Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study.

[Figure: see text].

European quality system for tissue banking.

AIM: The aims of this project were to analyze the factors that influence quality and safety of tissues for transplantation and to develop the method to ensure standards of quality and safety in relation to tissue banking as demanded by European Directive 2004/23/EC and its technical annexes. It is organized in 4 Working Groups, the objectives of each one being focused in a specific area. STANDARDS: The Guide of Recommendations for Tissue Banking is structured into 4 parts: (1) quality systems that apply to tissue banking and general quality system requirements, (2) regulatory framework in Europe, (3) standards available, and (4) recommendations of the fundamental quality and safety keypoints. REGISTRY: This Working Group handled design of a multinational musculoskeletal tissue registry prototype. TRAINING: This Working Group handled design and validation of a specialized training model structured into online and face-to-face courses. The model was improved with suggestions from students, and 100% certification was obtained. AUDIT: The Guide for Auditing Tissue Establishments provides guidance for auditors, a self-assessment questionnaire, and an audit report form. The effectiveness and sustainability of the outputs were assessed. Both guides are useful for experienced tissue establishments and auditors and also for professionals that are starting in the field. The registry prototype proves it is possible to exchange tissues between establishments throughout Europe. The training model has been effective in educating staff and means having professionals with excellent expertise. Member states could adapt/adopt it. The guides should be updated periodically and perhaps a European organization should take responsibility for this and even create a body of auditors.

The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease.

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and NTproBNP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.

Distal embolic protection during percutaneous intervention of aorto-coronary venous bypass grafts: the FIRST Trial.

OBJECTIVE: Interventions in aorto-coronary venous bypass grafts (CABG) can cause acute procedural complications due to distal embolization of debris. In the FIRST (First European Investigation Regarding the Systematic use of the TriActiv device) multicenter trial the distal endovascular protection system TriActiv (Kensey Nash) was evaluated during intervention of CABG. METHODS: 195 patients in 17 centers in Germany with significant disease of a vein graft were enrolled. Inclusion and exclusion criteria were comparable to the SAFER trial. RESULTS: Acute procedural success was achieved in 98% of cases. Aspirated debris was found in 96.5% of patients. Primary endpoints (MACE at 30 days) occurred in 8.7% of all pts. (ITT). No patient died and 7.2% of patients suffered from MI. The rate of early revascularization was 1.5%. Secondary endpoints (MACCE at 30 days) were found in 9.2% and at hospital discharge in 8.7% of patients. CONCLUSIONS: The TriActiv system is safe and effective. Normal post procedural flow can be preserved and the MACE rate is with 8.7% considerably low. The FIRST trial supports the growing belief that PCI of CABG should be performed with protection systems.

[Intravascular ultrasound-guided diagnosis after transmural anterior ischemia and cardiogenic shock]. / Ulzerierter LCA-Hauptstamm-Plaque: IVUS-geführte Diagnose nach transmuraler Vorderwand-Ischämie und kardiogenem Schock.

Acute coronary syndrome, if complicated by cardiogenic shock, has a high mortality. Urgent coronary angiography is important for decision of therapy. The present paper reports on a patient without angiographically high grade stenosis after thrombolysis. The intravascular ultrasound examination (IVUS) was important for diagnosis of ruptured plaque of the left main stem. Therapy options are discussed.

Detection of Helicobacter pylori specific DNA in human atheromatous coronary arteries and its association to prior myocardial infarction and unstable angina.

