Deep learning to predict long-term mortality from plain chest X-ray in patients referred for suspected coronary artery disease.

Background: The hypothesis that a deep learning (DL) model can produce long-term prognostic information from chest X-ray (CXR) has already been confirmed within cancer screening programs. We summarize our experience with DL prediction of long-term mortality, from plain CXR, in patients referred for angina and coronary angiography. Methods: Data of patients referred to an Italian academic hospital were analyzed retrospectively. We designed a deep convolutional neural network (DCNN) that, from CXR, could predict long-term mortality. External validation was performed on patients referred to a Dutch academic hospital. Results: A total of 6,031 were used for model training (71%; n=4,259) and fine-tuning/validation (10%; n=602). Internal validation was performed with the remaining patients (19%; n=1,170). Patients' stratification followed the DL-CXR risk score quartiles division. Median follow-up was 6.1 years [interquartile range (IQR), 3.3-8.7 years]. We observed an increment in estimated mortality with the increase of DL-CXR risk score (low-risk 5%, moderate 17%, high 29%, very high 46%; P<0.001). The DL-CXR risk score predicted median follow-up outcome with an area under the curve (AUC) of 0.793 [95% confidence interval (CI): 0.759-0.827, sensitivity 78%, specificity 68%]. Prediction was better than that achieved using coronary angiography findings (AUC: 0.569, 95% CI: 0.52-0.61, P<0.001) and age (AUC: 0.735, 95% CI: 0.69-0.77, P<0.004). At Cox regression, the DL-CXR risk score predicted follow-up mortality (P<0.005, hazard ratio: 3.30, 95% CI: 2.35-4.64). External validation confirmed the DL-CXR risk score performance (AUC: 0.71, 95% CI: 0.49-0.92; sensitivity 0.838; specificity 0.338). Conclusions: In patients referred for coronary angiogram because of angina, the DL-CXR risk score could be used to stratify mortality risk and predict long-term outcome better than age and coronary artery disease status.

NLRP3-Inflammasome Inhibition with IZD334 Does Not Reduce Cardiac Damage in a Pig Model of Myocardial Infarction.

NLRP3-inflammasome-mediated signaling is thought to significantly contribute to the extent of myocardial damage after myocardial infarction (MI). The purpose of this study was to investigate the effects of the NLRP3-inflammasome inhibitor IZD334 on cardiac damage in a pig model of myocardial infarction. Prior to in vivo testing, in vitro, porcine peripheral blood mononuclear cells and whole blood were treated with increasing dosages of IZD334, a novel NLRP3-inflammasome inhibitor, and were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). After determination of the pharmacological profile in healthy pigs, thirty female Landrace pigs were subjected to 75 min of transluminal balloon occlusion of the LAD coronary artery and treated with placebo or IZD334 (1 mg/kg, 3 mg/kg, or 10 mg/kg once daily) in a blinded randomized fashion. In vitro, NLRP3-inflammasome stimulation showed the pronounced release of interleukin (IL)-1ß that was attenuated by IZD334 (p < 0.001). In vivo, no differences were observed between groups in serological markers of inflammation nor myocardial IL-1ß expression. After 7 days, the ejection fraction did not differ between groups, as assessed with MRI (placebo: 45.1 ± 8.7%, 1 mg/kg: 49.9 ± 6.1%, 3 mg/kg: 42.7 ± 3.8%, 10 mg/kg: 44.9 ± 6.4%, p = 0.26). Infarct size as a percentage of the area at risk was not reduced (placebo: 73.1 ± 3.0%, 1 mg/kg: 75.5 ± 7.3%, 3 mg/kg: 80.3 ± 3.9%, 10 mg/kg: 78.2 ± 8.0%, p = 0.21). In this pig MI model, we did not observe attenuation of the inflammatory response after NLRP3-inflammasome inhibition in vivo. Consecutively, no difference was observed in IS and cardiac function, while in vitro inhibition successfully reduced IL-1ß release from stimulated porcine blood cells.

Prophylactic Impella CP versus VA-ECMO in Patients Undergoing Complex High-Risk Indicated PCI.

