Effects Of Ischemia Research Articles

A PROMPT Update on Partial REBOA: Initial Clinical Data and Overview of the DoD-Funded Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) Study.

Retrograde Endovascular Balloon Occlusion of the Aorta (REBOA) is an effective management for the transient responder, but the ischemic consequences of complete aortic occlusion currently limit its use. Multiple DoD-funded preclinical studies have clearly demonstrated that partial REBOA reduces distal ischemia to potentially extend safe occlusion times, while still providing effective temporization of noncompressible torso hemorrhage. Early versions of REBOA devices were designed to completely occlude the aorta and had little ability to provide partial occlusion. Recently, a new REBOA device (pREBOA-PRO) was designed specifically to allow for partial occlusion, with the hypothesis that this may reduce the complications of aortic occlusion and extend safe occlusion times while maintaining the benefits on cardiac and cerebrovascular circulation as well as reductions in resuscitation requirements. To ascertain the impact of a new purpose-built partial REBOA device on the extension of safe occlusion time, the Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) trial compared available data from the pREBOA-PRO with existing data from 200 clinical uses of pREBOA-PRO and available data in the AAST AORTA Registry were reviewed to design primary endpoints and clinical evidence for a prospective multi-center trial, the PROMPT Study. Together with the endpoints identified in preclinical studies of partial REBOA, primary endpoints for the PROMPT study were identified and power analyses were conducted to determine the target patient enrollment goals. Results from the clinical implementation of partial REBOA at a single trauma center were used to conduct the initial power analysis for the primary endpoint of Acute Kidney Injury (AKI) after prolonged occlusion. The rate of AKI after complete REBOA was 55% (12/20) compared to 33% (4/12) after partial REBOA (Madurska etal., 2021). With an alpha of 0.05 and power (β) of 0.8, the projected sample size for comparison on a dichotomous outcome is 85 patients for the assessment of AKI. Initial power and endpoint analyses have been confirmed and extended with the ongoing analysis of partial and complete REBOA reported in the AORTA database. These analyses confirm preclinical findings which show that compared to complete REBOA, partial REBOA is associated with extended occlusion time in zone 1 (complete: 31 min vs. partial: 45 min, P = 0.003), lower rates of AKI after zone 1 occlusion (complete: 33% vs. partial: 19%, P = 0.05) and reduced resuscitation requirements (e.g., 25% reduction in pRBC administration: complete: 18 units vs. partial: 13 units, P = 0.02). The DoD-funded PROMPT study of partial REBOA will provide prospective observational clinical data on patients being treated with pREBOA-PRO. Outcomes will be stratified based on partial or complete occlusion to address whether partial REBOA has additional clinical benefits over complete REBOA, such as decreased distal ischemia, extension of safe occlusion time, improved hemodynamics during transition to and from occlusion, and reduced interoperative bleeding and blood product use. The results from this study are expected to confirm previous data demonstrating reduction of ischemic sequalae, improved transition to reperfusion, and reduced resuscitative requirements compared to complete REBOA.

Association Between Diagnosis-to-Limb Revascularization Time and Clinical Outcomes in Outpatients With Chronic Limb-Threatening Ischemia: Insights From the CLIPPER Cohort.

The extent and consequences of ischemia in patients with chronic limb-threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis-to-limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk-adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time <30 days, there was no association between D2L time and all-cause death or major lower extremity amputation. However, among patients with D2L time >30 days, each additional 10-day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014-1.036]). There was no association between D2L time and all-cause death. A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

Determination of Maximum Tolerable Cold Ischemia Time in a Mouse Model of Cervical Heterotopic Uterus Transplantation.

