Hypotensive State Research Articles

Usefulness of presepsin as a prognostic indicator for patients with trauma in the emergency department in Korea: a retrospective study.

Trauma is an important public health concern, and it is important to increase the survival rate of patients with trauma and enable them to return to society in a better condition. Initial treatment in the emergency department (ED) is closely associated with the prognosis of patients with trauma. However, studies regarding laboratory biomarker tests that can help predict the prognosis of trauma patients are limited. Presepsin is a novel biomarker of inflammation that can predict a poor prognosis in patients with sepsis. This study aimed to determine whether presepsin could be used as a prognostic indicator in patients with polytrauma. The study included patients with trauma who had visited a single regional ED from November 2021 to January 2023. Patients who had laboratory tests in the ED were included and analyzed retrospectively through chart review. Age, sex, injury mechanism, vital signs, surgery, the outcome of ED treatment (admission, discharge, transfer, or death), and trauma scores were analyzed. Overall, 550 trauma patients were enrolled; 59.1% were men, and the median age was 64 years (interquartile range, 48.8-79.0 years). Patients in a hypotensive state (systolic blood pressure, <90 mmHg; n=39) had higher presepsin levels (1,061.5±2,522.7 pg/mL) than those in a nonhypotensive state (n=511, 545.7±688.4 pg/mL, P<0.001). Patients hospitalized after ED treatment had the highest presepsin levels (660.9 pg/mL), followed by those who died (652.0 pg/mL), were transferred to other hospitals (514.9 pg/mL), and returned home (448.0 pg/mL, P=0.041). Serum presepsin levels were significantly higher in trauma patients in a hypotensive state than in those in a nonhypotensive state. Additionally, serum presepsin levels were the highest in hospitalized patients with trauma, followed by those who died, were transferred to other hospitals, and returned home.

A flexible framework for coding and predicting acute hypotensive episodes using Markov chains

Over the past decade, the prediction of acute hypotensive episodes (AHEs) using computational models has gained significant attention. AHEs in patients admitted to intensive care units can lead to severe or life-threatening conditions. AHEs are defined as a drop in the mean arterial pressure (MAP) below a threshold during an observation period. However, adaptable AHE modeling approaches are required to account for patient-specific definitions caused by inter-patient variability. This study proposes a flexible three-stage framework for the AHE prediction problem capable of modeling different hypotension states. The initial stage involves encoding the MAP time series using the proposed scheme. A clustering process is then performed to determine the k≥2 hypotension states and transition probabilities between them. The proposed AHE prediction model is built using a cohort of 453 MAP waveforms from MIMIC-II. In the third stage, we use 173 MAP waveforms to validate the proposed prediction method. Given a patient’s MAP time series, we compute the initial probability distribution by considering (a) an encoded observation interval and (b) a similarity measure to determine the closest kth cluster (state) to the encoded interval. Based on the properties of the Markov process, we predict the most probable state for look-ahead times h ranging from 1 to 30 min. The proposed framework offers competitive performance for h=7 with an accuracy of 0.965, which is clinically relevant for medical practitioners. We also provide a comparative analysis to validate the effectiveness of the proposed approach, which exhibits a significant statistical difference (α=0.05) compared with other state-of-the-art methods.

Predicting Preoperative Rupture from Imaging Alone in Acute Type A Aortic Dissection

Objective. To establish risk factors for predicting preoperative ruptures in patients with acute type A aortic dissection (ATAAD) based on computed tomography angiography (CTA) imaging features alone. Methods. We retrospectively reviewed patients with ATAAD treated between January 2017 and December 2021 in Fujian Medical University Union Hospital, China. The primary outcome was preoperative rupture after admission. Multivariate logistic regression analysis was performed based on basic characteristics and CTA imaging variables selected by the application of the least absolute shrinkage and selection operator. Results. A total of 564 patients were enrolled. The rate of preoperative rupture was 14.2% (n = 80). Patients who experienced rupture were significantly older ( P = 0.002) and had a higher rate of DeBakey II ( P = 0.016), syncope ( P = 0.003), ventilator-assisted ventilation ( P = 0.008), preoperative shock ( P = 0.040), hypotensive state ( P = 0.009), hepatic insufficiency ( P = 0.002), acute kidney injury ( P = 0.045), and moderate or massive pericardial effusion ( P = 0.007). Multivariate analysis identified the following independent risk factors for preoperative rupture based on CTA imaging features: DeBakey II (odds ratio (OR) = 1.988, 95% confidence interval (CI) 1.211–3.676, P = 0.009), ascending aorta diameter (OR = 2.077, 95% CI 1.335–4.045, P &lt; 0.001), ascending aorta false lumen diameter (OR = 2.988, 95% CI 2.055–4.291, P &lt; 0.001), ascending aorta false lumen/true lumen diameter ratio &gt;4 : 1 (OR = 3.129, 95% CI 2.031–6.225, P &lt; 0.001), and number of branch arteries involved in dissection &gt;6 (OR = 1.154, 95% CI 1.036–2.006, P = 0.036). Conclusions. CTA imaging features are one of the most convenient indicators for the early prediction of preoperative rupture in patients with ATAAD.

