Restoration Of Perfusion Research Articles

European Society for Vascular Surgery (ESVS) 2025 Clinical Practice Guidelines on the Management of Vascular Trauma.

The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with vascular trauma with the aim of assisting physicians in selecting the optimal management strategy. The guidelines are based on scientific evidence completed with expert opinion. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to the ESVS evidence grading system, where the strength (class) of each recommendation is graded from I to III, and the letters A to C mark the level of evidence. A total of 105 recommendations have been issued on the following topics: general principles for vascular trauma care and resuscitation including technical skill sets, bleeding control and restoration of perfusion, graft materials, and imaging; management of vascular trauma in the neck, thoracic aorta and thoracic outlet, abdomen, and upper and lower extremities; post-operative considerations after vascular trauma; and paediatric vascular trauma. In addition, unresolved vascular trauma issues and the patients' perspectives are discussed. The ESVS clinical practice guidelines provide the most comprehensive, up to date, evidence based advice to clinicians on the management of vascular trauma.

Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.

The gastrointestinal tract can be deranged by ailments including sepsis, trauma and haemorrhage. Ischaemic injury provokes a common constellation of microscopic and macroscopic changes that, together with the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow, are collectively known as ischaemia-reperfusion injury (IRI). Although much of the gastrointestinal tract is normally hypoxemic, intestinal IRI results when there is inadequate oxygen availability due to poor supply (pathological hypoxia) or abnormal tissue oxygen use and metabolism (dysoxia). Intestinal oxygen uptake usually remains constant over a wide range of blood flows and pressures, with cellular function being substantively compromised when ischaemia leads to a>50% decline in intestinal oxygen consumption. Restoration of perfusion and oxygenation provokes additional injury, resulting in mucosal damage and disruption of intestinal barrier function. The primary cellular mechanism for sensing hypoxia and for activating a cascade of cellular responses to mitigate the injury is a family of heterodimer proteins called hypoxia-inducible factors (HIFs). The HIF system is connected to numerous biochemical and immunologic pathways induced by IRI and the concentration of those proteins increases during hypoxia and dysoxia. Activation of the HIF system leads to augmented transcription of specific genes in various types of affected cells, but may also augment apoptotic and inflammatory processes, thus aggravating gut injury. KEY POINTS: During intestinal ischaemia, mitochondrial oxygen uptake is reduced when cellular oxygen partial pressure decreases to below the threshold required to maintain normal oxidative metabolism. Upon reperfusion, intestinal hypoxia may persist because microcirculatory flow remains impaired and/or because available oxygen is consumed by enzymes, intestinal cells and neutrophils.

Prehospital Trauma Compendium: Vasopressors in Trauma – a Position Statement and Resource Document of NAEMSP

Acutely injured trauma patients may develop shock from several potential mechanisms, including hypovolemic shock from hemorrhage, neurogenic shock from traumatic brain injury (TBI) or spinal cord injury, obstructive shock from tension pneumothorax or pericardial tamponade, or a mix of several of these mechanisms. Regardless of the cause, restoration of adequate perfusion is of critical importance to reduce the morbidity and mortality of trauma patients with shock. Multiple interventions including hemorrhage control, volume resuscitation with intravenous fluids or blood products, and pleural decompression procedures are used to address some of these issues and are discussed elsewhere in the trauma compendium. The prehospital use of vasopressors to augment organ perfusion pressures seems theoretically appealing for settings where trauma patients have hemorrhagic shock that is refractory to volume resuscitation strategies alone, where blood products are not available, in cases of hypoperfusion caused by neurogenic shock, or to address mean arterial pressure (MAP) goals in severe spinal cord injury. The National Association of Emergency Medical Services Physicians (NAEMSP) reviewed the available evidence surrounding the prehospital use of vasopressors in shock related to trauma to develop the following recommendations as supported by the evidence summarized in the subsequent resource document.

Ferroptosis and its Potential Determinant Role in Myocardial Susceptibility to Ischemia/Reperfusion Injury in Diabetes.