BACKGROUND: Chronic infections have been proposed to play a role in the aetiology or progression of atherosclerotic plaques. Increased risk of coronary artery disease has been suggested in patients seropositive for Helicobacter pylori. AIM: To analyse coronary specimens in patients with severe (coronary artery disease) for Helicobacter pylori specific DNA. PATIENTS AND METHODS: Atherosclerotic plaques were obtained in 46 consecutive patients (9 female, 37 male, mean age 62.7+/-9.17 years) during coronary bypass procedures. Serum was analysed for IgG -/cagA-antibodies specific for Helicobacter pylori. Polymerase chain reaction and sequence analysis were used to identify bacterial DNA. Coronary artery biopsies from 19 autopsies without coronary artery disease were examined as a control group. RESULTS: Of the 46 coronary artery disease patients, 32 (69.6%) were Helicobacter pylori seropositive. Positive results for Helicobacter pylori DNA showed 18 seropositive and 4 seronegative (with anamnesis of eradication therapy). A total of 22 patients (47.8%) of the coronary artery disease group but none of controls revealed positive DNA. In the coronary artery disease group, a correlation between DNA presence and prior myocardial infarction (p=0.008) and unstable angina (p<0.001) was found. CONCLUSION: Identification of DNA in atherosclerotic plaques of patients with severe coronary artery disease supports the hypothesis that Helicobacter pylori infection may influence the development of atherosclerosis. Our results may indicate an direct involvement of Helicobacter pylori in the progression and instability of plaques in these patients.

[Cerebral embolism as the first manifestation of left ventricular metastatic bronchial carcinoma]. / Zerebrale Embolie als Erstmanifestation eines linksventrikulär metastasierten Bronchialkarzinoms.

Commonly the diagnosis of cardiac metastases in extracardiac cancer is difficult because of predominant symptoms of the underlying disease. In the reported case, a cerebral embolization was the first manifestation of a bronchogenic carcinoma with left ventricular metastasis. A 58-year-old male patient was admitted to the hospital with symptoms of an incomplete left-sided hemiparesis that occurred without prodromi. Other clinical abnormalities were not found. The two-dimensional echocardiogram showed a small space-occupying lesion in the left ventricle. Clinical symptoms completely disappeared within 3 days of heparin therapy. In order to prevent repeated embolization (after angiographic exclusion of coronary stenoses), the tumor was excised by cardiac surgery. In the histologic examination, malignant tumor cells were found. As primary origin, a small peripheral bronchogenic carcinoma with (clinically silent) additional metastases to the left adrenal gland and the right pelvic bone was found. The patient died 7 months later because of progressive metastatic cancer disease. Thus (on one hand) the reported case underlines the value of echocardiographic examination in suspected heart manifestation of cancer disease. On the other hand, in patients with heart tumors prior to curative therapy, additional diagnostic procedures (such as CT or MRI) should be performed in order to detect extracardiac tumor manifestations.

Platelet CD62 expression and PDGFAB secretion in patients undergoing PTCA and treatment with abciximab.

AIMS: To investigate a correlation of the platelet activation marker CD62 and secretion of the growth factor PDGF from platelets in coronary patients under therapy with the GPIIb/IIIa-inhibitor abciximab. METHODS: Flow cytometric assessment of fibrinogen binding (GPIIb/IIIa-binding site) and CD62 expression, as well as PDGF release of human platelets (immunoassay) and platelet aggregation with 20 microM ADP and 2 microg ml(-1) collagen were evaluated in nine patients with stable coronary artery disease. Patients were undergoing elective balloon angioplasty and were treated with aspirin (100 mg day(-1)), heparin (ACT < 220 s) and abciximab (bolus and infusion over 12 h). Blood samples were obtained before initiation of abciximab therapy (under aspirin and heparin) (I), 3 h after angioplasty under abciximab (II) and 12 h after termination of abciximab infusion (III). RESULTS: Compared with sample I before abciximab therapy, fibrinogen binding was reduced to 37% (+/- 34 s.d., P < 0.05) (II) and 55% (+/- 40 s.d., P < 0.05) (III). Reduced fibrinogen binding also led to a significant reduction of the aggregation response to ADP (down to 37% +/- 20) and collagen (down to 0%). Mean fluorescence intensity of CD62-expression was 78 units (+/- 20 s.d.) (I), 72 units (+/- 14 s.d.) (II) and 64 units (+/- 12 s.d., P < 0.05) (III). PDGF release from isolated, washed platelets was 99 (+/- 33 s.d.) ng/10(9) platelets at (I), 82 (+/- 31 s.d.) ng/10(9) platelets and 96 (+/- 30 s.d.) ng/10(9) platelets. CONCLUSIONS: The results indicate that despite a strong reduction of GPIIb/IIIa-binding and platelet aggregation, CD62 as a marker of platelet secretion and the secretion product PDGF were only slightly reduced under abciximab treatment. No direct correlation between CD62 expression and PDGF release could be demonstrated.

