Experience with the Berlin Heart Assist Device

Abstract: Different mechanical circulatory support systems (MCSS) have been in clinical use since 1987 to keep patients alive by assisting the heart during cardiac recovery after open heart surgery, myocardial infarction, acute graft failure after heart transplantation, or as a bridge to transplantation in heart transplant candidates. Four different hospitals in Germany used the Berlin Heart Assist Device. Up until 1993, there were 22 patients in the "recovery" group; 4 patients were weaned from the system, and only 1 patient was discharged from the hospital. In 112 patients the Berlin Heart Assist Device was implanted for the purpose of a bridge to transplantation, 68 were transplanted and 46 patients left the hospital. It was concluded that patients may be kept alive with this system for weeks and months after any kind of cardiogenic shock. Complete cardiac recovery may be achieved in patients with early posttransplant graft failure. Reliable prediction of outcome in bridge–to–transplantation patients requires further experience and improvement of system components.     

Ostial PV Isolation:

Pulmonary vein (PV) isolation by elimination of spike potentials has been reported to cure drug refractory atrial fibrillation. Because of the heterogenous morphology of the PVs, sequential electroanatomic reconstruction of the PVs was performed in 39 patients (group A), who underwent subsequent PV isolation by interruption of all conductive myocardial fibers by distinct RF current applications using a "lasso" approach. In group B (157 patients), only biplane two-dimensional fluoroscopy was performed to guide the diagnostic and the ablation catheters. After reprocedures (in 7% of patients in group A and 22% of group B), which depicted a recurrence of a spike potential inside or at the ostium of  >1 previously isolated PV in all restudied patients, stable sinus rhythm was documented in 69% of patients in group A and 60% of patients in group B. Reasons for the relapse of the previously eliminated spike potentials include a temporary ablation effect and a too distal interruption of the conducting myocardial fiber. Detailed knowledge of the individual three-dimensional morphology enhanced the clinical success rate of PV isolation but is time-consuming using CARTO   (8.0 ± 1.7 vs 5.0 ± 1.6, P < 0.001)   . Further technical improvement to fuse the individual three-dimensional anatomy and the electrophysiological markers to a composed "electroanatomic" map may overcome this limitation in the future. (PACE 2003; 26[Pt. II]:1624–1630)     

E-SELECTIN EXPRESSION IN EXPERIMENTAL MODELS OF INFLAMMATION IN MICE

E-selectin (CD62E, formerly termed ELAM-1) is a cytokine-inducible adhesion molecule which mediates the binding of neutrophils, monocytes, and skin homing T-cells. The murine homologue of E-selectin has been cloned. A monoclonal antibody (21KC10) was used here to study immunohistochemically the expression and regulation of murine E-selectin in vitro and in vivo . As described for the human system, there was no staining of normal endothelium in skin and other tissues. LPS and tumour necrosis factor-alpha (TNF-α ), but not interleukin-4 (IL-4) or interferon-gamma (IFN- γ), induced a transient expression of E-selectin, both when injected in vivo and when added to endothelial cell lines in vitro. To analyse temporal expression of E-selectin under pathophysiological conditions in vivo, we chose two murine models of inflammation: allergic (ACD) and irritant contact dermatitis (ICD). Expression of E-selectin was found to be induced on vascular endothelium of post-capillary venules in both ACD and ICD. In ICD, maximal staining of endothelial cells occurred earlier than in ACD. Expression of E-selectin during ICD and ACD was then compared between strains of mice which differ with regard to the intensity of their inflammatory reaction. BALB/c mice, which in contrast to C57BI/6 mice show a denser infiltrate and prolonged influx of granulocytes and monocytes, revealed a more pronounced and more prolonged expression of E-selectin than C57BI/6 mice. This held true for both ACD and ICD, and in each case, peak expression of E-selectin was associated with the highest density of the leukocytic infiltrate. This study thus reveals regulatory mechanisms involved in the expression of murine E-selectin in vivo and in vitro . It also demonstrates a correlation between endothelial expression of E-selectin and the genetically determined intensity of the inflammatory response.     

Doppler Sonographic Evaluation of the CarboMedics Bileaf let Valve Prosthesis: One-Year Experience

Between April 1989 and March 1991, 237 CarboMedics bileaflet valve prosthesis carriers (165 aortic and 72 mitral valves, mean age 54.4 years) were studied prospectively with pulsed- and continuous-wave Doppler at a mean interval of 11.4 months following surgery in order to establish ranges of normal flow velocities and pressure gradients. Physical examination revealed no signs of prosthetic dysfunction or heart failure. Postoperative left ventricular function as measured by fractional shortening was 37% for aortic valve carriers and 30% for mitral valve carriers (p = NS). Mean peak velocity (+/- SD) across the aortic valve was 2.6 m/sec (+/- 0.4) and calculated instantaneous peak pressure gradient ranged from 11 to 58 mmHg (mean 28.1 +/- 10.3). It has to be emphasized that occasional patients with normally functioning valve prostheses can show unusual high gradients. Ring diameters between 21 and 27 mm showed no significant difference with regard to flow velocities and pressure gradients, whereas in 19-mm valves, significantly higher values could be demonstrated. The 123 aortic valve carriers with normal left ventricular function (fractional shortening greater than 25%) showed significantly higher pressure gradients than the 19 patients with reduced left ventricular function (28.6 +/- 11.6 mmHg vs 16.2 +/- 5.1 mmHg, p less than 0.05). In the mitral position, the mean of peak velocity (+/- SD) was 1.7 +/- 0.4 m/sec and pressure half-time was 108 +/- 26 msec, representing a calculated valve area between 1.4 to 3.1 cm2 (mean orifice size 2.1 +/- 0.5 cm2). No significant difference between valves of different sizes was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Solution structure of the cytoplasmic domain of the human immunodeficiency virus type 1 encoded virus protein U (Vpu)

