Elevated Mean Arterial Pressure Research Articles

Does Elevated Mean-Arterial Pressure Lead to Better Outcomes in Degenerative Cervical Myelopathy?- A Prospective, Pilot Randomized Control Trial.

Randomized Control Trial. DCM refers to compression of spinal cord either due to static/dynamic causes or commonly, a result of combination of both. Number of variables exist, which determine prognosis post-surgery. Role of intra-operative blood pressure has not been analyzed in depth in current literature. Elevating MAP post SCI is widely practiced and forms a recommendation of AANS/CNS Joint Committee Guidelines. This led us to investigate role played by elevated MAP during surgery for DCM, in order to optimize outcomes. This prospective randomized comparative pilot study was conducted at a tertiary care spine centre. 84 patients were randomly divided in two groups. Group 1 had intra-operative MAP in normal range. Group 2, had intra-operative BP 20 mmHg higher than preoperative average MAP with a variation of + 5mmHg. Outcomes were recorded at 3 months, 6 months and 1 year by mJOA, VAS and ASIA scale. Neurological improvement was documented in 19/30 (63.3%) patients of hypertensive group compared to 16/30 (53.3%) patients of normotensive group. Improvements in mJOA scores were better for hypertensive group during the 1-year follow-up. Improvement in VAS scores were comparable between two groups, but at 1-year follow-up the VAS score of hypertensive groups was significantly lower. MAP should be individualized according to preoperative average blood pressure assessment of patient. Keeping intraoperative MAP at higher level (preoperative MAP + 20mmHg) during surgery for DCM can result in better outcomes.

Lower vascular conductance responses to handgrip exercise are improved following acute antioxidant supplementation in young individuals with post-traumatic stress disorder.

Young individuals with post-traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study examined haemodynamic responses to handgrip exercise in young individuals with PTSD following acute antioxidant (AO) supplementation. Thirteen young individuals with PTSD (age 23±3years), and 13 age- and sex-matched controls (CTRL) participated in the study. Exercise-induced changes to arm blood flow (BF), mean arterial pressure (MAP) and vascular conductance (VC) were evaluated across two workloads of rhythmic handgrip exercise (3 and 6kg). The PTSD group participated in two visits, consuming either a placebo (PL) or AO prior to their visits. The PTSD group demonstrated significantly lower VC (P=0.04) across all exercise workloads (vs. CTRL), which was significantly improved following AO supplementation. In the PTSD group, AO supplementation improved VC in participants possessing the lowest VC responses to handgrip exercise, with AO supplementation significantly improving VC responses (3 and 6kg: P<0.01) by blunting elevated exercise-induced MAP responses (3kg: P=0.01; 6kg: P<0.01). Lower VC responses during handgrip exercise were improved following AO supplementation in young individuals with PTSD. AO supplementation was associated with a blunting of exercise-induced MAP responses in individuals with PTSD displaying elevated MAP responses. This study revealed that young individuals with PTSD exhibit abnormal, peripherally mediated exercise responses that may be linked to a redox imbalance.

Exercise Mitigates Angiotensin II-Mediated Sympathetic Nerve-Macrophage Interaction in Aortic Adventitia Leading to Vascular Remodeling