Aortic rupture and concomitant transection of the left bronchus after blunt chest trauma.

We report a patient with traumatic aortic rupture and preoperatively unrecognized complete disruption of the bronchus for the left lower lobe. Preoperative state was complicated by inadequate oxygenation due to total atelectasis of the unventilated collapsed left lower lobe with consequent significant shunting of the unoxygenated blood. The patient had no massive pneumothorax because the intact peribronchial tissue and pleura covered the injured place, preventing important air leakage. The suspicion of possible concomitant tracheobronchial injury and early diagnostic bronchoscopy are important in patients with aortic rupture after blunt chest trauma.

Effect of nitro groups and alkyl chain length on the negative ion tandem mass spectra of alkyl 3-hydroxy-5-(4'-nitrophenoxy) and alkyl 3-hydroxy-5-(2', 4'-dinitrophenoxy) benzoates

Tandem mass spectrometric behaviour was studied for a small combinatorial library of alkyl 3-hydroxy-5-(4'-nitrophenoxy) benzoates (A1-A5) and alkyl 3-hydroxy-5-(2', 4'-dinitrophenoxy) benzoates (B1-B5). The spectra were recorded by negative ion electrospray low-energy collision induced dissociation (CID) tandem mass spectrometry. The product ion spectra of [M - H](-) of the benzoates A1-A5 are similar, as are those of benzoates B1-B5. However, the spectra of the B series compounds differ significantly from those of the A series owing to the second electron-withdrawing nitro substituent in the B compounds. In addition, the length of the alkyl chain has an effect on the fragmentation. However, both series of compounds exhibit an abundant nitrophenoxy ion formed by the loss of 3-hydroxybenzoate. This is at m/z 138 in A1-A5 and at m/z 183 in B1-B5. A precursor ion scan of the nitrophenoxy ion provides a rapid method to identify the synthesised compounds in this type of combinatorial mixture. Copyright 1999 John Wiley & Sons, Ltd.

Lethal mutations defining 112 complementation groups in a 4.5 Mb sequenced region of Caenorhabditis elegans chromosome III.

The central gene cluster of chromosome III was one of the first regions to be sequenced by the Caenorhabditis elegans genome project. We have performed an essential gene analysis on the left part of this cluster, in the region around dpy-17III balanced by the duplication sDp3. We isolated 151 essential gene mutations and characterized them with regard to their arrest stages. To facilitate positioning of these mutations, we generated six new deficiencies that, together with preexisting chromosomal rearrangements, subdivide the region into 14 zones. The 151 mutations were mapped into these zones. They define 112 genes, of which 110 were previously unidentified. Thirteen of the zones have been anchored to the physical sequence by polymerase chain reaction deficiency mapping. Of the 112 essential genes mapped, 105 are within these 13 zones. They span 4.2 Mb of nucleotide sequence. From the nucleotide sequence data, 920 genes are predicted. From a Poisson distribution of our mutations, we predict that 234 of the genes will be essential genes. Thus, the 105 genes constitute 45% of the estimated number of essential genes in the physically defined zones and between 2 and 5% of all essential genes in C. elegans.

Interpreting a sequenced genome: toward a cosmid transgenic library of Caenorhabditis elegans.

