Ischemia-reperfusion Injury In Organs Research Articles

Mechanisms of oxidative stress in myocardial ischemia-reperfusion injury and protective effects of traditional Chinese medicines

Myocardial ischemia is a disease characterized by high morbidity and mortality rates, restoring blood supply to the ischemic area through reperfusion is an effective intervention method. However, numerous studies have shown that reperfusion may cause severe myocardial damage, resulting in myocardial systolic and diastolic dysfunction and seriously affecting myocardial function. This phenomenon is called myocardial ischemia reperfusion injury(MIRI). The physiological and pathological mechanisms of MIRI include oxidative stress, calcium overload, autophagy, pyrolysis, endoplasmic reticulum stress, apoptosis, etc. Oxidative stress plays an important role in MIRI-related cell death and is considered to be the main mechanism of MIRI. The occurrence of oxidative stress is mainly due to the excessive production of reactive oxygen species(ROS), which disrupts the balance of the redox system of the body or tissue. A large number of highly reactive ROS exceed the antioxidant defense capacity of cardiomyocytes, causing modifications in biological macromolecules such as DNA and proteins and resulting in severe reactions like DNA damage, protein dysfunction, cell damage or death, and local inflammation. Oxidative stress mediates apoptosis, autophagy, and inflammatory injury through various pathways, resulting in irreversible cardiomyocyte injury and myocardial dysfunction, which brings significant challenges for clinical treatment and prognosis. In recent years, remarkable progress has been made in understanding oxidative stress in ischemia reperfusion(I/R) injury of different organs and tissue. However, the injury mechanism caused by oxidative stress in restoring blood supply to the ischemic area and the protective effect of TCM remain largely unexplored. This article reviewed the role of oxidative stress in MIRI, the main production pathways of ROS, and the protective effects of TCM on oxidative stress injury during ischemic myocardial reperfusion, so as to provide a reference for future research and clinical treatment in this field.

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury.

Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of the main causes of fatal diseases, which is an urgent clinical problem to be solved. Although great progress has been made in therapeutic methods, including surgical, drug, gene therapy, and transplant therapy for I/R injury, the development of effective methods to cure the injury remains a worldwide challenge. In recent years, exosomes have attracted much attention for their important roles in immune response, antigen presentation, cell migration, cell differentiation, and tumor invasion. Meanwhile, exosomes have been shown to have great potential in the treatment of I/R injury in organs. The study of the exosome-mediated signaling pathway can not only help to reveal the mechanism behind exosomes promoting reperfusion injury recovery, but also provide a theoretical basis for the clinical application of exosomes. Here, we review the research progress in utilizing various exosomes from different cell types to promote the healing of I/R injury, focusing on the classical signaling pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, and AMPK. The results suggest that exosomes regulate these signaling pathways to reduce oxidative stress, regulate immune responses, decrease the expression of inflammatory cytokines, and promote tissue repair, making exosomes a competitive emerging vector for treating I/R damage in organs.

7-Dehydrocholesterol dictates ferroptosis sensitivity.

Ferroptosis, a form of regulated cell death that is driven by iron-dependent phospholipid peroxidation, has been implicated in multiple diseases, including cancer1-3, degenerative disorders4 and organ ischaemia-reperfusion injury (IRI)5,6. Here, using genome-wide CRISPR-Cas9 screening, we identified that the enzymes involved in distal cholesterol biosynthesis have pivotal yet opposing roles in regulating ferroptosis through dictating the level of 7-dehydrocholesterol (7-DHC)-an intermediate metabolite of distal cholesterol biosynthesis that is synthesized by sterol C5-desaturase (SC5D) and metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis. We found that the pathway components, including MSMO1, CYP51A1, EBP and SC5D, function as potential suppressors of ferroptosis, whereas DHCR7 functions as a pro-ferroptotic gene. Mechanistically, 7-DHC dictates ferroptosis surveillance by using the conjugated diene to exert its anti-phospholipid autoxidation function and shields plasma and mitochondria membranes from phospholipid autoxidation. Importantly, blocking the biosynthesis of endogenous 7-DHC by pharmacological targeting of EBP induces ferroptosis and inhibits tumour growth, whereas increasing the 7-DHC level by inhibiting DHCR7 effectively promotes cancer metastasis and attenuates the progression of kidney IRI, supporting a critical function of this axis in vivo. In conclusion, our data reveal a role of 7-DHC as a natural anti-ferroptotic metabolite and suggest that pharmacological manipulation of 7-DHC levels is a promising therapeutic strategy for cancer and IRI.

Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.

Design, synthesis, and biological evaluation of 2-amino-6-methyl-phenol derivatives targeting lipid peroxidation with potent anti-ferroptotic activities

The suppression of ferroptosis is emerging as a promising therapeutic strategy for effectively treating a wide range of diseases, including neurodegenerative disorders, organ ischemia-reperfusion injury, and inflammatory conditions. However, the clinical utility of ferroptosis inhibitors is significantly impeded by the limited availability of rational drug designs. In our previous study, we successfully unraveled the efficacy of ferrostatin-1 (Fer-1) attributed to the synergistic effect of its ortho-diamine (-NH) moiety. In this study, we present the discovery of the ortho-hydroxyl-amino moiety as a novel scaffold for ferroptosis inhibitors, employing quantum chemistry as well as in vitro and in vivo assays. 2-amino-6-methylphenol derivatives demonstrated remarkable inhibition of RSL3-induced ferroptosis, exhibiting EC50 values ranging from 25 nM to 207 nM. These compounds do not appear to modulate iron homeostasis or lipid reactive oxygen species (ROS) generation pathways. Nevertheless, they effectively prevent the accumulation of lipid peroxides in living cells. Furthermore, compound 13 exhibits good in vivo activities as it effectively protect mice from kidney ischemia-reperfusion injury. In summary, compound 13 has been identified as a potent ferroptosis inhibitor, warranting further investigation as a promising lead compound.

Toll-Like Receptor 4 Induction During Renal Ischemia Correlates with Serum Creatinine in a Pig Model.

Objectives: To determine whether toll-like receptor 4 (TLR4), a mediator of organ ischemia-reperfusion injury, is overexpressed during warm ischemia in a porcine solitary kidney model, and whether its expression correlates with creatinine, a surrogate for kidney function. Materials and Methods: Eight adult Yorkshire pigs underwent initial laparoscopic nephrectomy. After 1 week, animals were randomized into two groups: group 1 underwent laparoscopic renal hilar dissection, renal ischemia by cross-clamping, and reperfusion (ischemia group); group 2 underwent laparoscopic renal hilar dissection alone (sham group). Animals were survived to day 7 postrandomization. Peripheral blood was sampled for serum creatinine (sCr) and TLR4 expression at the following time points or corresponding intervals: prenephrectomy, 1-week postnephrectomy (preischemia), after 90 minutes of ischemia, 30 minutes postreperfusion, and at sacrifice. Intragroup TLR4 expression changes were analyzed using repeated measures ANOVA. Intergroup TLR4 expression was compared using Mann-Whitney's test. Correlation between sCr and TLR4 was assessed using Spearman's test. Results: Seven animals completed the experiment (four ischemia and three sham). Relative TLR4 expression significantly increased from baseline levels during ischemia, reperfusion, and sacrifice time points only in the ischemia group, and was significantly higher for the ischemia group after 90 minutes of ischemia (p = 0.034). sCr was significantly higher for the ischemia group during the reperfusion phase (p = 0.048). Relative TLR4 expression level significantly correlated with sCr in the overall cohort (Spearman's rho = 0.69) and in the ischemia group (Spearman's rho = 0.82; p < 0.0001 for each). Conclusions: Warm ischemia in a porcine solitary kidney induces acute overexpression of TLR4 in peripheral blood leukocytes, which is detectable. Relative TLR4 expression level strongly correlated with sCr but had an observable change sooner than change in sCr. Pending further investigation, TLR4 overexpression during renal ischemia may represent a sensitive quantitative marker of unilateral renal injury sustained during nephron-sparing surgery.