Uterus transplantation (UTx) is an emerging treatment for uterine factor infertility. Determining the maximum tolerable cold ischemia time is crucial for successful UTx. However, the limit for cold ischemia in the uterus is unclear. This study aimed to examine cold ischemia's effects on mouse uteri and identify the maximum cold ischemia duration that uteri can endure. We systematically assessed the tolerance of mouse uteri to extended cold ischemia, 24 h, 36 h, and 48 h, using the cervical heterotopic UTx model. Multiple indicators were used to evaluate ischemia-reperfusion injury, including reperfusion duration, macroscopic examination, oxidative stress, inflammation, and histopathology. The function of transplants was evaluated through estrous cycle monitoring and embryo transfer. Mouse uteri subjected to 48 h of cold ischemia exhibited significant delays and insufficiencies in reperfusion, substantial tissue necrosis, and loss of the estrous cycle. Conversely, uteri that underwent cold ischemia within 36 h showed long survival, regular estrous cycles, and fertility. Our study demonstrated that mouse uteri can endure at least 36 h of cold ischemia, extending the known limits for cold ischemia and providing a pivotal reference for research on the prevention and treatment of cold ischemic injury in UTx.

Effect of collateral circulation in patients with multiple craniocervical artery stenoses.

Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long-term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro-basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743-0.857, p < 0.001; Tan scores: OR: 0.478, 95% CI: 0.336-0.679, p < 0.001). Meanwhile, the collateral circulation scores were significantly associated with the recurrence of AIS within 3 years (rLMC scores: OR: 0.926, 95% CI: 0.860-0.997, p = 0.042; Tan scores: OR: 0.467, 95% CI: 0.306-0.712, p < 0.001). Most associations remained significant in the subgroup of patients with VBA stenosis. Favorable collateral circulation in multiple craniocervical artery stenosis patients reduced long-term ischemic event recurrence. Stratifying treatment risks is essential for optimizing outcomes.

Normothermic ex vivo perfusion of deceased donor kidneys and its clinical potential in kidney transplantation outcomes.

In recent years, normothermic machine perfusion (NMP) has emerged in conversation surrounding organ preservation and transplantation techniques with the goal of improving patient and clinical outcomes. This is in great attempt to address the rate of non-utilization and the shortage of available organs in kidney transplantation. This focus in mind, normothermic perfusion presents itself as a potential tool to mimic physiological conditions and improve current preservation methods, such as static cold storage. This review serves to improve understanding of the observed connection between the consequences of ischemia and reperfusion injury and traditional preservation techniques as well as how renal NMP may mitigate these issues. Previous studies suggest that reducing time in static cold storage methods by promoting the normothermic perfusion model results in decreased delayed graft function and post-transplant complications. This review also aims to present the immense clinical potential NMP has on future kidney transplantation success and what this means for the fields of nephrology and transplantation. While great strides have been made to evaluate normothermic perfusion's impact on kidney graft viability and transplant success, future research into unified protocol, clinically relevant biomarkers, cost-utility analysis, and use with associated therapeutic and imaging modalities is paramount.

Late Decrease in Cerebral Blood Flow in Bacterial Meningitis: More than a Simple Normalization of Acute Inflammatory Vessel Wall Architecture?

Acute bacterial meningitis is a disease with an overwhelmingly high mortality rate and high incidence of adverse neurological sequelae and poor neurological recovery amongst survivors. Amongst the numerous complications of bacterial meningitis, the presence of cerebrovascular disease represents a severe disease form. Vascular involvement during bacterial meningitis has long been established by numerous pathological and angiographic studies. Cerebrovascular changes known to occur in bacterial meningitis ranging from narrowing of large arteries by vasospasm to critical stenosis/obliteration of small to medium sized arteries/arterioles by vasculitis. Not surprisingly, alterations in CBF velocities have commonly been described during the inflammatory process and may represent an important component of brain injury during meningitis. In accordance with previous studies observing a biphasic cerebral flow pattern characterized by an early but transient increase in flow velocity, mostly due to reflexive vasospasm, and later by a sustained decrease in flow velocity, likely attributable to stenotic vasculitis, cerebral ischemia is a notable complication of bacterial meningitis during the advanced disease phase. Impaired cerebral perfusion during the late stages of disease may result from a variety of factors that contribute to a vital component of cerebral injury in bacterial meningitis. The pathogenesis of cerebral ischemia with progression of disease course is less clearly understood but may involve a complex interaction between inflammatory processes, systemic dysfunction, energy impairment, neuronal damage and intracranial pressure, factors of which we aim to more precisely understand and assign a more definite contributory role in the development of cerebrovascular ischemic consequences with advanced stages of bacterial meningitis.

