Rat experiments give new hope for heart failure patients
A majority of patients who’ve suffered heart failure die. Danish researchers have carried out experiments on rats that may help save more patients.
Every year 3,500 Danes suffer heart failure outside of a hospital and only one in ten of them are alive a month later.
But new Danish research now suggests that help could be on the way to these patients.
“We’ve developed a brand new treatment and have got some fantastic results in our experiments on rats,” says professor Lars Edvinsson of the Department of Clinical Experimental Research at the Glostrup Hospital Research Park. “I’m optimistic we can make this treatment work on people.”
Edvinsson is one of the researchers behind the new study that was recently been published in the scientific journal PLOS ONE.
Dramatic improvement of survival rates
Cardiac arrest, or heart failure, means that the heart stops pumping blood around the body. This causes damage to the vital organs as their oxygen supply is stopped.
Most people will be inflicted with permanent damages or die if they do not get help within roughly ten minutes.
After four to six minutes the brain starts to die, and with each minute that passes without basic first aid the chance of survival is reduced by 7-10 percent.
Even if resuscitation is successful and the blood supply to the brain is re-established, further damage to the brain may still develop in the time following the heart failure, because the blood vessels in the brain have contracted.
This is the damage the Danish researchers hope their new treatment can prevent.
Even with modern equipment a majority of patients who suffers cardiac arrest die before they reach the hospital.
According to Edvinsson, even patients who receive immediate first aid and survive the trip to the hospital often die within the following weeks due to brain damage from the heart failure.
However, Lars Edvinsson’s experiments on rats indicate that treatment with a drug called ‘MEK 1/2 inhibitor’ can slow the development of further brain damage and thereby increasing the chance of survival.
“We saw a dramatic improvement of the survival rate in rats that’d been treated with MEK 1/2 inhibitor,” he says.
No other options
Associate professor Anders Hay-Schmidt of the Department of Neuroscience and Pharmacology at the University of Copenhagen calls the new study very interesting and thorough.
“There really aren’t that many options when it comes to helping this specific group of heart failure -- apart from getting their heart started as quickly as possible, of course,” says Hay-Schmidt. “But this experiment points to a new way of treating heart failure survivors.”
Effect on people yet to be proven
Schmidt points out that even though the experiments carried out on rats look promising it’s too early for celebrations.
“This type of study has to be repeated on a greater number of animals and then we’ll have to see if it can be applied to people. It’s fairly likely that the treatment will also work on people, but there are no guarantees,” he says.
There’s still a long way to go before the new method does -- or doesn’t -- become a new treatment for people, says Hay-Schmidt.
He did not take part in the study but works with brain research and animal experiments himself.
Why does heart failure cause brain damage?
But why does heart failure cause damage to the brain?
The immediate answer is that the brain needs oxygen which is delivered through the blood.
If a person experiences cardiac arrest the heart stops pumping blood to the brain, and after as little as a few minutes the lack of oxygen starts to damage the brain.
But even if the heart is started again quickly, thereby re-establishing the supply of blood and oxygen to the brain, new and life threatening damage to the brain will still continue to develop in the weeks following the heart failure.
The brain’s own destruction programme
In the course of the past ten years of his research, Edvinsson has worked to solve the mystery of why these damages to the brain progress even after the heart has started beating again.
“Our rat model shows that when the heart stops it sets off a destruction programme in the brain,” he says.
This means that the blood vessels in the brain start to contract which then leads to some parts of the brain not getting a sufficient supply of oxygen.
“So in the days following cardiac arrest, brain damage will develop,” says Edvinsson.
He has attempted to map the molecular mechanisms behind the ‘destruction programme’ in the brain and the rat experiments suggest that the programme consists of myriad signals and receptors that in unison cause the blood vessels to contract, thereby causing damage to the brain cells.
The idea behind Edvinsson’s new treatment is to stop the destruction programme in the beginning of the process: before the chain of signals starts is set off and causes blood vessels to contract.
“MEK 1/2 inhibitor stops the destruction programme early in the chain of events and shuts s down the destruction programme, preventing the negative effects on the brain,” says Edvinsson.
Rats received treatment after heart failure
In the new study, Edvinsson has tested the treatment by inducing ‘heart failures’ in the rats and subsequently resuscitating them, ensuring that the blood supply to the brain was re-established.
Following resuscitation six of the rats were treated with MEK 1/2 inhibitor while eleven of the rats where not treated.
“A week after the heart failure half of the rats that had not been treated with MEK 1/2 inhibitor had died and none of the rats that’d been treated had died. So it was very convincing,” says Edvinsson.
The researchers assessed the rats’ behaviour to see whether or not they behaved like healthy rats. They found that the rats treated with MEK 1/2 inhibitor performed much better than the non-treated rats.
Edvinsson hopes he and his colleagues can raise sufficient funding for further testing of the drug MEK 1/2 inhibitor which would enable them to get permission to test the treatment on people.
“But before we can go any further and test the treatment on people, we will have to test MEK 1/2 inhibitor further, for instance to test for side effects,” he says.
A drug similar to MEK 1/2 inhibitor has already been tested on people in connection with trials of a new cancer treatment.
Translated by: Iben Gøtzsche Thiele
- 'Early MEK1/2 inhibition after global cerebral ischemia in rats reduces brain damage and improves outcome by preventing delayed vasoconstrictor receptor upregulation.' PLOS ONE, 2014, DOI: 10.1371/journal.pone.0092417.