Kathrin Watzinger

The crucial impact of iron deficiency definition for the course of precapillary pulmonary hypertension

Imbalances of iron homeostasis are associated with an adverse clinical outcome of pulmonary hypertension (PH). Herein, we aimed to analyze the impact of iron deficiency (ID) in a real-life PH patient cohort according to different currently used ID definitions. In a retrospective study including 153 precapillary PH patients followed over a mean period of five years, iron deficiency was assessed according to five clinical definitions used in previous trials. The impact of ID on clinical, hematological and hemodynamic parameters was investigated. Depending on the different cutoff levels for serum ferritin and transferrin saturation, currently used ID definitions indicated a prevalence of either true or functional ID in 11 to 75 percent of PH patients. A good diagnostic accuracy was achieved by using the sTFRF/log ferritin (sTFRF) index, which identified 33 to 42 percent of PH patients as being iron deficient. The sTFRF index had the best prediction for the association between ID and clinical outcome. Iron deficient patients with precapillary PH had a significantly higher mortality as compared to non-iron deficiency subjects, which was true for both, PH patients with and without anemia. Although levels of the iron hormone hepcidin were rather affected by ID than by inflammation, they were not associated with the clinical course or mortality of PH subjects. To conclude, ID had a significant impact on the clinical course of precapillary PH patients. The appropriate use of robust biomarkers to define ID is a prerequisite to further evaluate the role of ID and the potential benefit of iron supplementation in precapillary PH patients.

Effects of arginine vasopressin on migration and respiratory burst activity in human leukocytes

Abstract Arginine vasopressin can bind to high-affinity vasopressin V1a receptors in human leukocytes. This study aims to investigate the effects of arginine vasopressin on migration and chemotaxis of neutrophils and oxygen free radical release by human leukocytes. Neutrophils and monocytes were obtained from peripheral blood samples of ten healthy volunteers. Leukocyte migration was microscopically assessed in a modified 48-blind well microchemotaxis chamber, and respiratory burst activity was estimated using 2’,7’-dichlorofluorescin diacetate in descending concentrations of arginine vasopressin. Arginine vasopressin stimulates migration of monocytes and neutrophils depending on concentration and on interaction with other chemoattractants. The strongest chemotactic responses of monocytes to arginine vasopressin were observed in the micro and nanomolar range and in the nanomolar range for neutrophils (p<0.001). Pre-incubation of leukocytes with arginine vasopressin decreased migration of leukocytes in a dose-dependent manner. Arginine vasopressin did not stimulate release of oxygen free radicals by neutrophils. Arginine vasopressin stimulates in a dose-dependent manner the migration of monocytes and neutrophils. However, pre-incubation of leukocytes with arginine vasopressin decreased the migratory response of monocytes and neutrophils to other chemoattractants. These findings may be of importance in the treatment regimen of patients with septic shock.