Role In Regulation Of Cerebral Blood Flow Research Articles

KATP channels in cerebral hemodynamics: a systematic review of preclinical and clinical studies.

Cumulative evidence suggests that ATP-sensitive potassium (KATP) channels act as a key regulator of cerebral blood flow (CBF). This implication seems to be complicated, since KATP channels are expressed in several vascular-related structures such as smooth muscle cells, endothelial cells and pericytes. In this systematic review, we searched PubMed and EMBASE for preclinical and clinical studies addressing the involvement of KATP channels in CBF regulation. A total of 216 studies were screened by title and abstract. Of these, 45 preclinical and 6 clinical studies were included. Preclinical data showed that KATP channel openers (KCOs) caused dilation of several cerebral arteries including pial arteries, the middle cerebral artery and basilar artery, and KATP channel inhibitor (KCI) glibenclamide, reversed the dilation. Glibenclamide affected neither the baseline CBF nor the baseline vascular tone. Endothelium removal from cerebral arterioles resulted in an impaired response to KCO/KCI. Clinical studies showed that KCOs dilated cerebral arteries and increased CBF, however, glibenclamide failed to attenuate these vascular changes. Endothelial KATP channels played a major role in CBF regulation. More studies investigating the role of KATP channels in CBF-related structures are needed to further elucidate their actual role in cerebral hemodynamics in humans. Systematic review registration: Prospero: CRD42023339278 (preclinical data) and CRD42022339152 (clinical data).

Human brain blood flow and metabolism during isocapnic hyperoxia: the role of reactive oxygen species.

It is unknown whether excessive reactive oxygen species (ROS) production drives the isocapnic hyperoxia (IH)-induced decline in human cerebral blood flow (CBF) via reduced nitric oxide (NO) bioavailability and leads to disruption of the blood-brain barrier (BBB) or neural-parenchymal damage. Cerebral metabolic rate for oxygen (CMR ) and transcerebral exchanges of NO end-products, oxidants, antioxidants and neural-parenchymal damage markers were simultaneously quantified under IH with intravenous saline and ascorbic acid infusion. CBF and were reduced during IH, responses that were followed by increased oxidative stress and reduced NO bioavailability when saline was infused. No indication of neural-parenchymal damage or disruption of the BBB was observed during IH. Antioxidant defences were increased during ascorbic acid infusion, while CBF, , oxidant and NO bioavailability markers remained unchanged. ROS play a role in the regulation of CBF and metabolism during IH without evidence of BBB disruption or neural-parenchymal damage. To test the hypothesis that isocapnic hyperoxia (IH) affects cerebral blood flow (CBF) and metabolism through exaggerated reactive oxygen species (ROS) production, reduced nitric oxide (NO) bioavailability, disturbances in the blood-brain barrier (BBB) and neural-parenchymal homeostasis, 10 men (24± 1years) were exposed to a 10min IH trial (100% O2 ) while receiving intravenous saline and ascorbic acid (AA, 3 g) infusion. Internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF) and total CBF (tCBF, Doppler ultrasound) were determined. Arterial and right internal jugular venous blood was sampled to quantify the cerebral metabolic rate of oxygen (CMR ), transcerebral exchanges (TCE) of NO end-products (plasma nitrite), antioxidants (AA and AA plus dehydroascorbic acid (AA+DA)) and oxidant biomarkers (thiobarbituric acid-reactive substances (TBARS) and 8-isoprostane), and an index of BBB disruption and neuronal-parenchymal damage (neuron-specific enolase; NSE). IH reduced ICABF, tCBF and , while VABF remained unchanged. Arterial 8-isoprostane and nitrite TCE increased, indicating that CBF decline was related to ROS production and reduced NO bioavailability. AA, AA+DA and NSE TCE did not change during IH. AA infusion did not change the resting haemodynamic and metabolic parameters but raised antioxidant defences, as indicated by increased AA/AA+DA concentrations. Negative AA+DA TCE, unchanged nitrite, reductions in arterial and venous 8-isoprostane, and TBARS TCE indicated that AA infusion effectively inhibited ROS production and preserved NO bioavailability. Similarly, AA infusion prevented IH-induced decline in regional and total CBF and re-established . These findings indicate that ROS play a role in CBF regulation and metabolism during IH without evidence of BBB disruption or neural-parenchymal damage.

Non-Linear Characterisation of Cerebral Pressure-Flow Dynamics in Humans.