Myocardial ischemia/reperfusion injury (MIRI) is a major cause of cardiac death particularly in patients with diabetes. When the coronary artery is partially or completely blocked, restoration of blood perfusion can normally be achieved within a certain time due to the development of advanced techniques such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery. However, cardiac tissue injury may aggravate progressively even after the ischemic myocardium is restored to normal perfusion. MIRI is often associated with various forms of cell death, including apoptosis, autophagy, programmed necrosis, pyroptosis, and ferroptosis, among others. Ferroptosis is known as iron-dependent cell death that is distinct from other programmed modes of cell death. Ferroptosis is under constitutive control by glutathione peroxidase 4 (GPX4), and the reduction of GPX4 may result in ferroptosis even if iron homeostasis is physiologically maintained. The essences of ferroptosis are substantial iron accumulation and lipid peroxidation that trigger cell death. Under impaired antioxidant system, cellular reactive oxygen species (ROS) accumulation leads to lipid peroxidation which consequently results in ferroptosis. Ferroptosis shares a few common features with several types of cell death and interplays with various forms of cell death such as autophagy and apoptosis in the development of cardiovascular diseases. More and more recent studies have demonstrated that ferroptosis plays an important role in MIRI. However, few studies have addressed the relative importance of ferroptosis in MIRI relative to other forms of cell deaths. In this review, we summarized the basic aspects and advances regarding the molecular pathogenesis of ferroptosis, evaluated its role in MIRI, and propose that the levels of ferroptosis may function as a major determinant of myocardial susceptibility to ischemia/reperfusion injury (IRI) in general and of the enhanced vulnerability to MIRI specifically in diabetes.

Probing the effects of polysaccharide hydrogel composition on the viability and pro‐angiogenic function of human adipose‐derived stromal cells

AbstractCell therapies harnessing the pro‐vascular regenerative capacities of mesenchymal stromal cell (MSC) populations, including human adipose‐derived stromal cells (hASCs), have generated considerable interest as an emerging treatment strategy for peripheral arterial disease (PAD) and its progression to critical limb ischemia (CLI). There is evidence to support that polysaccharide hydrogels can enhance therapeutic efficacy when applied as minimally‐invasive delivery systems to support MSC survival and retention within ischemic tissues. However, there has been limited research to date on the effects of hydrogel composition on the phenotype and function of encapsulated cell populations. Recognizing this knowledge gap, this study compared the pro‐angiogenic function of hASCs encapsulated in distinct but similarly‐modified natural polysaccharide hydrogels composed of methacrylated glycol chitosan (MGC) and methacrylated hyaluronic acid (MHA). Initial in vitro studies confirmed high viability (>85%) of the hASCs following encapsulation and culture in the MGC and MHA hydrogels over 14 days, with a decrease in the cell density observed over time. Moreover, higher levels of a variety of secreted pro‐angiogenic and immunomodulatory factors were detected in conditioned media samples collected from the hASCs encapsulated in the MGC‐based hydrogels compared to the MHA hydrogels. Subsequent testing focused on comparing hASC delivery within the MGC and MHA hydrogels to saline controls in a femoral artery ligation‐induced CLI (FAL‐CLI) model in athymic nu/nu mice over 28 days. For the in vivo studies, the hASCs were engineered to express tdTomato and firefly luciferase to quantitatively compare the efficacy of the two platforms in supporting the localized retention of viable hASCs through longitudinal cell tracking with bioluminescence imaging (BLI). Interestingly, hASC retention was significantly enhanced when the cells were delivered in the MHA hydrogels as compared to the MGC hydrogels or saline. However, laser Doppler perfusion imaging (LDPI) indicated that the restoration of hindlimb perfusion was similar between the treatment groups and controls. These findings were corroborated by endpoint immunofluorescence (IF) staining showing similar levels of CD31+ cells in the ligated limbs at 28 days in all groups. Overall, this study demonstrates that enhanced MSC retention may be insufficient to augment vascular regeneration, emphasizing the complexity of designing biomaterials platforms for MSC delivery for therapeutic angiogenesis. In addition, the data points to a potential challenge in approaches that seek to harness the paracrine functionality of MSCs, as strategies that increase the secretion of immunomodulatory factors that can aid in regeneration may also lead to more rapid MSC clearance in vivo.

