UR logoEmotions such as fear and anger are all experienced by a strong heartbeat. Experts share that body’s natural response to these emotions seemingly helps fight heart failure. A new study from University of Rochester Medical Center revealed that two experimental drugs have the ability to revive failing heart’s pumping strength by controlling the fight-or-flight response that permits the heart to beat stronger.

The main highlight is the hormone adrenalin that usually stabilizes the heart’s pumping strength, enabling it to beat with force during a problem. The new drug ensures that adrenalin’s capability to stimulate the heart beat is maintained and not let down among heart patients. Heart failure was found to slow down and stop the development of the disease in some cases.

Burns C. Blaxall, Ph.D., associate professor within the Aab Cardiovascular Research Institute at the Medical Center, and senior author of the study shares, “Considering the limited efficacy of current drug therapies for heart failure, this discovery is both exciting and promising. We are now taking a closer look at how these compounds compare to standard heart failure therapies, such as beta blockers, to further determine their efficacy in treating the disease.”

The body responds when the heart stops pumping effectively by transmitting adrenalin. The heart’s energy is revived when adrenalin is increased however as time passes heart muscle cells reduce in number and respond limitedly to high levels of adrenalin. This stimulates the body to pump more of the hormone towards the heart but increased adrenalin leads to heart failure. Anxiety increases the hormone and a recent study has associated anxiety with heart disease or heart attacks later in life among teens and young adults.

Experts reveal have connected adrenalin’s capability to drive heartbeat strength towards a key protein, the beta adrenergic receptor. Heart muscle cells contract with increased speed and force when adrenalin combines with this receptor. Among heart patients these receptors do not respond to adrenalin that causes the heart to grow weak and pump inefficiently.

Blaxall quotes, “While adrenalin desensitization has been studied extensively, this is the first report of compounds that effectively target this specific process to reduce heart failure”.

Experts identified compounds that restrict GRK2 formation by G proteins. They conducted wide spread screening and testing to evaluate these experimental compounds. They highlighted two compounds namely M119 and Gallein and further put them to test.

Alan Smrcka, Ph.D., professor in the Department of Pharmacology & Physiology at the Medical Center reveals, “In this study we took an entirely new pharmacological approach by altering signaling pathways after the beta adrenergic receptor rather than altering the receptor itself. In this way the actions of adrenalin are modified rather than blocked as with other therapies, such as beta blockers. This novel approach is applicable in heart failure and may be useful in other conditions as well.”

Galleon was observed to not only slow down but stop development of heart failure when tested among mice with pre-existing heart failure. M119 lowered two features of the disease namely strain related thickening of muscle tissue and scar tissue formation. The force of heart muscle contraction was normalized by both the compounds by making sure the beta adrenergic receptors continued to respond to adrenalin. This was done by lowering GRK2 in the heart and by reducing it effectiveness.

M119 and Gallein were used similarly to mark the receptors in other conditions such as chronic pain. Experts have revealed that M119 can overturn the desensitization of opiate receptors that gradually improve the effects of painkillers namely morphine. Previously M119 and Gallein were not known to have therapeutic effects and were known as compounds that act as dyes, or stains.

This analysis may be a boon to many as heart problem affects nearly 6 million Americans. Problems like coronary artery disease, high blood pressure or heart attack damage reduces the ability of the heart to pump effectively and lowers the ability to meet blood requirements. Experts reveal half of patients will not live for more than 5 years from the day they are diagnosed. Such analyses are required as transplant is the only option for heart patients. Just over 2000 transplants are conducted every year and more than 3000 people are on waiting list at any given time.

The findings were published online in the journal Circulation Research.
http://www.urmc.rochester.edu/news/story/index.cfm?id=2909