Abstract
Background: There is widespread debate regarding the use of albumin in ischemic stroke. We tested the hypothesis that an iso-oncotic solution of albumin (5%), administered earlier after acute ischemic stroke (3 h), could provide neuroprotection without causing kidney damage, compared to a hyper-oncotic albumin (20%) and saline.Objective: To compare the effects of saline, iso-oncotic albumin, and hyper-oncotic albumin, all titrated to similar hemodynamic targets, on the brain and kidney.Methods: Ischemic stroke was induced in anesthetized male Wistar rats (n = 30; weight 437 ± 68 g) by thermocoagulation of pial blood vessels of the primary somatosensory, motor, and sensorimotor cortices. After 3 h, animals were anesthetized and randomly assigned (n = 8) to receive 0.9% NaCl (Saline), iso-oncotic albumin (5% ALB), and hyper-oncotic albumin (20% ALB), aiming to maintain hemodynamic stability (defined as distensibility index of inferior vena cava <25%, mean arterial pressure >80 mmHg). Rats were then ventilated using protective strategies for 2 h. Of these 30 animals, 6 were used as controls (focal ischemic stroke/no fluid).Results: The total fluid volume infused was higher in the Saline group than in the 5% ALB and 20% ALB groups (mean ± SD, 4.3 ± 1.6 vs. 2.7 ± 0.6 and 2.6 ± 0.5 mL, p = 0.03 and p = 0.02, respectively). The total albumin volume infused (g/kg) was higher in the 20% ALB group than in the 5% ALB group (1.4 ± 0.6 vs. 0.4 ± 0.2, p < 0.001). Saline increased neurodegeneration (Fluoro-Jade C staining), brain inflammation in the penumbra (higher tumor necrosis factor-alpha expression), and blood-brain barrier damage (lower gene expressions of claudin-1 and zona occludens-1) compared to both iso-oncotic and hyper-oncotic albumins, whereas it reduced the expression of brain-derived neurotrophic factor (a marker of neuroregeneration) compared only to iso-oncotic albumin. In the kidney, hyper-oncotic albumin led to greater damage as well as higher gene expressions of kidney injury molecule-1 and interleukin-6 than 5% ALB (p < 0.001).Conclusions: In this model of focal ischemic stroke, only iso-oncotic albumin had a protective effect against brain and kidney damage. Fluid therapy thus requires careful analysis of impact not only on the brain but also on the kidney.
Highlights
In ischemic stroke, maintenance of appropriate systemic perfusion is an important therapeutic goal [1]
For achievement of the same hemodynamic targets, the total volume of fluid infused was higher in the Saline group than in 5% ALB and 20% ALB (p = 0.03 and p = 0.02, respectively)
The total amount of albumin infused normalized by body weight (g/kg) in the 5% ALB group was lower than in the 20% ALB (0.42 ± 0.22 vs. 1.42 ± 0.56, p < 0.001)
Summary
Maintenance of appropriate systemic perfusion is an important therapeutic goal [1]. The ALIAS II trial, which compared hyper-oncotic albumin (25%) with an equivalent volume of isotonic saline infusion within 5 h after onset of clinical signs of acute ischemic stroke, was stopped prematurely for futility [9]. Based on the foregoing, we tested the hypothesis that an iso-oncotic solution of albumin (5%), administered earlier after acute ischemic stroke (3 h), could provide neuroprotection without causing kidney damage, compared to a hyper-oncotic albumin (20%) and saline. The effects of saline, 5% albumin, and 20% albumin were evaluated on neurodegeneration, blood-brain barrier permeability, as well as brain and kidney damage in experimental focal ischemic stroke. We tested the hypothesis that an iso-oncotic solution of albumin (5%), administered earlier after acute ischemic stroke (3 h), could provide neuroprotection without causing kidney damage, compared to a hyper-oncotic albumin (20%) and saline
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