Search

Bei Patienten mit zentralvenosen Infusionskathetern oder implantierten Hickman-Kathetern bzw. Portsystemen kommt es durch Materialermudung oder Behandlungsfehler in 0,1–2,8% der Falle zu einer Katheterembolie. Bei einem 58-jahrigen gefaschirurgischen Patienten wurde postoperativ erfolgreich transfemoral das Fragment eines zentralvenosen Katheters aus der A. pulmonalis mit einem Schlingenkatheter geborgen. Anhand dieses Falls werden Inzidenz, Klinik, Diagnostik und interventionelle Therapie der Katheterembolie dargestellt.

During the past few years major conceptual and technical advances have been made towards the therapeutic modulation of cardiac gene expression for the treatment of cardiac diseases. Among these are 1) the identification of new molecular therapy targets in cardiac disorders, often derived from genetic animal models. 2) A better understanding of the molecular and cellular determinants of cardiac gene transfer in vivo, in animal models and in first clinical trials. 3) The development of novel regulatable and long-term stable vector systems. This review is focused on nucleic acid-based modulation of cardiac calcium homeostasis as a paradigm for the new gene therapeutic approaches, since recent landmark papers have suggested this to be a molecular target of key importance in heart failure. In particular, the development of severe heart failure in the genetic MLP(-/-) animal model could be completely abolished by the targeted ablation of phospholamban (PL), a key regulator of cardiac calcium homeostasis. This impressive effect of permanent germline PL ablation provides-in conjunction with former important work on disturbed calcium handling in the failing human heart-a rationale for the gene therapeutic approach of ad hoc suppression of PL by antisense strategies (antisense RNAs, ribozymes, RNA interference) or PL variants. Based on the broad spectrum of methods employed to characterize this general strategy, PL-targeted approaches may be considered as a paradigm of future genetic treatments of cardiac disorders, although the differences between animal models and humans must be kept in mind. High safety of any such therapy will be a prerequisite for any possible clinical application and therefore novel methods to improve control are being devised: 1) The regulation of gene therapy vectors by biochemical abnormalities associated with the target disease itself (" Induction-by-Disease" gene therapy). 2) External control of vector activity by the employment of drug-sensitive promotors. In addition, the important goal of cardiac long-term stability of the therapeutic vectors has recently been achieved in animal models using vectors derived from adeno-associated viruses (AAVs).

The use of restricted replication-competent adenoviruses (RRCAs) inducing tumor cell-specific lysis is a promising approach in cancer gene therapy. However, the use of RRCAs in humans carries considerable risk, since after injection into the patient, further regulation or inhibition of virus replication from the outside is impossible. Therefore, we have developed a novel system allowing external pharmacological control of RRCA replication. We show here that a tumor-selective E1B-deleted RRCA can be tightly regulated by use of doxycycline (dox)-controlled adenoviral E1A gene expression, which in turn determines vector replication. RRCA replication is switched on by addition and switched off by withdrawal of dox. The system results in efficient tumor cell killing after induction by dox, whereas cells are unaffected by the uninduced system. It was also employed for efficient external control of transgene expression from cotransfected replication-deficient adenovectors. Furthermore, the use of a liver cell-specific human alpha1-antitrypsin (hAAT)-promoter driving a tetracycline-controlled transcriptional silencer allowed specific protection of cells with hAAT-promoter activity in the absence of dox in vitro and in vivo, delineating a new principle of 'tissue protective' gene therapy. The concept of external control of RRCAs may help to improve the safety of cancer gene therapy.

We report the case of a 45 year old man presenting to our emergency ward with acute onset of typical chest pain. The ECG showed ST-segment depression in the postero-lateral leads without elevation of any cardiac enzymes. The coronary angiogram showed a three-vessel disease with a subtotal, short stenosis of the right coronary artery and a severe ostial stenosis of the left main coronary artery. An operative revascularization with a venous graft to the right coronary artery and a angioplasty with an autologous vein patch of the left main coronary artery were performed. No peri- or postoperative complications occurred. Because of the importance of the left main coronary artery, the patient underwent an early post-operative coronary angiogram with intravascular ultrasound (IVUS) to confirm the patency of the patch angioplasty. We discuss the historical development, the indications and the main advantages of the patch angioplasty in comparison to conventional CABG procedures. The main issue of the presentation is the special value of IVUS in the pre- and postoperative assessment of the left main coronary artery. Within the last few years, IVUS has emerged from a pure research tool to the gold standard of coronary imaging. It is playing a more and more important role in the assessment of angiographically unclear lesions, mainly in the left main stem and its bifurcation. In addition, IVUS has a large influence in clinical decision making, e.g., reverral to CABG or PCI. It is also a powerful tool for optimizing the operative setting and provides the best possible postoperative control.

