Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial.

BACKGROUND: Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain. METHODS: BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310. FINDINGS: Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988). INTERPRETATION: In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation. FUNDING: Biotronik.

Ultrathin-strut vs thin-strut drug-eluting stents for multi and single-stent lesions: A lesion-level subgroup analysis of 2 randomized trials.

BACKGROUND: Whether ultrathin-strut stents are particularly beneficial for lesions requiring implantation of more than 1 stent is unknown. METHODS: In a post-hoc lesion-level analysis of 2 randomized trials comparing ultrathin-strut biodegradable polymer Sirolimus-eluting stents (BP-SES) vs thin-strut durable polymer Everolimus-eluting stents (DP-EES), lesions were stratified into multistent lesions (MSL) vs single-stent lesions (SSL). The primary endpoint was target lesion failure (TLF), a composite of lesion-related unclear/cardiac death, myocardial infarction (MI), or revascularization, at 24 months. RESULTS: Among 5328 lesions in 3397 patients, 1492 (28%) were MSL (722 with BP-SES, 770 with DP-EES). At 2 years, TLF occurred in 63 lesions (8.9%) treated with BP-SES and 60 lesions (7.9%) treated with DP-EES in the MSL-group (subdistibution hazard ratio [SHR], 1.13; 95% CI, 0.77-1.64; P = .53), and in 121 (6.4%) and 136 (7.4%) lesions treated with BP-SES and DP-EES respectively (SHR, 0.86; 95% CI, 0.62-1.18; P = .35) in the SSL-group (P for interaction = .241). While the rates of lesion-related MI or revascularization were significantly lower in SSL treated with BP-SES as compared to DP-EES (3.5% vs 5.2%; SHR, 0.67; 95% CI 0.46-0.97; P = .036), no significant difference was observed in MSL (7.1% vs 5.4%; SHR, 1.31; 95% CI 0.85-2.03; P = .216) with significant interaction between groups (P for interaction = .014). CONCLUSIONS: Rates of TLF are similar between ultrathin-strut BP-SES and thin-strut DP-EES in MSL and SSL. The use of ultrathin-strut BP-SES vs thin-strut DP-EES did not prove to be particularly beneficial for the treatment of multistent lesions. TRIAL REGISTRATION: Post-hoc analysis from the BIOSCIENCE (NCT01443104) and BIOSTEMI (NCT02579031) trials.

[The influence of summer temperatures on the incidence of Takotsubo cardiomyopathy : a retrospective study]. / Influence des canicules sur l'incidence du syndrome de Takotsubo : étude rétrospective en Valais.

Takotsubo cardiomyopathy (TK-CM) is a reversible acute left ventricular dysfunction that cannot be explained by an obstructive coronary lesion. The aim of our study was to explore the possible correlation between the incidence of TK-CM in summer and the average temperature, number of heat waves or number of days hotter than 30°C. 482 patients presented an acute coronary syndrome in the summers of 2012 until 2017 in our region. 15 patients met the inclusion and exclusion criteria and were diagnosed as TK-CM. The study analysis showed a statistically correlation between the number of heatwaves and the incidence of TK-CM (coefficient of correlation: 0.77; p = 0.04). This comforts the hypothesis of climatic influence on this pathology.

Le syndrome de Takotsubo (STK) est une dysfonction ventriculaire gauche aiguë, le plus souvent réversible, sans rapport avec une maladie coronarienne. L'objectif de notre étude était d'explorer le lien entre l'incidence de cette maladie en été et divers paramètres météorologiques; température moyenne, nombre de canicules et nombre de jours au-dessus de 30 °C. 482 patients ayant présenté un syndrome coronarien aigu entre les étés 2012 et 2017 ont été analysés dans notre région (Valais, Suisse). Après application des critères d'éligibilité et d'exclusion, 15 avec un STK avéré ont été inclus dans l'étude. Les résultats montrent que l'incidence de STK était statistiquement plus élevée pendant les canicules (coefficient de corrélation: 0,77; p = 0,04), ce qui conforte l'hypothèse de l'influence des températures extrêmes sur l'incidence saisonnière de cette pathologie.