Pre-Treatment of Transplant Donors with Hydrogen Sulfide to Protect against Warm and Cold Ischemia-Reperfusion Injury in Kidney and Other Transplantable Solid Organs

Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon's enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditions are discussed.

Effect of remote ischemic preconditioning in patients undergoing laparoscopic colorectal cancer surgery: a randomized controlled trial

Background Remote ischemic preconditioning (RIPC) is reported to reduce ischemia-reperfusion injury (IRI) in many vital organs by inhibiting a systemic inflammatory response. Inflammation also plays an essential role in the pathophysiology of prolonged post-operative ileus (PPOI) in patients undergoing colorectal cancer (CRC) surgery. However, the role of RIPC is unclear in reducing the incidence of PPOI in patients undergoing CRC surgery. Methods This was a prospective, randomized trial of RIPC vs. placebo-controlled in patients undergoing elective laparoscopic CRC surgery. Eighty patients were randomized to either a RIPC group or a control group (40 per arm), with computer-generated randomization. The aim was to determine whether RIPC improved the recovery of gut function. The primary outcomes assessed were time to gastrointestinal tolerance and incidence of PPOI. Results Median time to stool of the RIPC group was significantly lower than that of the control group [RIPC vs. control, 4.0 (3.0, 6.0) vs. 5.0 (4.0, 7.8) days, p = 0.027]. Median time to gastrointestinal tolerance and incidence of PPOI in the RIPC group were lower than the control group; however, there were no statistical differences between the two groups [RIPC vs. control: 5.0 (3.0, 7.0) vs. 6.0 (4.0, 8.8) days, p = 0.178; 15 vs. 30%, p = 0.108]. Conclusion RIPC could shorten the median time to stool in patients undergoing laparoscopic CRC surgery, but did not improve the overall recovery time of gut function or reduce the incidence of PPOI. Registration number ChiCTR2100043313 (http://www.chictr.org.cn). Key points Question: In patients undergoing laparoscopic CRC surgery, does RIPC improve time to the overall recovery of gut function and reduce the incidence of PPOI? Findings: In this randomized clinical trial that included 80 patients undergoing elective laparoscopic CRC surgery, no significant difference was found between the RIPC group and the control group concerning median time to gastrointestinal tolerance and incidence of PPOI. Meaning: RIPC did not improve the time for overall recovery of gut function or reduce the incidence of PPOI in patients undergoing laparoscopic CRC surgery.

Application of polymerized porcine hemoglobin in the ex vivo normothermic machine perfusion of rat livers.

Background: In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion (NMP) may reduce preservation injury, improve graft viability and potentially allows ex vivo assessment of graft viability before transplantation. The polymerized porcine hemoglobin is a kind of hemoglobin oxygen carrier prepared by crosslinking porcine hemoglobin by glutaraldehyde to form a polymer. The pPolyHb has been proved to have the ability of transporting oxygen which could repair the organ ischemia-reperfusion injury in rats. Objective: In order to evaluate the effectiveness of rat liver perfusion in vitro based on pPolyHb, we established the NMP system, optimized the perfusate basic formula and explored the optimal proportion of pPolyHb and basal perfusate. Methods: The liver was removed and perfused for 6h at 37°C. We compared the efficacy of liver perfusion with different ratios of pPolyHb. Subsequently, compared the perfusion effect using Krebs Henseleit solution and pPolyHb perfusate of the optimal proportion, and compared with the liver preserved with UW solution. At 0h, 1h, 3h and 6h after perfusion, appropriate samples were collected for blood gas analysis and liver injury indexes detection. Some tissue samples were collected for H&E staining and TUNEL staining to observe the morphology and detect the apoptosis rate of liver cells. And we used Western Blot test to detect the expression of Bcl-2 and Bax in the tissues. Results: According to the final results, the optimal addition ratio of pPolyHb was 24%. By comparing the values of Bcl-2/Bax, the apoptosis rate of pPolyHb group was significantly reduced. Under this ratio, the results of H&E staining and TUNEL staining showed that the liver morphology was well preserved without additional signs of hepatocyte ischemia, biliary tract injury, or hepatic sinusoid injury, and hepatocyte apoptosis was relatively mild. Conclusion: Through the above-mentioned study we show that within 6h of perfusion based on pPolyHb, liver physiological and biochemical activities may essentially be maintained in vitro. This study demonstrates that a pPolyHb-based perfusate is feasible for NMP of rat livers. This opens up a prospect for further research on NMP.

