnocchi—all respectable meals. And one mustn’t forget potato-chips when searching for alight snack.
Oh potatoes, how I love you. And when asked what to eat exclusively for the rest of my life, I will enthusiastically respond “potatoes!”, for by picking one, I choose an abundance.
To a casual onlooker, this question may appear inconsequential in its hypothetical nature, but as they say; you are what you eat.
My inclination towards the varied is not contained to my food habits—it is a recurring theme throughout my life. I regularly switch from my mom’s house to my dad’s. I’ve moved twelve times.
I have a fifteen-year-old sister and a two-year-old brother. I’m a dog and a cat person.
This variation tends not to leave me with an aversion to commitment, but a disposition towards diversity. I am interested in many things. So one must understand how I have struggled, faced throughout my education with the question, “If you had to choose one subject to study, one occupation to pursue, one thing to do, for the rest of your life, what would it be?”
I love to play viola; I get a rush communicating without-words to my quartet members in order to convey a musical message. I am at my happiest reading a good book; their complex stories captivate me and I aspire to write a novel of my own.
I want to make laws that improve my country; all people should have a shot at the American dream. I am passionate about protecting the environment; reducing our effect on global-warming is of the utmost importance to me.
I want to help those in need; people still don’t have access to clean water and I want to use my privilege to help change that. I strive to become fluent in Spanish; traveling the world is a dream of mine.
Recently, I have discovered that I really to code; I’m sure in the coming years I will explore things I didn’t know I was interested in.
I don’t have an answer to what exactly it is I want to do for the rest of my life. I love English and political science, but I have yet to find such an all-encompassing response as potatoes. What I’ve realized though, is that I don’t have to sacrifice all for one.
From each of my interests I learn things that contribute to who I am and shape how I see the world. Eventually, I will focus my path.
And when I do have an answer, I will go forth with the knowledge I’ve gathered from each of my varied interests; and I will never stop learning.
How Viagra puts a brake on a master growth regulator to treat heart disease
When normal cells grow, divide or do any job in the body, they do so in response to a whole slew of internal sensors that measure nutrients and energy supply, and environmental cues that inform what happens outside the cell.
A protein called mTOR receives information from these signals and then directs the cell to take action.
And now, with data from cells and mice, researchers at Johns Hopkins Medicine say they have uncovered a long-sought built-in molecular switch that behaves much a car-brake — slowing mTOR's action — and in this particular study prevents overworked hearts from enlarging.
The researchers report their findings on Jan. 30 in Nature, and say their discovery has potential implications for manipulating the molecular switch to treat not only heart disease — the focus of the current study — but also diabetes, kidney and lung disease, cancer and autoimmune disorders.
The protein mTOR, which stands for mechanistic target of rapamycin, has long been a focus of scientists because it is so important to normal cells yet also plays major roles in many diseases. It combines with other proteins to form a complex, the major one being known as mTORC1.
Too much active mTORC1 is known to be bad for the heart and leads to damage and disease, and it is thought that controlling mTORC1 could effectively treat heart disease.
Overworked hearts with too much active mTORC1 enlarge abnormally similar to body muscle that bulks up after lifting weights.
mTORs name derives from the immune-suppressant drug rapamycin, first extracted from Easter Island soil bacteria in the early 1970s, and later shown to block mTORC1 cold. The drug is prescribed to prevent transplanted organ rejection, and treat some rare cancers and genetic diseases.
But the complete shut-down of mTORC1 has its downside as it does so many things in normal cells, limiting prospects for using protein blockers as broader disease therapies, researchers say.
“The problem with the few drugs that we have to manipulate mTORC1 is that they are essentially turning it off, which also shuts down its normal function in the cells,” says senior study report author David Kass, M.D.
, the Abraham and Virginia Weiss Professor of Cardiology, professor of medicine, pharmacology and biomedical engineering at the Johns Hopkins University School of Medicine.
“That means if you use it to, say, treat a tumor, you suppress the immune system as well, and might cause diabetes, or kidney and other organ damage by blocking mTORC1 in the other cells.”
Kass says researchers have spent decades in search of a simple switch to fine-tune mTORC1 activity — up and down — rather than making it be totally on or off, and he now has done it starting with a discovery with another protein of interest they had been studying for its role in heart disease.