Protective effects of gallic acid and SGK1 inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats.

Oxidative stress and serum and glucocorticoid-induced Kinase 1 gene (SGK1) perform a central role in the consequences of ischemia in the heart. This research aimed to investigate the effect of coadministration of gallic acid and the GSK650394 (as SGK1 gene inhibitor) on the ischemic complications of a rat model of cardiac ischemia/reperfusion (I/R) injury. Sixty male Wistar rats were divided into 6 groups with or without pretreatment with gallic acid for 10 days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A 30 min of ischemia was performed followed by a 60 min reperfusion. In 2 groups, GSK650394 was infused 5 min before ischemia induction. Ten minutes after reperfusion commencement, cardiac marker enzyme (CK-MB, LDH, and cTn-I) activities were measured in the cardiac perfusate. At the end of reperfusion, the activity of anti-oxidant enzymes (Catalase, Superoxide dismutase, and Glutathione peroxidase), lipid peroxidation (MDA), total anti-oxidant capacity (TAC), intracellular reactive oxygen species (ROS), infarct size, and SGK1 gene expression were measured in the heart tissue. The results indicated that dual therapy with both drugs significantly improved endogenous anti-oxidant enzyme activity and TAC more than each drug alone. However, the heart marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK1 gene expression were reduced significantly compared with the ischemic group. The results of this study suggest that concomitant administration of both drugs in the case of cardiac I/R injury may have a more beneficial effect than each one alone.

Uterine Perforation as a Complication of the Intrauterine Procedures Causing Omentum Incarceration: A Review.

Omentum involvement resulting from uterine perforation is a rare complication following intrauterine procedures that might require immediate intervention due to severe ischemic consequences. This review examines the prevalence of this complication, risk factors, the mode and timing of diagnosis, the proper management and the outcome. A systematic literature search was conducted on PubMed, PubMed Central and Scopus using uterine perforation, D&C, abortion and omentum as keywords. The exclusion criteria included the presence of the uterus or placenta's malignancy and uterine perforation following delivery or caused by an intrauterine device. The review included 11 articles from 133 screened papers. We identified 12 cases that three evaluators further analysed. We also present the case of a 32-year-old woman diagnosed with uterine perforation and omentum involvement. The patient underwent a hysteroscopic procedure with resectioning the protruding omentum into the uterine cavity, followed by intrauterine device insertion. This paper highlights the importance of a comprehensive gynaecological evaluation following a D&C procedure that includes a thorough clinical examination and a detailed ultrasound assessment. Healthcare providers should not overlook the diagnosis of omentum involvement in the presence of a history of intrauterine procedures.

A case of incarcerated umbilical hernia in a 9-year-old child and review article on pediatric umbilical hernia

Umbilical hernia in children is a relatively common condition with a higher prevalence in premature, low-birth weight and black children. By contrast, complicated umbilical hernia rarely occurs. Early recognition of this condition is essential in order to prevent potential ischemic consequences. Most authors recommend a conservative stance of watchful waiting for the uncomplicated pediatric umbilical hernias up to the age of 4 years, with an emergent surgical correction in complicated cases. We report an uncommon case of a 9-year-old male who presented with sharp abdominal pain, irreducible umbilical mass, and vomiting following strenuous physical activity. Additionally, we provide insight on the current knowledge of pediatric umbilical hernia with a particular focus on its complications.