Role of Endovascular Thrombectomy in Improving the Functional Outcome in Acute Stroke Patients Presenting 6-12 Hours after Stroke Onset

Abstract Background Based on the World Health Organization (WHO) statistics, there are 15 million strokes annually. The aim of the treatment in acute ischemic stroke is rapid restoration of perfusion to the ischemic area by minimizing the time between the occurrence of symptoms and the treatment. This is crucial for saving the salvageable brain tissue (penumbra) by restoration of flow and metabolism to normal Aim of Work The aim of work is to evaluate the safety and efficacy of endovascular thrombectomy (EVT) in patients presenting 6-12 hours from onset of stroke symptoms secondary to large vessel occlusion. Patients and Methods 50 Patients presenting with acute ischemic stroke with causative occlusion of major vessels in anterior circulation, underwent mechanical thrombectomy Results Two-thirds of the patients had their intracranial arterial occlusion at M1 segment of the middle cerebral artery. The median baseline NIHSS score, ASPECTS, and mRS score of the studied patients was 16 (IQR 11-20), 8 (IQR 7-9) and 0 (IQR 0-1), respectively. The median final infarct volume, NIHSS score, ASPECTS post-intervention and mRS score at 90 days of the studied patients was 40 ml (IQR 26.5-70) (P < 0.001), 9 (IQR 4-16) (P < 0.001), 8(IQR 5-9) (P < 0.01), and 2 (IQR1-4) (P < 0.001), respectively and (90 %) of them had revascularization type TICI 2b- 3. More than half of the studied patients (52%) had mRS score at 90 days of ≤ 2 and mortality rate was 12%. Conclusions The current study showed that endovascular thrombectomy techniques are safe and effective in the treatment of acute ischemic stroke.

Acute Limb Ischemia Secondary to Thrombosis in Persistent Sciatic Artery: A Case Report and Review of Management Strategies

Persistent sciatic artery (PSA) is a rare vascular anomaly with potential for significant vascular complications. We present a case of a 39-year-old male with acute limb ischemia secondary to thrombosis in a PSA, highlighting the challenges in diagnosis and management. Despite the absence of aneurysmal formation, the patient presented with severe pain and absent distal pulses, prompting urgent intervention. Computed tomography angiography revealed thrombosis extending into the left common iliac artery. Catheter-directed thrombolysis (CDT) was successfully performed, resulting in complete resolution of the thrombus and restoration of limb perfusion. The patient experienced symptomatic relief postoperatively and regained ambulatory function. This case underscores the importance of considering PSA in the differential diagnosis of acute limb ischemia and highlights CDT as an effective treatment modality. Further research is needed to optimize the management of acute limb ischemia associated with PSA and to evaluate long-term outcomes.

Ghrelin alleviates intestinal ischemia-reperfusion injury by activating the GHSR-1α/Sirt1/FOXO1 pathway.

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 μg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.

Improvement of neuronal and cognitive functions following treatment with 3′,4′ dihydroxyflavonol in experimental focal cerebral ischemia-reperfusion injury in rats

IntroductionIschemia/reperfusion is a pathological condition by the restoration of perfusion and oxygenation following a period of restricted blood flow to an organ. To address existing uncertainty in the literature regarding the effects of 3′, 4′-dihydroxy flavonol (DiOHF) on cerebral ischemia/reperfusion injury, our study aims to investigate the impact of DiOHF on neurological parameters, apoptosis (Caspase-3), aquaporin 4 (AQP4), and interleukin-10 (IL-10) levels in an experimental rat model of brain ischemia-reperfusion injury. Materials/methodsA total of 28 Wistar-albino male rats were used in this study. Experimental groups were formed as 1-Control, 2-Sham, 3-Ischemia-reperfusion, 4-Ischemia-reperfusion + DiOHF (10 mg/kg). The animals were anaesthetized, and the carotid arteries were ligated (ischemia) for 30 min, followed by reperfusion for 30 min. Following reperfusion, DiOHF was administered intraperitoneally to the animals at a dose of 10 mg/kg for 1 week. During the one-week period neurological scores and new object recognition tests were performed. Then, caspase 3 and AQP4 levels were determined by PCR method and IL-10 by ELISA method in hippocampus tissue samples taken from animals sacrificed under anaesthesia. ResultsBrain ischemia reperfusion significantly increased both caspase 3 and AQP4 values in the hippocampus tissue, while decreasing IL-10 levels. However, 1-week DiOHF supplementation significantly suppressed increased caspase 3 and AQP4 levels and increased IL-10 values. While I/R also increased neurological score values, it suppressed the ability to recognize new objects, and the administered treatment effectively ameliorated the adverse effects observed, resulting in a positive outcome. ConclusionsThe results of the study show that brain ischemia caused by bilateral carotid occlusion in rats and subsequent reperfusion causes tissue damage, but 1-week DiOHF application has a healing effect on both hippocampus tissue and neurological parameters.

