Mean Arterial Pressure Monitoring Research Articles

Venoarterial Extracorporeal Membrane Oxygenation Implementation in Septic Shock Rat Model.

Septic shock, a global health concern, boasts high mortality rates. Research exploring the efficacy of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in septic shock remains limited. Our study aimed to establish a rodent model employing VA-ECMO in septic shock rats, assessing the therapeutic impact of VA-ECMO on septic shock. Nineteen Sprague-Dawley rats were randomly assigned to sham, septic shock, and (septic shock + VA-ECMO; SSE) groups. Septic shock was induced by intravenous lipopolysaccharides, confirmed by a mean arterial pressure drop to 25-30% of baseline. Rats in the SSE group received 2 hours of VA-ECMO support and 60 minutes of post-weaning ventilation. Sham and septic shock groups underwent mechanical ventilation for equivalent durations. Invasive mean arterial pressure monitoring, echocardiographic examinations, and blood gas analysis revealed the efficacy of VA-ECMO in restoring circulation and ensuring adequate tissue oxygenation in septic shock rats. Post-experiment pathology exhibited the potential of VA-ECMO in mitigating major organ injury. In summary, our study successfully established a stable septic shock rat model with the implementation of VA-ECMO, offering a valuable platform to explore molecular mechanisms underlying VA-ECMO's impact on septic shock.

Cryptotanshinone ameliorates hemorrhagic shock-induced liver injury via activating the Nrf2 signaling pathway.

Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activitywere suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.

Is Continuous Intraoperative Monitoring of Mean Arterial Pressure as Good as the Hypotension Prediction Index Algorithm?: Research Letter.

Is Continuous Intraoperative Monitoring of Mean Arterial Pressure as Good as the Hypotension Prediction Index Algorithm?: Research Letter.

Experimental model of acute blood loss using rats for screening evalution of non-specific activity of infusion solutions

BACKGROUND: In accordance with the current regulations, preclinical evaluation of the effectiveness of plasma substitutes for acute blood loss is carried out mainly on large laboratory animals (dogs, pigs) using a wide range of methods for assessing the structural and functional state of organs and systems of a biological object. It requires large expenditure of material resources and time, which is impractical at the stage of screening the effectiveness of newly developed infusion agents. In this regard, an urgent task is to develop a standardized model of acute blood loss on small laboratory animals for screening evaluation of the specific activity of infusion solutions with a subsequent research involving large laboratory animals. It is advisable to use laboratory rats as a biological object as they are the most suitable of the group of small laboratory animals for similarity of physiological laboratory indicators with humans.
 AIM: To develop a model of acute blood loss using small laboratory animals for screening evaluation of specific infusion solution activity.
 MATERIALS AND METHODS: Experiments were carried out on rats of the Vistar line with a weight of 330 41 g. The animals were divided into 3 groups: 1 experimental (20 individuals with acute blood loss simulation without treatment), 2 experimental (20 individuals with acute blood loss simulation and its replacement with Rheopolyglucin), intact (10 individuals without modeling of blood loss). The study design included: general anesthesia (intramuscular injection Zoletil 100 and Xylazin 2% in a ratio of 1 : 5 at the rate of 0.01 ml/kg of weight), catheterization of the femoral artery followed by controlled hardware exfusion of blood at a rate of 0.5 ml/min until the establishment of persistent (for 2 minutes) arterial hypotension; hardware synchronous monitoring of mean arterial pressure (MAP) (by direct tonometry through the contralateral femoral artery); calculation of the percentage of blood loss from the estimated circulating blood volume (CBV) equal to 5% of the animals weight; heart rate (HR) (by electrocardiogram) during the first three hours after blood exfusion. In its capacity as a test drug Rheopolyglucin, which was administered through an arterial femoral catheter immediately after blood exfusion in volume and speed, equal to volume and speed of exfusion, was used. Additionally, for a comprehensive assessment of the mechanisms of maintaining hemodynamic parameters individual dynamic calculated indicators for each individual are proposed: the reduced shock volume of blood and the infusion efficiency indicator.
 RESULTS: All rats in the experimental group died, 25% of which 1720 minutes after blood exfusion, 75% in range from 45 to 90 minutes. Rheopoliglyukin infusion reduced the death of animals by up to 35% and delayed the average death time to 4555 minutes. A single exfusion of blood in rats resulted in loss of 79 ml of blood (4651% of circulating blood volume), which was accompanied by a decrease in mean arterial pressure and heart rate. Compensation for the decrease in circulating blood volume, including due to infusion, was manifested by an increase in these indicators. A sign of inefficiency of compensation was a slight increase of mean arterial pressure with dynamically increasing heart rate. It is proved that an increase in the values of calculated indicators (the given stroke volume of blood and the infusion efficiency indicator) are benchmarks for effective compensation of hemodynamic disorders, including as a result of infusion of hemodynamic drugs.
 CONCLUSIONS: The acute blood loss model with the calculation of the reduced shock volume of blood and the infusion efficiency index is advisable to use to assess the specific activity of infusion solutions in acute blood loss.