The role of hyperbaric oxygen for acute traumatic ischemias

Acute traumatic ischemias are an array of disorders that range from crush injuries to compartment syndromes, from burns to frostbite and from threatened flaps to compromised reimplantations. Two unifying components common to these conditions are a history of trauma be it physical, thermal, or surgical coupled with ischemia to the traumatized tissues. Their pathophysiology resolves around the self-perpetuating cycle of edema and ischemia, and their severity represents a spectrum from mild, almost non-existent, to tissue death. Since ischemia is a fundamental component of the traumatic ischemias and hypoxia is a consequence of ischemia, hyperbaric oxygen is a logical intervention for those conditions where tissue survival, infection control and healing is at risk. Unfortunately, even with mechanisms of hyperbaric oxygen that strongly support its usefulness in traumatic ischemias coupled with supportive clinical data, clinicians are disinclined to utilize it for these conditions. This focuses on the orthopedic aspects of the traumatic ischemias, namely crush injury and compartment syndrome, and show how hyperbaric oxygen treatments can mitigate their severity.

Minocycline as heart conditioning agent in experimental type 2 diabetes mellitus - an antibacterial drug in heart protection.

Cardiovascular diseases, and among them certainly myocardial infarction, remain leading cause of death worldwide. Diabetes increases risk of occurrence as well as adverse outcome of myocardial infarction. Conditioning maneuvers are the most attractive method for alleviating both the consequences of ischemia and reperfusion. Minocycline is a tetracycline derivative which exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. The aim of this study was to assess the protective ability of preconditioning and postconditioning of isolated hearts from healthy and rats with experimentally induced type 2 diabetes with minocycline on functional recovery and redox status after ischemia and reperfusion. The hearts from healthy and diabetic rats were excised and retrogradely perfused according to the Langendorff technique. Using sensor in the left ventricle, the cardiodynamic parameters were recorded and in the samples of the coronary venous effluent oxidative stress biomarkers were analyzed. Minocycline was injected directly into the coronary vessels, in preconditioning 5min before global ischemia, and in postconditioning during the first 5min of reperfusion. Results of this study clearly show beneficial effects of minocycline applied both before ischemia and in the first minutes of reperfusion fashion in both healthy and diabetic rat hearts. The most prominent protective effect regarding oxidative stress is related to the decreased production of superoxide anion radical due postconditioning with minocycline in diabetic hearts. Cardiodynamic parameters were significantly improved in minocycline conditioned groups. Superoxide anion radical stands out as the most susceptible to changes induced by minocycline.

Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease

BackgroundLeukoencephalopathy with brain calcifications and cysts (LCC; also known as Labrune syndrome) is a rare genetic microangiopathy caused by biallelic mutations in SNORD118. The mechanisms by which loss-of-function mutations in SNORD118 lead to the phenotype of leukoencephalopathy, calcifications and intracranial cysts is unknown.Case presentationWe present the histopathology of a 36-year-old woman with ataxia and neuroimaging findings of diffuse white matter abnormalities, cerebral calcifications, and parenchymal cysts, in whom the diagnosis of LCC was confirmed with genetic testing. Biopsy of frontal white matter revealed microangiopathy with small vessel occlusion and sclerosis associated with axonal loss within the white matter.ConclusionsThese findings support that the white matter changes seen in LCC arise as a consequence of ischemia rather than demyelination.

Peribiliary Intravascular Fibrin Occlusions and Bile Duct Necrosis in DCD Livers During Ex Situ Perfusion: Prevention With Tissue Plasminogen Activator and Fresh Frozen Plasma.