Ein 48-jahriger Patient mit dilatativer Kardiomyopathie bemerkte erstmals Ruhe- und Belastungsdyspnoe sowie eine Verschlechterung des Allgemeinzustandes. Bis auf ein leises Systolikum uber der Herzspitze war die klinische Untersuchung unauffallig. In der Echokardiographie stellte sich ein global schwer eingeschrankt kontrahierender und dilatierter linker Ventrikel ohne Ventrikelthromben dar. In der Herzkatheteruntersuchung wurden nach Ausschluss einer koronaren Herzerkrankung mehrere Endomyokardbiopsien entnommen. Die immunhistologische Auswertung der Biopsien zeigte als Ausdruck einer myokardialen Entzundungreaktion in das Myokardgewebe infiltrierende Lymphozyten sowie eine verstarkte interstitielle und endotheliale HLA-Expression. Als ein Mas der intravasalen Thrombozytenaktivierung wurden Thrombozytenoberflachenproteine am Durchflusszytometer quantitativ analysiert. Bei unserem Patienten zeigte sich eine signifikante Erhohung der Thrombozytenaktivierung sowohl im Vergleich zu einer gesunden Kontrollgruppe als auch zu 20 Patienten mit dilatativer Kardiomyopathie. Die Herzinsuffizienz des Patienten wurde medikamentos mit einem ACE-Hemmer, einem Schleifendiuretikum, einem Spironolacton sowie einem Digitalispraparat behandelt. Bei hochgradig eingeschrankter Pumpfunktion des linken Ventrikels erfolgte zeitgleich eine antikoagulatorische Therapie mit Phenprocoumon und mit Acetylsalicylsaure (ASS). Nach einem halben Jahr stellte sich in der erneut durchgefuhrten Echokardiographie bei weiterhin hochgradig eingeschrankter Kontraktilitat trotz adaquater Antikoagulation ein wandstandiger Ventrikelthrombus dar. Trotz antithrombotischer Therapie mit ASS und Phenprocoumon konnte die Entstehung eines Ventrikelthrombus nicht verhindert werden. Bei unserem Patienten mit dilatativer Kardiomyopathie lag eine erhohte Thrombozytenaktivierung (>4fache SD) vor. Es ist zu diskutieren, ob eine zusatzliche antiaggregatorische Therapie mit Clopidogrel bei Patienten mit dilatativer Kardiomyopathie und erhohter Plattchenaktivierung angezeigt ist. Thromboembolische Ereignisse sind bedeutende Komplikationen bei dilatativer Kardiomyopathie. Bei ca. 10–40% der Patienten treten im Verlauf der Erkrankung Embolien auf (5, 7). Oftmals kann dabei ein in der Echokardiographie sichtbarer Ventrikelthrombus nachgewiesen werden (6). Eine orale antikoagulatorische Therapie mit Marcumar wird deshalb bei Patienten mit dilatativer Kardiomyopathie empfohlen (9). Wir berichten uber einen Patienten mit inflammatorischer Kardiomyopathie und global hochgradig eingeschrankter Pumpfunktion, der in der durchflusszytometrischen Analyse von Thrombozytenoberflachenproteinen eine uberdurchschnittliche hohe Plattchenaktivierung zeigte und trotz adaquater Marcumarisierung und Therapie mit Acetylsalicylsaure innerhalb von einem halben Jahr einen Ventrikelthrombus entwickelte.

Ein 49jahriger Patient erlitt nach laparoskopischer Leistenhernien-Operation einen Herzkreislaufstillstand. Das nach Einleitung der kardiopulmonalen Reanimation abgeleitete Elektrokardiogramm zeigte Kammerflimmern, nach Defibrillation eine Tachyarrhythmia absoluta mit neu aufgetretenem Rechtsschenkelblock sowie deutlichen ST-Hebungen im Bereich der Vorderwand. Nach einer Reanimationsdauer von ca. 20 min wurde unter Einsatz von Katecholaminen eine Kreislaufstabilisierung erreicht. Echokardiographisch kam ein Perikardergus von 7 mm mit geringer Imprimierung des leicht vergroserten rechten Ventrikels zur Darstellung. Unter dem Verdacht einer akuten Lungenarterienembolie (Differentialdiagnose: akuter Myokardinfarkt) wurde eine Katheteruntersuchung mit Darstellung der Lungenstrombahn und anschliesender Koronarangiographie durchgefuhrt. Die im Bereich des linken Pulmonalarterienhauptastes dokumentierten flottierenden Thromben konnten mit einem Pigtail-Katheter mechanisch fragmentiert werden. Koronarangiographisch fanden wir bei ansonsten unauffalligen Gefasen den Ramus interventricularis anterior (RIVA) proximal scharfkantig verschlossen. Die Anamnese, die Morphologie des RIVA-Verschlusses, der begleitende Perikardergus und die Rippen- und Sternumfrakturen liesen eine reanimationsbedingte Koronarperforation formal vom Typ III nach Sutton und Ellis wahrscheinlich erscheinen. Der RIVA wurde daraufhin rekanalisiert und bei fortbestehendem Kontrastmittelubertritt in den Perikardspalt zur Abdeckung der Perforation mit einem 19 mm langen Stent-Graft (Jostent®) versorgt. Diese Stents, die primar zur Behandlung von Koronaraneurysmata und rezidivierenden Instent-Restenosen entwickelt wurden, bestehen aus zwei coaxial ineinanderliegenden Edelstahl-Stents mit dazwischen eingebrachter Polytetrafluorethylen-Membran. In der abschliesenden Darstellung fand sich kein Kontrastmittelubertritt mehr.