Cerebrovascular Pressure Reactivity According to Long-Pressure Reactivity Index During Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage

BackgroundSpreading depolarization (SD) has been linked to the impairment of neurovascular coupling. However, the association between SD occurrence and cerebrovascular pressure reactivity as a surrogate of cerebral autoregulation (CA) remains unclear. Therefore, we analyzed CA using the long-pressure reactivity index (L-PRx) during SDs in patients with aneurysmal subarachnoid hemorrhage (aSAH).MethodsA retrospective study of patients with aSAH who were recruited at two centers, Heidelberg (HD) and Berlin (BE), was performed. Continuous monitoring of mean arterial pressure (MAP) and intracranial pressure (ICP) was recorded. ICP was measured using an intraparenchymal probe in HD patients and was measure in BE patients through external ventricular drainage. Electrocorticographic (ECoG) activity was continuously recorded between 3 and 13 days after hemorrhage. Autoregulation according to L-PRx was calculated as a moving linear Pearson’s correlation of 20-min averages of MAP and ICP. For every identified SD, 60-min intervals of L-PRx were averaged, plotted, and analyzed depending on SD occurrence. Random L-PRx recording periods without SDs served as the control.ResultsA total of 19 patients (HD n = 14, BE n = 5, mean age 50.4 years, 9 female patients) were monitored for a mean duration of 230.4 h (range 96–360, STD ± 69.6 h), during which ECoG recordings revealed a total number of 277 SDs. Of these, 184 represented a single SD, and 93 SDs presented in clusters. In HD patients, mean L-PRx values were 0.12 (95% confidence interval [CI] 0.11–0.13) during SDs and 0.07 (95% CI 0.06–0.08) during control periods (p < 0.001). Similarly, in BE patients, a higher L-PRx value of 0.11 (95% CI 0.11–0.12) was detected during SDs than that during control periods (0.08, 95% CI 0.07–0.09; p < 0.001). In a more detailed analysis, CA changes registered through an intraparenchymal probe (HD patients) revealed that clustered SD periods were characterized by signs of more severely impaired CA (L-PRx during SD in clusters: 0.23 [95% CI 0.20–0.25]; single SD: 0.09 [95% CI 0.08–0.10]; control periods: 0.07 [95% CI 0.06–0.08]; p < 0.001). This group also showed significant increases in ICP during SDs in clusters compared with single SD and control periods.ConclusionsNeuromonitoring for simultaneous assessment of cerebrovascular pressure reactivity using 20-min averages of MAP and ICP measured by L-PRx during SD events is feasible. SD occurrence was associated with significant increases in L-PRx values indicative of CA disturbances. An impaired CA was found during SD in clusters when using an intraparenchymal probe. This preliminary study validates the use of cerebrovascular reactivity indices to evaluate CA disturbances during SDs. Our results warrant further investigation in larger prospective patient cohorts.

Exploiting moving slope features of PPG derivatives for estimation of mean arterial pressure.

