How to Restore Vital Cellular Functions to Pigs one Hour After Death

Within minutes of the final heartbeat, a cascade of biochemical events triggered by a lack of blood flow, oxygen, and nutrients begins to destroy a body’s cells and organs. But a team of Yale scientists has found that massive and permanent cellular failure doesn’t have to happen so quickly.

Using a new technology the team developed that delivers a specially designed cell-protective fluid to organs and tissues, the researchers restored blood circulation and other cellular functions in pigs a full hour after their deaths, they report in the Aug. 3 edition of the journal Nature. The findings may help extend the health of human organs during surgery and expand availability of donor organs, the authors said.

All cells do not die immediately, there is a more protracted series of events,” said David Andrijevic, associate research scientist in neuroscience at Yale School of Medicine and co-lead author of the study. “It is a process in which you can intervene, stop, and restore some cellular function.”The research builds upon an earlier Yale-led project that restored circulation and certain cellular functions in the brain of a dead pig with technology dubbed BrainEx. Published in 2019, that study and the new one were led by the lab of Yale’s Nenad Sestan, Professor of Neuroscience.

If we were able to restore certain cellular functions in the dead brain, an organ known to be most susceptible to ischemia [inadequate blood supply], we hypothesized that something similar could also be achieved in other vital transplantable organs,” Sestan said.

In the new study — which involved senior author Sestan and colleagues Andrijevic, Zvonimir Vrselja, Taras Lysyy, and Shupei Zhang, all from Yale — the researchers applied a modified version of BrainEx called OrganEx to the whole pig. The technology consists of a perfusion device similar to heart-lung machines — which do the work of the heart and lungs during surgery — and an experimental fluid containing compounds that can promote cellular health and suppress inflammation throughout the pig’s body. Cardiac arrest was induced in anesthetized pigs, which were treated with OrganEx an hour after death.

Six hours after treatment with OrganEx, the scientists found that certain key cellular functions were active in many areas of the pigs’ bodies — including in the heart, liver, and kidneys — and that some organ function had been restored. For instance, they found evidence of electrical activity in the heart, which retained the ability to contract.

We were also able to restore circulation throughout the body, which amazed us,” Sestan said.

Normally when the heart stops beating, organs begin to swell, collapsing blood vessels and blocking circulation, he said. Yet circulation was restored and organs in the deceased pigs that received OrganEx treatment appeared functional at the level of cells and tissueUnder the microscope, it was difficult to tell the difference between a healthy organ and one which had been treated with OrganEx technology after death,” Vrselja said.

Source: https://news.yale.edu/

Lasers and Ultrasound Combine to Pulverize Arterial Plaque

Lasers are one of the tools physicians can lean on to tackle plaque buildup on arterial walls, but current approaches carry a risk of complications and can be limited in their effectiveness. By bringing ultrasound into the mix, scientists at the University of Kansas have demonstrated a new take on this treatment that relies on exploding microbubbles to destroy plaque with greater safety and efficiency, while hinting at some unique long-term advantages.

Scientists have demonstrated a new technique to take out arterial plaque, using low-power lasers and ultrasound to break it apart with tiny bubbles

The novel ultrasound-assisted laser technique builds off what’s known as laser angioplasty, an existing treatment designed to improve blood flow in patients suffering from plaque buildup that narrows the arteries. Where more conventional treatments such as stents and balloon angioplasty expand the artery and compress the plaque, laser angioplasty destroys it to eliminate the blockage.

The laser is inserted into the artery with a catheter, and the thermal energy it generates turns water in the artery into a vapor bubble that expands, collapses and breaks up the plaque. Because this technique calls for high-power lasers, it has the potential to perforate or dissect the artery, something the scientists are looking to avoid by using low-power lasers instead.

They were able to do so in pork belly samples and ex vivo samples of artery plaque with the help of ultrasound. The method uses a low-power nanosecond pulsed laser to generate microbubbles, and applying ultrasound to the artery then causes these microbubbles to expand, collapse and disrupt the plaque.

In conventional laser angioplasty, a high laser power is required for the entire cavitation process, whereas in our technology, a lower laser power is only required for initiating the cavitation process,” said team member Rohit Singh. “Overall, the combination of ultrasound and laser reduces the need for laser power and improves the efficiency of atherosclerotic plaque removal.

