Pressure Recordings Research Articles

Hyperosmolar therapy response in traumatic brain injury: Explainable artificial intelligence based long-term time series forecasting approach

In the neurological intensive care setting implementing tier-based therapy, osmotic therapy serves as an intermediate approach for reducing intracranial pressure (ICP). However, discussions regarding quantitative and specific criteria for the maintenance and transition of treatment remain limited. This study proposes an explainable neural network forecasting of physiological responses after osmotic therapy administration for the purpose of treatment guidance. Recordings of arterial blood pressure and intracranial pressure were obtained from 107 patients with traumatic brain injury. To maintain adequate intracranial pressure, arterial blood pressure, and cerebral perfusion pressure, 20 % mannitol (100 ml; no. infusion, 3,571) and 11.3 % hypertonic saline (40 ml; no. infusion, 574) were administered. The LTSF-NLinear model was used to predict the target signal response for the subsequent 1 h. Six prediction models were derived by combining two agents (mannitol or hypertonic saline) and three target signals (mean arterial blood pressure, mean intracranial pressure and cerebral perfusion pressure). To validate the model’s robustness while considering patient heterogeneity, group (5)-fold cross-validation was implemented. To assess the predictive ability of the proposed model for adverse clinical events, binary classification of hypotension, intracranial hypertension, and cerebral hypoperfusion was performed. The overall function of the model was elucidated using linear weight visualization. Additionally, the DeepSHAP application allows for a detailed investigation of the prediction process for a single case. The relationship between response to osmotic therapy and patient outcomes was statistically significant. The proposed models achieved reasonable performance, with R2 score > 0.8 for physiological signal predictions and accuracy > 0.9 for event predictions. Through global explanation, the recent values of mean arterial blood pressure, mean intracranial pressure, and cerebral perfusion pressure of input signals significantly influenced physiological responses after osmotic treatment. In the context of local explanation (a single case), it was possible to determine how physiological state influenced the response. The proposed model is expected to provide objective and quantitative information on osmotherapy in neurological intensive care environments, enabling guidance for alternative and aggressive treatments. Thus, it can potentially aid in enhancing the prognosis of patients with traumatic brain injury and improving the clinical workflow. Moreover, the global and local explanations of the proposed model can provide valuable insights for future researchers.

Role of Apigenin in Rats with Type 1 Diabetic Complications

Abstract Background and Aim The main factor contributing to diabetes morbidity and mortality is cardiovascular problems. Apigenin, a naturally occurring flavonoid with anti-inflammatory and anti-diabetic characteristics, was investigated for its cardioprotective potential. Methods Type 1 diabetes model was induced using single injection of streptozotocin and diabetic rats were injected with apigenin. ECG recording and measurement of blood pressure were performed. Biochemical analyses of serum glucose, lipid profile, and creatine kinase were done. Histological examination of cardiac tissues was also performed. Results Diabetic rats had higher levels of glucose and creatine kinase, and impaired lipid profile as compared to the control group. Apigenin improved glycemic control, dyslipidemia, and cardiac function markers. Diabetic group had significantly higher blood pressure values as compared to the control group. The mean systolic and diastolic blood pressure levels dropped after apigenin treatment. ECG showed decrease in heart rate and increase in R-voltage after apigenin-injection as compared to diabetic rats. Moreover, apigenin-injection resulted in reduced histological changes of cardiac tissues compared to diabetic rats. Conclusion Apigenin could serve as potential therapeutic agent to reverse effects of hyperglycemia and its cardiovascular complications in diabetes.

Characteristic Pressure Waveforms Can Distinguish Airway Collapse Patterns in Sleep Apnea Patients: A Pilot Study.

To use pharyngeal pressure recordings to distinguish different upper airway collapse patterns in obstructive sleep apnea (OSA) patients, and to assess whether these pressure recordings correlate with candidacy assessment for hypoglossal nerve stimulator (HGNS) implantation. Prospective case series. Single tertiary-quaternary care academic center. Subjects with OSA prospectively underwent simultaneous drug-induced sleep endoscopy (DISE) and transnasal pharyngeal pressure recording with a pressure-transducing catheter. Pressure was recorded in the nasopharynx and oropharynx, and endoscopic collapse patterns were classified based on site, extent, and direction of collapse. Pressure recordings were classified categorically by waveform shape as well as numerically by inspiratory and expiratory amplitudes and slopes. Waveform shape, amplitude, and slope were then compared with the endoscopic findings. Twenty-five subjects with OSA were included. Nasopharyngeal waveform shape was associated with the extent of collapse at the level of the palate (P = .001). Oropharyngeal waveform shape was associated with anatomical site of collapse (P < .001) and direction of collapse (P = .019) below the level of the palate. Pressure amplitudes and slopes were also associated with the extent of collapse at various sites. Waveform shape was also associated with favorable collapse pattern on endoscopy for HGNS implantation (P = .043), as well as surgical candidacy for HGNS (P = .004). Characteristic pharyngeal pressure waveforms are associated with different airway collapse patterns. Pharyngeal pressure is a promising adjunct to DISE in the sleep surgery candidacy evaluation.