Monitoring Mean Arterial Pressure (MAP) helps calculate the arteries' flow, resistance, and pressure. It allows doctors to check how well the blood flows through our body and reaches all major organs. Photoplethysmogram technology is gaining momentum and popularity in smart wearable devices to monitor cuff-less blood pressure (BP). However, the performance reliability of the existing PPG-based BP estimation devices is still poor. Inaccuracy in estimating systolic and diastolic blood pressure leads to an overall imprecision in resultant MAP values. Hence, there is a need for robust and reliable MAP estimation algorithms. This work exploits the moving slope features of PPG contour in its first and second derivatives that directly correlate with MAP and does not require estimating systolic and diastolic blood pressure values. The proposed approach is evaluated using two different data sets (i.e., MIMIC-I and MIMIC-II) to demonstrate the robustness and reliability of the work for personalized non-invasive BP monitoring devices to estimate MAP directly. A mean absolute error of and a standard deviation of is obtained with MIMIC-II data-set using GridSearchCV random forest regressor that outperformed most of the existing related works.

Heart rate and diastolic arterial pressure in cardiac arrest patients: A nationwide, multicenter prospective registry.

Guidelines have recommended monitoring mean arterial pressure (MAP) and systolic arterial pressure (SAP) in cardiac arrest patients, but there has been relatively little regard for diastolic arterial pressure (DAP) and heart rate (HR). We aimed to determine the prognostic significance of hemodynamic parameters at all time points during targeted temperature management (TTM). We reviewed the SAP, DAP, MAP, and HR data in out-of-hospital cardiac arrest (OHCA) survivors from the prospective multicenter registry of 22 teaching hospitals. This study included 1371 patients who underwent TTM among 10,258 cardiac arrest patients. The hemodynamic parameters were recorded every 6 hours from the return of spontaneous circulation (ROSC) to 4 days. The risks of those according to time points during TTM were compared. Of the included patients, 943 (68.8%) had poor neurological outcomes. The predictive ability of DAP surpassed that of SAP and MAP at all time points, and among the hemodynamic variables HR/DAP was the best predictor of the poor outcome. The risks in patients with DAP < 55 to 70 mmHg and HR > 70 to 100 beats/min were steeply increased for 2 days after ROSC and correlated with the poor outcome at all time points. Bradycardia showed lower risks only at 6 hours to 24 hours after ROSC. Hemodynamic parameters should be intensively monitored especially for 2 days after ROSC because cardiac arrest patients may be vulnerable to hemodynamic instability during TTM. Monitoring HR/DAP can help access the risks in cardiac arrest patients.

Clinical Significance of Multiparameter Intracranial Pressure Monitoring in the Prognosis Prediction of Hypertensive Intracerebral Hemorrhage.

Objective: The present study aimed to investigate the clinical significance of multiparameter intracranial pressure (ICP) monitoring in the prediction of the prognosis of hypertensive intracerebral hemorrhage (HICH). Methods: A retrospective analysis was performed on the clinical data of 53 HICH patients. The patients underwent removal of intracranial hemorrhage and decompressive craniectomy after admission. A ventricular ICP monitoring probe was used to continuously and invasively monitor mean arterial pressure (MAP) and ICP after surgery. The NEUMATIC system was used to collect ICP data, including pressure reactivity index (PRx), ICP dose (DICP), amplitude and pressure regression (RAP), and cerebral perfusion pressure (CPP). The mean PRx, CPP, RAP, ICP, and DICP20 mmHg × h were calculated with 1 h as the time segment. According to the Glasgow outcome scale (GOS) scores after discharge, the patients were grouped into the poor prognosis group (GOS I–III) and the good prognosis group (GOS IV and V). The two groups were compared in terms of GOS scores in the treatment and prediction of prognosis of patients. Results: The good prognosis group showed significantly lower values of mean ICP, DICP20 mmHg × h, RAP, and PRx than the poor prognosis group, while CPP was significantly higher (p < 0.001). Conclusions: PRx, DICP, RAP, and CPP could reflect intracranial changes in patients and were significantly correlated with the prognosis of the patients. Mean ICP, PRx, DICP20 mmHg × h, and RAP were negatively correlated with prognosis, while CPP was positively correlated with prognosis.

Remote Ischemic Preconditioning Attenuates Hepatic Ischemia/Reperfusion Injury after Hemorrhagic Shock by Increasing Autophagy.

