Blood Reperfusion Research Articles

A novel technique for pancreatic juice drainage to the remaining graft duodenum after blood reperfusion in pancreas transplantation

TechniqueIn pancreatic transplantation, during bench surgery, the oral and anal sides of a graft duodenum are cut with linear staplers to be as short as possible in order to ascertain blood flow to the graft duodenum stumps. However, this can lead to a distended graft duodenum owing to the large amount of pancreatic juice produced after blood reperfusion during the recipient operation. Controlling bleeding after blood reperfusion and ensuring complete hemostasis are difficult due to obstructed vision caused by the distended graft duodenum. Additionally, the edematous mucosa due to the distended graft duodenum makes it difficult to anastomose the graft duodenum to the recipient's small intestine. Herein, we developed a novel technique during bench surgery to overcome these disadvantages of a distended graft duodenum, by initially leaving the anal side of the graft duodenum uncut to drain the produced pancreatic juice following blood reperfusion. After confirming the hemostasis and anastomosing the graft duodenum to the small intestine, the anal side of the graft duodenum is cut with a linear stapler at the point where sufficient blood flow is confirmed based on duodenal color. ResultsThis technique enables us to concentrate on the hemostasis and anastomosis without attending to the distended graft duodenum. Furthermore, stump issues due to insufficient blood flow can be avoided. ConclusionThis pancreatic juice drainage technique in pancreas transplantation can be useful to reduce postoperative complications.

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: an initial cohort study.

Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. The authors here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. The median operation time was 495 (range 420-630). The median time of explant hepatectomy and inferior vena cava anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than 12 months follow-up. LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

Nanoparticle-Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia-Reperfusion Injury.

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia-reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle-patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle-patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle-patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.

Downregulation of HDAC6 mitigates lung ischemia/reperfusion injury depending on activation of Nrf2/HO-1 signaling pathway and inactivation of ERK/NF-κB signaling pathway

IntroductionLung ischemia/reperfusion injury (LIRI) is a pathological process caused by the deficiency and subsequent reperfusion of oxygen and blood to the lung. Literature reports that the catalytic activity and expression of HDAC6 can be induced in response to IRI. HDAC6 inhibition confers protective effects against a series of IRI and also exerts pulmonary protection against various lung damage. The present study was formulated to investigate the functional role of HDAC6 inhibitor in LIRI and to probe into the intrinsic mechanisms underlying the protective role of HDAC6 inhibitor against LIRI. MethodsLung epithelial cell line MLE-12 cells were subjected to H/R injury to construct in vitro cell culture model of LIRI. For functional experiments, MLE-12 cells were pre-treated with various concentrations of selective HDAC6 inhibitor ACY-1215 (1, 5, 10 μM) to evaluate the biological role of HDAC6 in LIRI. For rescue experiments, MLE-12 cells were pre-treated with Nrf2 inhibitor ML385 (10 μM) or ERK activator LM22B-10 (50 μM) to discuss the molecular mechanisms. ResultsIt was verified that HDAC6 inhibition repressed H/R-induced apoptosis, oxidative stress, inflammation and mitochondrial dysfunction of MLE-12 cells. HDAC6 inhibition activated Nrf2/HO-1 signaling pathway and inactivated ERK/NF-κB signaling pathway in MLE-12 cells. The repressing effects of HDAC6 inhibition on H/R-induced apoptosis, oxidative stress, inflammation and mitochondrial dysfunction of MLE-12 cells were partially abolished upon pre-treatment with Nrf2 inhibitor ML385 or ERK activator LM22B-10. ConclusionHDAC6 inhibition may mitigate H/R-induced lung epithelial cell injury depending on activation of Nrf2/HO-1 signaling pathway and inactivation of ERK/NF-κB signaling pathway.

Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury.

