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Ubiquinol cytochrome c reductase hinge protein (UQCRH) is required for the electron transfer between cytochrome c1 and c of the mitochondrial cytochrome bc1 Complex (CIII). A two-exon deletion in the human UQCRH gene has recently been identified as the cause for a rare familial mitochondrial disorder. Deletion of the corresponding gene in the mouse (Uqcrh-KO) resulted in striking biochemical and clinical similarities including impairment of CIII, failure to thrive, elevated blood glucose levels, and early death. Here, we set out to test how global ablation of the murine Uqcrh affects cardiac morphology and contractility, and bioenergetics. Hearts from Uqcrh-KO mutant mice appeared macroscopically considerably smaller compared to wildtype littermate controls despite similar geometries as confirmed by transthoracic echocardiography (TTE). Relating TTE-assessed heart to body mass revealed the development of subtle cardiac enlargement, but histopathological analysis showed no excess collagen deposition. Nonetheless, Uqcrh-KO hearts developed pronounced contractile dysfunction. To assess mitochondrial functions, we used the high-resolution respirometer NextGen-O2k allowing measurement of mitochondrial respiratory capacity through the electron transfer system (ETS) simultaneously with the redox state of ETS-reactive coenzyme Q (Q), or production of reactive oxygen species (ROS). Compared to wildtype littermate controls, we found decreased mitochondrial respiratory capacity and more reduced Q in Uqcrh-KO, indicative for an impaired ETS. Yet, mitochondrial ROS production was not generally increased. Taken together, our data suggest that Uqcrh-KO leads to cardiac contractile dysfunction at 9 weeks of age, which is associated with impaired bioenergetics but not with mitochondrial ROS production. Graphical abstract Global ablation of the Uqcrh gene results in functional impairment of CIII associated with metabolic dysfunction and postnatal developmental arrest immediately after weaning from the mother. Uqcrh-KO mice show dramatically elevated blood glucose levels and decreased ability of isolated cardiac mitochondria to consume oxygen (O2). Impaired development (failure to thrive) after weaning manifests as a deficiency in the gain of body mass and growth of internal organ including the heart. The relative heart mass seemingly increases when organ mass calculated from transthoracic echocardiography (TTE) is normalized to body mass. Notably, the heart shows no signs of collagen deposition, yet does develop a contractile dysfunction reflected by a decrease in ejection fraction and fractional shortening.

The aim of this study was to compare outcomes of transcatheter and surgical aortic valve implantation in chronic dialysis patients with aortic valve stenosis (AS). Chronic dialysis patients undergoing heart valve surgery are at higher risk for morbidity and mortality. Whether interventional techniques can reduce this risk is unclear because dialysis patients have thus far been excluded from randomized trials. Chronic dialysis patients with AS enrolled in the German Aortic Valve Registry (GARY) between 2012 and 2015 were analyzed to compare transcatheter aortic valve implantation (TAVI n = 661) with surgical aortic valve replacement (SAVR n = 457). Propensity scores for inverse probability of treatment weighting (IPTW) were used to adjust the comparison of the two treatment groups for potential confounders. TAVI patients were older (78 ± 7.3 vs. 69 ± 10.2 years, p

In den letzten Jahren hat sich im therapeutischen Bereich der stabilen koronaren Herzkrankheit (KHK) die folgende Erkenntnis kontinuierlich konsolidiert: Die Bypass-Chirurgie bleibt der Goldstandard bei komplexer KHK, insbesondere bei Dreigefaserkrankung mit oder ohne Hauptstammbeteiligung. Sie ist die einzige Therapieform, die nach den aktuellen Daten das Potenzial birgt, das Leben des Patienten zu verlangern. Die Bypass-Operation kann damit eine prognostische Indikation haben. Die 2018 neu erschienenen Leitlinien zur Myokardrevaskularisation haben die Unterscheidung zur perkutanen Koronarintervention (PCI) jetzt genauer differenziert und geben erstmals Empfehlungen zu operativen Details der Revaskularisation. Der Fokus dieser Literaturubersicht liegt auf den chirurgisch relevanten Aspekten. Weitere therapierelevante Informationen zu Diagnostik und medikamentoser Therapie sind ebenfalls ubersichtlich zusammengefasst. Die aus dem Jahr 2018 masgebliche Literatur zur chirurgischen Revaskularisation lasst sich in folgende Punkte untergliedern: 1. PCI vs. Bypass-Chirurgie, 2. neue diagnostische Verfahren fur die Bypass-Chirurgie, 3. Rolle der medikamentosen Therapie fur die Bypass-Chirurgie und 4. technische Aspekte der Bypass-Chirurgie.

