Changes In Arterial Blood Pressure Research Articles

Influence of Blood Pressure Reduction on Pulse Wave Velocity in Primary Hypertension: A Meta-Analysis and Comparison With an Acute Modulation of Transmural Pressure.

Increased arterial stiffness and pulse wave velocity (PWV) of the aorta and large arteries impose adverse hemodynamic effects on the heart and other organs. Antihypertensive treatment reduces PWV, but it is unknown whether this results from an unloading of stiffer elements in the arterial wall or is due to an alternate functional or structural change that might differ according to class of antihypertensive drug. We performed a systematic review and meta-analysis of the effects of different antihypertensive drug classes and duration of treatment on PWV with and without adjustment for change in mean arterial blood pressure (BP; study 1) and compared this to the change in PWV after an acute change in transmural pressure, simulating an acute change in BP (study 2). A total of 83 studies involving 6200 subjects were identified. For all drug classes combined, the reduction of PWV was 0.65 (95% CI, 0.46-0.83) m/s per 10 mm Hg reduction in mean arterial BP, a change similar to that induced by an acute change in transmural pressure in a group of hypertensive subjects. When adjusted for change in mean arterial BP, the reduction in PWV after treatment with beta-blockers or diuretics was less than that after treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists or calcium channel antagonists. Reduction in PWV after antihypertensive treatment is largely explained by the reduction in BP, but there are some BP-independent effects. These might increase over time and contribute to better outcomes over the long term, but this remains to be demonstrated in long-term clinical trials.

Hemodynamic effects of withholding vs. continuing angiotensin II receptor blockers on the day of prone positioning spinal surgery in elderly patients.

The hemodynamic effects of withholding vs. continuing angiotensin II receptor blockers (ARBs) before surgery in elderly patients undergoing spinal surgery in a prone position during anesthesia induction to skin incision are still unknown. In this prospective study, 80 patients undergoing spinal surgery in a prone position with general anesthesia, aged 60-79 years, American Society of Anesthesiologists (ASA) II or III, were enrolled. Patients who had ARBs only in their preoperative medication list were randomly divided into two groups at a 1:1 ratio: In Group A, ARBs were continued on the morning of surgery, while in Group B, they were withhold. Norepinephrine was infused to maintain the blood pressure at the baseline level of ±20% during anesthesia induction in all patients. The primary outcome was the consumption of norepinephrine in each group from anesthesia induction to skin incision. The secondary outcomes include changes in invasive arterial blood pressure and heart rate, the fluid infusion volumes, the amounts of anesthetic drugs, and the total time from induction to skin incision. There were no significant differences in the demographics, the fluid infusion volumes, the amounts of anesthetic drugs, the total time from induction to skin incision, and hemodynamics at different time points (p > 0.05), while significant differences were found in norepinephrine consumption between the two groups (p < 0.001). Compared with Group B, the consumption of norepinephrine increased significantly in Group A (93.3 ± 29.8 vs. 124.1 ± 38.7 μg, p = 0.000). In addition, the same trend was illustrated in the pumping rate of norepinephrine between Group B (0.04 ± 0.01 μg·kg-1·min-1) and Group A (0.06 ± 0.02 μg·kg-1·min-1) (p = 0.004). Our study conducted in elderly patients with hypotension undergoing prone spinal surgery demonstrated a greater pumping rate of norepinephrine during anesthesia induction in patients with ARBs continuing before surgery than those withholding, indicating that it was more difficult to maintain hemodynamic stability.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=141081, ChiCTR2100053583.

The impact of a single high-fat meal on indices of cerebrovascular function &amp; health

