Biomedical subjects

R Virmani

Publications and source records attributed to R Virmani.

348 records · Page 20Linked to original sources

PubMedDate not supplied

Effects of perfluorochemical on phagocytic function of leukocytes.

Oxygen-carrying perfluorochemical emulsions may become useful for transfusions when red cells cannot be used. Since accumulation of perfluorochemicals in reticuloendothelial cells has been demonstrated, we tested the phagocytic function of monocytes and neutrophils in rabbit and human blood exposed in vivo and in vitro, respectively, to perfluorotributylamine (Oxypherol) a perfluorochemical blood substitute. Neutrophil and monocyte phagocytosis was assessed by determining the uptake of serum-coated fluorescent beads by monocytes and neutrophils in whole blood. Morphologic changes were assessed by electron microscopy. The phagocytic activity of monocytes and neutrophils in the blood of four rabbits injected 4 hours earlier with 70 to 85 ml of Oxypherol (28 ml/kg) was depressed by 87 +/- 1.0 percent. Neutrophils in this blood showed morphological alterations characterized by swelling and extensive vacuole formation. Similar changes were found in neutrophils and monocytes of human blood incubated with Oxypherol (10-50%, V/V) at 37 degrees C for 1 hour. The phagocytic activity of human neutrophils and monocytes exposed to 20 percent, V/V Oxypherol was depressed by 35 +/- 9.9 percent. We conclude that caution should be exercised when administering perfluorochemical blood substitutes in patients exposed or at risk of infection.

Animals↗

PubMedDate not supplied

Effect of perfluorochemical blood substitutes on human neutrophil function.

This investigation was undertaken to determine the influence of perfluorochemical blood substitutes (PFCs) on human neutrophil function. Neutrophils isolated from blood of healthy donors were incubated at 37 degrees C for 1 hour with 25 percent Oxypherol (perfluorotributylamine) or Fluosol-DA (perfluorodecalin and perfluorotripropylamine) in the presence of fresh autologous serum. In comparison to cells incubated with Hank's balanced salt solution (buffer), neutrophils exposed to PFCs were markedly inhibited in their chemotactic and phagocytic responses. With 25 percent PFCs, chemotaxis to zymosan-activated serum was inhibited to approximately 25 percent of control by Fluosol-DA and 11 percent by Oxypherol. Phagocytosis of polystyrene beads in the presence of fresh serum was decreased to 52 and 50 percent of control by both Oxypherol and Fluosol-DA, respectively. Neutrophils exposed to PFCs aggregated slower and with an extended activation time upon addition of phorbol myristate acetate (PMA). When activated with n-formyl-methionyl-leucyl-phenylalanine (FMLP), neutrophils exposed to PFCs aggregated at a faster rate but with a longer lag phase in comparison to control cells. Neutrophil superoxide (O-2) release stimulated by PMA also was depressed by prior exposure of cells to Oxypherol (6 nmoles O-2/1.5 X 10(6) neutrophils) compared to buffer (32 nmoles O-2/1.5 X 10(6) neutrophils). PMA-stimulated neutrophil adherence was depressed significantly by prior exposure to Fluosol-DA compared to control. In contrast, Oxypherol had insignificant influence on stimulated adherence. Since PFCs have a profound influence on several important neutrophil functions, patients receiving PFC should be monitored closely for possible infectious complications.

Blood Substitutes↗

PubMedDate not supplied

Perfluorochemical blood substitutes differentially alter human monocyte procoagulant generation and oxidative metabolism.

Human blood mononuclear leukocytes exposed in vitro to perfluorochemical blood substitutes (Fluosol-DA and FC-43) generated increased procoagulant activity that was time dependent. Mononuclear leukocytes incubated with 10 percent Fluosol-DA for 4 hours generated 3.43-fold more procoagulant activity than control cells. At 24 hours of incubation with 10 percent Fluosol-DA, cells generated 10.49-fold more procoagulant than control. Cells incubated with 10 or 20 percent FC-43 generated 2.5- or 3.4-fold greater procoagulant than controls, respectively. The perfluorochemical emulsifier (Pluronic F68) also stimulated 3.4-fold more activity than control cells. Stimulated oxidative metabolism (superoxide anion generation) was significantly impaired by Fluosol-DA but not by FC-43 or Pluronic F68. No significant perfluorochemical-induced cytotoxicity was measured by trypan blue dye exclusion or lactate dehydrogenase release. Electron microscopic analysis showed progressive uptake of the perfluorochemicals by monocytes but not by lymphocytes. Thus, perfluorochemicals may differentially activate cellular initiators of coagulation while impairing other metabolic responses of mononuclear phagocytes. Patients receiving perfluorochemical preparations should be monitored for abnormalities of hemostasis and for disorders of the mononuclear phagocyte system.

Blood Coagulation Factors↗

PubMedDate not supplied

Pathology of acute and chronic coronary stenting in humans.

BACKGROUND: Despite the increasing use of stents, few reports have described human coronary artery morphology early and late after stenting. METHODS AND RESULTS: Histology was performed on 55 stents in 35 coronary vessels (32 native arteries and 3 vein grafts) from 32 patients. The mean duration of stent placement was 39+/-82 days. Fibrin, platelets, and neutrophils were associated with stent struts </=11 days after deployment. In stents implanted for </=3 days, only 3% of struts in contact with fibrous plaque had >20 associated inflammatory cells compared with 44% of struts embedded in a lipid core and 36% of struts in contact with damaged media (P<0.001). Neointimal growth determined late histological success, and increased neointimal growth correlated with increased stent size relative to the proximal reference lumen area. Neointimal thickness was greater for struts associated with medial damage than struts in contact with plaque (P<0.0001) or intact media (P<0.0001). When matched for time since treatment, neointimal cell density in stented arteries was similar to that in unstented arteries that had undergone balloon angioplasty and showed similar proteoglycan deposition. CONCLUSIONS: Morphology after coronary stenting demonstrates early thrombus formation and acute inflammation followed by neointimal growth. Medial injury and lipid core penetration by struts result in increased inflammation. Neointima increases as the ratio of stent area to reference lumen area increases. Deployment strategies that reduce medial damage and avoid stent oversizing may lower the frequency of in-stent restenosis.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Increased prevalence of aortic fatty streaks in cholesterol-fed rabbits administered intravenous cocaine: the role of vascular endothelium.

