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Humorale und zelluläre Effektormechanismen des Immunsy-stems können über multiple Interaktionen passagere oder per-manente Änderungen der systolischen und diastolischen Myo-kardfunktion hervorrufen. Dies kann über molekulare, metabo-lische, rezeptormediierte und ebenso auch strukturelle Verän-derungen am Myozyten (z.B. Hypertrophie), am Interstitium und an der extrazellulären Matrix (z.B. Fibrose) und der Zellularität (z.B. Myokarditis) erfolgen. In dieser Übersicht liegt der Schwerpunkt der Beschreibung solcher Veränderun-gen beim Krankheitsbild der entzündlichen Herzmuskelerkran-kungen und bei den Pathomechanismen, über die Viren, zyto-toxische T-Zellen, Zytokine und antikardiale Antiköφer in tierexperimentellen Untersuchungen und beim Menschen diese funktionellen und strukturellen Vorgänge beeinflussen.

The six serotypes of the group B coxsackieviruses (CVB) are common human enteroviruses linked etiologically to inflammatory cardiomyopathies. This has been demonstrated by molecular detection of enteroviral RNA in human heart tissue, serologic associations with disease, and virus isolation from cases of fulminant myocarditis. The murine model of CVB-associated myocarditis has demonstrated that CVB can be attenuated through mutations at different genomic sites. Human CVB3 isolates demonstrate varying degrees of cardiovirulence in the murine model; one site of virulence determination has been mapped to domain II of the 5′ non-translated region. The interplay of CVB replication and the immune response to that replication in the heart is a complex interaction determining the extent to which the virus replication is limited and the degree to which a pathogenic inflammation of cardiac muscle occurs. Studies of CVB3-induced myocarditis in murine strains lacking subsets of the immune system or genes regulating the immune response have demonstrated a pivotal role of the T cell response to the generation of myocarditis. While CVB are associated with 20-25% of cases of myocarditis or cardiomyopathy, the severity of the disease and the existence of attenuated strains shown to generate protective immunity in animal models indicates that vaccination against the CVBs would be valuable. Copyright © 2001 John Wiley & Sons, Ltd.

Our purpose was to evaluate the efficacy and safety of atorvastatin, a potent cholesterol- and triglyceride-lowering agent, in peritoneal dialysis patients with dyslipidaemia.

