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After the abolition of the milk quota in the European Union, milk price volatility is expected to increase because of the liberalized market conditions. At the same time, investment appraisal methods have not been updated to capture the increased uncertainty. Therefore, the objective of this paper is to assess the effect of changing price volatility due to quota abolition on investment decisions at the dairy farm level. To contribute to the objective and to approximate milk price volatility after the European milk quota abolition, the risk-adjusted discount rate for risk-averse dairy farmers is derived based on the milk price volatility of a milk price series from New Zealand. New Zealand dairy farmers have faced liberalized market conditions for more than 3 decades. Afterward, the risk-adjusted discount rate is applied to appraise milking technology investments for an average German dairy farmer. The results show that it is still more reasonable to invest in a parlor system than an automated milking system, although the net present value of the parlor system investment varies between €191,723 for risk-neutral dairy farmers and €100,094 for modestly risk-averse dairy farmers. For the automated milking system investment, the same calculations lead to €132,702 for risk-neutral dairy farmers and €31,635 for risk-averse dairy farmers. According to higher levels of milk price volatility after milk quota abolition, the reduction of the expected utility of the underlying investment decision for modest risk-averse dairy farmers is almost similar to a milk price decrease of 5% for risk-neutral dairy farmers. Therefore, the findings urge finance providers and extension services to consider the change of increasing milk price volatility after dairy quota abolition when giving dairy farmers financial advice. The risk-adjusted discount rate is a flexible tool to do so., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Since the very beginning of coronary artery bypass grafting, the search for optimal myocardial protection has fascinated both clinicians and basic researchers. This retrospective review of a large patient cohort aims to display the advantages of one of the protective procedures, namely simple, intermittent aortic cross-clamping (IAC). Thus, this review aims to significantly contribute to daily bypass surgery. This review reports on coronary patients who were all operated on in international centers using IAC such that this review presents the state of the art on IAC. In addition, this review reports on the usage of IAC for more than 2 decades in the clinic of Dr. Bircks, Duesseldorf (DE) and the clinics of his former students. A meta-analysis of published data of international centers summarizes 7 837 operated patients with a total mortality of 123 (=1.6%). This excellent outcome compares well to the results of the Bircks'-related centers, where between 1978 and 2001, a total of 41 573 patients were revascularized with the help of IAC according to the original protocol. The total mortality was 778 (1.9%), with the lowest mortality rate (1.2%) in the largest center (Bad Oeynhausen, DE). According to the presented experience, IAC for coronary revascularization proves to be a highly effective method for myocardial protection; it has convincingly proven to be simple, safe and cost-efficient.

Background: It was the aim of the present study to elaborate criteria for the assessment of rapid hemodynamic progression of valvar aortic stenosis. These criteria are of special importance when cardiac surgery is indicated for other reasons but the established criteria for aortic valve replacement are not yet fulfilled. Such aspects of therapeutic planing were mostly disregarded in the past so that patients had to undergo cardiac reoperation within a few years., Methods: Hemodynamic, echocardiographic, and clinical data of 169 men and 88 women with aortic stenosis, aged 55.2 +/- 15.7 years at their first and 63.4 +/- 15.6 years at their second cardiac catheterization, were analyzed., Results: The progression rate of aortic valve obstruction was found to be dependent on the degree of valvar calcification ([VC] scoring 0 to III) and to be exponentially correlated with the aortic valve opening area (AVA) at initial catheterization. Neither age nor sex of the patient nor etiology of the valvar obstruction significantly influence the progression of aortic stenosis. If AVA decreases below 0.75 cm(2) with a present degree of VC = 0, or AVA of 0.8 with VC of I, AVA of 0.9 with VC of II, or AVA of 1.0 with VC of III, it is probable that aortic stenosis will have to be operated upon in the following years., Conclusions: The present data indicate that for clinical purposes and planning of valvar surgery the progression of asymptomatic aortic stenosis can be sufficiently predicted by the present aortic valve opening area and the degree of valvar calcification.

After a shortened history of conventional closed and open heart surgery, including hypothermia by surface cooling and extracorporeal circulation, the first application of a new membrane oxygenator developed by ML Bramson with an integrated temperature exchange system and a heart-lung machine (HLM) was reported in 1972. The aim was to have an efficient oxygenating and gas exchange artificial lung that allowed prolonged perfusions in patients with cardiogenic shock or acute respiratory insufficiency. After in vitro closed recirculation studies comparing different bubble, vertical screen, and the new membrane oxygenators, the Bramson HLM was used in dog experiments before starting clinical cardiac surgery with routine interventions (closure of an atrial septal defect). The first clinically prolonged support for more than three hours after a double valve replacement in a NYHA class IV patient failed. A partial venoarterial prolonged perfusion for 42 hours and 43 minutes in a 10-year-old girl after surgical correction of a partial av canal defect and postoperative development of consistent lung edema caused by myocardial failure after an ischemic time of 43 minutes was the first successful long-term perfusion case in Europe. These first experiences with the Bramson membrane lung formed the basis, in our group, for further investigations of different perfusion routes and cannulations in animal experiments. Also, scanning electron microscopy studies could be performed with experimentally and clinically used membranes. The development of disposable membrane lung devices, for instance, Lande-Edwards, Kolobow Scimed, and General Electric Peirce membrane lungs, ameliorated and improved the use of these devices considerably. Also, BRAMSON had developed a disposable membrane lung device that had proved to be very effective in animal experiments by 1972, but, unfortunately, this device did not become commercially available.