Large artery stiffness is a significant risk factor for cardiovascular diseases. Our previous study suggested that angiotensin II (Ang II) stimulates sympathetic innervation in aortic adventitia (AA) leading to elevated mean arterial blood pressure and increased arterial fibrosis, while voluntary wheel-running (VWR) reduces them. The aim of this study is to explore mechanism under Ang II-induced the aortic remodeling through sympathetic nerves and immune cell interactions using transcriptomics. We isolated cells in AA from Ang II (1.5 mg/kg/day) vs. Vehicle (Saline) infused C57BL/6 male mice (n=3 of each group), and we performed single-cell RNA-sequencing (scRNAseq). We profiled 23,419 cells after quality control and filtering steps and annotated 9 cell types in the AA employing a uniform manifold approximation and projection (UMAP) to visualize the remaining cells and the Leiden cluster algorithm. Firstly, we identified the Adrb2 gene for β2-adrenergic receptor (β2-ADR) was predominantly expressed in macrophages/monocytes as compared to other cell types, and significantly more expressed in macrophages vs. monocytes (adjusted p-value, &lt;0.05). We validated the transcriptomic results using immunostaining for β2-ADR and synapsin with CD68 in AA. In addition, Ang II increased AA macrophage proportion which displays M1 phenotype (pro-inflammatory) (adjusted p-value, &lt;0.05). These findings suggest that Ang II promotes M1 like macrophages which interact with sympathetic nerves in AA. Next, we performed Gene Ontology (GO) enrichment test in macrophages and fibroblasts. Ang II Macrophages were enriched in GO terms with inflammation and cytokines, and Ang II fibroblasts were enriched in GO terms involved in extracellular matrix deposition. The GO results indicate that Ang II induced inflammatory macrophages activates fibroblasts to accumulate ECM deposition in AA. Congruent with the scRNAseq results, we found that number of macrophages, ECM accumulation, and vascular stiffness measured by pulse wave velocity were increased with Ang II vs. Vehicle (all, p &lt;0.05), whereas interestingly VWR ameliorated the Ang II effects. This study provides the evidence that Ang II promotes aortic remodeling by interaction between sympathetic nerves and macrophage which results in ECM deposition in AA using transcriptomics approach, while VWR countermeasure to these detrimental effects. 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.

Potassium Ion Channel Modulation as a Potential Remedy for Cadmium-induced Hypertension

Objective: Hypertension remains a chief non-communicable lifestyle disease that is negatively associated with dietary cadmium (Cd). The exact mechanism of Cd toxicity and the mitigating role of potassium supplementation are not fully known, hence, this study aimed to investigate their effects on the aorta. Hypothesis: We hypothesized that potassium supplementation can modulate Cd-induced vascular dysfunction. Method: Six cohorts of control, Cd-exposed, and potassium supplemented male Sprague-Dawley rats were selected. Hypertension was induced using cadmium chloride (2.5 or 5 mg/kg b.w.). Blood pressure was measured twice weekly. Reactivity to pharmacological agents with and without potassium ion channel modulation was assessed in thoracic aortic rings after eight weeks, using an organ bath set-up. Data: Statistical analysis was done using one-way analysis of variance and the results were reported as mean ± standard error of the mean. The Games-Howell or Bonferroni post hoc test was used for multiple comparisons. Summary of Results: Cadmium significantly (p&lt;0.05) elevated systolic, diastolic, mean arterial, and pulse pressures, reduced (p&lt;0.001) phenylephrine-induced contraction mostly via BKCa channels, and augmented (p&lt;0.05) sodium nitroprusside-induced relaxation via K-ATP, KV, and KIR channels, without affecting acetylcholine-induced relaxation. Potassium supplementation ameliorated these effects via KIR and BKCa channels. Conclusions: The results indicate that modulation of potassium ion channels in the vasculature might provide therapeutic management for environmentally-induced hypertension and should be further explored. Funding source: The Mona Campus Committee for Research and Publications and Graduate Awards, School for Graduate Studies and Research, University of the West Indies. 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.

The Association Between Obesity Measures and Metabolic Syndrome Risk in Korean Adolescents Aged 10-18 Years.

Childhood obesity is strongly linked to an increased risk of metabolic syndrome (MetS), type 2 diabetes, and cardiovascular disease in adulthood, endangering the global healthcare system. No single tool for detecting MetS is suitable for all pediatric populations. This study aimed to investigate the association between obesity measures and MetS in Korean children and adolescents. The data were obtained from 1663 children and adolescents aged 10-19 years (771 girls) who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Surveys. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHtR) were included as obesity measures. Fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, and resting blood pressure were included as metabolic risk factors. MetS was defined as the clustering of metabolic risk factors such as elevated fasting blood glucose, elevated mean arterial pressure, elevated triglycerides, and low high-density lipoprotein cholesterol. Regardless of the obesity measures used, obese children and adolescents were more likely to have a clustering of metabolic risk factors compared to their non-obese counterparts: BMI-based obesity (odds ratio, OR=4.151, 95% confidence interval, CI=2.763~6.238, p<0.001), WC-based obesity (OR=1.917, 95% CI=1.066~3.446, p=0.010), and WHtR-based obesity (OR=2.160 and 95% CI=1.203~3.878, p=0.003). A receiver operating curve analysis showed that BMI (area under the curve, AUC=0.849, 95% CI=0.8270.871) outperformed WC (AUC=0.833, 95% CI=0.8090.856) and WHtR (AUC=0.794, 95% CI=0.7670.821) in detecting the presence of MetS. Study findings suggest that obese teenagers are more likely to have metabolic syndrome than non-obese teens. Concerning accuracy, convenience, and ease of use and calculation, BMI is the best screening tool for detecting MetS in Korean children and adolescents.