[Heart failure in year 2021: a review for the general practitioner]. / Insuffisance cardiaque en 2021 : un tour d'horizon pour le généraliste.

Heart failure has become a real public health problem impacting both the hospital system and the outpatient sector. In constant evolution, the therapeutic armamentarium has been enriched with new molecules, making treatment more effective. Optimal management of patients suffering from heart failure are multileveled and require a multidisciplinary team. The team consists of the in-charge general physician, a cardiologist, a trained nurse in therapeutic education, and optimally a dietician and/or physiotherapist. A limiting step towards the efficiency of patient management is the communication skills of the network.

À l'heure actuelle, l'insuffisance cardiaque est devenue un réel problème de santé publique qui impacte le système hospitalier comme le secteur ambulatoire. En constante évolution, le traitement médicamenteux s'est étoffé de nouvelles molécules, rendant la prise en charge plus efficace. Les défis pour une prise en charge optimale des patients souffrant d'insuffisance cardiaque sont multiples et requièrent une approche multidisciplinaire incluant bien évidemment le généraliste, le cardiologue mais aussi l'infirmière spécialisée en éducation thérapeutique, la diététicienne ou encore le physiothérapeute. L'augmentation du nombre d'intervenants nécessite une communication optimale et active entre les intervenants de l'hôpital et du cabinet.

[Heart and thromboembolic events: situation in 2021]. / Cœur et événements thromboemboliques : situation en 2021.

In daily practice, ischemia of embolic origin is frequent. The clinical spectrum can range from minor ischemia to stroke or myocardial infarction. This article summarizes the common etiologies of a cardioembolic event, such as atrial fibrillation or atrial flutter, presence of a patent foramen ovale or intracardiac masses (endocarditis, thrombi or tumors). This paper aims to serve as a short repository of information to guide every physician might need to initiate the diagnostic investigations and therapy according to recent recommendations.

Dans son quotidien, le praticien sera couramment confronté à une ischémie d'origine embolique. L'éventail clinique va d'une ischémie mineure à un AVC ou un infarctus du myocarde. Cet article résume les étiologies courantes d'un événement cardioembolique, notamment la fibrillation ou le flutter auriculaire, la présence d'un foramen ovale perméable ou de masses intracardiaques (végétations, thrombi, tumeurs). Il vise à guider le praticien dans sa prise en charge diagnostique et thérapeutique selon les recommandations cliniques récentes. Cette prise en charge est très souvent multidisciplinaire.

Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI): a single-blind, prospective, randomised superiority trial.

BACKGROUND: Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS: The BIOSTEMI trial was an investigator-initiated, multicentre, prospective, single-blind, randomised superiority trial at ten hospitals in Switzerland. Patients aged 18 years or older with acute STEMI who were referred for primary PCI were eligible to participate. Patients were randomly allocated (1:1) to either biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Central randomisation was done based on a computer-generated allocation sequence with variable block sizes of 2, 4, and 6, which was stratified by centre, diabetes status, and presence or absence of multivessel coronary artery disease, and concealed using a secure web-based system. Patients and treating physicians were aware of group allocations, whereas outcome assessors were masked to the allocated stent. The experimental stent (Orsiro; Biotronik; Bülach, Switzerland) consisted of an ultrathin strut cobalt-chromium metallic stent platform releasing sirolimus from a biodegradable polymer. The control stent (Xience Xpedition/Alpine; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut cobalt-chromium stent platform that releases everolimus from a durable polymer. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial reinfarction (Q-wave and non-Q-wave), and clinically-indicated target lesion revascularisation, within 12 months of the index procedure. All analyses were done with the individual participant as the unit of analysis and according to the intention-to-treat principle. The trial was registered with ClinicalTrials.gov, number NCT02579031. FINDINGS: Between April 26, 2016, and March 9, 2018, we randomly assigned 1300 patients (1623 lesions) with acute myocardial infarction to treatment with biodegradable polymer sirolimus-eluting stents (649 patients and 816 lesions) or durable polymer everolimus-eluting stents (651 patients and 806 lesions). At 12 months, follow-up data were available for 614 (95%) patients treated with biodegradable polymer sirolimus-eluting stents and 626 (96%) patients treated with durable polymer everolimus-eluting stents. The primary composite endpoint of target lesion failure occurred in 25 (4%) of 649 patients treated with biodegradable polymer sirolimus-eluting stents and 36 (6%) of 651 patients treated with durable polymer everolimus-eluting stents (difference -1·6 percentage points; rate ratio 0·59, 95% Bayesian credibility interval 0·37-0·94; posterior probability of superiority 0·986). Cardiac death, target vessel myocardial reinfarction, clinically-indicated target lesion revascularisation, and definite stent thrombosis were similar between the two treatment groups in the 12 months of follow-up. INTERPRETATION: In patients with acute STEMI undergoing primary PCI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 1 year. This difference was driven by reduced ischaemia-driven target lesion revascularisation in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents. FUNDING: Biotronik.

