Albumin therapy improves local vascular dynamics in a rat model of primary microvascular thrombosis: a two-photon laser-scanning microscopy study.
OBJECTIVE
High-dose human albumin is robustly neuroprotective in preclinical ischemia models and is currently in phase III clinical trial for acute ischemic stroke. To explore the hypothesis that albumin's protective effect is mediated in part by salutary intravascular mechanisms, we assessed microvascular hemodynamics in a model of laser-induced cortical arteriolar thrombosis.


METHODS
The cortical microcirculation of anesthetized, physiologically monitored Sprague-Dawley rats was studied in vivo via a frontoparietal cranial window (intact dura) by two-photon laser-scanning microscopy after plasma-labeling with fluorescein-dextran. Focal thrombosis was produced in 30- to 50-mum cortical arterioles by laser irradiation. Arteriolar flow velocity was measured repeatedly by line-scanning. At 30 minutes post-thrombosis, animals were treated with either human albumin, 2 g/kg, or with saline control.


RESULTS
Baseline arteriolar flow velocity averaged 3.5+/-1.8 mm/s and was reduced to 10% to 13% of control values by laser-induced thrombosis, which also led to focal vasodilatation (mean, 49% above baseline diameter). Saline treatment at 30 minutes post-thrombosis failed to influence arteriolar flow velocity, which remained depressed at 10% to 22% of control throughout the subsequent 60- to 90-minute observation period. By contrast, albumin treatment induced a prompt rise in median flow velocity to 38% of control by 10 minutes post-treatment, and to 61% to 67% of control by 50 to 60 minutes.


CONCLUSIONS
High-dose albumin therapy induces a prompt, sustained improvement in microvascular hemodynamics distal to a cortical arteriolar thrombosis; these data support an important intravascular component to albumin's protective effect in acute cerebral ischemia.
Nimmagadda
Anitha
A
Cerebral Vascular Disease Research Center, Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, FL 33101, USA.
Park
Hee-Pyoung
HP
Prado
Ricardo
R
Ginsberg
Myron D
MD
D000418:Albumins / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001160:Arterioles / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020767:Intracranial Thrombosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D007834:Lasers / Q000009:adverse effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
D000418:Albumins