Accurate assessment of the aortic annulus is crucial for successful transcatheter aortic valve replacement (TAVR), in particular to prevent paravalvular regurgitation (PVR). We compared aortic annular sizing using multidetector computed tomography (MDCT) and three-dimensional transoesophageal echocardiography (3-D TEE) to determine the predictive value of MDCT. All patients admitted for transfemoral TAVR [n = 227; 48.9% balloon expandable (Edwards Sapien 3); 51.1% self-expandable (Core Valve, Evolut R)] at our institution from January 2015 until December 2016 were analysed retrospectively. Aortic annular parameters were obtained either by MDCT or 3-D TEE. Additionally, we included a cohort of patients (n = 27) assessed by both MDCT and 3D TEE between October 2017 and April 2018 to enable intra-individual comparison of the two methods. Indications for TAVR were severe degenerative aortic stenosis (AS; 94.7%) or re-stenosis after surgical AVR (5.3%). 74.4% were classified as high-gradient AS. The mean age was 80 (37–94) years and 75.8% presented with NYHA III/IV. STS risk of mortality was intermediate (3.5 ± 2.3). MDCT and 3-D TEE were performed in 116 and 111 patients for aortic annulus sizing, respectively. Significantly larger implants were chosen in the CT group irrespective of prosthesis type or post-dilatation. Follow-up (median at 79 days) revealed significantly less PVR in the MDCT compared to 3-D TEE group (absence of PVR in 59.3% and 40.7%, p = 0.016), without differences in mortality. Patients without PVR or mild PVR had a better clinical performance according to NYHA class (p = 0.016). MDCT is superior to 3-D TEE in terms of sizing accuracy and clinical outcomes. Reduction of PVR after TAVR with MDCT is likely due to valve annulus undersizing by TEE.

For the year 2018, more than 22,000 published references can be found in PubMed when entering the search term "cardiac surgery". As in the last 4 years, this review focusses on conventional cardiac surgery publications which provide important and interesting information especially relevant for non-surgical colleagues. Interventional techniques have been considered if they were published in the context of classic surgical techniques. We have again reviewed the fields of coronary revascularization and valve surgery and briefly touched on aortic surgery and surgery for terminal heart failure. For revascularization of complex coronary artery disease, bypass grafting was reconfirmed as gold standard and computer-tomographic angiography established equipoise for decision-making with classic angiography. For aortic valve treatment, some new longer-term outcomes from TAVI vs. SAVR trials confirmed equipoise of both treatments for high and medium risk. New information was provided for INR-management of mechanical aortic valves as well as long-term experiences for alternatives to mechanical valves (i.e., Ross and the relatively new Ozaki procedure). In the mitral and tricuspid field, prevalence data illustrate a significant amount of under-treatment for mitral and tricuspid valve regurgitation and evidence for life prolonging-effects of surgery. Finally, elongation of the ascending aorta was identified as new risk factor for aortic dissection and 2 years outcome of the newest generation of left ventricular assist devices demonstrate impressive improvements in outcome. While this article attempts to summarize the most pertinent publications, it does not expect to be complete and cannot be free of individual interpretation. As in recent years, it provides a condensed summary that is intended to give the reader "solid ground" for up-to-date decision-making in cardiac surgery and a stimulus for in-depth reading.

Intraoperative vasopressor and fluid application are common strategies against hypotension. Use of processed electroencephalographic monitoring (pEEG) may reduce vasopressor application, a known risk factor for organ dysfunction, in elective cardiac surgery patients. Randomized single-centre clinical trial at Jena University Hospital. Adult patients operated on cardiopulmonary bypass or off-pump coronary artery bypass grafting were randomised to receive anesthesia with visible or blinded pEEG using Narcotrend™. In blinded-Narcotrend (NT) depth of anesthesia was extrapolated from clinical signs, hemodynamic response and anesthetic concentration, supplemented by target indices between 37 and 64 in the visible-NT group. Intraoperative norepinephrine requirement (primary endpoint), fluid balance, extubation time, delirium occurrence and adverse events were evaluated. Patients of the intent-to-treat population (visible-NT: n = 123, blinded-NT: n = 122) had similar patient and procedural characteristics. Adjusted for type of surgery intraoperative Norepinephrine application was significantly reduced in visible-NT (n = 120, robust mean of cumulative dose 4.71 µg/kg bodyweight) compared to blinded-NT patients (n = 119, 6.14 µg/kg bodyweight) (adjusted robust mean difference 1.71 (95% CI 0.33-3.10) µg/kg bodyweight). Although reduction in patients operated on cardiopulmonary bypass was higher the interaction was not significant in post-hoc subgroup analysis. Intraoperative fluid balance was similar among both groups and strata. Extubation time was non-significantly lower in visible than in blinded-NT group. Overall postoperative delirium risk was 16.4% without differences among the groups. Adverse events-sudden movement/coughing, perspiration or hypertension-occurred more often with visible-NT, while one blinded-NT patient experienced intraoperative awareness. Titration of depth of anesthesia in elective cardiac surgery patients using pEEG allows to reduce application of norepinephrine.