High-fat diets contribute to elevated risk for cardiovascular, cerebrovascular, metabolic, and neurocognitive diseases with reduced vascular health being a contributing factor. It is well documented that a single high-fat meal (HFM) reduces peripheral vascular function. Despite the elevated risk for/prevalence of cerebrovascular and neurocognitive disease with a high-fat diet, the impact of a single HFM on cerebrovascular function/health is less known. Cerebrovascular pulsatility index (PI) (measure of cerebral vascular stiffness) and cerebral autoregulation (ability of the cerebral vasculature to maintain constant blood flow during changes in arterial blood pressure) are indices of cerebral vascular function/health that are impaired in populations with elevated disease risk. To our knowledge, the impact of a HFM on these indices have not been studied. Accordingly, this study tested the hypothesis that a single HFM will blunt cerebrovascular function/health as indexed by increased PI and transfer function gain. Methods: Fifteen individuals (13 male; age: 28±11yr; BMI: 24±4 kg/m²) participated. Measures were made before and 2hr post-consumption of a HFM (990 kcal, 55g fat, 89g CHO, 35 g protein, 2120 mg sodium) which was purchased from McDonald’s. The HFM consisted of the following: 1 Sausage Biscuit, 1 Egg McMuffn, 2 hash browns, and 1 bottle of water. Continuous measures of beat-to-beat blood pressure and middle cerebral artery blood velocity (MCAV) were obtained during a minimum of 6-min quiet supine rest. Pulsatility index (measure of cerebrovascular stiffness) was calculated as MCAVsystolic − MCAVdiastolic / MCAVmean. Cerebral autoregulation was calculated as transfer function gain between spontaneous beat-to-beat changes in mean blood pressure and MCAVmean. Results: Cerebrovascular stiffness (PI) was increased following the HFM (pre: 0.81±0.12, post: 0.92±0.15; p&lt;0.001). Cerebrovascular autoregulation indexed as transfer function gain was elevated following the HFM in the very low, low, and high frequency ranges ( p=0.01 for all). Pulsatility index and transfer function gain were correlated in the low frequency range before (R=0.77, p&lt;0.01) and after (R=0.64, p=0.02) the HFM. Conclusion: These preliminary data indicate that a single HFM reduces indices of cerebral vascular function/health. Lastly, there is a positive relationship between PI and transfer function gain. Future work will continue to build upon these findings in a larger data set and will consider the impact of long-term exposure to a traditional HFM diet. Funding: The University of Texas at Arlington College of Nursing and Health Innovation and Institutional Start up Funds to Dr. Brothers. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dysfunction of M channels in the insular cortex is involved in pathogenesis of primary hypertension

Heightened sympathetic nerve activity is critically involved in the pathogenesis of primary hypertension. However, the sources driving increased sympathetic vasomotor tone remain unclear. The posterior insular cortex (PIC) is a brain region involved in regulating blood pressure and sympathetic tone. Neurons in the PIC project to the rostral ventrolateral medulla (RVLM), a key brain stem region in regulating sympathetic nerve activity and blood pressure. The non-inactivating voltage-dependent K+ channels, M channels (Kv7/KCNQ channel family) encoded by KCNQ2/3 genes, play a unique role in stabilizing the neuronal membrane potential and regulating neuronal excitability. Here, we determined if the M channel activity of neurons in the PIC is altered in a primary hypertension. Compared with Wistar-Kyoto (WKY) rats, the mRNA and protein expression levels of Kv7.2/Kv7.3 in the PIC tissue were significantly reduced in spontaneously hypertensive rats (SHRs). Microinjection of M channel blocker 10, 10-bis (4-pyridinylmethyl)-9(10H)-anthracnose (XE-991) into the PIC increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized WKY rats, while induced minimal changes of ABP and RSNA in SHRs. M currents recorded from PIC neurons in brain slices labeled by retrograde tracer, Fluospheres, injected into the RVLM were significantly smaller in SHRs than in WKY rats. Furthermore, bath application of specific M channel blocker XE-991 increased the firing rate of PIC-RVLM output neurons in WKY rats while caused a minimal increase in firing rate of PIC-RVLM output neurons in SHRs. In addition, M currents recorded from PIC-RVLM output neurons in SHRs were significantly smaller than those recorded from WKY rats. These data suggest that M channel activity is diminished in PIC-RVLM output neurons in SHRs, and the diminished Kv7 channel activity contributes to elevated sympathetic outflow in primary hypertension. This novel information provides new a mechanistic insight into the pathogenesis of neurogenic hypertension. Supported by grants from National Institutes of Health (HL139523, HL142133, and HL159157 to DPL). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A retrospective case-control study evaluating systemic blood pressure and heart rate in dogs with brain herniation under general anesthesia