Objectives: To compare two different forms of mechanical circulatory support (MCS) in patients with complex high-risk indicated PCI (CHIP): the Impella CP system and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Background: To prevent hemodynamic instability in CHIP, various MCS systems are available. However, comparable data on different forms of MCS are not at hand. Methods: In this multicenter observational study, we retrospectively evaluated all CHIP procedures with the support of an Impella CP or VA-ECMO, who were declined surgery by the heart team. Major adverse cardiac events (MACE), mortality at discharge, and 30-day mortality were evaluated. Results: A total of 41 patients were included, of which 27 patients were supported with Impella CP and 14 patients with VA-ECMO. Baseline characteristics were well-balanced in both groups. No significant difference in periprocedural hemodynamic instability was observed between both groups (3.7% vs. 14.3%; p = 0.22). The composite outcome of MACE showed no significant difference (30.7% vs. 21.4%; p = 0.59). Bleeding complications were higher in the Impella CP group, but showed no significant difference (22.2% vs. 7.1%; p = 0.22) and occurred more at the non-Impella access site. In-hospital mortality was 7.4% in the Impella CP group versus 14.3% in the VA-ECMO group and showed no significant difference (p = 0.48). 30-Day mortality showed no significant difference (7.4% vs. 21.4%; p = 0.09). Conclusions: In patients with CHIP, there were no significant differences in hemodynamic instability and overall MACE between VA-ECMO or Impella CP device as mechanical circulatory support. Based on this study, the choice of either VA-ECMO or Impella CP does not alter the outcome.

Ventricular TLR4 Levels Abrogate TLR2-Mediated Adverse Cardiac Remodeling upon Pressure Overload in Mice.

Involvement of the Toll-like receptor 4 (TLR4) in maladaptive cardiac remodeling and heart failure (HF) upon pressure overload has been studied extensively, but less is known about the role of TLR2. Interplay and redundancy of TLR4 with TLR2 have been reported in other organs but were not investigated during cardiac dysfunction. We explored whether TLR2 deficiency leads to less adverse cardiac remodeling upon chronic pressure overload and whether TLR2 and TLR4 additively contribute to this. We subjected 35 male C57BL/6J mice (wildtype (WT) or TLR2 knockout (KO)) to sham or transverse aortic constriction (TAC) surgery. After 12 weeks, echocardiography and electrocardiography were performed, and hearts were extracted for molecular and histological analysis. TLR2 deficiency (n = 14) was confirmed in all KO mice by PCR and resulted in less hypertrophy (heart weight to tibia length ratio (HW/TL), smaller cross-sectional cardiomyocyte area and decreased brain natriuretic peptide (BNP) mRNA expression, p < 0.05), increased contractility (QRS and QTc, p < 0.05), and less inflammation (e.g., interleukins 6 and 1ß, p < 0.05) after TAC compared to WT animals (n = 11). Even though TLR2 KO TAC animals presented with lower levels of ventricular TLR4 mRNA than WT TAC animals (13.2 ± 0.8 vs. 16.6 ± 0.7 mg/mm, p < 0.01), TLR4 mRNA expression was increased in animals with the largest ventricular mass, highest hypertrophy, and lowest ejection fraction, leading to two distinct groups of TLR2 KO TAC animals with variations in cardiac remodeling. This variation, however, was not seen in WT TAC animals even though heart weight/tibia length correlated with expression of TLR4 in these animals (r = 0.078, p = 0.005). Our data suggest that TLR2 deficiency ameliorates adverse cardiac remodeling and that ventricular TLR2 and TLR4 additively contribute to adverse cardiac remodeling during chronic pressure overload. Therefore, both TLRs may be therapeutic targets to prevent or interfere in the underlying molecular processes.

