Submitted on February 1, 2005
Accepted on October 3, 2005
Effect of Benzodiazepine Hypnotic Triazolam on the Relationship of Blood Pressure and Paco2 to Cerebral Blood Flow during Human Non Rapid Eye Movement Sleep
Masahiko Hiroki1*, Naofumi Kajimura2, Takeshi Uema3, Kenichi Ogawa4, Masami Nishikawa2, Masaaki Kato2, Tsuyoshi Watanabe2, Toru Nakajima5, Harumasa Takano2, Etsuko Imabayashi6, Takashi Ohnishi6, Yutaka Takayama2, Hiroshi Matsuda6, Makoto Uchiyama7, Masako Okawa8, Kiyohisa Takahashi2, and Hidenao Fukuyama2
1 Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan
2 Psychiatry, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan
3 Psychiatry, Osaka Prefectural General Hospital, Osaka, Osaka, Japan
4 Anesthesiology, National Center Hospital for Mental, Nervous, and Muscular Disorders, NCNP, Kodaira, Tokyo, Japan
5 Psychiatry, Teikyo University School of Medicine, Kawasaki, Kanagawa, Japan
6 Radiology, National Center Hospital for Mental, Nervous, and Muscular Disorders, NCNP, Kodaira, Tokyo, Japan
7 Psychiatry, National Institute of Mental Health, NCNP, Ichikawa, Chiba, Japan
8 Psychiatry, Shiga University of Medical Science, Otsu, Shiga, Japan
* To whom correspondence should be addressed. E-mail: CYI01752{at}nifty.com.
We sought to clarify the effect of short-acting benzodiazepine hypnotic on the relationship of arterial blood pressure and arterial partial pressure of carbon dioxide (Paco2) to regional cerebral blood flow (rCBF) during human non-rapid-eye-movement (REM) sleep. Nine young normal volunteers were treated in a randomized, double-blind, crossover design with triazolam or placebo and underwent positron emission tomography at night. During wakefulness and stage 2 and slow-wave (stages 3 and 4) sleep, we measured mean arterial blood pressure (MAP), Paco2, and absolute CBF. With triazolam compared to placebo, MAP reduced gradually. During stage 2 sleep, Paco2 increased and whole-brain mean CBF decreased. With triazolam, relative rCBF of the left orbital basal forebrain significantly more extensively decreased during stage 2 compared to slow-wave sleep, whereas absolute CBF of the occipital cortex and cerebral white matter remained constant. During stage 2 triazolam-induced sleep, absolute CBF of the cerebral white matter correlated significantly more highly to both MAP and Paco2 compared to placebo, and it also correlated similarly did to both MAP and Paco2 compared with absolute CBF of the occipital cortex. In the frontal white matter, during stage 2 triazolam-induced sleep compared to wakefulness, absolute CBF was significantly more highly correlated to MAP, but not to Paco2. During stage 2 triazolam-induced sleep relating to the predominant deactivation of the basal forebrain, the cerebral white matter may receive a modulated CBF regulation having the strengthened relationship of Paco2 to CBF, and, more locally, the frontal white matter may subsist precariously on CBF regulation.
