[Restrictive cardiomyopathy in childhood]. / Restriktive Kardiomyopathie. Ein seltenes Krankheitsbild im Kindesalter.

Restrictive cardiomyopathy is a rare heart muscle disease in childhood. By presenting a case report of a 15 year old adolescent, the aim of this article is to describe diagnosis, pathogenesis and therapy of restrictive cardiomyopathy. A review of the literature comprising pediatric studies on restrictive cardiomyopathy serves as a basis to discuss recommendations for therapeutic strategies in pediatric patients with this rare disease.

Effects of ultrafiltration and peritoneal dialysis on proinflammatory cytokines during cardiopulmonary bypass surgery in newborns and infants.

OBJECTIVES: To assess the impact of balanced ultrafiltration and peritoneal dialysis (PD) on plasma and urinary cytokines and renal dysfunction after cardiopulmonary bypass (CPB) surgery in newborns and infants. METHODS: Twenty-three newborns and infants weighing less than 7 kg and scheduled for operation on congenital malformation were enrolled in this descriptive open clinical study. All patients received conventional ultrafiltration in the CPB rewarming period. Eleven newborns underwent Tenckhoff-catheter implantation in the operation theatre as a routine institutional procedure and received PD after admission to the ICU (the PD [+] group). No PD was used in another 12 patients (the PD [-] group). Interleukins (IL) 6 and 8 were measured four times pre- and post-operatively. Kidney function was assessed by creatinine clearances and urine protein and enzyme analyses. RESULTS: All patients had an uneventful clinical course. Age (10+/-2 days, PD [+] vs. 96+/-19 days, PD [-]), CPB duration (215+/-23 vs. 143+/-20 min), and degree of hypothermia (26+/-1.3 vs. 31+/-0.1 degrees C) differed significantly between the groups. Age, CPB duration and ultrafiltration influenced post-operative IL-levels in an analysis of variance. While there were few differences immediately after the end of ultrafiltration, post-operative levels of IL-6 and IL-8 were higher and more sustained in the newborns (PD [+]) than in the older infants (PD [-]). The median amount of IL-6 and IL-8 removed by ultrafiltration came to 28 and 59% compared to the amount of IL-6 and IL-8 remaining in the blood at the end of CPB. IL-clearance by ultrafiltration was more than 1000-fold and by PD more than 100-fold as effective as IL-clearance by the kidney. While the kidneys showed an unselective mixed glomerular and tubular pattern of injury, during CPB higher serum IL-concentrations correlated with lower urinary IL-clearances in both study groups. CONCLUSIONS: Ultrafiltration and PD are highly effective in removing proinflammatory cytokines. Impaired kidney function was associated with proinflammatory IL-serum concentrations. Thus, we raise the hypothesis that glomerular-filtered proinflammatory ILs damage the proximal tubular cells of the kidney in newborns and infants, thus contributing to post-operative renal dysfunction. Conversely, we conclude that removing proinflammatory ILs by ultrafiltration and PD acts renoprotectively. A future prospective randomised study could demonstrate whether this can indeed improve clinical outcome.

Impact of harmonic imaging and transducer frequency on 'ventricular volume' measurements using real-time three-dimensional echocardiography: studies in an in vitro model.