A visceral organ function-focused therapeutic strategy using a 6-hour time window for patients with acute type a aortic dissection complicated by mesenteric malperfusion

BackgroundAcute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion.MethodsThis was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h.ResultsThere were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences.ConclusionsOur novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate.

Ca2+ oscillation in vascular smooth muscle cells control myogenic spontaneous vasomotion and counteract post-ischemic no-reflow

Ischemic stroke produces the highest adult disability. Despite successful recanalization, no-reflow, or the futile restoration of the cerebral perfusion after ischemia, is a major cause of brain lesion expansion. However, the vascular mechanism underlying this hypoperfusion is largely unknown, and no approach is available to actively promote optimal reperfusion to treat no-reflow. Here, by combining two-photon laser scanning microscopy (2PLSM) and a mouse middle cerebral arteriolar occlusion (MCAO) model, we find myogenic vasomotion deficits correlated with post-ischemic cerebral circulation interruptions and no-reflow. Transient occlusion-induced transient loss of mitochondrial membrane potential (ΔΨm) permanently impairs mitochondria-endoplasmic reticulum (ER) contacts and abolish Ca2+ oscillation in smooth muscle cells (SMCs), the driving force of myogenic spontaneous vasomotion. Furthermore, tethering mitochondria and ER by specific overexpression of ME-Linker in SMCs restores cytosolic Ca2+ homeostasis, remotivates myogenic spontaneous vasomotion, achieves optimal reperfusion, and ameliorates neurological injury. Collectively, the maintaining of arteriolar myogenic vasomotion and mitochondria-ER contacts in SMCs, are of critical importance in preventing post-ischemic no-reflow.

Switching from VA-ECMO to a Percutaneous right Ventricular assist device as a Bridge to Recovery in a Case of right Ventricular Myocardial Infarction

Acute right heart failure (RHF) is associated with high morbidity and mortality. Temporary mechanical circulatory support (MCS) is now part of the advanced management strategy for refractory cardiogenic shock (CS). Among such support systems, veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) remains the fastest MCS system to set up. The ProtekDuo cannula can be used as a temporary and percutaneous right ventricular assist device (RVAD) in relay with VA-ECMO in the context of prolonged weaning. This case report describes the clinical course of a 69-year-old patient who underwent elective aortic valve replacement surgery complicated by acute RHF due to iatrogenic ligation of the right coronary artery. VA-ECMO was initiated in the context of refractory cardiogenic shock. Faced with prolonged MCS weaning, due to lack of recovery of the right ventricle associated with the absence of any other therapeutic option, a percutaneous RVAD via a ProtekDuo cannula was implanted as a bridge to recovery. The ProtekDuo was gradually weaned while the patient began rehabilitation. The patient was transferred to the medical ward after 5 weeks in the ICU, stayed 5 months in an acute medical setting, went to a rehabilitation center afterward and returned home 6 months after the initial surgery without any neurological sequalae or organ failures. In total, she remained on MCS for 39 days (21 on VA-ECMO and 18 on ProtekDuo). In cases of refractory RHF, after stabilization and organ perfusion restoration under VA-ECMO, it is feasible to switch to a percutaneous RVAD, allowing early mobilization of patients during prolonged MCS weaning until the right ventricle adapts to new loading conditions.

