Improve Tissue Perfusion Research Articles

Hemodynamic effects of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock waiting heart transplant

Abstract Background The use of intra-aortic ballon pump (IABP) as a bridge therapy in patients with advanced heart failure (HF) and cardiogenic shock (CS) waiting heart transplant (HTx) remains under debate. IABP can be an available device to improve hemodynamic conditions of these patients until HTx. Purpose Evaluate the hemodynamic effects of IABP and its efficacy in patients with advanced HF and CS waiting HTx. Methods We retrospectively analyzed from a single center intensive care unit, between 2009 and 2020, patients with advanced HF with optimized intravenous drugs that required IABP placement before HTx. Changes in oxygen central venous saturation (ScvO2), arterial lactate, renal function, and use of vasoactive drugs before and 96 hours after IABP insertion were evaluated. Patients with acute myocardial infarction and implant of ventricular assist device before HTx were excluded. Results A total of 199 patients (mean age 46,5 ± 12 years) were included. Median time of IABP onset to HTx was 20 days. Mean left ventricle ejection fraction was 23,5 ± 5,9%, 53,7% of patients had moderate to severe right ventricular dysfunction and the most frequent etiology was Chagas disease (47,2%, n=94). Before the IABP placement, 97,47% of patients were using dobutamine, 19,29% milrinone, 58,08% nitroprusside and 17,7% norepinephrine. Clinical and laboratory data were compared before and 96 hours after IABP therapy. ScvO2 increased from 49,9% to 66,85% (p<0,001), lactate decreased from 21,91 mg/dl to 12,6 mg/dl (p<0,001), creatinine decreased from 2,04 mg/dL to 1,72 mg/dL (p=0,301) and urine output increased from 1690,12 mL/24h to 2193,12 mL/24h (p<0,001). These differences were maintained until the day before HTx. Use of nitroprusside increased from 58,08 to 63,59% (p=0,154), and the use of norepinephrine decreased from 17,7% to 6,63% (p<0,001). Conclusion IABP improves tissue perfusion, renal function, and hemodynamic status in patients with advanced HF and CS and can be an effective method of circulatory support as a bridge therapy to HTx.Laboratory data pre and post-IABPVasoactive Drugs pre and post-IABP

"TRATAMENTO DA CETOACIDOSE DIABÉTICA NA UNIDADE DE TERAPIA INTENSIVA"

Introduction: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes caused by a lack of insulin, leading to hyperglycemia and acidosis. Factors such as infections and poor insulin administration can trigger it, and its urgent treatment in the ICU involves fluid replacement, intravenous insulin, and control of complications. Methodology: This article is a literature review on the treatment of diabetic ketoacidosis in the ICU, based on studies from the last 10 years available in English and Portuguese in the PubMed, SciELO, and BVS databases. Complete and free articles were included, excluding those that did not directly address the topic. Results and Discussion: The treatment of diabetic ketoacidosis (DKA) in the ICU follows protocols to quickly correct metabolic and hemodynamic alterations. Initial replacement of isotonic fluids treats severe dehydration and improves tissue perfusion. Low-dose intravenous insulin corrects ketosis and hyperglycemia, but should be adjusted accordingly, with potassium levels also need to be monitored and replaced. Continuous monitoring of blood glucose and electrolytes is crucial to avoid complications such as cerebral edema. Identifying and treating the underlying cause of DKA, such as infections, is essential to prevent recurrences. Conclusion: The treatment of diabetic ketoacidosis in the ICU is mainly based on rapid fluid replacement, controlled insulin administration, and continuous monitoring. Potassium management and identification of the cause are essential to prevent recurrences and improve prognosis, with the ICU being the ideal setting for intensive care and reducing mortality.

