Abstract 3448: Moderate Hypertension Increases Potassium Loss from Ischemic Cortex and Reduces Infarct Volume in Experimental Stroke
After experimental focal ischemia, pronounced changes of brain tissue sodium, MAP2, water content, and potassium concentration ([K%]br) occur in the periphery of the ischemic region which we have defined as the ‘Ischemic Edge’ (IE) (Kharlamov et al., JCBFM, 2009: S230). We hypothesize that the lower [K%]br in the IE is related to residual collateral flow and that an increase in this collateral flow will result in a further decrease in [K%]br in the IE.
Focal ischemia was induced by MCA transection and bilateral CCA occlusion in Sprague-Dawley rats (isoflurane, N2O) for 4 h. CBF (% of control) was monitored by laser speckle imaging in three different regions on the stroke side (NC, normal cortex; IE region at the periphery of the ischemic region; and IC, ischemic core) and in corresponding regions of non-lesioned hemisphere. In phenylephrine group (Phe, n=5) mild hypertension (132 mmHg) was maintained by constant (2 h) phenylephrine infusion (0.5 mg/ml, 0.02 ml/m, IV) started at 5 m after ischemia (Shin et al., Stroke, 2008: 1548). In the control group (Con, n=3) saline was similarly infused (blood pressure, 102 mmHg).
The cortical distribution of [K%]br from calibrated images of brain sections histologically stained for K% was analyzed using a “ribbon” tool. CBF and [K%]br over treatment group, side, zone and time were analyzed using SAS Proc Mixed. To assess the loss of K% in the IE region, we determined the IE volume and calculated (V * [K%]) the amount of K% lost for each group.
Moderate hypertension (Phe group) doubled CBF in IC and IE regions of the ischemic hemisphere compared to the Con group (p<0.05) and decreased infarct volume (11.2% vs 6%, p=0.03). Fig. 1 shows the K%-depletion from the IE 4 hr after MCAo. The IE volume is ∼40% of the hemispheric volume and ∼80% of the ischemic region volume (Fig. 1A), the amount of K% lost in the Phe group was x2 that lost in the Con group (Fig. 1B), and was ∼20% of the amount of K% in the hemisphere (Fig. 1C). There were no differences in the minimal amount of K% lost in the central ischemic core, underscoring the importance of collateral flow at the Ischemic Edge.
We suggest that the lower [K%]br in IE in the Phe group results from higher residual collateral flow. These data demonstrate that the IE is a major component of stroke pathology, suggest that moderate hypertension’s effect to reduce infarct volume (Shin et al., Stroke, 2008, 1548) and improve patient outcome (Hillis et al., Cerebrovasc Dis, 2003, 236) is partially based on K%-depletion at the IE, and give support to the importance of K%-loss in ischemic stroke.
Support: NIH NS30839, NS66292 1
- © 2012 by American Heart Association, Inc.