Impact of transient hypotension on regional cerebral blood flow in humans

Abstract We examined the impact of progressive hypotension with and without hypocapnia on regional extracranial cerebral blood flow (CBF) and intracranial velocities. Participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope to inflict hypotension. End-tidal carbon dioxide was clamped at baseline levels (isocapnic trial) or uncontrolled (poikilocapnic trial). Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities (transcranial Doppler; TCD), heart rate, blood pressure and end-tidal carbon dioxide were obtained continuously. Measurements of internal carotid artery (ICA) and vertebral artery (VA) blood flow (ICA BF and VA BF respectively) were also obtained. Overall, blood pressure was reduced by ∼20 % from baseline in both trials (P < 0.001). In the isocapnic trial, end-tidal carbon dioxide was successfully clamped at baseline with hypotension, whereas in the poikilocapnic trial it was reduced by 11.1 mmHg (P < 0.001) with hypotension. The decline in the ICA BF with hypotension was comparable between trials (−139 + − 82 ml; ∼30 %; P < 0.0001); however, the decline in the VA BF was −28 + − 22 ml/min (∼21 %) greater in the poikilocapnic trial compared with the isocapnic trial (P = 0.002). Regardless of trial, the blood flow reductions in ICA (−26 + − 14 %) and VA (−27 + − 14 %) were greater than the decline in MCA (−21 + − 15 %) and PCA (−19 + − 10 %) velocities respectively (P 0.01). Significant reductions in the diameter of both the ICA (∼5 %) and the VA (∼7 %) contributed to the decline in cerebral perfusion with systemic hypotension, independent of hypocapnia. In summary, our findings indicate that blood flow in the VA, unlike the ICA, is sensitive to changes hypotension and hypocapnia. We show for the first time that the decline in global CBF with hypotension is influenced by arterial constriction in the ICA and VA. Additionally, our findings suggest TCD measures of blood flow velocity may modestly underestimate changes in CBF during hypotension with and without hypocapnia, particularly in the posterior circulation

Extra and intra-cranial blood flow regulation during the cold pressor test:influence of age

We determined how the extra- and intra-cranial circulations respond to generalized sympathetic activation evoked by a cold pressor test (CPT) and whether this was affected by healthy aging. Ten young (23±2 yr; mean±SD) and nine older (66±3 yr) individuals performed a 3-min CPT by immersing the left foot into 0.8±0.3°C water. Common carotid artery (CCA) and internal carotid artery (ICA) diameter, velocity and flow were simultaneously measured (duplex ultrasound), along with middle cerebral artery and posterior cerebral artery mean blood velocity (MCAvmean and PCAvmean), and cardiorespiratory variables. The increases in heart rate (~6 bpm) and mean arterial blood pressure (~14 mmHg) were similar in young and older groups during the CPT (P&lt;0.01 vs. baseline). In the young group, the CPT elicited a ~5% increase in CCA diameter (P&lt;0.01 vs. baseline) and tendency for an increase in CCA flow (~12%; P=0.08); in contrast, both diameter and flow remained unchanged in the older group. Although ICA diameter was not changed during the CPT in either group, ICA flow increased (~8%; P=0.02) during the first minute of the CPT in both groups. While the CPT elicited an increase in MCAvmean and PCAvmean in the young group (by ~20% and ~10%, respectively; P&lt;0.01 vs. baseline), these intra-cranial velocities were unchanged in the older group. Collectively, during the CPT, these findings suggest a differential mechanism(s) of regulation between the ICA compared to the CCA in young individuals, and a blunting of the CCA and intra-cranial responses in older individuals.</p

Shear-Mediated Dilation of the Internal Carotid Artery Occurs Independent of Hypercapnia.

Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial carbon dioxide was recently demonstrated in humans during sustained elevations in CO2 (hypercapnia); however, the relative contributions of CO2 and shear stress to this response remains unclear. We examined the hypothesis that, following a 30-second transient increase in arterial CO2 tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants the partial pressures of end-tidal O2 and CO2, ventilation (pneumotachography), blood pressure (finger-photoplethysmography), heart-rate (electrocardiogram), internal carotid artery flow, diameter and shear stress (high resolution duplex ultrasound) and middle cerebral artery blood velocity (transcranial Doppler) were measured during 4-minute steady state and transient 30-second hypercapnic tests (both +9mmHg CO2). Internal carotid artery dilation was lower in the transient, compared to the steady state hypercapnia (3.3±1.9% vs. 5.3±2.9%, respectively; P<0.03). Increases in internal carotid artery shear stress preceded increases in diameter in both the transient (time: 16.8±13.2s vs. 59.4±60.3s; P<0.01) and steady state (time: 18.2±14.2s vs. 110.3±79.6s; P<0.01) tests. Internal carotid artery dilation was positively correlated with shear rate area under the curve in the transient (r(2)=0.44; P<0.01), but not steady state (r(2)=0.02; P=0.53) trial. Collectively, these results suggest that hypercapnia induces shear-mediated dilation of the internal carotid artery in humans. This study further promotes the application and development of hypercapnia as a clinical strategy for the assessment of cerebrovascular vasodilatory function and health in humans

Cerebrovascular Function in the Large Arteries Is Maintained Following Moderate Intensity Exercise

Exercise has been shown to induce cerebrovascular adaptations. However, the underlying temporal dynamics are poorly understood, and regional variation in the vascular response to exercise has been observed in the large cerebral arteries. Here, we sought to measure the cerebrovascular effects of a single 20-min session of moderate-intensity exercise in the one hour period immediately following exercise cessation. We employed transcranial Doppler (TCD) ultrasonography to measure cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) before, during, and following exercise. Additionally, we simultaneously measured cerebral blood flow (CBF) in the internal carotid artery (ICA) and vertebral artery (VA) before and up to one hour following exercise cessation using Duplex ultrasound. A hypercapnia challenge was used before and after exercise to examine exercise-induced changes in cerebrovascular reactivity (CVR). We found that MCAv and PCAv were significantly elevated during exercise (p = 4.81 × 10-5 and 2.40 × 10-4, respectively). A general linear model revealed that these changes were largely explained by the partial pressure of end-tidal CO2 and not a direct vascular effect of exercise. After exercise cessation, there was no effect of exercise on CBFV or CVR in the intracranial or extracranial arteries (all p &gt; 0.05). Taken together, these data confirm that CBF is rapidly and uniformly regulated following exercise cessation in healthy young males