Reperfusion Period Research Articles

Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption.

Intestinal ischemia-reperfusion injury (i-IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti-inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i-IRI. i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 µg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 µg/mL; non-treated, 1.18 ± 0.07 µg/mL; curcumin 1.76 ± 0.3 µg/mL; DEX5, 2.29 ± 0.2 µg/mL; DEX20, 2.25 ± 0.26 µg/mL; and α-tocopherol 1.66 ± 0.21 µg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.

Preservation of Testicular Tissue and Alleviation of Oxidative Stress by Carvacrol Following Torsion/ Detorsion in Adult Male Rats

Objectives: Testicular torsion is a critical medical condition necessitating prompt diagnosis and intervention. This study aimed to explore the potential safeguarding effect of carvacrol against histological damage and oxidative stress resulting from torsion/detorsion (T/D) in rat testes. Materials and Methods: A total of 32 adult male rats were randomly divided into four groups. The sham group did not undergo any intervention. The second group received an intraperitoneal injection of 75 mg/kg carvacrol half an hour before detorsion application. The third group was administered 80 mg/kg carvacrol intraperitoneally without detorsion. The fourth group (control) experienced (T/D) through the administration of saline. Following a 5-hour reperfusion period, the left testis was excised for histological slide preparation. Blood serum was used to measure antioxidant enzyme levels. Data analysis was performed using the SPSS version 19 software and analysis of variance tests. Results: Significant histological alterations were observed between the sham and other three groups. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and testosterone significantly decreased in all treatment groups compared to the control group (P<0.05). Conversely, malondialdehyde (MDA) levels increased in the torsion control group in contrast to the sham group (P<0.05). Carvacrol administration mitigated MDA levels in the treatment groups. Also, there were significant differences in tissue parameters between the sham and the other groups (P<0.05). Conclusions: According to the results of this study, carvacrol possesses the potential to mitigate testicular tissue damage, enhance testicular function, and ameliorate oxidative stress consequential to testicular rotation.

The potential renoprotective effect of Raloxifene in renal ischemia-reperfusion injury in a male rat model.

Renal ischemia-reperfusion injury is caused by a temporary reduction in oxygen-carrying blood flow to the kidney, followed by reperfusion. During ischemia, kidney tissue damage induces overproduction of reactive oxygen species, which produces oxidative stress. The blood flow restoration during the reperfusion period causes further production of reactive oxygen species that ends with apoptosis and cell death. This study aimed to investigate the potential renoprotective effects of Raloxifene on bilateral renal ischemia-reperfusion injury in rats by looking into kidney function biomarkers, urea and creatinine, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Additionally, antioxidant markers such as total antioxidant capacity (TAC) and the pro-apoptotic marker caspase-3 were assessed. Histopathological scores were also employed for evaluation. Our experimental design involved 20 rats divided into four groups: the sham group underwent median laparotomy without ischemia induction, the control group experienced bilateral renal ischemia for 30 minutes followed by 2 hours of reperfusion, the vehicle group received pretreatment with a mixture of corn oil and dimethyl sulfoxide (DMSO) before ischemia induction, and the Raloxifene-treated group was administered Raloxifene at a dose of 10 mg/kg before ischemia induction, followed by ischemia-reperfusion. Urea and creatinine, TNF-α, IL-1β, and caspase-3 in the Raloxifene group were significantly lower compared to the control and vehicle groups. On the other hand, TAC levels in the Raloxifene group were significantly higher than in the control and vehicle groups. This study concluded that Raloxifene had a renoprotective impact via multiple actions as an anti-inflammatory, anti-apoptotic, and antioxidant agent.

