Levine B D, Giller C A, Lane L D, Buckey J C, Blomqvist C G
Department of Internal Medicine, University of Texas, Southwestern Medical Center at Dallas.
Circulation. 1994 Jul;90(1):298-306. doi: 10.1161/01.cir.90.1.298.
Orthostatic syncope is usually attributed to cerebral hypoperfusion secondary to systemic hemodynamic collapse. Recent research in patients with neurocardiogenic syncope has suggested that cerebral vasoconstriction may occur during orthostatic hypotension, compromising cerebral autoregulation and possibly contributing to the loss of consciousness. However, the regulation of cerebral blood flow (CBF) in such patients may be quite different from that of healthy individuals, particularly when assessed during the rapidly changing hemodynamic conditions associated with neurocardiogenic syncope. To be able to interpret the pathophysiological significance of these observations, a clear understanding of the normal responses of the cerebral circulation to orthostatic stress must be obtained, particularly in the context of the known changes in systemic and regional distributions of blood flow and vascular resistance during orthostasis. Therefore, the specific aim of this study was to examine the changes that occur in the cerebral circulation during graded reductions in central blood volume in the absence of systemic hypotension in healthy humans. We hypothesized that cerebral vasoconstriction would occur and CBF would decrease due to activation of the sympathetic nervous system. We further hypothesized, however, that the magnitude of this change would be small compared with changes in systemic or skeletal muscle vascular resistance in healthy subjects with intact autoregulation and would be unlikely to cause syncope without concomitant hypotension.
To test this hypothesis, we studied 13 healthy men (age, 27 +/- 7 years) during progressive lower body negative pressure (LBNP). We measured systemic flow (Qc is cardiac output; C2H2 rebreathing), regional forearm flow (FBF; venous occlusion plethysmography), and blood pressure (BP; Finapres) and calculated systemic (SVR) and forearm (FVR) vascular resistances. Changes in brain blood flow were estimated from changes in the blood flow velocity in the middle cerebral artery (VMCA) using transcranial Doppler. Pulsatility (systolic minus diastolic/mean velocity) normalized for systemic arterial pressure pulsatility was used as an index of distal cerebral vascular resistance. End-tidal PACO2 was closely monitored during LBNP. From rest to maximal LBNP before the onset of symptoms or systemic hypotension, Qc and FBF decreased by 29.9% and 34.4%, respectively. VMCA decreased less, by 15.5% consistent with a smaller decrease in CBF. Similarly, SVR and FVR increased by 62.8% and 69.8%, respectively, whereas pulsatility increased by 17.2%, suggestive of a mild degree of small-vessel cerebral vasoconstriction. Seven of 13 subjects had presyncope during LBNP, all associated with a sudden drop in BP (29 +/- 9%). By comparison, hyperventilation alone caused greater changes in VMCA (42 +/- 2%) and pulsatility but never caused presyncope. In a separate group of 3 subjects, superimposition of hyperventilation during highlevel LBNP caused a further decrease in VMCA (31 +/- 7%) but no change in BP or level of consciousness.
We conclude that cerebral vasoconstriction occurs in healthy humans during graded reductions in central blood volume caused by LBNP. However, the magnitude of this response is small compared with changes in SVR or FVR during LBNP or other stimuli known to induce cerebral vasoconstriction (hypocapnia). We speculate that this degree of cerebral vasoconstriction is not by itself sufficient to cause syncope during orthostatic stress. However, it may exacerbate the decrease in CBF associated with hypotension if hemodynamic instability develops.
直立性晕厥通常归因于全身血流动力学崩溃继发的脑灌注不足。最近对神经心源性晕厥患者的研究表明，直立性低血压期间可能会发生脑血管收缩，损害脑自动调节功能，并可能导致意识丧失。然而，此类患者的脑血流量（CBF）调节可能与健康个体有很大不同，尤其是在与神经心源性晕厥相关的快速变化的血流动力学条件下进行评估时。为了能够解释这些观察结果的病理生理意义，必须清楚了解脑循环对直立应激的正常反应，特别是在已知直立期间全身和局部血流分布及血管阻力变化的背景下。因此，本研究的具体目的是在健康人体不存在系统性低血压的情况下，研究中心血容量逐步减少期间脑循环发生的变化。我们假设由于交感神经系统激活，会发生脑血管收缩且CBF会降低。然而，我们进一步假设，与具有完整自动调节功能的健康受试者的全身或骨骼肌血管阻力变化相比，这种变化的幅度较小，并且在没有伴随低血压的情况下不太可能导致晕厥。
为了验证这一假设，我们在进行渐进性下肢负压（LBNP）期间研究了13名健康男性（年龄，27±7岁）。我们测量了全身血流量（Qc为心输出量；C2H2重呼吸法）、局部前臂血流量（FBF；静脉阻塞体积描记法）和血压（BP；Finapres），并计算了全身（SVR）和前臂（FVR）血管阻力。使用经颅多普勒根据大脑中动脉血流速度（VMCA）的变化估计脑血流量的变化。将经全身动脉压搏动归一化后的搏动性（收缩压减去舒张压/平均速度）用作远端脑血管阻力的指标。在LBNP期间密切监测呼气末PACO2。从静息状态到症状发作或系统性低血压发作前的最大LBNP，Qc和FBF分别下降了29.9%和34.4%。VMCA下降较少，为15.5%，这与CBF较小的下降一致。同样，SVR和FVR分别增加了62.8%和69.8%，而搏动性增加了17.2%，提示存在轻度小血管脑血管收缩。13名受试者中有7名在LBNP期间出现前驱晕厥，均与血压突然下降（29±9%）有关。相比之下，单独过度通气导致VMCA（42±2%）和搏动性的变化更大，但从未导致前驱晕厥。在另一组3名受试者中，在高水平LBNP期间叠加过度通气导致VMCA进一步下降（31±7%），但血压或意识水平无变化。
我们得出结论，在由LBNP引起的健康人体中心血容量逐步减少期间会发生脑血管收缩。然而，与LBNP期间或已知诱导脑血管收缩（低碳酸血症）的其他刺激期间的SVR或FVR变化相比，这种反应的幅度较小。我们推测这种程度的脑血管收缩本身不足以在直立应激期间导致晕厥。然而，如果出现血流动力学不稳定，它可能会加剧与低血压相关的CBF下降。
