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.

[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.

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.

[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.

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.

[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.

Late perforation of a right ventricular pacing lead: a potentially dangerous complication.

Four days after uncomplicated implantation of a two-chamber pacemaker and a normal postoperative course, a patient was referred to our hospital with left-sided hemothorax and early hemorrhagic shock. Chest X-ray and CT scan were suspicious of a right ventricular lead perforation with additional pericardial and pleural injury. Immediate surgery was performed via a lateral thoracotomy and the perforation was repaired via direct suture. An epimyocardial ventricular lead was implanted simultaneously. The patient made an uneventful recovery.

Epicardial versus transvenous left ventricular lead placement in patients receiving cardiac resynchronization therapy: results from a randomized prospective study.

BACKGROUND: The aim of this prospective study was to determine the differences in left ventricular (LV) lead positioning for cardiac resynchronization therapy (CRT): comparing a percutaneous transvenous approach via the coronary sinus versus epimyocardial placement via a left lateral mini-thoracotomy. METHODS: Eighty consecutive patients with symptomatic left ventricular dysfunction and an indication for CRT were randomized to receive either a transvenous (n = 40) or epicardial (n = 40) LV-lead placement. Postoperative follow-up included assessment of NYHA functional class, ECG and echocardiography. RESULTS: The transvenous group had a shorter ICU stay (0.66 vs. 3.8 days) and shorter ventilation times (0.34 vs. 3.2 h). The epicardial group had less exposure to radiation (7.4 vs. 23 min) and required less use of contrast medium (3.24 vs. 61 ml). At 6 months follow-up, no major differences in LV-lead parameters (threshold, sensing, and impedance) were observed. CONCLUSION: Both epicardial and transvenous LV-lead placement for CRT therapy are safe and effective. The transvenous approach is less invasive and should be considered the standard procedure for patients without renal insufficiency. However, in a case of difficult coronary venous anatomy with the inability to position the lead as desired, epicardial LV-lead placement remains an alternative option.

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.

[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.

Stentless mitral valve implantation in comparison to conventional mitral valve repair or replacement at five years.

OBJECTIVE: A chordally supported stentless mitral valve (SMV) may be a suitable prosthesis for patients with severe degenerative mitral valve disease. We analyzed the five-year results and compared them with results after conventional mitral valve repair or replacement. METHODS: 155 patients, operated on since August 1997, were evaluated. 53 patients (ages, 68 +/- 8 years, 37 female, valve repair not feasible) received a SMV (Quattro), 51 patients (69 +/- 9 years, 32 female) had mitral valve repair (MVR) and 51 patients (66 +/- 9 years, 32 female) had a conventional mitral valve replacement (MVP). There were no significant differences with respect to preoperative NYHA functional class, left ventricular ejection fraction, cardiac index and surgical risk, according to the EuroSCORE. Mean follow-up is 64 +/- 18 (21-89) months. RESULTS: Surgery was performed using a median sternotomy (32 [SMV]/20 [MVR]/34 [MVP]) or a lateral mini-thoracotomy 21/31/17 approach. The SMV was safely attached to the papillary muscles. In-hospital mortality was 1, 2 and 4 respectively; re-operation was required in 6, 2 and 3 patients. Five-year survival rate was 80.6 +/- 4.4 % (SMV), 80.2 +/- 5.6 % (CMV) and 82.6 +/- 5.6 % (MVP), p = n.s. After hospital discharge, there was no significant difference in mortality in comparison to an age-matched control population. Echocardiography revealed acceptable SMV hemodynamics with preservation of left ventricular function. CONCLUSION: Midterm results after SMV implantation are comparable to conventional approaches. Complete preservation of the annulo-ventricular continuity is advantageous and close to physiologic hemodynamics can be achieved. Long term follow-up is required.

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.

Diabetes in patients undergoing coronary artery bypass grafting. Impact on perioperative outcome.

Diabetes mellitus is an established risk factor related to significant morbidity and mortality after coronary artery bypass grafting. Data on 9682 patients undergoing coronary artery bypass grafting either with (n=8917) or without cardiopulmonary bypass (off-pump coronary artery bypass grafting; n=765) were subjected to an univariate analysis to identify potential associations between diabetes mellitus and 26 a priori selected perioperative outcome variables. Those having a significant association with diabetes were then subjected to a stepwise logistic regression model to identify the impact of diabetes as compared to additional 22 different a priori chosen patient related risk factors and treatment variables. Prevalence of outcome variables independently associated with diabetes has been determined in the subgroup of diabetics undergoing coronary artery bypass grafting with cardiopulmonary bypass or off-pump coronary artery bypass grafting surgery to evaluate the effect of avoiding cardiopulmonary bypass on perioperative patient outcome. Diabetes mellitus was defined as glucose intolerance either treated dietary, with oral hypoglycemics or with insulin. According to this definition of diabetes mellitus we found an overall prevalence of 37.1% (coronary artery bypass grafting with cardiopulmonary bypass: 37.5%; off-pump coronary artery bypass grafting: 32.5%). Eleven outcome variables having a significant association with diabetes were identified. Diabetes could be identified as an independent predictor of postoperative delirium, renal dysfunction and respiratory insufficiency. Prevalence of these three variables was lower in diabetics undergoing off-pump coronary artery bypass grafting as in those undergoing coronary artery bypass grafting with cardiopulmonary bypass surgery reaching statistical significance with regard to postoperative delirium and respiratory insufficiency. In conclusion, diabetes mellitus is a significant independent predictor for three postoperative outcome variables in coronary artery bypass surgery. Avoiding cardiopulmonary bypass in diabetics seems to have a beneficial effect.

Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies.

OBJECTIVE: To test the hypothesis that atrial fibrillation (AF) is associated with changes in the expression of connexins 40 and 43 in the left atrium with more pronounced changes in mitral valve disease than in lone AF. METHODS: Protein concentrations of connexin 40 and connexin 43 were analysed in left atrial tissue of patients undergoing cardiac surgery. One group of patients had lone AF (n = 41), one group had AF and mitral valve repair (n = 36), and one group in sinus rhythm served as controls (n = 15). RESULTS: Western blot analysis of connexin 40 and connexin 43 expression showed an increase of both gap junctional proteins (connexin 43 > connexin 40) in patients with AF of all forms compared with patients in sinus rhythm (p = 0.01 and p = 0.011, respectively). Subgroup analysis showed increased concentrations of connexin 40 in lone AF and AF with mitral valve disease compared with sinus rhythm (p = 0.06 and p = 0.029, respectively), whereas the same analysis for connexin 43 reached significance only in the mitral valve disease group (p = 0.031). No differences in connexin 40 and connexin 43 expression were detectable between lone AF and AF with mitral valve disease. Within the groups connexin 40 and connexin 43 expression did not differ between patients with paroxysmal AF and patients with chronic AF. CONCLUSION: The present study shows for the first time that AF can induce changes in the left atrium with increased connexin expression. Furthermore, no systematic differences between patients with paroxysmal and chronic AF were detected.

Requirement for renal replacement therapy in patients undergoing cardiac surgery.

BACKGROUND: Despite refinements in perioperative patient management renal insufficiency requiring renal replacement therapy (RRT) is still a common complication after cardiac surgical procedures associated with impaired patient outcome and increased costs. METHODS: Prospective data on 16,184 patients undergoing different cardiac surgical procedures (CABG, n = 8917; beating heart CABG, n = 1842 [OPCAB, n = 765; MIDCAB, n = 1077]; aortic valve surgery, n = 1830; mitral valve surgery, n = 708; double valve surgery, n = 381; CABG and valve surgery, n = 2506) between April 1996 and August 2001 were subjected to univariate and multivariate logistic regression analysis. Postoperative RRT was defined as any postoperative renal insufficiency requiring first time hemofiltration or dialysis during the postoperative stay. Patients with preoperative dialysis dependent renal insufficiency were excluded from further analysis. RESULTS: The overall prevalence of postoperative RRT was 4.7% which varied according to different surgical procedures. 45 out of 49 selected pre- and intraoperative patient- and treatment-related variables had a significant association with postoperative RRT. 10 of these (renal disease, myocardial infarction, diabetes, cardiogenic shock, urgent operation, NYHA > or = 3, intraoperative hemofiltration, perfusion time > or = 2 hours, intraoperative low cardiac output, perioperative high transfusion requirement) were independent predictors. OPCAB surgery and younger patient age were identified as having a significantly lower predictive value for postoperative RRT. Patients with postoperative RRT were found to have a significantly longer ICU- and total postoperative hospital stay as well as a higher 30-day mortality. CONCLUSION: Identifying perioperative risk factors associated with postoperative RRT will help to reduce the incidence of this complication. Avoiding cardiopulmonary bypass seem to be beneficial with regard to the prevalence of postoperative RRT.

Epicardial treatment of atrial fibrillation using cryoablation in an acute off-pump sheep model.

BACKGROUND: The purpose of this study was to test the feasibility and effectiveness of cryoablation therapy (SurgiFrost trade mark CryoCath, Endocare Inc., Irvine, California, USA) for linear epicardial treatment of atrial fibrillation in an acute off-pump sheep model. METHODS: After thoracotomy, we performed epicardial cryoablation (2 min intervals at -160 degrees C) with pacing electrodes positioned at the left atrial appendage (LAA), the pulmonary veins (PVs), the right atrial appendage (RAA), and the vena cava cranialis (VCC) in 8 sheep. Circular epicardial ablations were performed with online temperature measurement in the ascending aorta and in the esophagus. The sheep were sacrificed two hours after ablation procedure, and heart, lungs, and esophagus were retrieved for histological examination. Out of all 8 sheep, histo-pathological analysis was performed on the RAA and VCC in 6 sheep and on the CAA and PV in all 8 sheep. RESULTS: Thin-walled structures such as PVs and VCC showed electrical isolation. No significant changes in temperature in the descending aorta and the esophagus were observed. There was evidence of extensive transmural alteration including vascular lesions, myocardial degeneration and necrosis as well as epi- and endocardial necrosis in the left atria in three of 8 cases, in the right atria in 5 of 6 cases, in the VCC in 6 of 6 cases, and in the PV in 5 of 8 cases. Mild lesions of the muscular layer of the esophagus were found in 7 of 8 cases. CONCLUSIONS: Epicardial cryoablation is not effective on thicker tissues like LAA and RAA due to the rewarming of the current blood flow. However, thin tissues like VCC and PV can be isolated. Further chronic studies are necessary to evaluate the potential for regeneration of adjacent structures.