Hybrid approach combining off-pump CABG with transapical aortic valve implantation via median sternotomy.

We report the case of a 75-year-old patient diagnosed with severe aortic stenosis and two-vessel coronary artery disease. Due to multiple comorbidities including chronic renal insufficiency, stroke and pulmonary hypertension (EuroSCORE: 34%; STS mortality risk: 14.9%), he was not a candidate for conventional aortic valve surgery. He underwent a novel hybrid treatment approach combining off-pump CABG and transapical aortic valve implantation via a median sternotomy. Extracorporeal circulation could be entirely avoided.

Pacemaker-associated thrombotic occlusion of the inferior vena cava causing liver failure.

Pacemaker implantation using endocardial leads can give rise to thrombotic venous occlusion. We report the case of a 23-year-old male with transposition of the great arteries, who had previously undergone a Senning repair at the age of one year. A sick sinus syndrome required pacemaker implantation with subsequent multiple lead revisions. Following the implantation of the last lead, the patient developed complete occlusion of the inferior vena cava (IVC) with stenosis of the superior vena cava (SVC) with pacemaker leads in both lesions. Liver failure, ascites and esophageal varices developed. Thrombolytic treatment was ineffective; finally the patient was listed for liver transplantation. We explanted the lead embedding the thrombosis, together with some lead remnants. The stenosis of the SVC and the occlusion of the IVC were dilatated and stabilized with four stents. Over a follow-up period of 4 months, NYHA class improved from NYHA III to NYHA I-II, the hepatic function showed complete remission, and a liver transplantation was not necessary.

A two-way molecular dialogue between embryo and endosperm is required for seed development.

The plant embryonic cuticle is a hydrophobic barrier deposited de novo by the embryo during seed development. At germination, it protects the seedling from water loss and is, thus, critical for survival. Embryonic cuticle formation is controlled by a signaling pathway involving the ABNORMAL LEAF SHAPE1 subtilase and the two GASSHO receptor-like kinases. We show that a sulfated peptide, TWISTED SEED1 (TWS1), acts as a GASSHO ligand. Cuticle surveillance depends on the action of the subtilase, which, unlike the TWS1 precursor and the GASSHO receptors, is not produced in the embryo but in the neighboring endosperm. Subtilase-mediated processing of the embryo-derived TWS1 precursor releases the active peptide, triggering GASSHO-dependent cuticle reinforcement in the embryo. Thus, a bidirectional molecular dialogue between embryo and endosperm safeguards cuticle integrity before germination.

A new role for extracellular Ca2+ in gap-junction remodeling: studies in humans and rats.

We wanted to elucidate whether extracellular calcium may regulate the expression of the cardiac gap-junction proteins connexin 40 and connexin43. In the free wall of the left atria of 126 cardiac surgery patients with either sinus rhythm (SR) or chronic atrial fibrillation (AF), we determined the expression of the cardiac gap-junction proteins Cx43 and Cx40 by Western blot and immunohistology. For deeper investigation, we incubated cultured neonatal rat cardiomyocytes at 2 or 4 mM Ca(++) for 24 h and determined intercellular coupling, Cx40, Cx43 protein and mRNA expression, protein trafficking and sensitivity to verapamil (10-100 nM), cyclosporin A (1 microM),and BMS605401 (100 nM), a specific inhibitor of Ca(2+)-sensing receptor (CaSR). We found in patients that both Cx are up-regulated in AF in the left atrium (by 100-200%). Interestingly, Cx40 was mainly up-regulated, if total serum calcium was >or=2.2 mM, while Cx43 was independent from extracellular [Ca(++)]. In cultured cells, 4 mM Ca(++)-exposure lead to up-regulation of Cx40, but not Cx43. We found enhanced Cx40 in the plasma membrane and reduced Cx40 in the Golgi apparatus. The membrane Cx40 up-regulation resulted in enhanced gap-junction intercellular coupling with a shift in the Boltzmann fit of voltage-dependent inactivation indicating a higher contribution of Cx40 as revealed by dual whole cell voltage clamp experiments. BMS605401 could prevent all Ca(2+)-induced changes. Moreover, cyclosporin A completely abolished the Ca(2+)-induced changes, while verapamil was ineffective. We conclude that extracellular calcium (24 h exposure) seems to up-regulate Cx40 but not Cx43.

Inhibition of polymorphonuclear leukocyte chemiluminescence for detection of immune complexes in human sera.