The effect of using low dose norepinephrine before hypotensive resuscitation in hemorrhagic shock; a randomized controlled trial

Background & Objectives: Hemorrhagic shock is not a very rare occurrence in big hospitals. It might be encountered in the emergency room (ER) or in the operating rooms (OR). A rapid response and systematic management will save the life of the victim. The objective of this research was to investigate the impact of a low dose of norepinephrine (NE) administered prior to the initiation of hypotensive resuscitation in patients with hemorrhagic shock. Methodology: This randomized controlled trial was conducted on 200 participants, at least 18 years old, classified as severely traumatized and had significant hemorrhage with mean arterial pressure ranging from 65 to 75 mmHg. We divided the patients into two equal groups. Group I received a low dose of NE (< 0.3 µg/kg/min) concurrently with resuscitation fluids. Group II received resuscitative fluids only. If the resuscitative fluids failed to keep mean arterial pressure (MAP) > 65 mmHg, the patient was progressively administered NE even with high doses (0.05 to more than 0.3 µg/kg/min). The primary outcome was 24-hour mortality. In-hospital mortality, incidence of acute kidney injury (AKI), and duration of hospital and intensive care unit (ICU) stay constituted the secondary outcomes. Results: Group I had lower 24-hour mortality compared to Group II (3% vs 13%; P < 0.05). Compared to Group II, Group I needed reduced amount of fluid resuscitation within 24 h, had lower serum lactate levels at 6 and 12 h, and lower serum creatinine at 6, 12, and 18 h (P < 0.001). Group I had a lower incidence of mechanical ventilation (13% vs 27%), hospital and ICU stays, and in-hospital mortality (9% vs 21%) (P < 0.05). There was a lack of disparity seen in the incidence of AKI and duration of mechanical ventilation. Conclusion: Low-dose norepinephrine infusion during the early period of hypotensive resuscitation reduces resuscitative fluid requirement, improves tissue perfusion, preserves renal function, and lowers mortality in hemorrhagic shock patients. Abbreviations: AKI - acute kidney injury; APACHE III - Acute Physiology And Chronic Health Evaluation III; HS - hemorrhagic shock; ICU - intensive care unit; MAP - mean arterial pressure; NE - Norepinephrine Keywords: Hemorrhagic Shock; Hypotensive Resuscitation; Norepinephrine; Fluid Therapy; Renal Protection; Mortality; Low Dose Citation: Mohamed RM, Anwar AG, Eid AA. The effect of using low dose norepinephrine before hypotensive resuscitation in hemorrhagic shock; a randomized controlled trial. Anaesth. pain intensive care 2024;28(5):914−921; DOI: 10.35975/apic.v28i5.2560 Received: April 17, 2024; Reviewed: August 03, 2024; Accepted: September 04, 2024

Safety and efficacy of up to 60h of iv istaroxime in pre-cardiogenic shock patients: Design of the SEISMiC trial.

Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre-CS patients. The SEISMiC study is a multinational, multicentre, randomized, double-blind, placebo-controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre-CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70-100mmHg for at least 2h] and clinically confirmed congestion, NT-proBNP ≥1400pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies. The study results will contribute to our understanding of the role of istaroxime in pre-CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population.

Combination treatment with cilostazol and isosorbide mononitrate attenuates microemboli-mediated vascular cognitive impairment and improves imaging and plasma biomarkers in diabetic rats

Diabetes is a major risk factor for all types of dementia. The underlying reasons are not fully understood, and preventive therapeutic strategies are lacking. Previously we have shown that diabetic but not control rats developed a progressive cognitive decline in a microemboli (ME) model of vascular contributions to cognitive impairment & dementia (VCID). Given the cerebrovascular dysfunction is a mutual pathological change between diabetes and VCID, we hypothesized that the cognitive impairment in this ME model can be prevented by improving the endothelial function in diabetes. Our treatment paradigm was based on the LACI-2 Trial which assessed the efficacy of isosorbide mononitrate (ISMN) and cilostazol (Cil) treatments in small vessel disease progression. Control and diabetic rats were treated with ISMN/Cil or vehicle for 4 weeks, then injected with cholesterol crystal ME and the behavioral outcomes were monitored. Brain microstructure integrity was assessed by diffusion MRI. Plasma biomarkers were assessed using angiogenesis, neurology and amyloid β 42/40 panels recommended by the MarkVCID consortium. Behavioral deficits and the loss of tissue integrity previously observed in untreated diabetic rats were not noted in the treated animals in this study. Treatment improved tissue perfusion but there were no differences in plasma biomarkers. These results suggest that restoration of endothelial function with ISMN/Cil before ME injection prevented the possible deleterious effects of ME in diabetic rats by improving the endothelial integrity and it is a practical preventive and therapeutic strategy for VCID.

