Role of polymorphonuclear leukocytes in collar-induced intimal thickening in the rabbit carotid artery

In this study, the involvement of polymorphonuclear leukocytes (PMNs) in the development of intimal thickening was investigated. A fibromuscular intima was induced by placing a silicone collar around the rabbit carotid artery for 3 days or 2 weeks; the contralateral artery was sham operated. Rabbits received placebo treatments (groups 1 and 3), granulocyte-colony stimulating factor (group 2; G-CSF, 20 microg x kg(-1) x d(-1), delivered by subcutaneous osmotic pumps), or an anti-CD18 monoclonal antibody (group 4; 1.5 mg/kg i.v.). The G-CSF treatment raised the peripheral PMN count 5- to 12-fold but had no effect on intimal thickening on day 3, 12, or 14. A single injection of anti-CD18 prevented PMN extravasation 6 hours after collar implantation without influencing intimal hyperplasia on day 14. Repeated daily administration of anti-CD18 strongly bound to CD18 on peripheral PMNs and inhibited both PMN-dependent plasma extravasation in the skin and accumulation of CD14-immunoreactive leukocytes in the intima and media. However, anti-CD18 did not suppress early intimal thickening or accumulation of alpha-smooth muscle actin-immunoreactive cells by day 3. It thus appears that the PMN influx in the intima and media evoked by the perivascular collar is of little functional relevance to the subsequent smooth muscle cell migration and intimal thickening in this model.     

Simvastatin inhibits myointimal hyperplasia following carotid artery injury in cholesterol-fed rabbits

The effect of simvastatin, a potent inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) was evaluated in an experimental model of myointimal hyperplasia in cholesterol-fed rabbits. Myointimal hyperplasia was induced by an air-drying injury of the left carotid artery followed by a 2%-cholesterol diet for 14 days. A 2-week oral treatment with simvastatin (6 mg/kg/day, p.o.) significantly lowered the circulating levels of cholesterol and triglycerides (41% and 49% inhibition respectively) as well as the low density lipoprotein (LDL)-cholesterol and high density lipoprotein (HDL)-cholesterol levels. Simvastatin also strongly affected the uptake of cholesterol in the arteries occurring as a consequence of vascular injury (44% inhibition, P < 0.001). Morphometric analysis revealed that both the intima and the media areas increased substantially 2 weeks after the lesion and showed a considerable smooth muscle cell accumulation in the neointima together with the presence of numerous foam cells. A 16-day oral treatment with simvastatin strongly reduced smooth muscle cells hyperplasia occurring in both the media and the intima following deendothelialization (19% and 60% inhibition respectively) suggesting that simvastatin may be a useful inhibitor of restenosis which occurs following vascular injury.     

The role of polymorphonuclear leukocytes in the resistance to cutaneous Leishmaniasis

The massive infiltration by polymorphonuclear leukocytes (PMN) soon after skin infection with Leishmania major suggests that PMN could participate in reducing parasite load and controlling the spreading of leishmanial infection. Yet, direct evidence for the participation of PMN in host defense against L. major was lacking. We investigated L. major infection in susceptible and resistant mice treated with the monoclonal (mAb) antibody RB6-8C5 that depletes the population of mature neutrophils and eosinophils. Both BALB/c and C57BL/6 mice depleted of PMN show accelerated parasite spreading and more severe footpad swelling than similarly infected untreated mice. In addition, significant higher parasite numbers were found in the lesion draining lymph nodes from PMN-depleted C57BL/6 mice. Histopathological analysis of the paw confirmed neutrophils containing ingested parasites as the dominant cell type in the infiltrate of the first days after infection and the nearly absolute neutrophil depletion in mAb-treated mice. Our data show the importance of PMN in early control of parasite load and parasitism spreading in cutaneous leishmaniasis.     