Testicular torsion is a critical urologic condition for which testicular detorsion surgery is considered irreplaceable as well as the golden method of reversal. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat blood reperfusion injuries. Salidroside (SAL) is one of the main effective substances in rhodiola, which has been shown to have antioxidant and antiapoptosis activities. This study was designed to determine whether SAL exerted a protective effect on testicular ischemia-reperfusion (I/R) injury. In this study, the I/R injury model of the testes and reoxygenation (OGD/R) model were used for verification, and SAL was administered at doses of 100mg/kg and 0.05mmol/L, respectively. After the experiments, the testicular tissue and TM4 Sertoli cells were collected for histopathologic and biochemical analyses. The results revealed that SAL improves the structure of testicular tissue and regulates the oxidation-antioxidation system. To further understand the molecular mechanisms of SAL in treating testicular I/R injuries, transcriptomics and metabonomics analyses were integrated. The results show that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway is enriched significantly, indicating that it may be the main regulatory pathway for SAL in the treatment of testicular I/R injuries. Thereafter, transfection with Nrf2 plasmid-liposome was used to reverse verify that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway was the main pathway for SAL anti-testicular I/R injury treatment. Thus, it is suggested that SAL can protect against testicular I/R injuries by regulating the Nfr2/HO-1/GPX4 signaling pathway to inhibit ferroptosis and that SAL may be a potential drug for the treatment of testicular I/R injuries.

Abstract 1159: Harnessing Limb Revascularization With Synthetic Probiotics

Peripheral arterial disease (PAD) is a critical vascular condition that results in impaired blood flow leading to chronic limb threatening ischemia (CLTI), tissue necrosis and oftentimes to lower-limb amputation. This is largely due to suboptimal revascularization and inflammatory programs, that fail to instigate neovascularization at sites of vessel stenosis. The incidence of CLTI is on the rise but yet there is a paucity of effective treatment options for patients. We hypothesized that the coordinated action of regenerative angiogenesis and immunosurveillance would likely stimulate effective revascularization in the ischemic leg. The neuroimmune cue, Netrin-1 has been shown to possess such properties. We have shown that Netrin-1 can assist atherosclerosis onset by modulating macrophage chemotaxis and shown its critical role in modulating vascular remodeling. Here we show that the conditional knock-down of Netrin-1 in myeloid cells (Ntn1 flox/flox LysM cre+ ), protects mice from revascularization following femoral artery ligation compared to WT littermates. The deletion of Netrin-1 in endothelial cells nor vascular smooth muscle cells was insufficient to produce such effects. Notably, in human amputated tissue sections, the expression of Netrin-1 was repressed at sites proximal to amputated sites compared to distal regions with preserved blood flow. Tissue macrophages were packed with Netrin-1 and it exerted its effects in an autocrine/paracrine manner via its receptor Unc5b. The use of synthetic biology to engineer bacteria with tailored functionalities presents a cutting-edge avenue for developing novel therapeutic tools. We therefore employed a synthetic biology approach to deliver exogenous Netrin-1 to the ischemic leg. The Nissle probiotic was genetically engineered to overexpress murine Netrin-1. The local administration of this probiotic to ischemic limb of Ntn1 flox/flox LysM cre+ mice was sufficient to recapitulate blood flow and reperfusion in the leg comparable to WT mice (and sham probiotic) in 2 weeks. Our results show the therapeutic potential of the use of synthetic microorganisms and Netrin-1 for innovative and adaptable solutions in limb regenerative medicine.

Combination Administration of Heparin and Nitroglycerin for the Treatment of Polycaprolactone-Induced Intravascular Embolism: A Preclinical Investigation.

As a new-generation collagen stimulator, polycaprolactone (PCL) containing filler has been extensively applied in facial dermal fillers and other medical aesthetic fields. However, inadvertent intravascular injection of PCL may result in complications such as tissue edema, flap necrosis, and even blindness. To date, there is no effective treatment for PCL-induced intravascular embolism. The aim of this study was to identify a viable resolution for the embolism resulting from intravascular administration of PCL-containing fillers. Two different animal experiments were performed: (1) PCL-induced rat inferior epigastric arteries embolism, followed by gross observation, histological evaluation, and cytokines analysis from serum; and (2) PCL-induced rabbit auricular artery embolism, immediately treated with heparin and nitroglycerin. The ears were then evaluated by gross observation, Laser speckle imaging, in vivo imaging system (IVIS) imaging, and histological evaluation. Saline and hyaluronic acids (HA) were used as controls, hyaluronidase was used as a positive drug. In a rat model of inferior epigastric arteries embolism, both intravascular injection of HA and PCL resulted in flap necrosis, indicating that the filler-induced intravascular embolism can lead to serious complications. In a rabbit model of auricular artery embolism, the combination treatment of heparin and nitroglycerin resulted in a relative blood reperfusion recovery of 80% in the ischemic area of the PCL group on day 7 post-operation, which was comparable to that of the HA group treated with hyaluronidase. Histological analysis revealed that the administration of heparin and nitroglycerin significantly attenuated intravascular thrombosis formation and inflammatory cell aggregation. The combination of heparin and nitroglycerin effectively restores blood flow reperfusion in the intravascular embolization caused by PCL filler injection, alleviates local tissue edema and flap necrosis. These findings offer a novel approach for future clinical management of intravascular embolization with PCL-containing filler injection. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prognostic Biomarkers and AKI: Potential to Enhance the Identification of Post-Operative Patients at Risk of Loss of Renal Function.