An assay for the detection and quantitation of immune complexes is described. Experimental immune complexes or aggregated human gamma globulin (AHG) were incubated with polymorphonuclear leukocytes (PMN). After challenge of the PMN with opsonized zymosan, chemiluminescence was recorded in a scintillation spectrometer. A quantitative inhibition of chemiluminescence could be demonstrated by the interaction of PMN with immune complexes or AHG. Experimental immune complexes of bovine serum albumin-anti-bovine serum albumin were formed and tested by this assay, and immune complexes formed near antigen excess were best described by this technique. The technique was used to demonstrate immune complexes in the sera from patients with systemic lupus erythematosus, rheumatoid arthritis, and vasculitis. Immune complexes were quantitated by reference to a standard curve using AHG. By this technique, normal human sera had < 10 micrograms of AHG per milliliter of serum. Immune complexes at levels above this were detected in 9/15 patients with systemic lupus erythematosus, 18/30 patients with rheumatoid arthritis, and 2/5 patients with vasculitis. Therefore, this assay is a sensitive, simple method for measurement of circulating immune complexes in the sera of patients with certain connective tissue diseases.

[Efficacy and safety of various energy sources and application techniques for the surgical treatment of atrial fibrillation]. / Experimentelle Evaluierung verschiedener Energiequellen und Applikationsverfahren zur chirurgischen Therapie des Vorhofflimmerns.

We investigated efficacy and safety of different energy sources and application techniques for the treatment of atrial fibrillation in an experimental acute sheep model. In particular, we focused on thermal damage to the adjacent structures and tissues. We also attempted to evaluate the efficacy of different application techniques such as endocardial or epicardial approaches. Overall 64 young Merino sheep were examined. It could be shown that endocardial ablation with different energy sources on cardiopulmonary bypass consistently caused histomorphologically and electrophysiologically transmural lesions. Depending on the energy source, different amounts of endocardial damage were induced. Cryoapplication produces the smallest endocardial laceration without thrombus formation. Dry radiofrequency energy and microwave produced very wide and diffuse endocardial damage with carbonisation and disruption of the endothelium. Epicardial ablation on a beating heart (off-pump) with bipolar radiofrequency was consistently effective. Due to the energy flow between the two jaws of the bipolar clamp, no collateral damage was observed. All other energy sources were unable to produce transmural lesions epicardially (off-pump) because the nearby blood flow rewarmed or recooled the myocardium and caused the so called "heat sink phenomenon". Depending on the energy source, different histomorphological changes in the esophagus could be observed. Changes in intraluminal-measured esophageal temperatures were not observed during ablation.

Autopsy findings in patients on postcardiotomy extracorporeal membrane oxygenation (ECMO).

OBJECTIVES: To assess the clinical sensitivity of causes of death, concomitant diseases and postoperative complications including thromboembolic events in ECMO patients. METHODS: Between January 2000 and December 2004 154/202 patients (76.2%) died after postcardiotomy ECMO circulatory support. Autopsy was performed in 78 (50.6%) consecutive patients. Clinical and post-mortem data were prospectively recorded and compared concerning causes of death and postoperative complications including venous and arterial thromboembolisms and significant comorbidities. RESULTS: Mean age was 62.1+/-11.3 years, ejection fraction was 43.4+/-17.3%. 39.7% were emergency operations including acute coronary syndrome in 25.6% and preoperative cardiogenic shock in 28.2%. Successful ECMO weaning rate was 43.6%. Mean postoperative survival was 11.3 days. Premortem unknown concomitant diseases were found in 63 patients (80.8%) with clinical relevance in 9 patients (11.5%). Clinically unrecognized postoperative complications were found in 59 patients (75.6%) including acute cerebral infarction (n=7), acute bowel ischemia (1), intestinal perforation (3), pneumonia (4), venous thrombus formation (25) and systemic thromboembolic events (24). Clinically based causes of death were cardiac in 62.8%, multi-organ failure in 10.3%, cerebral in 5.1%, respiratory in 10.3%, fatal pulmonary embolism in 2.6%, technical in 5.1%, and others in 3.8%. Unexpected causes of death were found by autopsy in 22 patients (28.2%) including myocardial infarction (n=5), acute heart failure (4), fatal pulmonary embolism (2), pneumonia (2), ARDS (1), lung bleeding (1), fatal cerebrovascular event (4) and multiorgan failure (3). CONCLUSIONS: In ECMO patients major discrepancies between clinical and post-mortem examination were found. The true incidence of thromboembolic events is highly underestimated by clinical evaluation.

