title: A novel system for transcutaneous application of carbon dioxide causing an "artificial Bohr effect" in the human body.
abstract: BACKGROUND
  Carbon dioxide (CO(2)) therapy refers to the transcutaneous administration of CO(2) for therapeutic purposes. This effect has been explained by an increase in the pressure of O(2) in tissues known as the Bohr effect. However, there have been no reports investigating the oxygen dissociation of haemoglobin (Hb) during transcutaneous application of CO(2)in vivo. In this study, we investigate whether the Bohr effect is caused by transcutaneous application of CO2 in human living body.
  
  
  METHODS
  We used a novel system for transcutaneous application of CO(2) using pure CO(2) gas, hydrogel, and a plastic adaptor. The validity of the CO(2) hydrogel was confirmed in vitro using a measuring device for transcutaneous CO(2) absorption using rat skin. Next, we measured the pH change in the human triceps surae muscle during transcutaneous application of CO(2) using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) in vivo. In addition, oxy- and deoxy-Hb concentrations were measured with near-infrared spectroscopy in the human arm with occulted blood flow to investigate O2 dissociation from Hb caused by transcutaneous application of CO(2).
  
  
  RESULTS
  The rat skin experiment showed that CO(2) hydrogel enhanced CO(2) gas permeation through the rat skin. The intracellular pH of the triceps surae muscle decreased significantly 10 min. after transcutaneous application of CO(2). The NIRS data show the oxy-Hb concentration decreased significantly 4 min. after CO(2) application, and deoxy-Hb concentration increased significantly 2 min. after CO(2) application in the CO(2)-applied group compared to the control group. Oxy-Hb concentration significantly decreased while deoxy-Hb concentration significantly increased after transcutaneous CO(2) application.
  
  
  CONCLUSIONS
  Our novel transcutaneous CO(2) application facilitated an O(2) dissociation from Hb in the human body, thus providing evidence of the Bohr effect in vivo.
authors.affiliation: Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan. sakai.yoshitada@gm.himeji-du.ac.jp
authors.forename: Yoshitada
authors.initials: Y
authors.lastname: Sakai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Miwa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueha
authors.forename: Akihiro
authors.initials: A
authors.lastname: Koh
authors.forename: Takahiro
authors.initials: T
authors.lastname: Niikura
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwakura
authors.forename: Sang Yang
authors.initials: SY
authors.lastname: Lee
authors.forename: Masaya
authors.initials: M
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005542:Forearm; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D020100:Hydrogels; D010108:Oxyhemoglobins; D002245:Carbon Dioxide; D010100:Oxygen