Zapping the vagus nerve promotes blood clotting, new research suggests.
These findings are the first evidence in humans of a "neural tourniquet," or a brain-based pathway that could reduce bleeding, said study co-author Dr. Jared Huston, a trauma surgeon at the Firestein Institutes for Medical Research at Northwell Health in New York.
If a future clinical trial directly shows that the nerve stimulation decreases blood loss, the technique could be used before planned surgeries to protect patients from excessive bleeding, Huston told Live Science.
Around 1.5% of surgeries are complicated by haemorrhaging, or excessive blood loss, and some degree of bleeding is associated with all surgeries. Surgeons currently rely on sutures, bandages and tourniquets — devices that stop blood from flowing to part of the body — to staunch bleeding.
But Huston wondered whether making blood less likely to escape in the first place would make surgery safer. "Preventing a problem is always better than dealing with it after the fact," he said.
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Huston and his collaborators first wondered if the vagus nerve might promote blood clotting nearly 20 years ago, after the nerve was found to modulate inflammation. The vagus nerve, which originates in the brain and branches out to other organs, controls the parasympathetic nervous system — the rest-and-digest counterpart to the "fight-or-flight" sympathetic nervous system.
Initial experiments in mice and pigs showed that stimulating the vagus could, indeed, reduce blood loss following a small cut. "We then spent the better part of a decade trying to figure out exactly how it works," Huston said.
Last year, Huston's team showed that vagus nerve stimulation activates a type of immune cell, called T cells, in the spleen, the organ that helps filter germs and old cells out of blood. These T cells then activate platelets in the spleen; platelets are the cell fragments that set off blood clot formation.
Upon re-entering circulation, the primed platelets are better able to respond to injury-related cues. In mice with hemophilia, a disorder in which blood can't clot properly, nerve stimulation reduced bleeding, the team found.
To test whether the same mechanism existed in humans, Huston's team collaborated with the Dallas-based biomedical company Five Liters to recruit healthy volunteers. They used an approved device to zap the auricular branch of vagus nerve, which runs behind the ear, for 30 minutes in each person. They collected blood samples before and after the treatment.
Following vagus nerve stimulation, the volunteers' blood contained higher levels of markers of blood platelet activation.
These results, presented in October at the Society for Neuroscience conference in Chicago, showed for the first time "that there is a neural tourniquet pathway in humans," Huston said. "And it appears that we can activate this neural tourniquet pathway non-invasively." More details of the trial can be found at ClinicalTrials.gov.
While the past study results in animals are "very intriguing," more work needs to be done to show vagus nerve stimulation can actually stop bleeding in humans, Peder Olofsson, a professor of bioelectronic medicine at the Karolinska Institute in Stockholm, Sweden, told Live Science.
"Ultimately, measurements of bleeding times, bleeding volumes, and patient outcomes will be key" to demonstrating the clinical value of activating the vagus nerve through the skin, said Olofsson, who was not involved in the study.
Huston agreed. "The next study will have to be in an actual clinical disease where the patients are bleeding one way or another," he said.
Another issue is showing that the stimulators can produce consistent results, Olofsson noted. "Non-invasive stimulators" — while much quicker and easier to use than implanted stimulators — "often show less consistent physiological effects."
Vagus nerve stimulation is already widely used in epilepsy and depression, so the risk of side effects is likely low, Huston added. If his findings can be replicated and extended in larger trials, surgeons might use a brief period of vagus nerve stimulation prior to planned surgeries.
"We administer antibiotics, so you don't get an infection during surgery. We administer pain medications pre-emptively, so the pain is less," Huston said. "What is missing is any way to take a normal, healthy person who's undergoing surgery to try and prevent bleeding ahead of time. That's an enormous unmet need."
Editor's note: This story was updated at 3 p.m. on Dec. 3, 2024 to note that the results were presented at the Society for Neuroscience conference.
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