A fixed 20:1 combination of cafedrine/theodrenaline increases cytosolic Ca2+ concentration in human tracheal epithelial cells via ryanodine receptor-mediated Ca2+ release

Mucociliary clearance is a pivotal physiological mechanism that protects the lung by cleaning the airways from pollution and colonization, thereby preventing infection. Ciliary function is influenced by various signal transduction cascades, and Ca2+ represents a key second messenger. A fixed 20:1 combination of cafedrine and theodrenaline has been widely used to treat perioperative hypotension and emergency hypotensive states since the 1960s; however, its effect on the intracellular Ca2+ concentration ([Ca2+]i) of respiratory epithelium remains unknown. Therefore, human tracheal epithelial cells were exposed to the clinically applied 20:1 mixture of cafedrine/theodrenaline and the individual substances separately. [Ca2+]i was assessed by FURA-2 340/380 fluorescence ratio. Pharmacological inhibitors were applied to elucidate relevant signal transduction cascades, and reverse transcription polymerase chain reaction (RT-PCR) was performed on murine tracheal epithelium to analyze ryanodine receptor (RyR) subtype expression. All three pharmacological preparations instantaneously induced a steep increase in [Ca2+]i that quickly returned to its baseline value despite the persistence of each substance. Peak [Ca2+]i following the administration of 20:1 cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone increased in a dose-dependent manner, with median effective concentrations of 0.35 mM (7.32 mM cafedrine and 0.35 mM theodrenaline), 3.14 mM, and 3.45 mM, respectively. When extracellular Ca2+ influx was inhibited using a Ca2+-free buffer solution, the peak [Ca2+]i following the administration of cafedrine alone and theodrenaline alone were reduced but not abolished. No alteration in [Ca2+]i compared with baseline [Ca2+]i was observed during β-adrenergic receptor inhibition. Depletion of caffeine-sensitive stores and inhibition of RyR, but not IP3 receptors, completely abolished any increase in [Ca2+]i. However, [Ca2+]i still increased following the depletion of mitochondrial Ca2+ stores using 2,4-dinitrophenol. RT-PCR revealed RyR-2 and RyR-3 expression on murine tracheal epithelium. Although our experiments showed that cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone release Ca2+ from intracellular stores through mechanisms that are exclusively triggered by β-adrenergic receptor stimulation, which most probably lead to RyR activation, clinical plasma concentrations are considerably lower than those used in our experiments to elicit an increase in [Ca2+]i; therefore, further studies are needed to evaluate the ability of cafedrine/theodrenaline to alter mucociliary clearance in clinical practice.

C4 (Clinical Case) Vascular Ehlers-Danlos Syndrome in the Paediatric Population: A Case Report of an Internal Bleed Caused by Ruptured Pseudoaneurysm

Abstract Introduction/Background Ehlers-Danols syndrome (EDS) is a connective tissue disease characterized by joint hypermobility, skin hyperextensibility and tissue fragility. EDS has six types. Type IV EDS: vascular EDS (vEDS), is rare but also the most malignant. Case Description We report a 15-year-old boy with a previous history of spontaneous colon perforation and two left shoulder dislocations. He presented with sudden onset abdominal pain, vomiting, dizziness, and lethargy with a Glasgow coma scale of 13. His abdomen was soft but mildly tender. He had a capillary refill of 3 seconds with cold extremities, was found to be in a hypotensive shock state requiring resuscitation with fluids and inotropes, as well as intubation and mechanical ventilation. His hemoglobin dropped by 30 g/L in 6 hours. Therefore, an abdominal ultrasound was done, revealing an intrabdominal hematoma. CT scan of the abdomen confirmed a ruptured fusiform pseudoaneurysm of the accessory left hepatic artery. This was successfully managed by coil embolization, see F1 and F2, below. Genetic workup was positive for the pathogenic COL3A1 gene that presents phenotypically as Ehlers-Danlos syndrome, particularly type IV. Discussion COL3A1 encodes pro-alpha1 chains of type III collagen. Inheritance is autosomal-dominant. It can present as a de novo variant with a negative family history, as was the situation for our patient. Estimated affected people with de novo variant vEDS is 33%-50%. Clinical diagnosis of vEDS involves one major and several minor criteria (2017). Major criteria include arterial aneurysms, dissection, or rupture; intestinal rupture; uterine rupture during pregnancy; family history of vEDS. Minor criteria include easy bruising; thin skin and visible veins; facial characteristics including prominent eyes, narrow nasal bridge, thin lips; club foot, congenital hip dislocation; inguinal hernia and pneumothorax. Our patient had two elements from the major criteria: arterial pseudoaneurysm and intestinal rupture. Conclusion vEDS has high morbidity and mortality due to the risk of spontaneous internal organ/vessel injury. This can be mitigated by increased awareness of systemic manifestations of vEDS and a high index of suspicion by both primary care and emergency physicians. Once diagnosed, surveillance is crucial, including regular blood pressure monitoring, frequent non-invasive imaging to identify emerging vascular lesions, and pregnancy counselling for potential uterine rupture and avoiding trauma, collision sports, and lifting heavy items.