AIMS: Harmonic imaging has increased the yield of quantifiable scans in two-dimensional echocardiography. Although real-time three-dimensional echocardiography avoids geometric assumptions in volume analysis, accurate measurement can be limited by image quality. This study compared volumes from a balloon model mimicking the left ventricle, scanned with and without harmonic imaging, using real time three-dimensional echocardiography. METHODS: Two balloons separated by ultrasound gel were suspended in a water bath. To mimic different chamber volumes, 12 volumes of water within the inner balloon (40-180ml) were scanned using a 3.5MHz probe at fundamental frequency and using a 2.5MHz probe with and without harmonic imaging. RESULTS: Scanning at 3.5MHz, the long axis (B) scans did not significantly underestimate the balloon volume but the 'short axis' (C) scans did (mean difference from actual volumes -0.7-1.4ml, P=0.14 - 3.9 +/- 1.2 ml,P < 0.0001 for B and C scans, respectively). Scanning at 2.5MHz both B and C scans significantly underestimated even more the true volume, C scans to a greater extent (mean difference -6.9 +/- 2.4ml and -11.2 +/- 4.0ml for B and C scans respectively,P < 0.0001 in both cases). However with harmonic imaging, transmitting at 1.7MHz and receiving at 2-4MHz, there was no significant difference of either B or C scans from the reference values (mean difference of B scans -1.2 +/- 1.9ml, P=0.06 and C scans -0.6 +/- 2.2ml, P=0.4). CONCLUSION: The enhanced resolution provided by harmonic imaging improves accuracy of volume analysis by real-time three-dimensional echocardiography.

Antithrombotic potency of hirudin is increased in nonhuman primates by fibrin targeting.

BACKGROUND: Inhibition of thrombin by either the indirect thrombin inhibitor heparin or by more potent direct thrombin inhibitors such as hirudin reduces thrombus formation after arterial injury. The present study was designed to determine if a fibrin-specific thrombin inhibitor could, by local thrombin inhibition, prevent thrombosis more effectively. METHODS AND RESULTS: We first studied antithrombotic potency in vitro, comparing fibrin-targeted hirudin (recombinant hirudin covalently linked to the Fab' fragment of the anti-fibrin monoclonal antibody 59D8) to recombinant hirudin in baboon plasma. Fibrin-targeted hirudin was nine times more effective than recombinant hirudin in inhibiting fibrin deposition on experimental clot surfaces in baboon plasma (P < .01). The potency of fibrin-targeted hirudin was then compared with that of recombinant hirudin in a baboon model of thrombus formation. 111In-labeled platelet deposition was measured in a synthetic graft segment of an extracorporeal arteriovenous shunt in control animals and in animals receiving either fibrin-targeted hirudin or hirudin. In these experiments, fibrin-targeted hirudin was 10-fold more potent than hirudin in inhibiting platelet deposition and thrombus formation (P < .05). CONCLUSIONS: These data indicate that targeting a thrombin inhibitors such as hirudin to an epitope present in thrombi results in increased antithrombotic potency.

Fibrin-targeted recombinant hirudin inhibits fibrin deposition on experimental clots more efficiently than recombinant hirudin.

BACKGROUND: Although the indirect thrombin inhibitor heparin and the more potent direct inhibitor hirudin are useful in preventing thrombosis, a substantial opportunity remains for improving the thrombus selectivity of thrombin inhibitors. METHODS AND RESULTS: To explore the effect of targeting an antithrombin to the surface of a clot, we covalently linked recombinant hirudin to the Fab' (or IgG) of a monoclonal antibody (59D8) that selectively binds to an epitope on fibrin that becomes exposed only after thrombin cleaves fibrinopeptide B. Antibody-coupled hirudin bound to an immobilized peptide of the fibrin beta-chain amino-terminal sequence and inhibited the peptidolytic activity of thrombin more efficiently than free hirudin. Thrombin inhibition dependent on binding to immobilized fibrin monomer was enhanced 1100-fold (P < .0001). Hirudin-59D8 Fab' was 10 times more effective than hirudin in inhibiting fibrin deposition on experimental clot surfaces in fibrinogen solution (P < .0001) and human plasma (P < .0001). The more effective inhibition of thrombin by the conjugate was supported by significantly diminished concentrations of fibrinopeptide A in the plasma supernatant of the clot (P = .0001). Inhibition of clotting by an uncoupled mixture of hirudin and 59D8 Fab' was indistinguishable from that by hirudin alone, indicating that the conjugate's greater inhibitory activity was due to the covalent linkage between antibody and hirudin. CONCLUSIONS: Fibrin-targeted hirudin (in comparison with unmodified hirudin) significantly reduces fibrin deposition on the surface of experimental clots.