S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Hepatic ischemia/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the deficit in SAMet-synthetase activity and contributes to intracellular ATP repletion. It also acts as a methyl group donor, stabilizing hepatocyte membranes, among other functions. This study investigated the effect of SAMet on bacterial translocation and levels of proinflammatory cytokines, oxidative stress and apoptosis markers in male Wistar rats subjected to hepatic IRI. Animals were randomly divided into six groups: (1) sham operation, (3) animals undergoing 60 min of ischemia of the right lateral lobe for temporary occlusion of the portal vein and hepatic artery plus 10 min of reperfusion, and (5) the same as (3) but with a reperfusion period of 120 min. Groups 2, 4 and 6, respectively, are the same as (1), (3) and (5), except that animals received SAMet (20 mg/kg) 15 min before ischemia. GSH, ATP, lipid peroxidation (LPO), TNF-α, IL-1β, IL-6, total caspase-1 and caspase-9, total and cleaved caspase-3, and phosphatidylcholine were determined in the liver. Endotoxin, TNF-α, IL-1β, IL-6, IL-10 and LPO in vena cava and portal vein blood samples were also measured. Endotoxin and LPO levels as well as proinflammatory cytokines and apoptotic markers increased significantly in animals undergoing IRI, both after 10 and 120 min of reperfusion. IRI produced a significant decrease in GSH, ATP, portal IL-10 and phosphatidylcholine. SAMet treatment prevented these effects significantly and increased survival rate. The study suggests that SAMet exerts protective effects in hepatic IRI.

Myocardial state in overweight individuals after coronary revascularization

Heart and vascular diseases, or cardiovascular diseases (CVDs), have remained relevant for many decades and remain the most serious health problem in many countries around the world, including Kazakhstan. Experts from the World Health Organization (WHO) predict that by 2030 death from CVD may occur in 23.6 million people of working age. The widespread use of reconstructive and interventional methods, ensuring the restoration of blood flow in the myocardium, has made progress in the treatment of cardiovascular diseases. At the same time, serious problems remain during the reperfusion period at various stages of rehabilitation. The purpose of the review was to analyze the results of studies on the state of the myocardium in overweight individuals, especially after undergoing coronary artery surgery. The depth of the sample of literary sources was 20 years.

Evaluation of the therapeutic effects of oestradiol on the systemic inflammatory response and on lung injury caused by the occlusion of the proximal descending aorta in male rats.

Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17β-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17β-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17β-oestradiol (280 µg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1β, IL-10 and tumour necrosis factor-α were quantified. After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17β-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17β-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1β increased after I/R and 17β-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1β and IL-10 in lung explants, reduced by 17β-oestradiol. Our results showed that 17β-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17β-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.

Detection of Ischemic ST-Segment Changes Using a Novel Handheld ECG Device in a Porcine Model

BackgroundPortable, smartphone-sized electrocardiography (ECG) has the potential to reduce time to treatment for patients suffering acute cardiac ischemia, thereby lowering the morbidity and mortality. In the UMC Utrecht, a portable, smartphone-sized, multi-lead precordial ECG recording device (miniECG 1.0, UMC Utrecht) was developed. ObjectivesThe purpose of this study was to investigate the ability of the miniECG to capture ischemic ECG changes in a porcine coronary occlusion model. MethodsIn 8 animals, antero-septal myocardial infarction was induced by 75-minute occlusion of the left anterior descending artery, after the first or second diagonal. MiniECG and 12-lead ECG recordings were acquired simultaneously before, during and after coronary artery occlusion and ST-segment deviation was evaluated. ResultsDuring the complete occlusion and reperfusion period, miniECG showed large ST-segment deviation in comparison to 12-lead ECG. MiniECG ST-segment deviation was observed within 1 minute for most animals. The miniECG was positive for ischemia (ie, ST-segment deviation ≥1 mm) for 99.7% (Q1-Q3: 99.6%-99.9%) of the occlusion time, while the 12-lead was only positive for 79.8% (Q1-Q3: 81.1%-98.7%) of the time (P = 0.018). ST-segment deviation reached maxima of 10.5 mm [95% CI: 6.5-14.5 mm] vs 5.0 mm [95% CI: 2.0-8.0 mm] for the miniECG vs 12-lead ECG, respectively. ConclusionsMiniECG ST-segment deviation was observed early and was of large magnitude during 75 minutes of porcine transmural antero-septal infarction. The miniECG was positive for ischemia for the complete occlusion period. These findings demonstrate the potential of the miniECG in the detection of cardiac ischemia. Although clinical research is required, data suggests that the miniECG is a promising tool for the detection of cardiac ischemia.