The mix of lasers and ultrasound has shown potential in other areas of medicine, with Singh and his colleagues pursuing similar therapies to tackle abnormal microvessels in the eye that cause blindness and blood clots in the veins. We’ve also seen ultrasound used to explode tiny bubbles in cancer research, providing a way of wiping out cancerous cells within a tumor.

Source: https://newatlas.com/

mRNA Breakthrough Offers a Potential Heart Attack Cure

King’s College London researchers are turning to the same technology behind the mRNA COVID-19 vaccines to develop the first damage-reversing heart attack cure. They used mRNA to deliver the genetic instructions for specific proteins to damaged pig hearts, sparking the growth of new cardiac muscle cells. “The new cells would replace the dead ones and instead of forming a scar, the patient has new muscle tissue,” lead researcher Mauro Giacca said. Researchers are turning to the same technology behind Pfizer and Moderna’s vaccines to develop the first damage-reversing heart attack cure.

Diseases of the heart are the leading cause of death around the world; the WHO estimates that 17.9 million people died from cardiovascular disease in 2019, representing almost a third of all deaths. Of those, 85% are ultimately killed by heart attacks and strokes. Heart attacks occur when blood flow to parts of the heart is blocked, often due to fat or cholesterol build up. The cardiac muscle cells — marvelous little powerhouses that keep you beating throughout your entire life — are starved of oxygen and can be damaged or killed. Left in its wake is not the smoothly pumping cardiac muscle, but instead scar tissue.

We are all born with a set number of muscle cells in our heart and they are exactly the same ones we will die with. The heart has no capacity to repair itself after a heart attack,” explained Giacca.

At least, until now. To develop their heart attack cure, the researchers turned to mRNA, which delivers the instructions for protein creation to cells. Whereas the Pfizer and Moderna vaccines instruct cells to make the spike protein of SARS-CoV-2, priming the immune system against the virus, the same technology can deliver a potential heart attack cure by carrying the code for proteins that stimulate the growth of new heart cellsPharmaTimes reported. In an experiment with pigs (a close match for the human heart), the mRNA treatment stimulated new heart cells to grow after a heart attackregenerating the damaged tissues and creating new, functional muscle rather than a scar.

According to BioSpace, harnessing mRNA in this way has been dubbed “genetic tracking,” named for the way the mRNA’s progress is tracked via the new proteins it is creating. The technique is being explored to create vaccines for pathogens like HIV, Ebola, and malaria, as well as cancers and autoimmune and genetic diseases. While thus far their heart attack cure has only been successfully tested in porcine pumpers, the team hopes to begin human clinical trials within the next couple years. “Regenerating a damaged human heart has been a dream until a few years ago,” Giacca said, “but can now become a reality.”

Source: https://www.freethink.com/

AI Predicts Heart Attacks

In a study published Feb. 14 in Circulation, researchers in the U.K. and the U.S. report that an AI program can reliably predict heart attacks and strokes. Kristopher Knott, a research fellow at the British Heart Foundation, and his team conducted the largest study yet involving cardiovascular magnetic resonance imaging (CMR) and AI. CMR is a scan that measures blood flow to the heart by detecting how much of a special contrast agent heart muscle picks up; the stronger the blood flow, the less likely there will be blockages in the heart vessels. Reading the scans, however, is time consuming and laborious; and it’s also more qualitative than quantitative, says Knott, subject to the vagaries of the human eyes and brain. To try to develop a more qualitative tool, Knott and his colleagues trained an AI model to read scans and learn to detect signs of compromised blood flow.

When they tested the technology on the scans of more than 1,000 people who needed CMR because they either at risk of developing heart disease or had already been diagnosed, they found the AI model worked pretty well at selecting out which people were more likely to go on to have a heart attack or stroke, or die from one. The study compared the AI-based analyses to health outcomes from the patients, who were followed for about 20 months on average. The researchers discovered that for every 1 ml/g/min decrease in blood flow to the heart, the risk of dying from a heart event nearly doubled, and the risk of having a heart attack, stroke or other event more than doubled.

Rather than a qualitative view of blood flow to the heart muscle, we get a quantitative number,” he says. “And from that number, we’ve shown that we can predict which people are at higher risk of adverse events.”

The study confirmed that CMR is a strong marker for risk of heart problems, but did not prove that the scans could actually be used to guide doctors’ decisions about which people are at higher risk. For that, more studies need to be done that document whether treating poor blood flow—with available medication or procedures—in people with decreased flow as predicted by the AI model, can reduce or eliminate heart attacks and strokes.

Source: https://time.com/