Abstract 4371214: Cerebral microcirculatory disturbances after experimental cardiac arrest: arterial vasoconstriction and capillary stalling

Abstract

Introduction: Cortical hypoperfusion occurs after cardiac arrest (CA). Microcirculatory disturbances have been detailed post-CA in a pediatric model, and consist of vasoconstriction and capillary stasis (intermittent flow or no-reflow). To date, there are no studies that detailed in vivo the microcirculation post-CA in adult models. We assessed the cortical microcirculation in vivo after CA using multiphoton microscopy. Methods: Three-month-old mice (n=5) underwent anesthesia with isoflurane, tracheal intubation, mechanical ventilation, and arterial and venous catheterization. A 4-mm craniotomy was created over the motor cortex, and a cover glass was cemented onto the skull for visual access to the brain. CA was induced for 8.5 minutes using KCl. Mice were resuscitated with chest compressions and epinephrine. The primary motor cortex was imaged using in vivo multiphoton microscopy at baseline and serially at 5-60 min post-CA. Z-stacks were acquired in 3 μm steps in a 400x400x600µm field-of-view. The diameters of pial and penetrating arterioles was assessed at baseline and at 5, 20, and 60 min after CA from Z stacks. Capillary flow was assessed from time series, where 300 frames were captured at ~3 frames/s. To quantify RBC flow, 30 sec time series were recorded at video rate in the same network of capillaries at baseline and post-CA, and RBC velocity was categorized as normal, intermittent flow or no-reflow. Data were analyzed using MATLAB (R2022a, The MathWorks, Inc., Natick, MA, USA). Results: All mice were resuscitated and survived to 60 min post-CA. Arteriolar vasoconstriction was observed at 20 and 60 min post-CA. The ratio of arteriolar diameters at baseline vs post-CA was 0.98 (1.06 ± 0.26) at 5 min (p=0.2), 0.85 (0.82 ± 0.15) at 20 mins (p<0.05) and 0.61 (0.60 ± 0.14) at 60 mins post-CA. Capillary stalling and stasis was observed post-CA in all imaged mice. Overall, normal flow was seen in 79% of capillaries before CA and 54% capillaries post-CA. Intermittent flow was seen in 7% of capillaries before CA and 16% capillaries post-CA. No-reflow was seen in 14% capillaries before CA and 30% of capillaries post-CA. Conclusion/Significance: We have uncovered cortical microvascular alterations in a clinically relevant model of adult CA in mice that consist of arteriolar vasoconstriction, multifocal capillary stasis (no-reflow) and stalling in cortical capillaries. This model can serve as a platform to assess in vivo vascular targeted therapies after CA.