[News about pericardial diseases in 2016]. / Maladies du péricarde : quoi de neuf en 2016 ?

The European Society of Cardiology published in 2015 the new Guidelines on the management of pericardial diseases. Based on experts' opinions and recent clinical studies of respectable size, the new guidelines thoroughly revisit the criteria for hospitalization and precisely define severe cases. Another highlight regards medication. From now, first-line medical therapy should include the association of colchicine to the traditional non steroidal anti-inflammatory drugs or aspirin. The bi-therapy is recommended as soon as the first episode of pericarditis, for duration of 3 months. The experts also recommend systematically performing a heart ultrasound for any form of pericardial disease and restricting physical activities especially if myocardial damage (perimyocarditis) is associated.

La Société européenne de cardiologie a publié de nouvelles recommandations en 2015 à propos des maladies du péricarde, apportant des précisions au niveau des thérapies avec notamment l'introduction en première ligne de la colchicine en association aux anti-inflammatoires non stéroïdiens (AINS) ou à l'aspirine, et ce dès le premier épisode de péricardite idiopathique. Les corticoïdes restent contre-indiqués en première ligne. Les experts préconisent en outre la réalisation systématique d'une échocardiographie cardiaque. Les critères d'hospitalisation sont précisés (fièvre, échec du traitement aux anti-inflammatoires non stéroïdiens) et il est rappelé la nécessité d'une restriction au niveau des activités sportives, en particulier lors d'une atteinte associée du myocarde.

[Cell-based regenerative therapy in cardiology: the future at present]. / Thérapie cellulaire régénérative en cardiologie: le futur au présent?

Cell-based regenerative therapy treatment of cardiovascular diseases considered as irreversible, as acute myocardial infarction, chronic ischemic heart failure, non-ischemic dilated cardiomyopathy and refractory angina pectoris. Large randomized clinical trials with hard clinical endpoints are still necessary before considering cell-based regenerative therapy as a valuable alternative therapeutic option in cardiology.

Biodegradable- Versus Durable-Polymer Drug-Eluting Stents for STEMI: Final 2-Year Outcomes of the BIOSTEMI Trial.

