Citations

Abstract Introduction Cardiac arrest (CA) is the sudden cessation of cardiac activity, leading to haemodynamic collapse and high mortality. Advanced life support (ALS) standardises resuscitation, but the post-return of spontaneous circulation (ROSC) period remains turbulent and poorly understood. Up to 50% of patients who achieve ROSC struggle to maintain spontaneous circulation, leading to re-arrest, typically within minutes. Post-cardiac arrest syndrome (PCAS), involving brain injury and ischaemia-reperfusion injury, plays a key role in re-arrest. Pressure-volume loop (PVL) analysis offers insight into load-independent cardiac biomechanics in the post-ROSC period. The aim of this study is to explore the feasibility of PVL analysis in a swine model of CA. Methods This swine study utilised a ventricular fibrillation (VF) cardiac arrest model in combination with PVL analysis. The experiment included four phases: animal preparation, VF induction, resuscitation, and post-ROSC care. Yorkshire swine (45-70 kg) were sedated, anaesthetised, and VF was induced via an endocavitary electrode attached to a battery. After that, the animals were divided into 3-minute and 6-minute arrest groups before commencing ALS. Standard ALS protocols were followed, including CPR, defibrillation, and drug administration. If ROSC was obtained, animals underwent a 3-hour critical care period. Cardiac indices were compared between baseline and end-of-study values. Results Eight adult Yorkshire swine were enrolled in the study, with a mean weight of 50.2 ± 2.9 kg. VF induction was successfully achieved, and PVL data were collected in all animals except one, establishing a successful porcine VF CA model. In the resuscitation phase, all animals in the 3-minute group achieved ROSC, as opposed to one in the 6-minute group. Post-ROSC metabolic changes included acidaemia, elevated lactate and potassium, partially resolving by study end. Right ventricle PVL data were unreliable, while left ventricle PVL was reliable in 3 of 5 ROSC animals. Preload-recruitable stroke work (PRSW) data were found to be more reliable than the End-Diastolic Pressure-Volume Relationship (ESPVR), with a significant increase in LV PRSW of 34 ± 12% observed post-ROSC in all surviving animals (p<0.001). Discussion This study demonstrates the feasibility of applying PVL analysis to a post-ROSC swine model of cardiac arrest (CA). As expected, warm ischaemic time predicted ROSC, but PVL analysis offered valuable insights into load-independent parameters. While data quality issues hindered ESPVR analysis, PRSW was successfully evaluated, revealing a significant increase post-ROSC, highlighting its potential to guide the development of future therapeutic targets for post-ROSC interventions. The small sample size and technical challenges limited the scope of conclusions, emphasising the need for larger studies.Kaplan-Meier Curve and cycles to ROSC (A) LV PVL, (B) PRSW Pre and Post-ROSC

BACKGROUND: Acute mesenteric ischemia (AMI) is a vascular emergency where delays in diagnosis or treatment can lead to irreversible bowel injury and death. Many patients initially present to hospitals without surgical or vascular capabilities and require interhospital transfer. The clinical impact of such transfers on treatment and outcomes in AMI remains poorly defined. STUDY DESIGN: We performed a retrospective cohort study using the National Inpatient Sample (2019 to 2021) to evaluate the association between interhospital transfer and outcomes in patients with AMI. Adult patients with a primary diagnosis of AMI were identified using ICD-10 codes. Patients were categorized by transfer status. Multivariable logistic regression was used to evaluate associations with in-hospital mortality and procedural interventions, adjusting for age and comorbidity burden. RESULTS: Of 39,690 hospitalizations for AMI, 14.6% involved interhospital transfer. Transferred patients had a higher comorbidity burden and were more often treated at rural or micropolitan hospitals. They were significantly more likely to undergo major surgical and vascular procedures, including bowel resection (odds ratio [OR] 3.48), mesenteric bypass (OR 3.32), and angioplasty (OR 2.66; all p < 0.0001). Markers of critical illness, such as intubation (OR 2.15) and dialysis (OR 1.30), were also more frequent in this group. In-hospital mortality was significantly higher among transferred patients (OR 2.05), and transfer remained independently associated with increased mortality after adjusting for age and comorbidity burden (adjusted OR 1.67, 95% CI 1.32 to 2.10). CONCLUSIONS: Interhospital transfer in AMI is strongly associated with increased clinical severity and in-hospital mortality. These findings emphasize the urgency of early diagnosis, rapid triage, and timely access to definitive care, supporting the need for structured regional systems and transfer protocols for AMI.