Performance of Near-Infrared Spectroscopy in Detecting Acute Tourniquet-Induced Upper-Extremity Ischemia Across Different Skin Phenotypes

Diagnosing acute tissue ischemia is challenging, particularly in patients with higher skin melanin content. We investigated whether near-infrared spectroscopy (NIRS) is effective and consistent in detecting upper extremity ischemia across various skin phenotypes. Volunteers underwent tourniquet-induced upper extremity ischemia. Skin color was evaluated by the Fitzpatrick scale (FP, range: I-VI) and the Von Luschan scale (vL, range: 1-36). A NIRS probe was placed on one finger. The tourniquet was inflated to 250 mmHg and perfusion was restricted for 7 minutes, followed by a 10-minute monitored reperfusion period. The percent tissue oxygenation (StO2) was recorded. A total of 55 volunteers were enrolled (22 self-identified as Caucasian, 21 African American, 7 Asian, 2 Latinx, and 2 Biracial). Average starting and ending StO2 for the cohort was 72.2% and 45.9%, respectively. However, there was variability based on skin melanin content. Increasing vL correlated with lower starting StO2, smaller StO2 decrease, and shorter time to reach ischemic steady state. High skin melanin (FP scale IV-VI) was associated with significantly lower starting StO2 (-7.1%) and shorter time to reach ischemic steady state (-0.3 mins). African Americans had lower starting StO2 (-8.6%) and 7.8% lesser total StO2 decrease than other groups. NIRS can rapidly detect acute onset tissue ischemia in the upper extremity. However, given the lower starting StO2 and smaller total StO2 decrease after tourniquet-induced ischemia for patients with higher skin melanin, using NIRS for clinical detection of acute ischemia may be more challenging in these patients. These inconsistencies may limit use of NIRS clinically for spot identification of ischemia. Although NIRS has utility in tracking tissue oxygenation, variable performance with different skin melanin content raises concerns as to whether different cutoff/threshold levels are needed for different groups, and whether NIRS is reliable for spot checks in acute events.

Long-term Ovariectomy Reduces Tolerance of Rats to Myocardial Ischemia-reperfusion Injury.

The harmful impact of ovariectomy on myocardial ischemia-reperfusion (M/IR) injury has been established in the short term. In this study, we aimed to investigate the long-term effects of ovariectomy on M/IR injury. Two methods involving dorsolateral skin incisions were used to induce the ovariectomized (OVX) rat model. The rats were divided into 2 groups: Control and OVX (n = 6). At the end of the study, the hearts were isolated and subjected to global ischemia using the Langendorff apparatus. Cardiac function indices (CFIs) were recorded, including left ventricular end-diastolic pressure (LVEDP), peak rates of positive (+dp/dt) and negative (-dp/dt) changes in LV pressure, and LV-developed pressure (LVDP). At the end of the reperfusion period, the hearts were used to measure the size of the infarct, levels of nitric oxide metabolites (NOx), and mRNA expression of NO synthase (NOS) enzymes, including endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). Compared to controls, OVX rats had larger infarct size by 51%, higher LVEDP by 29%, and lower recovery of +dp/dt, -dp/dt, and LVDP by 29%, 22%, and 35%, respectively. Furthermore, in heart tissue, rats that underwent OVX had significantly higher concentrations of nitrate, nitrite, and NOx by 79%, 82%, and 83%, respectively. Additionally, these rats had lower mRNA levels of eNOS by 38% and higher mRNA levels of iNOS by 71%. The long-term deficiency of estrogen increased the expression of iNOS and decreased the expression of eNOS in the heart tissue of OVX rats. Imbalanced NOS expressions were associated with exacerbated responses to M/IR injury in OVX rats.

