Kazuhiko Fukuda, M.D., Ph.D. Professor
The original purpose of anesthesiology was reduction of surgery-induced pain. However, the present goal of anesthesiology is control of excessive biological responses induced by a variety of stresses and protection of patients from stress-induced complications. Clinical activity of this department is divided into anesthesia in the operation theater, pain control for a variety of diseases and critical care medicine. Our ultimate goal is elucidation of mechanism for stress responses and development of treatment and care for suppression of excessive stress responses.。
Research and EducationThe goal of research in this department is to elucidate mechanisms of responses induced by a variety of stresses and to develop management to control stress responses. We are analyzing actions of anesthetics and opioids from many aspects. To analyze pharmacological actions of opioids at the molecular level, we have cloned cDNAs of opioid receptors, and have analyzed intracellular signal transduction mechanisms activated by opioids. Using genetically engineered mice, we are testing the role of the opioid receptor family in the pharmacological actions of inhaled anesthetics, and have demonstrated the possible involvement of the nociceptin receptor and the κ-opioid receptor in the analgesic action of nitrous oxide. During perioperative period, oxygen supply is often reduced by anemia and changes in the cardio-respiratory system, and organs are exposed to hypoxia, which induces hypoxic responses at the organ, cellular and molecular levels. We have analyzed hypoxia-inducible factor (HIF), which plays important roles in cellular hypoxic responses, and demonstrated that perioperatively used drugs and hypothermia can change cellular hypoxic responses by affecting HIF activity and gene expression controlled by HIF.
This department is responsible for instruction and clinical training of anesthesiology and critical care medicine for undergraduate and postgraduate students. Residents are trained to obtain the basic capability of life support and anesthetic care in the operation room. Doctors aiming to be board certified anesthesiologists are trained for anesthetic management of special operations, intensive care for various systemic diseases and control of pain caused by various diseases.
Figure 1. Intracellular signal transduction mechanism mediated by the opioid
Activation of the opioid receptors induces a variety of cellular responses, including inhibition of adenylate cyclase, activation of the inwardly rectifier K+ channel and inhibition of the voltage-dependent Ca2+ channel, via activation of the G-protein. Furthermore, activation of mitogen-activated protein kinases by the opioid receptors leads to changes in gene expression and activation of phospholipase A2.
Figure 2. Clinical anesthesia in the operating theater
Staffs of the department of anesthesia perform anesthetic management and teach residents in the operating theater.
Recent Publications1.Tanaka, T., Wakamatsu, T., Daijo, H., Oda, S., Kai, S., Adachi, T., Kizaka-Kondoh, S., Fukuda, K. and Hirota, K.: Persisting mild hypothermia suppresses hypoxia-inducible factor 1a protein synthesis and HIF-1-mediated gene expression. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298, R661-671 (2010).
2.Tanaka, T., Takabuchi, S., Nishi, K., Oda, S., Wakamatsu, T., Daijo, H., Fukuda, K. and Hirota, K.: The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor 1 activation and suppresses the glucose metabolism in macrophages. J. Anesth. 24, 54-60 (2010).
3.Koyama, T. and Fukuda, K.: Involvement of the k-opioid receptor in nitrous oxide-induced analgesia in mice. J. Anesth. 24, 297-299 (2010).
4.Kai, S., Tanaka, T., Daijo, H., Harada, H., Kishimoto, S., Suzuki, K., Takabuchi, S., Takenaga, K., Fukuda, K. and Hirota, K.: Hydrogen sulfide inhibits hypoxia- but not anoxia-induced hypoxia-inducible factor 1 activation in a von hippel-lindau- and mitochondria-dependent manner. Antioxid. Redox. Signal. 16, 203-216 (2011).
5.Fukagawa, H., Koyama, T., Kakuyama, M. and Fukuda, K.: Microglial
activation involved in morphine tolerance is not mediated by toll-like receptor 4. J. Anesth. 27, 93-97 (2013).
AnesthesiaProfessor: Kazuhiko Fukuda
Lecturer: Hajime Segawa・Masahiro Kakuyama
Assistant Professor: Takehiro Shoda・Keiji Tanimoto・Taizo Hisano・Tomoharu Tanaka・Toshiyuki Mizota・Hiroki Daijo・Masami Sato