Abstract WP303: Hypertension Disrupts the Relationship Between Pial Collateral Flow and Tissue Oxygenation During Ischemic Stroke

Abstract

Introduction: Chronic hypertension decreases collateral blood flow through leptomeningeal anastomoses (LMAs) during ischemic stroke, which has been linked to worsened stroke outcome. Given the important relationship between LMA flow, tissue oxygenation and cortical cerebral blood flow (CBF), we characterized the interplay between CBF and tissue oxygenation during the sub-acute progression of ischemia in normotensive Wistar (n=6) and spontaneously hypertensive rats (SHR, n=5). Methods: Transient middle cerebral artery occlusion was used to induce ischemia for 2 hours. Relative change in LMA flow, normalized to initial drop after occlusion, was measured via surface laser Doppler; tissue oxygenation and change in parenchymal CBF were measured using a combined laser Doppler-oxygen sensor placed in the expected cortical peri-infarct region. Recording was done at 400Hz, and data analyzed in 20 second blocks over the first hour of ischemia. Data reported as mean ± SEM, statistical comparisons done via Mann-Whitney tests. Results: CBF through LMAs was significantly higher in Wistars compared to SHR at 60 min of occlusion (156±18% vs 80±4% p<0.05). Pial LMA flow strongly correlated with tissue CBF (Wistar: r=0.91, SHR: r=0.75), which was also greater in Wistars at 60 min compared to SHR (80±14% vs.19±3%, p<0.05). Tissue oxygenation initially dropped below 10mmHg in all animals, increasing in Wistars over the course of ischemia to 22.8±0.34 mmHg at 60 min. However, oxygenation did not recover in SHR (5.9±0.23 mmHg). The relationship between CBF and oxygenation was strongly correlated in Wistar rats with both LMA (r=0.88) and tissue CBF (r=0.88). However, in SHR, oxygenation had an inverse relationship with CBF (LMA: r= - 0.56, tissue CBF r= - 0.37). Conclusion: Under normotensive conditions the relationship between CBF and oxygenation had a strong, linear relationship. However, this relationship was disrupted by chronic hypertension, with LMA and tissue CBF increasing without an increase in tissue oxygenation. This uncoupling was potentially due to cerebrovascular dysfunction and metabolic dysregulation due to chronic hypertension. These findings could be an important consideration for the development of stroke therapeutics in hypertensive patients.