Fluid resuscitation after hemorrhagic shock is a model of systemic ischemia/reperfusion injury (SI/RI), and the liver is one of the main target organs. Ischemic preconditioning (IPC) can reduce hepatic ischemia-reperfusion injury (I/RI) via autophagy. However, whether remote ischemic preconditioning (RIPC) can alleviate the liver injury that is secondary to hemorrhagic shock and the role of autophagy in this process remain unclear. Thus, we constructed a hemorrhagic shock model in rats with or without RIPC to monitor mean arterial pressure (MAP) and investigate liver secondary injury levels via serum aminotransferase, ultrasound, HE staining and TUNEL fluorescence staining. We also detected levels of serum inflammatory factors including tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) by enzyme-linked immunosorbent assay (ELLSA), observed autophagosomes by Transmission electron microscopy (TEM), and analyzed LC3, Beclin-1, p62 protein expression levels by immunohistochemical (IHC) and western blot (WB). We found that RIPC increased blood pressure adaptability, decreased lactate (Lac) and aminotransferase levels, and delayed the decrease in liver density. Levels of inflammatory factors TNF-α, IL-1β and apoptosis were attenuated, autophagosomes was increased in the RIPC group compared with controls. IHC and WB both revealed increased LC3 and Beclin-1 but decreased p62 protein expression levels in the RIPC group. Together, our data suggest that RIPC-activated autophagy could play a protective role against secondary liver injury following hemorrhagic shock.

Associations between mean systemic filling pressure and acute kidney injury: An observational cohort study following cardiac surgery.

Venous congestion has been implied in cardiac surgery-associated acute kidney injury (CSA-AKI). The mean systemic filling pressure may provide a physiologically more accurate estimate of renal venous pressure and renal perfusion pressure but its association with CSA-AKI has not been reported. Patients admitted to ICU following cardiac surgery without pre-operative renal dysfunction were included with monitoring of mean arterial pressure (MAP) and central venous pressure (CVP) and cardiac output (CO) to calculate the mean systemic filling pressure analogue (Pmsa ). The AKI-KDIGO guidelines were used to define CSA-AKI. Logistic regression models including CO, heart rate, MAP, CVP and Pmsa were used to ascertain the association with CSA-AKI and reported by odds ratio (OR) with 95% confidence interval (95%CI) and area under the curve (AUROC). One hundred and thirty patients (out of 221 screened) were included of whom 66 (51%) developed CSA-AKI. Patients with CSA-AKI were older, with greater weight and increased stay in ICU while the proportion of comorbidities, type of surgical procedures, APACHE III scores and fluid volumes administered were similar to patients without AKI. The Pmsa , but not CVP, was associated with CSA-AKI (OR 1.2 95%CI [1.16-1.25]). Renal perfusion pressure was associated with CSA-AKI estimated as MAP-Pmsa (OR 0.81 [0.76-0.86]) and MAP-CVP (OR 0.89 [0.85-0.93]) with the former generating a higher AUROC (median difference 0.10 [0.07-0.12], P<.001) in the regression model. The Pmsa in post-operative cardiac surgery patients was associated with the development of CSA-AKI also when incorporated into estimates of renal perfusion pressure.

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension*

BACKGROUNDModerate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVETo observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGNA randomized controlled trial. SETTINGDepartment of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALSTwenty healthy little pigs, either male or female, weighing 4.5 – 5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODSThe experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n = 10) and moderate hypothermia group (n = 10). (1) Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3-]. (2) Rectal temperature was monitored with mercurial thermometer. (3) Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. (4) Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3 and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 °C using ice bags, and the body temperature was maintained at 33 – 35 ºC for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES(1) MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; (2) Results of blood gases analysis in the moderate hypothermia group. RESULTSAll the 20 pigs were involved in the analysis of results. (1) MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ºC, P < 0.05]. (2) Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSIONModerate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.

Cerebral Hemodynamic Profile in Ischemic and Hemorrhagic Brain Injury Acquired During Pediatric Extracorporeal Membrane Oxygenation.

To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation. A retrospective cohort study. Tertiary PICU. Forty-seven neonatal and pediatric patients (0-15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018. Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group. This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.