Acute kidney injury (AKI) is a common complication after surgery and the more complex the surgery, the greater the risk. During surgery, patients are exposed to a combination of factors all of which are associated with the development of AKI. These include hypotension and hypovolaemia, sepsis, systemic inflammation, the use of nephrotoxic agents, tissue injury, the infusion of blood or blood products, ischaemia, oxidative stress and reperfusion injury. Given the risks of AKI, it would seem logical to conclude that early identification of patients at risk of AKI would translate into benefit. The conventional markers of AKI, namely serum creatinine and urine output are the mainstay of defining chronic kidney disease but are less suited to the acute phase. Such concerns are compounded in surgical patients given they often have significantly reduced mobility, suboptimal levels of nutrition and reduced muscle bulk. Many patients may also have misleadingly low serum creatinine and high urine output due to aggressive fluid resuscitation, particularly in intensive care units. Over the last two decades, considerable information has accrued with regard to the performance of what was termed "novel" biomarkers of AKI, and here, we discuss the most examined molecules and performance in surgical settings. We also discuss the application of biomarkers to guide patients' postoperative care.

Effects of Electronic Cigarette Vaping on Cardiac and Vascular Function, and Post-myocardial Infarction Remodeling in Rats

The effect of electronic cigarette (E-cig) vaping on cardiac and vascular function during the healing phase of myocardial infarction (MI), and post-MI remodeling was investigated. Sprague Dawley rats were subjected to left coronary artery ligation to induce MI. One week later, rats were randomized to receive either 12 weeks of exposure to purified air (n = 37) or E-cig vapor (15 mg/ml of nicotine) (n = 32). At 12 weeks, cardiac and vascular function, and post-MI remodeling were assessed. Baseline blood flow in the femoral artery did not differ between groups, but peak reperfusion blood flow was blunted in the E-cig group (1.59 ± 0.15 ml/min) vs. the air group (2.11 ± 0.18 ml/min; p = 0.034). Femoral artery diameter after reperfusion was narrower in the E-cig group (0.54 ± 0.02 mm) compared to the air group (0.60 ± 0.02 mm; p = 0.023). Postmortem left ventricular (LV) volumes were similar in the E-cig (0.69 ± 0.04 ml) and air groups (0.73 ± 0.04 ml; p = NS); and myocardial infarct expansion index did not differ between groups (1.4 ± 0.1 in E-cig group versus 1.3 ± 0.1 in air group; p = NS). LV fractional shortening by echo did not differ between groups at 12 weeks (E-cig at 29 ± 2% and air at 27 ± 1%; p = NS). Exposure to E-cig during the healing phase of MI was associated with altered vascular function with reduced femoral artery blood flow and diameter at reperfusion, but not with worsened LV dilation or worsened cardiac function.

Ramelteon attenuates renal ischemia and reperfusion injury through reducing mitochondrial fission and fusion and inflammation.

Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI). This study explored the function and mechanisms of ramelteon on IRI-induced AKI. Mice were randomly divided into five groups: Sham, IRI, IRI + ramelteon (0.3 mg/kg), IRI + ramelteon (1 mg/kg), and IRI + ramelteon (3 mg/kg). Mice were intraperitoneally treated with ramelteon for 7 days before IRI. IRI was accomplished by bilateral renal artery clamping for 30 minutes, after which the clamps were removed for blood reperfusion. HK-2 cells were randomly divided into five groups: control, hypoxia/reoxygenation (H/R), H/R + ramelteon (10 nM), H/R + ramelteon (30 nM), and H/R + ramelteon (60 nM). HK-2 cells were prophylactically treated with ramelteon and then exposed to H/R. Ramelteon attenuated renal injury, inhibited cell apoptosis, decreased reactive oxygen species (ROS) generation, and suppressed levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β). Ramelteon decreased apoptosis-related protein Bax and TLR4-related proteins (TLR4, MyD88, p-IκBα, and p-p65 NF-κB), enhanced apoptosis-related protein Bcl-2. Furthermore, ramelteon increased mitochondrial membrane potential in H/R cells. Mitochondrial-related proteins (Drp1, Fis1, and Mff) were abated, whereas Mfn1 and Mfn2 were enhanced in H/R induced cells. Ramelteon attenuates renal injury induced by IRI and H/R, which is involved in apoptosis, mitochondrial damage, and inflammation.

Sulfated oligosaccharide activates endothelial Notch for inducing macrophage-associated arteriogenesis to treat ischemic diseases.

Ischemic diseases lead to considerable morbidity and mortality, yet conventional clinical treatment strategies for therapeutic angiogenesis fall short of being impactful. Despite the potential of biomaterials to deliver pro-angiogenic molecules at the infarct site to induce angiogenesis, their efficacy has been impeded by aberrant vascular activation and off-target circulation. Here, we present a semisynthetic low-molecular sulfated chitosan oligosaccharide (SCOS) that efficiently induces therapeutic arteriogenesis with a spontaneous generation of collateral circulation and blood reperfusion in rodent models of hind limb ischemia and myocardial infarction. SCOS elicits anti-inflammatory macrophages' (Mφs') differentiation into perivascular Mφs, which in turn directs artery formation via a cell-to-cell communication rather than secretory factor regulation. SCOS-mediated arteriogenesis requires a canonical Notch signaling pathway in Mφs via the glycosylation of protein O-glucosyltransferases 2, which results in promoting arterial differentiation and tissue repair in ischemia. Thus, this highly bioactive oligosaccharide can be harnessed to direct efficiently therapeutic arteriogenesis and perfusion for the treatment of ischemic diseases.

Abstract 13361: The Effect of Electronic Cigarette Exposure on Flow Mediated Vasodilation and LV Remodeling in a Chronic Myocardial Infarction Model

Introduction: There is little information about the effect of electronic cigarette (e-C) exposure on the cardiovascular system in the setting of myocardial infarction (MI) and whether e-C’s could alter vascular or cardiac function during the healing phase of MI. We determine the effect of e-C on endothelial function, cardiac remodeling and function during the healing phase of MI. Methods: Sprague Dawley rats (both sexes) were anesthetized and subjected to a proximal left coronary artery occlusion to induce a large anterior wall MI. At one week, rats were randomized to receive either 12 weeks of exposure to purified air (n=37) or e-cig vapor plus 15 mg/ml of nicotine (e-Cn=32). At 12 weeks endothelial function was tested by assessing femoral artery diameter and blood flow following a 5- minute femoral artery occlusion and reperfusion (ultrasound and flow probe). Cardiac function was assessed by echocardiography; remodeling was also assessed by quantitative histologic analysis. Results: Baseline blood flow in the femoral artery did not differ between groups, but peak reperfusion blood flow was blunted in the e-Cn group (1.59 ± 0.15 ml/min) vs. the air group (2.11 ± 0.18 ml/min; p=0.034). Femoral artery diameter after reperfusion was narrower in the e-Cn group (0.54 ± 0.02mm) compared to the air group (0.60 ± 0.02mm; p=0.023). Postmortem left ventricular (LV) volumes were similar in the e-Cn (0.69 ± 0.04 ml) and air groups (0.73 ± 0.04 ml; p=NS); and myocardial infarct expansion index did not differ between groups (1.4 ± 0.1 in e-Cn group versus 1.3 ± 0.1 in air group; p=NS). Gross pathology LV wall thickness was greater in the e-Cn group (1.38 ± 0.12 mm) versus the air group (1.04 ± 0.10 mm) despite no increase in blood pressure at 12 weeks in the e-CN group. LV fractional shortening by echo did not differ between groups at 12 weeks (e-Cn at 29 ± 2% and air at 27 ± 1%; p=NS). Conclusion: Exposure to e-Cn during the healing phase of MI was associated with altered endothelial function with reduced femoral artery blood flow and diameter at reperfusion, but not with worsened LV dilation or worsened cardiac function. E-Cn did increase gross pathologic LV wall thickness. E-Cn exposure during the healing phase of MI has deleterious effects on the CV system but does not dilate the LV.