Effectiveness of "Healthy Living Training Program" on Obese Policemen.

Considering the concerns of obesity problems, Mumbai Police authorities had launched full-day residential "Healthy Living Training Program" in February 2019 for obese policemen. We studied the effectiveness of the program by assessing health profile of the participants, and change in anthropometric measurements and blood pressure readings. Permission from the concerned authorities and approval from the Institutional Ethics Committee (IEC) were taken. Health profiles of 143 policemen were assessed. Anthropometric measurements and blood pressure recordings were done on the first and the last day of the 28-day program. The data were coded and entered in password-protected Microsoft Excel. Paired t-test was applied to test statistically significant differences. The association of some of the variables with weight change was assessed by the Chi-square test for categorical variables. The mean age of participants was 49.6 ± 5 years. The proportion of hypertensive, diabetics, vision problems, and bone and joint problems were 48.2%, 23.2%, 57.1%, and 46.4%, respectively. Only 70% of them had home-cooked food in the lunch. Daily, 50% of the participants do physical activity. There was statistically significant weight reduction (105.6 ± 12.1s vs. 103.3 ± 12 kg), body mass index (BMI) (36.3 ± 3.4 vs. 35.5 ± 3.3), waist circumference (110.8 ± 7.9 vs. 109.5 ± 7.9), and hip circumference (115.6 ± 8.1 vs. 106.8 ± 15.0) of the participants after 28 days of training program. "Healthy Living Training Program" was effective in reducing weight, blood pressure, BMI, and waist and hip circumference. The program benefitted the participants by inculcating healthy lifestyles and raising awareness of health issues.

Comparison of electrocardiogram and blood pressure recording methods in non-rodent toxicology studies: A retrospective analysis

Our study retrospectively examines 51 non-rodent general toxicology studies conducted over the past 8 years to ascertain the influence of recording methodologies on baseline cardiovascular (CV) parameters and statistical sensitivity. Specifically, our work aims to evaluate the frequency of cardiovascular parameter recording categorized by therapeutic modality and study type, to assess the variability in these parameters based on measurement techniques, and to determine the sample sizes needed for detecting relevant changes in heart rate (HR), blood pressure (BP), and QTc interval in non-human primate (NHP) studies.Results indicate that electrocardiogram (ECG) measurements in dogs and NHP were recorded in 63% of studies, combined with BP recording in 18% of studies, while BP was never recorded alone. Trend analysis reveals a decline in the utilisation of restraint-based methods for ECG measurements post-2017, to the benefit of telemetry-based recordings, particularly Jacketed External Telemetry (JET). There was a marked difference in baseline values, with restraint-based methods showing significantly higher HR and QTc values compared to JET, likely linked to animal stress.Further analysis suggests an unrealistic and unethical sample size requirement in NHP studies for detecting biologically meaningful CV parameter changes using restraint-based methods, while JET methods necessitate significantly smaller sample sizes.This retrospective study indicates a notable shift from snapshots short-duration, restraint-based methods towards telemetry approaches over the recent years, especially with an increased usage of implanted telemetry. The transition contributes to potential consensus within industry or regulatory frameworks for optimal practices in assessing ECG, HR, and BP in general toxicology studies.

The Use of Pressure Recording Analytical Method in Patients Undergoing Endovascular Repair for Abdominal Aortic Aneurysm: The Impact on Clinical Decisions for the Appropriate Postoperative Setting and Cost-effective Analysis.

To analyze the use of the Pressure Recording Analytical Method (PRAM), an hemodynamic monitoring system, in evaluating intraoperative and postoperative hemodynamic instability in patients undergoing endovascular repair for abdominal aortic aneurysm, and to evaluate if the decision to refer patients to a ordinary ward or to a Cardiac Step-Down Unit (CSDU) after the intervention on the basis of intraoperative hemodynamic monitoring could be more cost-effective. After preoperative clinical evaluation, 44 patients were divided in this non-randomised study into two groups according to their postoperative destination: Group 1-ward (N=22) and Group 2-CSDU (N=22). All patients underwent monitoring with PRAM during the intervention and in the 24 postoperative hours, measuring several indices of myocardial contractility and other hemodynamic variables. According to the variability of two parameters, Stroke Volume Variation and Pulse Pressure Variation, patients were classified as stable or unstable. Unstable patients showed a significant alteration in several hemodynamic indices, in comparison to stable ones. According to the intraoperative monitoring, eight high risk patients could have been sent to an ordinary ward due to their stability, with a reduction in the improper use of CSDU and, consequently, in costs. Hemodynamic monitoring with PRAM can be useful in these patients, both for intraoperative management and for the choice of the more appropriate postoperative setting, possibly reducing the improper use of CSDU for hemodynamically stable patients who are judged to be at high risk preoperatively, and re-evaluating low surgical risk patients with an unstable intraoperative pattern, with a possible reduction in costs.

Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.

Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor voclosporin causes hypomagnesemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally. Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric blood pressure recordings, and analysis of mRNA and protein levels of distal tubular transporters at day 28. Compared to vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased blood pressure, whereas voclosporin caused a gradual but persistent increase in blood pressure which was further characterized by high renin, normal aldosterone, and low endothelin-1. In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two calcineurin inhibitors.

Feasibility Study of Using the Integrated Telemedicine Platform “IS-cardio” for Outpatient Cardiological Rehabilitation: Single-Centered Cohort Study

INTRODUCTION. The implementation of remote cardiac rehabilitation (RCR) technology based on telemedicine platforms (TMP) requires a preliminary assessment of the feasibility of use. AIM. A preliminary study of the feasibility of using the integrated TMP “IS-cardio” to perform RCR in patients with cardiovascular diseases (CVD) in the context of need, feasibility and acceptability. MATERIALS AND METHODS. Single-center cohort study of patients (n = 33; 75 % men; mean age 56 ± 8 years) with CVD. Testing of the TMP «IS-cardio» was carried out during 12-week physical training (PT) programs with an intensity of 55 %. Feasibility was assessed according to the following criteria: need, feasibility, acceptability. Data on need and acceptability were obtained from a patient survey. Feasibility was assessed as the proportion of patients completing RCR. Remote monitoring was performed using heart rate, blood pressure, electrocardiogram and mobile application recorders. Feedback was provided in the form of electronic reports and delayed consultation. Patient satisfaction was assessed in points. RESULTS. 79.2 % of respondents were interested in telemedicine monitoring. 100 % of patients completed RCR; 12 patients (39.6 %) fully completed the PT program. The patients’ activity amounted to 2.4 ± 0.7 PT sessions per week; the average duration of PT was 56.5 ± 29.8 min/week. With a total satisfaction of 29.0 ± 3 points, the level of RCR was highly rated (3.85 ± 0.16 points) as a real solution to the problem associated with the presence of CVD (3.67 ± 0.34 points). DISCUSSION. The medical-technological solution TMP “IS-cardio”, combining the principles of traditional cardiac rehabilitation with telecardiology tools (monitoring based on digital recorders, automatic data transfer and feedback) met the criteria for the feasibility of using TMP with a similar concept. CONCLUSION. The high demand for remote monitoring, feasibility, and patient satisfaction of RCR may indicate the feasibility of its use for implementation of its programs.

Gastric Pressure Monitoring Unveils Abnormal Patient-Ventilator Interaction Related to Active Expiration: A Retrospective Observational Study.

Patient-ventilator dyssynchrony is frequently observed during assisted mechanical ventilation. However, the effects of expiratory muscle contraction on patient-ventilator interaction are underexplored. The authors hypothesized that active expiration would affect patient-ventilator interaction and they tested their hypothesis in a mixed cohort of invasively ventilated patients with spontaneous breathing activity. This is a retrospective observational study involving patients on assisted mechanical ventilation who had their esophageal pressure (Peso) and gastric pressure monitored for clinical purposes. Active expiration was defined as gastric pressure rise (ΔPgas) greater than or equal to 1.0 cm H2O during expiratory flow without a corresponding change in diaphragmatic pressure. Waveforms of Peso, gastric pressure, diaphragmatic pressure, flow, and airway pressure (Paw) were analyzed to identify and characterize abnormal patient-ventilator interaction. 76 patients were identified with Peso and gastric pressure recordings, of whom 58 demonstrated active expiration with a median ΔPgas of 3.4 cm H2O (interquartile range = 2.4 to 5.3) observed in this subgroup. Among these 58 patients, 23 presented the following events associated with expiratory muscle activity: (1) distortions in Paw and flow that resembled ineffective efforts, (2) distortions similar to autotriggering, (3) multiple triggering, (4) prolonged ventilatory cycles with biphasic inspiratory flow, with a median percentage (interquartile range) increase in mechanical inflation time and tidal volume of 54% (44 to 70%) and 25% (8 to 35%), respectively and (5) breathing exclusively by expiratory muscle relaxation. Gastric pressure monitoring was required to identify the association of active expiration with these events. Respiratory drive, assessed by the rate of inspiratory Peso decrease, was significantly higher in patients with active expiration (median [interquartile range] dPeso/dt: 12.7 [9.0 to 18.5] vs 9.2 [6.8 to 14.2] cmH2O/sec; P < 0.05). Active expiration can impair patient-ventilator interaction in critically ill patients. Without documenting gastric pressure, abnormal patient-ventilator interaction associated with expiratory muscle contraction may be mistakenly attributed to a mismatch between the patient's inspiratory effort and mechanical inflation. This misinterpretation could potentially influence decisions regarding clinical management.