Ferroptosis-A New Dawn in the Treatment of Organ Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) is a common pathological phenomenon that occurs in numerous organs and diseases. It generally results from secondary damage caused by the recovery of blood flow and reoxygenation, followed by ischemia of organ tissues, which is often accompanied by severe cellular damage and death. Currently, effective treatments for I/R injury (IRI) are limited. Ferroptosis, a new type of regulated cell death (RCD), is characterized by iron overload and iron-dependent lipid peroxidation. Mounting evidence has indicated a close relationship between ferroptosis and IRI. Ferroptosis plays a significantly detrimental role in the progression of IRI, and targeting ferroptosis may be a promising approach for treatment of IRI. Considering the substantial progress made in the study of ferroptosis in IRI, in this review, we summarize the pathological mechanisms and therapeutic targets of ferroptosis in IRI.

Necrostatin-1 Alleviates Lung Ischemia-Reperfusion Injury via Inhibiting Necroptosis and Apoptosis of Lung Epithelial Cells.

Lung ischemia-reperfusion injury (LIRI) is associated with many diseases, including primary graft dysfunction after lung transplantation, and has no specific and effective therapies. Necroptosis contributes to the pathogenesis of ischemia-reperfusion injury. Necrostatin-1 (Nec-1), the necroptosis inhibitor targeting RIPK1, has been reported to alleviate ischemia-reperfusion injury in various organs. However, the underlying mechanism of Nec-1 in LIRI remains unclear. In this paper, an in vivo LIRI model was built up by left lung hilar clamping in mice, and an in vitro cold ischemia-reperfusion (CI/R) model using BEAS-2B cells was applied to mimic the lung transplantation setting. We found Nec-1 significantly alleviated ischemia-reperfusion-induced lung injury, cytokine releasing, and necroptosis of epithelial cells in mouse lungs. In vitro, Nec-1 also mitigated CI/R-induced cell death and inflammatory responses in BEAS-2B cells, and these protective effects were achieved by simultaneously inhibiting the formation of necrosome and RIPK1-dependent apoptosis. However, Nec-1 decreased the necrosome number but increased the apoptosis level in lung tissues after ischemia reperfusion. We further clarified that Nec-1 could also attenuate lung injury by promoting neutrophil apoptosis from flow cytometry. In conclusion, Nec-1 alleviated lung ischemia-reperfusion injury by inhibiting necroptosis and apoptosis of epithelial cells and promoting the apoptosis of neutrophils. Thus, Nec-1 could be a promising medication against primary graft dysfunction after lung transplantation.

The Effect of Hypothermic Machine Perfusion to Ameliorate Ischemia-Reperfusion Injury in Donor Organs.

Hypothermic machine perfusion (HMP) has become the new gold standard in clinical donor kidney preservation and a promising novel strategy in higher risk donor livers in several countries. As shown by meta-analysis for the kidney, HMP decreases the risk of delayed graft function (DGF) and improves graft survival. For the liver, HMP immediately prior to transplantation may reduce the chance of early allograft dysfunction (EAD) and reduce ischemic sequelae in the biliary tract. Ischemia-reperfusion injury (IRI), unavoidable during transplantation, can lead to massive cell death and is one of the main causes for DGF, EAD or longer term impact. Molecular mechanisms that are affected in IRI include levels of hypoxia inducible factor (HIF), induction of cell death, endothelial dysfunction and immune responses. In this review we have summarized and discussed mechanisms on how HMP can ameliorate IRI. Better insight into how HMP influences IRI in kidney and liver transplantation may lead to new therapies and improved transplant outcomes.