Ketone ester supplementation suppresses cardiac inflammation and improves cardiac energetics in a swine model of acute myocardial infarction

BackgroundMyocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the cardiovascular effects of ketone bodies in acute MI are unclear. We examined the effects of oral ketone supplementation as a potential treatment strategy in a swine acute MI model. MethodsFarm pigs underwent percutaneous balloon occlusion of the LAD for 80 min followed by 72 h reperfusion period. Oral ketone ester or vehicle was administered during reperfusion and continued during the follow-up period. ResultsOral KE supplementation induced ketonemia 2–3 mmol/l within 30 min after ingestion. KE increased ketone (βHB) extraction in healthy hearts without affecting glucose and fatty acid (FA) consumption. During reperfusion, the MI hearts consumed less FA with no change in glucose consumption, whereas hearts from MI-KE-fed animals consumed more βHB and FA, as well as improved myocardial ATP production. A significant elevation of infarct T2 values indicative of inflammation was found only in untreated MI group compared to sham. Concordantly, cardiac expression of inflammatory markers, oxidative stress, and apoptosis were reduced by KE. RNA-seq analysis identified differentially expressed genes related to mitochondrial energy metabolism and inflammation. ConclusionsOral KE supplementation induced ketosis and enhanced myocardial βHB extraction in both healthy and infarcted hearts. Acute oral supplementation with KE favorably altered cardiac substrate uptake and utilization, improved cardiac ATP levels, and reduced cardiac inflammation following MI.

The apelin-apela receptor APJ is necessary for formation and healing of ischemia reperfusion-induced gastric ulcer in rats

The apelinergic system widely expressed and regulates hormone-enzyme secretion, motility, and protective mechanisms of the stomach. This system consists of the apelin receptor (APJ) and two peptides known as apela and apelin. The IR-induced experimental gastric ulcer model is a well-known and commonly used one that induces hypoxia and causes the release of proinflammatory cytokines. Expressions of apelin and its receptor APJ are induced by hypoxia and inflammation in the gastrointestinal tract. Apelin has been shown to affect angiogenesis positively, considered the most critical component of the healing process. Although it is known that apelin and AJP expressions are induced by inflammatory stimuli and hypoxia, stimulate endothelial cell proliferation and have a role in regenerative angiogenesis, no information or has been found in the literature regarding the role of APJ in the formation and healing of gastric mucosal lesions induced by I/R. So, we conducted a study to clarify the role of APJ in formation and healing mechanisms of IR-induced gastric lesions. Male Wistar rats were divided into five groups; control, sham-operated, IR, APJ antagonist treated-IR group (F13A+IR), and the healing groups. F13A was intravenously given to the animals. Gastric lesion index, mucosal blood flow, PGE2, NOx, 4-HNE-MDA, HO activity, and protein expressions of VEGF and HO-1 were measured. F13A application before the IR increased the mucosal injury, F13A application following the ischemia delayed the mucosal healing during the reperfusion period. Consequently, blocking apelin receptors may worsen gastric injury due to the IR and delay mucosal healing.

Neutrophil extracellular traps (NETs), transfusion requirements and clinical outcomes in orthotopic liver transplantation.

Inflammatory phenomena have a direct impact on the prognosis of orthotopic liver transplantation (OLT). Neutrophil extracellular traps (NETs) contribute to OLT inflammation and hemostasis imbalance in OLT. The association between NETosis, clinical outcomes and transfusion requirements is not determined. To evaluate NETs release during OLT and the effect of NETosis ontransfusion requirements and adverse outcomes in a prospective cohort of patients submitted to OLT. We quantified citrullinated histones (cit-H3) and circulating-free-DNA (cf-DNA) in ninety-three patients submitted to OLT in three periods: pre-transplant, after graft reperfusion and before discharge. NETs markers were compared between these periods using ANOVA test. The association of NETosis and adverse outcomes was evaluated using regression models adjusted for age, sex and corrected MELD. We observed a peak of circulating NETs following reperfusion, evidenced by a 2.4-fold increase in cit-H3 levels in the post-graft reperfusion period (median levels of cit-H3 pre transplant: 0.5ng/mL, after reperfusion: 1.2ng/mL and at discharge 0.5ng/mL, p < 0.0001). We observed an association between increased levels of cit-H3 and in-hospital death (OR = 1.168, 95% CI 1.021-1.336, p = 0.024). No association was found between NETs markers and transfusion requirements. There is a prompt release of NETs after reperfusion that is associated with poorer outcomes and death. Intraoperative NETs release seems to be independent of transfusion requirements. These findings highlight the relevance of inflammation promoted by NETS and its impact on OLT adverse clinical outcomes.