A 20:1 synergetic mixture of cafedrine/theodrenaline accelerates particle transport velocity in murine tracheal epithelium via IP3 receptor-associated calcium release.

Background: Mucociliary clearance is a pivotal physiological mechanism that protects the lung by ridding the lower airways of pollution and colonization by pathogens, thereby preventing infections. The fixed 20:1 combination of cafedrine and theodrenaline has been used to treat perioperative hypotension or hypotensive states due to emergency situations since the 1960s. Because mucociliary clearance is impaired during mechanical ventilation and critical illness, the present study aimed to evaluate the influence of cafedrine/theodrenaline on mucociliary clearance. Material and Methods: The particle transport velocity (PTV) of murine trachea preparations was measured as a surrogate for mucociliary clearance under the influence of cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone. Inhibitory substances were applied to elucidate relevant signal transduction cascades. Results: All three applications of the combination of cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone induced a sharp increase in PTV in a concentration-dependent manner with median effective concentrations of 0.46µM (consisting of 9.6µM cafedrine and 0.46µM theodrenaline), 408 and 4μM, respectively. The signal transduction cascades were similar for the effects of both cafedrine and theodrenaline at the murine respiratory epithelium. While PTV remained at its baseline value after non-selective inhibition of β-adrenergic receptors and selective inhibition of β1 receptors, cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone increased PTV despite the inhibition of the protein kinase A. However, IP3 receptor activation was found to be the pivotal mechanism leading to the increase in murine PTV, which was abolished when IP3 receptors were inhibited. Depleting intracellular calcium stores with caffeine confirmed calcium as another crucial messenger altering the PTV after the application of cafedrine/theodrenaline. Discussion: Cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone exert their effects via IP3 receptor-associated calcium release that is ultimately triggered by β1-adrenergic receptor stimulation. Synergistic effects at the β1-adrenergic receptor are highly relevant to alter the PTV of the respiratory epithelium at clinically relevant concentrations. Further investigations are needed to assess the value of cafedrine/theodrenaline-mediated alterations in mucociliary function in clinical practice.

Present-day features of maladjustment states in English medium students

Background. During studying, international students require integration into a new linguistic and socio-cultural environment, an unusual climate, large volumes of rather complex new information, new forms and methods of educational process organization, emerging problems outside the educational process, separation from relatives and friends, all this inevitably causes students have new emotional experiences and mental states. The aim of the research was to study the modern features of the states of psychological maladjustment of international medical English medium (EM) students. Materials &amp; Methods. 372 international year 1-6 EM students of Kharkiv National Medical University (223 men and 149 women) with an average age of (19±3) years were examined. All the examinees were divided into three groups: Group 1 – 194 students from India; Group 2 – 96 students from other Asian countries (Pakistan, Lebanon, and Syria); Group 3 – 82 students from African countries (Sudan, Tunisia, Morocco, Egypt, Namibia, and Israel). Results &amp; Conclusions. The conducted psychodiagnostic study showed that students with a high and moderate level of maladjustment have clinical manifestations of anxiety according to Hamilton Anxiety and Depression Rating Scales (29.8% of students of Group 1, 30.1% of Group 2, 29.9% of Group 3) and subclinical manifestations of anxiety (36.2%; 39.5% and 41.1% of students, respectively). Clinical manifestations of depression were typical for 12.4% of students of Group 1, 14.2% of students of Group 2, and 13.4% of students of Group 3; subclinical manifestations of depression – for 21.1%, 19.6% and 19.9%, respectively. The analysis of the expressiveness of the manifestations of hypotensive states allowed distinguishing asthenodepressive (23.1% of the examined Group 1, 15.8% of Group 2 and 25.6% of Group 3), hypersthenic (29.9%; 29.8% and 22.2% of the examinees, respectively), anxious (25.5% of the students of Group 1, 18.9% – of Group 2, 31.1% – of Group 3) and dysphoric (21.5%; 35.5% and 21.1%, respectively) syndromes. Keywords: maladaptation, international students of higher education, anxiety, depression.