Regression of left ventricular hypertrophy after surgical therapy for aortic stenosis is associated with changes in extracellular matrix gene expression.

BACKGROUND: Regression of left ventricular hypertrophy (LVH) after surgical correction for aortic stenosis is not fully understood on the molecular level. The aim of this study was to examine whether there is an association between LVH regression and extracellular matrix (ECM) gene expression. METHODS AND RESULTS: A standard model of controlled LVH induction by supracoronary banding (A=baseline) was applied in 44 growing sheep (age, 6 to 8 months). Surgical correction to release the pressure gradient was performed 8.3+/-1 months later (B). The animals were killed after another 10.1+/-2 months (C). At all time points, hemodynamic evaluations and quantitative analysis of mRNA and protein expression for matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) was performed. Left ventricular mass index was 82+/-21 (A) versus 150+/-33 (B), P<0.01, and 78+/-18 g/m(2) (C), P<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter index was 9.1+/-1.2 (A) versus 12.3+/-1.4 (B), P<0.01, and 8.4+/-1.3 micrometer/m(2) (C), P<0.01. In parallel to the development of LVH at B, gene expression was increased significantly for MMP-1, MMP-2, MMP-3, and MMP-9 and for TIMP-1 and TIMP-2 and decreased significantly for TIMP-3. After surgical correction (C), there was a complete regression of gene expression to baseline measures. CONCLUSIONS: Controlled induction of compensated LVH leads to significant increase in ECM gene expression. The regression of LVH after surgical therapy is associated with complete regression of ECM gene expression. However, no cause-and-effect relation could be demonstrated.

Humoral immune response during coronary artery bypass grafting: A comparison of limited approach, "off-pump" technique, and conventional cardiopulmonary bypass.

BACKGROUND: The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques. METHODS AND RESULTS: Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-alpha receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (P:<0.05). TNF-alpha receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach. CONCLUSIONS: There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma. The release of immune mediators is enhanced by the use of CPB during various perioperative and postoperative phases. The type of operative approach did not influence this immune response.

High dose nicotinamide fails to prevent diabetes in BB rats.

Nicotinamide which is an inhibitor of poly (ADPR) synthetase and precursor of NAD has been observed to prevent diabetes in some experimental models possibly by protecting beta cells. To determine whether nicotinamide could cure or prevent type 1 diabetes, we administered large doses (0.5 g/Kg/d) to BB rats. When used in the 45 days following diagnosis nicotinamide failed to bring remission. As a preventive treatment, nicotinamide administered between the 40th and 90th day of age, alone or in association with desferrioxamine did not significantly lower the incidence of diabetes (23% and 30.8% respectively vs. 56.6%). When used earlier, immediately after weaning, nicotinamide did not affect the incidence of diabetes in this model (62.5%). The degree of protection was not comparable with that obtained with cyclosporin A (15% of diabetic animals). Histology study of the pancreas from the animals killed either immediately or 1 year after treatment revealed no endocrine tumor. These findings suggest that in BB rats nicotinamide has little or no effect on the course of autoimmune diabetes mellitus thus dampening the high hopes for this drug in the treatment of human diabetes.

Minimally invasive saphenous vein harvesting techniques: morphology and postoperative outcome.

BACKGROUND: Conventional saphenous vein harvest is associated with numerous complications, which may be reduced by minimally invasive vein-harvesting techniques. The integrity of the venous endothelium must be guaranteed before using new saphenous vein harvesting techniques. This short-term study compared the clinical outcome of two minimally invasive techniques with the conventional technique, and compared morphology as documented by light and electron microscopy. METHODS: Ninety-two patients were prospectively randomized into three groups. Two different minimally invasive techniques of greater saphenous vein harvesting were used in sixty-two patients. One used a video-assisted dissector (group A, n = 31), and one used a light-coupled retractor (group B, n = 31). Thirty patients were treated by the conventional technique (group C). RESULTS: Incision lengths were 7.6+/-2.1 cm in group A and 9.3+/-3.2 cm in group B, as compared with 38.9+/-8.7 cm in the conventional group. Harvesting time was prolonged by a mean of 26% when using a minimally invasive technique. Conversion rate to the open technique was 3 of 31 (9.3%) in group A and 2 of 31 (6.2%) in group B. No wound complications were noted in group A, but one wound inflammation was seen in group B; only a mild hematoma was seen in both groups. Edge necrosis, wound separation and inflammation were noted in the conventional group. Light and electron microscopy revealed no significant denudation of the endothelial layer in groups A and B as compared with group C. CONCLUSIONS: These data show an excellent postoperative result when using the minimally invasive technique as compared with the conventional group. The safety of the technique is demonstrated by the preservation of endothelial integrity.

Pain is significantly reduced by cryoablation therapy in patients with lateral minithoracotomy.

BACKGROUND: In minimally invasive cardiac surgery use of a lateral minithoracotomy is associated with early postoperative rehabilitation but also relatively high pain levels during the first 3 postoperative days. Cryoablation therapy was evaluated prospectively. METHODS: From April 1999 until September 1999, 57 patients underwent lateral minithoracotomy for mitral valve operation (n = 18) or minimally invasive direct coronary artery bypass grafting (n = 39). Intraoperatively, patients were randomly assigned to cryoablation or intercostal application of local anesthetic agents. A standardized questionnaire was used for prospective pain assessment on postoperative days 1 to 7. RESULTS: From postoperative day 1 to 7 pain levels declined in all groups. Overall pain levels were significantly lower in the cryo group than in the control group (p < 0.0001, GLM). According to diagnoses, pain levels were significantly lower after MIDCABG and cryo versus control; after mitral valve operation they were lower in the cryo group and almost reached significance. CONCLUSIONS: Cryoablation is easy to perform and leads to a significant reduction in pain and lower request for additional pain medication after lateral minithoracotomy in minimally invasive cardiac operation.

Immunologic techniques utilized in the diagnosis of occupational lung disease.

Numerous immunologic diagnostic modalities are available to the clinician investigating the etiology of occupational lung disorders. Certain tests--immunoassays for specific anti-IgE antibody, gel diffusion reactions, and immunoelectrophoretic techniques--may aid in the identification of specific antigens or analysis of antigens involved in the pathogenesis of environmental lung diseases. Other techniques--ANA assays, complement studies, and immune complex assays--should be regarded as complementary. For example, a specific non-histone nucleoprotein "marker," ANA has not been identified in any of the environmental fibrotic lung diseases, and ANA positivity does not always correlate with severity or progression of disease. Additionally complement assays and detection of circulating immune complexes do not identify specific antigens. Clearly, there are other assays useful in determining immunologic mechanisms that may be important in occupational lung diseases but were not discussed in this article. Bronchoalveolar lavage with cellular identification and therapeutically important when considering the activity of various lung disorders. Also, lymphokine and leukotriene identification, lymphocyte transformation studies, and assessment of macrophage function are contributing greatly to our understanding of the possible immunologic mechanisms involved in different environmental pulmonary diseases. Thus, the investigation of immunologic mechanisms offers an exciting and rewarding future in the evaluation of the pathologic mechanisms of occupational and environmental pulmonary disease.

Immunopathogenesis of asbestosis, silicosis, and coal workers' pneumoconiosis.

From these discussions, it is apparent that immunologic aberrations occur in several inorganic dust diseases. Although the role of these immunologic mechanisms in disease pathogenesis remains speculative, recent studies demonstrating the regulation of fibroblast proliferation by macrophage and asbestos or silica interaction support a role for this cell type in the immunopathogenesis of disease. Future cellular and humoral investigations of the bronchoalveolar lavage in workers with pneumoconiosis may clarify the immunologic contributions in the development of fibrosis observed in these diseases.

Immunologic techniques utilized in the diagnosis of occupational lung disease.

Humoral and/or cell-mediated immune responses may contribute to the tissue injury in patients with certain types of occupational asthma, hypersensitivity pneumonitis, silicosis, and asbestosis. Numerous diagnostic modalities are available to the clinician investigating the etiology of these disorders. Among the current immunologic techniques discussed in this article are immunoassays for specific anti-IgE antibody, gel diffusion reactions, immunoelectrophoresis, ANA assays, complement studies, and immune complex assays.

Women and coronary disease: relationship between descriptors of signs and symptoms and diagnostic and treatment course.