We have generated a library of transgenic Caenorhabditis elegans strains that carry sequenced cosmids from the genome of the nematode. Each strain carries an extrachromosomal array containing a single cosmid, sequenced by the C. elegans Genome Sequencing Consortium, and a dominate Rol-6 marker. More than 500 transgenic strains representing 250 cosmids have been constructed. Collectively, these strains contain approximately 8 Mb of sequence data, or approximately 8% of the C. elegans genome. The transgenic strains are being used to rescue mutant phenotypes, resulting in a high-resolution map alignment of the genetic, physical, and DNA sequence maps of the nematode. We have chosen the region of chromosome III deleted by sDf127 and not covered by the duplication sDp8(III;I) as a starting point for a systematic correlation of mutant phenotypes with nucleotide sequence. In this defined region, we have identified 10 new essential genes whose mutant phenotypes range from developmental arrest at early larva, to maternal effect lethal. To date, 8 of these 10 essential genes have been rescued. In this region, these rescues represent approximately 10% of the genes predicted by GENEFINDER and considerably enhance the map alignment. Furthermore, this alignment facilitates future efforts to physically position and clone other genes in the region. [Updated information about the Transgenic Library is available via the Internet at http://darwin.mbb.sfu.ca/imbb/dbaillie/cos mid.html.]

Acute influence of beta-adrenergic antagonists on left ventricular diastolic function: contrasting results after administration of celiprolol and metoprolol.

Various beta-adrenergic receptor antagonists have different effects on myocardial function. A clinical study was performed in 30 patients with symptomatic coronary artery disease and systemic hypertension to compare the effects of single intravenous doses of 0.15 mg/kg celiprolol (n = 16) (third generation beta-blocking agent) and metoprolol (n = 14) (second generation) on left ventricular diastolic function. Parameters derived from pressure, volume, flow, time intervals and their combination were used to characterise diastolic function. After celiprolol administration, parameters of diastolic myocardial function improve (dp/dtip-; relaxation time constant T1, peak filling rate PFR; first-third filling rate FF1/3 or diastolic wall stress-time integral Sigdiasc) or remain unchanged. In contrast, after metoprolol administration parameters of diastolic function seem to be deteriorated (dp/dtip-, T1; Sigdiasc). This indicates an improvement in myocardial relaxation and filling under the influence of celiprolol but not under metoprolol. The left shift of the pressure-volume loops after celiprolol (n = 13), in contrast to metoprolol, supports this interpretation. Celiprolol did not show any deterioration of diastolic function in patients with coronary heart disease and arterial hypertension under these acute conditions.

Heart transplantation in Berlin--1993 update.

Heart transplantation has become a routine procedure. Surgical techniques have been standardized and triple-drug immunosuppression has proven to be the most effective posttransplantation medical treatment. A shortage of donor organs has remained the major factor inhibiting extensive application of heart transplantation. Improved techniques of organ protection may eventually contribute to an extension of the donor pool. However, it seems to be more important to develop alternative procedures further (artificial heart, xenotransplantation, extended use of conservative surgical or medical treatment). The patient population undergoing heart transplantation will undoubtedly include more older, severely ill, polymorbid patients who are not suitable for alternative procedures. Pediatric heart transplantation may increase in the coming years and mechanical circulatory support will surely gain in importance for both adult and pediatric patients awaiting heart transplantation.

Acute haemodynamic profile of celiprolol in patients with coronary heart disease and hypertension: a double-blind comparison with metoprolol.

Celiprolol is a 'third generation' beta-blocking agent which is claimed to avoid problems associated with simpler beta-blockers, such as vasoconstriction, bronchoconstriction and myocardial depression. A double-blind randomized study was undertaken in 30 patients with coronary artery disease and hypertension to compare the haemodynamic effects of single intravenous doses of 0.15 mg kg-1 celiprolol (N = 16) and metoprolol (N = 14). Following celiprolol administration, the tendency was for myocardial function to improve or remain unchanged; left ventricular end-systolic volume and ejection fraction improved significantly (P less than 0.05). However, following metoprolol administration, the tendency was for myocardial function to deteriorate, with significant falls in cardiac output (P less than 0.05), ejection fraction (P less than 0.05) and velocity of circumferential shortening (P less than 0.01). There was a tendency for peripheral resistance to fall slightly with celiprolol but to rise markedly with metoprolol (pNS). Left ventricular pressure-volume loops showed improved performance with celiprolol and deterioration with metoprolol. Both drugs resulted in increases in coronary flow and myocardial oxygen consumption (P less than 0.05). Metoprolol, but not celiprolol, resulted in some deterioration in regional left ventricular wall motion (P less than 0.05). Celiprolol appears to be haemodynamically advantageous compared to metoprolol in patients with coronary artery disease and hypertension.

