The study shows nutrients used by normal and failing hearts

The study shows nutrients used by normal and failing hearts
The study shows nutrients used by normal and failing hearts

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A team led by scientists from the Perelman School of Medicine at the University of Pennsylvania has created a detailed picture of the fuel and nutrient consumption of the human heart. The study, published this week in sciencewas the first of its kind to draw blood from dozens of human participants simultaneously from different parts of the circulatory system in order to record the levels of related molecules going in and out of the beating heart.

The resulting data have uncovered key fuel economy features in both the normal heart and heart failure, and created a new framework for studying the heart for health and disease.

“Understanding how the heart handles fuel and nutrients at this level of detail should influence the development of future treatments for heart failure and related diseases,” said the study’s lead author, Dr. Zoltan Arany, Professor of Medicine and Medical Director of the Cardiovascular Metabolism Program at Penn Medicine. “Now that we have a clear picture of how the heart drives itself, we can start thinking about how we can improve heart metabolism in heart failure.”

There are more than 6 million adults living with heart failure in the United States, according to the Centers for Disease Control and Prevention. Heart failure often occurs as a result of coronary artery disease or a heart attack, and results in the blood not being pumped around the body sufficiently to support other organs normally. Current treatments for heart failure focus primarily on its symptoms, such as treating fluid build-up in the lungs and lower extremities, using equipment to assist pumping, and, for some, performing a heart transplant. A deeper understanding of how the heart works could enable researchers to develop more effective therapies that restore the heart’s pumping ability.

For the study, Arany and his team took simultaneous heart and heart blood samples from 87 subjects – men and women who had already undergone a procedure to treat a common condition called atrial fibrillation but did not have heart failure. The researchers performed a similar sample in 23 patients with atrial fibrillation who had heart failure. In all patients, the researchers also took blood samples in and out of the leg for comparison.

The team then used state-of-the-art tools to quantify the levels of hundreds of different “metabolites” – molecules involved in fuel consumption and cell growth – in the blood samples. The main aim was to uncover in detail which metabolites the working heart consumes in equilibrium and which it supplies as by-products.

The analysis was particularly important in order to obtain a first clear and detailed picture of the normal uptake and release of metabolites in the heart – a snapshot that future studies can expand on. In total, the researchers reliably determined 277 metabolites in the blood of human participants and found that in 65 of these, the values ​​emanating from the heart differed significantly from the incoming values.

The team also made initial comparisons to highlight the potentially unique features of normal heart metabolism. For example, the data showed that when compared to the legs, the heart was apparently much more dependent on the uptake of small organic molecules called fatty acids as a source of energy. At the same time, analysis suggests that the heart releases relatively large amounts of another class of molecules called amino acids – the building blocks and breakdown products of proteins – suggesting that relatively intense breakdown of proteins in the heart is a possibility that the working Heart muscle promotes its activity.

One big difference between healthy hearts and heart failure in the study was that the latter consumed more ketones – molecules the body uses as intermediates in converting stored fats into energy – although researchers suggest that this inequality was only due to the slower ones is the passage of blood through the heart, which leaves more time for ketone absorption. Compared to normal hearts, the failing hearts also release more amino acids, which indicates greater protein breakdown and turnover.

“Whether this increased protein breakdown in heart failure is adaptive or maladaptive requires further studies,” said Arany. “The next steps require rigorous testing of these and other similar questions in model organisms. After that, we can return to human studies with a much deeper understanding and new insights into improving cardiac function in heart failure. ”

Ketones buy time for heart failure, but are only more fuel for a healthy one, study says

Provided by the Perelman School of Medicine at the University of Pennsylvania

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