Acute Administration of Gut Microbial Metabolites Reduces Blood Pressure and Cardiac Contractility

Metabolites produced by the gut microbiota can affect host physiology; one class of these metabolites are short chain fatty acids (SCFAs). Prior work by our laboratory has shown that intravenous administration of SCFAs causes acute hypotension (Pluznick, Protzko et al. 2013) and that treating vessels with SCFAs ex vivo results in vasorelaxation (Natarajan, Hori et al. 2016). To expand upon these findings, we performed IP injections of acetate in mice that were implanted with DSI telemetry transmitters to monitor mean arterial pressure (MAP) and heart rate (HR) in real time. Sodium acetate (acetate is the most abundant SCFA in the circulation) was given at a 1g/kg dose via IP, which elevates plasma acetate by 3–4 fold over baseline (Shubitowski, Poll et al. 2019). Upon sodium acetate IP injection, we observed a rapid and reproducible drop in MAP (−49.2 +/− 10.7 mmHg maximum drop, n=10 males + females, p&lt;0.05) when compared to an IP injection of saline. Surprisingly, in addition to a significant depression of MAP, mice injected with acetate also showed a significant depression in HR (−257.6 +/− 55.8 bpm maximum drop, p&lt;0.05). IP injections of propionate and butyrate, two other SCFA microbial metabolites, had similar depressive effects on MAP and HR, but lactate (control) had no effect. Had SCFAs been solely acting on the vasculature, we would have expected the baroreflex to increase HR. To determine if acetate was having a direct cardiac effect, we used isolated perfused Langendorff hearts from mice. During acetate infusion, Langendorff hearts showed a significant decrease in HR, suggesting a direct mechanism of action (353.8 +/− 39.5 bpm baseline vs 274.6 +/− 21.3 bpm acetate n=5, p&lt;0.05), however the HR drop was on a much slower time scale than seen in vivo. To further probe the effects of acetate on cardiac contractility, pressure volume loops were performed on anesthetized mice and acetate was administered by IP. Inferior vena cava occlusion after acetate IP showed a significant decrease in Preload Recruitable Stroke Work (PRSW, 73.06 +/− 20.98 vs. 49.06 +/− 22.11 mmHg*μl baseline vs acetate, n=7 males + females, p&lt;0.05) and end‐systolic elastance (Ees, 3.493 +/−1.139 vs. 1.519 +/− 0.5781 mmHg/μl baseline vs. acetate, n=7 males + females, p&lt;0.05), two parameters of load‐independent cardiac contractility. Finally, pre‐treatment of conscious mice with cardioselective β antagonist metoprolol blocked the acetate mediated drop in HR in mice implanted with telemetry devices, but the drop in MAP remained intact. We hypothesize that acetate acts independently on the peripheral vasculature and the cardiac muscle, with direct and indirect effects on cardiac function. Both components are likely contributing to the MAP and HR effects seen in whole animals. Together these data demonstrate a previously unknown and potentially detrimental effect of short chain fatty acids on cardiac function.Support or Funding InformationF31HL144061, R01HL128512, R01DK107726

The Comparison of High Flow Nasal Cannula Oxygen and Conventional Oxygen Therapy on Early Effect Hemodynamic Indicators in Post – Upper Abdominal Surgery Patients

Background&#x0D; The effect of high-flow nasal cannula (HFNC) on hemodynamic data of the patients is still unknown. This was a pilot study to evaluate the effect of HFNC and conventional oxygen therapy (COT) on post-upper abdominal surgery.&#x0D; &#x0D; Methods&#x0D; This was an open-label randomized controlled trial (RCT) at tertiary hospital between February-June 2019. Inclusion criteria were ASA III, aged 18-65 years, BMI 18,5-29 kg/m2. Exclusion criteria were patients with unstable hemodynamic with vasopressors, general oedema, and uncooperative. Thirty patients were recruited and divided into HFNC group (n=15) and COT group (n=15). Hemodynamic parameters were recorded using the bedside monitor (heart rate, respiratory rate, and mean arterial pressure) as well as the electrical cardiometry using ICON® measurements (stroke volume index, cardiac index and systemic vascular resistance index); laboratory parameters were ScVO2 and lactate serum. Data were collected at 0, 30 and 60 minutes post-extubation.&#x0D; Results&#x0D; The General Linear Model (GLM) tests on clinical parameters (HR, RR and MAP) were P= 0.20; P=0.72; P = 0.18, ICON® parameters (SVI, CI and SVRI) were P= 0.02;P =0.64; P =0.64 meanwhile ScVO2 and lactate were P = 0.35 and P = 0.22. Despite those results, at some period of measurements there were a tendency of a better outcomes of most parameters for the HFNC group.&#x0D; Conclusion&#x0D; According to the results, the only statistically significant outcome was SVI (P =0.02) after the analysis between those two groups. However, the HFNC group showed a clinically improvement of the other outcomes among post-upper abdominal surgery patients.&#x0D; Keywords &#x0D; High flow nasal cannula, conventional oxygen therapy, haemodynamic, abdominal surgery

