Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses.
OBJECTIVE
To study whether intravascular or hemodynamic factors contribute to the marked neuroprotective effect of albumin therapy in focal cerebral ischemia, 2 complementary methods were applied: laser-scanning confocal microscopy (LSCM) and laser-Doppler perfusion imaging (LDPI).


METHODS
In the LSCM study, Sprague-Dawley rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed over the dorsolateral frontoparietal cortex. Rats received 2-hour middle cerebral artery occlusion (MCAO) by an intraluminal suture and were treated with human albumin (1.25 g/kg; n=4) or saline (n=3) after 30 minutes of recirculation. Video images of cortical vessels were continually acquired and were digitized offline to measure diameters and fluorescent erythrocyte velocities. In the LDPI study, cortical perfusion was measured in anesthetized Sprague-Dawley rats that received 2-hour MCAO and were treated with albumin (2.5 g/kg; n=6) or saline (n=5) at 30 minutes after recirculation.


RESULTS
In the LSCM study, MCAO was associated with arteriolar dilation and slowing of capillary and venular erythrocyte perfusion. During the first 15 to 30 minutes of postischemic recirculation, prominent foci of vascular stagnation developed within cortical venules, associated with thrombuslike foci and adherent corpuscular structures consistent in size with neutrophils. Saline administration failed to affect these phenomena, while albumin therapy was followed by significant increases in arteriolar diameter ( approximately 12%; P=0.007) and by a prompt improvement of venular and capillary erythrocyte perfusion and a partial disappearance of adherent thrombotic material. Albumin therapy increased erythrocyte flow velocity in both capillaries (288+/-73% versus 76+/-18% in the saline group; P=0.023) and venules (2.7-fold [P=0.001] versus 1.0-fold in the saline group [P=NS]). In the LDPI study, cortical perfusion declined during MCAO and rose initially with recirculation (to approximately 135% of baseline) in both groups. Mean cortical perfusion improved slightly (approximately 14%; P=NS) in albumin-treated animals.


CONCLUSIONS
These results reveal a beneficial effect of albumin therapy in reversing stagnation, thrombosis, and corpuscular adherence within cortical venules in the reperfusion phase after focal ischemia and support its utility in the treatment of acute ischemic stroke.
Belayev
Ludmila
L
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Miami, Fla 33101, USA. lbelayev@stroke.med.miami.edu
Pinard
Elisabeth
E
Nallet
Helene
H
Seylaz
Jacques
J
Liu
Yitao
Y
Riyamongkol
Panomkhawn
P
Zhao
Weizhao
W
Busto
Raul
R
Ginsberg
Myron D
MD
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D018613:Microscopy, Confocal; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010841:Pia Mater / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014699:Venules / Q000187:drug effects / Q000503:physiopathology
D018696:Neuroprotective Agents; D012709:Serum Albumin