O0490 Oct.4: 4:48pm - Epinephrine administration at cardiopulmonary resuscitation worsens cerebral cortical microcirculatory blood flow after experimental pediatric cardiac arrest

Background
Hypoxic ischemic brain injury after cardiac arrest (CA) is the principal factor limiting intact neurological recovery. Epinephrine (EPI), the fundamental therapy that facilitates restoration of spontaneous circulation (ROSC) after CA, has been identified as potentially contributing to brain injury. EPI’s detrimental effects are often attributed to cerebral microvascular constriction, however its effects on cortical microcirculatory blood flow after pediatric asphyxial CA have not been defined.
Hypothesis
Administration of EPI compared to normal saline (NS) produces vasoconstriction and capillary stasis after pediatric asphyxial CA.
Methods
Anesthetized and tracheally intubated immature 16-day old rats had arterial and venous catheters placed. CA of 9.5 min was induced by cessation of mechanical ventilation. Rats were then resuscitated with chest compressions and received EPI or an equal volume of NS at resuscitation (n=8/group). Cortical microcirculatory blood flow was evaluated in vivo using multiphoton laser scanning microscopy through a 5-mm cranial window. We assessed cortical vessel diameters, the presence of capillary stasis (absence of red blood cell flow), and the capillary transit time (plasma flow through the capillaries) from baseline to 60 min post-ROSC. Repeated measures ANOVA and mixed model with bootstrapping for time > 0 was used for statistical analysis.
Results
All rats were successfully resuscitated. CPR time was shorter in EPI-treated rats (34 ± 12s vs 63 ± 26s, EPI vs. NS, p<0.05). Post-ROSC, penetrating arteriolar vasoconstriction was worse in EPI-treated rats (-16.5 ± 4.9% vs 0.5 ± 4.7% at 30 mins post-ROSC, % changed from baseline, EPI vs NS, figure 1c). Capillary diameters were increased in NS-treated rats vs EPI-treated rats (16.9 ± 6.1% vs -2.3 ± 7.0% at 60 mins post-ROSC, % changed from baseline, p<0.05, figure 1e). Capillary stasis was worse in rats treated with EPI vs. NS, (25.9 ± 6.4% vs 14.5 ± 4.7% at 30 mins, and 22.6 ± 3.5% vs 10.5 ± 3.1% at 60 mins, % of capillaries, p<0.05, figure 2a). Capillary plasma transit time was markedly prolonged at 30 mins post-ROSC vs baseline in EPI-treated rats (76.5 ± 12.8% vs 12.8 ± 10.9%, % changed from baseline, EPI vs NS, p<0.05, figure 2b).
Conclusion
EPI administered at resuscitation produced vasoconstriction of the penetrating arterioles and disrupted capillary blood flow: blunted compensatory vasodilation and worsened intra-capillary RBC stasis. The compromised cortical microcirculatory blood flow likely contributes to the worse neurological outcome previously observed in our model in EPI-treated rats. Further studies evaluating therapies to mitigate the deleterious effect of epinephrine on the cortical microcirculation are underway.