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Disease and treatment

Heartwarming micromolecules save lives

Acute heart attacks are the most frequent cause of death and subsequent illness. Danish researchers have developed a method using a simple blood pressure cuff in the ambulance on the way to the hospital that can prevent permanent damage to the heart muscle. While testing the method for clinical use, the researchers are searching for the life-saving signal molecules that create the effect, so they can save even more lives by treating people with them.

One in seven people die from heart disease, and heart attacks are by far the most frequent cardiovascular killer. If people experiencing an acute heart attack can get to the hospital in time, doctors today can save the lives of most of them by using a stent to open a narrowed or blocked artery (angioplasty). Researchers and doctors from Skejby Hospital in Aarhus have discovered how to keep the heart muscle from being permanently damaged by using a simple blood pressure cuff until the patient reaches the hospital.

“Although we do not yet understand how it works in detail, it does work. We are therefore carrying out a major international project with 5200 patients, in which half receive treatment in the ambulance on the way to a hospital. We are also examining what signals are transmitted within the body to enable the heart muscle to keep functioning and even spare the patient from serious permanent damage,” explains Hans Erik Bøtker, Professor, Department of Clinical Medicine, Aarhus University.

Oxygen-starved pigs

The technique that Hans Erik Bøtker’s research group is testing is called remote ischaemic conditioning. The idea builds on an old theory that depriving part of the body of oxygen induces the body to transmit numerous signals that benefit organs in other parts of the body, such as the heart. Initially, the researchers from Aarhus University Hospital experimented on a pig by putting a tourniquet around its back legs.

“An angioplasty, similar to the one performed on humans who have a blocked artery, was then carried out on the pig’s heart. If the tourniquet had been applied to the pig’s legs before the operation, it fared much better after the operation.”

The researchers therefore developed a similar technique for people. Instead of a tourniquet around the legs, they simply put a blood pressure cuff around the arm and alternately tightened and loosened it in the ambulance on the way to the hospital: 5 minutes at a pressure of 200 mmHg to cut off the blood supply to the arm followed by 5 minutes with no pressure. Repeating this five times was enough to create a long-lasting effect.

“The experiment worked. The people treated had noticeably less damage to the heart muscle after the heart attack. The patients were followed up for up to 4 years and they had fewer side-effects and a lower mortality rate following the heart attack.”

What is happening?

However, before the method can become a fixed routine for ambulance paramedics, the procedure needs to be repeated on many patients to ensure that there are no side-effects and that it is clinically effective enough for an ambulance paramedic to use valuable time on it. Currently, trials are underway in international collaboration with researchers in the United Kingdom, Serbia and Spain.

“In Denmark, 2600 patients will be participating. We hope that the ischaemic conditioning will provide such good benefits that we can demonstrate longer survival after heart attacks, less damage to the heart muscle and preservation of the heart’s pumping function.”

While the researchers wait for the results, they have initiated a study of methods that may be even more effective. They are examining what exactly happens inside the body when pressure is applied through a blood pressure cuff. Although this leads to a complex cascade of signals, the researchers nevertheless believe that they are on the trail of some of the life-saving signals.

“Copies of tiny DNA molecules called microRNA that are transmitted from the clamped location to the organ that is damaged appear to facilitate at least some of the protective processes. We thus suspect that humans can be successfully treated directly with the microRNA molecules and thereby reduce the damage following a stroke or a heart attack.”

The Aarhus researchers are developing a new imaging method to enable them to track the microscopic effects of both mechanical treatment with a blood pressure cuff and potential pharmaceutical treatment with microRNAs. Using magnetic resonance–based imaging, they can potentially monitor whether the heart muscle cells survive.

“We already know that more than one signalling compound is involved in saving these people’s hearts. There is a cascade of signals, so we need to understand the processes in detail to understand and copy the processes pharmaceutically so we can save the lives of even more people who have had a heart attack.”

Hyperpolarized [1,4-13C2]fumarate enables magnetic resonance–based imaging of myocardial necrosis” has been published in JACC: Cardiovascular Imaging and “Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial” has been published in The Lancet. Hans Erik Bøtker received the Foundation’s 2018 Marie and August Krogh Prize and was awarded a Novo Nordisk Foundation Interdisciplinary Synergy Programme grant in 2016.

Hans Erik Bøtker
Clinical Professor and chair
Remote ischemic conditioning (RIC) is an experimental medical procedure that aims to reduce the severity of ischaemic injury to an organ such as the heart or the brain, most commonly in the situation of a heart attack or a stroke, or during procedures such as heart surgery when the heart may temporary suffer ischaemia during the operation by triggering the body's natural protection against tissue injury. Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. A larger trial to establish the effect of remote conditioning on clinical outcomes is currently in progress.