Introduction Lower Extremity Extracorporeal Distal Revascularization (LEEDR) is a novel, preclinically tested technique designed to provide temporary limb perfusion in cases of acute limb ischemia when immediate revascularization is not feasible. Methods LEEDR employs an extracorporeal pump and circuit to draw arterial blood from a proximal inflow site and deliver it to an outflow artery within the ischemic limb. The system is designed for bedside initiation using percutaneous access. Results ALI from embolism, thrombosis, or trauma rapidly leads to irreversible tissue damage. Delays in revascularization are associated with high rates of limb loss and systemic complications. LEEDR offers a time-sensitive intervention aimed at mitigating these risks and preserving limb viability until definitive treatment is available. Conclusion LEEDR is a promising temporary perfusion strategy for limb salvage in ALI. This manuscript outlines its procedural components, technical considerations, and anticipated role in bridging patients to definitive revascularization.

Objectives Traditionally, acute mesenteric ischemia studies are performed by utilizing an open superior mesenteric artery (SMA) occlusion, which is an invasive technique with potentially devastating effects. A new endovascular technique for SMA occlusion using a catheter-balloon system was designed and compared to the open SMA occlusion to test its efficacy and animal safety. Methods All animals underwent open instrumentation of the superior mesenteric vein (SMV) for blood flow monitoring. The animals were grouped into an open SMA occlusion technique group and an endovascular SMA occlusion group. The open SMA occlusion technique group involved exposure of the SMA via left medial visceral rotation with vascular clamping. In the endovascular group, an endovascular balloon was placed in the SMA and inflated to produce occlusion. Results Complete cessation of flow to the SMV was observed in the endovascular group, compared to the residual SMV flow in the open occlusion group. Following a 30-min post-occlusion period, the MAP in the endovascular group increased, compared to a decline of MAP in the open occlusion group. Conclusions This study indicates the endovascular technique provides a more potent SMA occlusion, with insignificant consequences on the overall health of the animal, in contrast to the open vascular clamping.

Background: Traumatic carotid artery pseudoaneurysms (PSAs) represent a vascular anomaly with potential for serious complications, including stroke. Traditional treatments involve endovascular stenting, which may not be ideally suited to otherwise healthy vessels that have the potential to remodel. Given the limitations of smaller animal models in replicating human vasculature and the need for improved treatment modalities, this study introduces a novel swine model for the creation and evaluation of carotid PSAs. Methods: The PSAs were created from bovine dura and anastomosed in an end-to-side fashion to bilateral carotid arteries. The PSAs were radiologically followed up post-operatively and were harvested at 3 and 10 days for histological analysis. Results: Pseudoaneurysms were successfully created in both animals without intra-operative or immediate post-operative complications. Radiological analysis showed well-perfused PSAs with intra-aneurysmal turbulence, hemodynamically mimicking human carotid artery PSAs. There was no evidence of thrombus or arterial stenosis. Histological examinations revealed thrombus maturation and tight anastomosis of the PSA sac with the native artery. Conclusions: This PSA swine model offers a replicable, cost-effective, and easily implemented tool with the potential to advance carotid PSA management and educational efforts in vascular surgery. Clinical Impact The model presented in this methodology paper allows for a standardized PSA animal model allowing for the standardization of a clinical entity which is frequently heterogenenous in morphology. This can allow for the development of new therapies or provide a ground truth for computer modelling for further in silico study.

