Department of Physiology, University of Toronto, Toronto, Canada.
Departments of Anaesthesia and Pain Management, University Health Network, Toronto, Canada.
Physiol Rep. 2022 Oct;10(19):e15472. doi: 10.14814/phy2.15472.
In patients with sickle cell disease (SCD), the delivery of oxygen to the brain is compromised by anemia, abnormal rheology, and steno-occlusive vascular disease. Successful compensation depends on an increase in oxygen supply such as that provided by an increase in cerebral blood flow (CBF). We used magnetic resonance imaging to provide a high-resolution assessment of the ability of SCD patients to respond to a vasoactive stimulus in middle, anterior, and posterior cerebral artery territories for both white and gray matter. Cerebrovascular reactivity (CVR) was measured as the blood oxygen level dependent signal (a surrogate for CBF) response to an increase in the end tidal partial pressure of CO (P CO ). The dynamic aspect of the response was measured as the time constant of the first order response kinetics (tau). To confirm and support these findings we used an alternative examination of the response, transfer function analysis (TFA), to measure the responsiveness (gain), the speed of response (phase), and the consistency of the response over time (coherence). We tested 34 patients with SCD and compared the results to those of 24 healthy controls participants. The results from a three-way ANOVA showed that patients with SCD have reduced CVR (p < 0.001) and lower coherence (p < 0.001) in gray matter and white matter and reduced gain in gray matter only (p < 0.001). In terms of the speed of the response to CO , tau (p < 0.001) and TFA phase (p < 0.001) were increased in SCD patients compared to healthy control subjects. These findings show that the cerebrovascular responsiveness to CO in patients with SCD is both decreased and slowed compared to healthy controls.
在镰状细胞病（SCD）患者中，由于贫血、异常流变学和狭窄闭塞性血管疾病，大脑的氧气输送受到影响。成功的代偿取决于氧气供应的增加，如脑血流量（CBF）的增加。我们使用磁共振成像（MRI）对 SCD 患者在大脑中动脉、前动脉和后动脉区域对血管活性刺激的反应能力进行高分辨率评估，包括白质和灰质。脑血管反应性（CVR）是通过血氧水平依赖信号（CBF 的替代物）来测量的，该信号是对呼气末二氧化碳分压（P CO ）增加的反应。反应的动态方面通过一阶反应动力学的时间常数（tau）来测量。为了证实和支持这些发现，我们使用了另一种反应测量方法——传递函数分析（TFA），来测量反应的响应性（增益）、响应速度（相位）和随时间的响应一致性（相干性）。我们测试了 34 名 SCD 患者，并将结果与 24 名健康对照组进行了比较。三因素方差分析的结果表明，SCD 患者的 CVR 降低（p<0.001），灰质和白质的相干性降低（p<0.001），灰质的增益降低（p<0.001）。就 CO 对反应的速度而言，与健康对照组相比，SCD 患者的 tau（p<0.001）和 TFA 相位（p<0.001）增加。这些发现表明，与健康对照组相比，SCD 患者对 CO 的脑血管反应性降低且速度减慢。