ObjectiveTo examine whether increased systemic arterial blood pressure (ABP) and decreased heart rate (HR) under inhalant anesthesia were suggestive of the Cushing reflex (CR) in dogs with neurological diseases based on magnetic resonance imaging (MRI) findings. Study designRetrospective case-control studyAnimals or Animal population: A sample of 137 client owned dogs admitted to two veterinary teaching hospitals for diagnosis and patient care due to suspected intracranial disease from 2005–2020. All dogs underwent general anesthesia for MRI of the brain. MethodsBased on MRI study reports, dogs were divided into three study groups: dogs with suspected brain herniation, dogs with an abnormal MRI finding but without suspicion of herniation, or dogs with structurally unremarkable brains (control). Initial evaluation by an anesthesiologist resulted in 58 cases selected for further review based on suspicion of having intracranial hypertension, as indicated by ABP and HR changes under anesthesia. Anesthetic records were randomized and independently reviewed by three board certified anesthesiologists blinded to MRI diagnosis who allocated each dog into one of three groups: (1) likely to have CR, (2) unlikely to have CR, or (3) insufficient data for determination. ResultsOf the 58 cases evaluated, 9 cases were considered likely to have CR and 48 were considered unlikely to have CR. In one case, the anesthesiologists were unable to determine whether CR occurred. Of the 9 dogs with likely CR, 3 had an MRI diagnosis of intracranial herniation. The remaining 6 dogs suspected of CR belonged to the normal brain group. Conclusions and Clinical RelevanceABP and HR changes associated with CR are not reliably associated with brain herniation in dogs undergoing general anesthesia.

Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury.

Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (p < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (p = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (p = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n = 11), whereas others responded minimally (<0.20 L/min/%, n = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.

Dynamic cerebral autoregulation is governed by two time constants: Arterial transit time and feedback time constant.

Dynamic cerebral autoregulation (dCA) is the mechanism that describes how the brain maintains cerebral blood flow approximately constant in response to short-term changes in arterial blood pressure. This is known to be impaired in many different pathological conditions, including ischaemic and haemorrhagic stroke, dementia and traumatic brain injury. Many different approaches have thus been used both to analyse and to quantify this mechanism in a range of healthy and diseased subjects, including data-driven models (in both the time and the frequency domain) and biophysical models. However, despite the substantial body of work on both biophysical models and data-driven models of dCA, there remains little work that links the two together. One of the reasons for this is proposed to be the discrepancies between the time constants that govern dCA in models and in experimental data. In this study, the processes that govern dCA are examined and it is proposed that the application of biophysical models remains limited due to a lack of understanding about the physical processes that are being modelled, partly due to the specific model formulation that has been most widely used (the equivalent electrical circuit). Based on the analysis presented here, it is proposed that the two most important time constants are arterial transit time and feedback time constant. It is therefore time to revisit equivalent electrical circuit models of dCA and to develop a more physiologically realistic alternative, one that can more easily be related to experimental data. KEY POINTS: Dynamic cerebral autoregulation is governed by two time constants. The first time constant is the arterial transit time, rather than the traditional 'RC' time constant widely used in previous models. This arterial transit time is approximately 1s in the brain. The second time constant is the feedback time constant, which is less accurately known, although it is somewhat larger than the arterial transit time. The equivalent electrical circuit model of dynamic cerebral autoregulation should be replaced with a more physiologically representative model.

Impaired cerebral autoregulation detected in early prevasospasm period is associated with unfavorable outcome after spontaneous subarachnoid hemorrhage: an observational prospective pilot study

BackgroundSubarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes.MethodsThe pilot observational study included 29 SAH patients whose CA status was estimated 2–3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2–3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device.ResultsStatistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p < 0.001). Early assessment of baroreflex sensitivity (BRS) during the deflation cycle showed statistically significant differences between the DCI and non-DCI patient groups (p = 0.039).ConclusionsA relatively small delay of ∆TCBFV <1.6 s between CBFV(t) and ABP(t) waves could be an early warning sign associated with unfavorable outcomes in SAH patients. The BRS during boot deflation can be used as a biomarker for the prediction of DCI.Trial registrationClinicalTrials.gov Identifier: NCT06028906. Registered 31 August 2023 - Retrospectively registered, https://www.clinicaltrials.gov/study/NCT06028906.

Comparison Between Erector Spinae Plane Block versus Serratus Anterior Plane Block Regarding Analgesia and Stress Response After Modified Radical Mastectomy: Randomized Controlled Trial.