Lactoferrin: its role as a Ga-67-binding protein in polymorphonuclear leukocytes

Gallium-67 bound to lactoferrin--an iron-binding protein found in high concentration in polymorphonuclear leukocytes--has been isolated from PMNs that have previously been incubated with Ga-67 citrate. Although the cell-labeling efficiency was highly variable (0.026-10%), much of the activity that did bind to the PNMs (74.8 +/- 10%) was recovered in the supernatant after sonication and centrifugation. About half (approximately 47%) of the PMN-bound activity was retained after dialysis and was presumably bound to macromolecules in the supernatant. When this retained activity was placed on a column containing immobilized antilactoferrin antibody, almost three quarters of the activity was bound to the column. This bound activity was (36 +/- 17%) of the total activity absorbed by the PMN. The addition to the antilactoferrin column of a known antigen-antibody-dissociating agent caused the disolution of the complex. No significant activity was bound to a control column. The findings indicate that lactoferrin is a major Ga-67-binding protein present in PMNs and suggest that it may play a major role in Ga-67 localization in an abscess. These results support the contention that molecules binding ferric iron have an important effect on Ga-67 distribution in vivo.     

Prostaglandin E2 inhibits apoptosis in human neutrophilic polymorphonuclear leukocytes: role of intracellular cyclic AMP levels

Routine detection and treatment of hypophosphataemia on the intensive care unit is commonplace. Hypophosphataemia has been associated with a multitude of clinical effects and there are many associations between correction of hypophosphataemia and improvement in symptoms. However, there is no evidence at present to support the routine correction of hypophosphataemia in the absence of clinical symptoms or signs.     

The ultrasonographic confirmation of the role of external carotid artery in blood supply of ischemic lesion in the big cerebral hemisphere

Using intraoperative monitoring of the blood flow linear speed in a. cerebralis media while total a. carotis interna occlusion in 10 patients the authors have concluded, that the degree of blood flow compensation in a. cerebralis media depends not only on collateral compensation possibilities by the contralateral side and rate of it inclusion, but largely-on a. carotis externa possibility on the lesion side.     

Predicting the effect of carotid artery occlusion during carotid endarterectomy: comparing transcranial doppler measurements and cerebral angiography

BACKGROUND and PURPOSE: We correlated the mean transcranial Doppler blood flow velocity (FVm) during carotid endarterectomy with the functional collateral pathway(s) documented by angiography. METHODS: Three patient groups were established: group 1 was dependent on the anterior communicating artery, group 2 on the anterior communicating artery and ipsilateral posterior communicating artery, and group 3 on the ipsilateral posterior communicating artery. Continuous middle cerebral artery FVm and electroencephalographic monitoring were performed in 45 patients during carotid endarterectomy. RESULTS: Clamped FVm was lowest in group 3 at 17+/-9 cm/s versus 36+/-16 and 33+/-11 cm/s for groups 1 and 2 (P<0.01). FVm values in groups 1 and 2 were similar. There was significant cerebral arterial vasodilation in group 3 patients on the basis of a pulsatility index of 0.38+/-0.15. The maximum FVm after clamp release was similar among the 3 groups. Normalized blood flow velocity 1 minute before release of the clamp was increased from the minimum flow velocity after clamping only in group 1 and 2 patients. CONCLUSIONS: The ipsilateral posterior communicating artery is a minor collateral pathway during acute carotid occlusion that contributes little to the collateral flow if there is a functional anterior communicating artery. Collateral flow through the middle cerebral artery is not recruited during occlusion in group 3 patients. The reperfusion FVm transient is independent of the primary collateral pathway. Documentation of functional collateral pathways on the basis of Doppler or angiographic examination may be advantageous in future studies since it can provide the basis for comparison among studies.     

Endothelium-dependent regulation of the carotid artery diameter by the flow in rabbits of various age

Endothelium-dependent flow-induced regulation leads to a decrease in the flow-induced response of arteries in male rabbits from a newly-born period to one-month period of life.     

Dissecting hematoma of the internal carotid artery following chiropractic cervical manipulation

A patient with a dissecting hematoma of the internal carotid artery following chiropractic neck manipulation is described. This injury, apparently previously unreported in the literature, is thought to be caused by trauma to the artery by rotatory movement of the neck and pressure against the artery by the transverse process of C-2.     

Thrombosis of the cerebral vessels following closed cranial trauma (author's transl)

The case histories are presented of 6 patients, 5 of whom developed carotid artery thrombosis (the left vessel being affected in 4 cases and the right only in 1 case) following closed cranio-cerebral trauma; the 6th patient developed thrombosis of the posterior cerebral artery, as confirmed at autopsy. The factors involved in the aetiology of these events are discussed on the basis of the case reports.     