Hypertrophic cardiomyopathy (HCM) can be caused by mutations in genes encoding for the ventricular myosin essential and regulatory light chains. In contrast to other HCM disease genes, only a few studies describing disease-associated mutations in the myosin light chain genes have been published. Therefore, we aimed to conduct a systematic screening for mutations in the ventricular myosin light chain genes in a group of clinically well-characterised HCM patients. Further, we assessed whether the detected mutations are associated with malignant or benign phenotype in the respective families. We analysed 186 unrelated individuals with HCM for the human ventricular myosin regulatory (MYL2) and essential light chain genes (MYL3) using polymerase chain reaction, single strand conformation polymorphism analysis and automated sequencing. We found eight single nucleotide polymorphisms in exonic and adjacent intronic regions of MYL2 and MYL3. Two MYL2 missense mutations were identified in two Caucasian families while no mutation was found in MYL3. The mutation Glu22Lys was associated with moderate septal hypertrophy, a late onset of clinical manifestation, and benign disease course and prognosis. The mutation Arg58Gln showed also moderate septal hypertrophy, but, in contrast, it was associated with an early onset of clinical manifestation and premature sudden cardiac death. In conclusion, myosin light chain mutations are a very rare cause of HCM responsible for about 1% of cases. Mutations in MYL2 could be associated with both benign and malignant HCM phenotype.

Background: Various molecular mechanisms are operative in altering the sarcomeric function of the heart under increased hemodynamic workload. Expression of the atrial isoform (ALC-1) of the essential myosin light chain, a shift from alpha-myosin heavy chain (MHC) to beta-MHC, increased phosphorylation of the regulatory myosin light chains and increased troponin I (TnI) phosphorylation have been reported to modulate cardiac contractility in rodents., Methods: TO ASSESS A POSSIBLE CONTRIBUTION OF THESE SARCOMERIC PROTEINS TO CARDIAC PERFORMANCE IN HUMAN MYOCARDIAL HYPERTROPHY, TWO DIFFERENT FORMS OF CARDIAC HYPERTROPHY WERE INVESTIGATED: 19 patients with hypertropic obstructive cardiomyopathy (HOCM) and 13 patients with aortic stenosis (AS) with marked left ventricular hypertrophy and normal systolic function., Results: There was no change in MHC gene expression, regulatory myosin light chain or TnI phosphorylation status in normal heart (NH), HOCM and AS patients. However, patients with hypertrophied myocardium expressed ALC-1 that was not detectable in NH. ALC-1 protein expression correlated positively with the left ventricular ejection fraction. In patients with hypertrophied myocardium, there was a mean ALC-1 protein expression of 12.7+/-3% (range 3.6% to 32%)., Conclusion: In humans, ALC-1 expression is in vivo a powerful molecular mechanism of the sarcomere to maintain or improve myocardial contractility under increased hemodynamic demands.

Background: Transaortic subvalvular myectomy (TSM) reduces left ventricular outflow tract gradient and improves symptoms and working capacity in patients with hypertrophic obstructive cardiomyopathy (HOCM). Nevertheless, TSM does not completely restore normal ventricular function, and some patients complain of symptoms despite optimal surgical results. Abnormal myocardial collagen structure in hypertrophic cardiomyopathy might be an indicator of impaired cardiac function., Methods: Nine patients with HOCM were investigated. Myocytic diameter, collagen volume fraction and light absorbance of immunohistochemically stained collagen subtype I and its product (Coll I(prod)) were measured quantitatively in myectomy specimens. Patients underwent symptom-limited bicycle exercise testing with equilibrium radionuclide angiocardiography to determine ejection fraction (EF). Right heart catheterization was performed simultaneously in order to measure pulmonary capillary wedge pressure (PCWP) as a parameter of global ventricular diastolic filling and cardiac index (CI) as a parameter of functional capacity., Results: Postoperatively, CI increased from 3.1 +/- 0.4 to 5.7 +/- 1.3 l/min/m(2) under exercise. EF was normal at rest (64 +/- 9 %) but did not increase significantly under exercise (66 +/- 14 %). Coll I(prod) (13.62 +/- 7.35 Vv%(prod)) correlated inversely with EF under exercise (r = -0.64; p = 0.05). PCWP increased under exercise from 8 +/- 2 mmHg at rest to 22 +/- 9 mmHg (p = 0.01). Coll I(prod) correlated with PCWP under exercise (r = 0.90; p = 0.001)., Conclusions: Increased collagen subtype I is a predictor of diastolic as well as systolic dysfunction under exercise in patients with HCM after successful TSM.