For the year 2017, more than 21,000 published references can be found in PubMed when entering the search term "cardiac surgery". This review focusses on conventional cardiac surgery, considering the new interventional techniques only if they were directly compared to classic techniques but also entails aspects of perioperative intensive care management. The publications last year provided a plethora of new and interesting information that helped to quantify classic surgical treatment effects and provided new guidelines for the management of structural heart disease, which made comparisons to interventional techniques easier. The field of coronary bypass surgery was primarily filled with confirmatory evidence for the beneficial role of coronary artery bypass grafting for complex coronary disease and equal outcomes for percutaneous coronary intervention for less complex disease including main stem lesions. For aortic valve treatment, the new guidelines provide an equal recommendation for surgical and transcatheter aortic valve replacement for high and intermediate risk giving specific check lists to individualize decision-making by the heart team. For low-risk aortic stenosis, surgical valve replacement remains the primary indication. For the mitral valve, the importance of surgical experience of the individual surgeon on short- and long-term outcome was presented and the prognostic impact of mitral repair for primary mitral regurgitation was emphasized. In addition, there were many relevant and interesting other contributions from the purely operative arena in the fields of tricuspid disease as well as terminal heart failure (i.e., transplantation and ventricular assist devices). While this article attempts to summarize the most pertinent publications, it does not have the expectation of being complete and cannot be free of individual interpretation. As in recent years, it provides a condensed summary that is intended to give the reader "solid ground" for up-to-date decision-making in cardiac surgery.

Die Koronarchirurgie ist ein wichtiger Bestandteil der Behandlung der koronaren Herzkrankheit (KHK). Seit der Einfuhrung der perkutanen Koronarintervention (PCI), speziell der „drug-eluting stents“, nimmt die Zahl der koronaren Bypass-Operationen kontinuierlich ab. Bisher hat keine Studie gezeigt, dass eine elektive Koronarintervention das Uberleben der Patienten verlangern oder das Auftreten neuer Herzinfarkte verringern kann. Die Bypass-Operation ist die einzige Therapieform, die diese Wirkung haben kann. Allerdings wird dieser Effekt von vielen Faktoren beeinflusst und ist v. a. bei Patienten mit komplexer KHK sichtbar. Das ist der Grund dafur, dass in den aktuellen Guidelines die PCI der Bypass-Operation bei weniger ausgepragter KHK (niedrigem SYNTAX-Score) therapeutisch gleichgestellt ist und dass die Bypass-Operation primar bei Patienten mit komplexer KHK (hoher SYNTAX-Score) empfohlen wird. Zu den Faktoren, die die Ergebnisse nach Bypass-Operation und die Langzeitoffenheitsraten beeinflussen, ist 2017 viel Interessantes publiziert worden. Folgende Aussagen werden unterstutzt: 1. Die Bypass-Operation bei komplexer Mehrgefaserkrankung beinhaltet einen moglichen Uberlebensvorteil gegenuber PCI und medikamentoser Therapie und bleibt der Goldstandard. 2. Die vollarterielle Revaskularisation ist mit den besten Ergebnissen verbunden. 3. „Off-pump“-Techniken konnen v. a. bei Vermeidung von Aortenmanipulationen der „On-pump“-Technik uberlegen sein. Die Ergebnisse scheinen abhangig vom Operateur zu sein. 4. Die nichtinvasive bildgebende Koronarcomputertomographie (Koronar-CT) nimmt einen immer groseren Stellenwert ein und kann die Entscheidungsfindung bei der Therapie der KHK stark beeinflussen.

The objective of this study was to investigate the usefulness of intraprocedural hemodynamic monitoring for MR evaluation during pMRV. Assessment of mitral regurgitation (MR) during percutaneous mitral valve repair (pMVR) procedure is challenging. 3D color Doppler allows exact quantification of MR, but is technically demanding. Sixty patients with moderate to severe MR (14 with structural and 46 functional MR) were included in the study. Intraprocedural pressure curves were continuously obtained in the left atrium (LA) and left ventricle (LV). Transesophageal echocardiography was performed using 3D color Doppler derived mean vena contracta area (VCAmean) and mitral regurgitation volume (RegVol) to quantify MR severity before and after each clip implantation. In the entire patient group, strongest correlations were observed firstly between VCA and the raise of the ascending limb of the left atrial V pressure wave (Vascend; r = 0.58, p

For the year 2015, almost 19,000 published references can be found in PubMed when entering the search term "cardiac surgery". The last year has been again characterized by lively discussions in the fields where classic cardiac surgery and modern interventional techniques overlap. Lacking evidence in the field of coronary revascularization with either percutaneous coronary intervention or bypass surgery has been added. As in the years before, CABG remains the gold standard for the revascularization of complex stable triple-vessel disease. Plenty of new information has been presented comparing the conventional to transcatheter aortic valve implantation (TAVI) demonstrating similar short- and mid-term outcomes at high and low risk, but even a survival advantage with transfemoral TAVI at intermediate risk. In addition, there were many relevant and interesting other contributions from the purely operative arena. This review article will summarize the most pertinent publications in the fields of coronary revascularization, surgical treatment of valve disease, heart failure (i.e., transplantation and ventricular assist devices), and aortic surgery. While the article does not have the expectation of being complete and cannot be free of individual interpretation, it provides a condensed summary that is intended to give the reader "solid ground" for up-to-date decision-making in cardiac surgery.

Infective endocarditis (IE) is still associated with high morbidity and mortality. The impact of pre-operative stroke on mortality and long-term survival is controversial. In addition, data on the severity of neurological disability due to pre-operative stroke are scarce. We analysed the impact of pre-operative stroke and the severity of its related neurological disability on short- and long-term outcome. We retrospectively reviewed our data from patients operated for left-sided IE between 01/2007 and 04/2013. We performed univariate (Chi-Square and independent samples t test) and multivariate analyses. Among 308 consecutive patients who underwent cardiac surgery for left-sided IE, pre-operative stroke was present in 87 (28.2 %) patients. Patients with pre-operative stroke had a higher pre-operative risk profile than patient without it: higher Charlson comorbidity index (8.1 ± 2.6 vs. 6.6 ± 3.3) and higher incidence of Staphylococcus aureus infection (43 vs. 17 %) and septic shock (37 vs. 19 %). In-hospital mortality was equal but 5-year survival was significantly worse with pre-operative stroke (33.1 % vs. 45 %, p = 0.006). 5-year survival was worst in patients with severe neurological disability compared to mild disability (19.0 vs. 0.58 %, p = 0.002). However, neither pre-operative stroke nor the degree of neurological disability appeared as an independent risk factor for short or long-term mortality by multivariate analysis. Pre-operative stroke and the severity of neurological disability do not independently affect short- and long-term mortality in patients with infective endocarditis. It appears that patients with pre-operative stroke present with a generally higher risk profile. This information may substantially affect decision-making.

For the year 2014, more than 17,000 published references can be found in Pubmed when entering the search term "cardiac surgery". The last year has been characterized by a vivid discussion in the fields where classic cardiac surgery and modern interventional techniques overlap. Specifically, there have been important contributions in the field of coronary revascularization with either percutaneous coronary intervention or bypass surgery as well as in the fields of interventional valve therapy. Here, the US core valve trial with the first demonstration of a survival advantage at 1 year with transcatheter valves compared to surgical aortic valve replacement or the 5-year outcome of the SYNTAX trial with significant advantages for bypass surgery has been the landmark. However, in addition to these most visible publications, there have been several highly relevant and interesting contributions. This review article will summarize the most pertinent publications in the fields of coronary revascularization, surgical treatment of valve disease, heart failure (i.e., transplantation and ventricular assist devices) and aortic surgery. This condensed summary will provide the reader with "solid ground" for up-to-date decision-making in cardiac surgery.

Das hamodynamische Ergebnis nach Aortenklappenersatz (AKE) mit einer Klappenprothese wird durch das Design und die prothesenspezifische Strategie zur Grosenauswahl („sizing“) beeinflusst. Das Design bestimmt die tatsachliche Offnungsflache der Prothese relativ zum Ausendurchmesser, wahrend durch das Sizing die Grose der jeweilig zu implantierenden Klappe festgelegt wird. Derzeitig wird das hamodynamische Ergebnis dieser Prozedur durch Messung der Restgradienten (nach Bernoulli) und/oder mit der effektiven Offnungsflache („effective orifice area“, EOA) bestimmt. Die EOA wird mithilfe der Kontinuitatsgleichung aus der Flussgeschwindigkeit des Blutstroms und der Querschnittsflache des linksventrikularen Ausflusstrakts („left ventricular outflow tract area“, LVOTA) bestimmt und entspricht einer virtuellen Offnungsflache der Klappe in dem jeweiligen Patienten. Sie stimmt nicht unbedingt mit der maximalen Offnungsflache der vorhandenen Klappe uberein. Unabhangig von dieser Erkenntnis wird die Frage, ob eine Klappenprothese die angemessene Grose fur den Patienten aufweist, derzeit durch eine Beziehung der EOA auf die Korperoberflache beantwortet [“effective orifice area indexed“ (EOAi)]. Die Klappe wird als zu klein eingestuft, wenn ein moderates (EOAi zwischen 0,65 und 0,85 cm2/m2) oder schweres (EOAi ≤ 0,65 cm2/m2) Patient-Prothese-Missverhaltnis (PPM) vorliegt. Derzeit bestreitet etwa die Halfte der Publikationen zu diesem Thema eine Auswirkung eines so gemessenen PPM auf das Langzeituberleben. Es ist aber gut moglich, dass eine Messproblematik Ursache fur diese Kontroverse ist. Der vorliegende Beitrag beschreibt die derzeitigen Standards in der Bewertung der Hamodynamik nach Klappenersatz und weist auf die Probleme in der Messmethode und der Bewertung von PPM hin. Weiterhin wird die Prosthesis-Annulus-Relation(PAR)-I-Studie vorgestellt, die ein neues Konzept zu Bewertung und Vorhersage von hamodynamischen Ergebnissen und von PPM beinhaltet.

Normal cardiac function requires high and continuous supply with ATP. As mitochondria are the major source of ATP production, it is apparent that mitochondrial function and cardiac function need to be closely related to each other. When subjected to overload, the heart hypertrophies. Initially, the development of hypertrophy is a compensatory mechanism, and contractile function is maintained. However, when the heart is excessively and/or persistently stressed, cardiac function may deteriorate, leading to the onset of heart failure. There is considerable evidence that alterations in mitochondrial function are involved in the decompensation of cardiac hypertrophy. Here, we review metabolic changes occurring at the mitochondrial level during the development of cardiac hypertrophy and the transition to heart failure. We will focus on changes in mitochondrial substrate metabolism, the electron transport chain and the role of oxidative stress. We will demonstrate that, with respect to mitochondrial adaptations, a clear distinction between hypertrophy and heart failure cannot be made because most of the findings present in overt heart failure can already be found in the various stages of hypertrophy.

Surgical reconstruction of physiological shape and size of a postischemically remodeled left ventricle has been advocated to improve ventricular function and improve patient long-term outcome. What initially started as linear aneurysm resection surgery developed over the years into the endoventricular repair techniques (surgical ventricular reconstruction, SVR) that have also been applied in patients with postischemically dilated ventricles and mainly anterior akinesia. SVR improved function as measured by the ejection fraction. Whether it affects survival was finally tested in the largest surgical trial ever conducted, the STICH trial (Surgical Treatment for IsChemic Heart failure). The trial, however, presented rather sobering information with its Hypothesis 2 outcome by demonstrating identical 5-year survival rates between SVR plus bypass grafting (CABG) and CABG alone. SVR also did not improve quality of life. This neutral finding spawned a series of critical responses with respect to trial design and conduct accompanied by appropriate responses by the trial's leadership. At the end of this dispute, it appears that SVR has been accepted as not very useful for most patients and is less and less performed in daily practice. What remains is a series of different perspectives that will be discussed in this review. The conclusion will be that SVR may be of low value for the patient with dilated and massively remodeled ventricles, but the technique bears therapeutic potential for some patients for different reasons so that the surgeon's ability to perform this operation should not get lost.

Aufgrund mehrerer Fehlpositionierungen des Ballons der intraaortalen Ballonpumpe (IABP), die in computertomographischen (CT) Aufnahmen festgestellt wurden, und der daraus folgenden Kompromittierung der Viszeralgefase, fuhrten wir eine systematische Nachbearbeitung der Daten kardiochirurgischer IABP-Patienten mit verfugbaren thorakoabdominalen CT-Aufnahmen durch. Ziel war es, Inzidenz, Ursachen und klinische Relevanz der IABP-Fehllage zu eruieren. Bei 63 von 621 Patienten (10,1%) wurde bei liegender IABP eine thorakoabdominale CT-Aufnahme durchgefuhrt. Dabei wurde unter Berucksichtigung der Beziehung zu den Viszeralarterien die proximale und distale Ballonposition analysiert. Des Weiteren wurden bei allen Patienten die anatomische Distanz zwischen A. subclavia sinistra und Truncus coeliacus (AS-TC) sowie der transverse Aortendurchmesser bestimmt. In 96,8% der Falle war in der Thoraxrontgenaufnahme die proximale Ballonlage korrekt, wobei eine adaquate Lage nach CT-Untersuchung nur in 38,1% vorlag. Bei 61 von 63 Patienten (96,8%) wurde die Kompromittierung mindestens einer Viszeralarterie festgestellt. Die AS-TC-Distanz betrug 241±23 mm. Die Ballonlange lag bei 248±17 mm und korrespondierte in 68,2% der Falle mit einem Missverhaltnis der Anatomie und Ballonlange. Eine Laparotomie, die aufgrund einer Mesenterialischamie durchgefuhrt wurde, war bei 23,8% der Patienten erforderlich. Die Gesamtkrankenhausmortalitat betrug 60,3%. Trotz Einhaltung aktueller Behandlungsleitlinien wurde bei fast allen Patienten eine IABP-Fehllage durch das CT nachgewiesen. Grunde waren eine falsche Positionierung des proximalen Ballonendes, sowie ein Missverhaltnis der Anatomie und Ballonlange. Ballonlangen, die kurzer sind als bislang empfohlen, und bessere Positionierungsstrategien scheinen daher angebracht.

Shifting substrate oxidation in heart muscle from fatty acids to glucose (substrate-switch) may improve contractile function in heart failure. We tested whether application of two agents (etomoxir and NVP-LAB121) capable of inducing a substrate-switch reverts the onset of heart failure in rats with chronic pressure-overload. Hypertrophy was induced by aortic banding in rats for 1 or 15 weeks. Rats were treated for 10 days with the CPT-1-inhibitor etomoxir [29.5 micromol/(kg day)] or with NVP-LAB121 [60 micromol/(kg day)], a pyruvate-dehydrogenase-kinase-inhibitor, before assessment by echocardiography and perfusion as isolated working hearts. We also analyzed PDH- and CPT1-activity and expression of alpha- and beta-MHC by RT-PCR. Aortic banding increased heart-to-body-weight-ratio (g/kg) from 3.44 +/- 0.26 to 4.14 +/- 0.48 after 1 week and from 2.80 +/- 0.21 to 6.54 +/- 0.26 after 15 weeks. Ejection fraction was impaired after 15 weeks (57 +/- 11 vs. 73 +/- 8%, P < 0.05) and rats exhibited signs of heart failure. Total PDH activity was the same in all groups. CPT-1 activity was unchanged after 1 week but decreased after 15 weeks (P < 0.01). Neither etomoxir nor NVP-LAB121 affected cardiac function in vivo, but etomoxir improved function of the isolated heart. The drugs did not affect total PDH and CPT-1 activity, but increased PDH-activity status, prevented a decrease in PDK4 expression in heart failure, increased alpha and beta-MHC expression and shifted substrate oxidation toward glucose in the isolated working rat heart. In conclusion, pharmacologic induction of substrate-switching is associated with changes in myofibrillar isoform expression but does not reverse heart failure in vivo. The improvement of function in vitro deserves further investigation.

Since the advent of implantable cardioverters/defibrillators (ICD) and percutaneous ablation, surgery for the treatment of ventricular arrhythmia has decreased tremendously. Nevertheless, surgical treatment of ventricular arrhythmias is still required, especially for cases where ICD discharge occurs very frequently or in patients with other indications for surgery. The choice of surgical therapy may range from radiofrequency- or cryoablation of a single focus (identified either intra- operatively or percutaneously) to more extensive surgical procedures such as surgical ventricular reconstruction with endocardial resection or even resection of the right ventricle and the creation of a cavo-pulmonary circulation for malignant arrhythmias and right ventricular failure in patients with arrhythmogenic right ventricular dysplasia. However, the choice of surgical procedure should be made based on the pathomechanism of the arrhythmia. This is important because any incision in the left or right ventricle or percutaneous ablation may also be the cause for ventricular arrhythmia. In this short review we will describe the most common underlying substrates for ventricular arrhythmia, indications for surgery, the techniques used for treatment and the results achieved. We will conclude that for most cases of patients with ventricular arrhythmia undergoing surgery, ischemia and the presence of a scar after myocardial infarction is the underlying cause and revascularization plus surgical ventricular reconstruction with endocardial resection may be the best treatment option.

Hypoadiponectinemia is an independent predictor of cardiovascular disease, impairs mitochondrial function in skeletal muscle, and has been linked to the pathogenesis of Type 2 diabetes. In models of Type 2 diabetes, myocardial mitochondrial function is impaired, which is improved by increasing serum adiponectin levels. We aimed to define the roles of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in adiponectin-evoked regulation of mitochondrial function in the heart. In isolated working hearts in mice lacking AdipoR1, myocardial oxygen consumption was increased without a concomitant increase in cardiac work, resulting in reduced cardiac efficiency. Activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes were reduced, accompanied by reduced OXPHOS protein levels, phosphorylation of AMP-activated protein kinase, sirtuin 1 activity, and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling. Decreased ATP/O ratios suggested myocardial mitochondrial uncoupling in AdipoR1-deficient mice, which was normalized by lowering increased mitochondrial 4-hydroxynonenal levels following treatment with the mitochondria-targeted antioxidant Mn (III) tetrakis (4-benzoic acid) porphyrin. Lack of AdipoR2 did not impair mitochondrial function and coupling in the heart. Thus, lack of AdipoR1 impairs myocardial mitochondrial function and coupling, suggesting that impaired AdipoR1 signaling may contribute to mitochondrial dysfunction and mitochondrial uncoupling in Type 2 diabetic hearts.

Insulin improves contractile function after ischemia, but does not increase glucose uptake in the isolated working rat heart. We tested the hypothesis that the positive inotropic effect of insulin is independent of the signaling pathway responsible for insulin-stimulated glucose uptake. We inhibited this pathway at the level of phosphatidyl inositol 3-kinase (PI3K) with wortmannin. Hearts were perfused for 70 min at physiological workload with Krebs-Henseleit buffer containing [2-3H] glucose (5 mM, 0.05 μCi/ml) and oleate (0.4 mM, 1% BSA) in the presence (WM, n = 5) or absence (control, n = 7) of wortmannin (WM, 3 μmol/L). After 20 min, hearts were subjected to 15 min of total global ischemia followed by 35 min of reperfusion. Insulin (1 mU/ml) was added at the beginning of reperfusion (WM + insulin n = 8, insulin n = 8). Cardiac power before ischemia was 8.1 ± 0.7 mW. Recovery of contractile function after ischemia was significantly increased in the presence of insulin (73.5 ± 8.9% vs. 38.5 ± 6.7%, p < 0.01). The addition of wortmannin completely abolished the effect of insulin on recovery (32.6 ± 6.4%). Glucose uptake was 1.84 ± 0.32 μmol/min/g dry before ischemia and was slightly elevated during reperfusion (2.68 ± 0.35 μmol/min/g dry, n.s.). Insulin did not affect postischemic glucose uptake. In the presence of wortmannin, glucose uptake was lowest during reperfusion (n.s.). The results suggest that PI3K is involved in the insulin-induced improvement in postischemic recovery of contractile function. This effect of insulin is independent of its effect on glucose uptake.

Hintergrund Wahrend des kardiopulmonalen Bypass (CPB) ist die Lunge vollstandig vom Pulmonalkreislauf getrennt und wird ausschlieslich uber die Bronchialarterien versorgt. Wir haben die Hypothen aufgestellt, dass 1.) der bronchialarterielle Blutfluss wahrend des CPB nicht ausreicht, um eine Ischamie der Lunge zu verhindern und dass 2.) durch eine kontrollierte Perfusion der Lunge der ischamische Lungenschaden verringert werden kann. Methoden Vierunddreisig Ferkel (5,0±0,5kg) wurden fur 90min und 120min an den CPB angeschlossen und anschliesend fur 60min reperfundiert. Der bronchialarterielle Blutfluss wurde vor, wahrend und nach dem CPB mittels fluoreszierender Mikrospheren quantifiziert. Bei 19 Tieren wurde die Lunge wahrend des Bypass kontrolliert perfundiert (kontinuierlich u. intermittierend). Im Anschluss an das Tierexperiment wurde das Konzept der Lungenperfusion in eine klinische Studie ubertragen und an 35 lungengesunden Patienten uberpruft. Ergebnisse Mit Beginn des CPB war der bronchialarterielle Blutfluss auf 13% des Ausgangswertes abgefallen (von 42,1±10,4ml/min auf 5,6±1,0ml/min; p