Sinigrin improves cerebral ischaemia-reperfusion injury by inhibiting the TLR4 pathway-mediated oxidative stress.

Cerebral ischaemia-reperfusion (CIR) injury occurs in stroke patients after the restoration of cerebral perfusion. Sinigrin, a phytochemical found in cruciferous vegetables, exhibits strong antioxidant activity. This study investigated the role of sinigrin in oxidative stress using a CIR injury model. The effects of sinigrin were studied in middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-injured SH-SY5Y cells. Sinigrin treatment improved brain injury and neurological deficits induced by MCAO surgery in rats. Sinigrin inhibited apoptosis in brain tissues and SH-SY5Y cells following OGD/R induction. Additionally, sinigrin elevated the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) while reducing malondialdehyde (MDA) levels. Furthermore, sinigrin inhibited the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signalling pathway. The anti-apoptotic and antioxidant activities of sinigrin in OGD/R-injured SH-SY5Y cells were reversed by TLR4 overexpression. In conclusion, sinigrin inhibits oxidative stress in CIR injury by suppressing the TLR4/MyD88 signalling pathway.

Cinnamaldehyde protects cardiomyocytes from oxygen-glucose deprivation/reoxygenation-induced lipid peroxidation and DNA damage via activating the Nrf2 pathway.

Rapid restoration of perfusion in ischemic myocardium is the most direct and effective treatment for coronary heart disease but may cause myocardial ischemia/reperfusion injury (MIRI). Cinnamaldehyde (CA, C9H8O), a key component in the well-known Chinese medicine cinnamomum cassia, has cardioprotective effects against MIRI. This study aimed to observe the therapeutic effect of CA on MIRI and to elucidate its potential mechanism. H9C2 rat cardiomyocytes were pretreated with CA solution at 0, 10, and 100 μM, respectively and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Then the cell viability, the NF-κB and caspase3 gene levels, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, superoxide dismutase (SOD) level, reactive oxygen species (ROS) generation, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were detected. The severity of DNA damage was assessed by tail moment (TM) values using alkaline comet assay. Besides, the DNA damage-related proteins and the key proteins of the Nrf2 pathway were detected by western blot. CA treatment increased the cell viability, GHS/GSSG ratio, SOD level, PARP1, Nrf2, PPAR-γ, and HO-1 protein levels of H9C2 cardiomyocytes, while reducing NF-κB, caspase3, ROS level, 4-HNE and MDA content, γ-H2AX protein level, and TM values. Inhibition of the Nrf2 pathway reversed the effect of CA on cell viability and apoptosis of OGD/R induced H9C2 cardiomyocytes. Besides, 100 μM CA was more effective than 10 μM CA. In the OGD/R-induced H9C2 cardiomyocyte model, CA can protect cardiomyocytes from MIRI by attenuating lipid peroxidation and repairing DNA damage. The mechanism may be related to the activation of the Nrf2 pathway.

Renal Artery Blood Flow and Surface Parenchymal Perfusion During Renal Artery Endoshunting in a Porcine Model

Ischaemia and reperfusion can result in permanent tissue damage. During complex open abdominal aortic surgery, transient clamping of the renovisceral arteries may be required to successfully complete the vascular repair. Endovascular shunting (endoshunting) presents an alternative technique for managing such temporary renovisceral ischaemia. This study aimed to investigate the performance of endoshunting to the renal circulation in a porcine model. This study of five domestic pigs investigated arterial volume flow rates during endoshunting of a single renal artery and the associated impact on renal perfusion parameters (laser Doppler renal parenchymal perfusion, renal oxygen extraction, and selective urinary output). The study was performed in three steps: baseline registrations (30 minutes), endoshunting (120 minutes), and restoration (60 minutes). The right kidney was used as the experimental side and the left kidney as control. The median arterial flow rate in the left control kidney remained constant throughout the experiment. On the right (endoshunted) side, the baseline median arterial flow rate was 267 (range, 160-404) mL/min. Following activation of the endoshunt, the median arterial volume flow dropped by 59%-110 (range, 45-150) mL/min (p= .018). During endoshunting, the median kidney surface perfusion decreased to 42% of the baseline value. On the control side, a rise in the median parenchymal perfusion was observed after endoshunt activation, which was again normalised following restoration of native right renal artery flow. During endoshunting, the median regional urine production was 0.32 (range, 0.12-0.50) mL/hour but resumed after renal artery flow restoration. On average, the endoshunted kidneys showed a rapid restoration of blood flow, parenchymal perfusion, and urine production after 120 minutes of endoshunting. This suggests that endoshunting to the kidney using an endoshunt system might be a promising strategy to preserve renal function when temporary interruption of native renal artery blood flow is needed during complex vascular surgical repairs involving the renal arteries.