Background: 'Post-Perfusion Syndrome' (PPS) after cardiopulmonary bypass (CPB) is known to be evoked by inflammatory reactions. The hypothesis of a pathogenetic role for the neutrophil granulocytes in this inflammation would be strengthened if elevated concentrations of a neutrophil product such as elastase could be demonstrated, particularly in case of a PPS or a systemic inflammatory response syndrome (SIRS)., Methods: In a randomized prospective double-blind study, 40 patients undergoing aortocoronary bypass grafting (CABG) were divided into 4 groups of 10 patients each. One group served as the control group, one received prostacyclin (PGl 2 ), the third group was substituted with high-dosed aprotinin and the last group was treated with a combination of PGl 2 and aprotinin. 6 blood samples were taken from every patient perioperatively, and plasma elastase (PE), procalcitonin (PCT), C 1 -esterase inhibitor (CEI) and parameters of coagulation and fibrinolysis were determined., Results: Levels of elastase increased significantly in all intra- and postoperative blood samples compared to the preoperative baseline values (< 30 microg/l, p < 0.05). The elastase release was even more pronounced in the control and aprotinin group (170 +/- 23 microg/l; 175 +/- 14 microg/l during ECC) compared to patients who received prostacyclin (142 = 21 microg/l, p < 0.05). Duration of myocardial ischemia could be directly correlated to elastase levels at the end of CPB. 10 of the 40 patients suffered postoperatively from a PPS or a SIRS; in these patients, elastase levels at the end of CPB were significantly higher (188 +/- 26 microg/l vs. 138 +/- 22 microg/l, p < 0.05). Immediately after the operation, these 10 patients also showed significant changes in the cascades of coagulation and fibrinolysis resulting in a hypercoagulatory state. Levels of PCT and CEI did not change significantly during and after ECC., Conclusions: Our results indicate that CPB initiates an elastase release that can be suppressed by prostacyclin. Increased intraoperative elastase levels in patients with PPS show that elastase may be an indicator of ongoing systemic inflammation, possibly causing complications due to a hypercoagulatory state. Myocardial ischemia seems to be one reason for this elastase release. It can be speculated that early PGl2-infusion could be a therapeutic option in inflammatory diseases caused by ECC.

Background: In animal models, increased signaling through the calcineurin pathway has been shown to be sufficient for the development of cardiac hypertrophy. Calcineurin activity has been reported to be elevated in the myocardium of patients with congestive heart failure. In contrast, few data are available about calcineurin activity in patients with pressure overload or cardiomyopathic hypertrophy who are not in cardiac failure., Methods and Results: We investigated calcineurin activity and protein expression in 2 different forms of cardiac hypertrophy: hypertrophic obstructive cardiomyopathy (HOCM) and aortic stenosis (AS). We found that the C-terminus of calcineurin A protein containing the autoinhibitory domain was less abundant in myocardial hypertrophy than in normal heart, which suggests the possibility of proteolysis. No new splice variants could be detected by reverse-transcription polymerase chain reaction. This resulted in a significant elevation of calcineurin enzymatic activity in HOCM and AS compared with 6 normal hearts. Increased calcineurin phosphatase activity caused increased migration of NF-AT2 (nuclear factor of activated T cells 2) in SDS-PAGE compatible with pronounced NF-AT dephosphorylation in hypertrophied myocardial tissue., Conclusions: Hypertrophy in HOCM and AS without heart failure is characterized by a significant increase in calcineurin activity. This might occur by (partial) proteolysis of the calcineurin A C-terminus containing the autoinhibitory domain. Increased calcineurin activity has functional relevance, as shown by altered NF-AT phosphorylation state. Although hypertrophy in AS and HOCM may be initiated by different upstream triggers (internal versus external fiber overload), in both cases, there is activation of calcineurin, which suggests an involvement of this pathway in the pathogenesis of human cardiac hypertrophy.

Background: The data of 111 (male: 64; female: 47) in the period of 1967 until 12/93 consecutive operated neonatals (<1 month) were studied retrospectively (mean weight 3270 g, mean age at operation 14 days)., Methods: Preductal anatomy was present in 96 patients. The coarctation was isolated in 30 patients (group I), 34 patients had additional large ventricular septal defects (group II) and 47 had complex heart disease (group III). The preoperative heart catheterization revealed a gradient of <20 mmHg in 35%, >20 mmHg in 51.4% and >50 mmHg in 12.9%. The indication for repair was conservatively untreatable heart insufficiency. In the vast majority (n=97) of patients resection and end-to-end anastomosis were performed, in 31 cases using an absorbable suture, in 18 of these using a continuous suture line. In 4 patients a subclavian flap angioplasty (SFA) was done, in 4 a patch enlargement, 4 times a repair was described as not possible and in 2 patients there was no gradient after division of the ductus., Results: Early lethality was 3.3% (n=1) in group I, 24.2% (n=8) died in group II and 39.1% (n=18) in group III; after introducing Prostaglandin E1 0% in group I, 15% in II and 25% in III. Relevant recoarctation (Gradient >20 mmHg) developed in 9 (among them 4 with hypoplastic arch, 2 after SFA) of the 77 long-term survivors; 6 of these were reoperated on, 5 without residual gradient, 1 with a gradient of 25 mmHg without clinical symptoms (after 4 years). In the last 3 patients a balloon dilation was carried out without residual gradient. Mean follow-up time was 6 (0-24) years. No patient needs antihypertensive treatment. The cumulative survival rate is 96.7% (+6.6%) for group I, 77.4% (+15.0%) for II and 51.9% (+16.6%) for III., Conclusions: Resection and end-to-end anastomosis using a continuous absorbable suture is the method of choice at theoretical considerations and in our experiences. The number of recoarctations in neonatal age is relatively high; reinterventions (operation respectively dilation) can be done safely and successfully.

Background and Aim of the Study: A treatment dilemma arises when endocarditis is complicated by cerebral embolism. Secondary cerebral hemorrhagic complications may arise following suppression of coagulation during extracorporeal circulation. Extensive valvular vegetation is regarded as an indicator for urgent surgery. The study aim was to determine the relative risk of thromboembolic complications, and to analyze the prognostic influence of different treatment strategies following onset of these complications, in particular, secondary cerebral hemorrhagic events after urgent surgery., Methods: Between 1978 and 1993, endocarditis was diagnosed in 288 consecutive patients. Patients treated before 1982 (6.9%) were analyzed retrospectively. The remaining patients (93.1%) were followed prospectively (mean 4.3+/-1.7 years)., Results: In 50 patients (17.4%), the clinical course was complicated by one embolism, and in 58 patients (20.2%) by recurrent embolisms. In total, 71% of all embolisms were cerebral events. The operated patients were categorized with regard to the time between recurrent thromboembolic events and cardiac surgery (<72 h, 3-8 days, and >8 days). The prognosis for patients operated within 72 h was significantly more favorable (p <0.0001) than for those treated medically. Patients undergoing cardiac surgery more than eight days after stroke, and those treated conservatively, had poor prognoses., Conclusion: When endocarditis is complicated by stroke, it is recommended that cardiac surgery be performed within 72 h of the cerebral embolism, when the risk of secondary cerebral hemorrhage appears to be low. Cranial computed tomography is obligatory immediately before surgery in order to identify patients with early reperfusion hemorrhages due to spontaneous fragmentation of the thrombus. In these patients, cardiac surgery must be postponed because of the high risk of severe cerebral bleeding during extensive perioperative anticoagulation, and is only justified in the case of an otherwise unfavorable prognosis.

A prospective randomized study was done including 1,000 patients undergoing routine open heart surgery. Patients were randomly assigned to either a roller pump or a BioMedicus centrifugal pump with identical extracorporeal circuits. There were no significant differences between study groups. Actual blood products transfused and predicted transfusion requirements (using Cardiac RiskMaster) were examined as was chest tube drainage (CTD). The predicted transfusion requirement was 885 of 1,000 patients. Transfusions were required by 472 of 1,000. Risk factors as significant predictors of increased CTD and use of blood products were emergency surgery status, increased cross-clamp time, and higher predicted risk of mortality. The only significant predictor of decreased CTD was the use of a centrifugal pump. Predictors of increased length of stay were myocardial infarction, preoperative urea, age, and massive transfusion. Data provide evidence that use of the centrifugal pump improves patient outcomes by decreasing CTD and decreasing the requirements for transfusion, which results in a shorter hospital stay.

Background: Operative strategies and early results concerning repair of Total Anomalous Pulmonary Venous Connection (TAPVC) are relatively well known. Less well defined data are available to evaluate the long-term outcome. We would therefore like to contribute our long-term data in this presentation., Patients and Methods: Between 1958 and 1992 52 consecutive patients aged two days to 42 years (15 neonates, 16 infants, 9 children and 12 adults) with TAPVC were operated on. The data were collected retrospectively from the records. In 24 patients, a current follow-up study was performed, including clinical evaluation, echocardiography, and a twenty-four-hour ambulatory ECG., Results: Early mortality was 34.6% (n = 18). The postoperative follow-up period ranged from 4 months to 28 years (mean 10.7 years). There were 4 late deaths, yielding an overall long-term mortality of 7.7% (4/52). Causes of death were severe hypoplasia of central pulmonary veins in 1, ventricular fibrillation (2) and non-cardiac in one case. 80% of the operative survivors were available for assessment. Preoperatively, 11 of these patients were in NYHA functional class II, six in class III and seven in class IV. After treatment, 22 patients were in class I and two in class II. Ventricular function was evaluated by echocardiography and invasive catheterization. Only two of 24 patients (8%) showed an abnormal IVS-motion and enlargement of the right ventricle. Cardiac catheterization revealed a mean PA pressure of 26 mmHg, the peak systolic pressure in the RV was 34 mmHg. All 24 long-term survivors underwent assessment of cardiac rhythm by 24 h electrocardiogramm (ECG) monitoring. Significant arrhythmias were recorded in 11 of 24 cases (46%), including sinus node dysfunction in 3 patients. Multiform ventricular ectopic beats were evaluated in 9 cases. According to the Lown classification, 7 patients were class I while 2 cases were considered to be class IV., Conclusions: A normal hemodynamic state can be achieved in most cases. Significant arrhythmias may exist in asymptomatic patients late after surgical correction of TAPVC, and therefore, long-term follow-up of these patients, including 24 h ECG monitoring, is recommended, even if they are asymptomatic.

Background: Former studies on sternal wound infections indicate predisposing factors like diabetes, obesity, use of bilateral internal mammary grafts, impaired renal function and reoperation. We wanted to evaluate whether the time of resternotomy for postoperative bleeding has any influence on the development of a sternal wound infection and other complications., Methods: In our department, 12,315 patients underwent median sternotomy for cardiac surgery between 1987 and 1998. We analyzed the clinical data of all patients which were reoperated on for postoperative bleeding, especially patients with subsequent operations caused by sternal wound infections. All data were compared by T-test respectively chi2-test, and p<0.05 was regarded as significant., Results: 406 of the 12,315 patients were re-explored because of postoperative bleeding (3.3%). 57 (14%) of these patients died in the postoperative period of non-infectious complications. The remaining patients were divided into two groups: Group A (286 patients) (70.4%) did not suffer from any sternal wound complications, where as group B patients (n = 63) (15.6%) needed subsequent surgery due to sternal infection. There were no significant differences in either concerning age, clinical data and first operation. All patients had an average blood loss of 223 ml/hr. The time before re-operation for bleeding was 5.3+/-1.7 hours in group A compared to 11.1+/-4.2 hours in group B (p<0.05). A significant delay of reoperation for bleeding could also be found for patients with postoperative septic complications (ø: 5.2+/-1.9 hours, +: 12.9+/-5.2 hours), renal failure, mechanical ventilation >48 hours and a stay in hospital >20 days., Conclusions: Early reoperation for postoperative bleeding decreases the number of subsequent complications, e.g. sternal wound infections, septic complications and prolonged mechanical ventilation.

Background: Ischemic heart disease is the major cause of death in patients with end-stage renal disease. The high prevalence of coronary artery disease results in a rising number of dialysis patients requiring myocardial revascularisation., Objective: The objective of this study was to compare the outcomes of recurrent angina, myocardial infarction, rate of reinterventions and cardiovascular death following percutaneous coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) in patients with end-stage renal disease., Patients and Methods: In a retrospective investigation 40 patients with chronic renal failure undergoing primarily PTCA and 65 patients undergoing CABG were included. Both groups were comparable for gender, duration on dialysis and the number of cardiovascular risk factors per patient. Patients undergoing PTCA were younger (53 +/- 12 years vs. 57 + 8 years; p < 0.05) and more often diabetics (30% vs. 14%; p < 0.05)., Results: Most patients in both groups had a multi-vessel disease (95% in the CABG group vs. 74% in the PTCA group), in the CABG group there were significantly more patients with a triple-vessel disease (62% with vs. 40% in the PTCA group; p < 0.01), PTCA was primarily successful in 95% of the patients while complete revascularization was achieved in 88% of patients undergoing CABG. The perioperative mortality after CABG was 4.8% as compared to none after interventional revascularisation. The cumulative freedom of angina after 6, 12 and 24 months after intervention was significantly lower after PTCA (54%, 40%, 29%) than after bypass grafting (97%, 94%, 90%, p < 0.001). The frequency of reinterventions following PTCA was significantly higher compared to patients following CABG (p < 0.001). After PTCA 15 patients needed further revascularisations, 8 of them underwent CABG, whereas after CABG only two patients required additional myocardial revascularisation. There was no significant difference in the overall mortality between both groups; the survival rate after 12 and 24 months was 95% and 82% after PTCA and 93% and 86% after CABG, respectively., Condition: Although patients receiving CABG had a more severe coronary artery disease the overall mortality was comparable and clinical and functional outcome was improved compared to patients after coronary angioplasty.

Purpose: Since it is of great importance to distinguish between a systemic inflammatory response syndrome (SIRS) and an infection caused by microbes especially after heart transplantation (HTX), we examined patients following heart surgery by determining procalcitonin (PCT), because PCT is said to be secreted only in patients with microbial infections., Methods: Sixty patients undergoing coronary artery bypass grafting (CABG) and 14 patients after heart transplantation were included in this prospective study. In the CABG group we had 30 patients without any postoperative complications (group A). Furthermore we took samples of 30 patients who suffered postoperatively from a sepsis (group B, n=15) or a systemic inflammatory response syndrome (C, n=15). In addition we measured the PCT-levels in 65 blood samples of 14 patients after heart transplantation (Group I: rejection > IIa, II: viral infection (CMV), III: bacterial/fungal infection, IV: controls)., Results: In all patients of group A the pre- and intraoperative PCT-values and the measurement at arrival on intensive care unit (ICU) were less than 0.2 ng/ml. On the second postoperative day the PCT-value was 0.33+/-0.15 ng/ml in the control group. At the same time it was 19.6+/-6.2 ng/ml in sepsis and 0.7+/-0.4 ng/ml in systemic inflammatory response syndrome patients (P<0.05). In transplanted patients we could find the following PCT-values: Gr.I: 0.18+/-0.06 II: 0.30+/-0.09 III: 1.63+/-1.16 IV: 0.21+/-0.09 ng/ml (P<0.05 comparing group III with I, II and IV)., Conclusions: These results show that extracorporeal circulation (ECC) and systemic inflammatory response syndrome do not initiate a PCT-secretion. Septic conditions cause a significant increase of PCT. In addition, PCT is a reliable indicator concerning the essential differentiation of bacterial or fungal--not viral--infection and rejection after heart transplantation.