The impact of blood pressure variability on the development of parenchymal hematoma in acute cerebral infarction with atrial fibrillation.

Although blood pressure variability (BPV) and reperfusion are associated with parenchymal hematoma (PH) after stroke, the relationship between BPV and PH in atrial fibrillation (AF) patients who are at risk of reperfusion injury with frequent spontaneous recanalization is unknown. This study aimed to investigate whether BPV within the first 48 h is associated with PH within 72 h in patients with AF and stroke in terms of major vessel occlusion status. A total of 131 patients with AF that were admitted within 24 h after stroke onset were enrolled. PH was defined as a confluent hemorrhage with mass effect. The maximum (max), minimum (min), and average blood pressure (BP) during the first 48 h after admission were calculated. BPV was analyzed by using range between maximum and minimum (max-min), successive variation (SV), standard deviation (SD), and coefficient of variation (CV). All parameters were applied for systemic (SBP), diastolic (DBP), and pulse pressure (PP). After adjusting for confounding variables, various BPV parameters were associated with PH, including SBPmax (p = 0.0426), SBPSV (p = 0.0006), DBPmax-min (p = 0.0437), DBPSV (p = 0.0358), DBPSD (p = 0.0393), PPmax-min (p = 0.0478), PPSV (p < 0.0001), PPSD (p = 0.0034), and PPCV (p = 0.0120). The relationship remained significant in patients with a patent major vessel responsible for infarction but not in patients with an occluded major vessel. In conclusion, this study revealed that high BPV was associated with PH in patients with AF and acute stroke, particularly for those with a patent major vessel. The control of BP and BPV after stroke may be considered in patients with AF.

Proteome profiling of hippocampus reveals the neuroprotective effect of mild hypothermia on global cerebral ischemia–reperfusion injury in rats

Cerebral ischemia is one of the leading causes of disability and mortality worldwide. Blood reperfusion of ischemic cerebral tissue may cause cerebral ischemia–reperfusion (IR) injury. In this study, a rat model of global cerebral I/R injury was established via Pulsinelli’s four-vessel occlusion (4-VO) method. The liquid chromatography-tandem mass spectrometry (LC–MS/MS) and bioinformatics analysis were employed to examine the ipsilateral hippocampus proteome profiles of rats with/without MH (32 °C) treatment after IR injury. Totally 2 122 proteins were identified, among which 153 proteins were significantly changed associated with MH (n = 7 per group, fold change-1.5, p < 0.05). GO annotation of the differentially expressed proteins (DEPs) revealed that cellular oxidant detoxification, response to zinc ions, aging, oxygen transport, negative regulation of catalytic activity, response to hypoxia, regulation of protein phosphorylation, and cellular response to vascular endothelial growth factor stimulus were significantly enriched with MH treatment. The KEGG analysis indicated that metabolic pathways, thermogenesis, pathways of neurodegeneration, chemical carcinogenesis—reactive oxygen species, fluid shear stress and atherosclerosis, and protein processing in endoplasmic reticulum were significantly enriched with MH treatment. Importantly, changes in 16 DEPs were reversed by MH treatment. Among them, VCAM-1, S100A8, CaMKK2 and MKK7 were verified as potential markers associated with MH neuroprotection by Western blot analysis. This study is one of the first to investigate the neuroprotective effects of MH on the hippocampal proteome of experimental models of cerebral IR injury. These DEPs may be involved in the most fundamental molecular mechanisms of MH neuroprotection, and provide a scientific foundation for further promotion of reparative strategies in cerebral IR injury.

