Endothelial cell swelling and brain perfusion.
BACKGROUND
Whereas the contribution of glial swelling to no-reflow conditions in the ischemic penumbra or during reperfusion after after global ischemia is widely discussed, little is known about cell volume control of endothelial cells under reperfusion conditions.


METHODS
The effect of extracellular acidosis-a key mediator of secondary brain damage-on cell volume was studied in the GM7373 endothelial cell line. Experiments were performed at pH = 6.0 in the presence or absence of bicarbonate, and during exposure to inhibitors of specific transport systems such as ethyl isopropyl amiloride or 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid.


RESULTS
Endothelial swelling to 111.1 +/- 3.4% was found at pHe = 6.0 in bicarbonate-buffered media. In hydroxyethyl piperin ethanesulfonic acid-buffered media, swelling was only 107.9 +/- 0.3%. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid reduced swelling to 102.8 +/- 0.6% in bicarbonate media, whereas swelling was completely prevented in the presence of ethyl isopropyl amiloride in hydroxyethyl piperin ethanesulfonic acid-buffered media.


CONCLUSIONS
Endothelial swelling can be expected to occur in severely ischemic tissue sections and may then advance no-reflow. Therapeutic strategies should be established to prevent acidosis-induced endothelial swelling, e.g., by specific antagonists of the transport systems involved, or to reduce swelling by osmotic treatment such as hypertonic-hyperoncotic solutions.
Kempski
O
O
Institute for Neurosurgical Pathophysiology, Johannes Gutenberg-University, Mainz, Germany.
Behmanesh
S
S
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002417:Cattle; D002460:Cell Line; D002463:Cell Membrane Permeability; D048429:Cell Size; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D008833:Microcirculation; D015427:Reperfusion Injury / Q000378:metabolism*