Working in Kass' laboratory, lead author and postdoctoral fellow Mark Ranek, Ph.D., was studying how this other protein called Protein Kinase G, protected heart tissue from damage and disease.
He made the surprising discovery that turning on protein kinase G blocked mTORC1, and then figured out how this happens.
The answer lies in a key regulator of mTORC1 called tuberin (dubbed TCS2 by researchers), which acts an “antenna” for biochemical signals triggering or blocking cell growth, and regulating metabolism.
the many other proteins known to alter tuberin, Ranek found protein kinase G altered tuberin by adding phosphates to it, but in a previously unidentified region that turned out to provide the sought after brake- effect. Protein kinase G is also the target of drugs sildenafil (commonly known as Viagra).
“Instead of turning mTORC1 off, we had something that looked more a car brake, that was effective only if the car (mTORC1) was on and active,” says Ranek.
Using genetic engineering tools in heart muscle and connective tissue cells, the team mutated human tuberin protein in the specific places that were altered by protein kinase G. The alterations made the cells behave in one of two ways: one type of mutation “turned up” the effect of tuberin all the time while the other essentially “turned down” its effect all the time.
In the cells with tuberin “turned down,” nothing changed in the cells at rest. But, when the researchers treated the cells with hormones that encourage them to grow, mTORC1 was super-activated and the cells enlarged more than the cells with normal tuberin.
When the researchers looked at the cells that had tuberin “turned up,” they saw no changes in the cells when the same hormones were added.
Kass says the research team concluded that keeping tuberin “turned down” was lifting the chemical foot off a brake pedal, triggering super-activity in mTORC1, while in the cells with tuberin “turned on,” the brake was pushed harder, and mTORC1 remained inactive despite the stimulating hormones.
To test the impact of the new tuberin mutations in living mice, the team used the same gene editing techniques to introduce the same types of tuberin mutations in the protein in all cells in live mice. The researchers then examined the hearts of mice with the mutant versions of tuberin compared to mice with normal tuberin.
Mice with tuberin “turned down” appeared normal and their hearts were the same as those in mice with normal tuberin.
However, when the researchers increased the blood pressure that the heart had to work against, the hearts in the mutated mice grew much bigger on average twice as heavy and more than half the mice died over the next couple of weeks from heart failure. The researchers say that keeping tuberin “off” led to a hyper-activation of mTORC1 which they show caused the fatal damage.
Next, the researchers looked at hearts in mice that had tuberin “turned up.” Hearts from these mice also looked healthy, but when they were stressed using the same conditions of increased blood pressure, they remained healthy. The hearts were still normal in size and the mice stayed alive.
Mice, humans have a pair of each chromosome in every cell.
Kass and team reasoned that if both copies of the tuberin gene mutated to “turned up” resulted in normal hearts, what would happen if only one copy of the gene was mutated? In the next experiments, the researchers looked at what would happen if mice had only one copy of the gene mutation that made tuberin behave as if it always had phosphates attached.
In those experiments the hearts stayed normal in size and had good function despite high blood pressure stress, showing just a single mutation was sufficient to protect the heart. On the flip side, they also found that only one copy of the mutation that “turned down” tuberin was all it took for larger hearts and early death to occur with pressure stress.
“We were struck by how potent the effect was, as only one copy of the gene mutation was needed to get the full protective effect,” says Ranek. “The benefit is that the new way to control mTORC1 by altering tuberin didn't prevent its normal roles, but could keep mTORC1 in check from being turned on to too high of a level.”
“It was as if you are driving a car with one foot on the accelerator pedal and the other on the brake,” says Kass. “Here we found the brake control on the mTORC1 engine. Pushing it more slows it but doesn't stop it completely, and lifting up on it speeds the car up,” adds Kass.
“The bottom line is that by mutating tuberin to mimic protein kinase G's effects, we slowed the engine, and mutating it so protein kinase G was ineffective, we cranked it up.
But neither changed anything unless mTORC1 was stimulated, and only then did you find out whether the foot pressed the brake or released it.”
The authors caution that any clinical application of their findings to the heart probably won't come by way of the genetic engineering of tuberin they performed in the lab.
“This would require some type of gene therapy, which means putting the gene into a virus that then transfers it to the heart,” says Kass. “However, the tuberin gene is too big to fit into viruses we currently have for this job.”