A Multi-Parametric Approach for Characterising Cerebral Haemodynamics in Acute Ischaemic and Haemorrhagic Stroke.

Early differentiation between acute ischaemic (AIS) and haemorrhagic stroke (ICH), based on cerebral and peripheral hemodynamic parameters, would be advantageous to allow for pre-hospital interventions. In this preliminary study, we explored the potential of multiple parameters, including dynamic cerebral autoregulation, for phenotyping and differentiating each stroke sub-type. Eighty patients were included with clinical stroke syndromes confirmed by computed tomography within 48 h of symptom onset. Continuous recordings of bilateral cerebral blood velocity (transcranial Doppler ultrasound), end-tidal CO2 (capnography), electrocardiogram (ECG), and arterial blood pressure (ABP, Finometer) were used to derive 67 cerebral and peripheral parameters. A total of 68 patients with AIS (mean age 66.8 ± SD 12.4 years) and 12 patients with ICH (67.8 ± 16.2 years) were included. The median ± SD NIHSS of the cohort was 5 ± 4.6. Statistically significant differences between AIS and ICH were observed for (i) an autoregulation index (ARI) that was higher in the unaffected hemisphere (UH) for ICH compared to AIS (5.9 ± 1.7 vs. 4.9 ± 1.8 p = 0.07); (ii) coherence function for both hemispheres in different frequency bands (AH, p < 0.01; UH p < 0.02); (iii) a baroreceptor sensitivity (BRS) for the low-frequency (LF) bands that was higher for AIS (6.7 ± 4.2 vs. 4.10 ± 2.13 ms/mmHg, p = 0.04) compared to ICH, and that the mean gain of the BRS in the LF range was higher in the AIS than in the ICH (5.8 ± 5.3 vs. 2.7 ± 1.8 ms/mmHg, p = 0.0005); (iv) Systolic and diastolic velocities of the affected hemisphere (AH) that were significantly higher in ICH than in AIS (82.5 ± 28.09 vs. 61.9 ± 18.9 cm/s), systolic velocity (p = 0.002), and diastolic velocity (p = 0.05). Further multivariate modelling might improve the ability of multiple parameters to discriminate between AIS and ICH and warrants future prospective studies of ultra-early classification (<4 h post symptom onset) of stroke sub-types.

The effect of the lateral hypothalamic leptin circuit on cardiorespiratory control

In addition to its well-known roles in regulating metabolic homeostasis, leptin signaling in the brain has also been critically involved in cardiovascular and respiration functions. Although the central mechanisms mediating leptin’s effect on metabolic control have been extensively studied and elucidated, the neural substrates by which leptin exert its effect on cardiovascular and respiratory functions remain incompletely understood. Leptin receptors (LepRs) are expressed distinct hypothalamic nuclei, including the lateral hypothalamic area (LHA), a brain region historically known as the “feeding center”. We recently performed anterograde tract-tracing of LHA LepR-positive neurons and observed a broad but regionally enriched pattern of projections throughout the brain, including, but not limited to the brain regions involved in sympathetic control of cardiovascular function and breathing, such as the periaqueductal gray and ventrolateral medullar. Based on these preliminary neuroanatomical observations, we hypothesized that the LHA leptin circuit is critically involved in cardiorespiratory control. To test this hypothesis, we generated mice expressing hM3Dq-mCherry or mCherry (control) specifically in LHA LepR+ neurons by performing stereotaxic microinjection of Cre-dependent AAV-DIO-hM3Dq-mCherry or AAV-DIO-mCherry into the LHA of LepR-Cre+ mice. These mice were then subjected to radiotelemetry recording of blood pressure and whole-body plethysmography to evaluate the respiratory function. We found that chemogenetic activation of LHA LepR+ neurons by intraperitoneal injection of deschloroclozapine (DCZ, 0.5 mg/Kg) significantly elevated blood pressure (p&lt;0.01) and heart rate (p&lt;0.01) independently of locomotor activity. Whole-body plethysmography further revealed that activation of LHA LepR+ neurons also drastically increased the respiratory rate (p&lt;0.0001) and minute ventilation (p&lt;0.001) without a significant change in the tidal volume. Increased respiratory rate was associated with shortening both inspiratory and expiratory durations. These results identify the LHA as a novel hypothalamic node through which the circulating metabolic hormone leptin might influence cardiorespiratory control. This work is supported by the grants from the National Institute of Health (HL127673 and HL153274 to HC). 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.

