When Roth first exposes mice to a low dose of hydrogen sulfide, causing their metabolic rates to decline as much as 90%, the animals sleep peacefully for hours in air that has 5% oxygen content instead of the normal 21%. (Typically this atmosphere would kill a mouse within 15 minutes.) When Roth turns on the oxygen again, the animals wake up with no discernible problems. “We use hydrogen sulfide as if it were a dimmer switch,” Roth explains. “The more we give, the more we suppress oxygen demand.”

Roth thinks that using hydrogen sulfide to suppress metabolism could go a long way toward saving victims of heart attacks and central nervous system trauma and even patients whose hearts have stopped from loss of blood. The therapeutic aim, he says, would parallel that of EPR: to preserve vital organs while medical teams tend to a primary injury.

Hydrogen sulfide might offer a faster, less invasive path to suspended animation, says Warren Zapol, chief of anesthesiology and critical care at the MGH. Gian Paolo Volpato, a postdoctoral fellow working with Zapol, has shown that even very low exposure to inhaled hydrogen sulfide can sharply reduce metabolism and heart rates in mice. What’s more, metabolic rates decreased even when Volpato kept the mice warm. That’s intriguing because the extreme cold of EPR lessens blood’s clotting ability and increases risk of infection. (Volpato’s results were published in April in the journal Anesthesiology.)

“Hypothermia is a good way to slow metabolism,” Zapol says. “But it has its problems, particularly when normal blood flow has been severely disrupted. It would be hard to rapidly cool the heart and brain if the aorta has been torn.”

Still, research with hydrogen sulfide is at an earlier stage than Tisherman’s work. The gas has yet to be thoroughly tested in larger mammals, which may be less sensitive to hydrogen sulfide and require larger inhaled doses, and that could pose challenges for delivery because the gas would harm the lungs at higher concentrations. Whereas Volpato used inhalable gas, an alternative approach uses a form of hydrogen sulfide that can be injected into veins. But human trials can’t begin until after this approach has been used safely and successfully in at least two larger animal species.

In the meantime, infusions of ice-cold saline are headed for the clinic to launch what could be a lifesaving shift in trauma care. “I’m hoping it will give us a chance to save as many as 100 people a year in our hospital alone,” says Scalea. “It’s unbelievably frustrating to see an 18-year-old die because you can’t restart her heart after repairing her injuries.”

  Dossier

1. “Hypothermia and Injury,” by Samuel A. Tisherman, Current Opinion in Critical Care, December 2004. An introduction to the concept of inducing suspended animation with profound hypothermia during the treatment of exsanguination cardiac arrest.

2. “Induction of Profound Hypothermia for Emergency Preservation and Resuscitation Allows Intact Survival After Cardiac Arrest Resulting From Prolonged Lethal Hemorrhage and Trauma in Dogs,” by X. Wu et al., Circulation, April 25, 2006. A detailed surgical description of the saline flush method.

3. “Inhaled Hydrogen Sulfide: A Rapidly Reversible Inhibitor of Cardiac and Metabolic Function in the Mouse,” by G.P. Volpato et al., Anesthesiology, April 2008. An intriguing report that hydrogen sulfide can suspend animation in mice without lowering body temperature or blood pressure, thus avoiding hypothermia’s attendant problems (increased infection risk, decreased blood clotting).