Clinical, sonographic and molecular changes in calcific tendinitis of the shoulder following extracorporeal shockwave therapy: a prospective case-control study.

Extracorporeal shockwave therapy (ESWT) is the primary treatment for calcific tendinitis of the shoulders, but what are the effects of clinical, sonographic, and molecular markers following ESWT in treating calcific tendinitis of the shoulder? Twenty-eight patients were categorized into radiodense and radiolucent subgroups. In addition, clinical assessments included the visual analogue scale (VAS), Constant-Murley (CM) score, American Shoulder and Elbow Surgeon (ASES) score, sonographic evaluation, and serum enzyme-linked immunosorbent assay (ELISA). The participants completed a one-year follow-up. All data were collected before and after treatment. After one year of follow-up, all patients showed notable improvement in VAS, CM, and ASES scores, with no significant clinical variations among the subgroups. However, the radiolucent group showed significant complete resorption and size reduction at the final follow-up. Sonographic evaluation revealed improved tissue perfusion and reduced calcification from 3 to 12 months in all patients, including those in the radiolucent group, but complete resorption of calcific deposits did not occur. The percentage of tissue perfusion was improved at 1 and 3 months after ESWT. There were no significant differences in the levels of the molecular markers interleukin-1 beta (IL-1 β) or IL-33, but the level of insulin-like growth factor 1 (IGF-1) was notably increased at 1 and 3 months post-ESWT. The BMP7 level was increased at 3 months and was then decreased significantly at 6 and 12 months. ESWT improved symptoms, reduced calcification, enhanced tissue perfusion, and promoted angiogenesis and BMP7 activity. In particular, it benefited radiolucent type patients with better calcification resorption. Partial resorption led to improvements in transparency, and a second ESWT session at 3 months was recommended for optimal results.

Nitroglycerin challenge identifies microcirculatory target for improved resuscitation in patients with circulatory shock

BackgroundCirculatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.MethodsSublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.Results54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock.ConclusionCritically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

CARDIORESPIRATORY EFFECTS OF VATINOXAN IN BLESBOK (DAMALISCUS PYGARGUS PHILLIPSI) IMMOBILIZED WITH THIAFENTANIL-MEDETOMIDINE.

Combinations of a low dose of opioid, such as thiafentanil, and a high dose of medetomidine, are increasingly being used for immobilization of African ungulates. Both drugs can have undesirable cardiorespiratory effects. In this study we assessed whether vatinoxan, a peripherally acting alpha2-adrenergic receptor antagonist, can be used to alleviate some of these effects without affecting the immobilization quality. Eight healthy, female, boma-confined blesbok (Damaliscus pygargus phillipsi), weighing a mean (SDtion) of 56.8 (4.4) kg, were immobilized twice in a randomized cross-over study with a 2-wk washout period using (1) 0.5 mg thiafentanil + 1.5 mg medetomidine (TM), (2) TM + vatinoxan: 0.5 mg thiafentanil + 1.5 mg medetomidine + 15 mg vatinoxan per milligram medetomidine (total of 22.5 mg, administered intramuscularly at 10 min post recumbency). Heart rate, respiratory rate, rectal temperature, oxygen saturation (SpO2), arterial blood pressure, and sedation scores from 1 to 5 (1 = limited effect; 5 = excessively deep) were measured every 5 min. Arterial blood gases (PaO2 and PaCO2) were measured at 10, 15, 25, and 35 min postrecumbency and the alveolar--arterial oxygen gradient (P[A-a]O2) was calculated. Induction times and immobilization quality did not differ between groups. The heart rate was significantly higher and the mean arterial pressure significantly lower in blesbok after receiving vatinoxan. All animals were hypoxemic and there were no significant differences in the respiratory rates, PaO2, PaCO2, SpO2, or P(A-a)O2 gradients at any time point. Although vatinoxan did not improve respiratory variables and blood oxygenation in these animals, the change in cardiovascular variables may suggest that it improves tissue perfusion, a positive outcome that requires further investigation.

