A cascade model of dynamic cerebral autoregulation

Patient rewarming after hypothermic cardiopulmonary bypass (CPB) has been linked to brain injury after cardiac surgery. In this study, we evaluated whether cooling and then rewarming of body temperature during CPB in adult patients is associated with alterations in cerebral blood flow (CBF)-blood pressure autoregulation. One hundred twenty-seven adult patients undergoing CPB during cardiac surgery had transcranial Doppler monitoring of the right and left middle cerebral artery blood flow velocity. Eleven patients undergoing CPB who had arterial inflow maintained at >35 degrees C served as controls. The mean velocity index (Mx) was calculated as a moving, linear correlation coefficient between slow waves of middle cerebral artery blood flow velocity and mean arterial blood pressure. Intact CBF-blood pressure autoregulation is associated with an Mx that approaches 0. Impaired autoregulation results in an increasing Mx approaching 1.0. Comparisons of time-averaged Mx values were made between the following periods: before CPB (baseline), during the cooling and rewarming phases of CPB, and after CPB. The number of patients in each phase of CPB with an Mx >4.0, indicative of impaired CBF autoregulation, was determined. During cooling, Mx (left, 0.29 +/- 0.18; right, 0.28 +/- 0.18 [mean +/- SD]) was greater than that at baseline (left, 0.17 +/- 0.21; right, 0.17 +/- 0.20; P <or= 0.0001). Mx increased during the rewarming phase of CPB (left, 0.40 +/- 0.19; right, 0.39 +/- 0.19) compared with baseline (P <or= 0.001) and the cooling phase (P <or= 0.0001), indicating impaired CBF autoregulation. After CPB, Mx (left, 0.27 +/- 0.20; right, 0.28 +/- 0.21) was higher than at baseline (left, P = 0.0004; right, P = 0.0003), no different than during the cooling phase, but lower than during rewarming (left, P <or= 0.0001; right, P <or= 0.0005). Forty-three patients (34%) had an Mx >or=0.4 during the cooling phase of CPB and 68 (53%) had an average Mx >or=0.4 during rewarming. Nine of the 11 warm controls had an average Mx >or=0.4 during the entire CPB period. There were 7 strokes and 1 TIA after surgery. All strokes were in patients with Mx >or= 0.4 during rewarming (P = 0.015). The unadjusted odds ratio for any neurologic event (stroke or transient ischemic attack) for patients with Mx >or= 0.4 during rewarming was 6.57 (95% confidence interval, 0.79 to 55.0, P < 0.08). Hypothermic CPB is associated with abnormal CBF-blood pressure autoregulation that is worsened with rewarming. We found a high rate of strokes in patients with evidence of impaired CBF autoregulation. Whether a pressure-passive CBF state during rewarming is associated with risk for ischemic brain injury requires further investigation.

If they are not delivered in a timely fashion, pregnancies complicated by severe intrauterine growth restriction (IUGR) can lead to fetal loss. Conventional fetal well-being tests, including ultrasound measurement of fetal growth rate, biophysical profile, nonstress test, and contraction stress test are used to manage these pregnancies. Some fetuses delivered based on abnormal fetal well-being tests show long-term sequelae. A better understanding of the malfunction of the placenta and its effect on the fetus is desperately required for better management of these cases. We are reporting our experience of 6 such pregnancies followed by fetal middle cerebral artery (MCA) blood flow velocity measurements. There was significant decrease in MCA flow velocities in all of these fetuses compared to normal population (p < 0.05). Reverting to normal values occurred prior to the appearance of abnormal conventional tests, on average 4 days earlier. In other words, normalization of MCA flow velocities was a harbinger of fetal jeopardy. Although our observation includes a small number of patients, there is a potential for use of MCA blood flow velocity measurement to aid us in understanding and managing fetuses with IUGR. This needs to be evaluated in a larger study.

Blood pressure control with glyceryl trinitrate during electroconvulsive therapy in a patient with cerebral aneurysm

The aim of this study was to evaluate the effects of propofol, isoflurane, and sevoflurane on middle cerebral arterial blood flow velocity during open heart surgery, and the relationship between these effects and hemodynamic parameters. Fifty-two patients undergoing coronary artery bypass on cardiopulmonary bypass were divided randomly into 3 groups: the first group received 100 microg x kg(-1) x min(-1) propofol, the other groups received one minimum alveolar concentration of sevoflurane or isoflurane for anesthesia maintenance. Middle cerebral arterial blood flow velocities were measured by transcranial Doppler, and hemodynamics were measured by the thermodilution technique. Middle cerebral arterial blood flow velocities decreased significantly after administration of isoflurane and propofol, but there was no significant difference between the groups. After weaning from cardiopulmonary bypass, cerebral blood flow increased and came close to the value after induction in all groups. The pulsatility index and resistivity index increased significantly only after the propofol infusion, but there was no significant difference between the groups.

