Abstract W MP91: Supply-demand Mismatch Transients Trigger Peri-infarct Depolarizations In Ischemic Penumbra
Background: Peri-infarct depolarizations (PIDs) worsen the outcome of ischemic stroke. Unlike their impact on metabolism and perfusion, triggering factors are virtually unknown. We hypothesized that transient worsening of O2 supply-demand mismatch precipitates a PID in critically hypoperfused penumbra.
Methods: We optically imaged cortical blood flow and oxygenation during distal middle cerebral artery occlusion in mice under full systemic physiological monitoring, and tested whether a transient (5 min) drop in O2 supply (hypotension or hypoxia) or increase in O2 demand (somatosensory cortical activation) can trigger PIDs during acute focal cerebral ischemia.
Results: Transient hypotension (<70 mmHg) or hypoxia (<90 mmHg) triggered a PID 90% of the time (p<0.01). Increasing the O2 demand by functional activation (tactile stimulation) of moderately ischemic cortex (contralesional forepaw or shoulder S1) increased the 5-min incidence of PIDs by approximately five-fold (p=0.001). Cortical oxyhemoglobin levels dropped by 35-40% in the activated S1 immediately before a PID (p=0.004) confirming increased O2 demand. Cortical foci from which PIDs originated during tactile stimulation had 27-32% residual CBF, indicating the presence of a critical range of ischemia vulnerable to PID initiation upon increased demand. Consistently, activation of non-ischemic cortex (hindpaw S1) or severely ischemic cortex (whisker S1) did not significantly increase the PID rate. Both tetrodotoxin (1 μM topical) and normobaric hyperoxia prevented somatosensory triggering of PIDs.
Conclusion: PIDs are triggered upon O2 supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. We propose that minimizing sensory stimulation and hypoxic or hypotensive transients in the early stages of stroke and brain injury would reduce PID incidence and their adverse impact on outcome.
Author Disclosures: D. von Bornstädt: None. J. Seidel: None. M. Houben: None. E. Dilekoz: None. T. Qin: None. N. Sandow: None. K. Eikermann-Haerter: None. D. Boas: None. M. Moskowitz: None. E. Lo: None. J. Dreier: None. J. Woitzik: None. S. Sakadzic: None. C. Ayata: None.
- © 2015 by American Heart Association, Inc.