Importance Vascular injuries require urgent repair to minimize loss of limb and life. Standard revascularization relies on autologous vein or synthetic grafts, but alternative options are needed when adequate vein is not feasible and when clinical conditions preclude safe use of synthetic materials. Objective To evaluate the performance of the acellular tissue engineered vessel (ATEV) in the repair of extremity arterial injuries. Design, Setting, and Participants Two open-label, single-arm, nonrandomized clinical trials, including 1 prospective civilian study (CLN-PRO-V005 [V005]) and 1 retrospective observational study in a war zone (CLN-PRO-V017 [V017]), were conducted from September 2018 to January 2024 (follow-up ongoing) at 19 level 1 trauma centers in the US and Israel and 5 frontline hospitals in Ukraine. Patients had vascular injury, no autologous vein available for emergent revascularization, and risk factors for wound infection. Data include the subset of patients with extremity injuries and were analyzed from September 2023 to January 2024. Intervention The ATEV is a bioengineered vascular conduit grown from human vascular cells, available off the shelf, and implantable without immunosuppression. Main Outcomes and Measures Primary patency at day 30 was the primary outcome. Secondary outcomes included limb salvage, graft infection, and patient survival. A systematic literature review identified synthetic graft benchmarks in the treatment of arterial trauma for the same end points. Results The arterial extremity injury subset included 51 of 69 participants in V005 and 16 of 17 participants in V017. The majority were male (V005, 38 [74.5%]; V017, 16 [100%]), the mean (SD) ages were similar (V005, 33.5 [13.6] years; V017, 34.2 [9.0] years), and the mean (SD) Injury Severity Scores were similar (V005, 20.8 [10.5]; V017, 20.1 [18.9]). Penetrating injuries dominated (V005, 29 patients [56.9%]; V017, 14 patients [87.5%]). At day 30 for the V005 and V017 trials, respectively, ATEV primary patency was 84.3% (95% CI, 72.0%-91.8%) and 93.8% (95% CI, 71.7%-98.9%); secondary patency was 90.2% (95% CI, 79.0%-95.7%) and 93.8% (95% CI, 71.7%-98.9%); amputation rate was 9.8% (95% CI, 4.3%-21.0%) and 0% (95% CI, 0.0%-19.4%); ATEV infection rate was 2.0% (95% CI, 0.4%-10.3%) and 0% (95% CI, 0.0%-19.4%); and death rate was 5.9% (95% CI, 2.0%-15.9%) and 0% (95% CI, 0.0%-19.4%) (no deaths attributed to the ATEV at day 30). Day 30 synthetic graft benchmarks were as follows: secondary patency, 78.9%; amputation, 24.3%; infection, 8.4%; and death, 3.4%. Conclusions and Relevance Results of analysis in the subset of patients with vascular extremity injuries in 2 single-arm trials in civilian and real-world military settings suggest that the ATEV provides benefits in terms of patency, limb salvage, and infection resistance. Comparing ATEV outcomes with synthetic graft benchmarks demonstrated improved outcomes in the treatment of acute vascular injuries of the extremities. The analyses reported herein are limited to the subset of 67 patients with vascular extremity injuries out of 86 patients enrolled in 2 trials and excluded 19 patients with iatrogenic and torso injuries. Had these 19 patients been included in these analyses, the efficacy and safety findings could have been attenuated. Trial Registration ClinicalTrials.gov Identifiers: NCT03005418 , NCT05873959

Background: Autologous arteriovenous fistulas (AVF) are the preferred choice for hemodialysis access due to their longevity, lower complication rates, and mortality benefit. Their use is limited by vein size and necessary maturation period, excluding up to a third of patients. A novel solution to this problem is pump-assisted vein dilation (PAVD), where the vein is “pre-matured” using a miniatured centrifugal pump that draws blood from a central vein, delivering it into the recipient vein (e.g., cephalic) under pressure. The aim of this study is to report the initial safety studies in sheep and a first-in-human (FIH) pilot study as a prelude to a phase 2 clinical study. Methods: Preclinical Study: Three anesthetized male sheep (50-70 kg) underwent cephalic PAVD using the Amplifi Vein Dilation System for 7 days (mean). These subjects and two control animals (no-PAVD) underwent brachiocephalic AVF creation and observation for 6 weeks, with weekly surveillance fistulagrams and duplex ultrasound (U/S). AVFs were then explanted for histological analysis. Clinical Study: Ten patients were recruited for a phase 1 study. They underwent cephalic PAVD for 7 days (mean), followed by brachiocephalic AVF creation and surveillance at 2 and 6 wks. Data on vein diameter and flow rates of the AVF were collected, as well as safety data on complications such as bleeding, infection, and embolism. Results: Preclinical Study: PAVD increased mean±SD vein diameter (mm) from 4.5±1.0 to 8.4±1.0 (p=0.005); leading to greater cephalic vein diameter at the time of AVF creation in the PAVD group vs no-PAVD (8.2±1.3 vs. 3.3±0.7; p<0.05). After 6 wks of maturation, mean vein diameter was still greater in the PAVD group compared to no-PAVD (12.8±2.8 vs. 8.4±0.7; p<0.05). Mean flow increased at 41 mL/min/day versus control animals at 5.2 mL/min/day. Clinical Study: All subjects saw an increase in vein diameter with PAVD at baseline vs. at 6 wks (2.3±0.5 vs. 5.2±0.7; p<0.05), as well as mean flows (mL/min) (285±30 vs. 724±149). There were no Amplifi-related or procedure-related serious adverse events. Conclusion: The translation of PAVD for AVF creation from bench-to-bedside provides safety and efficacy data on a novel solution that can increase the availability of autologous AVFs in patients excluded due to size criteria. The Amplifi vein dilation system can effectively and rapidly dilate peripheral veins without stimulating neointimal hyperplasia. PAVD should be explored in a phase 2 clinical study.