We have observed epithelial loss from the luminal surface of the bile ducts, often in conjunction with underlying stromal necrosis, in livers donated after circulatory death (DCD) undergoing ex situ normothermic machine perfusion (NMP).1 On occasion, the overlying epithelium has been intact but the underlying stroma necrotic, suggesting a vascular occlusive process as opposed to an intraluminal cause. With Research Ethics Committee approval (14/EE/0137), we perfused 5 DCD livers for at least 4 h using the metra (OrganOx, Oxford, United Kingdom). Livers were then formalin-fixed, and the extrahepatic biliary tree and major septal ducts dissected out and cross-sections examined, noting stromal necrosis on hematoxylin and eosin staining, intravascular fibrin deposition with Martius Scarlet Blue (MSB) stain, and vessel density with CD31 stain. Histological appearances were normal in 1 liver; 4 had stromal necrosis affecting hilar and septal ducts involving between 25% and 100% of the circumference. Fibrin/erythrocyte plugs were visible on MSB in between 25 and 50% of vessels where there was stromal necrosis, but not in its absence (Figure 1A and B are typical examples). In total, 26 duct profiles were reviewed in the 4 affected livers, and 24 exhibited necrosis/fibrin plugs. A second series of 5 liver perfusions were performed with 50 mg tissue plasminogen activator (TPA, Alteplase, Boehringer Ingelheim, Germany) and 250 mL fresh frozen plasma (FFP) infused into the perfusate; no intravascular fibrin and no septal duct necrosis was observed in any liver (Figure 1C and D). Lastly, TPA alone was added to 2 livers with similar appearances to the no-TPA group.FIGURE 1.: Hematoxylin and eosin (H&E) and Martius Scarlet Blue (MSB) stained sections of bile ducts. A, H&E stained section showing widespread stromal necrosis and epithelial loss in an intrahepatic bile duct. Eosinophilic inclusions are present in the subendothelial vessels (arrowed in the magnified panels). B, Corresponding MSB stained section showing that the same subendothelial areas are intravascular aggregates of fibrin and erythrocytes (also arrowed in the panels). These stain red and yellow; collagen stains blue with MSB. C, H&E section of intrahepatic bile duct from a liver treated with fresh frozen plasma (FFP) and tissue plasminogen activator (TPA). The stroma is viable with no subepithelial eosinophilic inclusions. D, Corresponding MSB stained section of the same liver showing no fibrin/erythrocyte intravascular aggregates.Intravascular deposition of fibrin has been noted to occur de novo after NMP in peripheral biopsies of DCD livers and kidneys.2,3 These observations, coupled with observations from our small series of perfusions, need further and more detailed investigation, with clinical evaluation, but have prompted us to suggest the following hypotheses/observations: Bile duct stromal infarcts occur secondary to occlusion of peribiliary vessels with fibrin/erythrocyte plugs. The fibrin/erythrocyte plugs develop after reperfusion as a consequence of ischemia, which is more profound in DCD livers. Stromal infarcts seen to occur during ex situ perfusion may correspond to nonanastomotic biliary strictures (NAS) in transplanted livers. FFP provides an exogenous source of plasminogen enabling TPA to generate sufficient plasmin to clear fibrin deposits in peribiliary vessels. Ex situ treatment of livers undergoing NMP with the combination of FFP and TPA appears to prevent the occurrence of stromal infarcts and may therefore prevent nonanastomotic biliary strictures. NAS have long been thought to be related to bile duct ischemia and occur even where donor heparinization before withdrawal of treatment is routine, suggesting that intravascular thrombosis per se is not a perimortem event. Administration of TPA into the hepatic artery during implantation is reported to reduce NAS, albeit with an increase in intraoperative bleeding due to its widespread fibrinolytic effect.4 This beneficial effect in vivo may be achievable ex situ without the associated intraoperative bleeding since the TPA half-life is very short (5 min) and the liver flushed before implantation.

