Differential regulation of endothelial cell permeability by high and low doses of oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine.

The generation of phospholipid oxidation products in atherosclerosis, sepsis, and lung pathologies affects endothelial barrier function, which exerts significant consequences on disease outcomes in general. Our group previously showed that oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (OxPAPC) at low concentrations increases endothelial cell (EC) barrier function, but decreases it at higher concentrations. In this study, we determined the mechanisms responsible for the pulmonary endothelial cell barrier dysfunction induced by high OxPAPC concentrations. OxPAPC at a range of 5-20 µg/ml enhanced EC barriers, as indicated by increased transendothelial electrical resistance. In contrast, higher OxPAPC concentrations (50-100 µg/ml) rapidly increased EC permeability, which was accompanied by increased total cell protein tyrosine (Tyr) phosphorylation, phosphorylation at Tyr-418, the activation of Src kinase, and the phosphorylation of adherens junction (AJ) protein vascular endothelial cadherin (VE-cadherin) at Tyr-731 and Tyr-658, which was not observed in ECs stimulated with low OxPAPC doses. The early tyrosine phosphorylation of VE-cadherin was linked to the dissociation of VE-cadherin-p120-catenin/ß-catenin complexes and VE-cadherin internalization, whereas low OxPAPC doses promoted the formation of VE-cadherin-p120-catenin/ß-catenin complexes. High but not low doses of OxPAPC increased the production of reactive oxygen species (ROS) and protein oxidation. The inhibition of Src by PP2 and ROS production by N-acetyl cysteine inhibited the disassembly of VE-cadherin-p120-catenin complexes, and attenuated high OxPAPC-induced EC barrier disruption. These results show the differential effects of OxPAPC doses on VE-cadherin-p120-catenin complex assembly and EC barrier function. These data suggest that the rapid tyrosine phosphorylation of VE-cadherin and other potential targets mediated by Src and ROS-dependent mechanisms plays a key role in the dissociation of AJ complexes and EC barrier dysfunction induced by high OxPAPC doses.

Coexisting hepatopulmonary syndrome and portopulmonary hypertension: implications for liver transplantation.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) represent pulmonary complications of liver disease and portal hypertension. The underlying pathophysiology behind these entities is complex and involves different effects of vasoactive substances on the pulmonary vasculature, among them endothelin-1 and nitric oxide (NO). Hepatopulmonary syndrome results from vasodilation, intrapulmonary shunting, and hypoxia. In contrast, portopulmonary hypertension is predominantly owing to generalized vasoconstriction that leads to remodeling and an increase in pulmonary vascular resistance, but is rarely associated with hypoxia. We present a case report in which these 2 processes with opposing pathologic mechanisms coexist in the same patient. We also conducted a literature search to identify other documented cases of coexisting hepatopulmonary syndrome and portopulmonary hypertension, common clinical features of these patients, and outcomes with or without treatment. Our case highlights the importance of recognizing the coexistence of these 2 disease processes, as they may occur simultaneously and affect the approach to treatment, including liver transplantation.

Safety and efficacy of single-balloon enteroscopy in management of gastrointestinal bleeding in patients with a left ventricular assist device.

Background and study aims Left ventricular assist devices (LVADs) are currently the standard of care in treatment of patients with end-stage heart failure waiting for heart transplant as well as destination therapy for non-transplant candidates. However, patients with LVADs are at increased risk of gastrointestinal bleeding due to the device's unique effects on hemodynamics. A major source of gastrointestinal bleeding in these patients are gastrointestinal angioectasias located within the small bowel that can only be reached with deep enteroscopy. The goal of our study was to determine the safety and efficacy of single-balloon enteroscopy (SBE) in treating gastrointestinal bleeding in patients with LVADs. Patients and methods We present a retrospective case series performed on patients with LVADs who underwent SBE to treat episodes of gastrointestinal bleeding. All procedures were performed at Emory University Hospital by a single endoscopist. Patient demographics, diagnosis and treatment of gastrointestinal bleeding, episodes of re-bleeding, and procedure-related complications were examined. Results A total of 27 SBE procedures performed in 14 patients were reviewed. SBE was performed in an antegrade approach in 89 % (24/27) of cases. Deep intubation was achieved in all antegrade procedures, with the distal jejunum reached in 79 % (19/24) of cases. The diagnostic yield was 78 %. There were no reported complications associated with the procedures. Conclusions SBE is a safe and effective modality to manage gastrointestinal bleeding in patients with LVADs.

Longer time to peak flow predicts better arterial flow parameters on penile Doppler ultrasound.

OBJECTIVES: To review the associations between measured variables in Penile Doppler ultrasound procedures. Penile Doppler ultrasound is useful in the evaluation of erectile dysfunction, but there is no uniform standard of performing the procedure. It is generally believed that a peak systolic velocity > 30 cm/s, minimal venous leak, and resistive index > 0.8 are essential for adequate erection. While the arterial parameters are well studied, data on the predictive value of time to peak flow are lacking. METHODS: Penile duplex Doppler ultrasounds performed for either erectile dysfunction or Peyronie's disease evaluation were reviewed. Clinical records, International Index of Erectile Function scores, and ultrasound variables were examined. "Fast" responders reached maximal peak systolic velocity (PSV) < or = 10 minutes, whereas "slow" responders reached maximal PSV between 15 and 25 minutes. RESULTS: Of 146 total patients, 36 (25%) were fast responders and 110 (75%), slow responders. No preprocedural characteristics, including the Erectile Function domain score of the International Index of Erectile Function, predicted time to peak flow. Compared with the fast responders, slow responders had higher mean PSV (left: 33.9 +/- 19.5 vs 25.0 +/- 11.7 cm/s, P = .01; and right: 36.4 +/- 21.3 vs 25.0 +/- 13.3 cm/s, P = .002). There was also a higher percentage of patients with average PSV > 30 cm/s in slow responders (58% vs 36%, P = .02). CONCLUSIONS: There were no significant differences in baseline characteristics between slow and fast responders. However, slow responders did seem to have significantly better arterial flow parameters, although penile dimensions, cavernosal artery diameter, Erectile Function domain scores, and subjective rigidity were similar.