Department of Biomedical Engineering, Duke University, Durham, North Carolina; Department of Biomedical Engineering, Tsinghua University, Beijing, China.
Department of Anesthesiology, Duke University, Durham, North Carolina.
Anesthesiology. 2023 Aug 1;139(2):173-185. doi: 10.1097/ALN.0000000000004592.
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. The authors 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.
The authors 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.
The authors report three main findings. First, after epinephrine administration, microvessels exhibited severe immediate vasoconstriction (57 ± 6% of baseline at 6 min, 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 min, 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 min, P < 0.0001, n = 6). Third, oxyhemoglobin desaturation did not indicate brain hypoxia; on the contrary, brain tissue oxygen increased after epinephrine application (from 31 ± 11 mmHg 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 desaturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.
在严重难治性低血压、休克或心脏骤停后给予肾上腺素可恢复全身血流和大血管灌注，但可能通过血管收缩导致脑微血管灌注和氧输送恶化。作者假设肾上腺素会引起大脑明显的微血管收缩，重复给药后和老年大脑中的严重程度增加，最终导致组织缺氧。
作者使用多模态体内成像，包括功能光声显微镜、脑组织氧传感和后续组织学评估，研究了健康年轻和老年 C57Bl/6 小鼠静脉内给予肾上腺素对脑微血管血流和氧输送的影响。
作者报告了三个主要发现。首先，给予肾上腺素后，微血管立即出现严重的血管收缩（6 分钟时为基础值的 57±6%，P<0.0001，n=6），持续时间超过动脉血压的同时增加，而较大的血管最初显示出流量增加（6 分钟时为基础值的 108±6%，P=0.02，n=6）。其次，脑内血管中的氧合血红蛋白显著下降，小血管中的下降更为明显（6 分钟时为基础值的 69±8%，P<0.0001，n=6）。第三，氧合血红蛋白饱和度降低并不表明脑缺氧；相反，肾上腺素应用后脑组织氧增加（从基础值的 31±11mmHg 增加到 56±12mmHg，增加 80%，P=0.01，n=12）。在老年大脑中，与年轻大脑相比，微血管收缩不那么明显，但恢复较慢，但组织氧合增加，证实存在相对的高氧血症。
静脉内给予肾上腺素可引起明显的脑微血管收缩、血管内血红蛋白饱和度降低，以及矛盾的是，脑组织氧水平增加，可能是由于通过时间异质性降低所致。