396 Creating a High-Precision, Dynamic Machine Learning Model Using Time Series Data to Predict Cerebral Vasospsm in Aneurysmal Subarachnoid Hemorrhage

INTRODUCTION: Cerebral vasospasm (CV) occurs in up to one-third of patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH) and can result in significant morbidity. Prior attempts to predict CV after aSAH have failed because they use static data collected on the day of presentation. We hypothesize that trending clinical and radiographic data including transcranial dopplers (TCDs) throughout 14 intensive care unit (ICU) days can be used to create a highly predictive, dynamic machine learning model for CV. METHODS: We conducted an IRB-approved retrospective study including 428 patients with aSAH hemorrhage treated at our institution between June 2014 and December 2018. For each patient, 74 features were trended including vital signs, lab values and ventriculostomy output. TCD measurements included anterior and posterior circulation velocities, Lindegaard Ratios and pulsatility indices. We employed a generative transformer-based model that uses patient representations from aggregate prior time points to predict the likelihood of CV. RESULTS: Of the 428 aSAH patients, 85 had angiographic-proven CV. There was no difference in demographic features including age, gender distribution and BMI between the CV and no-CV groups. Throughout 14 ICU days, the CV patients consistently displayed elevated mean arterial pressure and cerebral perfusion pressure. All TCD measurements were higher for the CV group. Initial logistic regression models based on static data from post-ictus days 1 through 4 showed steadily increasing F1 scores from 0.67 to 0.76. Feature analysis identified Lindegaard Ratios as the most heavily weighted features. CONCLUSIONS: Daily TCDs paired with additional longitudinal clinical data can be used to create a high-precision dynamic machine learning model for predicting CV after aSAH. These methods could also permit identification of patients at low risk of CV for reduced ICU length of stay.

Hemodynamic Determinants of Cardiac Surgery-Associated Acute Kidney Injury.

Examine the: 1) relative role of hemodynamic determinants of acute kidney injury (AKI) obtained in the immediate postcardiac surgery setting compared with established risk factors, 2) their predictive value, and 3) extent mediation via central venous pressure (CVP) and mean arterial pressure (MAP). Retrospective observational study. The main outcome of the study was moderate to severe AKI, per kidney disease: improving global outcomes, within 14 days of surgery. U.S. academic medical center. Adult patients undergoing cardiac surgery between January 2000 and December 2019 (n = 40,426) in a single U.S.-based medical center. Pulmonary artery catheter measurements were performed at a median of 102 minutes (11, 132) following cardiopulmonary bypass discontinuation. None. The median age of the cohort was 67 years (58, 75), and 33% were female; 70% had chronic hypertension, 29% had congestive heart failure, and 3% had chronic kidney disease. In a multivariable model, which included comorbidities and traditional intraoperative risk factors, CVP (p < 0.0001), heart rate (p < 0.0001), cardiac index (p < 0.0001), and MAP (p < 0.0001), were strong predictors of AKI, and superseded factors such as surgery type and cardiopulmonary bypass duration. The cardiac index had a significant interaction with heart rate (p = 0.026); a faster heart rate had a differentiating effect on the relationship of cardiac index with AKI, where a higher heart rate heightened the risk of AKI primarily in patients with low cardiac output. There was also significant interaction observed between CVP and MAP (p = 0.009); where the combination of elevated CVP and low MAP had a synergistic effect on AKI incidence. Hemodynamic factors measured within a few hours of surgery showed a strong association with AKI. Furthermore, determinants of kidney perfusion, namely CVP and arterial pressure are interdependent; as are constituents of stroke volume, that is, cardiac output and heart rate.

Montelukast Ameliorates 2K1C-Hypertension Induced Endothelial Dysfunction and Associated Vascular Dementia.

Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are serious public health concerns, which highlights the urgent need for study on the risk factors for cognitive decline. Cysteinyl leukotriene (CysLT1) receptors are concerned with regulating cognition, motivation, inflammatory processes, and neurogenesis. This research aims to examine the consequence of montelukast (specific CysLT1 antagonist) in renovascular hypertension 2-kidney-1-clip-2K1C model-triggered VaD in experimental animals. 2K1C tactics were made to prompt renovascular hypertension in mature male rats. Morris water maze was employed to measure cognition. Mean arterial pressure (MAP), serum nitrite levels, aortic superoxide content, vascular endothelial activity, brain's oxidative stress (diminished glutathione, raised lipid peroxides), inflammatory markers (IL-10, IL-6, TNF-α), cholinergic activity (raised acetylcholinesterase), and cerebral injury (staining of 2, 3, 5- triphenylterazolium chloride) were also examined. Montelukast in doses of 5.0 and 10.0 mg kg-1 was used intraperitoneally as the treatment drug. Along with cognitive deficits, 2K1C-operated rats showed elevated MAP, endothelial dysfunction, brain oxidative stress, inflammation, and cerebral damage with diminished serum nitrite/nitrate. Montelukast therapy significantly and dose-dependently mitigated the 2K1Chypertension-provoked impaired behaviors, biochemistry, endothelial functions, and cerebral infarction. The 2K1C tactic caused renovascular hypertension and associated VaD, which was mitigated via targeted regulation of CysLT1 receptors by montelukast administration. Therefore, montelukast may be taken into consideration for the evaluation of its complete potential in renovascular-hypertension-induced VaD.

Application and reduction of a nonlinear hyperelastic wall model capturing ex vivo relationships between fluid pressure, area, and wall thickness in normal and hypertensive murine left pulmonary arteries.

Pulmonary hypertension is a cardiovascular disorder manifested by elevated mean arterial blood pressure (>20 mmHg) together with vessel wall stiffening and thickening due to alterations in collagen, elastin, and smooth muscle cells. Hypoxia-induced (type 3) pulmonary hypertension can be studied in animals exposed to a low oxygen environment for prolonged time periods leading to biomechanical alterations in vessel wall structure. This study introduces a novel approach to formulating a reduced order nonlinear elastic structural wall model for a large pulmonary artery. The model relating blood pressure and area is calibrated using ex vivo measurements of vessel diameter and wall thickness changes, under controlled pressure conditions, in left pulmonary arteries isolated from control and hypertensive mice. A two-layer, hyperelastic, and anisotropic model incorporating residual stresses is formulated using the Holzapfel-Gasser-Ogden model. Complex relations predicting vessel area and wall thickness with increasing blood pressure are derived and calibrated using the data. Sensitivity analysis, parameter estimation, subset selection, and physical plausibility arguments are used to systematically reduce the 16-parameter model to one in which a much smaller subset of identifiable parameters is estimated via solution of an inverse problem. Our final reduced one layer model includes a single set of three elastic moduli. Estimated ranges of these parameters demonstrate that nonlinear stiffening is dominated by elastin in the control animals and by collagen in the hypertensive animals. The pressure-area relation developed in this novel manner has potential impact on one-dimensional fluids network models of vessel wall remodeling in the presence of cardiovascular disease.

Cadmium induces microcytosis and anisocytosis without anaemia in hypertensive rats.

Dietary cadmium (Cd2+) intake is implicated in the pathogenesis of hypertension and anaemia, but there is a paucity of information on the haematological changes in hypertensive conditions. This study, therefore, aims to evaluate the effects of Cd2+ on blood pressure (BP) and haematological indices in the Sprague-Dawley rat model. Three cohorts (n = 10 each) of control and Cd2+-fed male Sprague-Dawley rats were selected. Cd2+-exposed rats received 2.5 or 5mg/kg b.w. cadmium chloride via gavage thrice-weekly for eight weeks, while control animals received tap water. BP and flow were measured non-invasively from rat tails twice-weekly using a CODA machine, while weights were measured thrice-weekly. Haematological indices were assessed using the Cell-Dyn Emerald Haematology Analyzer. Data were reported as mean ± SEM, and statistically analyzed using One-Way Analysis of Variance. Bonferroni post hoc test was used for multiple comparisons. Cd2+-exposure induced hypertension by significantly (p < 0.05) elevating systolic, diastolic, and mean arterial BPs, pulse pressure, and heart rate (HR), and increased (p < 0.05) blood flow. Mean cell volume (MCV) and haemoglobin (MCH) were significantly (p < 0.05) reduced, and red cell distribution width (RDW) significantly (p < 0.01) increased by exposure to 5mg/kg b.w. Cd2+. Haemoglobin concentration (MCHC), haematocrit, haemoglobin, red blood cell, platelet, mean platelet volume, and white blood cell counts were unaffected by Cd2+-exposure. Cd2+ induced hypertension, microcytosis, hypochromicity, and anisocytosis without anaemia, which may be precursor to microcytic anaemia and coronary artery disease. This study is important in Cd2+-exposed environments and warrants further investigations.

Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats.

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine β-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals.NEW & NOTEWORTHY Exercise training reduces high blood pressure and cardiovascular autonomic modulation in aged hypertensive rats. The dysfunction in the baroreflex sensitivity and impaired parasympathetic tone to the heart of aged hypertensive rats are restored by exercise training. Exercise induces beneficial neuroplasticity in the brain nuclei involved with autonomic control of cardiovascular function of aged hypertensive rats.

Abstract 179: Reversal of Clinical Death by Intra-Arterial Infusion of Phospholipid Nanoparticles (VBI-1)

Introduction: Ninety percent of deaths from potentially survivable injuries on the battlefield are attributed to hemorrhagic shock, leading to clinical death (CD) with the loss of pulse and respiratory drive before reaching a surgeon. However, currently available fluids are inadequate for rescuing warfighters who have experienced exsanguination. Furthermore, these fluids have the potential to cause reperfusion injury in vital organs. We developed a rat model of CD to evaluate the effectiveness of two phospholipid nanoparticle formulations (VBI-1, VBI-S) and compared intra-arterial (IA) versus intravenous (IV) infusion on resuscitation. Hypothesis: We hypothesized that the nanoparticles would restore breathing and blood pressure (BP) in rats after CD induced by hemorrhagic shock. Goals: To establish a model that reliably restores breathing and maintains a survivable BP for 240 minutes after CD. Methods: Male and female Sprague Dawley rats were divided into four groups (n=6-7). The rats were anesthetized with isoflurane, followed by cannulation of femoral arteries. Blood was withdrawn over two minutes until respiration ceased. Equal volumes of either Ringer’s Lactate (LR), shed blood, VBI-1, or VBI-S were infused over one minute, with continuous monitoring of BP. Results: Loss of respiration occurred with blood withdrawal ranging from 39.8% to 43.2% of the predicted total blood volume. Post-IA infusion, the survival rates of the four groups for 240 minutes were as follows: 100% with VBI-1 (n=6), 83.3% with blood (n=7), 66.7% with VBI-S (n=6), and 0% with LR (n=6). Two-way ANOVA analysis revealed a significant difference in mean arterial pressure (MAP) among the four fluids (p=0.0004). Post-hoc analysis indicated the fluid responsiveness in elevating MAP as follows: VBI-1 &gt; VBI-S = shed blood &gt; LR. Regarding the VBI-1 infusion routes, the IA infusion demonstrated 100% survival (n=6) compared to the IV infusion with 40% (n=6) survival. Conclusion: VBI-1 outperformed all other fluids, including blood, in achieving reanimation and elevating MAP. IA infusion of VBI-1 demonstrated a higher reanimation rate compared to IV infusion. Based on these findings, VBI-1 is a promising new treatment for CD due to severe hemorrhagic shock; potentially saving lives.

Adjunctive hyperbaric oxygen therapy for spinal cord ischemia after complex aortic repair