Hemodynamic Monitoring of Pediatric Patients With Heart Failure and Pulmonary Hypertension Using CardioMEMS

BackgroundThe CardioMEMS is an implantable device for hemodynamic monitoring approved by the US Food and Drug Administration for adult patients with heart failure. It has been used in the adult population without structural heart disease and with congenital heart diseases, but we do not have data in the pediatric population. MethodsWe report the initial single-center experience of the CardioMEMS implantation in children. Feasibility of device implantation, procedural outcomes, and clinical utility in the pediatric population were evaluated. ResultsThe CardioMEMS device was implanted without technical complications in 8 pediatric patients (mean age 7 years and mean weight 27.9 kg) with pulmonary hypertension (6/8, 75%) and heart failure (2/8, 25%). The device was delivered via femoral access in 7 (85%) patients and implanted in the left pulmonary artery in 7 (85%). The noninvasive recording of pulmonary pressures in patients with pulmonary hypertension allowed the monitoring of the evolution of mean pulmonary artery pressure, intensifying vasodilator treatment, and avoiding control cardiac catheterizations. In patients with heart failure, pulmonary hemodynamic monitoring guided the decongestive treatment prior to heart transplantation. ConclusionsThe implantation of CardioMEMS in the pediatric population is a feasible procedure that allows the noninvasive hemodynamic monitoring of patients with heart failure and pulmonary hypertension. Its implementation in selected patients aids in outpatient follow-up and therapeutic management of patients with complex cardiac conditions, avoiding invasive procedures that require hospitalization. Further large-scale studies in the pediatric population are recommended.

LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 ACTIVITY IS NEGATIVELY ASSOCIATED WITH DECREASED BAROREFLEX SENSITIVITY IN HIGH NORMAL BLOOD PRESSURE

Objective: The relationship between baroreflex sensitivity (BRS) and inflammatory vascular biomarker Lipoprotein associated phospholipase A2 (Lp-PLA2) in subjects with high normal blood pressure (HNBP, prehypertensives) with a positive family history of hypertension (FHH+) to hypertension history free control subjects (FHH-) was evaluated. Design and method: A total of 24 HNBP participants (age 39.5 ± 2.5 years, 18 male/ 6 female) were studied. 14 HNBP subjects FHH+ were compared to 10 HNBP participants FHH-, being of similar age and body mass index. BRS (ms/mmHg) and BRSf (Hz/mmHg) were determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and inter-beat interval, controlled breathing at a frequency of 0.1 Hz). Venous blood was analysed for Lp-PLA2 biomarker of vascular inflammation and atherothrombotic activity. Results: A significant negative correlation between spontaneous BRS obtained by both methods and blood pressure (BP) was present (BRS spect r = –0.54, p&lt;0.001, BRS seq r = –0.59, p&lt;0.001). BRS obtained by sequence and spectral methods were reduced in HNBP FHH+ compared to group of HNBP without history of hypertension (P= 0.0317 BRS seq, P = 0.0395 BRS spect). There was no difference between both groups of HNBP subjects in BRSf values. Lp-PLA2 was significantly higher in HNBP FHH+ compared to FHH- controls (P = 0.025). Lp-PLA2 was negatively correlated with BRS obtained by sequence method (r = - 0.6758, P = 0.00028) and BRS obtained by spectral method (r = - 0.5935, P = 0.00031). Conclusions: Lipoprotein associated phospholipase A2 is negatively associated with decreased baroreflex sensitivity in subjects with high normal blood pressure and positive family history of hypertension. These findings demonstrate that reduced baroreflex sensitivity as marker of autonomic dysfunction is linked with vascular inflammation predominantly in otherwise healthy participants with positive history of hypertension that could predispose to increased risk of hypertension. Further research is needed.

MASKED HYPERTENSION IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE – AN UNDERESTIMATED RISK?

