Standard PAH therapy improves long term survival in CTEPH patients.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH), subsequent to pulmonary embolism is a relatively frequent cause of pulmonary hypertension. Similar to patients with pulmonary arterial hypertension (PAH), CTEPH carries a poor prognosis. There is no hard evidence for any other therapy except pulmonary endarterectomy and none for those patients that are not eligible for this procedure. PATIENTS AND METHODS: Fifty patients with confirmed, inoperable CTEPH receiving specific vasodilative therapy (prostanoids, endothelin receptor antagonists, PDE 5-inhibitors or combination) were included in this retrospective study (mean age 55 years, range 16-76 years; 36 female, 14 male). Kaplan-Meier plots of these patients were compared with Kaplan-Meier plots of two historical CTEPH patient groups without any specific vasodilative treatment by log rank tests. RESULTS: CTEPH patients treated with specific vasodilative compounds as used for therapy of PAH were followed up for 52 +/- 30 months and had a significantly improved survival compared with patients treated without PAH type vasodilators (p < or = 0.0002). CONCLUSION: Our data may generate the hypothesis that specific vasodilative treatment improves outcome in patients with inoperable CTEPH.

Free reactive oxygen species and nephrotoxicity of contrast agents.

BACKGROUND: The nephrotoxicity induced by contrast media remains a serious clinical problem, and the underlying mechanism has not been completely understood. Experimental and clinical investigations suggest that reactive oxygen species (ROS) are critical determinants of radiocontrast nephropathy (RCN), and that antioxidants can prevent this damage. METHODS: Cultured human proximal renal tubule cells (HK-2) were exposed to hydrogen peroxide (H2O2) at different concentrations. H2O2-induced tubular DNA damage was examined in the presence of the antioxidant MESNA (sodium-2-mercaptoethane sulphonate). The induction of DNA damage was measured with the alkaline comet assay (single cell gel electrophoresis). We also studied 12 patients with stable renal impairment (median baseline creatinine 296 micromol/l; range: 203-495 micromol/l) undergoing cardiac catheterization/intervention prospectively. Patients received 800 mg MESNA intravenously 30 min before exposure to the contrast agent in addition to 0.9% saline hydration. RESULTS: In the cell cultures, oxidative stress on HK-2 cells induced increased DNA migration in the comet assay. Treatment of tubular cells with the antioxidant MESNA prior to the addition of H2O2 significantly reduced DNA migration in the comet assay. In the clinical study, treatment of the patients with MESNA prevented the adverse renal effect of contrast media (median serum creatinine 293; range: 187-433 micromol/l) 48 h after coronary angiography/intervention. CONCLUSION: Both the in vivo and the in vitro studies suggest that the ROS-mediated renal injury could be inhibited by a potent antioxidant such as MESNA.

Regional heterogeneity of cerebral blood flow response to graded pressure-controlled hemorrhage.

BACKGROUND: Little is known about the regional distribution of cerebral blood flow (CBF) in nonanesthetized animals during periods of lowered blood pressure. The present investigation addresses the specific reaction patterns of local cerebral blood flow (LCBF) in comparison with mean CBF during graded pressure-controlled hemorrhagic shock in conscious rats. METHODS: Conscious rats were subjected to graded pressure-controlled hemorrhage (to 85, 70, 55, or 40 mm Hg) by arterial blood withdrawal. After a period of 30 minutes, blood pressure was stabilized by withdrawal or reinfusion of blood. LCBF was determined autoradiographically by the iodo(14C)antipyrine method in 34 brain structures, and mean CBF was calculated and compared with the values of nonhemorrhaged control animals. RESULTS: Mean CBF remained unchanged except for the group with the lowest blood pressure of 40 mm Hg (decrease in CBF of 28%). Otherwise, LCBF was increased in some brain structures at an unchanged mean CBF. Congruently, at 40 mm Hg, the decrease in mean CBF did not show up in all brain structures, the local pattern of CBF varying between an unchanged and a profoundly decreased CBF. The mean coefficient of variation of CBF was increased with the severity of hemorrhagic shock, which indicates an enhanced heterogeneity of CBF. CONCLUSION: Because of the substantial heterogeneity in the responses of LCBF to pressure-controlled hemorrhage, autoregulation of CBF during pressure-controlled hemorrhagic shock has to be reconsidered on a regional basis.