Department of Anesthesiology and Pain Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
J Appl Physiol (1985). 2024 May 1;136(5):1245-1259. doi: 10.1152/japplphysiol.00858.2023. Epub 2024 Feb 22.
Anemia and renal failure are independent risk factors for perioperative stroke, prompting us to assess the combined impact of acute hemodilutional anemia and bilateral nephrectomy (2Nx) on microvascular brain Po (Po) in a rat model. Changes in Po (phosphorescence quenching) and cardiac output (CO, echocardiography) were measured in different groups of anesthetized Sprague-Dawley rats (1.5% isoflurane, = 5-8/group) randomized to Sham 2Nx or 2Nx and subsequently exposed to acute hemodilutional anemia (50% estimated blood volume exchange with 6% hydroxyethyl starch) or time-based controls (no hemodilution). Outcomes were assessed by ANOVA with significance assigned at < 0.05. At baseline, 2Nx rats demonstrated reduced CO (49.9 ± 9.4 vs. 66.3 ± 19.3 mL/min; = 0.014) and Po (21.1 ± 2.9 vs. 32.4 ± 3.1 mmHg; < 0.001) relative to Sham 2Nx rats. Following hemodilution, 2Nx rats demonstrated a further decrease in Po (15.0 ± 6.3 mmHg, = 0.022). Hemodiluted 2Nx rats did not demonstrate a comparable increase in CO after hemodilution compared with Sham 2Nx (74.8 ± 22.4 vs. 108.9 ± 18.8 mL/min, = 0.003) that likely contributed to the observed reduction in Po. This impaired CO response was associated with reduced fractional shortening (33 ± 9 vs. 51 ± 5%) and increased left ventricular end-systolic volume (156 ± 51 vs. 72 ± 15 µL, < 0.001) suggestive of systolic dysfunction. By contrast, hemodiluted Sham 2Nx animals demonstrated a robust increase in CO and preserved Po. These data support the hypothesis that the kidney plays a central role in maintaining cerebral perfusion and initiating the adaptive increase in CO required to optimize Po during acute anemia. This study has demonstrated that bilateral nephrectomy acutely impaired cardiac output (CO) and microvascular brain Po (Po), at baseline. Following acute hemodilution, nephrectomy prevented the adaptive increase in CO associated with acute hemodilution leading to a further reduction in Po, accentuating the degree of cerebral tissue hypoxia. These data support a role for the kidney in maintaining Po and initiating the increase in CO that optimized brain perfusion during acute anemia.
贫血和肾衰竭是围手术期卒中的独立危险因素，促使我们在大鼠模型中评估急性血液稀释性贫血和双侧肾切除（2Nx）对微血管脑 Po（Po）的综合影响。麻醉 Sprague-Dawley 大鼠（1.5%异氟醚，每组 5-8 只）的 Po（磷光猝灭）和心输出量（CO，超声心动图）变化在不同组中进行了测量，随机分配至假手术 2Nx 或 2Nx 组，随后暴露于急性血液稀释性贫血（50%估计血容量用 6%羟乙基淀粉置换）或基于时间的对照（无血液稀释）。采用方差分析评估结果，显著性水平设定为 < 0.05。在基线时，与假手术 2Nx 大鼠相比，2Nx 大鼠的 CO（49.9±9.4 与 66.3±19.3 mL/min； = 0.014）和 Po（21.1±2.9 与 32.4±3.1 mmHg； < 0.001）降低。血液稀释后，2Nx 大鼠的 Po 进一步降低（15.0±6.3 mmHg， = 0.022）。与假手术 2Nx 大鼠相比，血液稀释后的 2Nx 大鼠 CO 没有出现类似的增加（74.8±22.4 与 108.9±18.8 mL/min， = 0.003），这可能导致观察到的 Po 降低。这种受损的 CO 反应与缩短分数降低（33±9 与 51±5%）和左心室收缩末期容积增加（156±51 与 72±15 µL， < 0.001）有关，提示收缩功能障碍。相比之下，血液稀释后的假手术 2Nx 动物表现出 CO 的显著增加和 Po 的保存。这些数据支持肾脏在维持脑灌注和启动急性贫血期间优化 Po 所需的 CO 适应性增加中发挥核心作用的假设。本研究表明，双侧肾切除术在基线时急性损害心输出量（CO）和微血管脑 Po（Po）。急性血液稀释后，肾切除术阻止了与急性血液稀释相关的 CO 的适应性增加，导致 Po 进一步降低，从而加剧了脑组织缺氧的程度。这些数据支持肾脏在维持 Po 和启动 CO 增加以优化急性贫血期间脑灌注方面的作用。