Association of blood pressure and cognitive function based on MoCA‐INA and MMSE scores among ischemic stroke patients at Atma Jaya Hospital in 2014‐2019

AbstractBackgroundCognitive impairment is a common finding among stroke patients and causing significant decline in survivors’ quality of life. Hypoperfusion is one of the mechanism of transient or permanent ischemia and cause of cognitive deficit. Hypertension causes right shift on cerebrovascular autoregulation, causing brain to be more vulnerable to hypoperfusion in hypotensive state. However, studies assessing the association of blood pressure on acute phase of stroke and cognitive function are still scarce.MethodA cross‐sectional study using secondary data from Atma Jaya Hospital Stroke Registry in 2014‐2019. Total sampling method resulted in 144 eligible samples. Blood pressure measurement was done at the time of admission, cognitive function was assessed at the time of discharge using MoCA‐INA and MMSE questionnaires. Data analysis was performed using Kruskall‐Wallis comparative test.ResultNo significant association of systolic blood pressure and cognitive function based on MoCA‐INA (p = 0,569) and MMSE (p = 0,147) scores. No significant association of diastolic blood pressure and cognitive function based on MoCA‐INA (p = 0,818) and MMSE (p = 0,184) scores.ConclusionNo significant association of blood pressure on acute phase of stroke and cognitive function based on MoCA‐INA and MMSE scores among ischemic stroke patients at Atma Jaya Hopital in 2014‐2019.

Evaluation of hemorrhagic shock and traumatic brain injury effects on hemodynamics and metabolomics

Traumatic brain injury (TBI) is often accompanied by hemorrhage. However, treatment of hemorrhagic shock (HS) after TBI is challenging because the treatment strategies for TBI and HS often conflict. Little is known about the complex pathophysiological differences between these two traumas when happening individually or combined. The aim of the present study was to evaluate effects of HS and TBI individually and combined on hemodynamics, baroreflex and brain metabolomics. Male Wistar rats were instrumented with catheters and subjected to TBI through a pneumatic controlled cortical impact. HS was induced by blood withdrawal to achieve a blood pressure (BP) between 35-40mmHg, and this hypotensive state was maintained for 90 min. Animals were separated into 4 groups (n=5): Sham (underwent surgery, but no TBI or HS was done), HS (animals were placed in the stereotaxic, but no TBI), TBI (TBI was performed and timeline was followed as described, but no HS was done), and TBI+HS. Rats were sacrificed 90 min after HS and tissues were harvested. BP, heart rate (HR), and indices of spontaneous baroreflex sensitivity were evaluated at baseline, 10 min after TBI, and at 10 and 90 min after HS. The brain was harvested and a metabolomic analysis for tricarboxylic acid (TCA) cycle, amino acids and lipids was performed in the impacted area. BP decreased in the TBI group compared to Sham and, as expected, it severely decreased in HS and TBI+HS groups, once they were kept at lower pressure levels for 90 min. Heart Rate (HR) was lower in the HS group compared to Sham and TBI groups. It was observed that HS decreases the BP alteration events’ number during a fixed 10 min period compared to Sham and TBI groups, however the association of TBI with HS normalized this parameter. This suggests that HS is decreasing BP variability in the HS group, while the association of HS with TBI did not show the same response. Baroreflex sensitivity was higher in both HS and HS+TBI compared to both Sham and TBI groups. TCA cycle and amino acids metabolites increased in all the groups with trauma compared to Sham, however the increase in the HS and TBI+HS was around 2.5X-fold, while for the TBI group it was around 1.5X-fold. Moreover, the lipids metabolites decreased for all the groups submitted to trauma, with the highest effects observed for the groups submitted to HS and TBI+HS. These results suggest that HS has a higher effect on metabolites abnormalities compared to TBI alone. Our results suggest that HS has a higher contribution for hemodynamics and metabolism abnormalities when compared to TBI alone. It is interesting that the association of TBI with HS does not seem to change parameters such HR and BP variability. However, further investigations are necessary to better understand the impact of the lack of alteration of these hemodynamics parameters, since this trauma combination is complex and the adequate treatment for these situations remains unclear. This study was supported by National Institutes of Health grants R01HL162120, R01HL159862 and the Department of Defense under grants W81XWH1810059. This is the full abstract presented at the American Physiology Summit 2023 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.

DIAGNOSTIC ACCURACY OF RAPID EMERGENCY MEDICINE SCORE (REMS) AS A PROGNOSTIC MARKER AND ITS COMPARISON WITH TRADITIONAL SCORING SYSTEMS IN TRAUMA

A Hospital-based screening test study was conducted at the Department of Emergency Medicine at Mahatma Gandhi Mission Medical College and Hospital, Kamothe, Navi Mumbai. The study aimed to compare the diagnostic accuracy of Rapid Emergency Medicine Score (REMS) with that of other traditional scoring systems like Injury Severity Score (ISS) and Revised Trauma Score (RTS). We also aimed to correlate in association with raised lactate values to predict in-hospital mortality in trauma patients as compared to REMS alone. The study included 100 consecutive trauma patients coming to our emergency department, fullling the eligibility criteria. Following observations were made during the study, Mean age of the study cases was 38.98 years with over half of them being between 21 to 40 years of age. Out of the 100 cases, 87% were males and 13% were females. Nature of trauma was a road trafc accident in the majority of the cases (63%). Other causes were falling (26%), assault (10%), and workplace injury (1%). Loss of consciousness was seen in 34% of cases while vomiting and seizures were seen in 21% and 6% cases respectively. Compromised airway was noted in 42% cases while the hypotensive and hypertensive state was observed in 68% and 3% cases respectively.Mortality rate in the present study was 11%.On ROC analysis, all the scores including REMS, ISS, and RTS were observed to be signicant predictors of mortality among trauma cases.

