Evaluation of demographic/clinical features and hemorrhagic complications in patients with ischemic stroke who underwent reperfusion therapy.

The relationship between demographic/clinical characteristics, clinical outcomes and the development of hemorrhagic complications in patients with ischemic stroke who underwent reperfusion therapy has not been studied sufficiently. We have aimed to compare genders and age groups in terms of clinical features and outcome; and types of reperfusion treatments and clinical features regarding the development of hemorrhagic complications in patients with ischemic stroke who underwent recombinant tissue plasminogen activator (rtPA) and/or thrombectomy. Patients with acute ischemic stroke undergoing rtPA and/or thrombectomy were divided into six age groups. Parameters including hemorrhagic complications, anticoagulant and antiaggregant use, hyperlipidemia, smoking status, biochemical parameters, and comorbidities were documented. National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Score (mRS) and Glasgow Coma Scale scores were recorded. Etiological classification of stroke was done. These parameters were compared in terms of age groups, genders, and hemorrhagic complications. Significant differences were found between age groups concerning hypertension, coronary artery disease, smoking status, and antiaggregant use. Rate of hemorrhagic complications in rtPA group was significantly lower when compared with other treatment groups. Hemorrhagic complications developed mostly in the rtPA+thrombectomy group. Among the patients who developed hemorrhagic complications, NIHSS scores on admission were found to be significantly lower in men than women. Admission, discharge, and 3rd month mRS values in men were significantly lower than those of women. Knowing demographic and clinical features of patients that may have an impact on the clinical course of ischemic stroke managed with reperfusion therapy will be useful in predicting the hemorrhagic complications and clinical outcomes.

A Modified Model Preparation for Middle Cerebral Artery Occlusion Reperfusion.

The middle cerebral artery occlusion reperfusion (MCAO/R) model is crucial for understanding the pathological mechanisms of stroke and for drug development.However, among the commonly used modeling methods, the Koizumi method often faces scrutiny due to its ligation of the common carotid artery (CCA) and its inability to achieve adequate reperfusion. Similarly, the Longa method has been criticized for disconnecting and ligating the external carotid artery (ECA). This study aims to introduce a modified model preparation method that preserves the integrity of the ECA, involves inserting a monofilament nylon suture through the CCA, repairing the ligated CCA incision, and maintaining reperfusion from the CCA. Reperfusion of blood flow was confirmed using laser speckle flow imaging. Evaluation methods such as the Longa scale, Modified Neurological Severity Score, triphenyltetrazolium chloride (TTC) staining, and immunofluorescence labeling of neurons demonstrated that this approach could induce stable ischemic nerve damage. This modified MCAO/R model protocol is simple and stable, providing valuable guidance for practitioners in the field of cerebral ischemia.

External Validation of a Model for Persistent Perfusion Deficit in Patients With Incomplete Reperfusion After Thrombectomy: EXTEND-PROCEED.

BACKGROUND AND OBJECTIVES: We recently developed a model (PROCEED) that predicts the occurrence of persistent perfusion deficit (PPD) at 24 hours in patients with incomplete angiographic reperfusion after thrombectomy. This study aims to externally validate the PROCEED model using prospectively acquired multicenter data. METHODS: Individual patient data for external validation were obtained from the Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection, Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke part 1 and 2 trials, and a prospective cohort of the Medical University of Graz. The model's primary outcome was the occurrence of PPD, defined as a focal, wedge-shaped perfusion delay on 24-hour follow-up perfusion imaging that corresponds to the capillary phase deficit on last angiographic series in patients with

Effect of liver transplants with retrograde reperfusion on early postoperative recovery of liver function and its risk factors.