Linopirdine-supplemented resuscitation fluids reduce mortality in a model of ischemia-reperfusion injury induced acute respiratory distress syndrome.

Previously, we demonstrated that supplementation of resuscitation fluids with the Kv7 voltage-activated potassium channel inhibitor linopirdine reduces fluid resuscitation requirements and stabilizes hemodynamics in various rat models of hemorrhagic shock. To further evaluate the therapeutic potential of linopirdine, we tested the effects of linopirdine-supplemented resuscitation fluids in a rat model of ischemia-reperfusion injury-induced acute respiratory distress syndrome (ARDS). Ventilated rats underwent unilateral lung ischemia from t=0-75 min, followed by lung reperfusion and fluid resuscitation to a mean arterial blood pressure of 60 mmHg with normal saline (NS, n=9) or NS supplemented with 50 µg/ml linopridine (NS-L), n=7) until t=360 min. As compared with NS, fluid resuscitation with NS-L stabilized blood pressure and reduced fluid requirements by 40% (p<0.05 vs. NS at t=240-360 min). While NS-L did not affect ARDS development, it reduced mortality from 66% with NS to 14% with NS-L (p=0.03, hazard ratio 0.14; 95% confidence interval of the hazard ratio: 0.03-0.65). Median survival time was 240 min with NS and >360 min with NS-L. As compared with NS treated animals that survived the observation period (n=3), however, plasma lactate and creatinine concentrations at t=360 min were higher with NS-L (n=6; p<0.05). Our findings extend therapeutic potential of NS-L from hypovolemic/hemorrhagic shock to hemodynamic instability under normovolemic conditions during organ ischemia-reperfusion injury. Possible adverse effects of NS-L, such as impairment of renal function and/or organ hypoperfusion, require further evaluation in long-term pre-clinical models.

Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells.

BackgroundLycopene is a naturally occurring carotenoid found in many fruits and vegetables, which has antioxidant effects. Although lycopene’s protective effect has been observed on ischemia reperfusion (IR) injury in different organs, the effect of lycopene on Kupffer cells (KCs) has not been clearly elucidated in IR-induced acute hepatic inflammatory injury.MethodsMice were administered with either olive oil (10 mL/kg body weight) as the control or lycopene (20 mg/kg body weight) by gavage for 2 weeks before undergoing hepatic IR injury.ResultsIn this study, we observed that the levels of aspartate aminotransferases (AST), alanine aminotransferase (ALT), and the percentages of hepatocellular apoptosis in mice pretreated with lycopene were significantly lower than control mice. Lycopene inhibited F4/80+ macrophage and Ly6G+ neutrophil accumulation, which further decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6). Interestingly, lycopene induced increased autophagy in KCs, which was evidenced by elevated autophagosomes and the increased protein level of LC3B. In these KCs, lycopene-induced upregulation of autophagy inhibited NOD-like receptor family pyrin domain-containing 3 protein (NLRP3) inflammasome activation, which was demonstrated by the reduced mRNA and protein levels of NLRP3, cleaved caspase-1, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and IL-1β. Furthermore, 3-methyladenine, an autophagy inhibitor, abolished lycopene’s inhibitory effect on the NLRP3 inflammasome in KCs, which led to increased hepatic IR injury. Intriguingly, we identified that the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were elevated in KCs isolated from IR-stressed mice pretreated with lycopene. Nrf2-siRNA or HO-1-siRNA could block the autophagy activation enhanced by lycopene in KCs, resulting in the activation of the NLRP3 inflammasome and aggravated hepatic IR injury.ConclusionsOur findings demonstrated that lycopene promoted Nrf2/HO-1 pathway activation and further suppressed the NLRP3 inflammasome via enhancing KC autophagy, which alleviated hepatic IR injury.