“Mephentermine Abuse” an Age-old Concern with New Challenges: Review of Literature with Case Series

Abstract Mephentermine, a stimulant drug, is used as vasoconstrictor to maintain blood pressure in hypotensive states and shock, but due to its stimulant effects on the central nervous system, it has also been used for performance enhancement by athletes. Here, we discuss three cases where the patients had used mephentermine to enhance their work performance. Case 1: A male in his 30’s, presented with palpitation, headache, and hypertension after 1 year of use of mephentermine which he had started using with the purpose of increasing his work performance. Case 2: A 22-year-old male presented with depressive symptoms following a 3-year history of use of mephentermine after being suggested by peers to enhance performance at gym. Case 3: A 22-year-old male with 2-year history of mephentermine, presented with withdrawal symptoms, after being introduced to mephentermine by his peers to improve physical performance and difficulty stopping its use on his own. It was found that the purpose of mephentermine abuse in all three discussed cases was to enhance performance, either at sports or workplace, which gradually lead to physical or mental complications or withdrawal symptoms. It thus seems imperative to create awareness about the harmful and addictive effects of mephentermine to masses, and simultaneously limiting its easy availability.

643 THE HEART WAS MADE TO BE BROKEN: RECURRENT TAKOTSUBO SYNDROME IN AMYOTROPHIC LATERAL SCLEROSIS

Abstract Takotsubo syndrome (TTS) is a rare cardiac disease, characterized by transient regional wall motion abnormalities without evidence of obstructive coronary artery stenoses, mainly triggered by emotion or physical stressors. Reverse Takotsubo syndrome (rTTS), an atypical variant with basal segments involvement, is frequently associated with neurological disorders, including patients with amyotrophic lateral sclerosis (ALS). We reported the case of a 54 years old woman who experienced two consecutive episodes of TTS with different wall motion patterns, complicated by a recurrent episode and arrhythmic events. A Caucasian woman, affected by ALS, was hospitalized in our department due to anemia and recurrent episodes of hematochezia. Following a week of relative clinical stability, the patient experienced acute deterioration with generalized malaise and worsening dyspnea. CT scan excluded pulmonary causes, whereas EKG (ST segment depression in the lower and lateral leads), blood test (increase in high-sensitive cardiac troponins) and TTE (severe impairment of LVEF, with akinesia of basal segments) revealed a cardiac etiology. Coronary angiography and left ventriculography were performed, documenting a wall motion pattern consistent with rTTS. After an initial management in intensive care unit, clinical stability was obtained with a complete recovery of left ventricular systolic function. The patient was discharged but one month later, due to bacterial pneumonia, she was readmitted in our ward and antibiotic therapy was started. Two days later an acute deterioration of clinical status occurred, characterized by dyspnea, altered state of consciousness and marked hypotension. TTE revealed a severe left ventricular systolic dysfunction with apical akinesia and preserved contractility of basal segments, so a diagnosis of typical TTS was made. Three weeks later the clinical scenario became more complicated due to advanced atrioventricular block, with phases of atrioventricular dissociation and ventricular escape-rhythm. Therefore, in light of the increased risk of infectious complications, she underwent implantation of a leadless pacemaker (PMK). This clinical case represents the first report of recurrent episodes of TTS, one of which as rTTS, in a patient affected by ALS. It is worth noting that the first episode of TTS had atypical clinical presentation (dyspnea without chest pain), the EKG showed diffuse ST-segment depression (totally different from classical TTS typical electrocardiographic alterations), and TTE confirmed a different phenotype of segment involvement (unsurprisingly InterTAK Diagnostic Score was low). TTS recurrence is an extremely rare event, even if in this case there were two well defined triggers such as anemia and pneumonia. On the other hand it is reasonable to think that non-use of BBs after the first episode may have contributed to the occurrence of the next event, affecting different segments compared to the previous episode. Furthermore, advanced atrioventricular (AV) block represents a rare complication of TTS, most probably due to catecholamine stress or increased vagal tone, often requiring PMK implantation. In conclusion TTS represents an important frequent cardiac complication in patients affected by ALS, often still underdiagnosed. Therefore clinicians must keep their guard up with TTS, especially in the cases with atypical clinical presentation.