Optimizing perfusion and volume in autologous breast reconstruction: dual-plane, conjoined and stacked flaps

Microsurgical breast reconstruction has continued to evolve to improve outcomes and minimize complications. Dual-plane, conjoined and stacked flaps represent one aspect of this evolution in an effort to improve tissue perfusion and flap volume. Dual-plane flaps combine the superficial and deep circulation in abdominally-based free flaps to augment perfusion. Conjoined flaps use additional pedicles to supply multiple perforasomes combined in a single flap. Stacked flaps utilize separate flaps on individual pedicles to increase volume at a single recipient site. Multiple donor sites, pedicle configurations and recipient vessel choices have been described, primarily focusing on using the cranial and caudal internal mammary system as well as intra-flap anastomoses. Though more technically demanding, dual-plane, stacked and conjoined flaps allow for improvement in flap perfusion and volume, and are important tools for optimizing results in autologous breast reconstruction.

Trimetazidine improves angiogenesis and tissue perfusion in ischemic rat skeletal muscle.

Introduction: Peripheral artery disease (PAD) is an increasingly common disease, causing significant complications for patients. Trimetazidine (TMZ) not only improves clinical symptoms in PAD patients but also facilitates angiogenesis in ischemic hind limbs. Our aim was to find the function of TMZ in promoting angiogenesis and tissue perfusion in ischemic rat skeletal muscle. Methods: The rats underwent femoral artery ligation (FAL) and then treated with TMZ and saline. Hematoxylin-eosin and Masson's trichrome stain in the ischemic gastrocnemius muscle to analyze muscle morphology and atrophy. To identify angiogenesis and the tissue perfusion, CD31 immunohistochemical staining and laser speckle contrast imaging was conducted. Additionally, hind limb motor ability was measured. Finally, qRT-PCR and Western blotting were used to statistically analyze the expression levels of HIF-1α and VEGF. Results: Our study demonstrated significant enhancement in angiogenesis and tissue perfusion after FAL when treated with TMZ compared to the saline group. Histologically, it mitigates ischemia-induced muscle atrophy and inflammation, as well as reduces fibrosis progression in the TMZ group. Additionally, hind limb motor ability improved in rats treated with TMZ during motor experiments. Discussion: It suggests that TMZ can promote angiogenesis and improve tissue perfusion in ischemic skeletal muscle of rats by activating the HIF-1α/VEGF signaling pathway. Additionally, it leads to significant improvement in ischemia-induced motor limitations in the hind limbs of rats.

Application of negative wound pressure therapy to skin grafts after coverage of uncertain granular sites: a case series

The split thickness skin graft (STSG) is one of the most popular tools used in reconstructive surgery. Developed for the first time by Olier in 1872, with perpetually improving techniques, this graft has since facilitated the reconstruction of skin defects. Negative wound pressure therapy (NPWT) is a therapeutic procedure that has been widely used for decades; it stabilizes the wound environment, improves tissue perfusion by stimulating granulation and angiogenesis, and reduces bacterial load and, consequently, wound edema. This case series of 3 patients aimed to show the advantages of applying NPWT over STSGs after the coverage of uncertain granular sites. The intake rate was 95% on average, with rapid wound healing, no hematoma formation, no need for regrafting, and no pain or signs of infection.

A multimodal tissue perfusion measurement approach for the evaluation of the effect of pimobendan, an inodilator, in a porcine sepsis model

Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters.Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of Pseudomonas aeruginosa. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature – tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO2 were also measured.Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO2 and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO2. There were fair correlations between the different perfusion parameters.In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.

