NEW YORK, May 17 (Reuters Health) - In novel research to examine the mechanisms that control breathing, scientists at the University of Chicago, Illinois, have defined the brain area that is responsible for the generation of normal breathing, gasping and sighs, according to senior investigator Dr. Jan Marino Ramirez.

      The findings, published in the June issue of Nature Neuroscience, may lead to better understanding of breathing disorders, including sudden infant death syndrome (SIDS).

      Ramirez told Reuters Health that though a group of cells called the pre-Botzinger complex, located in the brainstem, was known to be associated with breathing in some way, its specific role was poorly understood.

      A slice of animal brainstem containing this area was used to "describe the neural mechanisms that define (normal breathing), gasping, and sighs," Ramirez explained, adding, "the sigh is not just a peculiar form of breathing, but...the most important arousal mechanism during sleep. (And) the gasps are the last chance to arouse during very extreme (oxygen-deprived) conditions."

      That this slice--"a piece of tissue which can be put under a microscope"--retains the ability to "generate all characteristics that are typical for a sigh...is astonishing, as this is just a thin slice of the medulla and there is not much else left from (the) animal," Ramirez said.

      "We can now start to investigate the cellular mechanisms of the sigh, without worrying about the cortex and other higher brain areas, and the whole animal," she continued. "It opens a new direction in understanding the...mechanisms that lead to the different forms of breathing."

      Sighing has been associated with many sleep disturbances, including SIDS and apnea. Apnea, or a cessation of breathing, causes a person to slowly become oxygen-starved. This lack of oxygen, or hypoxia, leads to the generation of sighs, which then trigger arousal, a change in position and a reduction in hypoxia.

      On the other hand, Ramirez pointed out, "the sigh also triggers an increase in blood pressure and heart rate, which makes sleep apnea...dangerous as it increases the risk of heart failure." When apnea is treated, sighing is reduced along with the possibility of attendant heart problems, she explained.

      In the case of SIDS, Ramirez said, "perhaps the 'arousal' mechanism which is essential to wake up during (hypoxia) is disturbed." It is known that babies who die of SIDS have "a significantly decreased number of sighs," she continued. And, these children also have disturbed gasps since "the gasps do not trigger an increased heart rate or blood pressure" as would normally be expected.

      Ramirez is mindful of the excitement that this work is bound to elicit in the scientific and medical communities. The researcher emphasizes, however, that these results are only the beginning. And, "we should have the right amount of caution when looking at results obtained from slices. We (will) have to expect differences between the slice and the human, (but) only in the slice is it possible to investigate the cellular mechanisms to an extent that will never be possible in a whole animal."

      The team's numerous ongoing research efforts include investigating how breathing frequency is regulated under conditions and "the effect of high temperature (fever) on these different forms of breathing," Ramirez said.

           SOURCE: Nature Neuroscience 2000; 3:600-607