A clear surgical field is critical during endoscopic sinus surgery (ESS). Hypotensive anesthesia and cardiac output (CO) may optimize the surgical field; however, evidence of their effect on bleeding and cerebral blood flow is conflicting. The aim of this study was to evaluate the effect of blood pressure (BP) and CO on intraoperative bleeding and middle cerebral artery blood flow velocity (Vmca ) during ESS. This was a prospective randomized controlled trial. Patients undergoing ESS for chronic rhinosinusitis at a tertiary institution in 2013 were randomized to receive BP manipulation using target-controlled noradrenaline infusion during surgery to either their left or right sinuses. The contralateral side in each patient served as control. Bleeding was scored using a 0 to 10 point bleeding assessment scale (BAS, 0-10) and Vmca was measured using transcranial Doppler ultrasonography every 10 minutes or when surgically opportune, and time-matched with BP and CO. Data was analyzed using Bland-Altman methods. A total of 105 time points were collected across a mean arterial pressure (MAP) range of 32 to 118 mmHg. Significant correlations were demonstrated between MAP and Vmca (r = 0.7, p < 0.0001), MAP and BAS (r = 0.50, p < 0.0001), CO and Vmca (r = 0.57, p < 0.0001), and CO and BAS (r = 0.42, p < 0.0001). The best surgical fields were seen at 40 to 59 mmHg MAP. However, MAP below 60 mmHg produced >50% reduction in Vmca in more than 10% of time points. Balancing surgical visibility with organ perfusion remains a challenge. The results of this study show that moderate hypotension significantly improves the surgical field; however reducing BP below 60 mmHg may risk cerebral hypoperfusion.

The cerebrovascular circulation can be assessed non-invasively in man using transcranial doppler (TCD) velocimetry (1). The change in flow velocity pulse wave is proportional to the change in blood flow in that vessel, assuming cross sectional area of the artery studied to be constant. Such changes have been shown to correlate well with changes in cerebral perfusion in response to hypercapnia (3). TCD estimates of cerebral blood flow is increased when subjects performed both physical and cognitive activities (6) or when they were presented with visual stimuli (2). This suggests that TCD is capable of detecting changes in cerebral blood flow which accompany cerebral activity. In this study we have tested the hypothesis that volitionally controlled breathing is accompanied by an increase in middle cerebral artery (MCA) blood flow velocity (bfv) independent of changes in PCO2.

Cerebrovascular Effects of Cilostazol in Patients With Atherosclerotic Disease

We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and would have more influence on blood pressure (BP) and less influence on middle cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv were measured continuously during normoxia and in acute hypoxia (inspired O2 fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O2 fraction, 1.0; n = 12). Dynamic CA was assessed using transfer-function gain, phase, and coherence between mean BP and MCAv. Arterial blood gases were also obtained. In matched volunteers, the same variables were measured during air breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1-2 days after arrival at HA ( approximately 5,400 m, n = 10). In acute hypoxia and hyperoxia, BP was unchanged whereas it was decreased during hyperoxia at HA (-11 +/- 4%; P < 0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute hyperoxia caused MCAv to fall to a greater extent than at HA (-12 +/- 3 vs. -5 +/- 4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the low-frequency range was reduced during acute hypoxia, indicating improvement in CA. In contrast, HA was associated with elevations in transfer-function gain in the very low- and low-frequency range, indicating CA impairment; hyperoxia lowered these elevations by approximately 50% (P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.

We sought to determine whether cerebral autoregulation (CA) is compromised during orthostatic stress superimposed with systemic hypotension. Transient systemic hypotension was produced by deflation of thigh cuffs previously inflated to suprasystolic pressure, combined with or without lower body negative pressure (LBNP). Cardiac output (CO) decreased from a baseline of 5.0+/-0.5 l/min by -8.3+/-1.7, -19.2+/-2.0, and -30.6+/-3.4% during LBNP of -15, -30, and -50 Torr, respectively. Mean arterial pressure (MAP) was maintained during LBNP, despite decreases in systolic and pulse pressures. Middle cerebral arterial blood flow velocity (VMCA) decreased significantly from a baseline of 64+/-3 to 58+/-4 cm/s (-9.7+/-2.4%) at -50 Torr of LBNP. The reduction in VMCA was associated with a decrease in regional cerebral O2 saturation. However, the percent decrease in VMCA was markedly less than that of CO. This suggests that the magnitude of the change in VMCA (an index of cerebral blood flow) is less than would be predicted, given the decrease in CO. Transient systemic hypotension decreased MAP by -21+/-2, -24+/-2, -28+/-3, and -26+/-3% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Likewise, this acute hypotension resulted in decreases in VMCA of -20+/-2, -21+/-2, -24+/-25, and -19+/-2% and regional cerebral O2 saturation of -5+/-1, -6+/-1, -6+/-1, and -7+/-2% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Complete recovery of VMCA to baseline values following transient hypotension (ranging from 5 to 8 s) occurred significantly earlier compared with MAP (from 10 to 12 s). No subjects experienced syncope during acute hypotension. We conclude that CA is preserved during LBNP, superimposed with transient systemic hypotension, despite the decrease in VMCA associated with sustained central hypovolemia in normal healthy individuals. This preserved CA is vital for the prevention of orthostatic syncope.