Effect of Centhaquine on the Coagulation Cascade in Normal State and Uncontrolled Hemorrhage: A Multiphase Study Combining Ex Vivo and In Vivo Experiments in Different Species.

Centhaquine is a novel vasopressor acting on α2A- and α2B-adrenoreceptors, increasing venous return and improving tissue perfusion. We investigated the effects of centhaquine on blood coagulation in normal state and uncontrolled hemorrhage using ex vivo and in vivo experiments in different species. Thromboelastography (TEG) parameters included clotting time (R), clot kinetics [K and angle (α)], clot strength (MA), and percent lysis 30 min post-MA (LY30). In normal rat blood, centhaquine did not alter R, K, α, MA, or LY30 values of the normal vehicle group or the antithrombotic effects of aspirin and heparin. Subsequently, New Zealand white rabbits with uncontrolled hemorrhage were assigned to three resuscitation groups: Sal-MAP 45 group (normal saline to maintain a mean arterial pressure, MAP, of 45 mmHg), Centh-MAP 45 group (0.05 mg kg-1 centhaquine plus normal saline to maintain a MAP of 45 mmHg), and Sal-MAP 60 group (normal saline to maintain a MAP of 60 mmHg). The Sal-MAP 45 group was characterized by no change in R, reduced K and MA, and increased α. In the Centh-MAP 45 group, TEG showed no change in R, K, and α compared to saline; however, MA increased significantly (p = 0.018). In the Sal-MAP 60 group, TEG showed no change in R, an increase in α (p < 0.001), a decrease in K (p < 0.01), and a decrease in MA (p = 0.029) compared to the Centh-MAP 45 group. In conclusion, centhaquine does not impair coagulation and facilitates hemostatic resuscitation.

The Effect of Implementing the Sepsis Early Goal-Directed Therapy (EGDT) Protocol on Patient Mortality in the Hospital ICU in Cairo, Egypt

Introduction: Sepsis is a life-threatening systemic inflammatory syndrome with a high mortality rate. Early goal-directed therapy (EGDT) is a structured therapy protocol that aims to improve tissue perfusion and oxygenation in sepsis patients.&#x0D; Methods: This retrospective observational study analyzed data on sepsis patients in the ICU of a Cairo hospital, Egypt (2020-2023). Patient mortality was compared before and after the implementation of the EGDT protocol.&#x0D; Results: Of the 220 sepsis patients, 120 were treated before and 100 after EGDT implementation. Patient mortality in the EGDT group was significantly lower (12% vs 25%, p&lt;0.05).&#x0D; Conclusion: Implementation of the EGDT protocol can reduce the mortality of sepsis patients in the hospital ICU in Cairo, Egypt.

Comparing the effectiveness of novel high-end compression garment with common compression garment and kinesio tape in preventing edema and improving tissue perfusion in lower extremities.

Global sales of compression garments have risen sharply in recent years. Due to the availability of a wide range of compression garments, this study aims to evaluate the effect of two types of compression garments and kinesio tape on edema formation and tissue perfusion in the lower extremities. Over-the-counter compression knee stockings and kinesio tape were compared with a prototype of high-end compression stockings that combine kinesio tape and a common knee bandage. The high-end compression stockings were designed by Cube with the aim of combining the positive effects of kinesio tape and compression garments on edema formation and tissue perfusion. Clinical cross-over study. Before and after a 6-hour compression period, the knee regions on both, the treated and non-treated leg, of participants were examined using a 3-D scan to detect changes in volume. Also measured were local temperature (°C), oxygen saturation (SpO2), perfusion index (Pi), blood pressure (mmHg), compression pressure (mmHg), range of motion, body-mass-index (BMI) and limb-circumference (cm). Two different types of compression garments were examined: a novel high-end compression stocking (A) and a common compression stocking (B). In addition, kinesio tape was compared to compression garments (C). After each experimental day, a one-day break was taken to prevent an unwanted overlay effect. Male and female participants between the ages of 18 and 60 were randomly selected. The high-end compression garment (A) showed a statistically significant (P = 0.009) reduction of edema intraindividually. Comparing the three treatment groups, compression (A) lead to a reduction of edema. However, the reduction was not statistically significant (P = 0.585). The compression garment B and kinesio tape showed an increase in edema in the lower limb. There was a positive correlation between the highest compression pressure (A: 9.8 mmHg) and volume decrease over the period of 6 hours. Lighter compression (B: 8.2 mmHg) led to an increase in leg volume after compression application over 6 hours. There was no significant difference in tissue oxygen saturation with the two types of compression and kinesio tape. The tissue temperature below the compression garment was highest in the compression group A. Nevertheless, we could not demonstrate a statistically significant correlation between tissue temperature and volume difference.The range in motion of the lower limb decreased after 6 hours with both compression A and B and with kinesio tape. The novel bandage showed a statistically significant reduction in edema when compared intraindividually, but no statistically significant advantage was found when compared with the other compression garment B and kinesio tape.Despite the widespread use of kinesio tape, we did not find any improvement in the range of motion, edema prevention and circulation in the lower limb after application of kinesio tape.