Effects of blood flow restriction on mechanical properties of the rectus femoris muscle at rest.

Introduction: This study examined the effects of blood flow restriction (BFR) and reperfusion on the mechanical properties of the rectus femoris muscle at rest (frequency and stiffness). Methods: Fourteen trained men (body weight = 81.0 ± 10.3kg; BMI = 25 ± 3.0m/kg2; height = 181 ± 4cm; training experience = 6.0 ± 2.2years) participated in an experimental session involving their dominant (BFR) and non-dominant leg (control). Muscle mechanical properties were measured using Myoton's accelerometer at the midpoint of the rectus femoris muscle at five time points. In the BFR leg, an 80% arterial occlusion pressure was applied by a cuff for 5min. No cuff was applied in the control leg. Femoral Myoton measurements were taken from both legs 2 and 4min after the start of BRF as well as 30s and 2min after the end of the occlusion period. Results: The two-way ANOVA revealed a statistically significant interaction effect for stiffness and frequency (p < 0.001; η2 > 0.67). The post hoc analysis showed that both stiffness and frequency increased during BFR compared with rest and then dropped to the resting levels post BFR period. Also, stiffness and frequency were higher than control only during the BFR period, and similar during rest and post BFR. Conclusion: These results indicate that the application of BFR at rest leads to significant changes in mechanical properties of the rectus femoris muscle.

The Distinct Innate Immune Response of Warm Ischemic Injured Livers during Continuous Normothermic Machine Perfusion.

Although normothermic machine perfusion (NMP) provides superior preservation of liver grafts compared to static cold storage and allows for viability testing of high-risk grafts, its effect on the liver immune compartment remains unclear. We investigated the innate immune response during 6 h of continuous NMP (cNMP) of livers that were directly procured (DP, n = 5) or procured after 60 min warm ischemia (WI, n = 5), followed by 12 h of whole blood (WB) reperfusion. WI livers showed elevated transaminase levels during cNMP but not after WB reperfusion. Perfusate concentrations of TNF-α were lower in WI livers during cNMP and WB reperfusion, whereas IL-8 concentrations did not differ significantly. TGF-β concentrations were higher in WI livers during NMP but not after WB reperfusion, whereas IL-10 concentrations were similar. Endoplasmic stress and apoptotic signaling were increased in WI livers during cNMP but not after WB reperfusion. Additionally, neutrophil mobilization increased to a significantly lesser extent in WI livers at the end of NMP. In conclusion, WI livers exhibit a distinct innate immune response during cNMP compared to DP livers. The cytokine profile shifted towards an anti-inflammatory phenotype during cNMP and WB reperfusion, and pro-apoptotic signaling was stronger during cNMP. During WB reperfusion, livers exhibited a blunted cytokine release, regardless of ischemic damage, supporting the potential reconditioning effect of cNMP.

Neuroprotective Effect of Platinum Nanoparticles Is Not Associated with Their Accumulation in the Brain of Rats.

Platinum nanoparticles (nPts) have neuroprotective/antioxidant properties, but the mechanisms of their action in cerebrovascular disease remain unclear. We investigated the brain bioavailability of nPts and their effects on brain damage, cerebral blood flow (CBF), and development of brain and systemic oxidative stress (OS) in a model of cerebral ischemia (hemorrhage + temporary bilateral common carotid artery occlusion, tBCAO) in rats. The nPts (0.04 g/L, 3 ± 1 nm diameter) were administered to rats (N = 19) intraperitoneally at the start of blood reperfusion. Measurement of CBF via laser Doppler flowmetry revealed that the nPts caused a rapid attenuation of postischemic hypoperfusion. The nPts attenuated the apoptosis of hippocampal neurons, the decrease in reduced aminothiols level in plasma, and the glutathione redox status in the brain, which were induced by tBCAO. The content of Pt in the brain was extremely low (≤1 ng/g). Thus, nPts, despite the extremely low brain bioavailability, can attenuate the development of brain OS, CBF dysregulation, and neuronal apoptosis. This may indicate that the neuroprotective effects of nPts are due to indirect mechanisms rather than direct activity in the brain tissue. Research on such mechanisms may offer a promising trend in the treatment of acute disorders of CBF.

