학술논문
The Tissue Response to Hypoxia: How Therapeutic Carbon Dioxide Moves the Response toward Homeostasis and Away from Instability
Document Type
Academic Journal
Source
International Journal of Molecular Sciences. March 2023, Vol. 24 Issue 6
Subject
Language
English
ISSN
1422-0067
Abstract
Author(s): Richard J. Rivers (corresponding author) [1,*]; Cynthia J. Meininger [2] 1. Introduction Oxygen (O[sub.2]) is carried in the blood and delivered to cells in tissues. O[sub.2] is necessary for [...]
Sustained tissue hypoxia is associated with many pathophysiological conditions, including chronic inflammation, chronic wounds, slow-healing fractures, microvascular complications of diabetes, and metastatic spread of tumors. This extended deficiency of oxygen (O[sub.2]) in the tissue sets creates a microenvironment that supports inflammation and initiates cell survival paradigms. Elevating tissue carbon dioxide levels (CO[sub.2]) pushes the tissue environment toward “thrive mode,” bringing increased blood flow, added O[sub.2], reduced inflammation, and enhanced angiogenesis. This review presents the science supporting the clinical benefits observed with the administration of therapeutic CO[sub.2]. It also presents the current knowledge regarding the cellular and molecular mechanisms responsible for the biological effects of CO[sub.2] therapy. The most notable findings of the review include (a) CO[sub.2] activates angiogenesis not mediated by hypoxia-inducible factor 1a, (b) CO[sub.2] is strongly anti-inflammatory, (c) CO[sub.2] inhibits tumor growth and metastasis, and (d) CO[sub.2] can stimulate the same pathways as exercise and thereby, acts as a critical mediator in the biological response of skeletal muscle to tissue hypoxia.
Sustained tissue hypoxia is associated with many pathophysiological conditions, including chronic inflammation, chronic wounds, slow-healing fractures, microvascular complications of diabetes, and metastatic spread of tumors. This extended deficiency of oxygen (O[sub.2]) in the tissue sets creates a microenvironment that supports inflammation and initiates cell survival paradigms. Elevating tissue carbon dioxide levels (CO[sub.2]) pushes the tissue environment toward “thrive mode,” bringing increased blood flow, added O[sub.2], reduced inflammation, and enhanced angiogenesis. This review presents the science supporting the clinical benefits observed with the administration of therapeutic CO[sub.2]. It also presents the current knowledge regarding the cellular and molecular mechanisms responsible for the biological effects of CO[sub.2] therapy. The most notable findings of the review include (a) CO[sub.2] activates angiogenesis not mediated by hypoxia-inducible factor 1a, (b) CO[sub.2] is strongly anti-inflammatory, (c) CO[sub.2] inhibits tumor growth and metastasis, and (d) CO[sub.2] can stimulate the same pathways as exercise and thereby, acts as a critical mediator in the biological response of skeletal muscle to tissue hypoxia.