Changes In Arterial Blood Pressure Research Articles

Effect of propofol infusion vs ketamine plus dexmedetomidine infusion on the amplitude of motor evoked potential in pediatric patients undergoing tethered spinal cord surgeries; a randomized, double blind controlled study

Background & objective: The use of intraoperative neurophysiologic monitoring (IOM) has increased over the past two decades for the detection and prevention of iatrogenic neurologic injuries. Motor evoked potentials (MEP) are extremely sensitive to changes in physiological variables and inhalational agents reduce MEPs in a dose dependent manner. So IV anesthetics (propofol or ketamine) and opioids (fentanyl or remifentanil), are frequently used in spinal surgeries under MEPs monitoring. We compared the effects of propofol and fentanyl to those of ketamine, dexmedetomidine, and fentanyl in terms of minimizing their effects on MEP amplitude and hemodynamic stability during surgery Methodology: This double blind, randomized, prospective study was conducted on 46 children, who were randomly allocated into 2 groups Ketamine–dexmedetomidine group: (n = 23) Maintenance throughout the procedure, by infusing Dexmedetomidine (0.4 -0.6 μg/.kg /.hr) ketamine, (1 -2m/.kg/.hr.) and giving bolus of fentanyl, (1-2μg/.kg/ ). Propofol-group:(n = 23) Maintenance throughout the procedure, By infusing propofol (100 ug L/kg/min) and giving bolus of fentanyl, (1-2μg/.kg/ ), with keeping mean arterial blood pressure changes within 25% of the baseline in both groups. Results: Right and left quadriceps muscle measurements were insignificantly different between both groups at base line and were significantly higher in Group KD than Group P at skin incision, surgical manipulation and surgical closure. Right and left adductor hallucis muscle measurements were insignificantly different between both groups at base line and were significantly higher in Group KD than Group P at 5 mins, 10 mins, 15 mins, skin incision, surgical manipulation and surgical closure (P value <0.001). Intraoperative fentanyl consumption was significantly lower in Group KD than Group P. Conclusion: The combination of dexmedetomidine and ketamine infusion is efficacious, safe, and has minimal effect on evoked potentials compared with the propofol-based TIVA group during spine pediatrics surgery. In addition, this combination increases the reliability and accuracy of MEP monitoring with hemodynamic stability and adequate post-operative pain relief. Using dexmedetomidine and ketamine infusions during pediatric spine surgery might successfully replace the typical propofol-based TIVA, although more studies are required . Registration: ClinicalTrials.gov registration number NCT05591001. Keywords: Motor evoked potential, dexmedetomidine, ketamine, propofol. Citation: Saleh AH, Hammad SH, Hassan PF. Effect of propofol infusion vs ketamine plus dexmedetomidine infusion on the amplitude of motor evoked potential in pediatric patients undergoing tethered spinal cord surgeries; a randomized, double blind controlled study. Anaesth. pain intensive care 2024;28(4):692−699; DOI: 10.35975/apic.v28i4.2218 Received: May 08, 2023; Reviewed: February 02, 2024; Accepted: July 03, 2924

Endobronchial Phenylephrine in Airway Bleeding During Bronchoscopy Does not Cause Hypertension: A Retrospective Observational Study.

Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29mmHg (IQR 19 to 41) compared with 31.8mmHg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.

The Impact of Chronic Oral Beta-Blocker Intake on Intravenous Bolus Landiolol Response in Hospitalized Intensive Care Patients with Sudden-Onset Supraventricular Tachycardia-A Post Hoc Analysis of a Cross-Sectional Trial.