Safety profile and efficacy of low and high oxygen affinity polymerized human hemoglobin in trauma model

Hemoglobin (Hb)‐based O2 carriers (HBOC) are being developed as alternatives to blood. Large molecular weight polymerized human Hb (PolyhHb) represents a new class of HBOC with promising results. It has been shown that PolyhHb can be locked in the T‐state (low O2 affinity) or R‐state (high O2 affinity) to control and target O2 delivery and avoid damage. The present study hypothesized that PolyhHb’s quaternary state could differently affect safety and hemodynamics restoration, by controlling O2 distribution. Thus, we aimed to compare PolyhHb T‐state and R‐state to restore hemodynamics after trauma, and toxicity 24 hrs after resuscitation. To test the efficacy to restore hemodynamics, Wistar rats were instrumented with catheters in the femoral artery and vein, and subjected to TBI through a pneumatic controlled cortical impact. Hemorrhagic Shock (HS) was induced by blood withdrawal to achieve a mean arterial pressure (MAP) between 35‐40mmHg, and the hypotensive state was maintained for 90 min. Animals were separated into 3 groups based on the resuscitation solution: Blood, PolyhHb T‐state, or R‐state and, followed for 2 hrs after resuscitation. For toxicity evaluation guinea pigs (GP) (a more clinically relevant model due to lack of ascorbic acid production) were anesthetized and the carotid artery and jugular vein were catheterized, HS was induced by 40 % blood volume (BV) withdrawal, and the hypovolemic state was maintained for 50 min. GP was divided into 2 groups, and 25% of their BV was reinfused with PolyhHb T‐state or R‐state. Rats resuscitated with Blood and T‐state had a higher increase in MAP 30 min after resuscitation when compared to R‐state. Showing higher efficacy of T‐state to restore hemodynamics compared to R‐state. The T‐state group showed lower O2 saturation 30 min after reperfusion compared to R‐state and Blood groups. However, 2 hrs after resuscitation both the Blood and T‐state groups presented lower O2 saturation compared to R‐state. Resuscitation with R‐state in the GP increased AST, ALT, and liver chemokine ligand‐1 (CXCL1) (markers of liver damage and inflammation), suggesting that R‐state caused greater liver damage compared to T‐state. It was also observed an increase in the BUN, urine NGAL, and serum creatinine in the R‐state group compared to the T‐state group, showing an increased kidney injury in the animals resuscitated with R‐State PolyhHb. Also was observed higher levels of serum Il‐6, CXCL‐1, and Il‐10, in the R‐state group compared to the T‐State group, showing elevated inflammation in this group. Finally, was observed by increased levels of cardiac IL‐6, tumor necrosis factor‐alpha, monocyte chemoattractant protein‐1, troponin, and c‐reactive protein, higher cardiac damage in the R‐sate group when compared to the T‐state group. Our results showed that T‐state has higher efficacy on restoring hemodynamics in a model of TBI followed by HS, and also presented reduced vital organs toxicity in GP, when compared to R‐state. These results are promising and encourage the use of this new generation of PolyhHb T‐state as an alternative when blood is not available.

A retrospective study of the effect of dexmedetomidine infusion in cochlear implant surgery among pediatric patients

Cochlear implantation surgery is usually performed in paediatric patient of 1 to 7 years of age with congenital deaf-mutism. Good results in this surgery are obtained by providing bloodless surgical field with controlled hypotension and postoperative smooth outcome. To anaesthetize these patients, we are using Inj Propofol, Inj fentanyl, Sevoflurane, Dexmedetomidine infusion and muscle relaxants. Dexmedetomidine is an active isomer of medetomidine and an agonist at α2 –adreno receptors. Medetomidine provides perioperative sedation and analgesia thus decreasing other general anaesthetic drug requirement, reduced postoperative pain score, postoperative delirium and other complications.To determine that inj. Dexmedetomidine infusion is a suitable agent for haemodynamic stability, decreases need of other general anesthetic drug requirement intraoperatively and improves post-operative outcome in cochlear implant surgery.This study was conducted at a rural tertiary care center, which included 100 samples of pediatric patients (1-7 years of age group) who went through cochlear implant surgeries in last 3 years. Among all patients, heart rate (HR) remained stable and there was no significant difference between baseline HR and intra-op HR (P=0.3098). The systolic blood pressure (SBP) was decreased significantly compared to baseline reading (P value &amp;#60; 0.0001), but the diastolic blood pressure was not decreased significantly (P= 0.0612).Dexmedetomidine provides stable haemodynamics, acceptable hypotensive state, good surgical field and excellent analgesia in pediatric patients undergoing cochlear implant surgery.

Hemodynamic Changes in Response to Hyperacute Spinal Trauma in a Swine Model.