[Coronary reserve determination by intracoronary papaverine: effects of various doses on coronary circulation and hemodynamics]. / Bestimmung der Koronarreserve durch intrakoronare Papaverinapplikation: Auswirkungen unterschiedlicher Dosen auf Koronarfluss and Hämodynamik.

In 40 male coronary patients during heart catheterization the coronary flow reserve was investigated by continuous thermodilution in the coronary sinus after intracoronary papaverine application. Simultaneously a number of heart function parameters were recorded. Already the lowest dosage of papaverine (5 mg) was able to induce a maximal flow acceleration. Higher dosages were accompanied with haemodynamic side effects (increase of heart rate and left ventricular end-diastolic pressure, decrease of left ventricular systolic pressure, appearance of myocardial ischemia) without further increase of coronary flow. After at most 5 minutes time the papaverine effects completely disappeared. In conclusion, a safe, short-lasting and repeatable determination of the coronary flow reserve (for instance during PTCA) proved to be possible after intracoronary papaverine injection in low dosages (5 mg).

[Value of diagnostic procedures in heart failure]. / Stellenwert diagnostischer Verfahren bei Herzinsuffizienz.

Strategy for the diagnosis of heart insufficiency is directed to the accomplishment of distinct therapeutic aims. Main factors for diagnostic approaches are pathophysiology and progression of qualitatively and quantitatively different disturbances in cardiac performance. Anamnesis and clinical investigations are irremissible for the evaluation of congestive heart failure. For the detection of noncongestive cardiac insufficiency investigations during exercise are often necessary. Ventriculography ist the standard reference technique for measurement of the systolic and diastolic ventricular functions. For exercise and follow-up investigations non-invasive methods are widely used. Accepted methods are two dimensional and Doppler-echocardiography, quantitative radiocardiography with single-pass bolus technique, and radionuclid-ventriculography. We found a good correlation for the measurement of stroke volume when comparing impedance cardiography with uniplane ventriculography at rest. M-mode echocardiography did not yield sufficiently reliable volumetric data. The new imaging methods, positron emission tomography, magnetic resonance technique, and cine computed tomography are future tools for cardiac output measurements.

[New aspects of the pathophysiology and pathogenesis of arterial hypertension--a review of the literature]. / Neue Aspekte zur Pathophysiologie und Pathogenese der arteriellen Hypertonie--eine Literaturübersicht.

The literature review reflects new aspects of pathophysiology and pathogenesis of arterial hypertension with special regard to the role of tissue renin-angiotensin-systems, endothelial and growth factors. The arteriolar wall as well as different organs produce angiotensin, which is of higher regulatory capability than the circulating angiotensin. Natriuretic hormones, endogenous opioids, neuropeptide Y and other vasoactive peptides are accepted as new humoral factors and neuromediators with different influence on the blood volume and the peripheral resistance. The vessel endothelium produces potent vasoconstricting (e.g. endothelin and vasodilating (e.g. EDRF) factors. Finally, growth factors with their potential role in vessel wall and myocardial hyperplasia/hypertrophy are analyzed. Tissue systems, endothelial and growth factors as new elements of arterial hypertension pathogenesis may influence the further development of new antihypertensive drugs.

[Transfemoral balloon occlusion of the coronary sinus in patients with angina pectoris]. / Die transfemorale Ballonokklusion des Sinus coronarius bei Patienten Angina pectoris.

The aim of the study was to demonstrate the possibility of transfemoral balloon occlusion of the coronary sinus and to detect changes of the left ventricular function during this occlusion in patients with angina pectoris. In 9 of 18 patients a stable occlusion over 15 seconds was performed. There were found only short term negative effects on the left ventricular contraction and relaxation. The coronary sinus pressure increased to 53 +/- 11 mm Hg. Numerous venous anastomoses made it difficult to occlude completely the sinus. The retrograde perfusion of the myocardium reached 20-30% of the antegrade one.