Background: Acute limb ischemia (ALI) requires prompt revascularization to preserve the extremity and minimize the effects of systemic reperfusion. Once ALI is recognized, delays in revascularization are generally due to system issues (e.g., transfer) and there is a need for a method of temporary extremity perfusion to reduce warm ischemic time. Lower Extremity Extracorporeal Distal Revascularization (LEEDR) is a percutaneous technique that uses a pump and circuit to deliver oxygenated blood into a pedal artery. Hypothesis: Extracorporeal perfusion can improve survival from ALI. Aims: The aim of this study is to use a swine model of prolonged hindlimb ischemia to compare survival and functional outcomes of LEEDR versus control (warm ischemia). Methods: Anesthetized female Yorkshire swine (40-60kg) underwent hindlimb ischemia using endovascular balloon occlusion and were randomized to control (n=6) or LEEDR (n=6). Controls underwent 9 hours of ischemia. LEEDR animals underwent contralateral femoral and ipsilateral posterior tibial artery cannulation followed by 8 hours of extracorporeal perfusion into the ischemic limb. Subjects were revascularized by removing the endovascular balloons, restoring extremity blood flow, and undergoing a 4-hour critical care period before extubation and observation for 48 hours. Primary outcome was survival and secondary outcomes included functional extremity scores (Tarlov Gait Score), compartment pressures (mmHg) and biochemical markers of reperfusion. Results: Survival was higher in animals undergoing LEEDR (83% vs. 0%; p=0.001), with most control animals succumbing to acute lung injury. LEEDR animals had a higher functional gait score (5.9±0.3 vs. 2.5±0.7; p<0.001) and lower compartment pressure (8±2 vs. 28±4; p=0.002) compared to controls. Biochemically, the LEEDR group had lower potassium (4.5±0.3 vs. 5.3±0.4; p=0.001) and lactate (1.2±0.5 vs. 2.0±0.7; p<0.001) measurements compared to controls during reperfusion and recovery. Conclusion: LEEDR can effectively mitigate 8 hours of extremity ischemia in a swine model, reducing mortality from reperfusion, while improving functional gait score and eliminating compartment syndrome. This percutaneous approach to ALI opens a new field of extracorporeal limb salvage, which can temporize extremity perfusion improving outcomes in patients who have traditionally had limited options due to prolonged warm ischemia.

Background The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. Objective To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department. Design Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone. Setting United Kingdom Major Trauma Centres. Participants Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta. Interventions Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta. Main outcome measures Primary: Mortality at 90 days. Secondary: Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. Health economic: Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon. Data sources Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data). Results Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at any time point. Death due to haemorrhage was more common in the standard care plus resuscitative endovascular balloon occlusion of the aorta group than in the standard care group. There were no serious adverse device effects. Resuscitative endovascular balloon occlusion of the aorta is less costly (probability 99%), due to the competing mortality risk but also substantially less effective in terms of lifetime quality-adjusted life-years (probability 91%). Limitations The size of the study reflects the relative infrequency of exsanguinating traumatic haemorrhage in the United Kingdom. There were some baseline imbalances between groups, but adjusted analyses had little effect on the estimates. Conclusions This is the first randomised trial of the addition of resuscitative endovascular balloon occlusion of the aorta to standard care in the management of exsanguinating haemorrhage. All the analyses suggest that a strategy of standard care plus resuscitative endovascular balloon occlusion of the aorta is potentially harmful. Future work The role (if any) of resuscitative endovascular balloon occlusion of the aorta in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and is published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information.

Traumatic injury leading to arterial damage has traditionally been repaired using autologous vein graft from the contralateral limb. This often requires a secondary surgical site and the potential of prolonged operative time for patients. We sought to assess the use of ipsilateral vs contralateral vein grafts in patients who experienced traumatic extremity vascular injury. A multicenter database was queried to identify arterial injuries requiring operative intervention with vein grafting. The primary outcome of interest was need for operative reintervention. Secondary outcomes included risk of thrombosis, infection, and intensive care unit length of stay. 358 patients (320 contralateral and 38 ipsilateral) were included in the analysis. The ipsilateral vein cohort did not display a statistically significant decrease in need for reoperation when compared to the contralateral group (11% vs 23%; OR 0.41, 95% CI −0.07-1.3; P = .14). Contralateral repair was associated with longer median intensive care unit (ICU) LOS (4.3 vs 3.1 days; P < .01).