Organ Ischemia-Reperfusion Injury by Simulating Hemodynamic Changes in Rat Liver Transplant Model

Organ Ischemia-Reperfusion Injury by Simulating Hemodynamic Changes in Rat Liver Transplant Model

Organ Ischemia-Reperfusion Injury by Simulating Hemodynamic Changes in Rat Liver Transplant Model.

Orthotopic liver transplantation (OLT) in rats is a tried and proven animal model used for preoperative, intraoperative, and postoperative studies, including ischemia-reperfusion injury (IRI) of extrahepatic organs. This model requires numerous experiments and devices. The duration of anhepatic phase is closely related to the time to develop IRI after transplantation. In this experiment, we used hemodynamic changes to induce extrahepatic organ damage in rats and determined the maximum tolerance time. The time until the most severe organ injury varied for different organs. This method can easily be replicated and can also be used to study IRI of the extrahepatic organs after liver transplantation.

Protection From the Second Warm Ischemic Injury in Kidney Transplantation Using an Ex Vivo Porcine Model and Thermally Insulating Jackets

BackgroundKidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury. MethodsA novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation. ResultsIn both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P < .001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants. ConclusionProtection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes.

Directly Cooling Gut Prevents Mortality in the Rat Model of Reboa Management of Lethal Hemorrhage.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving technique for the management of lethal torso hemorrhage. Its benefit, however, must be weighed against the lethal distal organ ischemia-reperfusion injury (IRI). This study uses a novel direct gut cooling technique to manage the distal organ IRI. A rat lethal hemorrhage model was established by bleeding of 50% of the estimated total blood volume via inferior vena cava. A novel TransRectal Intra-Colon (TRIC) temperature management device was positioned in the descending colon either to maintain intra-colon temperature at 37°C or 12°C. The upper body temperature was maintained at as close to 37°C as possible in both groups. A 2F Fogarty balloon catheter was inserted via the femoral artery into the descending thoracic aorta for the implementation of REBOA. After REBOA, the balloon was deflated, and the shed blood was returned. The temperature managements were continued for additional 180 to 270 min during the post-REBOA period. All rats subjected to REBOA management of lethal hemorrhage at 37°C had severe histopathological gut and abdominal organ IRI, severe functional deficits, and died within 24 h with 100% mortality. By contrast, directly cooling the colon to 10°C to 12°C with the novel TRIC device abolished mortality, and dramatically improved ABG parameters, prevented the abdominal organ injury, and reduced the functional deficits during the 7-day post-REBOA period. Direct trans-rectal colon cooling during REBOA management of lethal hemorrhage offers extraordinary functional improvement and amazing tissue protection, and abolishes mortality.

Editorial introductions.

Editorial introductions.

Isoflurane suppresses lung ischemia-reperfusion injury by inactivating NF-κB and inhibiting cell apoptosis.

Patients with lung ischemia-reperfusion injury (LIRI), involving cytokines, including interleukin (IL)-6 and IL-8, display poor clinical outcomes. Isoflurane displays protective effects against ischemia-reperfusion injury in numerous organs. In the present study, the effects of isoflurane on LIRI were investigated in vitro using a hypoxia-reoxygenation (HR) cell model. The mRNA expression levels of specific genes were analyzed by reverse transcription-quantitative PCR and protein expression levels were measured by ELISA and western blotting. Cell apoptosis and proliferation were assessed by flow cytometry and the Cell Counting Kit-8 assay, respectively. Isoflurane pretreatment decreased HR-induced IL-6 and IL-8 expression levels in A549 cells. Isoflurane pretreatment also inhibited HR-induced cell apoptosis and Bax expression, and reversed HR-induced downregulation of Bcl-2 expression. Moreover, isoflurane pretreatment decreased HR-induced NF-κB phosphorylated-p65 protein expression and NF-κB activation. Furthermore, HR-induced increases in malondialdehyde concentration and decreases in superoxide dismutase activity were reversed by isoflurane pretreatment. In conclusion, the results indicated that isoflurane suppressed LIRI by inhibiting the activation of NF-κB and the induction of cell apoptosis.