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.

Abstract

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-microm 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.

• Authors: Hee-Pyoung Park, Anitha Nimmagadda, Richard A DeFazio, Raul Busto, Ricardo Prado, Myron D Ginsberg
• Journal: Stroke (Stroke) Vol. 39 Issue 5 Pg. 1556-62 (May 2008) ISSN: 1524-4628 [Electronic] United States
• PMID: 18323493 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Albumins
• Drug Combinations
• Fibrinolytic Agents
• Recombinant Proteins
• reteplase
• Tissue Plasminogen Activator

Topics

• Albumins (pharmacology, therapeutic use)
• Animals
• Arterioles (drug effects, pathology, physiopathology)
• Brain Ischemia (drug therapy, physiopathology)
• Cerebral Arteries (drug effects, physiopathology, radiation effects)
• Cerebrovascular Circulation (drug effects, physiology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Combinations
• Drug Synergism
• Fibrinolytic Agents (pharmacology, therapeutic use)
• Intracranial Thrombosis (drug therapy, physiopathology)
• Lasers (adverse effects)
• Male
• Microscopy, Confocal (methods)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (pharmacology, therapeutic use)
• Recovery of Function (drug effects, physiology)
• Thrombolytic Therapy (methods)
• Tissue Plasminogen Activator (pharmacology, therapeutic use)
• Treatment Outcome