Cerebral metabolism is critically dependent on the regulation of cerebral blood flow (CBF), so it would be expected that vascular mechanisms that play a critical role in CBF regulation would be tightly conserved across individuals. However, the relationships between blood pressure (BP) and cerebral blood velocity fluctuations exhibit inter-individual variations consistent with heterogeneity in the integrity of CBF regulating systems. Here we sought to determine the nature and consistency of dynamic cerebral autoregulation (dCA) during the application of oscillatory lower body negative pressure (OLBNP). In 18 volunteers we recorded BP and middle cerebral artery blood flow velocity (MCAv) and examined the relationships between BP and MCAv fluctuations during 0.03, 0.05 and 0.07Hz OLBNP. dCA was characterised using project pursuit regression (PPR) and locally weighted scatterplot smoother (LOWESS) plots. Additionally, we proposed a piecewise regression method to statistically determine the presence of a dCA curve, which was defined as the presence of a restricted autoregulatory plateau shouldered by pressure-passive regions. Results show that LOWESS has similar explanatory power to that of PPR. However, we observed heterogeneous patterns of dynamic BP-MCAv relations with few individuals demonstrating clear evidence of a dCA central plateau. Thus, although BP explains a significant proportion of variance, dCA does not manifest as any single characteristic BP-MCAv function.

Dynamic cerebral autoregulation after bed rest: effects of volume loading and exercise countermeasures

This study assessed effects of head-down-tilt (HDT) bed rest on dynamic cerebral autoregulation (CA) in 21 healthy young adults with volume loading and exercise countermeasures. Of these, seven underwent an 18-day bed rest without exercise countermeasures (sedentary group). Volume loading with dextran infusion was performed after bed rest to restore reduced plasma volume to levels before bed rest. In the other 14 subjects, supine cycling during bed rest was performed to preserve cardiac work from before bed rest (exercise group). Volume loading was also performed in a subgroup of these subjects (Ex+Dex, n = 7). Dynamic CA was estimated by transfer function analysis of changes in arterial pressure and cerebral blood flow (CBF) velocity in the very low (VLF, 0.02-0.07 Hz), low (LF, 0.07-0.20 Hz), and high frequency ranges (HF, 0.20-0.35 Hz). After bed rest, transfer function gain was reduced in the sedentary group (VLF, 0.93 ± 0.23 to 0.61 ± 0.23 cm(-1)·s(-1)·mmHg; P = 0.007) and in the exercise group (LF, 1.22 ± 0.43 to 0.94 ± 0.26 cm(-1)·s(-1)·mmHg; P = 0.005, HF, 1.32 ± 0.55 to 1.00 ± 0.32 cm(-1)·s(-1)·mmHg; P = 0.010). After volume loading, transfer function gain increased in the sedentary group but not in the Ex+Dex group. Taken together, these findings suggest that dynamic CA was preserved or improved after HDT bed rest in both sedentary and exercise subjects. Furthermore, increases of transfer function gain with volume loading suggest that changes in plasma volume may play an important role in CBF regulation.

Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity.

The functional role of the alpha-1 adrenergic receptors in cerebral blood flow regulation

Cerebral vasculature is richly innervated by the α-1 adrenergic receptors similar to that of the peripheral vasculature. However, the functional role of the α-1adrenergic receptors in cerebral blood flow (CBF) regulation is yet to be established. The traditional thinking being that during normotension and normocapnia sympathetic neural activity does not play a significant role in CBF regulation. Reports in the past have stated that catecholamines do not penetrate the blood brain barrier (BBB) and therefore only influence cerebral vessels from outside the BBB and hence, have a limited role in CBF regulation. However, with the advent of dynamic measurement techniques, beat-to-beat CBF assessment can be done during dynamic changes in arterial blood pressure. Several studies in the recent years have reported a functional role of the α-1adrenergic receptors in CBF regulation. This review focuses on the recent developments on the role of the sympathetic nervous system, specifically that of the α-1 adrenergic receptors in CBF regulation.

Plasma viscosity and cerebral blood flow

We hypothesized that the response of cerebral blood flow (CBF) to changing viscosity would be dependent on "baseline" CBF, with a greater influence of viscosity during high-flow conditions. Plasma viscosity was adjusted to 1.0 or 3.0 cP in rats by exchange transfusion with red blood cells diluted in lactated Ringer solution or with dextran. Cortical CBF was measured by H(2) clearance. Two groups of animals remained normoxic and normocarbic and served as controls. Other groups were made anemic, hypercapnic, or hypoxic to increase CBF. Under baseline conditions before intervention, CBF did not differ between groups and averaged 49.4 +/- 10.2 ml. 100 g(-1). min(-1) (+/-SD). In control animals, changing plasma viscosity to 1. 0 or 3.0 cP resulted in CBF of 55.9 +/- 8.6 and 42.5 +/- 12.7 ml. 100 g(-1). min(-1), respectively (not significant). During hemodilution, hypercapnia, and hypoxia with a plasma viscosity of 1. 0 cP, CBF varied from 98 to 115 ml. 100 g(-1). min(-1). When plasma viscosity was 3.0 cP during hemodilution, hypercapnia, and hypoxia, CBF ranged from 56 to 58 ml. 100 g(-1). min(-1) and was significantly reduced in each case (P < 0.05). These results support the hypothesis that viscosity has a greater role in regulation of CBF when CBF is increased. In addition, because CBF more closely followed changes in plasma viscosity (rather than whole blood viscosity), we believe that plasma viscosity may be the more important factor in controlling CBF.