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension are major cardiovascular risk factors sharing a bi-directional relationship. Although nearly half of MASLD patients are suffering from arterial hypertension, data on the prevalence of different hypertension phenotypes (e.g. masked hypertension) in this patient population are scarce. Masked hypertension, which is defined by normal office blood pressure but elevated blood pressure in the ambulatory 24-hour blood pressure measurement (24-h-ABPM), often remains undetected, although it has a comparable risk for adverse cardiovascular events as sustained hypertension. Therefore, the identification of this hypertension phenotype in MASLD patients seems highly relevant. Design and method: To analyze the prevalence of masked hypertension and to improve hypertension management in MASLD patients we integrated a 24-h-ABPM-based hypertension screening and control program among MASLD patients in our outpatient liver department. A total of 226 MASLD patients were recruited during regular follow-up visits and recording of office blood pressure and 24-h-ABPM measurements were performed according to a standardized protocol. Results: For the final analysis, 218 data sets were evaluated. The median age of the included 218 patients was 51 years, 48.2% were female. 101 (46.3%) MASLD patients had prior history of hypertension. At the time of ABPM 93 (92.1%) of these patients received antihypertensive treatment. Masked hypertension was identified in 46 (21.1%) MASLD patients, 20 (43.5%) of whom were receiving antihypertensive treatment (masked uncontrolled hypertension). Interestingly, 14 (30.4%) MASLD patients with masked hypertension had isolated nocturnal masked hypertension. Furthermore, a non-dipping blood pressure pattern was recognized in 28 (60.9%) MASLD patients with masked hypertension. Conclusions: Due to the high rates of masked hypertension and abnormal nocturnal blood pressure dipping, which both represent important risk factors for adverse cardiovascular events, the establishment of hypertension screening and management programs in this high-risk population seems urgently needed. Controlled hypertension reduces the risk of cardiovascular events in this vulnerable population and, due to the strong link between MASLD and hypertension, possibly also slow the progression of MASLD to advanced liver fibrosis or cirrhosis.

Toll-like Receptor 4 Promotes Salt-Sensitivity in Dahl SS Rats: An Investigation into the Mechanism

Renal inflammation accompanies hypertension and renal damage in Dahl Salt-Sensitive (SS) rats fed a high salt diet (HS, Dyets AIN-76A 4.0% NaCl). Previous studies demonstrated that toll-like receptor 4 (TLR4), a component of innate immune activation, is upregulated in macrophages infiltrating the kidneys of Dahl SS rats fed high salt. Preliminary studies in our laboratory indicated that mean arterial pressure (MAP) (SS: 162.5 ± 4.9 vs. SSTLR4−/−: 147.1 ± 3.5 mmHg, p&lt;0.0001, n=10/group) and albuminuria (321.3 ± 62.7 vs. 170.6 ± 27.1 mg/day, p&lt;0.05, n=10/group) were significantly reduced in male Dahl SS TLR4 knockout rats (SSTLR4−/−) compared to male SS after three weeks of HS. Furthermore, peritoneal macrophages isolated from SSTLR4−/− produce significantly less IL-1β compared to SS macrophages upon stimulation with lipopolysaccharide (LPS) . Since TLR4 is widely expressed in many tissues, we examined the specific effects of TLR4 deletion in immune cells via a total body irradiation/bone marrow transfer approach. The present study tested the hypothesis that TLR4 deletion specifically in hematopoietic cells would attenuate male Dahl SS hypertension and renal damage. At 6 weeks of age, Dahl SS male recipients were irradiated (11Gy) then received either SS or SSTLR4−/− bone marrow transplantation via tail vein injection (~15-20 million cells). Following recovery, rats (maintained on a low salt chow (LS, Dyets AIN-76A 0.4% NaCl)) underwent telemeter implantation at approximately 8 weeks of age for continuous monitoring of blood pressure. Animals were switched to HS following recovery and baseline blood pressure recordings. Urine samples were collected once during the LS period and weekly throughout a 3-week HS challenge. Upon euthanasia, kidneys were flushed and harvested for analysis. MAP was not found to be different between groups during the LS baseline period (SS: 113.4 ± 1.6 vs. SSTLR4−/−: 116.5 ± 2.3 mmHg, n=5-6/group), and our preliminary data also revealed that MAP was not different between groups throughout the high salt challenge (HS day 20: 136.4 ± 10.5 vs 144.8 ± 9.2). Urinary albumin excretion was also not found to be different between rats receiving either SS or TLR4−/− bone marrow transfer (165.2 ± 38.5 vs. 247.9 ± 58.7 mg/day, n=7/group). Furthermore, assessment of BUN at the conclusion of the experiment revealed no differences (33.0 ± 6.1 vs. 29.3 ± 3.2 mg/dL, n=7/group). Immune cells were isolated from the blood and kidneys of these animals and characterized by flow cytometric analysis. There was no difference in the number of circulating leukocytes or lymphocytes (2.1x106 vs. 2.3x106 CD45+ cells per mL blood, n=6-7/group) indicating comparable reconstitution of immune cells in both groups. We also found no difference in renal infiltrating leukocytes or lymphocytes (3.1 x106 vs. 3.2x106 CD45+ cells per kidney, n=7/group). Together, these data contrast the effects of whole-body TLR4 knockout and suggest that TLR4 in hematopoietic cells may not be responsible for promoting Dahl SS hypertension and renal damage in males. Further studies are needed to assess the inflammatory status of immune cells from these animals as well as alternative TLR4-expressing cell types responsible for promoting disease. 23PRE1020121, HL161231, HL166458. 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.