Spontaneous coronary artery dissection is a rare cause of ischemic heart disease. Incidence, etiology and optimal treatment are ill-defined. Between July 1995 and December 1997, we prospectively identified 42 patients (36 men, six women, mean age 59 +/- 12 years) with spontaneous coronary artery dissection among 3803 consecutive angiographic examinations in which the diagnosis of coronary artery disease was established for the first time (incidence 1.1%). In comparison to the remaining study population with stable angina pectoris (8 cases of spontaneous coronary artery dissection among 2852 patients; incidence: 0.3%), the incidence of spontaneous coronary artery dissection was significantly higher in the patient subgroups with acute myocardial infarction (13/450; 2.9%) and with unstable angina pectoris or postinfarction angina (21/501; 4.2%). Dissection was most frequently located in the left anterior descending coronary artery (19 cases), followed by the right coronary artery (15 cases) and the left circumflex coronary artery (8 cases). Because of an ambiguous angiographic lesion appearance intravascular ultrasound imaging was performed in 13 patients to confirm the diagnosis. The presumed etiology of spontaneous coronary artery dissection was atherosclerotic plaque rupture in 35 cases, heavy physical exercise in four cases and hormonal influences related to pregnancy and contraception in one case. In two cases, no obvious risk factor could be identified. Therapy consisted of intracoronary stenting in 24 patients (including ten patients with acute myocardial infarction), coronary artery bypass grafting (CABG) in 8 patients and balloon angioplasty (PTCA) in seven patients. Three patients were treated conservatively. During a mean follow-up period of 13.5 +/- 9.9 months, two patients died and 31 patients remained entirely asymptomatic, including all patients who were treated with CABG. Restenosis developed in three patients after stent implantation (restenosis rate: 12.5%). Following primary PTCA, spontaneous coronary artery dissection recurred in two patients, one of whom subsequently died.

The role of enteroviral myocardial infection in the development of dilated cardiomyopathy could only be substantiated after the introduction of molecular biological techniques (polymerase chain reaction, in-situ hybridization) in virological diagnostics of dilated cardiomyopathy. By using histological and especially immunohistological techniques for the detection of myocardial inflammation in patients with the tentative clinical diagnosis of dilated cardiomyopathy, a differentiation between inflammatory cardiomyopathy and idiopathic dilated cardiomyopathy on the basis of the WHO classification 1995 (31) was made. Inflammatory cardiomyopathy is defined by myocarditis in association with cardiac dysfunction and is diagnosed by established histological and especially immunohistological techniques. The combination of histological, immunohistological, and molecularbiological techniques enabled a subgroup analysis of the incidence of enteroviral myocardial RNA in patients with inflammatory cardiomyopathy in comparison to patients with idiopathic dilated cardiomyopathy. The study involved a total of 75 patients with impaired left ventricular function (EF or = 2,0 CD3 T-lymphocytes/ visual field at 400 magnification (HPF); > or = 7 CD3 T-lymphocytes/mm2). These patients were diagnosed as having inflammatory cardiomyopathy. To differentiate between patients with and without myocardial inflammation, cases with focal cellular infiltration and an average cell number between 2.5 and 2.0 CD3 T-lymphocytes/HPF and an increased expression of additional immune markers, i.e., MHC antigens, were not addressed in the group of patients with inflammatory cardiomyopathy. This is in contrast to Kuhl et al (19). Consequently these patients were classified as patients with idiopathic dilated cardiomyopathy. These criteria of diagnosing myocardial inflammation were based on published results (20, 23, 26, 27, 49) and on our own control group (n = 85) (19) in which mean CD3 T-lymphocyte count/HPF in normal myocardial tissue were 0.7 (range 0.0-1.4). In addition, a subgroup analysis was performed of patients with a CD3 T-lymphocyte count > or = 3 CD3 T-lymphocytes/HPF (> or + 11 CD3 T-lymphocytes/mm2). The other 49/75 patients without myocardial inflammation ( or = 3 CD3 T-lymphocytes/HPF (> or = 11 CD3 T-lymphocytes/mm2) (mean 4.4 +/-2.1 CD3 T-lymphocytes/HPF), three of the ten patients were enteroviral RNA positive (30%). In summary, the introduction of histological and immunohistological techniques in the extended diagnostics of dilated cardiomyopathy enables a subgroup analysis of the incidence of enteroviral myocardial RNA in

