Nav: Home

CNIC scientists discover how a decades-old drug reduces the size of a heart attack

April 18, 2017

Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have discovered a new mechanism of action of metoprolol, a drug that can reduce the damage produced during a heart attack if administered early. The team led by Dr. Borja Ibáñez, Clinical Research Director at the CNIC and cardiologist at the Fundación Jiménez Díaz University Hospital Health Research Institute (IIS-FJD), has identified the mechanism that explains why this drug is so beneficial: rapid administration of metoprolol during a heart attack directly inhibits the inflammatory action of neutrophils, a type of blood cell. The reduced inflammation translates into a smaller area of damaged tissue in the post-infarcted heart. The finding, published in Nature Communications, opens the way to new applications for this cheap, safe, and simple drug.

Acute myocardial infarction is a serious disease that affects more than 50 000 people a year in Spain. Treatment has advanced a great deal in recent years, especially in the extensive use of coronary angioplasty, in which a catheter is used to re-establish blood flow through the blocked coronary artery. Nevertheless, many heart attack survivors have seriously impaired heart function that limits their long-term health and generates major costs to the health system. The search for treatments to limit the irreversible damage caused by a heart attack is an extremely important research area in terms of both patient care and health policy.

Neutrophils


Neutrophils are white blood cells that target and fight infections. In noninfectious diseases, neutrophils mount an excessive response, and after a myocardial infarction these cells attack the heart, contributing to the long-term injury and impaired function. "In an infarction," explained Dr. Ibañez "the most important thing is to re-establish blood flow as soon as possible. But unfortunately the incoming blood sets off an inflammatory process, started by neutrophils, that causes additional, permanent damage to the heart." This additional damage due to blood flow restoration is known as reperfusion injury, and has been regarded as a necessary evil because it is essential to unblock the coronary artery as rapidly as possible.

Metoprolol is a beta-blocker that has been in clinical use for more than 30 years and is a cheap drug (costing less than €2 per dose) of little commercial interest. In 2013, the METOCARD-CNIC clinical trial, led and coordinated by the same CNIC research team, showed that administration of metoprolol very early after an infarction reduces the size of the cardiac injury and improves long-term health. It has taken the team 7 years to determine why this simple and cheap pharmacological strategy is so effective.

The study published today in Nature Communications shows that early administration of metoprolol protects the heart by acting directly on neutrophils. "Metoprolol stuns the blood neutrophils, altering their behavior and limiting their injurious inflammatory action on cardiac muscle," explained first author Jaime García-Prieto. When coronary blood flow is re-established, neutrophils launch a complex and organized inflammatory reaction, with negative consequences. According to García-Prieto, "when neutrophils enter the infarcted heart tissue after the restoration of blood flow, they act disproportionately, inducing the death of cells that, while weakened, have survived the infarction." As Andrés Hidalgo, CNIC scientist and expert on neutrophils, explained, "neutrophil tissue invasion is intimately related to their interactions with platelets. Metoprolol blocks these interactions, drastically limiting the number of neutrophils arriving in the infarcted tissue." Moreover, impeding neutrophil invasion also prevents the formation of blood-cell aggregates that block the microcirculation in the post-infarction heart.

Dr. Antonio Fernández-Ortiz, study co-author and a cardiologist at the Hospital Clínico San Carlos, clarified that "we knew that platelets were an important factor in the clotting that causes an infarct, but until now we could not be certain that they also act together with neutrophils to magnify injury after blood flow restoration." Dr. Ibañez concluded that "the priority after a heart attack remains the restoration of blood flow as soon as possible, but we need to prepare the heart for this by administering metoprolol."

Also an author on the study is Dr. Valentín Fuster, CNIC General Director and Physician in Chief at the Mount Sinai Hospital in New York. Commenting on the study, he emphasized that "the imaging technology at the CNIC has allowed us to rapidly determine the status of a patient's heart after a heart attack, and this has enabled us to discover a new mechanism of action of this drug that we have been using for decades."
-end-
The study, coordinated by the CNIC, is an example of multidisciplinary networked collaboration involving not only the CNIC and the IIS-FJD but also the San Carlos Clinical Hospital, the Quirón Madrid University Hospital, Asturias Central Hospital, the Ruber Juan Bravo Hospital Complex, Basurto Hospital, and Mount Sinai Hospital in New York. Most of these centers are members of the recently created CIBER research network on cardiovascular diseases (CIBERCV) within the group led by Dr. Ibáñez. The study is the fruit of collaboration among cardiologists, ambulance emergency service staff, veterinarians, biochemists, physicists, and engineers, all of them participants in the CIBERCV consortium.

Centro Nacional de Investigaciones Cardiovasculares

Related Heart Attack Articles:

Where you live could determine risk of heart attack, stroke or dying of heart disease
People living in parts of Ontario with better access to preventive health care had lower rates of cardiac events compared to residents of regions with less access, found a new study published in CMAJ (Canadian Medical Association Journal).
Activated T-cells drive post-heart attack heart failure
Chronic inflammation after a heart attack can promote heart failure and death.
ICU care for COPD, heart failure and heart attack may not be better
Does a stay in the intensive care unit give patients a better chance of surviving a chronic obstructive pulmonary disease (COPD) or heart failure flare-up or even a heart attack, compared with care in another type of hospital unit?
Heart attack treatment might be in your face
Researchers at the University of Cincinnati have received $2.4 million in federal funding to pursue research on a novel cell therapy that would repair heart damage using modified cells taken from the patient's own facial muscle.
Tissue engineering advance reduces heart failure in model of heart attack
Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer.
Study shows functional effects of human stem cell delivery to heart muscle after heart attack
Researchers delivered human stem cells seeded in biological sutures to the damaged heart muscles of rats following induced acute myocardial infarction and assessed the effects on cardiac function one week later.
Younger heart attack survivors may face premature heart disease death
For patients age 50 and younger, the risk of premature death after a heart attack has dropped significantly, but their risk is still almost twice as high when compared to the general population, largely due to heart disease and other smoking-related diseases The risk of heart attack can be greatly reduced by quitting smoking, exercising and following a healthy diet.
After the heart attack: Injectable gels could prevent future heart failure (video)
During a heart attack, clots or narrowed arteries block blood flow, harming or killing cells in the heart.
Heart failure after first heart attack may increase cancer risk
People who develop heart failure after their first heart attack have a greater risk of developing cancer when compared to first-time heart attack survivors without heart failure, according to a study today in the Journal of the American College of Cardiology.
1 in 4 patients develop heart failure within 4 years of first heart attack
One in four patients develop heart failure within four years of a first heart attack, according to a study in nearly 25,000 patients presented today at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure by Dr.

Related Heart Attack Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...