Severe muscle damage after a short period of ischemia and reperfusion in an animal model

BackgroundSkeletal muscle ischemia-reperfusion injuries result in a loss of contractile function, leading to limb disability or amputation. Ischemia causes hypoxia and cellular energy failure, which is aggravated by reperfusion due to the inflammatory response and oxidative stress. The consequences of the injury vary according to the duration of the period of ischemia and reperfusion. Therefore, the present work aims to evaluate ischemia-reperfusion injuries induced in the skeletal muscles of Wistar rats submitted to 3 different application periods based on morphological and biochemical parameters. MethodsFor this, a tourniquet was applied to the root of the animals’ hind limbs, occluding arterial and venous blood flow, and it was followed by reperfusion—the removal of the tourniquet. The groups were: control (without tourniquet); I30'/R60' (30 minutes of ischemia and 1 hour of reperfusion); I120'/R120' (2 hours and 2 hours); and I180'/R180' (3 hours and 3 hours). ResultsAll ischemia-reperfusion groups showed characteristics of muscle injury. Microscopic analyses of the extensor digitorum longus, soleus, tibialis anterior, and gastrocnemius muscles showed a significant increase in the number of injured muscle fibers in the ischemia-reperfusion groups compared to the control group. There were also significant differences between the ischemia-reperfusion groups in all muscles, showing a progressive increase in the degree of injury. The quantification of the number of injured muscle fibers between the muscles revealed that at I30'/R60', the soleus muscles had a higher number of injuries in relation to the other muscles, with statistical significance. In the I120'/R120' group, the gastrocnemius muscles presented a significantly greater number of injured fibers. There were no significant differences in the I180'/R180' group. The serum levels of creatine kinase in the I180'/R180' group were significantly higher than in the control and I30'/R60' groups. ConclusionsTherefore, it was evident that the 3 ischemia-reperfusion models used were capable of causing cell damage, with these findings being more pronounced in the I180'/R180' group.

The effect of JQ1 systemic administration on oxidative stress and apoptotic markers in renal ischemic reperfusion injury in a rat model.

This study aimed to investigate the effects of JQ1 in a renal ischemia-reperfusion (IR) rat model. Twenty-four adult male Wistar Albino rats were randomly divided into four equal groups. The sham group underwent laparotomy without ischemia-reperfusion induction. The control group experienced bilateral renal ischemia for 30 minutes, followed by a 2-hour reperfusion period. The vehicle group (IR group + DMSO) and JQ1 group (same as in control IR + 25 mg/kg JQ1). Kidney and blood samples were collected 2 hours after reperfusion. Blood samples were used to analyze serum creatinine and blood urea nitrogen levels. Renal tissue was assessed for TNF-alpha, caspase-3, FOXO4, PI3K/AKT signaling pathway, and histological analysis. The control group exhibited significantly higher serum creatinine, blood urea nitrogen, caspase-3, TNF-alpha, and FOXO4 levels in renal tissue compared to the sham group. Additionally, the PI3K/AKT signaling pathway was significantly decreased in the control group. Histopathological examination revealed severe kidney damage in the control group compared to the sham group. In rats treated with JQ1, serum creatinine, BUN, caspase-3, TNF-alpha, and FOXO4 levels in renal tissue significantly improved. The PI3K/AKT signaling pathway was substantially increased (p-value 0.01) compared to the Vehicle and Control groups. The tubular severity score was also significantly reduced in the JQ1-treated groups compared to the Control and Vehicle groups. In conclusion, JQ1 significantly ameliorated renal ischemia-reperfusion injury in rats by suppressing apoptosis and inflammatory pathways.