LncRNA PART1 Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating TFAP2C/DUSP5 Axis via miR-302a-3p.

Myocardial ischemia-reperfusion injury (MIRI) refers to the damage of cardiac function caused by restoration of blood flow perfusion in ischemic myocardium. However, long non-coding RNA prostate androgen regulated transcript 1 (PART1)'s role in MIRI remain unclear. Immunofluorescence detected LC3 expression. Intermolecular relationships were verified by dual luciferase reporter assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and transferase-mediated dUTP nick-end labeling (TUNEL) assays analyzed cell viability and apoptosis. The release of lactate dehydrogenase was tested via enzyme-linked immunosorbent assay (ELISA). Left anterior descending coronary artery surgery induced a MIRI mouse model. Infarct area was detected by 2,3,5-triphenyltetrazolium chloride staining. Hematoxylin and eosin staining examined myocardial injury. ELISA evaluated myocardial marker (creatine kinase MB) level. PART1 was decreased in hypoxia/reoxygenation (H/R) induced AC16 cells and MIRI mice. PART1 upregulation attenuated the increased levels of Bax, beclin-1 and the ratio of LC3II/I, and enhanced the decrease of Bcl-2 and p62 expression in H/R-treated cells. PART1 upregulation alleviated H/R-triggered autophagy and apoptosis via miR-302a-3p. Mechanically, PART1 targeted miR-302a-3p to upregulate transcription factor activating enhancer-binding protein 2C (TFAP2C). TFAP2C silencing reversed the protected effects of miR-302a-3p inhibitor on H/R treated AC16 cells. We further established TFAP2C combined to dual-specificity phosphatase 5 (DUSP5) promoter and activated DUSP5. TFAP2C upregulation suppressed H/R-stimulated autophagy and apoptosis through upregulating DUSP5. Overexpressed PART1 reduced myocardial infarction area and attenuated MIRI in mice. PART1 improved the autophagy and apoptosis in H/R-exposed AC16 cells through miR-302a-3p/TFAP2C/DUSP5 axis, which might provide novel targets for MIRI treatment.

Indications and techniques for endovascular revascularization of visceral arteries in mesenteric ischemia

Endovascular revascularization of visceral arteries is an important cornerstone of an interdisciplinary treatment concept for both acute and chronic forms of mesenteric ischemia. The advantages lie in the minimally invasive procedure and the speed of restoration of perfusion. This article provides an overview of the indications, techniques and current state of the clinical literature with respect to endovascular revascularization.

Non-ST-elevation infarction, the stepchild of interventional myocardial salvage: experience of a single institute

