A Novel System for Transcutaneous Application of Carbon Dioxide Causing an "Artificial Bohr Effect" in the Human Body

Background: Carbon dioxide (CO2) therapy refers to the transcutaneous administration of CO2 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 CO2 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 CO2 using pure CO2 gas, hydrogel, and a plastic adaptor. The validity of the CO2 hydrogel was confirmed in vitro using a measuring device for transcutaneous CO2 absorption using rat skin. Next, we measured the pH change in the human triceps surae muscle during transcutaneous application of CO2 using phosphorus-31 magnetic resonance spectroscopy (P-31-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 CO2. Results: The rat skin experiment showed that CO2 hydrogel enhanced CO2 gas permeation through the rat skin. The intracellular pH of the triceps surae muscle decreased significantly 10 min. after transcutaneous application of CO2. The NIRS data show the oxy-Hb concentration decreased significantly 4 min. after CO2 application, and deoxy-Hb concentration increased significantly 2 min. after CO2 application in the CO2-applied group compared to the control group. Oxy-Hb concentration significantly decreased while deoxy-Hb concentration significantly increased after transcutaneous CO2 application. Conclusions: Our novel transcutaneous CO2 application facilitated an O-2 dissociation from Hb in the human body, thus providing evidence of the Bohr effect in vivo.