[Heparin-induced type II thrombocytopenia as the etiology of severe recurrent pulmonary embolism]. / Heparininduzierte Thrombozytopenie Typ II als Ursache eines schweren Rezidivs einer Lungenembolie.

Heparin-induced thrombocytopenia (HIT) is a rare complication of anticoagulative heparin therapy. The more severe HIT type II is defined by peripheral thrombocytopenia combined with thrombotic and thromboembolic events. We report the case of a 24 year old male patient who was admitted to our ICU with thromboembolic obstruction of the right central pulmonary artery, and deep venous thrombosis (DVT) of the right superficial femoral vein. Systemic thrombolytic therapy with urokinase for seven days resulted in nearly complete resolution of the thromboembolic material in the pulmonary arteries. Antithrombotic therapy with intravenous heparin and overlapping oral phenoprocoumon was continued on the regular ward. Six days later, the patient had to be readmitted to the ICU with evidence of hemodynamic compromise due to massive bilateral pulmonary thromboembolism that could be confirmed by CT scan--DVT had extended to the right iliacal vein. Additionally, peripheral thrombocyte counts had markedly declined from 112.000 to 35.000/microliter within 3 days, indicating the presence of a Hit type II. This was verified by positive ELISA testing for antibodies against platelet factor 4 (PF4)-heparin-complex. A filter device was temporarily implanted into the inferior vena cava. The patients condition stabilized upon reinitiated systemic thrombolysis and replacement of heparin therapy against recombinant hirudin. Pulmonary artery pressures normalized. Peripheral thrombocytopenia diminished within three days. HIT type II is a severe complication of anticoagulative therapy with heparin. Here we report a case, and discuss diagnostic procedures as well as differential diagnosis to HIT type I.

Effects of chronic hypoxia on renal PDGF-A, PDGF-B, and VEGF gene expression in rats.

BACKGROUND: There is evidence from in vitro studies to suggest that the genes of platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) are, like the erythropoietin gene, regulated by oxygen tension. Hypoxia-induced stimulation of, for example, PDGF or VEGF might be involved in the pathogenesis of acute or chronic renal failure and in renal 'inflammatory' diseases (glomerulonephritis, vasculitis, allograft rejection). METHODS: Male Wistar rats were exposed to chronic normobaric hypoxia (10% O(2), 90% N(2)) for 4 weeks. Additional groups of rats were treated with the endothelin receptor antagonist LU13525 and the NO donor molsidomine. Renal mRNA levels of PDGF-A, PDGF-B, and VEGF were semiquantitated using RNase protection assays. RESULTS: Renal gene expression of PDGF-A and PDGF-B was neither affected by 2 or 4 weeks of hypoxia nor by concomitant treatment with LU135252 or molsidomine. Chronic hypoxia did also not change VEGF gene expression; however, concomitant treatment with LU135252 increased all VEGF subtypes (188, 164, 120). CONCLUSIONS: The findings of the present study suggest that renal PDGF and VEGF gene expression in vivo during chronic hypoxia for 2 and 4 weeks is not sensitive to tissue hypoxia in contrast to cell culture experiments. During chronic hypoxia with concomitant blockade of endothelin receptors, all VEGF subtypes were increased, suggesting an inhibitory action of endothelins with regard to renal VEGF gene expression.

Effects of growth hormone on renal renin gene expression in normal rats and rats with myocardial infarction.

BACKGROUND: Published data regarding effects of growth hormone (GH) on the renin system are controversial. The aim of this study therefore was to evaluate the effects of GH on the renin system in normal rats and rats with myocardial infarction (MI). METHODS: Normal rats received 2, 5, or 10 IU GH/kg/day or vehicle subcutaneously for 4 weeks. Furthermore rats with MI were randomized to receive 2 IU GH/kg/day or vehicle for 4 weeks. Subdivision into MI groups (mild, moderate, and large) was by histological determination of infarct size. Renal renin gene expression was assessed by RNAase protection assay and plasma renin activity by radioimmunoassay. In addition, isolated mouse juxtaglomerular cells were exposed to GH for 20 h, and renin secretion rates were assessed. RESULTS: GH treatment in normal rats for 4 weeks increased body weight, and kidney weight to body weight ratio, but did not affect renin secretion and renal renin gene expression. In rats with large MI, renal renin gene expression increased about fourfold, but was unchanged in rats with small and moderate MI as compared to normal rats. In rats with MI, body weight decreased and this decrease was partially reversed by GH treatment. GH treatment did not change renal renin gene expression, and renin secretion in rats with MI. Renin secretion of isolated juxtaglomerular cells was unaffected by GH. CONCLUSIONS: Our study demonstrates that GH treatment has no significant effect on renin secretion and on renal renin gene expression in normal rats and in rats with stimulated renin system due to MI in vivo. In isolated juxtaglomerular cells in vitro, renin secretion was also unaffected by GH.

Chloride channel blockers attenuate the inhibition of renin secretion by angiotensin II.

The aim of this study was to assess the relevance of chloride channels to the inhibitory effect of angiotensin II (ANGII) on renin secretion. We thus examined the effects of the chloride channels blockers IAA-94 and niflumic acid, the Na-K-Cl cotransport blocker bumetanide and substitution of isethionate for extracellular chloride on the action of ANGII on renin secretion from isolated perfused rat kidneys. Renin secretion prestimulated by isoproterenol (10 nmol/l) was almost completely blocked by ANGII with a concentration yielding a half-maximal response (EC50) of around 150 nmol/l. In the presence of IAA-94 and niflumic acid the EC50 for ANGII was shifted to about 400 nmol/l. In the presence of bumetanide and isethionate renin secretion responded more sensitively to ANGII and the EC50 for ANGII was below 100 nmol/l. On the assumption that the chloride equilibrium potential in renin-secreting cells is more positive than the membrane potential, our findings would suggest that the inhibitory effect of ANGII is enhanced when chloride entry is blocked and attenuated when chloride efflux is impaired. Activation of chloride channels therefore probably contributes to the inhibitory action of ANGII on renin secretion.