Reverse remodeling after percutaneous transluminal septal myocardial ablation in severe but asymptomatic LVOT obstruction (RASTA) study: Rationale and design of transcatheter septal reduction in asymptomatic patients with severe hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The aim of this study is to evaluate the impact of percutaneous transluminal septal myocardial ablation (PTSMA) on remodeling in asymptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular outflow tract (LVOT) obstruction. BACKGROUND: Symptoms justify invasive treatment in HOCM patients with LVOT obstruction. Adverse structural and functional changes (remodeling) in the heart occur preceding heart failure and sudden cardiac death. Early invasive treatment in asymptomatic patients may reverse adverse remodeling to the same extent as in symptomatic patients. METHODS: Reverse remodeling after PTSMA in severe but asymptomatic LVOT obstruction (RASTA) study is a prospective single-blind randomized trial (ClinicalTrials.gov number: NCT04230551). Ten asymptomatic HOCM patients with an exertional LVOT gradient ≥50 mmHg (or >30 mmHg in rest) are randomized 1:1 to PTSMA versus conservative therapy, in the absence of mitral valve disease or other indications for cardiac surgery. Five symptomatic (reference group) will undergo PTSMA according to the current guidelines. RESULTS: Remodeling is assessed using extensive cardiac imaging with transthoracic echocardiography and late gadolinium enhancement cardiac magnetic resonance at baseline and during follow-up at 1, 12, and 24 months. Extracellular volume fraction, global, and regional strain analysis, geometry, pressure gradients and changes in four-dimensional velocity mapping are primary parameters to study (reversal of) adverse remodeling. CONCLUSIONS: The RASTA study gives insight in cardiac remodeling that may occur in asymptomatic patients after PTSMA. It will provide arguments whether to pursue (or not) a larger trial with clinical endpoints in asymptomatic HOCM patients with severe LVOT obstruction.

A reliable method to avoid contamination during cartilage graft preparation in septorhinoplasty.

PURPOSE: The aim of the study is to determine the risk of contamination in the cartilage graft materials prepared on the swester table and those prepared in a sterile package, and to reveal a more reliable method by performing the microbiological examination of these materials. METHODS: Cartilages removed from the nasal septum were divided into four pieces. The first part (Sample A) was directly placed into the medium. Sample B was prepared by being crushed in a sterile package. Sample C was prepared on the auxiliary swester table, and Sample D was prepared on the main swester table actively used by surgery team. All samples were transferred in a 1 ml brain heart(BH) liquid medium. From each BH medium, 100 µl culture was performed on blood agar, eosin-methylene blue-lactose-sucrose agar and chocolate agar. RESULTS: Bacterial growth was detected in 2 of the samples A, in 4 of the samples B, in 24 of the samples C, and in 36 of the samples D. The number of patients with bacterial growth in the samples C and/or D despite no growth in the sample B was 35. When the samples A/B and C/D were compared in terms of bacterial growth, a significant difference was found in all matchings (p < 0.001 for all comparisons).  CONCLUSION: These findings showed that preparation of the cartilage grafts on the swester table was extremely risky for microbiological contamination. Arslan and his colleagues suggest that preparing a graft material in a sterile package is extremely simple, cheap, and it also reduces contamination risk significantly.

Results of minimally invasive surgical treatment of allograft lithiasis in live-donor renal transplant recipients: a single-center experience of 3758 renal transplantations.

Allograft lithiasis is a rare urologic complication of renal transplantation (RT). Our aim is to present our experience with minimally invasive surgical treatment of allograft lithiasis in our series of live-donor renal transplant recipients. In a retrospective analysis of 3758 consecutive live-donor RTs performed in our center between November 2009 and January 2017, the results of minimally invasive surgery for the treatment of renal graft lithiasis diagnosed at follow-up were evaluated. Twenty-two (0.58%) patients underwent minimally invasive surgery for renal graft lithiasis. The mean age was 41.6 years, and duration between RT and surgical intervention was 27.3 months (range 3-67). The mean stone size was 11.6 mm (range 4-29). Stones were located in the urethra in 1, bladder in 2, ureter in 9, renal pelvis in 7 and calices in 3 patients. Surgical treatment included percutaneous nephrolithotomy in 1, cystoscopic lithotripsy in 3, flexible ureteroscopic lithotripsy in 6 and rigid ureteroscopic lithotripsy in 12 patients. No major complications were observed. One patient (4.5%) who underwent flexible ureteroscopy developed postoperative urinary tract infection. All patients were stone-free except two (9%) patients who required a second-look procedure after flexible ureteroscopic lithotripsy for residual stones. Stone recurrence was not observed in any patient during a mean follow-up duration of 30.2 months (range 8-84). Renal transplant lithiasis is uncommon and minimally invasive surgical treatment is rarely performed for its treatment. Endourological surgery may be performed safely, effectively and with a high success rate in these patients.