Acute spinal cord injury (ASCI) is a devastating event that can have severe hemodynamic consequences, depending on location and severity of the lesion. Knowledge of hyperacute hemodynamic changes is important for researchers using porcine models of thoracic ASCI. The goal of this study was to determine the hyperacute hemodynamic changes observed after ASCI when using pigs as their own controls. Five Yucatan gilts were anesthetized, and a dorsal laminectomy performed at T10-T12. Standardized blunt trauma was applied for 5 consecutive min, and hemodynamic variables were collected 5 min before ASCI, and at 2, 4, 6, 8, 10, 20, 30, 60, 80 and 120 min after ASCI. Arterial blood gas samples were collected at 60 min and 10 min before, and at 30 min and between 120 and 240 min after ASCI. Parametric data were analyzed using a mixed effects model with time point as the fixed factor and subject as the random factor. We found no effect on heart rate, pulse pressure, SpO₂, EtCO₂, and respiratory rate between baseline and timepoints after ASCI. Diastolic arterial pressure, mean arterial pressure, and systolic arterial pressure fell significantly by 18%, 16%, and 15%, respectively, at 2 min after ASCI. However, none of the decrements in arterial pressures resulted in hypotension at any time point. Heart rate did not change significantly after ASCI. Blood glucose progressively increased to 50% above baseline between 120 and 240 minutes after ASCI. Low thoracic ASCI caused a consistent and statistically significant but clinically minor hyperacute decrease in arterial pressures (-15%) that did not produce hypotension or metabolic changes suggestive of tissue hypoperfusion. Our findings using this model suggest that mean arterial pressures should be maintained above 85 mm Hg prior to spinal trauma in order to avoid hypotensive states after ASCI.

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Hypercoagulable States Therapy in Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)

Background Ischemic optic neuropathy is one of the main causes of blindness or visual impairment in middle age or elderly population. Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the most common type of ischemic optic neuropathy. Systemic risk factors such as hypertension, diabetes mellitus, nocturnal hypotension, sleep apnea, cardiovascular disease and hypercoagulable states are related to NAION. The aim of the study was to evaluate the clinical outcome of hypercoagulable states therapy in NAION patients. Methods This study is a retrospective study conducted at Cipto Mangunkusumo Hospital Jakarta. All NAION patients with age more than 19 y.o were included. Patients were divided into 4 group; group 1: NAION patients treated with hypercoagulable states therapy, group 2: NAION patients treated with anticoagulant therapy, group 3: NAION patients treated with antiplatelet therapy and group 4: NAION patient without anticoagulant, antiplatelet or hypercoagulable states therapy. Results The total sample were 49 patients (49 eyes). Twenty-six patients (56.5%) were diagnosed with hypercoagulable state. In group 1 – 3 half of the patients (50%) had clinical improvements with anticoagulant, antiplatelet and hypercoagulable therapy. Conclusion Hypercoagulable states therapy may improve clinical outcome of NAION.

The alteration of neuronal activities of the cuneiform nucleus in non-hypovolemic and hypovolemic hypotensive conditions.

The cuneiform nucleus is located in the center of the circuit that mediates autonomic responses to stress. Hemorrhagic hypotension leads to chemoreceptor anoxia, which consequently results in the reduction of baroreceptor discharge and stimulation of the chemoreceptor. Using the single-unit recording technique, the neuronal activities of the cuneiform nucleus were investigated in hypotensive states induced by hemorrhage and administration of an anti-hypertensive drug (hydralazine). Thirty male rats were divided into the control, hemorrhage, and hydralazine groups. The femoral artery was cannulated for the recording of cardiovascular responses, including systolic blood pressure, mean arterial pressure, and heart rate. Hydralazine was administered via tail vein. The single-unit recording was performed from the cuneiform nucleus. The maximal systolic blood pressure and the mean arterial pressure significantly decreased and heart rate significantly increased after the application of hydralazine as well as the following hemorrhage compared to the control group. Hypotension significantly increased the firing rate of the cuneiform nucleus in both the hemorrhage and hydralazine groups compared to the control group. The present data indicate that the cuneiform nucleus activities following hypotension may play a crucial role in blood vessels and vasomotor tone.

ECHOCARDIOGRAPHY AND DIRECT ARTERIAL BLOOD PRESSURE MEASUREMENT IN CAPTIVE CHIMPANZEES (PAN TROGLODYTES) DURING TWO PHASES OF AN ANESTHETIC PROTOCOL.