The diagnosis of acute myocardial infarction is based on ECG abnormalities besides to chest pain and dyspnea. It is caused by myocardial hypoperfusion, in most patients due to severe coronary artery narrowing or occlusion, but it can also occur without visible coronary artery changes. The non-ST-elevation form (NSTEMI) is usually associated with less complaints compared to the ST-elevation form (STEMI), the ECG changes are not so typical, so its recognition is more difficult in the early stage. Possibility of myocardial cell damage reduction is the restoration of perfusion with coronary intervention. To investigate how much time elapses in acute NSTEMI from the onset of the complaint to the opening of the coronary vasodilator balloon. From 3733 acute coronary interventions performed in NSTEMI between 01. 01. 2016 and 12. 31. 2020, in 1376 patients who underwent percutaneous intervention for the first time, the onset of the complaints, the date of the first medical contact and opening of the balloon, as well as the 30-day or 1-year mortality were known. The median values of the time differences and the mortality data were compared with the similar data of 1718 STEMI patients of this period. The median times were given in hours:minutes, incidence in percent, a two-sample t-test was calculated for the comparison of mortality data. In NSTEMI, the median time between the first medical contact (5:35 vs. 2:05 h:min) and PTCA balloon opening (18:12 vs. 4:05 h:min) was longer compared to the onset of the complaint as in STEMI. Within 2 hours, 21.3% of NSTEMI patients reached the first medical contact and 1.2% had the PTCA balloon opened, in STEMI this ratios were 48.7% and 11.7%. Within 4 hours, these were in NSTEMI 36.3% and 6.1%, in STEMI 64.1% and 46.8%. The 30-day mortality rate in NSTEMI was lower than in STEMI (5.9% vs. 7.9%, p = 0.03), the 1-year rate was higher (16.1% vs. 12.5%, p = 0.004). In 554 primarily admitted patients who met the study criteria, the median P-B time intervals were shorter (10:55 h:min), the mortality data showed a mild but statistically insignificant difference (5.6% at 30 days, 13.9% at 1 year). Based on the 1-year mortality data, NSTEMI cannot be considered less harmful compared to STEMI. After the onset of hypoperfusion, myocardium necrosis proportional to the elapsed time increases the likelihood of subsequent heart failure. For this reason, it seems advisable for patients to reach the intervention center earlier than at present due to the invasive diagnostic and therapeutic options. Orv Hetil. 2023; 164(47): 1865-1870.

Abstract 17130: Metabolic and Epigenetic Coupled Regulation in Angiogenic Transdifferentiation and Vascular Recovery

Recent studies from our group and others have characterized the phenomenon of "angiogenic transdifferentiation” from fibroblasts to endothelial cells as a novel endogenous mechanism for microvasculature expansion and perfusion restoration in murine models of hindlimb ischemia and myocardial infarction. Metabolic regulation of epigenetic reprogramming has emerged as a key regulatory process controlling cell fate transition. To study the comprehensive role of metabolism in this healing process, we conducted liquid chromatography-mass spectrometry (LC-MS) based untargeted and targeted metabolomics during transdifferentiation. Our analysis revealed the upregulation of key metabolites, including UDP-GlcNAc (substrate for post-translational modification O-GlcNAcylation) and acetyl-CoA (substrate for histone acetylation). With our in vitro transdifferentiation protocol, we found that pharmacologic or genetic inhibition of OGT (O-GlcNAc transferase, the enzyme responsible for protein O-GlcNAcylation) or ACL (ATP citrate lyase, the enzyme converting citrate to acetyl-CoA) in human BJ fibroblasts impairs transdifferentiation. Employing a preclinical peripheral arterial disease (PAD) hindlimb ischemia model with fibroblast lineage tracing mice, we discovered that O-GlcNAcylation and ACL were accumulated in fibroblast lineage cells in ischemic limbs, and pharmacologic inhibition of OGT or ACL diminished the transdifferentiation cell population in the ischemic tissue. Furthermore, we identified fibroblast-specific OGT or ACL KO impaired vascular recovery post femoral artery ligation in the mice. Finally, we showed that metabolism-dependent post-translational modifications on histones (acetylation of H3K9, H3K27, H3K14) or histone chaperons (O-GlcNAcylation of HIRA, a histone H3.3 chaperone) mechanistically enhanced chromatin openness, thereby facilitating cell fate plasticity and vascular regeneration. In conclusion, our studies demonstrate the significant regulatory potential of metabolic factors in angiogenic transdifferentiation which presents an innovative avenue to enhance vascular recovery in ischemic vascular diseases such as PAD.

Effect of serum from patients with ST-segment elevation myocardial infarction on endothelial cells

Introduction and objectives Clinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction).Methods Human coronary artery endothelial cells were incubated with serum isolated 24 hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer.Results Serum from STEMI patients increased apoptosis (P < .01) and necrosis (P < .05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P < .01), due to enlarged intercellular spaces (P < .05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P < .05) and with more extensive CMR-derived indices of reperfusion injury and infarct size.Conclusions Postreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure.