Influence of Heart Rate and Change in Wavefront Direction through Pacing on Conduction Velocity and Voltage Amplitude in a Porcine Model: A High-Density Mapping Study.

BACKGROUND: Understanding the dynamics of conduction velocity (CV) and voltage amplitude (VA) is crucial in cardiac electrophysiology, particularly for substrate-based catheter ablations targeting slow conduction zones and low voltage areas. This study utilizes ultra-high-density mapping to investigate the impact of heart rate and pacing location on changes in the wavefront direction, CV, and VA of healthy pig hearts. METHODS: We conducted in vivo electrophysiological studies on four healthy juvenile pigs, involving various pacing locations and heart rates. High-resolution electroanatomic mapping was performed during intrinsic normal sinus rhythm (NSR) and electrical pacing. The study encompassed detailed analyses at three levels: entire heart cavities, subregions, and localized 5-mm-diameter circular areas. Linear mixed-effects models were used to analyze the influence of heart rate and pacing location on CV and VA in different regions. RESULTS: An increase in heart rate correlated with an increase in conduction velocity and a decrease in voltage amplitude. Pacing influenced conduction velocity and voltage amplitude. Pacing also influenced conduction velocity and voltage amplitude, with varying effects observed based on the pacing location within different heart cavities. Pacing from the right atrium (RA) decreased CV in all heart cavities. The overall CV and VA changes in the whole heart cavities were not uniformly reflected in all subregions and subregional CV and VA changes were not always reflected in the overall analysis. Overall, there was a notable variability in absolute CV and VA changes attributed to pacing. CONCLUSIONS: Heart rate and pacing location influence CV and VA within healthy juvenile pig hearts. Subregion analysis suggests that specific regions of the heart cavities are more susceptible to pacing. High-resolution mapping aids in detecting regional changes, emphasizing the substantial physiological variations in CV and VA.

[Isthmus-dependent right atrial flutter : Clinical course after isthmus ablation]. / Rechtsatriales isthmusabhängiges Vorhofflattern : Klinischer Verlauf nach Isthmusablation.

Ablation of the cavotricuspid isthmus (CTI) to create bidirectional isthmus blockade is the most effective way to achieve rhythm control in typical atrial flutter. Compared with drug therapy, ablation reduces cardiovascular mortality, all-cause mortality, stroke risk, and the risk of cardiac decompensation. Concomitant arrhythmia of atrial flutter is atrial fibrillation (AF); therefore the duration of oral anticoagulation should be adapted according to the risk of stroke and bleeding. A combined procedure of CTI ablation and pulmonary vein isolation (PVI) in patients with typical atrial flutter but without evidence of AF should be evaluated individually especially in patients aged > 54 years depending on (cardiac) comorbidities. The comprehensive diagnostic view should keep in mind not only arrhythmias but also possibly underlying coronary artery disease.

Electroanatomical Conduction Characteristics of Pig Myocardial Tissue Derived from High-Density Mapping.

BACKGROUND: Ultra-high-density mapping systems allow more precise measurement of the heart chambers at corresponding conduction velocities (CVs) and voltage amplitudes (VAs). Our aim for this study was to define and compare a basic value set for unipolar CV and VA in all four heart chambers and their separate walls in healthy, juvenile porcine hearts using ultra-high-density mapping. METHODS: We used the Rhythmia Mapping System to create electroanatomical maps of four pig hearts in sinus rhythm. CVs and VAs were calculated for chambers and wall segments with overlapping circular areas (radius of 5 mm). RESULTS: We analysed 21 maps with a resolution of 1.4 points/mm2. CVs were highest in the left atrium (LA), followed by the left ventricle (LV), right ventricle (RV), and right atrium (RA). As for VA, LV was highest, followed by RV, LA, and RA. The left chambers had a higher overall CV and VA than the right. Within the chambers, CV varied more in the right than in the left chambers, and VA varied in the ventricles but not in the atria. There was a slightly positive correlation between CVs and VAs at velocity values of <1.5 m/s. CONCLUSIONS: In healthy porcine hearts, the left chambers showed higher VAs and CVs than the right. CV differs mainly within the right chambers and VA differs only within the ventricles. A slightly positive linear correlation was found between slow CVs and low VAs.

Structured Reporting in Cross-Sectional Imaging of the Heart: Reporting Templates for CMR Imaging of Ischemia and Myocardial Viability and for Cardiac CT Imaging of Coronary Heart Disease and TAVI Planning. / Strukturierte Befundung in der Schnittbilddiagnostik des Herzens: Befundvorlagen für die Herz-MRT bezüglich Ischämie- und Vitalitätsdiagnostik sowie für die Herz-CT bezüglich Koronardiagnostik und Planung vor TAVI.

BACKGROUND: Structured reporting allows a high grade of standardization and thus a safe and unequivocal report communication. In the past years, the radiological societies have started several initiatives to base radiological reports on structured reporting rather than free text reporting. METHODS: Upon invitation of the working group for Cardiovascular Imaging of the German Society of Radiology, in 2018 an interdisciplinary group of Radiologists, Cardiologists, Pediatric Cardiologists and Cardiothoracic surgeons -all experts on the field of cardiovascular MR and CT imaging- met for interdisciplinary consensus meetings at the University Hospital Cologne. The aim of these meetings was to develop and consent templates for structured reporting in cardiac MR and CT of various cardiovascular diseases. RESULTS: Two templates for structured reporting of CMR in ischemia imaging and vitality imaging and two templates for structured reporting of CT imaging for planning Transcatheter Aortic Valve Implantation (TAVI; pre-TAVI-CT) and coronary CT were discussed, consented and transferred to a HTML 5/IHR MRRT compatible format. The templates were made available for free use on the website www.befundung.drg.de. CONCLUSION: This paper suggests consented templates in German language for the structured reporting of cross-sectional CMR imaging of ischemia and vitality as well as reporting of CT imaging pre-TAVI and coronary CT. The implementation of these templates is aimed at providing a constant level of high reporting quality and increasing the efficiency of report generation as well as a clinically based communication of imaging results. KEY POINTS: · Structured reporting offers a constant level of high reporting quality and increases the efficiency of report generation as well as a clinically based communication of imaging results.. · For the first time templates in German language for the structured reporting of CMR imaging of ischemia and vitality and CT imaging pre-TAVI and coronary CT are reported.. · These templates will be made available on the website www.befundung.drg.de and can be commented via strukturierte-befundung@drg.de.. ZITIERWEISE: · Soschynski M, Bunck AC, Beer M et al. Structured Reporting in Cross-Sectional Imaging of the Heart: Reporting Templates for CMR Imaging of Ischemia and Myocardial Viability and for Cardiac CT Imaging of Coronary Heart Disease and TAVI Planning. Fortschr Röntgenstr 2023; 195: 293 - 296.

Potential of remote monitoring to prevent sensing and detection failures in implantable cardioverter defibrillators.

BACKGROUND: Sensing malfunction and misinterpretation of intracardiac electrograms (IEGMs) in patients with implantable cardioverter defibrillators (ICDs) may lead to inadequate device activity such as inappropriate shock delivery or unnecessary mode-switching. Remote monitoring has the potential for early detection of sensing malfunction or misclassification and may thus prevent adverse device activity. Therefore, the authors analyzed the amount, nature, and distribution of misclassification in current ICD and cardiac resynchronization therapy defibrillator technology using the device transmissions of the IN-TIME study population. METHODS: All transmitted tachyarrhythmic episodes in the 664 IN-TIME patients, comprising 2214 device-classified atrial fibrillation (DC-AF) episodes lasting ≥ 30 s and 1330 device-classified ventricular tachycardia or fibrillation (DC-VT/VF) episodes, were manually analyzed by two experienced cardiologists. RESULTS: After evaluation of all DC-VT/VF episodes, a total of 300 VT/VF events (23.1%) were false-positive, with supraventricular tachycardia being the most frequent cause (51.7%), followed by atrial fibrillation (21.3%) and T­wave oversensing (21.0%). A total of 15 patients with false-positive DC-VT/VF received inappropriate shocks. According to the inclusion criteria, 616 IEGMs with DC-AF were assessed. A total of 19.7% were false-positive AF episodes and R­wave oversensing was the most common reason (55.9%). CONCLUSIONS: Remote monitoring offers the opportunity of early detection of signal misclassification and thus early prevention of adverse device reaction, such as inappropriate shock delivery or mode-switching with intermittent loss of atrioventricular synchrony, by correcting the underlying causes.

Virtual Reality Analysis of Three-Dimensional Echocardiographic and Cardiac Computed Tomographic Data Sets.

BACKGROUND: Three-dimensional echocardiographic (3DE) imaging and cardiac computed tomographic (CCT) imaging are important cardiac imaging tools. Despite the three-dimensional nature of these image acquisitions and reconstructions, they are visualized on two-dimensional monitors with shading and coloring to create the illusion of three dimensions. Virtual reality (VR) is a novel tool that allows true three-dimensional visualization and manipulation. The aims of this study were to test the feasibility of converting 3DE and CCT data into three-dimensional VR models, compare the variability of measurements performed in VR and conventional software, assess the diagnostic quality of VR models, and understand the value of VR over conventional viewing. METHODS: Custom software with clinically relevant postprocessing tools (interactively adjustable visualization parameters, multiplanar reconstructions, cropping planes, and nonplanar measurements) was developed to convert 3DE and CCT data into VR models. Anatomic measurements of 15 3DE and 15 CCT data sets of the mitral valve were compared using conventional software and in the VR environment. Additionally, the diagnostic quality of the VR models created from 3DE and CCT data sets was assessed. RESULTS: The 3DE and CCT data sets were successfully converted into VR models in <3 min. The measurement variabilities were reduced by 40% (20.1% vs 12.2%) for 3DE imaging and 34% (15.3% vs 10.1%) for CCT imaging by using VR. The mean time needed for measurements was reduced by 31% (from 61 to 42 sec) for 3DE imaging and 39% (from 37 to 23 sec) for CCT imaging. Most users reported facile manipulation of VR models, diagnostic quality visualization of the anatomy, and high confidence in the measurements. CONCLUSIONS: This study demonstrates the feasibility of converting 3DE and CCT data into diagnostic-quality VR models. Compared with conventional imaging, VR analysis is associated with faster navigation and accurate measurements with lower variability.

Preparation of PCI Balloons: What Is the Best Method to Avoid Air in the Balloon? A Comparison of Different Methods of Connecting PCI Balloons and the Inflation Syringe while Removing Air from the Balloon.

As the techniques to connect percutaneous coronary intervention (PCI) balloons and the inflation syringe vary in the instructions for use and in practice, we measured the amount of air in PCI balloons after testing three connection methods to an inflation syringe. Following the preparation using one of the three methods, 114 balloons and stent balloons were tested four times. Method 1 connected the syringe and the balloon catheter directly after purging and filling the lumen, while method 3 omitted the purging and filling process. With method 2, the catheter lumen was purged, filled and fully vented via a three-way valve. The primary endpoint answered whether air remained in the balloon, and if so, the secondary endpoint indicated the total volume of remaining air. The connection with a three-way valve achieved significantly less air in the inflated balloon as compared with either direct connection approach (27% vs. 44% and 51%; p = 0.015). For the direct connection, no significant difference between purging and filling the lumen prior to making the connection or not existed. According to these findings, the best method to connect a PCI balloon to the inflation syringe while removing air involves using a three-way valve.

Structured Reporting in Cross-Sectional Imaging of the Heart: Reporting Templates for CMR Imaging of Cardiomyopathies (Myocarditis, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Siderosis). / Strukturierte Befundung in der Schnittbilddiagnostik des Herzens: Befundvorlagen für die MRT bei Kardiomyopathien (Myokarditis, dilatative Kardiomyopathie, hypertrophe Kardiomyopathie, arrhythmogene rechtsventrikuläre Kardiomyopathie und Siderose).

BACKROUND: Structured reports have numerous benefits through standardizing the way imaging findings are reported and communicated. Nevertheless, the adoption of structured reports in everyday radiological practice is still limited. In view of the irrefutable benefits, various national and international radiological societies have started initiatives which aim at promoting a broader use of structured reports. Up to now, no consented templates in German language existed for the reporting of cross-sectional imaging studies of the heart. METHOD: Upon invitation of the working group for Cardiovascular Imaging of the German Society of Radiology a panel of radiologists, cardiologists, pediatric cardiologists and cardiothoracic surgeons, experts on the field of cardiovascular imaging and structured reporting, met for two interdisciplinary consensus meetings at the University Hospital Cologne in 2018. The aim of these meetings was to develop and agree on templates for the reporting of MR and CT studies of various cardiovascular disease entities. RESULTS: During the meetings the panel of experts developed and reached consensus on 11 different templates for the structured reporting of the following: myocarditis, dilated cardiomyopathy, hypertrophic (obstructive) cardiomyopathy, arrythmogenic right ventricular cardiomyopathy, siderosis, ischemia and vitality imaging, tetralogy of Fallot, aortic coarctation, coronary CT and CT for Transcatheter Aortic Valve Implantation (TAVI) planning. The first five templates are presented in this publication and are currently being transferred to a HTML 5/IHR MRRT compatible format. Subsequently, the templates will be made available for free use on the website www.befundung.drg.de. CONCLUSION: For the first time, consented templates in German language for the structured reporting of cross-sectional imaging studies of the heart are presented. These templates are aimed at providing a constant level of high reporting quality and increasing the efficiency of the generation and communication of imaging reports. KEY POINTS: · Structured reporting offers numerous benefits by standardizing generation and communication of imaging reports.. · For the first time templates in German language for the structured reporting of CMR imaging studies of cardiomyopathies are presented. · These templates will be made available on the website www.befundung.drg.de and can be commented via agit-sr@googlegroups.com.. CITATION FORMAT: · Bunck AC, Baeßler B, Ritter C et al. Structured Reporting in Cross-Sectional Imaging of the Heart: Reporting Templates for CMR Imaging of Cardiomyopathies (Myocarditis, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular cardiomyopathy and Siderosis). Fortschr Röntgenstr 2020; 192: 27 - 37.

Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies.

The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of this therapy. Besides an assessment of the effectiveness of the therapy in specific patients groups, comparisons with pharmacological stroke prophylaxis, surgical approaches, and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies, and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available.

Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints and data collection requirements for clinical studies.

The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of this therapy. Besides an assessment of the effectiveness of the therapy in specific patient groups, comparisons with pharmacological stroke prophylaxis, surgical approaches and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available.

Sphingosine-1-Phosphate Receptor 1 Regulates Cardiac Function by Modulating Ca2+ Sensitivity and Na+/H+ Exchange and Mediates Protection by Ischemic Preconditioning.

BACKGROUND: Sphingosine-1-phosphate plays vital roles in cardiomyocyte physiology, myocardial ischemia-reperfusion injury, and ischemic preconditioning. The function of the cardiomyocyte sphingosine-1-phosphate receptor 1 (S1P1) in vivo is unknown. METHODS AND RESULTS: Cardiomyocyte-restricted deletion of S1P1 in mice (S1P1 (α) (MHCC) (re)) resulted in progressive cardiomyopathy, compromised response to dobutamine, and premature death. Isolated cardiomyocytes from S1P1 (α) (MHCC) (re) mice revealed reduced diastolic and systolic Ca(2+) concentrations that were secondary to reduced intracellular Na(+) and caused by suppressed activity of the sarcolemmal Na(+)/H(+) exchanger NHE-1 in the absence of S1P1. This scenario was successfully reproduced in wild-type cardiomyocytes by pharmacological inhibition of S1P1 or sphingosine kinases. Furthermore, Sarcomere shortening of S1P1 (α) (MHCC) (re) cardiomyocytes was intact, but sarcomere relaxation was attenuated and Ca(2+) sensitivity increased, respectively. This went along with reduced phosphorylation of regulatory myofilament proteins such as myosin light chain 2, myosin-binding protein C, and troponin I. In addition, S1P1 mediated the inhibitory effect of exogenous sphingosine-1-phosphate on ß-adrenergic-induced cardiomyocyte contractility by inhibiting the adenylate cyclase. Furthermore, ischemic precondtioning was abolished in S1P1 (α) (MHCC) (re) mice and was accompanied by defective Akt activation during preconditioning. CONCLUSIONS: Tonic S1P1 signaling by endogenous sphingosine-1-phosphate contributes to intracellular Ca(2+) homeostasis by maintaining basal NHE-1 activity and controls simultaneously myofibril Ca(2+) sensitivity through its inhibitory effect on adenylate cyclase. Cardioprotection by ischemic precondtioning depends on intact S1P1 signaling. These key findings on S1P1 functions in cardiac physiology may offer novel therapeutic approaches to cardiac diseases.

Imaging Reveals the Connection Between Spontaneous Coronary Plaque Ruptures, Atherothrombosis, and Myocardial Infarctions in HypoE/SRBI-/- Mice.

UNLABELLED: The hyperlipidemic mouse model HypoE/SRBI(-/-) has been shown to develop occlusive coronary atherosclerosis followed by myocardial infarctions and premature deaths in response to high-fat, high-cholesterol diet (HFC). However, the causal connection between myocardial infarctions and atherosclerotic plaque rupture events in the coronary arteries has not been investigated so far. The objective of this study was to assess whether diet-induced coronary plaque ruptures trigger atherothrombotic occlusions, resulting in myocardial infarctions in HFC-fed HypoE/SRBI(-/-) mice. METHODS: HypoE/SRBI(-/-) mice were characterized with respect to the individual dynamics of myocardial infarctions and features of infarct-related coronary atherosclerosis by serial noninvasive molecular and functional imaging, histopathology, and a pharmaceutical intervention. Detailed histologic analysis of whole mouse hearts was performed when spontaneously occurring acute myocardial infarctions were diagnosed by imaging. RESULTS: Using the imaging-triggered approach, we discovered thrombi in 32 (10.8%) of all 296 atherosclerotic coronary plaques in 14 HFC-fed HypoE/SRBI(-/-) mice. These thrombi typically were found in arteries presenting with inflammatory plaque phenotypes. Acetylsalicylic acid treatment did not attenuate the development of atherosclerotic coronary plaques but profoundly reduced the incidence of premature deaths, the number of thrombi (7 in 249 plaques), and also the degree of inflammation in the culprit lesions. CONCLUSION: HFC-induced ruptures of coronary plaques trigger atherothrombosis, vessel occlusions, myocardial infarctions, and sudden death in these mice. Thus, the HypoE/SRBI(-/-) mouse model mimics major features of human coronary heart disease and might therefore be a valuable model for the investigation of molecular and cellular parameters driving plaque rupture-related events and the development of new interventional approaches.

Soluble Flt-1 links microvascular disease with heart failure in CKD.

Chronic kidney disease (CKD) is associated with an increased risk of heart failure (HF). Elevated plasma concentrations of soluble Flt-1 (sFlt-1) have been linked to cardiovascular disease in CKD patients, but whether sFlt-1 contributes to HF in CKD is still unknown. To provide evidence that concludes a pathophysiological role of sFlt-1 in CKD-associated HF, we measured plasma sFlt-1 concentrations in 586 patients with angiographically documented coronary artery disease and renal function classified according to estimated glomerular filtration rate (eGFR). sFlt-1 concentrations correlated negatively with eGFR and were associated with signs of heart failure, based on New York Heart Association functional class and reduced left ventricular ejection fraction (LVEF), and early mortality. Additionally, rats treated with recombinant sFlt-1 showed a 15 % reduction in LVEF and a 29 % reduction in cardiac output compared with control rats. High sFlt-1 concentrations were associated with a 15 % reduction in heart capillary density (number of vessels/cardiomyocyte) and a 24 % reduction in myocardial blood volume. Electron microscopy and histological analysis revealed mitochondrial damage and interstitial fibrosis in the hearts of sFlt-1-treated, but not control rats. In 5/6-nephrectomised rats, an animal model of CKD, sFlt-1 antagonism with recombinant VEGF121 preserved heart microvasculature and significantly improved heart function. Overall, these findings suggest that a component of cardiovascular risk in CKD patients could be directly attributed to sFlt-1. Assessment of patients with CKD confirmed that sFlt-1 concentrations were inversely correlated with renal function, while studies in rats suggested that sFlt-1 may link microvascular disease with HF in CKD.

The endocannabinoid-CB2 receptor axis protects the ischemic heart at the early stage of cardiomyopathy.