The beta-myosin heavy chain gene (MYH7) encodes the motor protein that drives myocardial contraction. It has been proven to be a disease gene for hypertrophic cardiomyopathy (HCM). We analyzed the DNA sequence variation of MYH7 (about 16 kb) of eight individuals: six patients with HCM and two healthy controls. The overall DNA sequence identity was up to 97.2% compared to Jaenicke and coworkers (Jaenicke et al. [1990] Genomics 8:194-206), while the corresponding amino acid sequences revealed 100% identity. In HCM patients, eleven nucleotide substitutions were identified but no causative disease mutation was found: six were detected in coding, four in intronic, and one in 5' regulatory regions. The average nucleotide diversity across this locus was 0.015% with an average of 0.02% in the coding and 0.012% in the noncoding sequence. Analysis of the kinetic behaviour of beta-MHC in the intact contractile structure of normal individuals and HCM patients revealed apparent rate constants of tension development ranging between 1.58 s(-1) and 1.48 s(-1)., (Copyright 2000 Wiley-Liss, Inc.)

Background and Objective: It is of great importance to assess progression of aortic valvar stenosis (AVS) when cardiac surgery is planned for other indications when established criteria for aortic valve replacement are not fulfilled at that moment. These considerations have often been ignored in prospective planning of treatment, necessitating a second cardiac surgical intervention just a few years later. The aim of this study was to establish criteria for estimating the rate of progression of AVS., Patients and Methods: Clinical, echocardiographic and haemodynamic data were analysed for 169 patients with aortic valvar stenosis (169 men, 88 women; mean age at first cardiac catheterization [CC] 55.2 +/- 15.7 years, at second CC 63.4 +/- 15.6 years., Results: The degree of AVS increases exponentially in relation to the extent of calcification (graded 0-3) and the fall in transaortic gradient (TG), from a TG > 0.6 mmHg/ml stroke volume and can be sufficiently predictable for clinical purposes. But neither age, sex nor the aetiology/pathology of the valvar defect have a sustained influence on the progression of AVS., Conclusions: These data indicate that knowing the current reduction in TG and the degree of calcification makes it possible to assess the likely progression of previously asymptomatic AVS and thus greatly facilitate the decision of whether or not to combine aortic valve replacement with another indicated cardiac operation.

Background: The increasing development of antimicrobial resistance of common bacterial pathogens presents one of the most significant challenges to clinical medicine, particularly intensive care medicine. One factor which has contributed to this development is the (over)use of antibiotic treatment. Therefore the objective of this study was to scrutinize the current practice of empiric antibiotic therapy in cardiac surgery in Germany for 1) perioperative prophylaxis and 2) postoperative therapy prior to the availability of susceptibility patterns for the infecting pathogen., Methods: A questionnaire was sent to all centers performing cardiac surgery in Germany. Questions referred to drugs used as well as dosage, homogeneity and duration of antibiotic prophylaxis, time and/or reason for changing this regimen, drugs used for first-, second-, and third-line empiric postoperative antibiotic treatment, and homogeneity of antibiotic usage., Results: All but 3 institutions (96.3%) answered. 1. Perioperative prophylaxis: All but 4 centers (94%) use first- (n = 32 = 43%) or second-generation cephalosporins (n = 38 = 51%) most commonly for 24 hours (n = 60 = 81%). Prophylaxis never exceeds 3 days. 74% of all institutions (n = 55) use the same antimicrobial agent for all cardiac procedures performed, while 26% (n = 19) change their regimen in selected patient groups, most commonly for heart transplantation. The entire prophylaxis is changed mainly according to susceptibility patterns (n = 63 = 85%), 7 centers (10%) change according to a fixed time schedule, while 4 institutions (5%) never change the antimicrobial drug. 2. Empiric postoperative therapy: A total of 29 different antibiotics out of 8 subclasses are used. No major differences between 1st-, 2nd-, and 3rd-line therapy could be detected, with the exception of a decreasing usage of beta-lactams (carbapenems excluded) from 60% in 1st-line to 23% in 3rd-line therapy and an increasing usage of glycopeptides from 5% in 1st-line to 18% in 3rd-line therapy. 41 institutions (55%) use the same antibiotic regimen on the intensive care unit and the normal ward, 9 centers (12%) use the same drug for perioperative prophylaxis and postoperative therapy, and 12 institutions (16%) prescribe a combination therapy., Conclusions: Perioperative prophylaxis in cardiac surgery in Germany is performed on a relatively uniform basis and at low cost. The heterogeneity of antibiotic regimens for postoperative therapy may indicate the need for recommendations and/or guidelines for this type of treatment. The indications for the usage of reserve antibiotics, e.g. vancomycin, implying the possible risk of creating pathogens with untreatable resistance patterns, as well as strategies aimed at preventing the development of resistance should be the subject of further discussions.