Background: Landiolol, a highly cardioselective agent with a short half-life (2.4-4 min), is commonly used as a perfusor or bolus application to treat tachycardic arrhythmia. Some small studies suggest that prior oral β-blocker use results in a less effective response to intravenous β-blockers. Methods: This study investigated whether prior chronic oral β-blocker (Lβ) or no prior chronic oral β-blocker (L-) intake influences the response to intravenous push-dose Landiolol in intensive care patients with acute tachycardic arrhythmia. Results: The effects in 30 patients (67 [55-72] years) were analyzed, 10 (33.3%) with and 20 (66.7%) without prior oral β-blocker therapy. Arrhythmias were diagnosed as tachycardic atrial fibrillation in 14 patients and regular, non-fluid-dependent, supraventricular tachycardia in 16 cases. Successful heart rate control (Lβ 4 vs. L- 7, p = 1.00) and rhythm control (Lβ 3 vs. L- 6, p = 1.00) did not significantly differ between the two groups. Both groups showed a significant decrease in heart rate when comparing before and after the bolus administration, without significant differences between the two groups (Lβ -26/min vs. L- -33/min, p = 0.528). Oral β-blocker therapy also did not influence the change in mean arterial blood pressure after Landiolol bolus administration (Lβ -5 mmHg vs. L- -4 mmHg, p = 0.761). Conclusions: A prior chronic intake of β-blockers neither affected the effectiveness of push-dose Landiolol in heart rate or rhythm control nor impacted the difference in heart rate or mean arterial blood pressure before and after the Landiolol boli.

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 study. AnimalsA sample of 137 client-owned dogs admitted to two veterinary teaching hospitals for diagnosis and patient care owing to suspected intracranial disease from 2005 to 2020. All dogs underwent general anesthesia for MRI of the brain. MethodsBased on MRI study reports, dogs were divided into three study groups: group A, dogs with suspected brain herniation; group B, dogs with an abnormal MRI finding but without suspicion of herniation; and group C, 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, nine 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 nine dogs with likely CR, three had an MRI diagnosis of intracranial herniation. The remaining six dogs suspected of CR belonged to the normal brain group. Conclusions and clinical relevanceThe ABP and HR changes associated with CR are not reliably associated with brain herniation in dogs undergoing general anesthesia.

Data-based modeling of cerebral hemodynamics quantifies impairment of cerebral blood flow regulation in type-2 diabetes.

We studied the regulation dynamics of cerebral blood velocity (CBv) at middle cerebral arteries (MCA) in response to spontaneous changes of arterial blood pressure (ABP), termed dynamic cerebral autoregulation (dCA), and end-tidal CO2 as proxy for blood CO2 tension, termed dynamic vasomotor reactivity (DVR), by analyzing time-series data collected at supine rest from 36 patients with Type-2 Diabetes Mellitus (T2DM) and 22 age/sex-matched non-diabetic controls without arterial hypertension. Our analysis employed a robust dynamic modeling methodology that utilizes Principal Dynamic Modes (PDM) to estimate subject-specific dynamic transformations of spontaneous changes in ABP and end-tidal CO2 (viewed as two "inputs") into changes of CBv at MCA measured via Transcranial Doppler ultrasound (viewed as the "output"). The quantitative results of PDM analysis indicate significant alterations in T2DM of both DVR and dCA in terms of two specific PDM contributions that rise to significance (p < 0.05). Our results further suggest that the observed DVR and dCA alterations may be due to reduction of cholinergic activity (based on previously published results from cholinergic blockade data) that may disturb the sympatho-vagal balance in T2DM. Combination of these two model-based "physio-markers" differentiated T2DM patients from controls (p = 0.0007), indicating diabetes-related alteration of cerebrovascular regulation, with possible diagnostic implications.

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.

