The administration of epinephrine after severe refractory hypotension, shock or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. We hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia.
We investigated the effects of intravenous epinephrine administration in healthy young and aged C57Bl/6 mice on cerebral microvascular blood flow and oxygen delivery using multimodal in vivo imaging, including functional photoacoustic microscopy, brain tissue oxygen sensing, and follow up histologic assessment.
We report 3 main findings. First, after epinephrine administration, microvessels exhibited severe immediate vasoconstriction (57 ± 6% of baseline at 6 minutes, p<0.0001, n = 6) that outlasted the concurrent increase in arterial blood pressure, while larger vessels demonstrated an initial increase in flow (108 ± 6% of baseline at 6 minutes, p = 0.02, n = 6). Second, oxyhemoglobin decreased significantly within cerebral vessels with a more pronounced effect in smaller vessels (microvessels to 69 ± 8% of baseline at 6 minutes, p<0.0001, n = 6). Third, oxyhemoglobin de-saturation did not indicate brain hypoxia; on the contrary, brain tissue oxygen increased after epinephrine application (tissue PO2 from 31 ± 11 at baseline to 56 ± 12 mmHg, 80% increase, p = 0.01, n = 12). In the aged brains, microvascular constriction was less prominent yet slower to recover compared to young brains, but tissue oxygenation was increased, confirming relative hyperoxia.
Intravenous application of epinephrine induced marked cerebral microvascular constriction, intravascular hemoglobin de-saturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.