The basic helix-loop-helix transcription factors eHAND and dHAND are involved in developmental cardiac growth and differentiation. We investigated HAND gene expression in the normal and in the hypertrophied right and left ventricle of patients with tetralogy of Fallot (ToF) and hypertrophic obstructive cardiomyopathy (HOCM). HAND mRNA was constitutively expressed in the hypertrophied heart and increased in the hypertrophic tissue of both patient groups. HAND genes had a complementary left-right cardiac asymmetry of expression with dHAND predominantly in the right and eHAND in the left ventricle. The two cardiac bHLH factors have the ability to form heterodimers with the ubiquitous bHLH protein E12, subsequently recognizing E-boxes in the promoter region of target genes like ALC-1. We found a highly significant positive correlation between HAND and ALC-1 mRNA. The total ALC-1 protein level in ToF was smaller than in HOCM, although ALC-1 mRNA as well as HAND mRNA levels were significantly higher. ToF patients expressed around four times more ALC-1 mRNA for similar amounts of ALC-1 than HOCM patients. Suggesting disturbed ALC-1 translation in ToF, we found ALC-1 antisense mRNA expression in the hypertrophied, but not in the normal, ventricles. The higher the antisense/sense ALC-1 mRNA ratio, the lower ALC-1 protein was expressed., (Copyright 1999 Wiley-Liss, Inc.)

The adult rodent heart adapts to increased work load by reexpression of its fetal genes, for example, beta-myosin heavy chain (MHC), in order to improve contractile function. However, the human ventricle regulates contractility by expression of atrial essential myosin light chain (ALC-1) rather than beta-MHC. We evaluated the impact of both mechanisms in patients with hypertrophic cardiomyopathy. MHC isoform expression was quantified at the mRNA and protein levels by reverse transcriptase polymerase chain reaction and immunoblotting, respectively. Although alpha-MHC mRNA was detected in control and hypertrophied human ventricular tissue, alpha-MHC protein was not observed. Similarly, we investigated the expression of ALC-1 by two-dimensional polyacrylamide gel electrophoresis and the clinical and hemodynamic parameters of the patients with hypertrophic cardiomyopathy. We found a significant positive correlation between ALC-1 protein expression and dP/dtmax in the hypertrophied human ventricle in vivo. Correlations between dP/dtmax and expression of protein for the ryanodine receptor and L-type Ca2+ channel were excluded. Our data suggest that reexpression of ALC-1 improves the contractile state of the adult human heart. We propose that two evolutionarily divergent compensatory mechanisms for increased work demand exist in the mammalian heart: MHC regulation in rodents and essential MLC regulation, of cardiac contractility, in humans.

Background: The natural history of Hypertrophic Obstructive Cardiomyopathy (HOCM), is well known from earlier investigations. The yearly death rate of medically or non-treated patients with HOCM is between 1.7% and 4%. After conservative management with beta-blockers and/or calcium antagonist, early improvement is followed in many patients by a symptomatic and clinical impairment, which today may lead to surgical or interventional treatment., Methods: From 1963 to 12/1998 a total of 519 patients were operated by transaortic subvalvular myectomy (TSM). The mean age was 49 +/- 11 years (range 3 months - 82 years) in 292 males and 227 females., Results: The early risk was related to the clinical class (NYHA) and the need for additional cardiac procedures during the same intervention. Total early mortality was 4.4% (n=23), in isolated myectomy 3.6% (n= 11). During the last 10 years it could be reduced to 1.9%. The first complete (100%) reinvestigation of 346 patients up to 26 years after surgery (1963-1991) demonstrated a disease-related mortality rate of 5.2% (n=20). The analysis of late deaths showed that disease-related lethal complications (sudden death, life-threatening arrhythmias, valve endocarditis, secondary LV dilatation) were relatively rare, the age-related death rate nearly followed the natural course because of other causes. The cumulative survival rate after 10 years was 88%, after 20-26 years 72%. The yearly disease-related death rate could be reduced to 0.6%. The long-lasting, symptomatic clinical improvement (NYHA I-II), and also the physical and mental capacity with enlargement of the acitivity radius and improvement of quality of life were remarkable. The positive effects of surgical enlargement of the LVOT could be confirmed in the meantime by hemodynamic, rhythmological, echocardiographic investigations as well as endurance tests., Conclusion: We have examined the outcome of a large series of patients treated surgically for HOCM since 1963. The majority of patients were in NYHA class III and came to surgery after long-term medical, but finally insufficient, management. The perioperative risk could be reduced considerably during recent years, despite the advanced cardiomyopathy status. The long-term postoperative observation of the patients demonstrated an unexpectedly continuing good outcome. Therefore these results may serve as a standard for assessing the results after the less invasive alcohol-induced transcoronary ablation of septal hypertrophy.

Background: This study aims to evaluate the early and late outcome of patients treated by surgery for myasthenia gravis and the diagnostic value of the Besinger Score, which is based on a correlation of severity of symptoms with specific antibodies to acetylcholine receptors, in the follow-up investigation after surgical therapy., Methods: Between June 1984 and April 1992 thoracotomy was performed in 51 myasthenia gravis cases at our department. The retrospective analysis considered patients with (n = 13) or without thymoma (n = 38). The Besinger score was used to describe the severity of disease preoperatively and up to 5 years postoperatively., Results: The Besinger score fell continually post surgery. Changes in relative serum concentrations of antibodies were similar to the Besinger score. Five years after thymectomy complete remission was diagnosed in 40% of the patients. The required dosage of pyridostigmine had fallen by two thirds after 5 years. Patients with follicular hyperplasia had significantly higher remission rates than those with thymoma., Conclusions: Surgery for myasthenia gravis is successful. The Besinger score well quantifies the severity of the disease.