Ascorbic Acid Infusion Improves Cerebrovascular Reactivity in Middle-Aged and Older Adults

Aging is associated with reductions in cerebrovascular reactivity (CVR) and cerebrovascular conductance (CVC), which may contribute to the development of neurodegenerative disease and stroke. In the peripheral vasculature, increased oxidative stress is linked to vascular dysfunction and is ameliorated following infusion of the antioxidant ascorbic acid (AA). However, oxidative stress’ effect on cerebrovascular function in humans is not entirely understood. PURPOSE: To determine whether oxidative stress reduces CVR and CVC in middle-aged and older adults (MA/O). We hypothesized that AA infusion would increase CVR and CVC in MA/O but not young adults (YA). METHODS: Young (18-29 years) and middle-aged and older (55-79 years) adults were recruited for two identical experimental visits. Each visit consisted of the same measures performed both before and after the infusion of either AA or saline (SAL). Middle cerebral artery blood velocity (MCAv) was recorded using a transcranial Doppler ultrasound probe. CVR was tested using a hypercapnia protocol that was achieved with a computer-based gas blender that increased the subjects’ end-tidal partial pressure of carbon dioxide (PETCO2) 9 mmHg above baseline for a 3-minute period. CVR was defined as the percent change in MCAv during hypercapnia divided by the absolute change in PETCO2. CVC was defined as the percent of CVR normalized for the changes in mean arterial blood pressure. Two-way ANOVAs were used to assess the effects of AA and SAL on CVR and CVC. Fisher’s LSD tests were used to assess main and interaction effects when necessary. RESULTS: 8 YA (25 + 2 years) and 14 MA/O (65 + 6 years) completed the experimental visits. There was a significant main effect of condition (pre/post) on CVR following SAL infusion (p = 0.016), and a significant age x condition interaction effect on CVR following AA infusion (p = 0.016). There were no significant main or interaction effects on CVC following SAL infusion, but there was a significant age x condition interaction effect on CVC following AA infusion (p = 0.012). Post hoc testing indicated that the difference in CVR following SAL infusion was due to an increase in YA (3.0 + 0.5 %/mmHg pre vs. 3.8 + 1.1 %/mmHg post, p = 0.047), whereas the difference in CVR following AA infusion was due to an increase in MA/O (3.3 + 1.7 %/mmHg pre vs. 4.1 + 1.9 %/mmHg post, p = 0.006). The difference in CVC was indicated to be due to both lower baseline CVC in MA/O (2.3 + 0.4 %/mmHg YA pre vs. 1.3 + 1.1 %/mmHg MA/O pre, p = 0.019) and an increase in CVC in MA/O following AA infusion (1.3 + 1.1 %/mmHg pre vs. 2.0 + 0.5 %/mmHg post, p = 0.047). CONCLUSION: Our main finding is that AA infusion restores CVR and CVC in MA/O, but not YA. This finding suggests that age-related increases in oxidative stress may impair cerebrovascular function. Supported by NIH Grant P20 GM113125. 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.

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 ± 5 mmHg. 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.

Modeling the mechanisms of non-neurogenic dynamic cerebral autoregulation.

Dynamic cerebral autoregulation (dCA) refers to a collection of mechanisms that act to maintain steady state cerebral blood flow (CBF) near constant despite changes in arterial blood pressure (ABP), but which is known to become impaired in various cerebrovascular diseases. Currently, the mechanisms of dCA and how they are affected in different physiological conditions are poorly understood. The objective of this study was to disentangle the magnitudes and time scales of the myogenic and metabolic responses of dCA, in order to investigate how each mechanism is affected in impaired dCA. A physiological model of dCA was developed, where both the myogenic and metabolic responses were represented by a gain and time constant. Model parameters were optimized with pressure-flow impulse responses under normocapnia, thigh cuff, and hypercapnia conditions. The impulse responses were derived by applying transfer function analysis (TFA) to experimental recordings of ABP (Finapres), end-tidal CO2 (capnograph), and CBF velocity (transcranial doppler ultrasound in bilateral middle cerebral arteries). The myogenic gain to time constant ratio was significantly smaller (p-values < 0.001 using both univariate and multivariate TFA), and the metabolic time constant was significantly larger (p-values < 0.001 using both univariate and multivariate TFA) in hypercapnia compared to normocapnia. Both the myogenic and metabolic responses were shown to be affected in impaired dCA, and the metabolic response was shown to be slowed down. This study contributes to the understanding of the complexities of dCA and how it is affected in different physiological conditions.