Modified radical mastectomy (MRM) is the primary surgical treatment for breast cancer, yet it leads to significant postoperative pain. This randomized controlled trial evaluates the effects of an erector spinae plane block (ESPB) versus a serratus anterior plane block (SAPB) on post-MRM pain management and stress response reduction. Sixty individuals scheduled for unilateral MRM under general anesthesia from October 2021 to October 2022 were divided into three groups. Group A comprised 20 patients who received ultrasound-guided ESPB (20 mL of 0.25% bupivacaine). Group B included 20 patients who received ultrasound-guided SAPB (20 mL of 0.25% bupivacaine). Group C was treated with intravenous morphine based on pain scores. Anesthesia was induced using 2 μg/kg of fentanyl and 2 - 3 mg/kg of propofol. The study compared the three groups regarding pain scores using a numerical rating scale, serum cortisol levels, total fentanyl, and morphine consumption, changes in mean arterial blood pressure (MAP) and heart rate (HR) during surgery, and the occurrence of postoperative complications. Statistically significant reductions in pain scores were observed in group A compared to groups B and C. Moreover, group A exhibited a significant decrease in postoperative morphine consumption, serum cortisol levels 1 hour post-surgery (P = 0.021), MAP, and postoperative vomiting and nausea compared to group B. Furthermore, groups A and B showed statistically significant improvements in all parameters compared to group C. The study demonstrates that ESPB provides superior analgesic effects compared to SAPB in patients undergoing MRM, with reduced morphine use and lower postoperative cortisol levels. Both blocks offer more effective pain control than intravenous morphine alone.

Social network enhanced behavioral interventions for diabetes and obesity: A 3 arm randomized trial with 2 years follow-up in Jordan.

While obesity and diabetes are rising pandemics, few low-cost and effective prevention and management strategies exist, especially in the Middle East. Nearly 20% of adults in Jordan suffer from diabetes, and over 75% are overweight or obese. Social network-based programs have shown promise as a viable public health intervention strategy to address these growing crises. We evaluated the effectiveness of the Microclinic Program (MCP) via a 6-month multi-community randomized trial in Jordan, with follow-up at 2 years. The MCP leverages existing social relationships to propagate positive health behaviors and information. We recruited participants from 3 community health centers in Amman, Jordan. Participants were eligible for the study if they had diabetes, pre-diabetes, or possessed ≥1 metabolic risk factor along with a family history of diabetes. We randomized participants into three trial arms: (A Group) received the Full MCP with curriculum-activated social network interactions; (B Group) received Basic MCP educational sessions with organic social network interactions; or (C Group-Control) received standard care coupled with active monitoring and parallel screenings. Groups of individuals were randomized as units in a 3:1:1 ratio, with resulting group sizes of n = 540, 186, and 188 in arms A, B, and C, respectively. We assessed the overall changes in body weight, fasting glucose, hemoglobin A1c (HbA1c) and mean arterial blood pressure between study arms in multiple evaluations across 2 years (including at 6-months and 2-years follow-up). We investigated the effectiveness of Full and Basic MCP social network interventions using multilevel models for longitudinal data with hierarchical nesting of individuals within MCP classrooms, within community centers, and within temporal cohorts. We observed significant overall 2-year differences between all 3 groups for changes in body weight (P = 0.0003), fasting blood glucose (P = 0.0015), and HbA1c (P = 0.0004), but not in mean arterial blood pressure (P = 0.45). However, significant changes in mean arterial pressure were observed for Full MCP versus controls (P = 0.002). Weight loss in the Full MCP exceeded (-0.97 kg (P<0.001)) the Basic MCP during the intervention. Furthermore, both Full and Basic MCP yielded greater weight loss compared to the control group at 2 years. The Full MCP also sustained a superior fasting glucose change over 2 years (overall P<0.0001) versus the control group. For HbA1c, the Full MCP similarly led to greater 6-month reduction in HbA1c versus the control group (P<0.001), with attenuation at 2 years. For mean arterial blood pressure, the Full MCP yielded a greater drop in blood pressure versus control at 6 months; with attenuation at 2 years. These results suggest that activated social networks of classroom interactions can be harnessed to improve health behaviors related to obesity and diabetes. Future studies should investigate how public health policies and initiatives can further leverage social network programs for greater community propagation. Trial registration. ClinicalTrials.gov Identifier: NCT01818674.

Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure.

Optimization of the highly potent and selective, yet metabolically unstable and poorly soluble hRXFP1 agonist AZ7976 led to the identification of the clinical candidate, AZD5462. Assessment of RXFP1-dependent cell signaling demonstrated that AZD5462 activates a highly similar panel of downstream pathways as relaxin H2 but does not modulate relaxin H2-mediated cAMP second messenger responsiveness. The therapeutic potential of AZD5462 was assessed in a translatable cynomolgus monkey heart failure model. Following 8 weeks of treatment with AZD5462, robust improvements in functional cardiac parameters including LVEF were observed at weeks 9, 13, and 17 without changes in heart rate or mean arterial blood pressure. AZD5462 was well tolerated in both rat and cynomolgus monkey and has successfully completed phase I studies in healthy volunteers. In summary, AZD5462 is a small molecule pharmacological mimetic of relaxin H2 signaling at RXFP1 and holds promise as a potential therapeutic approach to treat heart failure patients.

Retraction Note: Gastric distension causes changes in heart rate and arterial blood pressure by affecting the crosstalk between vagal and splanchnic systems in anesthetised rats.

Retraction Note: Gastric distension causes changes in heart rate and arterial blood pressure by affecting the crosstalk between vagal and splanchnic systems in anesthetised rats.

Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin II type 2 receptor agonist.

Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open-label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra-arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 μg/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 μg/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra-arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3-200 μg/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra-arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.

Cerebral autoregulation derived blood pressure targets in elective neurosurgery.

Poor postoperative outcomes may be associated with cerebral ischaemia or hyperaemia, caused by episodes of arterial blood pressure (ABP) being outside the range of cerebral autoregulation (CA). Monitoring CA using COx (correlation between slow changes in mean ABP and regional cerebral O2 saturation-rSO2) could allow to individualise the management of ABP to preserve CA. We aimed to explore a continuous automated assessment of ABPOPT (ABP where CA is best preserved) and ABP at the lower limit of autoregulation (LLA) in elective neurosurgery patients. Retrospective analysis of prospectively collected data of 85 patients [median age 60 (IQR 51-68)] undergoing elective neurosurgery. ABPBASELINE was the mean of 3 pre-operative non-invasive measurements. ABP and rSO2 waveforms were processed to estimate COx-derived ABPOPT and LLA trend-lines. We assessed: availability (number of patients where ABPOPT/LLA were available); time required to achieve first values; differences between ABPOPT/LLA and ABP. ABPOPT and LLA availability was 86 and 89%. Median (IQR) time to achieve the first value was 97 (80-155) and 93 (78-122) min for ABPOPT and LLA respectively. Median ABPOPT [75 (69-84)] was lower than ABPBASELINE [90 (84-95)] (p < 0.001, Mann-U test). Patients spent 72 (56-86) % of recorded time with ABP above or below ABPOPT ± 5mmHg. ABPOPT and ABP time trends and variability were not related to each other within patients. 37.6% of patients had at least 1 hypotensive insult (ABP < LLA) during the monitoring time. It seems possible to assess individualised automated ABP targets during elective neurosurgery.

Posture-Induced Changes in Intraocular, Orbital, Cranial, Jugular Vein, and Arterial Pressures in a Porcine Model.

The purpose of this study was to determine posture-induced changes in arterial blood pressure (ABP), intraocular pressure (IOP), orbital pressure (Porb), intracranial pressure (ICP), and jugular vein pressure (JVP) at various tilt angles in an in vivo pig. Anesthetized and ventilated pigs (n = 8) were placed prone on a tiltable operating table. ABP, IOP, Porb, ICP, and JVP were monitored while the table was tilted at various angles between 15degrees head up tilt (HUT) and 25degrees head down tilt (HDT) either in stepwise changes (5 degrees per step) or continuously. The mean pressure was calculated from digitized pressure waveforms from each compartment. For stepwise changes in tilt angle the pressures were plotted as a function of tilt angle. For continuous tilt changes, the pressures were plotted as a function of time. In the case of stepwise changes, ABP remained relatively stable whilst IOP, Porb, ICP, and JVP demonstrated significant differences between most angles (typically P < 0.0001). The difference was greatest for IOP (P < 0.0001) where the average IOP increased from 13.1 ± 1.23mm Hg at 15degrees HUT to 46.3 ± 2.03mm Hg at 25 degrees HDT. The relationship between pressure and tilt angle was almost linear for ICP and JVP, and sigmoidal for IOP and Porb. Interestingly, the effect of changes in tilt angle occurred very rapidly, within a few seconds. Our results in a pig model demonstrate that changes in posture (tilt angle) induce rapid changes in IOP, Porb, ICP, and JVP, with IOP affected most severely.

