Hydrogen sulfide gas can induce a state of suspended animation in mice while maintaining normal blood pressure, a finding that researchers hope will one day help treat critically-ill patients.
Hydrogen sulfide gas, sometimes called sewer gas, produces a noxious odor often described as a rotten egg smell. The gas occurs naturally in swamps, springs and volcanoes. While usually harmless, it can be toxic if breathed in sufficient quantity, explained Gian Paolo Volpato, one of the study's authors.
The study, entitled "Cardiovascular response to breathing hydrogen sulfide in a murine model: separating the effects of body temperature," will be presented Sunday, Oct. 8, at The American Physiological Society conference, "Comparative Physiology 2006: Integrating Diversity," in Virginia Beach, VA, Oct. 8-11. Gian Paolo Volpato, Robert J. Searles, Marielle Scherrer-Crosbie, Oleg V. Evgenov, Kenneth D. Block, Fumito Ichinose and Warren M. Zapol of the Massachusetts General Hospital in Boston carried out the study.
The research built on a 2005 study from the University of Washington in Seattle and the Fred Hutchinson Cancer Research Center, which found that when mice breathed the gas, they went into a hibernation-like state. Their metabolic rate dropped by 90% and their body temperature decreased to nearly the temperature of the surrounding air.
New research looks at cardiovascular effects
"We wanted to confirm the Seattle study and record the effects the gas has on blood pressure, heart rate, respiratory rate and the activity level of the mice," Volpato explained. They administered 80 parts per million of hydrogen sulfide gas to their mice and found their:
- heart rate fell from 500 beats per minute to 200 beats per minute
- respiration rate decreased from 120 breaths to 25 breaths per minute
- core body temperature fell from 38° C to 30° C
- activity level fell dramatically, moving only when the researchers touched them or shook their chambers
After the mice returned to breathing normal air, they quickly returned to normal. These changes were expected, based on the Seattle research. But the physiologists found something they did not expect. Normally, as oxygen consumption goes down and heart rate decreases, blood pressure decreases also. Since the heart rate of the mice fell by more than 50%, the researchers expected blood pressure to fall, but it didn't, Ichinose said.
Surprisingly, blood pressure stays normal
"We were surprised to find that blood pressure didn't change, even though the mouse's heart beat fell to 200 beats per minute," Volpato said. "We don't know why, but it may be a physiological response to maintain body temperature," Ichinose added.
An animal's blood pressure needs to remain at a certain level to ensure blood reaches the vital organs. Normally, a mouse with that heart rate would have very low blood pressure and would be close to death. But these mice returned to normal two hours after the gas was discontinued.
The researchers then repeated the experiment with a new set of mice, but this time they raised the "room" temperature from 27° C (81° F) used in the first experiment, to 35° C (95° F). They found that heart rate and respiration rate still fell significantly, but not as much as the first experiment when the room was cooler.
They also found that in the warmer room, blood pressure increased, whereas it had remained unchanged in the colder environment. The researchers also measured the cardiac output of the mice in this experiment by echocardiography, and found that stroke volume, that is, the amount of blood the mice pumped with each beat, was unchanged by the gas. However, total cardiac output decreased because the heart was beating much slower.
Could help surgery patients
"These findings demonstrate that mice that breathe 80 parts per million of hydrogen sulfide become hypothermic and decrease their respiration rate, heart rate and cardiac output without affecting stroke volume or mean arterial pressure," the authors said.
This line of research could have a variety of helpful applications, including sustaining the function of organs of critically ill people, Ichinose said. It may also be possible to use the finding for patients undergoing surgery. This would be an advance, because anesthesia usually causes blood pressure to drop.
"Currently, hypothermia is the only proven way to decrease metabolic rate and confer some protection when blood flow to the organs is impaired or intentionally reduced, such as during complex cardiac surgery," Ichinose said. "However, hypothermia has some adverse effects, including depressing cardiovascular functions and blood clotting. If we can figure out how hydrogen sulfide reduces metabolic rate without depressing myocardial function, we may be able to reduce metabolism and protect organs without using hypothermia."
One caveat to this research so far is that hydrogen sulfide might produce this result in mice and other naturally hibernating species much more readily than other species, including humans, Ichinose said. The researchers intend to extend the study to bigger animals, such as sheep and pigs to see if they have the same cardiac and hemodynamic reaction. "If the same thing happens in those species that would be much more interesting," Ichinose said.
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