BACKGROUND: The purpose of this study was to investigate effect of liver Transplants (LT) with retrograde reperfusion on early postoperative recovery of liver function and its risk factors. METHODS: We conducted a retrospective analysis of clinical data from 136 liver transplantation (LT) patients at the 900th Hospital of the Chinese People's Liberation Army Joint Support Army, covering the period from January 2015 to January 2021. All participants provided informed consent, adhering to medical ethics guidelines. Patients were stratified into two groups based on the liver perfusion technique used: retrograde reperfusion (RTR, n = 108) and initial portal reperfusion (IPR, n = 28). Our study focused on a subset of 23 patients from each group to compare postoperative liver function recovery. The final analysis included 86 RTR and 28 IPR cases after excluding 8 RTR patients who underwent initial hepatic artery reperfusion and 14 who received simultaneous hepatic artery and portal vein reperfusion. Further subdivision within the RTR group identified 19 patients with early hepatic allograft dysfunction (EAD) and 67 without, allowing for an assessment of the influence of preoperative and intraoperative parameters, as well as perfusion methods, on EAD incidence post-LT. RESULTS: Alanine aminotransferase (ALT) was 329 (211 ~ 548) and 176 (98 ~ 282) U/L on the 3rd and 7th day after RTR, respectively, which was significantly lower than 451 (288 ~ 918) and 251 (147 ~ 430) U/L in the IPR group (Z =-1.979, -2.299, P = 0.048, 0.021). Aspartate aminotransferase (AST) on postoperative days 3, 5, and 7 was 252 (193, 522), 105 (79, 163), and 93 (41, 135) U/L in the RTR group, respectively; it was also significantly lower than 328 (251, 724), 179 (129, 306), and 150 (91, 200)U/L in the IPR group (Z=-2.212, -3.221, -2.979; P = 0.027, 0.001, 0.003). Logistic regression analysis showed that MELD score was an independent risk factor for EAD after LT. CONCLUSION: RTR LT is more favorable for patients' early postoperative liver function recovery. For patients undergoing LT for RTR, preoperative MELD score was an independent risk factor for their postoperative development of EAD.

Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356-364.

Long term outcome after endovascular treatment for large ischemic core acute stroke is associated with hypoperfusion intensity ratio and onset-to-reperfusion time.

BACKGROUND: Endovascular treatment (EVT) is effective for large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined core. However, the influence of perfusion imaging during thrombectomy on the functional outcomes of patients with large ischemic core (LIC) stroke at both early and late time windows is uncertain in real-world practice. METHOD: A retrospective analysis was performed on 99 patients who underwent computed tomography angiography (CTA) and CT perfusion (CTP)-Rapid Processing of Perfusion and Diffusion (RAPID) before EVT and had a baseline ischemic core ≥ 50 mL and/or Alberta Stroke Program Early CT Score (ASPECTS) score of 0-5. The primary outcome was the three-month modified Rankin Scale (mRS) score. Data were analyzed by binary logistic regression and receiver operating characteristic (ROC) curves. RESULTS: A fair outcome (mRS, 0-3) was found in 34 of the 99 patients while 65 had a poor prognosis (mRS, 4-6). The multivariate logistic regression analysis showed that onset-to-reperfusion (OTR) time (odds ratio [OR], 1.004; 95% confidence interval [CI], 1.001-1.007; p = 0.008), ischemic core (OR, 1.066; 95% CI, 1.024-1.111; p = 0.008), and the hypoperfusion intensity ratio (HIR) (OR, 70.898; 95% CI, 1.130-4450.152; p = 0.044) were independent predictors of outcome. The combined results of ischemic core, HIR, and OTR time showed good performance with an area under the ROC curve (AUC) of 0.937, significantly higher than the individual variables (p < 0.05) using DeLong's test. CONCLUSIONS: Higher HIR and longer OTR time in large core stroke patients were independently associated with unfavorable three-month outcomes after EVT.

Stent Retriever Deployment Tracing Susceptibility Vessel Sign in the M2 Branch Predicts the Effective First-Pass Reperfusion in Thrombectomy for M1 Occlusion.

BACKGROUND AND PURPOSE: Successful first-pass reperfusion is associated with better functional outcomes after mechanical thrombectomy (MT) for acute ischemic stroke, but its treatment strategies remain unclear. MATERIALS AND METHODS: We retrospectively recruited patients who underwent MT for M1 occlusion between December 2020 and May 2023 at our institution. The locations of susceptibility vessel sign (SVS) on magnetic resonance imaging were classified into M1 only, M1 to single M2 branch, or M1 to both M2 branches. Patients were included in the SVS tracing group when the stent retriever of the first pass covered the entire SVS length. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale 2b-3. Any intracranial hemorrhage detected at 24-hour postoperatively was included as a hemorrhagic complication. RESULTS: The SVS was detected in M1 only, M1 to single M2 branch, and M1 to both M2 branches in 8, 22, and 4 patients, respectively. Among the 34 patients, 27 were included in the SVS-tracing group. Successful first-pass reperfusion was significantly more frequent in the SVS-tracing group compared with the non-SVS tracing group (odds ratio, 14.4; 95% confidence interval, 2.0 - 101; P = 0.007). The procedural time was significantly reduced in the SVS tracing group (median, 29 [interquartile range, 22 - 49] minute vs. 63 [43 - 106] minute; P = 0.043). There was a trend toward less frequent hemorrhagic complications in the SVS tracing group (odds ratio, 0.17; 95% confidence interval, 0.029 - 1.0; P = 0.052). CONCLUSIONS: This study provides a thrombus imaging-based MT strategy to efficiently achieve first-pass reperfusion in M1 occlusion.