Hypothermia promotes mitochondrial elongation In cardiac cells via inhibition of Drp1

Hypothermia is a valuable clinical tool in mitigating against the consequences of ischemia in surgery, stroke, cardiac arrest and organ preservation. Protection is afforded principally by a reduction of metabolism, manifesting as reduced rates of oxygen uptake, preservation of ATP levels, and a curtailing of ischemic calcium overload. The effects of non-ischemic hypothermic stress are relatively unknown. We sought to investigate the effects of clinically mild-to-severe hypothermia on mitochondrial morphology, oxygen consumption and protein expression in normoxic hearts and cardiac cells.Normoxic perfusion of rat hearts at 28–32 °C was associated with inhibition of mitochondrial fission, evidenced by a reduced abundance of the active phosphorylated form of the fission receptor Drp1 (pDrp1S616). Abundance of the same residue was reduced in H9c2 cells subjected to hypothermic culture (25–32 °C), in addition to a reduced abundance of the Drp1 receptor MFF. Hypothermia-treated H9c2 cardiomyocytes exhibited elongated mitochondria and depressed rates of mitochondrial-associated oxygen consumption, which persisted upon rewarming. Hypothermia also promoted a reduction in mRNA expression of the capsaicin receptor TRPV1 in H9c2 cells. When normothermic H9c2 cells were transfected with TRPV1 siRNA we observed reduced pDrp1S616 and MFF abundance, elongated mitochondria, and reduced rates of mitochondrial-associated oxygen consumption, mimicking the effects of hypothermic culture.In conclusion hypothermia promoted elongation of cardiac mitochondria via reduced pDrp1S616 abundance which was also associated with suppression of cellular oxygen consumption. Silencing of TRPV1 in H9c2 cardiomyocytes reproduced the morphological and respirometric phenotype of hypothermia. This report demonstrates a novel mechanism of cold-induced inhibition of mitochondrial fission.

Atrioventricular block as a predictor of major adverse cardiac events in acute coronary syndrome patients

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf Portuguese Registry of Acute Coronary Syndromes Background Atrioventricular block (AVB) can be a consequence of ischemia in acute coronary syndrome (ACS). Then, its expected, that AVB occurrence is associated with higher rates of major adverse cardiac events (MACE). Objective Evaluate if sustained AVB was a predictor of MACE in ACS hospitalized patients. Methods Multicenter retrospective study, based on the Portuguese Registry of ACS between 1/10/2010-3/05/2020. Patients were divided into two groups: A – patients without AVB, and B – patients that presented AVB. Were excluded patients without a previous cardiovascular history or clinical data regarding AVB occurrence. MACE was defined as re-infarction, congestive heart failure, cardiogenic shock, a mechanical complication of myocardial infarction, completed atrioventricular block, sustained ventricular tachycardia, cardiac arrest, stroke, major hemorrhage, transfusion and hospitalization death. Univariate logistic regression was performed to assess if AVB in ACS patients was a predictor of MACE. Results A total of 32157 patients was analyze and 23774 had information regarding AVB. From the group of patients that presented AVB, 214 (0.9%) had re-infarction, 3847 (16.2%) had congestive heart failure, 1018 (4.3%) had cardiogenic shock, 1069 (4.5%) had atrial fibrillation, 152 (0.6%) had a mechanical complication of myocardial infarction, 354 (1.5%) had sustained ventricular tachycardia, 706 (3.0%) had cardiac arrest, 152 (0.6%) had stroke, 364 (1.5%) had major hemorrhage, 353 (1.5%) had blood transfusion and 928 (3.0%) died. AVB did not predict re-infarction (p = 0.145), congestive heart failure (p = 0.334), atrial fibrillation (p = 0.171), mechanical complication of myocardial infarction (p = 0.465) and cardiac arrest (p = 0.142). Logistic regression revealed that AVB in ACS patients was a predictor of cardiogenic shock (odds ratio (OR) 2.350, p = 0.012, confidence interval (CI) 1.207-4.572), sustained ventricular tachycardia (OR 2.269, p = 0.013, CI 1.187-4.340), stroke (OR 2.231, p &amp;lt; 0.001, CI 1.779-5.852), major hemorrhage (OR 3.863, p &amp;lt; 0.001, CI 2.667-5.558), blood transfusion (OR 4.291, p &amp;lt; 0.001, CI 3.002-6.137) and hospitalization death (OR 2.699, p &amp;lt; 0.001, CI 1.725-4.222). Conclusions AVB in ACS patients predict MACE, namely cardiogenic shock, sustained ventricular tachycardia, stroke, major hemorrhage, blood transfusion and hospitalization death.