BACKGROUND: Heart disease is the No. 1 killer among women in the United States. Differences in the clinical features of coronary heart disease among men and women have been reported, along with various approaches to the diagnostic workup and therapeutic interventions. PURPOSE: To explore the relationship between descriptors of signs and symptoms of coronary heart disease and follow-up care and to investigate any differences between male and female patients. METHODS: Structured interviews with patients and chart audits were used to assess initial signs and symptoms, associated cardiac-related signs and symptoms, and the diagnostic tests and interventions used for treatment. The sample consisted of 98 patients (51 women and 47 men) who were admitted with a medical diagnosis of myocardial infarction. RESULTS: Chest pain was the most common sign or symptom reported by both men and women. The 4 most common associated signs and symptoms were identical in men and women: fatigue, rest pain, shortness of breath, and weakness. However, significantly more women than men reported loss of appetite, paroxysmal nocturnal dyspnea, and back pain. Women were also less likely than men to have angiography and to receive i.v. nitroglycerin, heparin, and thrombolytic agents as part of acute management of myocardial infarction. CONCLUSION: Chest pain remains the initial symptom of acute myocardial infarction in both men and women. However, women may experience some different associated signs and symptoms than do men. Despite these similarities, men still are more likely than women to have angiography and to receive a number of therapies.

Hypertension: the rediscovery of combination therapy.

Awareness and treatment of hypertension in the United States has been improving for older patients, but hypertension continues in many cases to be poorly controlled. Three options exist if initial therapy fails to achieve target blood pressure: upward drug titration, substituting another drug, or combination drug therapy. Combination therapy is the attempt to optimize blood pressure control by using two or more agents with additive or synergistic effects. Problems with this approach include noncompliance due to complicated regimens, adverse drug reactions, and the added expense of multiple medications. However, the newer fixed-dose combination products have been shown to offer improved blood pressure control, simplification of drug regimens, decreased adverse reactions, improved compliance, and cost-effectiveness.

[GSTCVS certificate for cardiac pacemaker, ICD and CRT therapy]. / DGTHG-Zertifizierung zur Herzschrittmacher-, ICD- und CRT-Therapie.

Medical qualifications to perform operations with cardiac electronic implantable devices as well as for preoperative and postoperative therapy, including follow-up in this patient population are not well defined. Based on recommendations which have been worked out and published by an interdisciplinary consensus of cardiac surgeons, cardiologists and electrophysiologists, a certificate with three modules has been developed by the Working Group for Electrophysiologic Surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS, Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie, DGTHG). First examinations for this certificate will be held in 2013 and transitional regulations apply until 1st April 2014. Further details are available on the homepage of the GSTCVS.

[Right heart failure resulting from pacemaker lead-induced tricuspid valve regurgitation]. / Rechtsherzversagen durch schrittmachersondeninduzierte Trikuspidalklappeninsuffizienz.

Pacemaker lead-induced tricuspid valve regurgitation is a severe and often underdiagnosed complication due to the widely variable time interval between implantation and the development of severe tricuspid valve insufficiency with ensuing right heart failure. Complete explantation of inactive pacemaker leads is necessary to avoid permanent damage to right heart structures. If performed in a timely fashion, regression of tricuspid insufficiency can be achieved without additional cardiac procedures.

[Registry and studies of the German Competence Network on Atrial Fibrillation (AFNET)]. / Register und Studien des Deutschen Kompetenznetzes Vorhofflimmern (AFNET).

The German Competence Network on Atrial Fibrillation (AFNET) is a national interdisciplinary research network funded by the Federal Ministry of Education and Research (BMBF). AFNET was initiated in 2003 and aims at improving treatment of atrial fibrillation (AF), the most frequent sustained cardiac arrhythmia. AFNET has established a nationwide patient registry on diagnostics, therapy, course and complications of AF in Germany. The data analyzed to date demonstrate that patients with AF are likely to have multiple co-morbidities, such as hypertension, valvular heart disease, coronary artery disease, diabetes mellitus and advanced age. Oral anticoagulation is provided to the majority of patients in accordance with the recommendations given by guidelines. Further areas of research deal with the optimal duration of antiarrhythmic therapy following electrical cardioversion of atrial fibrillation and the value of strategies to prevent arrhythmogenic changes, such as fibrosis in the atria, for prevention of further episodes of atrial fibrillation. Additional registry projects were established for patients with catheter-based interventional therapy of atrial fibrillation and surgical ablation to define success, complications and long term results of these recently developed procedures more clearly. Data and insights gathered from these projects were used to further develop standards of care in two international conferences.