Impact of carotid stenosis on the outcome of stroke patients submitted to reperfusion treatments: a narrative review.

Intravenous thrombolysis (IT) and mechanical thrombectomy (MD) are the two interventional approaches that have changed the outcome of patients with acute ischemic stroke (AIS). Ipsilateral and contralateral carotid stenosis (ICS, CCS) play an important role in regulating cerebral hemodynamics, both in chronic and acute situations such as AIS. Several studies have explored their role in the incidence and severity of stroke, but very few have investigated the possible impact of ICS and CCS on the efficacy of interventional procedures. The purpose of this review was to I) highlight the incidence and prevalence of carotid stenosis (CS); II) assess the impact of ICS and CCS on cerebral hemodynamics; III) evaluate the effect of carotid stenosis on the efficacy of interventional therapies (IT and MT) for AIS; and IV) report therapeutic complications related to CS. We searched PubMed/Medline for case reports, reviews, and original research articles on English-language review topics during the period from January 1, 2000 to October 1, 2023. CS is associated with 15-20 % of the total number of AIS. ICS and CCS had a negative influence on both cerebral hemodynamics before AIS and outcome after interventional procedures (IT, MT alone or in bridging). Available data on cerebral hemodynamics and efficacy of interventional therapies for AIS suggest a negative role of CS. Therefore, early diagnosis of CS may be considered relevant to preventive and post-stroke treatment strategies.

Impact of reperfusion therapies on clot resolution and long-term outcomes in patients with pulmonary embolism.

OBJECTIVE: Major progress in reperfusion strategies has substantially improved the short-term outcomes of patients with pulmonary embolism (PE), however, up to 50% of patients report persistent dyspnea after acute PE. METHODS: A retrospective study of the PE response team registry and included patients with repeat imaging at 3 to 12 months. The primary outcome was to determine the incidence of residual pulmonary vascular obstruction following acute PE. Secondary outcomes included the development of PE recurrence, right ventricular (RV) dysfunction, chronic thromboembolic pulmonary hypertension, readmission, and mortality at 12 months. RESULTS: A total of 382 patients were included, and 107 patients received reperfusion therapies followed by anticoagulation. Patients who received reperfusion therapies including systemic thrombolysis, catheter-directed thrombolysis, and mechanical thrombectomy presented with a higher vascular obstructive index (47% vs 28%; P < .001) and signs of right heart strain on echocardiogram (81% vs 43%; P < .001) at the time of diagnosis. A higher absolute reduction in vascular obstructive index (45% vs 26%; 95% confidence interval, 14.0-25.6; P < .001), greater improvement in RV function (82% vs 65%; P = .021), and lower 12-month mortality rate (2% vs 7%; P = .038) and readmission rate (33% vs 46%; P = .031) were observed in the reperfusion group. No statistically significant differences were found between groups in the development of chronic thromboembolic pulmonary hypertension (8% vs 5%; P = .488) and PE recurrence (8% vs 6%; P = .646). CONCLUSIONS: We observed a favorable survival and greater improvement in clot resolution and RV function in patients treated with reperfusion therapies.

Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.

Implementation of a retinal stroke-code protocol results in visual recovery in patients receiving reperfusion therapies.