The HIV-1-specific Vpu protein is an 81 amino acid class I integral membrane phosphoprotein that induces degradation of the virus receptor CD4 in the endoplasmic reticulum and enhances the release of virus particles from infected cells. Vpu is of amphipathic nature and consists of a hydrophobic N-terminal membrane anchor proximal to a polar C-terminal cytoplasmic domain. In our recent work, focussed on the structural analysis of the cytoplasmic tail, we established an α-helix-flexible-α-helix-turn model. Now we present the experimental solution structure of the Vpu cytoplasmic domain which has been elucidated in aqueous 50% trifluoroethanol solution by 2D ¹H NMR spectroscopy, and restrained molecular dynamics and energy minimization calculations. Under these conditions the peptide, Vpu^32-81, is predominantly monomeric and adopts a well defined helix-interconnection-helix-turn conformation, in which the four regions are bounded by residues 37-51, 52-56, 57-72 and 73-78. The presence of the cis isomer of Pro-75 manifests itself as a doubling of cross peaks of neighbouring residues in the 2D spectra. A related variant peptide, Vpum^32-81, in which the Vpu-phosphoacceptor sites Ser⁵² and Ser⁵⁶ were exchanged for Asn, adopts a very similar structure and, taken together, provides evidence that the second helix and the turn form a comparatively rigid region. Both helices are amphipathic in character, but show different charge distributions. In general the cytoplasmic region is N-terminally positively charged, passes through a region of alternating charges in helix 1 and then becomes negatively charged. The flexibility of the interconnection permits orientational freedom of the two helices. The motif found here is the first experimentally refined solution structure of the cytoplasmic domain of Vpu, and it is conceivable that these α-helices are important for a previously defined physical interaction with an α-helical Vpu-responsive element located within the cytoplasmic tail of CD4. © Munksgaard 1996.     

Age-dependent differences in the effect of phenprocoumon on the vitamin K1-epoxide cycle in rats†

The anticoagulant activity and the pharmacokinetics of phenprocoumon as well as the effect of phenprocoumon on the vitamin K₁-epoxide cycle in younger (12 weeks) and older (36 weeks) male inbred Lewis rats has been examined in a study of the mechanism responsible for the increase in the responsiveness to oral anticoagulant drugs (OAD's) with increasing age. After a single i.v.-dose of phenprocoumon (0?355 mg kg^?1 the anticoagulant effect obtained was greater in older than in younger rats. There were no differences between younger and older rats in the rate of elimination, volume of distribution and in the free fraction and free concentration values of phenprocoumon in plasma and liver. After i.v.- injection of 64·3 μg kg^?1 [³ H]vitamin K₁ and different doses of phenprocoumon (0·02 to 3 mg kg^?1) the [³ H]vitamin K₁ concentration in the liver decreased and the [³ H] vitamin K₁-2, 3-epoxide concentration increased dependent on the dose and the liver concentration of phenprocoumon. These changes were more pronounced in the older than in the younger rats. Concentration-response curves gave similar EC50-values for both age-groups but a 1·6-fold higher maximal response (expressed as vitamin K₁-epoxide/vitamin K₁ ratios) in the older rats. Since OAD's exert their anticoagulant effect most probably by inhibiting an enzyme (vitamin K₁-epoxide reductase) which regenerates vitamin K₁ from the epoxide metabolite and since the vitamin K₁-epoxide/vitamin K₁ ratios in the liver may reflect the degree of inhibition of the epoxide reductase by OAD's, our results may indicate that the inhibitory effect of phenprocoumon on this enzyme is more pronounced in older than in younger rats. This could explain the age-dependent differences in the anticoagulant activity.     

ANIMAL MODELS OF CHRONIC HEART FAILURE

Chronic heart failure is associated with multiple pathophysiological alterations and adaptations, such as marked anatomic and biochemical changes of the myocardium, left ventricular dysfunction and dilatation, increased systemic vascular resistance, and activation of neurohumoral and cytokine systems. The use of animal models has provided a new insight into the complex pathogenesis of this syndrome and supplemented clinical experience. However, all of the animal models used have advantages and limitations, and the transfer from experimental to human heart failure needs critical evaluation. The current review will focus upon new aspects of rat and rabbit models of heart failure.     

Change in HIV-antibody seroprevalence rates in i.v. drug dependent prisoners

In 1985 a high HIV-seroprevalence (44.2%) was found in a cohort of parenteral drug addicted prisoners in Innsbruck, Austria. In a longitudinal study from March 1985 to March 1989 we investigated the epidemiology of HIV-infection as well as possible changes in the drug taking behaviour of this defined population at risk. During the study HIV-seroprevalence rates in drug dependent prisoners showed a statistical decrease to 30%. A concomitant increase in admission to any kind of therapy programmes as well as an increasing change from ‘heavy use’ (mainly taking heroin i.v.) to ‘non-heavy use’ (mainly taking drugs orally) could be noted. The influence of preventive measures, such as comprehensive AIDS-information, special therapy programmes including the methadone substitution programme, and the unrestricted availability of needles and syringes is discussed.