ObjectiveSpinal cord ischemia (SCI) with paraplegia or paraparesis is a devastating complication of complex aortic repair (CAR). Treatment includes cerebrospinal fluid drainage, maintenance of hemoglobin concentration (>10 g/L), and elevating mean arterial blood pressure. Animal and human case series have reported improvements in SCI outcomes with hyperbaric oxygen therapy (HBOT). We reviewed our center’s experience with HBOT as a rescue treatment for spinal cord ischemia post-CAR in addition to standard treatment. MethodsA retrospective review of the University Health Network’s Hyperbaric Medicine Unit treatment database identified HBOT sessions for patients with SCI post-CAR between January 2013 and June 2021. Mean estimates of overall motor function scores were determined for postoperative, pre-HBOT, post-HBOT (within 4 hours of the final HBOT session), and at the final assessment (last available in-hospital evaluation) using a linear mixed model. A subgroup analysis compared the mean estimates of overall motor function scores between improvement and non-improvement groups at given timepoints. Improvement of motor function was defined as either a ≥2 point increase in overall muscle function score in patients with paraparesis or an upward change in motor deficit categorization (para/monoplegia, paraparesis, and no deficit). Subgroup analysis was performed by stratifying by improvement or non-improvement of motor function from pre-HBOT to final evaluation. ResultsThirty patients were treated for SCI. Pre-HBOT, the motor deficit categorization was 10 paraplegia, three monoplegia, 16 paraparesis, and one unable to assess. At the final assessment, 14 patients demonstrated variable degrees of motor function improvement; eight patients demonstrated full motor function recovery. Seven of the 10 patients with paraplegia remained paraplegic despite HBOT. The estimated mean of overall muscle function score for pre-HBOT was 16.6 ± 2.9 (95% confidence interval [CI], 10.9-22.3) and for final assessment was 23.4 ± 2.9 (95% CI, 17.7-29.1). The estimated mean difference between pre-HBOT and final assessment overall muscle function score was 6.7 ± 3.1 (95% CI, 0.6-16.1). The estimated mean difference of the overall muscle function score between pre-HBOT and final assessment for the improved group was 16.6 ± 3.5 (95% CI, 7.5-25.7) vs −4.9 ± 4.2 (95% CI, −16.0 to 6.2) for the non-improved group. ConclusionsHBOT, in addition to standard treatment, may potentially improve recovery in spinal cord function following SCI post-CAR. However, the potential benefits of HBOT are not equally distributed among subgroups.

Surgical resection of lumbar intradural metastatic renal cell carcinoma.

A 60-year-old male with renal cell carcinoma (RCC) presented with back pain, weakness, and bowel and bladder urgency. MRI demonstrated a cauda equina tumor at L2. Following L1-3 laminectomies, intraoperative ultrasound localized the tumor. After dural opening, a vascular tumor was adherent to the cauda equina. Intraoperative nerve stimulation helped to identify the nerve rootlets. Tumor was removed in a piecemeal fashion. Tumor dissection caused periodic spasms in L1-3 distributions. A neuromonitoring checklist was used to recover motor evoked potential signals with elevated mean arterial pressures. Hemostasis was challenging with the vascular tumor. Intraoperative ultrasound confirmed tumor debulking. Pathology confirmed metastatic RCC.

Hemodynamic Determinants of Elevated Blood Pressure and Hypertension in the Middle to Older-Age UK Population: A UK Biobank Imaging Study.

Increased systemic vascular resistance and, in older people, reduced aortic distensibility, are thought to be the hemodynamic determinants of primary hypertension but cardiac output could also be important. We examined the hemodynamics of elevated blood pressure and hypertension in the middle to older-aged UK population participating in the UK Biobank imaging studies. Cardiac output, systemic vascular resistance, and aortic distensibility were measured from cardiac magnetic resonance imaging in 31 112 (distensibility in 21 178) participants (46.3% male, mean age±SD 63±7 years). Body composition including visceral adipose tissue volume and abdominal subcutaneous adipose tissue volume were measured in 19 645 participants. Participants with higher blood pressure had higher cardiac output (higher by 17.9±26.6% in hypertensive compared with those with optimal blood pressure) and higher systemic vascular resistance (higher by 11.4±27.9% in hypertensive compared with those with optimal blood pressure). These differences were little changed after adjustment for body size and adiposity. The contribution of cardiac output relative to systemic vascular resistance was more marked in younger compared with older subjects. Aortic distensibility decreased with age and was lower in participants with higher compared with lower blood pressure but with a greater difference in younger compared with older subjects. In the middle to older-aged UK population, cardiac output plays an important role in contributing to elevated mean arterial blood pressure, particularly in younger compared with older subjects. Reduced aortic distensibility contributes to a rise in pulse pressure and systolic blood pressure at all ages.

Total Diz Artroplastisinde Cerrahi Yara Kapatılması Öncesinde Kontrollü Arteriyel Hipertansiyon ile Yapılan Hemostazis Kanama Miktarını ve Transfüzyon İhtiyacını Etkiler mi?