Effects of endoluminal vacuum sponge therapy on the perfusion of gastric conduit in a porcine model for esophagectomy.

After esophagectomy, the postoperative rate of anastomotic leakage is up to 30% and is the main driver of postoperative morbidity. Contemporary management includes endoluminal vacuum sponge therapy (EndoVAC) with good success rates. Vacuum therapy improves tissue perfusion in superficial wounds, but this has not been shown for gastric conduits. This study aimed to assess gastric conduit perfusion with EndoVAC in a porcine model for esophagectomy. A porcine model (n = 18) was used with gastric conduit formation and induction of ischemia at the cranial end of the gastric conduit with measurement of tissue perfusion over time. In three experimental groups EndoVAC therapy was then used in the gastric conduit (- 40, - 125, and - 200 mmHg). Changes in tissue perfusion and tissue edema were assessed using hyperspectral imaging. The study was approved by local authorities (Project License G-333/19, G-67/22). Induction of ischemia led to significant reduction of tissue oxygenation from 65.1 ± 2.5% to 44.7 ± 5.5% (p < 0.01). After EndoVAC therapy with - 125 mmHg a significant increase in tissue oxygenation to 61.9 ± 5.5% was seen after 60 min and stayed stable after 120 min (62.9 ± 9.4%, p < 0.01 vs tissue ischemia). A similar improvement was seen with EndoVAC therapy at - 200 mmHg. A nonsignificant increase in oxygenation levels was also seen after therapy with - 40 mmHg, from 46.3 ± 3.4% to 52.5 ± 4.3% and 53.9 ± 8.1% after 60 and 120 min respectively (p > 0.05). An increase in tissue edema was observed after 60 and 120 min of EndoVAC therapy with - 200 mmHg but not with - 40 and - 125 mmHg. EndoVAC therapy with a pressure of - 125 mmHg significantly increased tissue perfusion of ischemic gastric conduit. With better understanding of underlying physiology the optimal use of EndoVAC therapy can be determined including a possible preemptive use for gastric conduits with impaired arterial perfusion or venous congestion.

Resuscitation with pre-hospital blood products in adults with trauma-related haemorrhagic shock: the RePHILL RCT