Ein 47jahriger Patient wurde mit einem akuten Vorderwandinfarkt eingewiesen. Eine dringlich durchgefuhrte koronarangiographische Untersuchung zeigte einen proximalen Verschlus des Ramus interventricularis anterior (RIVA). Nach mechanischer Rekanalisation stellte sich eine Kaliberreduktion des Gefases an der Verschlusstelle dar; es wurde eine Ballondilatation (PTCA) mit konsekutiver Stent-Implantation aufgrund einer Dissektion durchgefuhrt. Danach verblieb bei normalem Koronarflus (TIMI 3) eine langstreckige Lumenreduktion des gesamten Gefassegments distal des Stents ohne erkennbare Stenose. Der RIVA wies am Beginn des mittleren Drittels eine Muskelbrucke auf, die auch einen abgehenden Diagonalast systolisch subtotal verschlos. Eine Dipyridamol-Thallium-Szintigraphie zeigte eine inkomplette anteroseptale Vernarbung und eine reversible anterolaterale Myokardischamie. Wir entschlossen uns daraufhin zur Implantation eines 3,0 mm-Stents im Bereich der Muskelbrucke. Die Wahl der Ballongrose wurde anhand der quantitativen koronarangiographischen Bestimmung des proximalen Referenzdurchmessers vorgenommen; es resultierte ein Misverhaltnis zwischen Gefas- und Ballondurchmesser im distalen Dilatationssegment mit konsekutiver Koronararterienperforation in den rechtsventrikularen Ausflustrakt. Der Patient blieb im Verlauf auch unter Ergometrie asymptomatisch und hamodynamisch stabil. In einer Kontroll-Koronarangiographie nach einer Woche war die Koronarfistel unverandert nachweisbar; der RIVA wurde rasch und vollstandig angefarbt (TIMI 3). Innerhalb von drei Monaten schlos sich die Fistel spontan.

Several findings pointed to an insufficient energy supply in heart muscle tissue of patients suffering from dilated cardiomyopathy (DCM). We found a lowered ANT transport capacity of the adenine nucleotide translocator (ANT), the only transport system for ATP and ADP in eucaryotic cells, in explanted hearts of DCM patients. The reduced ANT transport rate was accompanied by a marked elevation in total ANT protein caused by an increase in ANT 1 isoform protein. Simultaneously, a reduction in ANT 2 transcripts and an unchanged ANT 3 expression was observed. In contrast, patients with ischemic or valvular heart disease showed no alteration in ANT function or expression, which indicates the disease-specificity of these findings.

In an effort to determine the effect of chronic ethanol ingestion on myocardial oligomycin sensitive ATPase, guinea pigs were fed 15% ethanol instead of drinking water for 34 weeks. Mg2+-ATPase activity of isolated mitochondria was determined in control and alcohol fed guinea pigs at 16, 20, 24 and 34 weeks. To prove a possible higher fragility of the mitochondria from alcohol fed animals, the ATPase activity was also determined in the supernatant after the isolation of mitochondria "100 000 g fraction". Mg2+-ATPase activity of the isolated mitochondria was time dependent reduced to 56% of the value obtained in the control animals. In the "100 000 g fraction" the ATPase activity, however, started to increase after 8 weeks and after 34 weeks it was about twice as high than in the control group. The findings of this study document a decrease in oligomycin sensitive ATPase activity and an increase in mitochondrial fragility after chronic ethanol ingestion. It supports in the thesis that chronic alcohol intake affects the activity of the intrinsic membrane enzymes by structural derangements of mitochondrial membrane. The changes may play a role in the development of alcoholic cardiomyopathy.

The isoenzyme pattern of the lactate-dehydrogenase (LDH) in different parts of the heart was measured by micro-isoelectric focusing. Samples were taken from the right and left auricle, the outer, middle and inner layer of the myocardial wall of both ventricles and from the papillary muscle of the left ventricle. The results show that the activity of LDH total and the isoenzyme pattern are different in the various parts of the heart. In both auricles the isoenzymes LDH 3,4,5 were mostly found, whereas in the ventricles a significant increase of LDH 1,2 could be seen. Additionally, there was a shift in the isoenzyme pattern from the outside to the inner part of the myocardium wall with a significant increase of LDH1.