The effect of nasal polyposis related nasal obstruction on cognitive functions.

Chronic rhinosinusitis with nasal polyposis is a chronic inflammatory disease of the respiratory mucosa of the nasal cavity and paranasal sinuses. The aim of this study was investigate the effect of nasal obstruction related to chronic rhinosinusitis with nasal polyposis on cognitive functions. Patients with chronic rhinosinusitis with nasal polyposis causing bilateral total or near total nasal obstruction were enrolled in the study. Symptoms of nasal congestion, loss of smell, postnasal drip, headaches, snoring, concentration difficulties and blunted affect were evaluated by Visual Analog Scale. Brief symptom inventory test, Stroop test, visual aural digit span, serial digit learning test and P300 test were used to evaluate cognitive functions. Three months after treatment, the tests done before surgery were repeated and the results were compared. A total of 30 patients were included in the study. On the Visual Analog Scale, all symptoms showed significant postoperative improvement in all patients (p < 0.001 for all symptoms). Preoperative nasal congestion accompanied with impaired concentration were detected in 27 patients (90%), and these symptoms recovered in all these patients after treatment (p = 0.035) (correlation coefficient 0.4). Only 22 patients completed the neuropsychological tests. The mean preoperative Stroop test (23.16 ± 5.30), visual aural digit span test (24.68 ± 3.52), and serial digit learning test (16.18 ± 5.35) scores were showed significant improvement compared with mean postoperative Stroop test (21.12 ± 5.69), visual aural digit span test (26.45 ± 2.98), and serial digit learning test (19.31 ± 4.47) scores (p = 0.047, p = 0.022, p = 0.005 respectively). The postoperative P300 latency values improved in 19 (63%) patients. The preoperative and postoperative latency values for P300 showed a significant difference (p = 0.029), whereas the preoperative and postoperative amplitude values for P300 did not differ (p = 0.096). In conclusion, the results of this study indicate that chronic rhinosinusitis with nasal polyposis (CRSwNP) has negative effects on cognitive functions, such as the ability to focus and maintain concentration. These cognitive functions improve after the patients undergo endoscopic sinus surgery to treat their CRSwNP.

Overexpression of a conserved HSP40 chaperone reduces toxicity of several neurodegenerative disease proteins.

TDP-43 and FUS are DNA/RNA binding proteins associated with neuronal inclusions in amyotrophic lateral sclerosis (ALS) patients. Other neurodegenerative diseases are also characterized by neuronal protein aggregates, e.g. Huntington's disease, associated with polyglutamine (polyQ) expansions in the protein huntingtin. Here we discuss our recent paper establishing similarities between aggregates of TDP-43 that have short glutamine and asparagine (Q/N)-rich modules and are soluble in detergents, with those of polyQ and PIN4C that have large Q/N-rich domains and are detergent-insoluble. We also present new, similar data for FUS. Together, we show that like overexpression of polyQ or PIN4C, overexpression of FUS or TDP-43 causes inhibition of the ubiquitin proteasome system (UPS) and toxicity, both of which are mitigated by overexpression of the Hsp40 chaperone Sis1. Also, in all cases toxicity is enhanced by the [PIN+] prion. In addition, we show that the Sis1 mammalian homolog DNAJBI reduces toxicity arising from overexpressed FUS and TDP-43 respectively in human embryonic kidney cells and primary rodent neurons. The common properties of these proteins suggest that heterologous aggregates may enhance the toxicity of a variety of disease-related aggregating proteins, and further that chaperones and the UPS may be key therapeutic targets for diseases characterized by protein inclusions.

A Practical Suggestion for Prepare Dorsal Onlay Graft.