#3285 EXTRACORPOREAL BLOOD PURIFICATION DURING OPEN HEART SURGERY WITH PROLONGED CPB: CYTOSORB 300 VS JAFRON HA330

Abstract Background and Aims Cardiac surgery is maintained by various complications. Major contribution associated with cardiopulmonary bypass (CBP). Cardiac surgery with CPB provokes activation of the cascade mechanism of inflammation with releasing of cytokines and a systemic inflammatory response syndrome (SIRS). Activation of the contact system due to exposure of artificial surface of the bypass circuit to blood cells, endotoxemia, ischemia and reperfusion injury and surgical trauma are all potential triggers of inflammation following CPB. This inflammatory reaction may leads to the development of postoperative complications, including vasoplegia, cytokine storm, myocardial dysfunction, respiratory failure, acute kidney injury, coagulopathy bleeding, and multiple organ dysfunction syndrome (MODS). A number of different strategies, including new pharmacologic agents, CPB circuits and components, and surgical techniques, have been employed during the last few years in attempts to minimize the impact of SIRS on the outcome of cardiac surgical patients. However, the complex pathophysiology of this problem has not allowed, until now, the use of a single strategy. The aim of our study is assessment of early application of extracorporeal cytokine adsorbers to the inflammation system during open-heart surgery with prolonged cardiopulmonary bypass. Method This prospective randomized single-center controlled trial observed patients, who were assigned a planned open cardiac surgery with a duration of cardiopulmonary bypass (CPB) more than 120 minutes between January 2021 to January 2023. Patients were randomized into three groups: CytoSorb -300 group, HA 330 group and the control group. A simple 1:1:1 randomization method was applied. Cytokine hemadsorption was conducted intraoperatively. Two types of cytokine cartridges were applied CytoSorb 300 (Cytosorbents Europe GmbH). НА330 (Jafron Biomedical Co., Ltd. China). The inclusion criteria: age ≥18 years, informed consent to participate in the study, CPB more than 120 min. The exclusion criteria: Age less than 18 years; refusal to participate in the study. Results The data of the HA 330 (n = 22) and CytoSorb300 (n = 22) groups were compared with the data of the control group (n = 22). The primary results and details of the work are given in Tables 1-3. Conclusion Intraoperative hemadsorption may be beneficial for patients who underwent open-heart surgery with prolonged CPB. The early hemadsorption has positive impact to postoperative period after cardiac surgery and may reduce requirement of renal replacement therapy.

Oxygen Penetration Through Full-Thickness Skin by Oxygen-Releasing Sutures for Skin Graft Transplantation

The transplantation of full-thickness skin grafts (FTSGs) is important for reconstructing skin barrier and promoting wound healing. Sufficient oxygen supply is closely related to the success of skin grafting. However, full-thickness oxygen delivery is limited by the poor oxygen permeability of skin. Oxygen-releasing sutures (O2 sutures) were developed to facilitate oxygen penetration through full-thickness skin. The O2 sutures delivered 100 times more oxygen than topical gaseous oxygen therapy at a 15 mm depth in the skin model. Under extreme hypoxia (< 0.5% O2, v/v), O2 sutures could also promote endothelial cell proliferation. After the transplantation of FTSGs in mice, O2 sutures accelerated blood re-perfusion and increased the survival area of the skin graft. It is expected that O2 sutures will be adopted in clinical applications to increase the success rate of full-thickness skin transplantation.

Utility of Cell Saver in Trauma Compared to Cardiac Surgery.

While reperfusion of autologous blood using the Cellsaver (CS) device is routine in cardiothoracic surgery, there is a paucity of evidence-based literature regarding its use in trauma. Utility of CS was compared in these two distinct populations at a Level 1 trauma center from 2017 to 2022. CS was successfully used in 97% and 74% of cardiac and trauma cases, respectively. The proportion of blood requirements provided by CS, compared to allogenic transfusion, was also significantly higher in cardiac surgery. However, there was still net benefit for CS in trauma surgery, with median salvaged transfusion volume of one unit, in both general & orthopedic trauma. Therefore, in centers where the cost of setting up CS, both in terms of equipment and personnel, is less than the cost of one unit of blood from blood bank, use of CS in trauma operations should be considered.