Catecholamines or ischemia may increase myocardial glucose uptake by an increase in intracellular calcium. We tested the hypothesis that increasing or decreasing extracellular calcium supply would change glucose uptake. Hearts were perfused for 60 min at a physiological workload with Krebs-Henseleit buffer containing glucose (5 mM) and oleate (0.4 mM; bound to 1% BSA). Calcium concentration was 2.5 mM. In group A (control; n = 12), insulin (1 mU/ml) was added at 30 min. In Group B (n = 7), the calcium concentration was increased to 5.0 and 7.5 mM at 20 min and 40 min, respectively. In Group C (n = 7), verapamil was added at 20 min (0.25 μM) and 40 min (1.0 μM) to decrease calcium influx. In group D (n = 7), EDTA was added at 20 min (0.5 mM) and at 40 min (1.5 mM) to decrease the free extracellular calcium. Glucose uptake was measured by 3H2O production from [2-3H]glucose and cardiac work was measured simultaneously. Cardiac power in group B was 8.24 ± 0.60 mW at 2.5 mM calcium, 9.45 ± 0.50 mW at 5 mM calcium and 7.99 ± 0.99 mW at 7.5 mM calcium (n.s.). The addition of verapamil decreased contractile function in a dose-dependent manner (8.50 ± 0.74 vs. 3.11 ± 0.84 vs. 1.48 ± 0.39 mW, p < 0.01) suggesting that verapamil decreased cytosolic calcium concentration. A similar dose-dependent reduction in contractile performance was observed in the EDTA group (8.44 ± 0.81 vs. 7.42 ± 0.96 vs. 4.03 ± 1.32 mW, p < 0.01). Glucose uptake was 1.35 ± 0.11 μmol/min/g dry weight under control conditions. Glucose uptake increased threefold with the addition of insulin. Increasing extracellular [Ca2+] did not affect glucose uptake. Decreasing Ca2+ availability showed a trend towards a decrease in glucose uptake (n.s.), which was minor compared to the decrease in contractile function. We conclude that extracellular calcium does not regulate glucose uptake in the isolated working rat heart in the presence of glucose and fatty acids as substrates. The trend of decreased glucose uptake when calcium supply was limited may be due to dramatically reduced energy demand and not directly due to changes in calcium.

Hintergrund: Obwohl die Reduktion der Wandspannung durch eine Resektion groser Teile des linken Ventrikels (Batista-Operation) in der Behandlung dilatativer Herzerkrankungen ein erfolgversprechendes Konzept darstellt, sind die klinischen Daten nicht uberzeugend. Trotz einer Vielzahl von Arbeiten auf diesem Gebiet ist es z. Z. noch unklar, ob Operationsverfahren, die die Grose des linken Ventrikels verkleinern, tatsachlich therapeutische Optionen bei Patienten mit dilativer Herzerkrankung sein konnen, da die Ursache der Erkrankung durch die Operation nicht beseitigt wird. Fallbeschreibungen: Wir prasentieren eine Serie von 5 Fallen, bei denen eine linksventrikulare Reduktion bei idiopathischer, dilatativer Kardiomyopathi nach einer Modifikation der endoventrikularen Patchplastik nach Dor durchgefuhrt wurde. Alle 5 Patienten zeigten unmittelbar nach der Operation eine Verbesserung der kontraktilen Funktion. Die 30-Tage-Sterblichkeit war 0%. Bei einem der Patienten war diese Verbesserung auch 18 Monate nach der Operation noch nachweisbar. Ein weiterer Patient entwickelte eine schwere Herzinsuffizienz aufgrund einer therapieresistenten, ventrikularen Arrhythmie (Lown Ivb). Er wurde 4 Monate nach der Ventrikelreduktion erfolgreich transplantiert. Zwei Patienten zeigten eine deutliche Redilatation 9 und 12 Monate nach der Operation und wurden zur Transplantation gelistet. Ein Patient mit schwerer chronisch obstruktiver Lungenerkrankung (COPD) verstarb 9 Wochen nach der Operation aufgrund einer Sepsis und respiratorischer Dysfunktion. Schlussfolgerung: Obwohl eine Ventrikelreduktion in modifizierter Dor Technik von den meisten Patienten gut toleriert wird und eine sofortige Verbesserung der Herzfunktion bewirkt, sind die Langzeitergebnisse dieses operativen Vorgehens bei Patienten mit idiopathischer, dilatativer Kardiomyopathie nicht ermutigend. Daher kann diese Operation z. Z. nicht als Alternative zur Herztransplantation empfohlen werden. Das Verfahren kann jedoch bei Patientenmit Kontraindikationen zur Transplantation als therapeutische Option in Erwagung gezogen werden.