To the Editor: Subudhi et al1 recently demonstrated that dynamic cerebral autoregulation (CA) became progressively impaired when volunteers were exposed to the hypoxia of simulated high-altitude, although this was unrelated to the onset of neurological symptoms ascribed to acute mountain sickness (AMS). Although their study describes some important findings, the authors’ interpretation of similar studies conducted by our groups2,3 warrants clarification and provides an opportunity to offer complementary insight into alternative mechanisms. The authors discuss deficiencies with the design and interpretation of our findings, thus “…making it difficult to draw conclusions regarding …

Although inhalation anesthetic agents are thought to impair cerebral autoregulation more than intravenous agents, there are few controlled studies in humans. In the first group (n = 24), dynamic autoregulation was assessed from the response of middle cerebral artery blood flow velocity (Vmca) to a transient step decrease in mean arterial blood pressure (MABP). The transient hypotension was induced by rapid deflation of thigh cuffs after inflation for 3 min. In the second group (n = 18), static autoregulation was studied by observing Vmca in response to a phenylephrine-induced increase in MABP. All patients were studied during fentanyl (3 micrograms.kg-1.h-1)/nitrous oxide (70%) anesthesia, followed by, in a randomized manner, isoflurane, desflurane, or propofol in a low dose (0.5 MAC or 100 micrograms.kg-1.min-1) and a high dose (1.5 MAC or 200 micrograms.kg-1.min-1). The dynamic rate of regulation (dROR) was assessed from the rate of change in cerebrovascular resistance (MABP/Vmca) with the blood pressure decreases using computer modeling, whereas the static rate of regulation (sROR) was assessed from the change in Vmca with the change in MABP. Low-dose isoflurane delayed (dROR decreased) but did not reduce the autoregulatory response (sROR intact). Low-dose desflurane decreased both dROR and sROR. During 1.5 MAC isoflurane or desflurane, autoregulation was ablated (both dROR and sROR impaired). Neither dROR nor sROR changed with low- or high-dose propofol. At 1.5 MAC, isoflurane and desflurane impaired autoregulation whereas propofol (200 micrograms.kg-1.min-1) preserved it.

BackgroundThe middle cerebral artery supplies long end-artery branches to perfuse the deep white matter and shorter peripheral branches to perfuse cortical and subcortical tissues. A generalized vasodilatory stimulus such as carbon dioxide not only results in an increase in flow to these various tissue beds but also redistribution among them. We employed a fast step increase in carbon dioxide to detect the dynamics of the cerebral blood flow response.Methodology/Principal FindingsThe study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. We used transcranial ultrasound to measure the time course of middle cerebral artery blood flow velocity in 28 healthy adults. Normoxic, isoxic step increases in arterial carbon dioxide tension of 10 mmHg from both hypocapnic and normocapnic baselines were produced using a new prospective targeting system that enabled a more rapid step change than has been previously achievable. In most of the 28 subjects the responses at both carbon dioxide ranges were characterised by more complex responses than a single exponential rise. Most responses were characterised by a fast initial response which then declined rapidly to a nadir, followed by a slower secondary response, with some showing oscillations before stabilising.Conclusions/SignificanceA rapid step increase in carbon dioxide tension is capable of inducing instability in the cerebral blood flow control system. These dynamic aspects of the cerebral blood flow responses to rapid changes in carbon dioxide must be taken into account when using transcranial blood flow velocity in a single artery segment to measure cerebrovascular reactivity.