Limb Remote Ischemic Postconditioning Improves Glymphatic Dysfunction After Cerebral Ischemia–Reperfusion Injury

BackgroundDelayed neuronal damage can be caused or aggravated after cerebral ischemia–reperfusion (I/R) injury. Recent studies have shown that glymphatic system dysfunction after cerebral ischemia–reperfusion injury is involved in ischemic brain edema and neuroinflammation, thereby regulating cerebral ischemia–reperfusion injury. The aim of this study is to investigate the changes of glymphatic system after cerebral ischemia–reperfusion injury and whether limb remote ischemic postconditioning (LRIP) can improve the function of glymphatic system to protect the brain. MethodsTo establish a focal brain I/R injury mouse model, this study utilized the middle cerebral artery occlusion/reperfusion (MCAO/R) method. The present study classified eight-week-old C57BL/6 male mice into three groups. The changes in glymphatic function in different periods of ischemia and reperfusion were analyzed through immunofluorescence, transmission electron microscopy (TEM), and Western-Blot (WB) assays. The contents of the evaluation included cerebrospinal fluid flow, swelling degree of brain tissue, aquaporin-4 (AQP4) expression and polarization, and amyloid-β (Aβ) excretion. ResultsIn the early stages of cerebral ischemia, cerebrospinal fluid (CSF) flow is disturbed, accompanied by a decrease in AQP4 polarization. The polarity of AQP4 decreased from 12 h to 72 h of reperfusion, the Aβ deposition. LRIP can increase the expression of β-DG and AQP4 polarization, reduce the deposition of Aβ, improve the function of the glymphatic system, and reduce the expression of AQP4 to play A protective role in brain. ConclusionGlymphatic system impaired after cerebral ischemia–reperfusion injury in mice. LRIP may play a neuroprotective role by improving glymphatic function after I/R.

The Acute Effects Of ATP-Sensitive Potassium Channel Opener (Pinacidil) And Blocker (Glimepride) On the Ischemia or Reperfusion-Induced Arrhythmias

Introduction: Myocardial ischemia due to coronary obstruction and reperfusion due to the opening of the coronary vessel occurring in the acute stage of myocardial infarction leads to lethal arrhythmia and sudden death in humans. That is why pharmacological drug research to decrease these arrhythmias have been researched intensively. In this study, the effect of acute administration of pinacidil and glimepride, on ischemia or reperfusion-induced arrhythmia was aimed to be researched. Methods: Two groups were produced; In the first group, only ischemia was produced by the ligation of the left coronary artery in 20 minutes, and in the second group 6 minutes of ischemia by the ligation of the artery and the subsequent 15 minutes of reperfusion were produced by the opening of the occluded artery. Drugs were administered intravenously at 2 minutes of ischemia in the first group and just following the reperfusion in the second group. The ECG and blood pressure were recorded during ischemia and reperfusion. The type, duration, incidence of arrhythmia, heart rate, blood pressure, and the death rate from the recording were determined. All data were first compared by one-way ANOVA. Then, the drug groups with their control, and control and drug groups with each other were compared by a one-tailed student t-test. The incidence of arrhythmia and the death rate between groups was compared by the Ki square test. Results: Pinacidil significantly decreased the arrhythmia score both in the ischemia and reperfusion period but glimepiride was not effective when they were given intravenously in the acute stage of ischemia or reperfusion. Discussion and Conclusion: This study suggests that pinacidil might be a candidate for drugs that can be used to decrease arrhythmia in the acute stage of myocardial infarction but more study is needed to reveal the antiarrhythmic or proarrhythmic effect of glimepride in the acute stage of myocardial infarction.