Several recent postmortem studies suggest an increased prevalence of atherosclerosis in young habitual cocaine abusers. However, little is known about the effects of cocaine abuse on the vascular endothelium and its relationship to atherosclerosis. Therefore, the consequence of chronic administration of intravenous cocaine on the induction of aortic sudanophilia was examined. Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 wk. During this period, animals were randomized to receive either cocaine-hydrochloride (0.25 mg/kg) intravenously (n = 17) twice daily; or an equivalent volume of 0.9% physiologic saline, control group (n = 16). Mean values for total circulating leukocytes and platelets and total plasma cholesterol and triglycerides were similar in both groups throughout the protocol. At the completion of the study, aortic sudanophilia was measured and expressed as a percentage of regional involvement (R1 = proximal 4 cm, R2 = middle 6 cm, and R3 = distal 10 cm). Statistical significance among groups was achieved in the proximal thoracic aorta (p = 0.057). No significant differences in sudanophilia were noted in the middle and distal segments. When animals were placed in subgroups according to percent total plaque involvement, there was a significant increased distribution of rabbits with a greater extent of sudanophilia in the cocaine-treated group as compared with control (p = 0.01, chi-square analysis). Immunocytochemical studies using the macrophage-specific and muscle actin-specific monoclonal antibodies demonstrated that sudanophilic areas in both groups were predominantly composed of macrophage-derived foam cells. Evaluation of plaque morphology showed an increase in intimal plaque thickness and in the number of macrophages and smooth muscle cells in cocaine-treated animals; however, group differences were not statistically significant. Because no significant differences were found in the cellular composition of atherosclerotic plaques between groups, further studies were performed to assess the effects of cocaine on the permeability function of cultured endothelial cell monolayers as a possible mechanism of increased sudanophilia. Cocaine (100 microM)-treated endothelial cell monolayers demonstrated an increased permeability to horseradish peroxidase during all time intervals studied (0-6 hr). Permeability differences were statistically significant at 30 min and 1 hr (p = 0.003 and 0.02, respectively). Collectively, these observations suggest that administration of cocaine to cholesterol-fed rabbits increases the prevalence of aortic sudanophilia via at least one possible mechanism involving enhanced vascular permeability.

Animals↗

PubMedDate not supplied

Comparative pathology: radiation-induced coronary artery disease in man and animals.

The occurrence of coronary artery disease following mediastinal radiation for malignancies has long been debated. However, the development of coronary pathology in young individuals following radiation who lack risk factors for atherosclerosis is highly suggestive of a cause-and-effect relationship. By far the most convincing pathologic changes are adventitial scarring and medial atrophy with severe intimal atherosclerotic disease consisting of necrotic core, fibrous tissue, and calcification. Initial clinical studies in patients with coronary atherosclerosis treated with intraluminal radiation following stenting hold great promise in the treatment and prevention of restenosis. There are little or no data, however, on long-term effects of intra-coronary radiation therapy in man. Therefore, it may be important to study the chronic effects of radiation in animal models in order to predict what is likely to occur in humans. We evaluated the effects of varying doses (0.15-23.0 microCi of 32P) of beta-particle-emitting radioactive stents in pig coronary arteries at 1 and 6 months. At 1 month, there were dose-dependent changes in the morphology of the intima and media. High activities (>3 microCi) caused medial necrosis with fibrin deposition in the media and intima, with interspersed red cells most marked in regions surrounding the stent struts. Only rare smooth muscle cells (SMCs) and inflammatory cells were seen away from the stent struts. In the intermediate (1 microCi) stent activity group, the neointima was expanded by SMCs and a proteoglycan-rich matrix with focal endothelialization of the luminal surface. Neovascular capillaries and extravascular red cells were present adjacent to stent struts. At low activities (<0.5 microCi), the neointima was significantly smaller than control stents and consisted of SMCs and matrix with complete endothelialization of the luminal surface. The neointimal cell density of the media and intima decreased with increasing doses of radiation. In pigs 6 months after radioactive stenting (activities ranging from 0.5-12 microCi 32P), >3.0 microCi radioactive stents induced marked neointimal thickening, with changes similar to atherosclerosis, consisting of necrotic debris containing cholesterol clefts surrounded by macrophage collections, fibrosis, and focal calcification. There was increased adventitial thickening in the radiated vs non-radiated arteries. The intermediate stent activity (1.0 microCi) also showed greater neointimal thickening (vs control stents) and consisted mostly of SMCs in a proteoglycan-rich matrix. At <1.0 microCi, there were minimal differences seen between radiated and control non-radiated stented arteries. The media was unevenly injured in all stent activities and varied from less than to significantly greater than controls. These data suggest that radiation-induced coronary atherosclerosis seen in man is partially simulated in normal porcine coronary arteries 6 months following high-dose beta-particle-emitting radioactive stent placement. There is greater fibrosis and thickness of the adventitia and focal attenuation of the media in man and severe luminal narrowing in pig coronary arteries treated with high doses of radiation. Only long-term clinical follow up and careful autopsy studies will determine if endoluminal or intra-arterial radiation is a viable means of reducing restenosis in man.

Animals↗