We examined the effects of exposure to 10-12 days intermittent hypercapnia [IHC: 5:5-min hypercapnia (inspired fraction of CO(2) 0.05)-to-normoxia for 90 min (n = 10)], intermittent hypoxia [IH: 5:5-min hypoxia-to-normoxia for 90 min (n = 11)] or 12 days of continuous hypoxia [CH: 1,560 m (n = 7)], or both IH followed by CH on cardiorespiratory and cerebrovascular function during steady-state cycling exercise with and without hypoxia (inspired fraction of oxygen, 0.14). Cerebrovascular reactivity to CO(2) was also monitored. During all procedures, ventilation, end-tidal gases, blood pressure, muscle and cerebral oxygenation (near-infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAv) were measured continuously. Dynamic cerebral autoregulation (CA) was assessed using transfer-function analysis. Hypoxic exercise resulted in increases in ventilation, hypocapnia, heart rate, and cardiac output when compared with normoxic exercise (P < 0.05); these responses were unchanged following IHC but were elevated following the IH and CH exposure (P < 0.05) with no between-intervention differences. Following IH and/or CH exposure, the greater hypocapnia during hypoxic exercise provoked a decrease in MCAv (P < 0.05 vs. preexposure) that was related to lowered cerebral oxygenation (r = 0.54; P < 0.05). Following any intervention, during hypoxic exercise, the apparent impairment in CA, reflected in lowered low-frequency phase between MCAv and BP, and MCAv-CO(2) reactivity, were unaltered. Conversely, during hypoxic exercise following both IH and/or CH, there was less of a decrease in muscle oxygenation (P < 0.05 vs. preexposure). Thus IH or CH induces some adaptation at the muscle level and lowers MCAv and cerebral oxygenation during hypoxic exercise, potentially mediated by the greater hypocapnia, rather than a compromise in CA or MCAv reactivity.

The purpose of this investigation was to use combined transcranial cerebral Doppler (TCD) and near-infrared spectroscopy cerebral oxygen saturation (NIRS) during total aortic arch replacement (TAAR) to monitor middle cerebral artery blood flow velocity and regional cerebral oximetry (rSO(2)) changes to provide a clinical basis for protective measures that may decrease injury of the central nervous system. Consecutive 12 adult patients underwent deep hypothermic circulatory arrest (DHCA) and antegrade selective cerebral perfusion (ASCP) during TAAR. A TCD probe was placed at the temporal windows after induction of anesthesia and the NIRS probe placed on the forehead of patients to collect perioperative, intraoperative, and postoperative hemodynamic parameters, and cerebral blood flow (CBF) and rSO(2) during cardiopulmonary bypass (CPB). In this retrospective case series, all patients survived, and there were no postoperative neurologic complications. There was no significant correlation between the mean arterial pressure and rSO(2). The middle cerebral artery mean velocity (VmMCA) and rSO(2) were significantly correlated, and main pump flow significantly correlated with rSO(2). After ASCP, VmMCA, rSO(2), and venous oxygen saturation were significantly lower than before ASCP, but VmMCA and rSO(2) returned to pre-CPB levels postoperatively. After off pump, the flow of ASCP showed a significant positive correlation with VmMCA and rSO(2). During DHCA when ASCP flow was lower than 5 ml/kg/min, TCD could not detect the MCA blood flow signal. When the flow of ASCP was above keeping around 10 ml/kg/min, MCA CBF velocity was maintained and rSO(2) > 45%. The combination of TCD and NIRS can be effective in monitoring brain function during DHCA with ASCP and may provide a guide for decreasing brain injury during the TAAR procedure.

Cerebral blood flow (CBF) increases from rest to ∼60% of peak oxygen uptake (VO(2peak)) and thereafter decreases towards baseline due to hyperventilation-induced hypocapnia and subsequent cerebral vasoconstriction. It is unknown what happens to CBF in older adults (OA), who experience a decline in CBF at rest coupled with a blunted ventilatory response during VO(2peak). In 14 OA (71 ± 10 year) and 21 young controls (YA; 23 ± 4 years), we hypothesized that OA would experience less hyperventilation-induced cerebral vasoconstriction and therefore an attenuated reduction in CBF at VO(2peak). Incremental exercise was performed on a cycle ergometer, whilst bilateral middle cerebral artery blood flow velocity (MCA V (mean); transcranial Doppler ultrasound), heart rate (HR; ECG) and end-tidal PCO(2) (P(ET)CO(2)) were monitored continuously. Blood pressure (BP) was monitored intermittently. From rest to 50% of VO(2peak), despite greater elevations in BP in OA, the change in MCA V(mean) was greater in YA compared to OA (28% vs. 15%, respectively; P < 0.0005). In the YA, at intensities >70% of VO(2peak), the hyperventilation-induced declines in both P(ET)CO(2) (14 mmHg (YA) vs. 4 mmHg (OA); P < 0.05) and MCA V(mean) (-21% (YA) vs. -7% (OA); P < 0.0005) were greater in YA compared to OA. Our findings show (1), from rest-to-mild intensity exercise (50% VO(2peak)), elevations in CBF are reduced in OA and (2) age-related declines in hyperventilation during maximal exercise result in less hypocapnic-induced cerebral vasoconstriction.