Researchers at Sweden’s Karolinska Institutet and Karolinska University Hospital found in a clinical study that the hunger hormone ghrelin can increase the pumping capacity of the heart in heart failure patients. The findings were published in the European Heart Journal.
Millions of people worldwide live with heart failure, a condition in which the heart’s pumping function is reduced, such as after a myocardial infarction or angina. In heart failure, the heart muscle weakens, making the heart unable to pump the amount of blood needed to supply the body with enough oxygen and nutrients. Treatments are available that slow the progression of the disease, but there are none that directly improve the heart’s pumping action.
Ghrelin is an endogenous hormone that has many receptors distributed in cardiac muscle tissues. It increases appetite and stimulates the release of growth hormones. Researchers believe that its receptors are a promising target for increasing the heart’s pumping function.
“Heart failure is the most common cause of hospitalization in older generations and is associated with poor quality of life and high mortality,” says lead researcher Lars Lund, professor at the Department of Medicine, Solna, Karolinska Institutet and senior advisor at Karolinska. University Hospital. “If we can find ways to increase the heart’s pump function, we can potentially improve the quality of life and prognosis for these patients.”
In this double-blind study, 30 heart failure patients at the Cardiology Unit of Karolinska University Hospital were randomly assigned to two groups, receiving active treatment with either ghrelin or an intravenous placebo for two hours. Participants were followed up two to five days later.
After two hours of treatment, cardiac output (ie, the amount of blood pumped by the heart in one minute) increased by an average of 28 percent in the ghrelin group, compared with a small decrease in the placebo group. As the heart rate remains unchanged or slows slightly due to the increase, more blood is pumped by the heart per beat. At the two- to five-day follow-up, pump capacity was 10 percent higher in the ghrelin group than in the placebo group.
The researchers observed no serious adverse reactions. For unknown reasons, the ghrelin group had slightly increased levels of heart failure biomarkers, but further studies will be needed to detect any real connection. Because the patient group in the current study was small and the follow-up was short, it is difficult to estimate the effectiveness of the treatment in a larger group over the long term.
To study the underlying mechanisms responsible for the increase in pump function, the researchers also studied mouse heart cells in the laboratory. They found that treatment with ghrelin increased the contractile function of heart cells, and they identified a novel molecular mechanism for this increase.
Researchers now want to conduct larger clinical studies and with the help of the KI Incubator, KI Innovations has launched AnaCardio, a start-up company that develops molecules designed to activate ghrelin receptors and thereby increase the heart’s pumping action.
Some researchers have reported potential conflicts of interest, including consulting and lecture fees from various pharmaceutical companies. Lars Lund is the founder of Anacardio, which is developing a ghrelin-based therapy for heart failure.
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