Immune Metabolic Reprogramming by Excess Dietary Salt in Salt Sensitive Hypertension via CXCL8

Salt sensitivity of blood pressure (SSBP) is when blood pressure changes parallel to salt loading/ depletion and is an independent risk factor for cardiovascular disease. Despite its importance, there is no feasible diagnosis, which limits investigational studies to identify therapeutic targets. We have found that immune cells mediate SSBP via Epithelial Sodium Channel (ENaC). CXCL8/(IL-8), a known chemoattractant plays a well-known role in glycolysis. We hypothesize that CXCL8 mediates immune metabolic reprogramming of immune cells to glycolysis via ENaC. To test this hypothesis, we performed bulk and single cell RNA sequencing in human monocytes from individuals from a modified Weinberger inpatient salt loading/ depletion protocol. The participants were instructed to refrain from taking their blood pressure medication for 2 weeks prior to the salt loading/depletion protocol. Blood and urine samples were collected, as well as ambulatory blood pressure recording. We found that changes in immune cell activation via isolevuglandin (IsoLG) protein-adducts mirror changes in salt balance and blood pressure in salt sensitive but not salt resistant individuals. We confirmed that these in vivo changes can be recapitulated in vitro. In addition, we found that salt-loading both in vivo and in vitro increases antigen presenting cell production of IL-8, which was reversed after salt depletion in salt sensitive, but not salt resistant people. ENaC inhibition by amiloride prevented the high salt-induced production of IL-8. Moreover, high salt induced blood pressure changes of expression of CXCL8 (p = 0.01553, r = 0.8067) were significant along with varying expression of glycolytic genes, including hexokinase 1(HK1)(p = 0.04190, r = -0.7249), phosphofructokinase (PFKP)(p = 0.05932, r = 0.6879) and galactose mutarotase (GALM) (p = 0.04176, r = 0.5138). Seahorse analysis revealed increased extracellular acidification rate (ECAR) in high salt conditioned monocytes, which was associated with mitochondrial dysfunction. Our results suggest that high salt intake reprograms antigen presenting cell metabolism to glycolysis via IL-8 signaling. Furthermore, targeting IL-8 and mitochondrial switching to glycolysis may not only provide novel therapeutic approaches, but also important biomarkers for diagnosis of salt sensitivity of blood pressure. 1R03HL155041-01 (Kirabo, PI), 1R01HL144941-01A1 (Kirabo, PI), 5R01HL147818-22 (Kleyman &amp; Kirabo), 1R01HL157584-01 (Shibao, Kirabo — MPI), R01DK135764 (Kon, Shelton, Kirabo — MPI), R21TW012635 (Kirabo, Masenga — MPI), Meharry Medical College: School of Graduate Studies T32AI007281, T32GM14492, andT32HL00773. 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.

Physical Modelling Of A Caisson Breakwater Under Impulsive Cyclonic Waves : Case Of Port East (Reunion Island)

The GPMDLR (Port Authority of La Réunion Island, France) has requested ARTELIA to carry out the preliminary studies for the enlargement of the containers terminal in Port East. In this context, the laboratory of ARTELIA has performed 2D physical model testing to evaluate the behavior of caissons exposed to cyclonic conditions. The solution based on a vertical breakwater has been proposed as an alternative to a rubble mound breakwater given the lack of quarries suitable to provide big quantities of large rocks. Main objectives of the study were: the evaluation of overtopping rates (mean and max), the verification of the stability of foot protection blocks and stones, and the recording of wave pressures (gauges) and loads (scale) on the caissons. Given the fact that most of the waves broke violently upon the caisson, the nature of efforts was impulsive and the scaling to prototype by classical Froude similarity principles was not appropriate. Results were therefore amended following Cuomo’s correction factors for the Froude scaling law (Cuomo et al. 2010). Times series of efforts (forces and pressures) were used to feed numerical models (static and dynamic) allowing for the verification of caissons’ geotechnical stability and the design of concrete parts. This article collects the concerns, feedback and further questioning related to the conducted experiment.