The aim of the present study was to assess the effects of carvedilol therapy in addition to conventional heart failure therapy on heart rate variability (HRV) and on left ventricular function in 14 patients with mild to moderate heart failure due to idiopathic dilated cardiomyopathy (IDC). After a 3- to 4-week titration period, carvedilol was titrated up to 50mg daily, or the highest dose tolerated (at least 25mg daily). Maintenance treatment was then continued for 8 weeks. Digital 24-hour Holter recordings were obtained at baseline and after 8 weeks of carvedilol therapy. HRV for the entire 24-hour period was computed in the time domain using the Oxford Medilog Excel 2 analysis system. Measures of HRV included the mean of all coupling intervals between normal beats (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences between adjacent normal RR intervals (rMSSD), and the proportion of adjacent normal RR intervals differing >50ms (pNN50). Additional treatment with carvedilol induced a significant increase in HRV: SDNN increased from 77±21ms to 110±22ms (p=0.001), rMSSD from 19±7ms to 26±7ms (p=0.02), and mean pNN50-value increased from 1.7±1.3% to 5.5±4.5% (p<0.01) under therapy with carvedilol. Mean heart rate on carvedilol calculated over 24 hours was 13 beats less than at baseline (75 bpm versus 88 bpm, p<0.01). After 2 months of additional treatment with carvedilol, both hemodynamic and clinical parameters improved: left ventricular ejection fraction increased from 24±7% to 30±10% (p<0.05), and New York Heart Association class decreased from 2.5±0.8 to 1.8±0.7 (p<0.05). In summary, eight weeks of additional carvedilol therapy induced a significant increase in HRV parameters related to parasympathetic activity in patients with IDC. Whether increased vagal tone may contribute to the protective effect of carvedilol has to be evaluated by further studies. In der vorliegenden prospektiven Studie wurde 14 Patienten mit dilatativer Kardiomyopathie (DCM) zusätzlich zu einer konventionellen Basistherapie bestehend aus Digitalis, Diuretika und ACE-Hemmern Carvedilol einschleichend bis zu einer maximalen Dosierung von 25–50mg/Tag verabreicht. Zu Beginn und nach 8 Wochen Therapie mit Carvedilol wurden aus digitalen 24-h-Langkeit-EKG-Registrierungen mittels des Oxford™ Medilog Excel 2 Analysesystems folgende Zeitbereichsparameter der Herzfrequenzvariabilität (HRV) bestimmt: RRm=Mittelwert aller normalen Kopplungsintervalle (NN), SDNN=Standardabweichung aller NNs, rMSSD=Quadratwurzel des quadratischen Mittelwertes der Differenzen aufeinanderfolgender NNs und pNN50=Anteil aller aufeinanderfolgenden NNs, die sich mehr als 50ms unterscheiden. Zusätzlich wurden vor und unter der Carvediloltherapie echokardiographische Untersuchungen durchgeführt sowie ein klinischer Status der Studienpatienten erhoben. Unter der additiven Gabe von Carvedilol besserten sich alle Zeitbereichsparameter der HRV signifikant: SDNN stieg unter Carvedilol von 77±21 auf 110±22ms (p=0,0001), rMSSD von 19±7 auf 26±7ms (p=0,02) und der mittlere pNN50-Wert von initial 1,7±1,3 auf 5,5±4,5% (p<0,01) an. Die über 24h gemittelte Herzfrequenz sank um 13 Schläge/min von zu Beginn 88±10 Schläge/min auf 75±10 Schläge/min (p<0,01). Die linksventrikuläre Auswurffraktion stieg von initial 24±7% auf 30±10% (p<0,05) unter Carvedilol an. Die mittlere NYHA-Klasse besserte sich unter Carvedilol von 2,5±0,8 auf 1,8±0,7 (p<0,05). Zusammenfassend verbesserte die additive Therapie mit Carvedilol sowohl die Herzfrequenzvariabilität als auch echokardiographische und klinische Parameter bei Patienten mit dilatativer Kardiomyopathie.

Automated peritoneal dialysis (APD) has been increasingly used in recent years. Our purpose was to investigate whether the good preservation of residual renal function (RRF) that has been reported in patients on continuous ambulatory peritoneal dialysis (CAPD) is also observed in APD.

We report the construction of chimeric coxsackievirus B3 (CVB3) strains in which sequences of an infectious cDNA copy of a noncardiovirulent CVB3 genome were replaced by the homologous sequences from a cardiovirulent CVB3 genome to identify which of 10 predicted genetic sites determine cardiovirulence. Cardiovirulent phenotype expression was consistently linked to nucleotide 234 (U in cardiovirulent CVB3 and C in avirulent CVB3) in the 5' nontranslated region. Reconstructions of the parental noncardiovirulent CVB3 genome from chimeras restored the noncardiovirulent phenotype when tested in mice. Inoculation of severe combined immunodeficient (scid) mice with the noncardiovirulent CVB3 strain resulted in massive cardiomyocyte necrosis in all animals. Sequence analysis of viral genomes isolated from twelve scid mouse hearts showed that only nucleotide position 234 was different (a C-->U transition) from that in the input parental noncardiovirulent CVB3 genome. Higher-order RNA structures predicted by two different algorithms did not demonstrate an obvious local effect caused by the C-->U change at nucleotide 234. Initial studies of parental and chimeric CVB3 replication in primary cultures of fetal murine heart fibroblasts and in adult murine cardiac myocytes demonstrated that viral RNA transcriptional efficiency is approximately 10-fold lower for noncardiovirulent CVB3 than for cardiovirulent CVB3. CVB3 did not shut off protein synthesis in murine cardiac fibroblasts, nor were levels of viral protein synthesis significantly different as a function of viral phenotype. Taken together, these data support a significant role for determination of the CVB3 cardiovirulence phenotype by nucleotide 234 in the 5' nontranslated region, possibly via a transcriptional mechanism.