Objective: We aimed to assess the efficacy of hemostasis while controlled augmentation of arterial blood pressure before surgical closure after total knee arthroplasty (TKA). &#x0D; Materials and Methods: This retrospective cohort involved data collected from the medical files of 87 patients (62 women, 25 men) who underwent TKA using hypotensive epidural anesthesia (HEA). Patients were allocated into two groups. Group I (n=44) received HEA, while Group II (n=43) had controlled arterial hypertension before surgical closure. Perioperative hemoglobin and hematocrit levels, systolic and diastolic blood pressure, and the amount of erythrocyte suspension transfusion were compared between the two groups. &#x0D; Results: The average age of our series was 66.41 ± 6.17 (range: 57-78) years. Notably, the amount of bleeding on postoperative 1st, 2nd, 4th, 12th, and 24th (p=0.031, 0.032, 0.001, 0.001, 0.001, respectively) hours was significantly less in Group II. There were no significant differences between the two groups for complications, operative duration, perioperative bleeding, duration of follow-up and hospitalisation, and compared descriptives. &#x0D; Conclusion: Our data indicated that controlled elevation of mean arterial pressure before surgical closure might allow the achievement of meticulous hemostasis after TKA. Further prospective, randomised, controlled trials on more extensive series are warranted to verify our preliminary results.

Abstract 028: Sex Differences In Hypertension And Cerebral Oxidative Stress Of Preeclamptic Rat Offspring

Intrauterine growth restriction (IUGR) occurs when the fetus doesn’t receive adequate nutrients. The leading cause of IUGR is placental ischemia, often seen in preeclampsia (PE). Adult IUGR offspring have an increased risk of HTN and oxidative stress (OS), with sex differences. Studies have shown that IUGR males have HTN, cerebrovascular dysfunction (CVD), and cerebral OS at 17 wks; IUGR females are NT with limited CVD and no significant OS. Our study aims to characterize the sex differences in timing and changes of cerebral OS in IUGR offspring. HTN and OS are both present in adult IUGR males, however, the order and timing is unknown. We hypothesize that OS leads to HTN. To test this, we examined the changes in brain OS in 12 wk IUGR and control (CON) males (before HTN), and 17 wk IUGR males (which have HTN) vs CON males. We investigated the same time points in NT females. We divided pups from normal pregnant and PE Sprague-Dawley rats into groups based on pregnancy status and sex. Pups were aged to 12 and 17 wks. We collected brains to measure OS via western blot (Manganese superoxide dismutase) and colorimetric assays: hydrogen peroxide (H 2 O 2 ) and total antioxidant capacity (TAC). 12 wk IUGR and CON offspring were NT with no changes between groups or sex. There were no changes in cerebral H 2 O 2 , TAC, and MnSOD for IUGR offspring compared to their CON. At 17 wks, IUGR males had elevated mean arterial pressure (MAP; 143.0 ± 1.7 vs 133.0 ± 2.7 mmHg; p &lt; 0.01). IUGR females were NT. Cerebral H2O2 levels in IUGR males were elevated (20.5 ± 8.0 vs 3.7 ± 1.0 uM/ mg Protein; p &lt; 0.05) and unchanged in IUGR females. TAC in IUGR males was decreased (157.7 ±21.9 vs 234.9 ± 22.0 mM Trolox/mg Protein; p &lt; 0.05) and unchanged in IUGR females. MnSOD was elevated in females with no differences between groups (150.4 ± 3.8 vs 110.9 ±7.1 IU/Protein/CON%; p &lt; 0.002). All 12 wk rats were NT with no changes in cerebral OS. At 17 wks, IUGR males were HTN with elevated cerebral OS, with no changes in females. The lack of increase in OS at 12 wks, suggest that it’s not a precursor to HTN in males, but rather OS is a downstream effect from HTN. Future studies will look at factors that contribute to HTN and CVD in in IUGR offspring. Studies will also examine why 17 wk female IUGR are protected from HTN and cerebral OS.

Abstract P370: Progranulin Regulates Vascular Function And Blood Pressure Dependent On Ephrin A2 And Sortlin1 Receptors And Nitric Oxide Production.