Slow‐breathing induced hypocapnia mitigates deficit of vasoreactivity measured in patients with cognitive impairment

AbstractBackgroundA multi‐center study in Los Angeles (USC), Kansas City (KUMC) and Dallas (UT‐SWMC) has been quantifying the dynamics of CO2 vasoreactivity in MCI/AD patients and cognitively normal controls under spontaneous resting conditions. The goal is to develop effective vasoreactivity physio‐markers for early diagnosis of MCI and pre‐clinical AD, based on previous findings of significantly reduced vasoreactivity in MCI patients [Marmarelis et al., J. Alzh. Dis. 56:89‐105, 2017]. Here, we report on the effects of slow‐paced breathing upon these physio‐markers.MethodSpontaneous changes in arterial blood pressure (ABP), end‐tidal CO2 (etCO2), and cerebral blood flow velocity (CBFV) in middle cerebral arteries were recorded under resting conditions over two 6‐8 min sessions, separated by session of slow‐paced breathing (6 breaths/minute), in 47 MCI and 25 AD patients and 58 age‐matched cognitively normal controls. Using our novel methodology, we obtained predictive models of the dynamic effects of ABP and etCO2 upon CBFV using the universal convolutional form of linear dynamic models, which are defined by the respective “kernels” estimated from time‐series data. The etCO2‐to‐CBFV kernel is used to compute indices (physio‐markers) that quantify the vasoreactivity in each participant.ResultThe vasoreactivity index for each participant is computed from the integrated etCO2‐to‐CBFV kernel as the time‐average over the first 30 sec. The average kernels for patients and controls are shown in Figures 1‐2 for the two sessions respectively. Note the smaller kernel values for patients – while the difference is reduced after slow‐paced breathing. The obtained vasoreactivity indices are significantly smaller for 72 patients (MCI and AD taken together) vs 58 controls for the first session [p = 0.018; mean (SD): 0.057 (0.539) vs 0.424 (1.076)] but NOT for the session after slow‐paced breathing [p = 0.237; mean (SD): 0.193 (0.731) vs 0.361 (0.863)]. Average etCO2 was lower after paced‐breathing [p = 10−6; mean (SD): 36.23 (6.18) vs 33.44 (6.36)].ConclusionQuantitative analysis of cerebral CO2 vasoreactivity under resting spontaneous conditions in 72 MCI/AD patients vs 58 age‐matched controls, before and after slow‐paced breathing, revealed that the significant vasoreactivity deficit in MCI/AD patients is mitigated (at least temporarily) after slow‐paced breathing. This effect may be due to observed hypocapnia induced by slow‐paced breathing.

Static autoregulation in humans.

The process by which cerebral blood flow (CBF) remains approximately constant in response to short-term variations in arterial blood pressure (ABP) is known as cerebral autoregulation. This classic view, that it remains constant over a wide range of ABP, has however been challenged by a growing number of studies. To provide an updated understanding of the static cerebral pressure-flow relationship and to characterise the autoregulation curve more rigorously, we conducted a comprehensive literature research. Results were based on 143 studies in healthy individuals aged 18 to 65 years. The mean sensitivities of CBF to changes in ABP were found to be 1.47 ± 0.71%/% for decreased ABP and 0.37 ± 0.38%/% for increased ABP. The significant difference in CBF directional sensitivity suggests that cerebral autoregulation appears to be more effective in buffering increases in ABP than decreases in ABP. Regression analysis of absolute CBF and ABP identified an autoregulatory plateau of approximately 20 mmHg (ABP between 80 and 100 mmHg), which is much smaller than the widely accepted classical view. Age and sex were found to have no effect on autoregulation strength. This data-driven approach provides a quantitative method of analysing static autoregulation that can be easily updated as more experimental data become available.