OBJECTIVES: The aim of this study was to investigate the safety and efficacy of biodegradable-polymer sirolimus-eluting stents (BP-SES) compared with durable-polymer everolimus-eluting stents (DP-EES) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Primary percutaneous coronary intervention (PCI) is an effective treatment for patients with STEMI, and long-term outcomes are determined by the safety and efficacy profile of the newest generation drug-eluting stents. METHODS: BIOSTEMI (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention) was an investigator-initiated, multicenter, assessor-blind, randomized superiority trial using Bayesian methods. Patients with STEMI undergoing primary PCI within 24 h of symptom onset were randomized in a 1:1 ratio to receive BP-SES (n = 649) or DP-EES (n = 651). The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial reinfarction, and clinically indicated target lesion revascularization (TLR) at 2 years. RESULTS: Between April 2016 and March 2018, 1,300 patients were included. Baseline characteristics were comparable between the 2 treatment groups. Follow-up through 2 years was complete in 1,221 patients (94%). At 2 years, TLF occurred in 33 patients (5.1%) treated with BP-SES and in 53 patients (8.1%) treated with DP-EES (rate ratio: 0.58; 95% Bayesian credible interval: 0.40 to 0.84; posterior probability of superiority = 0.998). The difference was driven by a lower incidence of clinically indicated TLR in patients treated with BP-SES compared with DP-EES (2.5% vs. 5.1%; rate ratio: 0.52; 95% Bayesian credible interval: 0.30 to 0.87; posterior probability of superiority = 0.993). There were no significant differences in rates of cardiac death, target vessel myocardial reinfarction, and definite stent thrombosis between the 2 treatment arms. CONCLUSIONS: In patients with STEMI undergoing primary PCI, BP-SES were superior to DP-EES with respect to TLF at 2 years. The difference was driven by lower rates of ischemia-driven TLR. (A Comparison of an Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent With a Durable Polymer Everolimus-Eluting Stent for Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention [BIOSTEMI]; NCT02579031).

A comparison of an ultrathin-strut biodegradable polymer sirolimus-eluting stent with a durable polymer everolimus-eluting stent for patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: rationale and design of the BIOSTEMI trial.

AIMS: A novel ultrathin-strut biodegradable polymer sirolimus-eluting stent (BP-SES) (Orsiro; Biotronik, Bülach, Switzerland) was shown to be superior to a thin-strut durable polymer everolimus-eluting stent (DP-EES) (XIENCE Xpedition/Alpine; Abbott Vascular, Santa Clara, CA, USA) with respect to the primary endpoint of target lesion failure (TLF) at 12 months in the pre-specified subgroup of patients with ST-segment elevation myocardial infarction (STEMI) included in the BIOSCIENCE trial. We designed a large-scale, randomised, clinical trial to assess the clinical superiority of ultrathin-strut BP-SES over thin-strut DP-EES among patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS: BIOSTEMI (NCT02579031) is a prospective, multicentre, randomised, controlled, superiority trial that will randomly assign 1,250 patients with STEMI undergoing PPCI to treatment with BP-SES or DP-EES. The primary endpoint of TLF, a composite of cardiac death, target vessel reinfarction, and clinically indicated target lesion revascularisation within 12 months, will be analysed with Bayesian models applied to the BIOSTEMI data set (n=1,250) using robust historical priors to incorporate historical information from the BIOSCIENCE STEMI subgroup (n=407). CONCLUSIONS: The BIOSTEMI trial will determine whether ultrathin-strut BP-SES are superior to thin-strut DP-EES with respect to TLF in patients with STEMI undergoing PPCI.

Left sinus of Valsalva aneurysm as a cause of chronic stable angina.

Sinus of Valsalva aneurysms are unusual, particularly when located on the left coronary sinus. They are mainly asymptomatic, however once ruptured, they are associated with high mortality. We present hereinafter an atypical case of a 71-year-old patient with an unruptured left sinus of Valsalva aneurysm causing myocardial ischaemia due to a compressed left main coronary artery. Surgical endoaneurysmorrhaphy was performed; however, a dehiscence of the suture line between the patch and the aortic wall required additional percutaneous implantation of a vascular occluder.

Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

BACKGROUND: Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. PURPOSE: To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. METHODS: Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. RESULTS: Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. CONCLUSIONS: Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01374607.

Time course of lung injury in rat acute pancreatitis.

