Monday August 20, 2018

Common Chemotherapy Drug may Lead to Heart Failure: Study

The drug also caused a wasting syndrome in the heart and the spleen

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Novel Microsoft-Apollo AI model to predict heart disease risk for Indians. Pixabay
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A chemotherapy drug, widely used for treatment of ovarian, bladder, lung, thyroid and stomach cancers, has the potential to cause heart toxicity that can lead to congestive heart failure, a study led by a professor of Indian origin, has found.

In the study, conducted on mice, doxorubicin induced fibrosis in the heart, increased the programmed cell death called apoptosis and impaired the pumping of the heart.

The drug also caused a wasting syndrome in the heart and the spleen.

The study, led by Ganesh Halade, Assistant Professor at the University of Alabama in the US, found that disruption of the metabolism that controls immune responses in the spleen and heart is vital for heart maintenance, repair and control of inflammation.

For the study, published in the American Journal of Physiology — Heart and Circulatory Physiology, the team used a mouse model to study the effect of doxorubicin on immunometabolism — the study of how metabolism regulates immune cell function.

A dysregulated immunometabolism impairs resolution of inflammation, and chronic, non-resolving inflammation can lead to advanced heart failure.

heart disease
Representational image. (IANS)

Halade’s team found that doxorubicin is also involved in the deleterious response to the spleen.

First, doxorubicin was shown to induce irreversible dysregulation that lowered the levels of enzymes in the left ventricle of the heart, which in turn reduced the levels of bioactive lipids mediators produced by these enzymes, mediators that usually would help resolve inflammation.

In the spleen, doxorubicin also poisoned a special group of marginal zone immune cells called CD169+ macrophages, causing the spleen to diminish in size.

It also caused an imbalance of the cell-signalling molecules called chemokines and cytokines, and this imbalance suggested suppressed defence capacity of spleen-leukocyte immune cells.

Specifically, the researchers found decreased levels of tumour necrosis factor-alpha in the spleen, and decreased levels of the immune-cells reparative marker MRC-1, also known as CD206, in the heart.

Thus, doxorubicin appears to have a splenocardiac impact in this non-cancer model, Halade said. (IANS)

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Stem Cell Therapy to Treat Heart-Failure

For the study, the team induced experimental heart attacks in macaque monkeys

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heart-rate
Heart Rate. (IANS)

Stem cells may potentially be used as a “one-and-done” approach to restore function in people with heart-failure, a study has found.

Reported in the journal Nature Biotechnology, the study showed human stem cell treatment can possibly return the hearts’ functioning to better than 90 per cent of normal in macaque monkeys with heart attacks.

Heart-failure that causes nearly 10 million deaths worldwide, is a condition caused by lack of blood flow. The stem cells will help “form new muscle that will integrate into heart so it may pump vigorously again,” said Charles “Chuck” Murry, Professor at the University of Washington.

“Our findings show that human embryonic stem cell-derived cardiomyocytes can re-muscularise infarcts in macaque monkey hearts and, in doing so, reduce scar size and restore a significant amount of heart function. This should give hope to people with heart disease,” Murry said.

For the study, the team induced experimental heart attacks in macaque monkeys.

Two weeks later, the researchers took heart cells that they had grown from embryonic human embryonic stem cells and injected them into and around the young scar tissue. Each animal received roughly 750 million of these human embryonic stem cell-derived cardiomyocytes.

heart beat rate
Representational image. Pixabay

At four weeks after treatment, the ejection fraction in the treated animals rose to 49.7 per cent, about half-way back to normal, as compared to the untreated control animals, which remained unchanged at about 40 per cent.

MRI scans showed that new heart muscle had grown within what had been scar tissue in the treated hearts, while no new muscle was seen in the untreated animals.

Moreover, the human heart cells had also formed new muscle tissue in the damaged region. The new muscle tissue had replaced 10 per cent to 29 per cent of the scar tissue, integrated with the surrounding healthy tissue and developed into mature heart cells, the researchers said.

Also Read: Virtual Reality Tech Transforming Heart Treatments

Murry said that the research aims to develop a treatment that could be given to people shortly after a heart attack to prevent heart failure.

Because heart cells are long-lived there should be no need for additional treatments, he said. The transplanted stem cells would also be genetically altered to reduce the risk of immune rejection, which often complicates organ transplantation.

“What we hope to do is create a “one-and-done” treatment with frozen “off-the-shelf” cells that, like O-negative blood, can go into any recipient with only moderate immune suppression,” Murry said. (IANS)