Ischemic heart disease is associated with inflammation, interstitial fibrosis and ventricular dysfunction prior to the development of heart failure. Endocannabinoids and the cannabinoid receptor CB2 have been claimed to be involved, but their potential role in cardioprotection is not well understood. We therefore explored the role of the cannabinoid receptor CB2 during the initial phase of ischemic cardiomyopathy development prior to the onset of ventricular dysfunction or infarction. Wild type and CB2-deficient mice underwent daily brief, repetitive ischemia and reperfusion (I/R) episodes leading to ischemic cardiomyopathy. The relevance of the endocannabinoid-CB2 receptor axis was underscored by the finding that CB2 was upregulated in ischemic wild type cardiomyocytes and that anandamide level was transiently increased during I/R. CB2-deficient mice showed an increased rate of apoptosis, irreversible loss of cardiomyocytes and persistent left ventricular dysfunction 60 days after the injury, whereas wild type mice presented neither morphological nor functional defects. These defects were due to lack of cardiomyocyte protection mechanisms, as CB2-deficient hearts were in contrast to controls unable to induce switch in myosin heavy chain isoforms, antioxidative enzymes and chemokine CCL2 during repetitive I/R. In addition, a prolonged inflammatory response and adverse myocardial remodeling were found in CB2-deficient hearts because of postponed activation of the M2a macrophage subpopulation. Therefore, the endocannabinoid-CB2 receptor axis plays a key role in cardioprotection during the initial phase of ischemic cardiomyopathy development.

Ultrasound-mediated gene delivery of naked plasmid DNA in skeletal muscles: a case for bolus injections.

Localized gene delivery has many potential clinical applications. However, the nucleic acids (e.g. pDNA and siRNA) are incapable of passively crossing the endothelium, cell membranes and other biological barriers which must be crossed to reach their intracellular targets. A possible solution is the use of ultrasound to burst circulating microbubbles inducing transient permeabilization of surrounding tissues which mediates nucleic acid extravasation and cellular uptake. In this study we report on an optimization of the ultrasound gene delivery technique. Naked pDNA (200 µg) encoding luciferase and SonoVue® microbubbles were co-injected intravenously in mice. The hindlimb skeletal muscles were exposed to ultrasound from a non-focused transducer (1 MHz, 1.25 MPa, PRI 30s) and injection protocols and total amounts as well as ultrasound parameters were systemically varied. Gene expression was quantified relative to a control using a bioluminescence camera system at day 7 after sonication. Bioluminescence ratios in sonicated/control muscles of up to 101× were obtained. In conclusion, we were able to specifically deliver genetic material to the selected skeletal muscles and overall, the use of bolus injections and high microbubble numbers resulted in increased gene expression reflected by stronger bioluminescence signals. Based on our data, bolus injections seem to be required in order to achieve transient highly concentrated levels of nucleic acids and microbubbles at the tissue of interest which upon ultrasound exposure should lead to increased levels of gene delivery. Thus, ultrasound mediated gene delivery is a promising technique for the clinical translation of localized drug delivery.

Cardioprotective effects of osteopontin-1 during development of murine ischemic cardiomyopathy.

Repetitive brief ischemia and reperfusion (I/R) is associated with ventricular dysfunction in pathogenesis of murine ischemic cardiomyopathy and human hibernating myocardium. We investigated the role of matricellular protein osteopontin-1 (OPN) in murine model of repetitive I/R. One 15-min LAD-occlusion followed by reperfusion was performed daily over 3, 5, and 7 consecutive days in C57/Bl6 wildtype- (WT-) and OPN(-/-)-mice (n = 8/group). After echocardiography hearts were processed for histological and mRNA-studies. Cardiac fibroblasts were isolated, cultured, and stimulated with TGF- ß 1. WT-mice showed an early, strong, and cardiomyocyte-specific osteopontin-expression leading to interstitial macrophage infiltration and consecutive fibrosis after 7 days I/R in absence of myocardial infarction. In contrast, OPN(-/-)-mice showed small, nontransmural infarctions after 3 days I/R associated with significantly worse ventricular dysfunction. OPN(-/-)-mice had different expression of myocardial contractile elements and antioxidative mediators and a lower expression of chemokines during I/R. OPN(-/-)-mice showed predominant collagen deposition in macrophage-rich small infarctions. We found lower induction of tenascin-C, MMP-9, MMP-12, and TIMP-1, whereas MMP-13-expression was higher in OPN(-/-)-mice. Cultured OPN(-/-)-myofibroblasts confirmed these findings. In conclusion, osteopontin seems to modulate expression of contractile elements, antioxidative mediators, and inflammatory response and subsequently remodel in order to protect cardiomyocytes in murine ischemic cardiomyopathy.