Background The treatment of traumatic haemorrhagic shock has been transformed through better haemorrhage control, use of tranexamic acid and use of blood products. The improved survival seen from these strategies has stimulated an interest in pre-hospital transfusion. Objectives To determine if the clinical effectiveness of resuscitation with red blood cells and lyophilised plasma was superior to 0.9% saline for improving tissue perfusion and reducing mortality in adults with haemorrhagic shock following major trauma. Design A multi-centre, allocation concealed, open-label, parallel group, randomised controlled trial (with internal pilot). Setting The trial was conducted in four civilian pre-hospital critical care services who operated within the National Health Service (NHS) England Major Trauma Networks. Participants Adults (aged ≥16 years) who had sustained traumatic injuries, were attended by a pre-hospital emergency medical team and were hypotensive (systolic blood pressure &lt;90 mmHg or absence of radial pulse) as a consequence of traumatic haemorrhage were eligible for inclusion. The exclusion criteria were known or apparently &lt;16 years, blood administered on scene prior to arrival of the RePHILL team, traumatic cardiac arrest where (1) the arrest occurred prior to arrival of the team and/or (2) the primary cause is not hypovolaemia, refusal of blood product administration, known Jehovah’s Witness, pregnancy, isolated head injury without evidence of external haemorrhage, prisoners in the custody of HM Prison and Probation Service. Interventions Participants were randomised to receive up to either two units each of red blood cells and lyophilised plasma or up to 1 L 0.9% saline. Treatment was administered through the intravenous or intraosseous route. Main outcome measures The primary outcome was a composite of episode mortality and/or impaired lactate clearance. The secondary outcomes included the individual components of the primary outcome. Results From 6 December 2016 to 2 January 2021, pre-hospital medical teams randomised 432 participants to red blood cell/lyophilised plasma (n = 209) or 0.9% saline (n = 223) out of a target sample size of 490. Most participants were white (62%), males (82%), median age 38 (interquartile range 26 to 58), involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, interquartile range 25 to 50). Prior to randomisation participants had received on average 430 ml crystalloid fluids and tranexamic acid (90%). The primary outcome occurred in 128/199 (64.3%) of participants randomised to red blood cell/lyophilised plasma and 136/210 (64.8%) randomised to 0.9% saline [adjusted risk difference –0.025% (95% confidence interval –9.0% to 9.0%), p = 0.996]. The event rates for the individual components of the primary outcome, episode mortality and lactate clearance were not statistically different between groups [adjusted average differences −3% (−12% to 7%); p = 0.57 and −5% (−14% to 5%), p = 0.33, respectively]. Limitations Recruitment stopped prematurely due to disruption caused by the COVID-19 pandemic. Future work Identify the characteristics of patients who may benefit from pre-hospital blood products and whether alternative transfusion regimens are superior to standard care. Conclusions The trial did not demonstrate that pre-hospital red blood cell/lyophilised plasma resuscitation was superior to 0.9% saline for trauma-related haemorrhagic shock. Trial registration This trial is registered as ISRCTN62326938. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/152/14) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 2. See the NIHR Funding and Awards website for further award information.

Neutralization of extracellular histones by sodium-Β-O-methyl cellobioside sulfate in septic shock

BackgroundExtracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-β-O-Methyl cellobioside sulfate (mCBS), a histone-neutralizing polyanion, on the severity and outcome of sepsis in an experimental model.MethodsThis randomized placebo-controlled experimental study was performed in 24 mechanically ventilated female sheep. Sepsis was induced by fecal peritonitis. Animals were randomized to three groups: control, early treatment, and late treatment (n = 8 each). mCBS was given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) just after sepsis induction in the early treatment group, and 4 h later in the late treatment group. Fluid administration and antimicrobial therapy were initiated 4 h T4 after feces injection, peritoneal lavage performed, and a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) between 65–75 mmHg. The experiment was blinded and lasted maximum 24 h.ResultsDuring the first 4 h, MAP remained > 65 mmHg in the early treatment group but decreased significantly in the others (p < 0.01 for interaction, median value at T4: (79 [70–90] mmHg for early treatment, 57 [70–90] mmHg for late treatment, and 55 [49–60] mmHg for the control group). mCBS-treated animals required significantly less norepinephrine to maintain MAP than controls (p < 0.01 for interaction) and had lower creatinine (p < 0.01), lactate (p < 0.01), and interleukin-6 (p < 0.01) levels, associated with reduced changes in H3.1 nucleosome levels (p = 0.02). Early treatment was associated with lower norepinephrine requirements than later treatment. Two control animals died; all the mCBS-treated animals survived.ConclusionsNeutralization of extracellular histones with mCBS was associated with reduced norepinephrine requirements, improved tissue perfusion, less renal dysfunction, and lower circulating IL-6 in experimental septic shock and may represent a new therapeutic approach to be tested in clinical trials.