INTRODUCTION: Reperfusion therapies represent promising treatments for patients with Central Retinal Artery Occlusion (CRAO), but access is limited due to low incidence and lack of protocols. We aimed to describe the benefit of implementing a Retinal Stroke-Code protocol regarding access to reperfusion, visual acuity and aetiological assessment. PATIENTS AND METHODS: Prospective cohort study performed at a Comprehensive Stroke Centre. Criteria for activation were sudden monocular, painless vision loss within 6 h from onset. Eligible patients received IAT when immediately available and IVT otherwise. All patients were followed by ophthalmologists to assess best-corrected visual acuity (BCVA) and visual complications, and by neurologists for aetiological workup. Visual amelioration was defined as improvement of at least one Early Treatment Diabetic Retinopathy Study (ETDRS) letter from baseline to 1 week. RESULTS: Of 49 patients with CRAO, 15 (30.6%) received reperfusion therapies (12 IVT, 3 IAT). Presentation beyond 6 h was the main contraindication. Patients receiving reperfusion therapies had better rates of visual improvement (33.3% vs 5.9%, p = 0.022). There were no complications related to reperfusion therapies. Rates of neovascular glaucoma were non-significantly lower in patients receiving reperfusion therapies (13.3% vs 20.6%, p = 0.701). Similar rates of atherosclerotic, cardioembolic and undetermined aetiologies were observed, leading to 10 new diagnosed atrial fibrillation and five carotid revascularizations. CONCLUSION: A comprehensive acute management of CRAO is feasible despite low incidence. In our study, reperfusion therapies were safe and associated with higher rates of visual recovery. A similar etiological workup than ischemic stroke led to of high proportion of underlying aetiologies.

Development and validation of outcome prediction model for reperfusion therapy in acute ischemic stroke using nomogram and machine learning.

OBJECTIVE: To develop logistic regression nomogram and machine learning (ML)-based models to predict 3-month unfavorable functional outcome for acute ischemic stroke (AIS) patients undergoing reperfusion therapy. METHODS: Patients undergoing reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) were prospectively recruited. Unfavorable outcome was defined as 3-month modified Rankin Scale (mRS) score 3-6. The independent risk factors associated with unfavorable outcome were obtained by regression analysis and included in the prediction model. The performance of nomogram was assessed by the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). ML models were compared with nomogram using AUC; the generalizability of all models was ascertained in an external cohort. RESULTS: A total of 505 patients were enrolled, with 256 in the model construction, and 249 in the external validation. Five variables were identified as prognostic factors: baseline NIHSS, D-dimer level, random blood glucose (RBG), blood urea nitrogen (BUN), and systolic blood pressure (SBP) before reperfusion. The AUC values of nomogram were 0.865, 0.818, and 0.779 in the training set, test set, and external validation, respectively. The calibration curve and DCA indicated appreciable reliability and good net benefits. The best three ML models were extra trees (ET), CatBoost, and random forest (RF) models; all of them showed favorable discrimination in the training cohort, and confirmed in the test and external sets. CONCLUSION: Baseline NIHSS, D-dimer, RBG, BUN, and SBP before reperfusion were independent predictors for 3-month unfavorable outcome after reperfusion therapy in AIS patients. Both nomogram and ML models showed good discrimination and generalizability.

Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open-label, controlled trial.

BACKGROUND AND PURPOSE: Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours. METHODS AND DESIGN: Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) were included and randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or standard medical therapy. Specially, we will exclude patients who are intended for direct thrombectomy. All will be followed up for 90 days. STUDY OUTCOMES: Primary efficacy outcome is modified Rankin Scale (mRS) score ≤1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, major neurological improvement defined by a decrease ≥8 points compared with the initial deficit or a score ≤1 on the National Institutes of Health Stroke Scale (NIHSS) at 72 hours, mRS score ≤2 at 90 days, the rate of improvement on Tmax >6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days. DISCUSSION: TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours. TRIAL REGISTRATION NUMBER: NCT05141305.

Implications of Post-recanalization Perfusion Deficit After Acute Ischemic Stroke: a Scoping Review of Clinical and Preclinical Imaging Studies.