Human whole-brain models of cerebral blood flow and oxygen transport

The cerebral vasculature plays a critical role in the transport of oxygen and other nutrients to brain tissue. However, the size, complexity, and paucity of detailed anatomical information of this system makes understanding cerebral behaviour in normal and pathological conditions, as well as its response to stimuli, highly challenging. Whole-brain mathematical models have a valuable role to play in the understanding and measurement of cerebral parameters. However, for the same reasons, whole-brain models are highly complex to construct. In this study, we propose a novel multi-compartment approach to blood flow and oxygen transport. Building on prior models, we propose a new formulation based on a multiple compartment porous medium approach. Using non-dimensional analysis, we derive the most compact form of the equations and constrain the parameter space using clinically measurable quantities, such as baseline perfusion and blood volume. We illustrate the spatially and temporally varying response of the brain by simulating the response to changes in both arterial blood pressure and arterial oxygen saturation, showing that the oxygen response is strongly dependent upon depth, with large but slow responses being found deep in the brain and small but fast responses nearer the surface, whereas the flow response is very rapid in comparison. Blood flow and oxygenation are thus shown to exhibit very different characteristic time scales. This has significant implications for how we consider the response of the brain to external stimuli, such the autoregulation and reactivity responses, and how we model the brain at different time scales.Statement of Significance: In this study we present a new mathematical model for simulations of blood flow and oxygen transport in the human brain. A compact representation is obtained from analysis of the governing equations and different time scales are identified. We show that the behaviour is strongly depth dependent and that 3D models exhibit very different behaviour from simplified 1D models. This will be important in developing further models of the brain, particularly in simulating its active response.

Quantification of dynamic cerebral autoregulation: welcome to the jungle!

Patients with dysautonomia often experience symptoms such as dizziness, syncope, blurred vision and brain fog. Dynamic cerebral autoregulation, or the ability of the cerebrovasculature to react to transient changes in arterial blood pressure, could be associated with these symptoms. In this narrative review, we go beyond the classical view of cerebral autoregulation to discuss dynamic cerebral autoregulation, focusing on recent advances pitfalls and future directions. Following some historical background, this narrative review provides a brief overview of the concept of cerebral autoregulation, with a focus on the quantification of dynamic cerebral autoregulation. We then discuss the main protocols and analytical approaches to assess dynamic cerebral autoregulation, including recent advances and important issues which need to be tackled. The researcher or clinician new to this field needs an adequate comprehension of the toolbox they have to adequately assess, and interpret, the complex relationship between arterial blood pressure and cerebral blood flow in healthy individuals and clinical populations, including patients with autonomic disorders.

Music Therapy During Basic Daily Care in Critically Ill Children: A Randomized Crossover Clinical Trial

To assess whether music therapy is effective to reduce pain during daily personal hygiene care (DPHC), a procedure performed in all patients in a pediatric intensive care unit. Fifty critically ill children were enrolled in a crossover controlled clinical trial with random ordering of the intervention, i.e., passive music therapy, and standard conditions, and blind assessment of pain on film recordings. Primary outcome was variation of the Face Legs Activity Cry Consolability (FLACC) score (range 0 to 10) comparing before and during DPHC. Secondary outcomes were changes in heart rate, respiratory rate, and mean arterial blood pressure, and administration of analgesic or sedative drugs during DPHC. Mixed-effects linear model analysis was used to assess effect size (95% CI). Median (Q25-Q75) age and weight of the patients were 3.5 (1.0, 7.6) years and 15.0 (10.0, 26.8) kg. Consecutive DPHC were assessed the 3rd (2, 5) and 4th days (3, 7) of hospitalization. In standard conditions, FLACC score was 0.0 (0.0, 3.0) at baseline and 3.0 (1.0, 5.5) during DPHC. With music therapy, these values were, respectively, 0.0 (0.0, 1.0) and 2.0 (0.5, 4.0). Rates of FLACC scores >4 during DPHC, which indicates severe pain, were 42% in standard conditions and 17% with music therapy (p=0.013). Mixed-effects model analysis found smaller increases in FLACC scores (-0.54 [-1.08 to -0.01]; p= 0.04) and heart rate (-9; [-14.53; -3.4]; p=0.001) with music therapy. Music therapy is effective to improve analgesia in critically ill children exposed to DPHC.