Hypertrophic cardiomyopathy (HCM) is a disease with different etiological, morphological, functional, clinical and therapeutic aspects. Recent investigations indicate that HCM is considerably widespread in the population (1:500). The causes seem to generate from familial or sporadic abnormalities (mutations). Depending on the clinical aspect, the complaints, and on the basis of morphologic and hemodynamic investigational results, we mainly have to consider two types of medical and surgical management. 1. Hypertrophic nonobstructive cardiomyopathy (HNCM) Patients may have no hemodynamic or morphologic deviations, but may be identified by familial moleculargenetic investigations. Others may have different types of rhythm disturbances which may indicate a higher risk of sudden death. Depending on the degree of hypertrophy, the clinical impairment indicates medical therapy with beta-blockers, Ca antagonists, and antiarrhythmic drugs. In the case of clinical deterioration and manifestation of myocardial insufficiency diuretics, digitalis, ACE inhibitors, and catecholamines are indicated. Further impairment may lead to heart transplantation or as a bridging procedure to implantation of a left ventricular or biventricular assist device until a suitable donor heart is available. 2. Hypertrophic obstructive cardiomyopathy (HOCM) Symptomatic patients may have different localizations of the left ventricular outflow tract obstruction (LVOTO) in the subaortic area (typical form) and in midventricular position of the LV (atypical form). The first therapeutic step is always medical therapy with beta-blockers, Ca antagonists, and antiarrhythmic drugs. Further deterioration toward clinical class III (NYHA) despite long-term medication until recently was generally accepted as indication for transaortic subvalvular myectomy (TSM). Today mostly two other techniques are preferred--if possible Double chamber pacing (DCP) (atrial triggered ventricular pacing), Transcoronary ablation of septal hypertrophy (TASH) (by selective injection of alcohol, 95%, into the first septal branch). Especially in younger patients, after syncope, life-threatening tachyarrhythmias, and after resuscitation, the implantation of a cardioverter defibrillator may be necessary. Comparative prospectively randomized studies between different therapeutic regimens for HOCM are not available. Retrospective analyses of patients after TSM show a considerable clinical improvement. The risk of sudden death is relatively low, but not excluded. Patients after TSM demonstrate advantages concerning the survival rate despite the more deteriorated condition against those after medical therapy only. According to the new interventional techniques, long-term results are not yet available, of course. However, the long-term results after TSM may serve as a comparative standard which have at least to be reached by DCP and/or TASH.

Background: The reasons for a systemic inflammatory response syndrome (SIRS) following ECC are not yet fully understood. Procalcitonin (PCT) blood levels may distinguish between bacterial infections and a non-bacterial systemic inflammation. We investigated the influence of ECC, ECC modified by application of aprotinin, systemic inflammation, and bacterial infection on the PCT values., Methods: 20 CABG patients were randomized and divided in two groups. Group A served as the control group, while group B perioperatively received a high dose of aprotinin. Blood samples for measurement of PCT were taken 6 times perioperatively. Furthermore, blood samples were taken from 20 preoperatively comparable patients who suffered from bacterial infection (n = 10) (group C) or a SIRS (n = 10) (group D) after ECC; in these groups PCT was determined daily after the onset of inflammation., Results: There was no significant elevation of PCT in group A or B at any time. In sepsis patients a significant elevation of PCT was seen, with the peak level of 18.6+/-6.3 ng/ml on the second day after diagnosis; the PCT level of SIRS patients remained constantly low (<0.9 ng/ml)., Conclusions: In this study it was demonstrated that ECC and the use of aprotinin did not have any influence on the secretion of PCT. A systemic bacterial infection caused a significant increase of PCT, whereas PCT values remained normal in case of a SIRS. So it seems to be possible to distinguish between a primary SIRS and a bacterial sepsis by means of PCT.

Collagen is an essential part of the cardiac interstitium. Collagen subtypes, their location, total amount and the architecture of the fibrillar network are of functional importance. Architecture in terms of density of the fibrillar network is assumed to be reflected by the intensity of immunohistochemical staining of collagen. The aim of this study was to evaluate a video-based microdensitometric method for quantifying density expressed as absorbance of collagen subtypes I and III stained with an indirect immunoperoxidase method in myectomy specimens of patients with hypertrophic obstructive cardiomyopathy. Various factors influencing the immunohistochemical staining product and the technical properties of the image analysis system were investigated. Linearity between collagen concentration and the absorbance of the immunohistochemical staining product was demonstrated for collagen I using a dot-blot technique. Immunohistochemical collagen staining and density measurement were easily reproducible. The cardiac disability of the patients was assessed according to the New York Heart Association (NYHA) criteria. There was a significant increase in collagen type I density with higher NYHA class, whereas no significant association was found for total collagen area fraction. Thus, video-based microdensitometry gives further insight into the structural remodelling of myocardial collagens and reveals their significance in the process of heart failure in hypertrophic cardiomyopathy.