The Effect of Clothes on Blood Pressure Measurement in Normotensive and Hypertensive Subjects in a Real-Life Setting

Introduction: The effect of clothing on the recording of blood pressure in a normotensive and hypertensive population remains essential to diagnosing and managing. Methods: This is a cross-sectional study to measure blood pressure using a validated oscillometric sphygmomanometer in two populations. The records were made over the thicker sleeve arm and non-sleeved arm (either on bare arm or indicating the removal of the outermost garment). Clothing was categorized according to how patients attended the outpatient clinic based on the real world. Results: A total of 75 patients were included with a diagnosis of hypertension whose mean age was 67.1 years (SD ± 16.3). The group of normotension included 63 patients whose mean age was 21.1 years (SD ± 2.2). There was not variability related to technique or inherent to the condition of the subject on the first and second measurements of blood pressure. In the comparative analysis, the group with normotension did not report a significant difference in systolic or diastolic blood pressure due to the effect of clothing during the first or second measurement (p > 0.05). In the group with hypertension, a significant difference was observed in the first measurement, between the group over-the-sleeve and non-sleeved arm (systolic blood pressure, p: 0.021 and diastolic, p: 0.001). However, when the variable order of measurement was analyzed by randomizing the initial registry with or without clothing was not found a statistical difference. Conclusion: Clothing does not a significant difference in the measure of blood pressure in a normotensive or hypertensive population.

Impact of distension pressure on saphenous vein endothelial injury in coronary artery bypass grafting.

Long saphenous vein grafts (LSVGs) are pivotal conduits in coronary artery bypass grafting (CABG), yet concerns persist regarding early failure and long-term patency. Endothelial damage, a potent initiator of graft failure, necessitates exploration of factors contributing to endothelial injury during LSVG preparation. A prospective, single-center study was conducted, assessing the impact of unregulated distension pressure on LSVG endothelium during CABG. Histological and CD31 (cluster of differentiation 31) immunohistochemical analyses were performed on 21 paired vein samples, categorized into non-distended (group A) and distended (group B) groups. Pressure recordings were obtained using different syringe sizes during vein distension. Histological examination revealed a significantly higher percentage of endothelial cell loss in distended veins (31.95% ± 31.31) compared to non-distended veins (11.67% ± 28.65) (p = 0.034). CD31 immunohistochemistry corroborated greater endothelial cell loss in distended veins (p = 0.001). The pressure recordings with a 20-cc syringe, as opposed to using a 10-cc syringe, were considerably lower (44.5mmHg vs. 92.75mmHg) emphasizing the inverse relationship between syringe size and pressure generated. In our study, pre-existing endothelial injury was observed in one-third of diabetic patients (36%), with all instances of such injury exclusively identified in individuals with diabetes. Unregulated distension pressure during LSVG preparation is associated with greater endothelial damage, as evidenced by histological and immunohistochemical analyses. The inverse relationship between syringe size and pressure underscores the importance of controlled distension.

The mesenteric entry site as a potential weak point in gastrointestinal anastomoses – findings from an ex-vivo biomechanical analysis

PurposeGastrointestinal disorders frequently necessitate surgery involving intestinal resection and anastomosis formation, potentially leading to severe complications like anastomotic leakage (AL) which is associated with increased morbidity, mortality, and adverse oncologic outcomes. While extensive research has explored the biology of anastomotic healing, there is limited understanding of the biomechanical properties of gastrointestinal anastomoses, which was aimed to be unraveled in this study.MethodsAn ex-vivo model was developed for the biomechanical analysis of 32 handsewn porcine end-to-end anastomoses, using interrupted and continuous suture techniques subjected to different flow models. While multiple cameras captured different angles of the anastomosis, comprehensive data recording of pressure, time, and temperature was performed simultaneously. Special focus was laid on monitoring time, location and pressure of anastomotic leakage (LP) and bursting pressures (BP) depending on suture techniques and flow models.ResultsSignificant differences in LP, BP, and time intervals were observed based on the flow model but not on the suture techniques applied. Interestingly, anastomoses at the insertion site of the mesentery exhibited significantly higher rates of leakage and bursting compared to other sections of the anastomosis.ConclusionThe developed ex-vivo model facilitated comparable, reproducible, and user-independent biomechanical analyses. Assessing biomechanical properties of anastomoses offers an advantage in identifying technical weak points to refine surgical techniques, potentially reducing complications like AL. The results indicate that mesenteric insertion serves as a potential weak spot for AL, warranting further investigations and refinements in surgical techniques to optimize outcomes in this critical area of anastomotic procedures.