Researchers at Massachusetts General Hospital in Boston have confirmed that hydrogen sulfide–a swamp gas that’s toxic at high concentrations–can be used to temporarily lower oxygen requirements in mice without adverse effects. The researchers say it could make some of the most difficult heart surgeries safer for patients and less stressful for surgeons.
In rare surgical cases–to fix severely damaged aortas and the worst congenital heart defects–surgeons must briefly shut off all blood and oxygen flow in the body, including to the brain. And when brain cells don’t get the oxygen they require, they die. To stave off a patient’s death, surgeons must cool his or her body (to around 15 degrees Celsius) in order to reduce brain cells’ need for oxygen and prevent damage.
But such extreme cooling has drawbacks, says Fumito Ichinose, a cardiac anesthesiologist and leader of the MGH team. It impairs blood clotting so much that patients need transfusions after surgery. And cold can only stave off brain damage for about 45 minutes–which means surgeons must rush to complete the procedure.
The MGH team believes hydrogen sulfide gas might work longer and better than cooling to reduce oxygen demand during these procedures. At a normal temperature, the researchers gave mice a low concentration (80 parts per million) of hydrogen sulfide gas. Within five minutes, the rodents’ oxygen demand was halved. Then their heart rate and breathing slowed. And the mice stayed in this suspended state for six hours. Two hours after breathing regular air again, their body functions returned to normal, and a day later they were behaving normally. By all appearances, the gas reduced their oxygen demand for hours–with no adverse effects.
Earlier research at the Fred Hutchinson Cancer Research Center in Seattle, WA, had suggested that this might be the case. In 2005, scientists there combined the cooling and hydrogen sulfide gas methods, and the mice were similarly revived with air, and resumed normal behavior.
MGH’s Ichinose hopes that people who require problematic heart surgery will one day be able to receive gas instead of being cooled, or get both procedures one after the other. Either way, it would allow surgeons to operate on a blood-free heart for a longer period of time.
Having extra time to operate while the flow of blood is stopped could make a difference, says Jeffrey Pearl, a pediatric cardiac surgeon at Children’s Hospital in Cincinnati. Operating in just 45 minutes “takes a lot of planning,” he says. “You need training. And you have to be more perfect because there’s no time to hesitate.”
But Pearl also notes that the MGH experiment leaves a lot of unanswered questions about the effects of the gas on humans. Mice are smaller than humans and may respond to the gas differently. Also, the mice in the experiment had no heart defects and didn’t undergo surgery. Furthermore, their brains weren’t assessed for a long enough time after the procedure. Some children who undergo long periods of blood flow stoppage to the brain, even when protected by cooling and seemingly fine post-operative care, experience “learning problems later in life,” Pearl says. Using hydrogen sulfide gas on humans “is an interesting concept,” he adds, “but that’s all it is at the moment.”
In fact, many heart surgeons are looking for ways to perform these complex operations while keeping the blood flowing to the brain, rather than searching for methods like gas or cooling to prevent brain damage from stopping the flow.
The MGH group will present their results this week at the American Physiological Society conference in Virginia Beach, VA. And they plan to keep investigating the gas technique; they will measure how long mice can stay under its influence with no harm to body, brain, or behavior; test different gas concentrations; and assess whether the gas is safe and effective on larger mammals such as pigs and sheep. “If this doesn’t work in bigger animals, that may be the end of the story,” Ichinose says.