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(Stroke. 2008;39:1556.)
© 2008 American Heart Association, Inc.

Original Contributions

Albumin Therapy Augments the Effect of Thrombolysis on Local Vascular Dynamics in a Rat Model of Arteriolar Thrombosis

A Two-Photon Laser-Scanning Microscopy Study

Hee-Pyoung Park, MD, PhD; Anitha Nimmagadda, MD; Richard A. DeFazio, PhD; Raul Busto, BS; Ricardo Prado, MD Myron D. Ginsberg, MD

From the Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami Miller School of Medicine, Miami, Fla, USA.

Correspondence to Myron D. Ginsberg, MD, Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, FL 33101. E-mail mginsberg{at}med.miami.edu

Background and Purpose— Results of our recent pilot clinical trial suggest that the efficacy of thrombolytic therapy in acute ischemic stroke may be enhanced by the coadministration of high-dose albumin. Here, we explored the microvascular hemodynamic effects of this combined therapy in a laboratory model of cortical arteriolar thrombosis.

Methods— We studied the cortical microcirculation of physiologically monitored rats in vivo by two-photon laser-scanning microscopy after plasma-labeling with fluorescein-dextran. We induced focal thrombosis in 30- to 50-µm cortical arterioles by laser irradiation and measured arteriolar flow velocity by repeated line-scanning. At 30 minutes post-thrombosis, we treated animals with the thrombolytic agent, reteplase, which was coadministered with either human albumin, 2 g/kg, or with saline control.

Results— Baseline arteriolar flow velocity averaged 3.8±0.7 mm/s, was immediately reduced by thrombosis to 22% to 25% of control values, and remained unchanged before treatment. Subthrombolytic doses of reteplase combined with saline led to a median increase in flow velocity to 37% of control distal to the thrombus (P=nonsignificant versus pretreatment). By contrast, reteplase combined with albumin therapy resulted in a prompt, highly significant increase of median flow velocity to 58% of control levels (P=0.013 versus reteplase+saline), which remained significantly higher than the reteplase+saline group at multiple time-points over the subsequent hour.

Conclusions— The beneficial effect of subthrombolytic doses of reteplase on microvascular hemodynamics distal to a cortical arteriolar thrombosis is markedly enhanced by the coadministration of high-dose albumin therapy; these results have important clinical implications for the management of patients with acute ischemic stroke.

Key Words: albumin • thrombolysis • microcirculation • flow velocity • two-photon microscopy • thrombotic stroke