Impact of collateral vessels on Fontan circulation by using 0-1 dimensional Fontan circulation model considering concepts of oxygen supply and consumption

Abstract Background/Purpose In patients with univentricular heart disease, the Fontan operation has played a significant role in improving cyanosis and reducing the volume load on the systemic ventricle. However, Fontan patients may develop various complications, and their hemodynamics may deteriorate gradually, resulting in a poor long-term survival rate. Development of collateral vessels before and/or after the Fontan operation is one of the significant problems, and the patients may suffer from advanced cyanosis and heart failure. Although recent studies about the collateral vessels by MRI showed that a significant amount of blood is flown through the collateral vessels, little is known about its effect on the Fontan circulation. Therefore, understanding the mechanism and impact of collateral vessels on the Fontan circulation is important. Methods A 0-1-dimensional Fontan circulation hemodynamic model was developed to reproduce the hemodynamic changes of the blood flow in the entire body by introducing two types of collateral vessels (VVC: veno-venous collateral, APC: aorto-pulmonary collateral) into the model considering clinical status. Also, giving various conditions by ranging catecholamine dose and introducing the concept of oxygen delivery and consumption by changing workloads, arterial and central venous oxygen saturations (SaO2 and SvO2) are predicted in the Fontan circulation models. To evaluate the cardiac function, considering the impact of collateral vessels, four representative values were examined: (1) cardiac output (CO) per minute; (2) Ees relative to arterial elastance (Ees/Ea); (3) ejection fraction; and (4) the stroke work (SW) to pressure-volume area (PVA) ratio (SW/PVA). Results SaO2 and SvO2 were less in Fontan circulations with both VVC and APC present (92% and 54%) than those without collateral vessels (96% and 62%). Also, with collateral vessels, Ees/Ea was decreased while SW/PVA was increased, leading to poor perfusion to the tissue. Regardless of the presence or absence of collateral circulation, SaO2 and SvO2, and systemic blood flow rate decreased when pulmonary vascular resistance was high. By administering catecholamine at 10 microgram/kg/min, in the presence of both VVC and APC, SvO2 was increased from 53% to 58%, while SaO2 was decreased from 92% to 88%. Conclusions The simulated results of arterial and venous blood oxygen saturations and systemic blood flow rate were well-reproduced, matching the previously reported clinical results. It is suggested that pulmonary vasodilators may be beneficial in increasing blood oxygen saturation and improving tissue perfusion, even in Fontan patients with collateral vessels. However, the catecholamine's positive effect is limited. For reproducing various conditions of Fontan circulations, it is necessary to collect actual measurement data from a variety of patients and validate the predicted value to increase the credibility of the model.Arterial and venous oxygen saturationsPressure and volume curves

Capillary pruning couples tissue perfusion and oxygenation with cardiomyocyte maturation in the postnatal mouse heart.

Introduction: Removal of poorly perfused capillaries by pruning contributes to remodeling the microvasculature to optimize oxygen and nutrient delivery. Blood flow drives this process by promoting the intravascular migration of endothelial cells in developing networks, such as in the yolk sac, zebrafish brain or postnatal mouse retina. Methods: In this study, we have implemented innovative tools to recognize capillary pruning in the complex 3D coronary microvasculature of the postnatal mouse heart. We have also experimentally tested the impact of decreasing pruning on the structure and function of this network by altering blood flow with two different vasodilators: losartan and prazosin. Results: Although both drugs reduced capillary pruning, a combination of experiments based on ex vivo imaging, proteomics, electron microscopy and in vivo functional approaches showed that losartan treatment resulted in an inefficient coronary network, reduced myocardial oxygenation and metabolic changes that delayed the arrest of cardiomyocyte proliferation, in contrast to the effects of prazosin, probably due to its concomitant promotion of capillary expansion. Discussion: Our work demonstrates that capillary pruning contributes to proper maturation and function of the heart and that manipulation of blood flow may be a novel strategy to refine the microvasculature and improve tissue perfusion after damage.