End-tidal Carbon Dioxide as an Indicator of Partial REBOA and Distal Organ Metabolism in Normovolemia and Hemorrhagic Shock in Anesthetized Pigs.

It is difficult to estimate the ischemic consequences when using partial resuscitative endovascular balloon occlusion of the aorta (REBOA). The aim was to investigate if end-tidal carbon dioxide (ETCO2) is correlated to degree of aortic occlusion, measured as distal aortic blood flow, and distal organ metabolism, estimated as systemic oxygen consumption (VO2), in a porcine model of normovolemia and hemorrhagic shock. Nine anesthetized pigs (25-32 kg) were subjected to incremental steps of zone 1 aortic occlusion (reducing distal aortic blood flow by 33%, 66%, and 100%) during normovolemia and hemorrhagic grade IV shock. Hemodynamic and respiratory variables, and blood samples, were measured. Systemic VO2 was correlated to ETCO2 and measures of partial occlusion previously described. Aortic occlusion gradually lowered distal blood flow and pressure, whereas ETCO2, VO2 and carbon dioxide production decreased at 66% and 100% aortic occlusion. Aortic blood flow correlated significantly to ETCO2 during both normovolemia and hemorrhage (R = 0.84 and 0.83, respectively) and to femoral mean pressure (R = 0.92 and 0.83, respectively). Systemic VO2 correlated strongly to ETCO2 during both normovolemia and hemorrhage (R = 0.91 and 0.79, respectively), blood flow of the superior mesenteric artery (R = 0.77 and 0.85, respectively) and abdominal aorta (R = 0.78 and 0.78, respectively), but less to femoral blood pressure (R = 0.71 and 0.54, respectively). ETCO2 was correlated to distal aortic blood flow and VO2 during incremental degrees of aortic occlusion thereby potentially reflecting the degree of aortic occlusion and the ischemic consequences of partial REBOA. Further studies of ETCO2, and potential confounders, in partial REBOA are needed before clinical use.

Prehospital aortic blood flow control techniques for non-compressible traumatic hemorrhage.

Non-compressible hemorrhage in the junctional areas and torso could be life-threatening and its prehospital control remains extremely challenging. The aim of this review was to compare commonly used techniques for the control of non-compressible hemorrhage in prehospital settings, and thereby provide evidence for further improvements in emergency care of traumatic injuries. Three techniques were reviewed including external aortic compression (EAC), abdominal aortic junctional tourniquet (AAJT), and resuscitative endovascular balloon occlusion of the aorta (REBOA). In prehospital settings, all three techniques have demonstrated clinical effectiveness for the control of severe hemorrhage. EAC is a cost- and equipment-free, easy-to-teach, and immediately available technique. In contrast, AAJT and REBOA are expensive and require detailed instructions or systematic training. Compared with EAC, AAJT and REBOA have greater potentials in the management of traumatic hemorrhage. AAJT can be used not only in the junctional areas but also in pelvic and bilateral lower limb injuries. However, both AAJT and REBOA should be used for a limited time (less than 1 hour) due to possible consequences of ischemia and reperfusion. Compared with EAC and AAJT, REBOA is invasive, requiring femoral arterial access and intravascular guidance and inflation. Mortality from non-compressible hemorrhage could be reduced through the prehospital application of aortic blood flow control techniques. EAC should be considered as the first-line choice for many non-compressible injuries that cannot be managed with conventional junctional tourniquets. In comparison, AAJT or REBOA is recommended for better control of the aorta blood flow in prehospital settings. Although these three techniques each have advantages, their use in trauma is not widespread. Future studies are warranted to provide more data about their safety and efficacy.

