Sustained endothelial dependent dilation in pial arterioles after crosslinked hemoglobin transfusion

Area of Science:

• Neuroscience
• Physiology
• Pharmacology

Background:

• Hemoglobin binds nitric oxide (NO), a key vasodilator.
• Plasma-based hemoglobin might interact differently with the endothelium than red cell-based hemoglobin.
• Cerebral vessels have tight junctions, potentially limiting plasma hemoglobin's access to brain tissue.

Purpose of the Study:

• To investigate if systemic transfusion of crosslinked hemoglobin affects NO-derived vasoreactivity in the brain.
• To determine if plasma hemoglobin interferes with endothelial-dependent and independent vasodilation in pial arterioles.

Main Methods:

• Cats were anesthetized and underwent cranial window surgery to visualize pial arterioles.
• Systemic transfusion of crosslinked hemoglobin was performed.
• Topical application of vasodilators (acetylcholine, SIN-1, adenosine diphosphate, sodium nitroprusside) and an NO synthase inhibitor (L-nitroarginine) was used to measure arteriole diameter changes.

Main Results:

• Systemic hemoglobin transfusion did not alter the dilator responses to acetylcholine, SIN-1, adenosine diphosphate, or sodium nitroprusside.
• Inhibition of NO synthase reduced responses to acetylcholine and adenosine diphosphate, but not SIN-1 or sodium nitroprusside.
• Topical application of hemoglobin directly to the brain surface showed concentration-dependent inhibition of vasodilation, suggesting limited blood-brain barrier penetration.

Conclusions:

• Systemic transfusion of crosslinked hemoglobin does not interfere with NO-dependent or independent vasodilation in feline pial arterioles.
• The blood-brain barrier appears to limit acute penetration of crosslinked hemoglobin into the brain parenchyma.
• Plasma hemoglobin, when systemically administered, does not inhibit critical NO-mediated cerebrovascular mechanisms.