Nocturnal Mean Arterial Pressure Rising Is Associated With Mortality in the Intensive Care Unit: A Retrospective Cohort Study

BackgroundDisrupted circadian rhythm of blood pressure is commonly observed in patients in the intensive care unit (ICU). This study assessed the association of nocturnal mean arterial pressure rising (NMAPR) with short‐ and long‐term mortality in critically ill adult patients.Methods and ResultsAdult patients with a complete record of mean arterial pressure monitoring during the first 24 hours of ICU stay in the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC‐II) database were included in this retrospective cohort study. All patients were divided into the non‐NMAPR group (≤1) or the NMAPR group (>1), according to the value of mean nighttime divided by daytime mean arterial pressure. The associations of NMAPR with ICU, hospital, 28‐day, and 1‐year mortality were assessed using multivariable logistic regression or a Cox proportional hazards model. Interaction and subgroup analyses were performed for those patients who had a first Sequential Organ Failure Assessment (SOFA) score of ≥8 or <8. The overall cohort comprised 5185 patients. The patients with NMAPR (n=1865) had higher ICU, hospital, 28‐day, and 1‐year mortality than the non‐NMAPR group (n=3320). After adjusting for covariates, the analysis showed that NMAPR was significantly associated with mortality in the ICU (odds ratio: 1.34; 95% CI, 1.10–1.65), in the hospital (odds ratio: 1.35; 95% CI, 1.12–1.63), at 28 days (hazard ratio: 1.27; 95% CI, 1.10–1.48), and at 1 year (hazard ratio: 1.24; 95% CI, 1.10–1.40). All results of the interaction analysis had no statistical significance, and similar results persisted in the patients with different SOFA scores.Conclusions NMAPR may aid in the early identification of critically ill patients at high risk of ICU, hospital, 28‐day, or 1‐year mortality.

Acute Spinal Cord Injury Causes Cardiac Contractile Dysfunction that when Treated Aids Spinal Cord Oxygenation

ObjectiveIn chronically injured humans and rodents with spinal cord injury (SCI) cardiac function is impaired. It is unknown whether such dysfunction is present acutely post‐SCI and if so whether it contributes to reduced spinal cord oxygenation. The aims of the present study, therefore, were to 1) define the acute cardiac and hemodynamic response to SCI, and 2) test the efficacy of a cardiac‐centered hemodynamic management strategy (β1‐receptor agonist dobutamine, DOB) vs. a traditional vasopressor‐based strategy (norepinephrine, NE) on intraparenchymal spinal cord oxygenation.DesignTo address aim 1, 7 Yucatan mini‐pigs received a T2 contusion SCI with 2 hours of compression and underwent measures of left‐ventricular (LV) function and spinal cord oxygenation pre‐ and up to 4 hrs post‐SCI. Pigs were instrumented with 1) a left‐ventricular (LV) pressure‐volume catheter for assessment of contractility (i.e., end‐systolic elastance, Ees) and LV hemodynamics, 2) a Swan‐Ganz pulmonary artery catheter for assessment of cardiac output (Q), 3) an inferior vena cava occlusion catheter, 4) a femoral arterial catheter to monitor mean arterial pressure (MAP), and 5) an intraparenchymal spinal cord oxygen sensor. To address aim 2, an additional 14 pigs were evenly assigned to either dobutamine (DOB, cardiac‐centered therapy), or norepinephrine (NE, vasopressor therapy) and were instrumented in the same way as aim 1. Drug infusions began 30 mins post‐SCI, and were continuously titrated to attain a targeted “normal” pre‐SCI Ees of ~2.5–2.9 mmHg/ml (DOB) or pre‐SCI MAP of ~85–90 mmHg (NE).ResultsEes and MAP were significantly reduced 4 hrs post‐SCI vs. pre‐ SCI (all p&lt;0.048), while Q was unchanged. When titrating DOB infusions to a pre‐established range of “normal” LV contractility, 3 animals received higher doses (≥3 mcg/kg/min) and 4 received lower doses (≤1 mcg/kg/min). Relative to their own pre‐drug baseline, animals receiving high‐dose DOB had significant increases in intraparenchymal spinal cord oxygenation at 4hr post‐SCI (p=0.014), whereas those treated with low‐dose DOB, NE or CON did not.ConclusionsSCI is associated with reductions to cardiac contractility in the acute setting. Normalizing reduced contractility with high‐dose DOB increased spinal cord oxygenation, whereas low‐dose DOB, NE or CON did not alter cord oxygenation. These findings have important clinical implications as a reduction in spinal cord oxygenation post‐SCI is known to be a major contributing factor the development of the secondary injury and poor neurological recovery.Support or Funding InformationUS Department of Defense, Craig Nielsen Foundation, Rick Hansen Institute, Michael Smith Foundation for Health ResearchThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P288: Bortezomib Reduces Blood Pressure and Proteinuria in the Dahl Salt Sensitive (S) Rat