The crucial role of polymorphonuclear leukocytes in resistance to Salmonella dublin infections in genetically susceptible and resistant mice

Macrophages are considered to be the mediators of resistance to extra-intestinal Salmonella infections. Nevertheless, the initial cellular response to Salmonella infections consists primarily of polymorphonuclear leukocytes (PMN). To determine whether PMN serve an important function for the infected host, we made mice neutropenic with the rat mAb to RB6-8C5 and infected them i.v. with approximately 10(3) Salmonella dublin or an isogenic derivative that lacks the virulence plasmid (LD842). We infected BALB/c mice, which have a point mutation in the macrophage-expressed gene Nramp1 that makes them susceptible to Salmonella, and BALB/c.D2 congenic mice, which have the wild-type Nramp1 gene that makes them resistant to Salmonella. Both mouse strains were resistant to LD842, and neutropenia made only the BALB/c strain susceptible to this infection. Neutropenic congenic mice, however, were susceptible only to wild-type S. dublin (plasmid+). These results show a complex interplay between plasmid-virulence genes in Salmonella, host macrophages, and PMN. Mice with normal macrophages need PMN to defend against nontyphoid Salmonella that carry a virulence plasmid but not against Salmonella without virulence plasmids. Mice with a mutant Nramp1 gene need PMN to defend against all Salmonella, even those that lack virulence plasmids. These results, plus the evidence that PMN kill Salmonella efficiently in vitro, suggest that Salmonella have adapted to grow inside macrophages where they are relatively sheltered from PMN. The adaptations that allow Salmonella to survive in macrophages do not protect them from PMN.     

Plastic repair of the carotid artery in carotid endarterectomy

The work is based on an analysis of results of 70 carotid endarterectomies performed on 68 patients aged from 43 to 67 years. 53% of the patients were operated upon at the stage of a relative compensation of brain blood circulation. Multiple character of injuries of the brachiocephalic arteries took place in 70.5% of the cases. Plasty of the internal carotid artery is thought by the authors to be necessary by means of using a flap of lyophylized allopericardium, with the diameter of its orifice less than 8 mm.     

Endothelial dysfunction in critically ill patients: the effect of haemofiltration

OBJECTIVES: To examine the effect of a single episode of continuous venovenous haemofiltration (CVVH) on indicators of endothelial injury and the protein C/S system in critically ill patients. DESIGN: Observational study. SETTING: University teaching hospital intensive care unit. PATIENTS: 12 critically ill patients with acute renal failure receiving their first episode of CVVH. INTERVENTIONS: Blood samples were collected prior to starting CVVH and at 15 min and 1, 3-4, 8-12, and 24 h, and at 24-h intervals thereafter until the filter clotted. MEASUREMENTS AND RESULTS: Soluble tissue factor, soluble thrombomodulin, E-selectin and endothelin-1 were measured as indicators of endothelial injury. Changes in the protein C/S system were assessed by measurement of protein C (PC) and both free and total protein S (PS). Levels of PC and both free and total PS were subnormal in 6 and 11 patients, respectively, prior to CVVH, but there were no further changes during CVVH. Levels of tissue factor, thrombomodulin, E-selectin, and endothelin-1 were raised prior to haemofiltration in 9, 10, 9 and 9 patients, respectively. There were further increases during CVVH in at least one, but not all, of the markers of endothelial injury in most patients. There was no consistency between the changes in different markers of endothelial injury during haemofiltration in individual patients. CONCLUSIONS: The PC/PS system and endothelial integrity is compromised in critically ill patients prior to haemofiltration, but a single episode of CVVH has little effect on the PC/PS system. The increase in markers of endothelial dysfunction seen during CVVH is more likely to be related to the underlying condition of the patient rather than any specific consequence arising from the technique itself.     