Ischemic Conditioning to Reduce Fatigue in Isometric Skeletal Muscle Contraction

Ischemic preconditioning (IPC) is a non-invasive protective maneuver that alternates short periods of occlusion and reperfusion of tissue blood flow. Given the heterogeneity in the magnitude and frequency of IPC-induced improvements in physical performance, here we aimed to investigate, in a well-controlled experimental set-up, the local effects of IPC in exposed muscles in terms of tissue oxygenation and muscle fatigue. Nineteen subjects were enrolled in one of the two groups, IPC (3 × 5/5 min right arm ischemia/reperfusion; cuff inflations 250 mmHg) and SHAM (3 × 5/5 min pseudo ischemia/reperfusion; 20 mmHg). The subjects performed a fatiguing contraction protocol before and 30 min after the IPC treatment, consisting of unilateral intermittent isometric elbow flexions (3 s ON/OFF, 80% of maximal voluntary contraction) until exhaustion. While muscle strength did not differ between groups, post- vs. pre-treatment endurance was significantly reduced in the SHAM group (4.1 ± 1.9 vs. 6.4 ± 3.1 repetitions until exhaustion, p < 0.05) but maintained in IPC (7.3 ± 2.0 vs. 7.1 ± 4.3, n.s.). The decrease in tissue oxygenation and the increase in deoxygenated hemoglobin were significantly reduced post- vs. pre-IPC (p < 0.05), but not post- vs. pre-SHAM. The results suggest that IPC delays the onset of fatigue likely through improved metabolic efficiency of muscles.

Hyperoxemia after reperfusion in cardiac arrest patients: a potential dose–response association with 30-day survival

BackgroundHyperoxemia may aggravate reperfusion brain injury after cardiac arrest. The aim of this study was to study the associations between different levels of hyperoxemia in the reperfusion period after cardiac arrest and 30-day survival.MethodsNationwide observational study using data from four compulsory Swedish registries. Adult in- and out-of-hospital cardiac arrest patients admitted to an ICU, requiring mechanical ventilation, between January 2010 and March 2021, were included. The partial oxygen pressure (PaO2) was collected in a standardized way at ICU admission (± one hour) according to the simplified acute physiology score 3 reflecting the time interval with oxygen treatment from return of spontaneous circulation to ICU admission. Subsequently, patients were divided into groups based on the registered PaO2 at ICU admission. Hyperoxemia was categorized into mild (13.4–20 kPa), moderate (20.1–30 kPa) severe (30.1–40 kPa) and extreme (> 40 kPa), and normoxemia as PaO2 8–13.3 kPa. Hypoxemia was defined as PaO2 < 8 kPa. Primary outcome was 30-day survival and relative risks (RR) were estimated by multivariable modified Poisson regression.ResultsIn total, 9735 patients were included of which 4344 (44.6%) were hyperoxemic at ICU admission. Among these, 2217 were classified as mild, 1091 as moderate, 507 as severe, and 529 as extreme hyperoxemia. Normoxemia was present in 4366 (44.8%) patients and 1025 (10.5%) had hypoxemia. Compared to the normoxemia group, the adjusted RR for 30-day survival in the whole hyperoxemia group was 0.87 (95% CI 0.82–0.91). The corresponding results for the different hyperoxemia subgroups were; mild 0.91 (95% CI 0.85–0.97), moderate 0.88 (95% CI 0.82–0.95), severe 0.79 (95% CI 0.7–0.89), and extreme 0.68 (95% CI 0.58–0.79). Adjusted 30-day survival for the hypoxemia compared to normoxemia group was 0.83 (95% CI 0.74–0.92). Similar associations were seen in both out-of-hospital and in-hospital cardiac arrests.ConclusionIn this nationwide observational study comprising both in- and out-of-hospital cardiac arrest patients, hyperoxemia at ICU admission was associated with lower 30-day survival.

The healing effect of topical tea tree oil on pressure ulcers in a rat model.