But drugs that activate protein kinase G, such as nitroglycerin and sildenafil, are currently used to relax arteries in patients with coronary heart disease, pulmonary hypertension, and erectile dysfunction, and they are already being actively explored for congestive heart failure. The new study shows how they may be particularly useful in heart diseases in which mTORC1 is too active.
“This is an important finding because it reveals a novel strategy that could be employed in future potential therapeutic efforts to protect the heart from damaging stress such as high blood pressure,” said Bishow Adhikari, Ph.D., a program officer for the study and a scientist with the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, which helped fund the study.
There are other conditions, however, where altering the tuberin gene may be easier to accomplish. In particular, he says, because mTORC1 also plays a critical role in immune cell activation and memory, and these cells are now being genetically modified for cancer therapy, the discovery of the new control brake may eventually enhance the effectiveness of cancer immunotherapy treatments.
Because of the promise, several authors have formed a company to pursue further development of immune system controllers.
Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.
Surprising Body Cues That Could Be a Heart Concern
Linkedin Pinterest Heart Health Know Your Heart Risks
The classic signs of heart trouble—chest tightness, pressure or pain—are far from its only signals.
People often fail to connect other symptoms they’re experiencing to their actual cause: the heart.
This can result in failing to get the help they need for an emergency heart issue, heart attack or stroke, or a critical delay in getting possible heart disease diagnosed and treated.
“Most people know their bodies better than any doctor does. In general, if you constantly feel something isn’t ‘right’ or isn't what you’re used to, that warrants medical attention,” says Parag Joshi, M.D., a cardiology fellow with the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease.
Your whole body can be involved in sending the message that something’s wrong with your heart.
Direct (but Surprising) Signs of Heart Problems
Many heart-related body cues are closely linked to inadequate blood flow through the arteries to the heart. But signs these may not seem obviously connected to the heart.
Jaw and neck pain. Chest pain doesn’t always center on the heart. It’s of concern when it radiates to the jaw and neck from the chest.
Nausea and bloating. Women in particular often describe this kind of discomfort, which can include vomiting, before they feel chest pain.
Overall fatigue. When your heart can’t pump effectively, less blood flows to your lungs and your muscles. Shortness of breath and fatigue when doing everyday activities, such as climbing stairs or walking across a parking lot, is a red flag.
Testing can reveal markers for heart disease that have no visible symptoms, such as high blood pressure and high cholesterol. A coronary calcium scan provides a picture of buildup in the arteries. All these tests can help identify high-risk individuals who can be treated appropriately before they have a serious event, says Johns Hopkins expert Parag Joshi, M.D.
Johns Hopkins research has found that an ultrafast CT scanner can accurately sort out which people with chest pain need an invasive procedure, such as bypass surgery, to restore blood flow to the heart.
Less Direct Signs of Heart Problems
Some problems may or may not have clear links to heart disease but are worth a heart checkup, especially if you have other risk factors for heart disease.
Sleep apnea. This temporary collapse of an airway puts a halt to breathing during sleep and has been linked to high blood pressure and an increased risk of heart attack.
Trouble achieving or maintaining an erection. Though men often don’t connect bedroom problems to the heart, erectile dysfunction can be a very early sign of the arterial damage of heart disease. “A problem with your blood vessels in one area of the body is associated with blood vessel problems in another area,” says Joshi.
Cramping, aching or numbness in the calves when you walk. This kind of leg pain, which is felt when you exercise and stops when you stop, can be a sign of peripheral vascular disease (PVD), a circulation disorder. People with PVD often have atherosclerosis, the buildup of damaging plaque in the arteries.
Arteries (are-te-rease): The blood vessels that carry oxygen-rich blood away from your heart for delivery to every part of your body. Arteries look thin tubes or hoses. The walls are made of a tough outer layer, a middle layer of muscle and a smooth inner wall that helps blood flow easily. The muscle layer expands and contracts to help blood move.
Blood vessels (veh-suls): The system of flexible tubes—arteries, capillaries and veins—that carries blood through the body.
Oxygen and nutrients are delivered by arteries to tiny, thin-walled capillaries that feed them to cells and pick up waste material, including carbon dioxide.
Capillaries pass the waste to veins, which take the blood back to the heart and lungs, where carbon dioxide is let out through your breath as you exhale.