Hypertension is a major health care disorder affecting up to one in three adults in the United States and is a major risk factor for multiple diseases including coronary artery disease, stroke, congestive heart failure, and end-organ damage. Previous studies have proposed that hypertension is partly driven by an increase in autoantibodies and immunological changes that lead to increased blood pressure. In this study, we tested the hypothesis that treatment with Bortezomib (BTZ), a proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma, would attenuate the increase in blood pressure and accompanying rise in urinary protein excretion in the Dahl S and Angiotensin II (Ang II) infused Sprague Dawley (SD) rat models of hypertension. Telemetry implants were placed in the femoral artery for continuous monitoring of mean arterial pressure (MAP) in male Dahl S and SD rats (~14 weeks old, maintained on a normal salt diet), and rats were allowed to recover for one week before baseline urine and MAP were collected. Then, Ang II (400ng/kg/hr) osmotic mini-pumps were implanted in SD rats, and BTZ treatment (0.2 mg/kg twice weekly, s.c.) was started in both Dahl S and SD rats. Ang II mini-pumps were replaced at 2 weeks, and urine was collected at weeks 2 and 4. MAP was reduced by BTZ in Dahl S rats, but no effect was observed in control or Ang II treated SD rats (Table 1). BTZ had no effect on urinary protein excretion (Bradford assay) in any group. These data show that administration of Bortezomib attenuates hypertension in Dahl S but not Ang II hypertension.

Timing of food intake differentially impacts urinary electrolyte and aldosterone excretion