OBJECTIVE: Lung injury is a severe complication of acute pancreatitis that increases the mortality rate of the disease. The pathophysiology of acute pancreatitis has been studied in several experimental models, but the kinetics of pulmonary complications in relation to the pancreatic disease is not completely understood. We then studied the severity of acute pancreatitis-associated lung injury over 18h in rats that had taurocholic acid injection in the pancreatic duct and determined whether blood collected from rats with pancreatitis is toxic enough to induce injury in normal lungs. DESIGN AND SETTING: Prospective, randomized, and controlled animal study in an animal research laboratory in a university hospital. INTERVENTIONS: We isolated lungs from rats with acute pancreatitis 2, 6, and 18h after taurocholic acid injection in the biliopancreatic duct and perfused them with blood collected from the same rats. Additionally, blood collected from rats with acute pancreatitis (time-points: 2 and 6h) was perfused in normal lungs. MEASUREMENTS AND RESULTS: Taurocholic acid injection induced a severe pancreatic injury that started as early as 2h after the injection and persisted without recovery over the 18-h study period. In contrast, the pulmonary injury was transient, appearing at the 6-h time point with recovery by the end of the study. Pulmonary injury was moderate and evidenced mostly during lung reperfusion. Interestingly, blood collected at the 2-h time point in pancreatic rats induced pulmonary injury in normal lungs while blood collected at the 6-h time-point was not toxic. CONCLUSIONS: While pancreatic injury persists over the full experimental period, pulmonary injury is transient in our experimental model. The recovery of lung injury by 18h might be explained by a decrease in the overall toxicity of pancreatic blood over time.

Relationship between time of day and periprocedural myocardial infarction after elective angioplasty.

OBJECTIVES: To test if the time of day significantly influences the occurrence of type 4A myocardial infarction in elective patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Recent studies have suggested an influence of circadian rhythms on myocardial infarction size and mortality among patients with ST-elevation myocardial infarction. The aim of the study is to investigate whether periprocedural myocardial infarction (PMI) is influenced by the time of day in elective patients undergoing PCI. METHODS: All consecutive patients undergoing elective PCI between 2007 and 2011 at our institutions with known post-interventional troponin were retrospectively included. Patients (n = 1021) were divided into two groups according to the starting time of the PCI: the morning group (n = 651) between 07:00 and 11:59, and the afternoon group (n = 370) between 12:00 and 18:59. Baseline and procedural characteristics as well as clinical outcome defined as the occurrence of PMI were compared between groups. In order to limit selection bias, all analyses were equally performed in 308 pairs using propensity score (PS) matching. RESULTS: In the overall population, the rate of PMI was statistically lower in the morning group compared to the afternoon group (20% vs. 30%, p < 0.001). This difference remained statistically significant after PS-matching (21% vs. 29%, p = 0.03). Multivariate analysis shows that being treated in the afternoon independently increases the risk for PMI with an odds ratio of 2.0 (95%CI: 1.1-3.4; p = 0.02). CONCLUSIONS: This observational PS-matched study suggests that the timing of an elective PCI influences the rate of PMI.

Functional identification of the alveolar edema reabsorption activity of murine tumor necrosis factor-alpha.

Tumor necrosis factor-alpha (TNF-alpha) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-alpha receptor-dependent and -independent effects were proposed for this activity in vitro, the latter mechanism mediated by the lectin-like domain of the molecule. In this study, the relative contribution of the receptor-dependent versus receptor-independent activities was investigated in an in situ mouse lung model and an ex vivo rat lung model. Fluid resorption due to murine TNF-alpha (mTNF-alpha) was functional in mice that were genetically deficient in both types of mTNF-alpha receptor, establishing the importance of mTNF-alpha receptor-independent effects in this species. In addition, we assessed the capacity of an mTNF-alpha-derived peptide (mLtip), which activates sodium transport by a receptor-independent mechanism, to reduce lung water content in an isolated, ventilated, autologous blood-perfused rat lung model. The results show that in this model, mLtip, in contrast to mTNF-alpha, produced a progressive recovery of dynamic lung compliance and airway resistance after alveolar flooding. There was also a significant reduction in lung water. These results indicate that the receptor-independent lectin-like domain of mTNF-alpha has a potential physiological role in the resolution of alveolar edema in rats and mice.