A. Hoffman

Angiotensin II stimulates macrophage-mediated oxidation of low density lipoproteins

Increased incidence of myocardial infarction was found in hypertensive patients with high plasma renin activity and increased susceptibility to oxidation was demonstrated in low density lipoprotein (LDL) that was obtained from hypertensive patients. As lipid peroxidation was demonstrated in areas of the atherosclerotic lesion, we sought to analyze the effect of angiotensin II (AN-II) on LDL oxidation, both in vitro and in vivo. Preincubation of J-774 A.1 macrophage-like cell line or mouse peritoneal macrophages (MPM) with AN-II (10(-7) M) for 1 h at 37 degrees C, followed by the addition of LDL for a further 18 h of incubation, resulted in a substantial increase in macrophage-mediated oxidation of LDL (by 55% and 19%, respectively). Similarly, incubation of LDL with MPM harvested from AN-II-injected mice resulted in a substantially increased oxidation of the lipoprotein by up to 90% in comparison to saline-injected mice. Analysis of cellular lipid peroxidation in the MPM themselves, in both the in vitro and the in vivo studies, revealed a 25% or 90% increased macrophage lipid peroxidation, respectively. The mechanism of AN-II-mediated cellular lipid peroxidation involved AN-II binding to its receptor on macrophages as saralasin, an AN-II receptor antagonist, completely inhibited this effect. Inhibitors of phospholipases A2, C and D substantially reduced macrophage lipid peroxidation, suggesting the involvement of phospholipases A2, C and D substantially reduced macrophage lipid peroxidation, suggesting the involvement of phospholipid metabolites in AN-II-mediated macrophage lipid peroxidation, suggesting the involvement of phospholipid metabolites in AN-II-mediated macrophage lipid peroxidation. Extracellular calcium ions, which active phospholipases, were also essential for AN-II-mediated macrophage lipid peroxidation since calcium channel blockers substantially inhibited cellular lipid peroxidation. Finally, the nature of the oxidant and oxygenase involved in AN-II-mediated cellular lipid peroxidation was studied using oxygenase inhibitors. Angiotensin II-mediated macrophage lipid peroxidation was found to involve the action of cellular NADPH oxidase as well as 15-lypoxygenase. We conclude that AN-II stimulates macrophage-mediated mediated oxidation of LDL secondary to cellular lipid peroxidation, and this may have a role in the accelerated atherosclerosis found in hypertensive patients.

Epithelioid angiosarcoma associated with a Dacron vascular graft.

Angiosarcoma developed at the site of a Dacron vascular prosthesis 8 years after an aortobifemoral bypass graft insertion. The tumor was composed of epithelioid cells, which showed positive staining for cytokeratin and expression of the common endothelial markers CD31, CD34, and von Willebrand factor. Ultrastructural examination showed aggregates of large cells with intercellular lumina and focal perinuclear whorls of intermediate filaments. The patient, who had abdominal pain and weight loss, died of disseminated pelvic and abdominal disease 6 months after diagnosis. Sarcomas associated with vascular Dacron grafts and angiosarcomas associated with metal or polymer foreign bodies are rare. Their development is probably analogous to the common experimental development of foreign body-associated sarcomas in rodents. Physicians caring for patients with vascular grafts or metal foreign bodies should be aware of this complication.

Determinants of Micro-embolic Signals in Patients with Atherosclerotic Plaques of the Internal Carotid Artery

BACKGROUND AND PURPOSE This study aimed to investigate the embolic potential of carotid plaques, employing both the presence and the rate of micro-embolic signals (MESs), based on the presence and timing (current or past) of symptoms, degree of stenosis and ultrasonic characteristics of plaques. METHODS We used the transcranial Doppler (TCD) to monitor MES and the Doppler ultrasound to classify carotid plaques in newly symptomatic (acute stroke or transient ischaemic attack (TIA)), formerly symptomatic (relevant stroke or TIA per anamnesis) and asymptomatic patients with internal carotid artery (ICA) stenosis. RESULTS Stroke-related arteries evidenced a significantly greater presence of MES than the TIA-related and asymptomatic arteries (p=0.04), with no significant difference found between the latter two groups (stroke: 42/90, 46.7%; TIA: 15/49, 30.6%; asymptomatic: 40/130, 30.8%). Adjustment for anti-platelet treatment did not change this finding. The degree of stenosis, ultrasonic characteristics of texture and the density of plaques were not found to be associated with the presence or quantity of MES. CONCLUSION MESs are present significantly more often in stenosed, stroke-related carotid arteries as compared with TIA-related or asymptomatic arteries. Neither the ultrasonic characteristics nor the degree of stenosis were found to influence the presence or rate of MES.

Multiple sequential posttraumatic pseudoaneurysms following high-energy injuries: case report and review of the literature.

A 15-year-old boy sustained severe multisystem injuries from a satchel charge while in his native village in southern Lebanon. After evacuation and resuscitation measures, he had successful intensive multidisciplinary surgical care. His long-bone fractures were stabilized by tubular external fixation systems, and his lacerated right tibialis anterior artery was grafted. Twenty days after injury, he developed a pseudoaneurysm of the left distal ulnar artery, which was surgically resected and the ulnar artery proximally ligated. Two weeks later, a pseudoaneurysm of the left peroneal artery, distal to the knee and coupled with an arteriovenous fistula, was diagnosed. This was treated by fluoroscopic controlled embolization with placement of stents. The patient recovered uneventfully. He was last seen two years after surgery, and no gross vascular compromise of any of his limbs was evident. This appears to be the only reported patient with late-developing multiple posttraumatic pseudoaneurysms after severe blast and shrapnel injuries. This development suggests that late sequelae of blast injuries may be topographically widespread and can evolve months after the injury. As such, these patients should be followed closely with a high degree of suspicion for the appearance of new signs or symptoms.

From arteritis to mycotic aneurysm: visualization of the progression of mycotic aneurysm development following femoral arterial line insertion in an infant

Although uncommon, mycotic aneurysms in infants can be lethal because of the high risk of rapid expansion and rupture. Most catheter-associated mycotic aneurysms reported in the first year of life develop following umbilical artery catheterizations. We describe the sonographic detection of an early stage mycotic aneurysm in a 4-month-old following femoral artery catheterization complicated by methicillin-resistant Staphylococcus aureus (MRSA) septicemia. We also describe the sonographic and radiographic progression of this mycotic aneurysm before surgery.