The time‐of‐day variation in sodium excretion can be regulated by many different peptides and hormones, such as aldosterone. Numerous studies have shown that the circadian clock modulates the ability of aldosterone to regulate sodium balance, indicating a functional consequence of their interaction. Normally, renal sodium excretion has a distinct diurnal pattern, independent of time of intake, yet the interaction between the time of intake and the amount of salt ingested has yet to be determined. Our lab sought to determine what effect the timing of food intake has on the diurnal rhythm of renal electrolyte excretion, and whether or not this timing affects aldosterone as well. Male Sprague Dawley rats were implanted with telemetry devices to monitor mean arterial pressure (MAP). Following at least 7 days of recovery, rats were housed in metabolic cages and placed on a normal salt diet (0.49% NaCl). Following two days of baseline urine collections at 12‐hour intervals (Zeitgeber Time [ZT] 0 to ZT12 [lights on] or ZT12‐ZT24 [lights off]) under ad libitum feeding conditions, we restricted their access to food for 7 days to only their inactive period (ZT0‐ZT12). Rats were given free access to water during the reverse feeding (RF) conditions. As expected, rats allowed food ad libitum had a diurnal rhythm in sodium excretion as evidenced by a significantly higher sodium excretion during their active period (P&lt;0.05); active:inactive (A/I) sodium excretion was (2.82 ± 0.20). The rhythm in sodium excretion was not significantly different after 7 days of RF compared to ad libitum rats (2.03 ± 0.28 A/I, P=NS vs. ad libitum). As expected, potassium excretion was significantly greater during the active period in rats fed under ad libitum conditions (P&lt;0.05; A/I = 2.32 ± 0.16). Interestingly, RF significantly reduced the diurnal variation in urinary potassium excretion (0.89 ± 0.16, P&lt;.05 vs. ad libitum) as potassium excretion remained high during the inactive period. Although urinary aldosterone levels were similar in both ad libitum and RF conditions during the active period (89 ± 17 vs. 97 ± 18 pg/12 hr, P=NS), RF prevented the normal diurnal rhythm in aldosterone excretion resulting in significantly higher levels during the inactive period compared to ad libitum (138 ± 25 pg/12 hr vs. 25 ± 8, respectively, P&lt;0.05). There were no differences in 12‐hour MAP or activity between ad libitum and reverse feeding conditions. Our findings suggest that consuming food during the inactive phase impairs the diurnal variation in aldosterone production. In addition, the inappropriately high aldosterone excretion during the inactive period appears to be consistent with elevated potassium excretion during this period as well.Support or Funding InformationThis research was supported in part by the NHLBI Program Project grant HL136267, the NIH Career Development Award K99 HL127178, the NIGMS Pre‐doctoral Training Grant in Cell and Molecular Biology (CMB) T‐32 Training Grant T32GM008111‐30, and the UAB School of Medicine AMC21 Multi‐Investigator Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A study of metoprolol in fess surgery with respect to monitoring of mean arterial pressure at tertiary health care centre

A study of metoprolol in fess surgery with respect to monitoring of mean arterial pressure at tertiary health care centre

Abstract P288: Systemic Administration of an Angiotensin Type-2 Receptor Agonist Decreases Renal Regulatory T Cells

There is increasing evidence supporting a critical role of the immune system in the development of hypertension. Our lab has previously reported sex differences in the renal T cell profile in both Spontaneously Hypertensive Rats (SHR) and Angiotensin II (Ang II) models of hypertension, with females having more anti-inflammatory regulatory T cells (Tregs) than males. Ang II has a well-defined role in the activation of pro-inflammatory T cells in hypertension via the angiotensin type-1 receptor (AT1R). Less is known about the role of the angiotensin type-2 receptor (AT2R) in the regulation of immune cells, although the AT2R has been shown to be cardioprotective and AT2R expression is greater in females than males. Based on the potential anti-hypertensive role of AT2Rs, we hypothesized that administration of an AT2R agonist, Compound 21 (C21), would increase renal Tregs, and this increase would be greater in females due to greater AT2R expression. Male and female SHR (10 weeks of age, n=3-4) were implanted with telemetry units for continuous monitoring of mean arterial pressure (MAP). Following 10 days of recovery, baseline MAP was recorded for 5 days. Rats were then divided into the following treatment groups: surgical controls, low dose C21 (150 ng/kg/min, sc by osmotic minipump), high dose C21 (300 ng/kg/min, sc by osmotic minipump). Kidneys were harvested after 2 weeks of treatment and flow cytometry was performed on whole kidney homogenates. MAP was not altered by C21 treatment in males (137±4 vs 134±4 vs 134±4 mmHg; n.s.) or females (128±2 vs 136±5 vs 134±4 mmHg; n.s.). Interestingly, despite having no effect on MAP, there was a significant decrease in renal CD3 + CD4 + FoxP3 + Tregs in females following both low and high doses of C21 (data expressed as % CD3 + CD4 + cells: 6±0.6 vs 3±0.6 vs 3.5±1.3 %, respectively; p=0.02). Tregs decrease in males following the high dose of C21 only (data expressed as % CD3 + CD4 + cells: 3.3±0.3 vs 3.3±0.5 vs 1.7±0.7 %, respectively; p=0.05). Total CD3 + T cells, CD3 + CD4 + T cells, and Th17 cells were not altered by C21 treatment. In conclusion, AT2R activation suppresses renal Tregs, and females are more sensitive than males. These data suggest a novel role for AT2R regulation in the kidney in hypertension.