The effects of α-2 agonists on echocardiographic findings in great apes are not well documented, and knowledge of these effects would expand the understanding of cardiac examinations of chimpanzees under anesthesia with protocols using these drugs. Ten adult chimpanzees (Pan troglodytes), four males and six females, underwent echocardiographic examinations after anesthesia with dexmedetomidine, midazolam, and ketamine (phase 1). Four animals required isoflurane to achieve an adequate plane of anesthesia. Atipamezole was used to antagonize dexmedetomidine, and all remaining animals were placed on isoflurane (phase 2), and then a second echocardiogram was performed. Direct arterial blood pressure was monitored during the anesthetic event. Measurements and recordings were assessed for statistically significant differences between the two phases and sex. There were no significant differences between phases or sex for any two-dimensional echocardiographic measurement of systolic function, although interventricular septum thickness at end systole approached a significant decrease from phase 1 to phase 2 (P = 0.058) when sex was considered a between-subject factor. Left ventricular outflow tract (P = 0.017) and pulmonary artery (P = 0.028) velocities increased after reversal of the dexmedetomidine. Diastolic transmitral flow was consistent with grade 3 diastolic dysfunction (median early to late ventricular filling velocities (E/A) of 2.02, interquartile range [IQR], 1.53-2.13) with a nonsignificant decrease of E velocity and increase in A velocity and decreased E/A after reversal. Trace mitral and tricuspid regurgitation were common findings in the sample population. Arterial blood pressure significantly decreased between phase 1 and phase 2 (P < 0.01). All chimpanzees entered a hypotensive state (mean arterial pressure < 60 mm Hg) during phase 2. Although limited by the small number of chimpanzees, this study showed an increase in afterload, potential diastolic dysfunction, and a decrease in blood pressure after the antagonism of dexmedetomidine. Additional studies to further assess the effects of α-2 agonists in chimpanzees are warranted.

Genesis of Antibiotic Resistance (AR) LXXI: Turbulence Modeling of Hemodynamics in Simplified Severe Sepsis Protocol‐2 (SSSP‐2) ‐ NCT01663701: Activated E‐Oligomer Complex Elicit Rapid Leucocyte‐Platelets‐Erythrocytes (LPE) Aggregation and Occlusion of Capillary by Impairing Energy Cascading and Starling Forces (Net Filtration Pressure)

Here we present a rationale for the fluid overload-induced accelerated LPE aggregates to occlude the arterial end of the capillary bed resulting in critical closing pressure (CCP). It is known that native purine/pyrimidine receptors have yet to be purified to homogeneity and characterization of receptor-ligand kinetics. Recombinant purine/pyrimidine receptors knockout genotype mice are not embryonic lethal, while its characterization in vivo is dependent of multifactorial factors of epigenetic origin namely (post-translational modification, lineage-specific developmental and hemodynamic heterogeneity; ex: meaning age, gender, morphological attribute(s) of the platelet(s), viscosity, and hematocrit). Every attempt to purify Ca2+ /Mg2+ ecto-ATPase (EC 3.6.1.15) to homogeneity, showed co-purification of CD36, PMID: 9925363); cell-CAM105 (PMID: 1637321 PMCID: PMC1132742, PMID: 8387753, PMID: 1985902); mmCGM1a (PMID: 1633107); PECAM-1,(PMID: 19558578); CBATP, (PMID: 9218468); BgP (PMID: 2527235); caldesmon (PMID: 1930128); NCAM (PMID: 8262246, PMID: 7804134); Ig gene superfamily (PMID: 2141577), Cadherin (PMID: 8489264); and chicken gizzard ecto-ATPase amino acid similarity to CD39 (PMID: 8995405). The fact remain that native CD39 has never been tested for mM [Ca2+] or [Mg2+] ecto-ATPase (EC 3.6.1.15) or E-NTPDase (NTPDase1) (EC 3.6.1.6) (PMID: 1672348, PMID: 1721639). Further, neither CAM nor CD39 knockout genotype is embryonic lethal. Experimental evidence shows that differential regulation of CD38, integrin's (CD11), and CD39 in the liver allograft, implicit of interdependency in host immune response (PMID: 31511354). We have obtained evidence that the phylogenetic tree analysis, neighbor-joining tree without distance correlation among CD36, CD38, CD39, CAM, P2Y/P2, and corona #2, receptors. The cladogram show a marked evolutionary conservancy between CD39 & P2X, CD36 & Corona virus-2, CAM & P2Y &cadherin, with a possibility of existence as an oligomer (ECpx). Taken together, it is hypothesized that nucleotide receptors (P2Y/P2X), CAM, and ectonucleotidases family of a protein complex (E-Cpx) could possibly exist as a membrane-bound oligomer. Subsequent activation of E-Cpx on LPE, aggregation, and rapid occlusion of the capillary by forming T-S waves, 3D distortion of T-S waves, in phase arrays of hairpin K-type vortices, turbulent spot formation, merging of turbulent spot formation, without energy cascading among the LPE aggregates and adherence to the damaged endothelial cells at the arterial end of the capillary, Refer Fig: 3.4, 3.5, 3.6 3.8; (ISBN: 978-0-13-127498-3), a robust anaerobic /aerobic persister (s) colonization eliciting CCP. In turn, a progressive hypotensive state induced endothelial damage and abrupt collapse of interstitial space would result in CCP ensuing hypoxia. Such a scenario may have been the cause for exacerbated mortality among the sepsis cohort in NCT01663701-SSSP-2 (PMID: 28973227).