Temporal expression of c-fos mRNA following balloon injury in the rat common carotid artery

OBJECTIVE: Restenosis is a common problem which limits the effectiveness of percutaneous transluminal coronary angioplasty (PTCA). The cellular mechanisms of restenosis appear to involve smooth muscle cell (SMC) migration to the neointima in response to mitogens and growth factors, resulting in proliferation and deposition of cells in the lumen of the vessel. An antibody directed against PDGF attenuates this response in the rat. Thus, signaling cascades induced by growth factors including PDGF may be important targets for therapeutic intervention. METHODS: Since a number of growth factors activate c-fos via the p21-ras signaling pathway, we examined c-fos expression in a time course experiment involving restenotic lesions in rat carotid arteries. Sections of arteries collected at 1, 3, 7, 14 and 28 days following balloon injury were hybridized using a fluorescein-labeled RNA probe to c-fos. Immunohistochemistry was performed with antibodies to proliferating cell nuclear antigen (PCNA) and alpha-smc actin to characterize cellular constituents of the neointima, and detect any correlation between fos expression and PCNA localization. RESULTS: Expression of c-fos was low at day 1. By day 3, the media and adventitia were positively stained. At days 7 and 14, most cells in the neointima were labeled. By day 28, c-fos was expressed mainly in scattered cells along the luminal surface. Control sections revealed little labeling and confirmed specific staining by the antisense strand, PCNA localization and c-fos expression were similar at days 1, 3, 7 and 28, but at day 14 c-fos was expressed throughout the lesion, with PCNA localized mainly along the luminal edge. The majority of the cells making up the neointima stained rather intensely for alpha-smc actin, identifying them as SMCs. CONCLUSIONS: Results of these experiments indicate that, while c-fos expression correlates with lesion formation, it may be associated with a cellular process distinct from proliferation in this model.     

Intracranial hemorrhage observed in the cases of cervical internal carotid artery occlusion associated with moyamoya disease-like vessels]

We report on two peculiar cases of intracranial hemorrhage due to the rupture of moyamoya disease-like vessels associated with unilateral internal carotid occlusion at its origin. The first case is 44-year-old male showing intraventricular hemorrhage associated with right internal carotid occlusion. The second case is 58-year-old female presenting sub-arachnoid hemorrhage associated with left internal carotid occlusion. Although both cases showed the unique appearance of collateral flow resembling moyamoya disease, they were not classified as moyamoya disease nor unilateral Moyamoya-like state. Vascular abnormality such as cerebral aneurysm and arteriovenous malformation were not at all detected. The etiology of hemorrhage for both cases is presumed as the rupture of moyamoya disease-like vessels, however, it is unable for us to determine why the one case showed IVH, yet the other showed SAH. The two cases showed hypoperfusion of ipsilateral cerebral hemisphere on SPECT that followed by the external-internal carotid revascularization surgery in the chronic stage. Post operative study proved the improvement of the CBF reserve. Nevertheless, whether the reconstructive vascularization prevent an occurrence of rebleeding needs the longer observation and the accumulation of the resembling cases.     

Fusiform dilatations of the internal carotid artery following surgery for pediatric suprasellar tumors

Fusiform dilatations of the internal carotid artery (FDCA) represent a vascular complication following surgery for suprasellar tumors in children. In a long-term follow-up of 62 children we identified 7 children (11.3%) with a FDCA. In all children the FDCA was present within 15 months following surgery. It was not related to radiotherapy or a distinct histology. In 3 children the FDCA remained unchanged during the follow-up, in 3 children there was a progression and 1 child revealed a regression within 6 months. Clinically the FDCA was inapparent in all cases and not treated. In a follow-up study of an adult population who underwent surgery for suprasellar tumors no case of FDCA was encountered. Potential pathomechanisms and indications for treatment are discussed.     

Ultrastructural changes in cerebral blood vessels following prolonged administration of L-dopa to laboratory animals

Patients with anomalous left coronary artery arising from the pulmonary artery rarely survive to adult life. Those who attain adulthood may present with angina indistinguishable from coronary artery disease and are liable to sudden death. Myocardial infarction, though rare in young adults, may occur and may be due to coronary artery steal. Accurate diagnosis requires coronary arteriography. Two further cases of coronary artery steal in adults with anomalous origin of the left coronary artery from the pulmonary artery are presented. In both patients aortocoronary bypass grafting using a reversed autogenous saphenous vein with closure of the origin of the anomalous left coronary artery was successfully performed. This operation provided complete symptomatic relief and may protect patients against the risk of sudden death.