The Endothelial Glycocalyx as a Target of Ischemia and Reperfusion Injury in Kidney Transplantation-Where Have We Gone So Far?

The damage of the endothelial glycocalyx as a consequence of ischemia and/or reperfusion injury (IRI) following kidney transplantation has come at the spotlight of research due to potential associations with delayed graft function, acute rejection as well as long-term allograft dysfunction. The disintegration of the endothelial glycocalyx induced by IRI is the crucial event which exposes the denuded endothelial cells to further inflammatory and oxidative damage. The aim of our review is to present the currently available data regarding complex links between shedding of the glycocalyx components, like syndecan-1, hyaluronan, heparan sulphate, and CD44 with the activation of intricate immune system responses, including toll-like receptors, cytokines and pro-inflammatory transcription factors. Evidence on modes of protection of the endothelial glycocalyx and subsequently maintenance of endothelial permeability as well as novel nephroprotective molecules such as sphingosine-1 phosphate (S1P), are also depicted. Although advances in technology are making the visualization and the analysis of the endothelial glycocalyx possible, currently available evidence is mostly experimental. Ongoing progress in understanding the complex impact of IRI on the endothelial glycocalyx, opens up a new era of research in the field of organ transplantation and clinical studies are of utmost importance for the future.

Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts

A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia.

Increased Immunosignals of Collagen IV and Fibronectin Indicate Ischemic Consequences for the Neurovascular Matrix Adhesion Zone in Various Animal Models and Human Stroke Tissue.

Ischemic stroke causes cellular alterations in the “neurovascular unit” (NVU) comprising neurons, glia, and the vasculature, and affects the blood-brain barrier (BBB) with adjacent extracellular matrix (ECM). Limited data are available for the zone between the NVU and ECM that has not yet considered for neuroprotective approaches. This study describes ischemia-induced alterations for two main components of the neurovascular matrix adhesion zone (NMZ), i.e., collagen IV as basement membrane constituent and fibronectin as crucial part of the ECM, in conjunction with traditional NVU elements. For spatio-temporal characterization of these structures, multiple immunofluorescence labeling was applied to tissues affected by focal cerebral ischemia using a filament-based model in mice (4, 24, and 72 h of ischemia), a thromboembolic model in rats (24 h of ischemia), a coagulation-based model in sheep (2 weeks of ischemia), and human autoptic stroke tissue (3 weeks of ischemia). An increased fibronectin immunofluorescence signal demarcated ischemia-affected areas in mice, along with an increased collagen IV signal and BBB impairment indicated by serum albumin extravasation. Quantifications revealed a region-specific pattern with highest collagen IV and fibronectin intensities in most severely affected neocortical areas, followed by a gradual decline toward the border zone and non-affected regions. Comparing 4 and 24 h of ischemia, the subcortical fibronectin signal increased significantly over time, whereas neocortical areas displayed only a gradual increase. Qualitative analyses confirmed increased fibronectin and collagen IV signals in ischemic areas from all tissues and time points investigated. While the increased collagen IV signal was restricted to vessels, fibronectin appeared diffusely arranged in the parenchyma with focal accumulations associated to the vasculature. Integrin α5 appeared enriched in the vicinity of fibronectin and vascular elements, while most of the non-vascular NVU elements showed complementary staining patterns referring to fibronectin. This spatio-temporal characterization of ischemia-related alterations of collagen IV and fibronectin in various stroke models and human autoptic tissue shows that ischemic consequences are not limited to traditional NVU components and the ECM, but also involve the NMZ. Future research should explore more components and the pathophysiological properties of the NMZ as a possible target for novel neuroprotective approaches.