Background: Progranulin (PGRN) is implicated in scar formation, cell proliferation, and anti-inflammation. Although high level of circulating PGRN was previously reported in hypertension, it is still not clear if PGRN can counteract the increases in blood pressure (BP) via modulating vascular tone. We sought to examine the role of PGRN maintaining the vascular tone and BP. Methods: we used male and female global PGRN deficient mice (PGRN-/-) and their counterparts (PGRN+/+) of 10-12-weeks of age to study vascular function and BP by wire myograph and radiotelemetry, respectively. Results: We found that two different mouse models of hypertension (angiotensin II or aldosterone treatments), elevated the levels of circulating PGRN. We also found that male and female PGRN-/- mice display elevated mean arterial pressure (MAP) (mmHg: PGRN+/+: 102.3 ± 3.9 vs PGRN-/-: 112.9 ± 3.7*, *P&lt;0.05) followed by vascular hypercontractility to noradrenaline (NA) [Maximal response (% of 60mM of KCl) male PGRN+/+: 121.9 ± 14.1 PGRN-/-: 152.6 ± 18.8*; female PGRN+/+: 102.6 ± 4.1 and PGRN-/- 131.3 ± 11.4*, *P&lt;0.05) in mesenteric arteries (MA), and increased circulating CCL2, IL-13, and interferon-γ. Whereas replacing PGRN with recombinant PGRN (rPGRN, 20ug/day/7-days) restored the MAP and vascular contractility in PGRN-/-. To explore the mechanisms by which PGRN modulates vascular tone, we treated MA from PGRN+/+, 1-hour prior NA curves, with rPGRN (600ng/mL) and found that PGRN attenuates the vascular contractility, such effect was abolished by blocking Ephrin A2 (EphA2) and Sortlin1 (Sort1) receptors or nitric oxide (NO) synthase (NOS). Next, we freshly isolated endothelial cells (EC) from mesentery of male and female PGRN+/+ mice via magnetic CD31+ microbeads to evaluate any sex difference on EphA2 and Sort1 expressions, which revealed that both receptors are equally expressed in EC from both sexes. In isolated mouse mesenteric EC, rPGRN stimulated NO formation and endothelial NOS activation, which were prevented by blocking EphA2 and Sort1. Conclusion: PGRN adjusts the vascular tone and BP via modulating NO formation and EphA2 and Sort1 receptors activation. Therefore, PGRN might be elevated in hypertension as a tentative to reduce BP by regulating vascular resistance.

Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?

Restoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS. Thirty-two pigs weighing 20-30kg were randomly allocated into four groups: control (no treatment), saline (60ml/kg of 0.9% NaCl), terlipressin (2mg of terlipressin), and saline plus terlipressin (20ml/kg of 0.9% NaCl + 2mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40mmHg. After 30min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05. The terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment. The treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.

Elevated preoperative blood pressure and its relationship to intraoperative mean arterial pressure and blood loss in posterior spinal fusion for adolescent idiopathic scoliosis.

The relationship between preoperative blood pressure (BP) and intraoperative mean arterial pressure (MAP) and estimated blood loss (EBL) in pediatric spine surgery is currently unknown. The objectives of this study were to determine if elevated preoperative BP is associated with elevated intraoperative MAP, EBL, and percentage estimated blood volume (EBV) lost, and to determine if intraoperative MAP is associated with percentage of EBV lost during posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). This is a retrospective cohort analysis of 209 patients undergoing PSF for AIS between 2016 and 2019 by a single surgeon. Data extracted included demographic characteristics, preoperative systolic and diastolic BP, continuous intraoperative MAP measured by arterial line, EBL, radiographic, and surgical characteristics. Time points of interest for MAP included incision and exposure. Elevated BP was defined as > 1 standard deviation above the mean BP of patients included in the study, and elevated MAP was defined as > 65mmHg. Elevated preoperative systolic BP was associated with elevated MAP at incision (p = 0.002). Patients with elevated preoperative diastolic BP had significantly higher MAP at exposure and throughout the procedure (p = 0.04). MAP > 65 at incision was associated with a 5% increase in EBV lost (p < 0.001). Patients with elevated preoperative BP parameters have increased MAPs at incision, exposure, and throughout surgery. Elevated MAP at incision is associated with an increased percentage of EBV lost in a small number of patients undergoing PSF for AIS.