Researchers at Cleveland Medical Center have identified a modified form of hemoglobin that can restore oxygen delivery to tissues. The findings appear in the journal PNAS.
The team notes a persistent puzzle in medicine: people can die from insufficient oxygen delivery even when blood oxygen levels seem adequate. At the same time, medications that simply boost blood flow do not always improve how well tissues are oxygenated.
The focus of the work is S-nitrosohemoglobin, a unique variant of hemoglobin found in both mice and humans. This molecule carries nitric oxide instead of oxygen, widens blood vessels, and markedly enhances tissue oxygenation by improving the distribution of oxygen to cells that need it most.
Clinical observations suggest that reduced tissue oxygenation is linked to low levels of S-nitrosohemoglobin in several conditions, including peripheral artery disease, sickle cell anemia, heart failure, stroke, and emphysema. In each case, tissues may suffer from compromised oxygen delivery even when overall blood oxygen content is not severely reduced.
Building on these insights, researchers are pursuing drugs that can shift hemoglobin toward the S-nitrosohemoglobin form. If successful, this strategy could yield new therapies aimed at correcting tissue hypoxia, offering a targeted approach where oxygen delivery to tissues is impaired rather than simply increasing the amount of oxygen circulating in the blood. The work signals a potential pathway to address a longstanding clinical challenge and could pave the way for the first medicines specifically designed to improve tissue oxygenation in a variety of diseases.