Albumin therapy improves local vascular dynamics in a rat model of primary microvascular thrombosis

A two-photon laser-scanning microscopy study

Anitha Nimmagadda, Hee Pyoung Park, Ricardo Prado, Myron Ginsberg

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE - 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-μm 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.

Original languageEnglish
Pages (from-to)198-204
Number of pages7
JournalStroke
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2008

Fingerprint

Photons
Confocal Microscopy
Blood Vessels
Albumins
Thrombosis
Lasers
Therapeutics
Hemodynamics
Phase III Clinical Trials
Arterioles
Microcirculation
Brain Ischemia
Vasodilation
Sprague Dawley Rats
Ischemia
Stroke
Observation

Keywords

  • Albumin
  • Flow velocity
  • Microcirculation
  • Rat
  • Thrombotic stroke
  • Two-photon microscopy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)
  • Medicine(all)

Cite this

Albumin therapy improves local vascular dynamics in a rat model of primary microvascular thrombosis : A two-photon laser-scanning microscopy study. / Nimmagadda, Anitha; Park, Hee Pyoung; Prado, Ricardo; Ginsberg, Myron.

In: Stroke, Vol. 39, No. 1, 01.01.2008, p. 198-204.

Research output: Contribution to journalArticle

@article{e41ce6edf3dc45acb935ac4ef623da87,
title = "Albumin therapy improves local vascular dynamics in a rat model of primary microvascular thrombosis: A two-photon laser-scanning microscopy study",
abstract = "BACKGROUND AND PURPOSE - 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-μm 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.",
keywords = "Albumin, Flow velocity, Microcirculation, Rat, Thrombotic stroke, Two-photon microscopy",
author = "Anitha Nimmagadda and Park, {Hee Pyoung} and Ricardo Prado and Myron Ginsberg",
year = "2008",
month = "1",
day = "1",
doi = "10.1161/STROKEAHA.107.495598",
language = "English",
volume = "39",
pages = "198--204",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Albumin therapy improves local vascular dynamics in a rat model of primary microvascular thrombosis

T2 - A two-photon laser-scanning microscopy study

AU - Nimmagadda, Anitha

AU - Park, Hee Pyoung

AU - Prado, Ricardo

AU - Ginsberg, Myron

PY - 2008/1/1

Y1 - 2008/1/1

N2 - BACKGROUND AND PURPOSE - 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-μm 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.

AB - BACKGROUND AND PURPOSE - 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-μm 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.

KW - Albumin

KW - Flow velocity

KW - Microcirculation

KW - Rat

KW - Thrombotic stroke

KW - Two-photon microscopy

UR - http://www.scopus.com/inward/record.url?scp=38149027855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38149027855&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.107.495598

DO - 10.1161/STROKEAHA.107.495598

M3 - Article

VL - 39

SP - 198

EP - 204

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 1

ER -