The goal of reperfusion therapy for acute ischemic stroke (AIS) is to restore cerebral blood flow through recanalization of the occluded vessel. Unfortunately, successful recanalization does not always result in favorable clinical outcome. Post-recanalization perfusion deficits (PRPDs), constituted by cerebral hypo- or hyperperfusion, may contribute to lagging patient recovery rates, but its clinical significance remains unclear. This scoping review provides an overview of clinical and preclinical findings on post-ischemic reperfusion, aiming to elucidate the pattern and consequences of PRPD from a translational perspective. The MEDLINE database was searched for quantitative clinical and preclinical studies of AIS reporting PRPD based on cerebral circulation parameters acquired by translational tomographic imaging methods. PRPD and stroke outcome were mapped on a charting table, creating an overview of PRPD after AIS. Twenty-two clinical and twenty-two preclinical studies were included. Post-recanalization hypoperfusion is rarely reported in clinical studies (4/22) but unequivocally associated with detrimental outcome. Post-recanalization hyperperfusion is more commonly reported (18/22 clinical studies) and may be associated with positive or negative outcome. PRPD has been replicated in animal studies, offering mechanistic insights into causes and consequences of PRPD and allowing delineation of possible courses of PRPD. Complex relationships exist between PRPD and stroke outcome. Diversity in methods and lack of standardized definitions in reperfusion studies complicate the characterization of reperfusion patterns. Recommendations are made to advance the understanding of PRPD mechanisms and to further disentangle the relation between PRPD and disease outcome.

Underuse of reperfusion therapy with systemic thrombolysis in high-risk acute pulmonary embolism in a Portuguese center.

INTRODUCTION: Reperfusion therapy is generally recommended in acute high-risk pulmonary embolism (HR-PE), but several population-based studies report that it is underused. Data on epidemiology, management and outcomes of HR-PE in Portugal are scarce. OBJECTIVE: To determine the reperfusion rate in HR-PE patients, the reasons for non-reperfusion, and how it influences outcomes. METHODS: In this retrospective cohort study of consecutive HR-PE patients admitted to a thromboembolic disease referral center between 2008 and 2018, independent predictors for non-reperfusion were assessed by multivariate logistic regression. PE-related mortality and long-term MACE (cardiovascular mortality, PE recurrence and chronic thromboembolic disease) were calculated according to the Kaplan-Meier method. Differences stratified by reperfusion were assessed using the log-rank test. RESULTS: Of 1955 acute PE patients, 3.8% presented with hemodynamic instability. The overall reperfusion rate was 50%: 35 patients underwent systemic thrombolysis, one received first-line percutaneous embolectomy and one rescue endovascular treatment. Independent predictors of non-reperfusion were: age, with >75 years representing 12 times the risk of non-treatment (OR 11.9, 95% CI 2.7-52.3, p=0.001); absolute contraindication for thrombolysis (31.1%), with recent major surgery and central nervous system disease as the most common reasons (OR 16.7, 95% CI 3.2-87.0, p<0.001); and being hospitalized (OR 7.7, 95% CI 1.4-42.9, p=0.020). At a mean follow-up of 2.5±3.3 years, the survival rate was 33.8%. Although not reaching statistical significance for hospital mortality, mortality in the reperfusion group was significantly lower at 30 days, 12 months and during follow-up (relative risk reduction of death of 64% at 12 months, p=0.013). Similar results were found for MACE. CONCLUSIONS: In this population, the recommended reperfusion therapy was performed in only 50% of patients, with advanced age and absolute contraindications to fibrinolysis being the main predictors of non-reperfusion. In this study, thrombolysis underuse was associated with a significant increase in short- and long-term mortality and events.

Role of perfusion medium in rewarming machine perfusion from hypo- to normothermia.

BACKGROUND: Gradual warming up of cold stored organ grafts using a controlled machine perfusion protocol facilitates restitution of cellular homeostasis and mitigates rewarming injury by adapted increase of temperature and metabolism. The aim of the present study was to compare intra- and extracellular type perfusion media for the use in machine perfusion-assisted rewarming from hypo- to normothermia. METHODS: Rat livers were retrieved 20 min after cardiac arrest. After 18 h of cold storage (CS) with or without additional 2 h of rewarming machine perfusion from 8°C up to 35°C with either diluted Steen solution or with Belzer MPS, liver functional parameters were evaluated by an established ex vivo reperfusion system. RESULTS: Rewarming machine perfusion with either solution significantly improved graft performance upon reperfusion in terms of increased bile production, less enzyme release, and reduced lipid peroxidation compared to CS alone. Cellular apoptosis (release of caspase-cleaved keratin 18) and release of tumor necrosis factor were only reduced significantly after machine perfusion with Belzer MPS. Histological evaluation did not disclose any major morphological damage in any of the groups. CONCLUSION: Within the limitation of our model, the use of Belzer MPS seems to be an at least adequate alternative to a normothermic medium like Steen solution for rewarming machine perfusion of cold liver grafts.