Nowadays, rhinoplasty is one of the most popular surgical procedures. Dorsal contour irregularities caused by various maneuvers, such as hump resection, are a major concern in patients who have undergone rhinoplasty. The most common graft used in this case is dorsal onlay graft which is made from sliced and crushed cartilage. Ear, nose and throat specialists usually use Swester table (mayo desk) for preparing the graft, if there is no other steril metal instrument. Crushed cartilage is done on a sterile gauze or on the tables' cover, as a result cartilage may be contaminated with particules from the tables' cover and sterile gauze.The authors recommend using the steril pack of a new sterilized surgical instrument opened on the table for the slicing or crushing process. In this way, the cartilage can be spared from contamination and the loss of some cartilage to the table during slicing or crushing can be prevented.

Statins Promote Cardiac Infarct Healing by Modulating Endothelial Barrier Function Revealed by Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE: The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI). APPROACH AND RESULTS: Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE-/-, and statin-treated ApoE-/- mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE-/- infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE-/- infarcts, indicated by reduced permeability. The infarcted tissue of ApoE-/- mice 3 days post-MI displayed an unbalanced Vegfa(vascular endothelial growth factor A)/Angpt1 (angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45+ leukocytes and inflammatory LY6Chi monocytes. Statins reversed the unbalanced Vegfa/Angpt1 expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE-/- mice. CONCLUSIONS: Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.

Leukocytic Toll-Like Receptor 2 Deficiency Preserves Cardiac Function And Reduces Fibrosis In Sustained Pressure Overload.

An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure overload. We induced pressure overload via transverse aortic constriction (TAC) in TLR2-/- and wild type (WT) mice, and followed temporal changes over 8 weeks. Despite similar increases in heart weight, left ventricular (LV) ejection fraction (EF) and diastolic function (mitral E/A ratio) were preserved in TLR2-/- mice but impaired in WT mice following TAC. TAC produced less LV fibrosis in TLR2-/- mice associated with lower mRNA levels of collagen genes (Col1a1 and Col3a1) and lower protein level of TGFbeta1, compared to WT mice. Following TAC, the influx of macrophages and CD3 T cells into LV was similar between TLR2-/- and WT mice, whereas levels of cyto/chemokines were lower in the heart and plasma in TLR2-/- mice. TLR2-/- bone marrow-derived cells protected against LVEF decline and fibrosis following TAC. Our findings show that leukocytic TLR2 deficiency protects against LV dysfunction and fibrosis probably via a reduction in inflammatory signaling in sustained pressure overload.

Bilateral Nasoalveolar Cyst Causing Nasal Obstruction.

Nasoalveolar cysts, which originate from epithelial remnants of nasolacrimal duct, are nonodontogenic soft tissue lesions of the upper jaw. These cysts are thought to be developmental and are presented with fullness in the upper lip and nose, swelling on the palate, and sometimes nasal obstruction. Because of cosmetic problems, they are often diagnosed at an early stage. These lesions are mostly revealed unilaterally but also can be seen on both sides. In this case report, a patient who complained of nasal obstruction and then diagnosed with bilateral nasoalveolar cysts and treated by sublabial excision is presented and clinical features and treatment approaches are discussed with the review of literature.

Effects of Nasal Obstruction due to Nasal Polyposis on Nasal Resonance and Voice Perception.

OBJECTIVE: The aim of this study was to use subjective and objective methods to investigate the effects of total or nearly total nasal obstruction due to nasal polyposis on nasal resonance and voice perception. PATIENTS AND METHODS: A total of 63 nasal polyposis patients (53 men and 10 women), aged between 19 and 72 years (mean age 37.01 ± 13.70), were included in the study. The severity of the nasal obstruction was assessed using a visual analog scale. Nasal resonance and voice perception were evaluated subjectively by the voice handicap index (VHI)-10 questionnaire and objectively by computerized analysis (nasometry) before and after treatment of patients with nasal polyposis. RESULTS: Significant improvement was seen in the nasal obstruction values in all patients (100%; p < 0.001) and in the VHI-10 scores in 62 patients (98%; p < 0.001). Nasalance scores increased in all patients following treatment (100%; p < 0.001). CONCLUSION: Voice perception is negatively affected by nasal obstruction due to nasal polyposis, and changes in voice perception may arise after the surgery. Before the surgery, informing the patient about potential voice perception changes may be useful for the prevention of legal disputes.