Objective: The effects of topical tea tree oil (TTO) on the healing of pressure ulcers (PUs) in an animal model was evaluated. Method: To induce PUs, ischaemia-reperfusion cycles were performed by the external application of magnetic plates, with an ischaemic period of eight hours and a reperfusion period of 16 hours. Male and female Wistar rats were divided into three equally sized groups (n=20): one group received topical glycerin twice daily, another group received topical 10% (volume/volume (v/v)) TTO in glycerin twice daily; and the remaining group was untreated. The animals were assessed after one, four, seven and 14 cycles of ischaemia-reperfusion by thermal camera imaging, and then euthanised and sampled to investigate the degree of inflammation, collagen synthesis and apoptosis in the PUs. Results: Although topical glycerin alone suppressed local inflammation and apoptosis, this suppressive effect was accentuated at all timepoints by the application of topical TTO + glycerin. Similarly, an increase in collagen synthesis was observed in the glycerin group and this was accentuated by TTO at all timepoints. Parallel to the histological findings, the local temperature had decreased significantly on days 4 and 7 for both treatment groups (glycerin and TTO+glycerin). Conclusion: In this study, treatment with 10% (v/v) TTO in glycerin effectively suppressed skin inflammation and apoptosis, while it increased collagen synthesis during PU formation.

Endogenous intoxication, oxidative stress and antioxidant system in acute lower limb ischemia

Aim. To study features of endogenous intoxication syndrome (EI), oxidative stress (LPO) and antioxidant defence (AOS) in patients with acute lower limb ischemia (LLI).Materials and methods. Some parameters of EI, LPO and AOS were studied. EI syndrome was studied in 86 patients with LLI who underwent complex examination and treatment in 2020-2021 in the Department of Vascular Surgery of the RNCfCS. POL and AOS parameters were studied in 14 patients out of 86. There were 51 (59.3%) men and 35 (40.7%) women, mean age was 56.0±5.8 years. Acute occlusion of the iliofemoral segments was noted in 33 (38.4%) patients, in 32 (37.2%) - the femoral segment, and in 21 (24.4%) - the popliteal and femoral vessels. In all cases, ischemia had a unilateral localization - on the right in 59 (68.6%) cases and on the left in 27 (31.4%) cases. In 52 (58.1%) cases, there were clinical signs of grade II b ischemia, and in 36 (41.9%) cases - grade III A (according to V.S. Saveliev, 1987). The average duration of ischemia was 77.9±28.3 hours.Results and discussion. In all cases of LLI before revascularization, there were signs of acute inflammatory reaction and EI syndrome in the form of increased ESR (42.3±7.1 mm/h), CRP concentration (16.1±4.2 mg/L), fibrinogen (8.5±0.9 g/L) and leukocytosis (12.7±1.5×109/L). Also, all patients had a slight elevation of blood glucose against the background of EI (7.5±1.8 mmol/L), a significant increase of creatinine concentration (128.9±6.1 µmol/L), urea (9.2±0.6 mmol/L) and aminotransferases as compared to normal indices. Results of LPO and AOS indices study in 14 patients showed that in LLI, malondialdehyde (MDA) increases 2.6-fold (3.9±0.1 μmol/L), diene conjugate increases 3.7-fold (0.77±0.04 units a/mL). However, after the elimination of ischemia, there was no significant decrease for 12.2±2.4 days, which confirms the presence of reperfusion syndrome. AOS indices - superoxide dismutase (20,8±1,0 u/l) and catalase (128,9±11,2 μl/l) increased 1,2 and 1,1 times in the examined patients cohort, respectively. Statistically significant associations were established between the following indices: Ischemia level and urea (r=0.89), Ischemia level and white blood cell count (r=-0.82), Hb and Er (r=0.99), Hb and creatinine (r=0.79), Hb and urea (r=0.79), Er and urea (r=0.79), creatinine and Er (r=0.90), ACTV and creatinine (r=-0.77), creatinine and urea (r=0.90).Conclusion. Acute lower limb ischemia is accompanied by ischemia-reperfusion damage manifested by endogenous intoxication syndrome, impaired glucose metabolism and activation of lipoperoxidation processes and antioxidant system. After the elimination of acute ischemia, there is not always a significant decrease in lipid peroxidation and some inflammation parameters. Therefore, prolonged use of antioxidants in the reperfusion period is recommended.