Induced "hibernation" state protects organs during heart surgery in mice
Japanese researchers have demonstrated that inducing a kind of hibernation state could be a new way to protect organs from damage when blood circulation is stopped during surgery. The technique slows down the metabolism and has been found to work well in tests in mice.
During some kinds of surgery on the heart or aorta, doctors need to interrupt the flow of blood, but of course the resulting oxygen deprivation would have a devastating effect on organs and tissues. For decades, the main solution has been to induce a deep hypothermia in patients during these surgeries, bringing their body temperatures right down to slow their metabolism. But this is a difficult process that carries some risk.
Scientists at RIKEN in Japan have now found a potential alternative, based on a discovery they made a few years ago. In that previous study, the researchers identified a set of neurons (Q neurons) in mice that, when stimulated, induce a sleep-like state called torpor, which animals like mice and birds enter to conserve energy by slowing their metabolism.
More intriguingly, the team was able to stimulate Q neurons to induce this state in rats, which don’t naturally undergo torpor. That opened the possibility that humans could eventually be put into this kind of hibernation, which could, for example, help for long space voyages or, as the new study explores, as an alternative to hypothermia in surgery.
“If we can induce them, there are many possibilities for using hibernation-like states in cardiovascular medicine, resuscitation medicine, or other cases in which organ protection via hypothermia is insufficient or inappropriate,” said Genshiro Sunagawa, co-lead author of the study.
The team tested the idea in four groups of mice undergoing aortic surgery. Two groups received injections of chemicals that activated the Q neurons – one of these groups was kept at a normal body temperature, while the other was put under hypothermia. The other two groups were controls that received placebo injections, with one under hypothermia and the other at normal temperature.
Afterwards, the scientists examined kidney damage and function by evaluating levels of certain biomarkers in the blood. And sure enough, mice that had had their Q neurons activated showed a similar level of organ protection as the control mice that had undergone hypothermia. There was no real difference between the Q neuron mice that had and hadn’t undergone hypothermia.
While the study is intriguing, the team cautions that it’s still very early days for the research. First and foremost, it’s unlikely Q neurons could be selectively activated in human brains to achieve the same effect. But the scientists say that understanding the mechanism behind it could reveal other ways to induce the state.
“Activating Q neurons triggers some sequence of biological events that allows organs to exist in a hypometabolic state for days,” said Sunagawa. “Once we know precisely what these events are, we are confident we can induce them pharmacologically in the body, without needing to first activate the Q neurons.”
The research was published in the journal JTCVS Open.