Fractalkine receptor polymorphism and chronic tonsillitis.

The objective of this study is to examine whether there is an association of fractalkine gene receptor polymorphisms with chronic tonsillitis. This is a cross-sectional study in the setting of a tertiary referral center. The study group included 79 patients with chronic tonsillitis and 76 controls without history of chronic tonsillitis. Genotypes were identified by restriction fragment length polymorphism analyses after polymerase chain reaction. c.745G>A (V249I) single nucleotide polymorphism and the frequencies of the G and A alleles did not differ in the patient and control groups (p = 0.363; p = 0.743, respectively). c.839C>T (T280M) single nucleotide polymorphism was found to be higher in controls than in the patients with chronic tonsillitis (p < 0.001). Consistent with this result, T allele frequency was higher in controls than in the patients with chronic tonsillitis (p < 0.001). In this study, we suggested that fractalkine gene receptor c.839C>T (T280M) single nucleotide polymorphism could be associated with a reduced risk of chronic tonsillitis.

Surgical treatment of carotid body tumors.

OBJECTIVES: In this study, we report our clinical experience in a series of patients with carotid body tumors along with diagnosis, treatment and follow-up procedures in the light of related literature data. PATIENTS AND METHODS: Between November 2001 and May 2012, 10 patients (5 males, 5 females; mean age 53.2 years; range 27 to 80 years) who underwent surgery due to a carotid body tumor in our clinic were included. Diagnosis was based on ultrasonography, computed tomography, magnetic resonance imaging, magnetic resonance angiography, selective carotid angiography, balloon occlusion test, biochemical tests and preoperative embolization. Complications were also recorded. RESULTS: Balloon occlusion test was performed in all patients preoperatively, while embolization was implemented in seven patients. All masses were dissected by carotid artery subadventitial approach. Carotid integrity was maintained in nine patients, while a vein graft was used in one patient. Neurological disorder was observed in one patient, whereas transient hypoglossal paresis was in one patient who underwent saphenous vein grafting. CONCLUSION: Our study results suggest that (i) carotid body tumors should be handled with multidisciplinary approach; (ii) balloon occlusion test should be performed in all patients undergoing surgery; (iii) a particular attention should be paid to cranial and phrenic nerves, if it is necessary to extend the surgical field while removing the tumor; and (iv) pathological examination should be carried out by an experienced team and in a multi-centered fashion, if necessary.

Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function.

RATIONALE: Mesenchymal precursor cells (MPCs) are a specific Stro-3+ subpopulation of mesenchymal stem cells isolated from bone marrow. MPCs exert extensive cardioprotective effects, and are considered to be immune privileged. OBJECTIVE: This study assessed the safety, feasibility, and efficacy of intracoronary delivery of allogeneic MPCs directly after acute myocardial infarction in sheep. METHODS AND RESULTS: Initially, intracoronary delivery conditions were optimized in 20 sheep. These conditions were applied in a randomized study of 68 sheep with an anterior acute myocardial infarction. Coronary flow was monitored during MPC infusion, and cardiac function was assessed using invasive hemodynamics and echocardiography at baseline and during 8 weeks follow-up. Coronary flow remained within thrombolysis in myocardial infarction III definitions in all sheep during MPC infusion. Global left ventricular ejection fraction as measured by pressure-volume loop analysis deteriorated in controls to 40.7±2.6% after 8 weeks. In contrast, MPC treatment improved cardiac function to 52.8±0.7%. Echocardiography revealed significant improvement of both global and regional cardiac functions. Infarct size decreased by 40% in treated sheep, whereas infarct and border zone thickness were enhanced. Left ventricular adverse remodeling was abrogated by MPC therapy, resulting in a marked reduction of left ventricular volumes. Blood vessel density increased by >50% in the infarct and border areas. Compensatory cardiomyocyte hypertrophy was reduced in border and remote segments, accompanied by reduced collagen deposition and apoptosis. No microinfarctions in remote myocardial segments or histological abnormalities in unrelated organs were found. CONCLUSIONS: Intracoronary infusion of allogeneic MPCs is safe, feasible, and markedly effective in a large animal model of acute myocardial infarction.