Risk factor: Anything that boosts your chances of getting a disease. For example, smoking is a risk factor for cancer, and obesity is a risk factor for diabetes.
Sleep apnea (ap-ne-ah): A disorder in which your breathing repeatedly stops or becomes very shallow as you sleep. Your breathing may pause anywhere from a few seconds to a few minutes. This ongoing condition disrupts your sleep, making you tired during the day and increasing your risk for heart problems, diabetes, obesity and driving or work-related accidents.
Johns Hopkins Study Suggests Intermittent Fasting for a Longer, Healthier Life
For many people, the New Year is a time to adopt new habits as a renewed commitment to personal health. Newly enthusiastic fitness buffs pack into gyms and grocery stores are filled with shoppers eager to try out new diets.
But, does scientific evidence support the claims made for these diets? In a review article published in the December 26, 2019, issue of The New England Journal of Medicine, Johns Hopkins Medicine neuroscientist Mark Mattson, Ph.D., concludes that intermittent fasting does.
The Benefits of Intermittent Fasting. Credit: Johns Hopkins Medicine
Mattson, who has studied the health impact of intermittent fasting for 25 years, and adopted it himself about 20 years ago, writes that “intermittent fasting could be part of a healthy lifestyle.
” A professor of neuroscience at the Johns Hopkins University School of Medicine, Mattson says his new article is intended to help clarify the science and clinical applications of intermittent fasting in ways that may help physicians guide patients who want to try it.
Intermittent fasting diets, he says, fall generally into two categories: daily time-restricted feeding, which narrows eating times to 6-8 hours per day, and so-called 5:2 intermittent fasting, in which people limit themselves to one moderate-sized meal two days each week.
An array of animal and some human studies have shown that alternating between times of fasting and eating supports cellular health, probably by triggering an age-old adaptation to periods of food scarcity called metabolic switching. Such a switch occurs when cells use up their stores of rapidly accessible, sugar-based fuel, and begin converting fat into energy in a slower metabolic process.
Mattson says studies have shown that this switch improves blood sugar regulation, increases resistance to stress and suppresses inflammation. Because most Americans eat three meals plus snacks each day, they do not experience the switch, or the suggested benefits.
In the article, Mattson notes that four studies in both animals and people found intermittent fasting also decreased blood pressure, blood lipid levels and resting heart rates.
Evidence is also mounting that intermittent fasting can modify risk factors associated with obesity and diabetes, says Mattson.
Two studies at the University Hospital of South Manchester NHS Foundation Trust of 100 overweight women showed that those on the 5:2 intermittent fasting diet lost the same amount of weight as women who restricted calories, but did better on measures of insulin sensitivity and reduced belly fat than those in the calorie-reduction group.
More recently, Mattson says, preliminary studies suggest that intermittent fasting could benefit brain health too.
A multicenter clinical trial at the University of Toronto in April found that 220 healthy, nonobese adults who maintained a calorie restricted diet for two years showed signs of improved memory in a battery of cognitive tests.
While far more research needs to be done to prove any effects of intermittent fasting on learning and memory, Mattson says if that proof is found, the fasting — or a pharmaceutical equivalent that mimics it — may offer interventions that can stave off neurodegeneration and dementia.
“We are at a transition point where we could soon consider adding information about intermittent fasting to medical school curricula alongside standard advice about healthy diets and exercise,” he says.
Mattson acknowledges that researchers do “not fully understand the specific mechanisms of metabolic switching and that “some people are unable or unwilling to adhere” to the fasting regimens. But he argues that with guidance and some patience, most people can incorporate them into their lives.
It takes some time for the body to adjust to intermittent fasting, and to get beyond initial hunger pangs and irritability that accompany it.
“Patients should be advised that feeling hungry and irritable is common initially and usually passes after two weeks to a month as the body and brain become accustomed to the new habit,” Mattson says.
To manage this hurdle, Mattson suggests that physicians advise patients to gradually increase the duration and frequency of the fasting periods over the course of several months, instead of “going cold turkey.” As with all lifestyle changes, says Mattson, it’s important for physicians to know the science so they can communicate potential benefits, harms and challenges, and offer support.
Rafael de Cabo, Ph.D., of the Translational Gerontology Branch of the National Institute on Aging Intramural Research Program, is a co-author of the published review.
This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health.