Women have increased risk of perioperative myocardial infarction and higher long-term mortality rates after lower extremity arterial bypass grafting.
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PURPOSE: The purpose of this study was to determine the effect of gender on the immediate and long-term postoperative morbidity, mortality, and patency rates for infrainguinal autogenous vein bypass grafts. METHODS: Data were abstracted for consecutive patients who were followed in a prospective surveillance protocol after undergoing infrainguinal autogenous vein bypass grafting during the years 1988 to 1994. There were 165 grafts constructed in 148 patients (101 in 87 men, and 64 in 61 women). Gender differences were analyzed with Student t test or chi2 test for risk factors, indications for reconstruction, and complications. The patency rates and the long-term survival rates were compared by means of life-table analysis. Eagle criteria and long-term survival rates were compared with multivariate analysis. RESULTS: The mean follow-up period was 36 months (39 months for men, and 32 months for women), with a range of 6 to 123 months for the total follow-up period. The two groups did not differ in age at the time of operation (66.6 +/- 1.2 years for men, and 66.7 +/- 1.5 years for women) or in history of diabetes (48% for men, and 56% for women). The risks were similar for hypertension (48% for men vs 45% women), preoperative myocardial infarction (23% for men vs 26% for women), and previous coronary artery bypass grafting (9% for men vs 8% for women). The thallium stress scintigraphy results showed a diagnosis of proportionately more preoperative defects in men (reversible, 34% vs 18%, P <.05; overall, 75% vs 43%, P <.05). The 30-day limb loss rates (0.9% for men, and 0% for women) and mortality rates (2.2% for men, and 5% for women) were similar. Women had statistically more perioperative myocardial infarctions than did men (6 of 61, 9.8% vs 2 of 101, 2%; P <.05), as was documented with electrocardiography and cardiac isoenzymes. Two of these women died within a 30-day postoperative period. The 3-year primary patency rate was 85% for the men and 88% for the women, and the primary assisted patency rate was 97% for the men and 97% for the women. The secondary patency rate was 98% for the men and 97% for the women. The limb salvage rate was slightly higher for the men than for the women (93% vs 87%), although this was not statistically significant. The 5-year survival rate for women was statistically less than for men, with life-table analysis (58% for men vs 42% for women; P <.05). CONCLUSION: After distal bypass grafting, men and women have similar rates of patency and limb salvage, but women have a higher incidence rate of perioperative myocardial infarction and a decreased 5-year survival rate. These data suggest that women have unrecognized cardiac disease that affects them adversely in the perioperative period and the long term when compared with men who undergo the same operation. (+info)
Selective in vivo inhibition of inducible nitric oxide synthase in a rat model of sepsis.
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Elevated production of nitric oxide (NO) by the inducible NO synthase (type II, iNOS) may contribute to the vascular hyporesponsiveness and hemodynamic alterations associated with sepsis. Selective inhibition of this isoenzyme is a possible therapeutic intervention to correct these pathophysiological alterations. Aminoguanidine has been shown to be a selective iNOS inhibitor and to correct the endotoxin-mediated vascular hypocontractility in vitro. However, to date aminoguanidine has not been shown to selectively block iNOS activity in vivo. The in vivo effects of aminoguanidine were assessed in the cecal ligation and perforation model of sepsis in rats. Aminoguanidine (1.75-175 mg/kg) was administered to septic and sham-operated rats for 3 h before euthanasia and harvest of tissues. NOS activities were determined in the thoracic aorta and lung from these animals. Aminoguanidine (17.5 mg/kg) did not alter the mean arterial pressure; however, it did inhibit induced iNOS (but not constitutive NOS) activity in the lung and thoracic aorta from septic animals. Only the higher dose of aminoguanidine (175 mg/kg) was able to increase the mean arterial pressure in septic and sham-operated animals. Thus selective inhibition of iNOS in vivo with aminoguanidine is possible, but our data suggest that other mechanisms, in addition to iNOS induction, are responsible for the loss of vascular tone characteristic of sepsis. (+info)
Correlation of VEGF expression by leukocytes with the growth and regression of blood vessels in the rat cornea.
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PURPOSE: To determine the temporal and spatial relationships between neovascularization and basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) mRNA and protein expression in the rat cornea after cautery with silver nitrate. METHODS: In female Sprague-Dawley rats, a silver nitrate applicator was placed on the central cornea to elicit circumferential angiogenesis, and blood vessel growth was quantified by digital image analysis of corneal flat-mounts. Total RNA or protein was extracted from whole corneas until 1 week after cautery, and bFGF and VEGF mRNA and protein levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). To localize VEGF mRNA and protein, paraformaldehyde-fixed and paraffin-embedded histologic cross sections of corneas were examined by in situ hybridization and immunohistochemistry. Macrophages were identified by ED2 immunohistochemistry. To examine the regulation of VEGF, rats were treated with dexamethasone (0.5 mg/kg per day) and hyperoxia (70% O2). RESULTS: The neovascular response progresses in three phases: (1) a nonproliferative phase preceding vessel growth (< or = 48 hours after cautery); (2) a proliferative phase with maximal growth rate between 3 and 4 days; and (3) a regressive phase (day 7) with a decrease in vessel density accompanying the completion of vessel elongation. In corneas after cautery, bFGF mRNA expression was unchanged, and bFGF protein concentration decreaseed by 97% after 24 hours and returned to control levels by day 7. In contrast, VEGF164 and VEGF188 mRNA splice variants and protein peaked 48 hours after cautery, remained elevated 4 days after cautery, and decreased to near baseline by day 7. The peak concentration of VEGF in the cornea at 48 hours was calculated to be 720 pM, which is sufficient to evoke a functional response. In situ hybridization and immunohistochemistry showed VEGF expressed initially in neutrophils (24 - 48 hours) and subsequently in macrophages (4 days) adjacent to the cautery site. Treatment with either dexamethasone or systemic hyperoxia inhibited both neovascularization and the increase in VEGF expression. Dexamethasone inhibited 27% of cautery-induced VEGF upregulation at 24 hours and 23% at 48 hours, hyperoxia inhibited 32% at 24 hours and 43% at 48 hours, and combined treatment with both dexamethasone and hyperoxia had an additive effect (56% inhibition at 24 hours). CONCLUSIONS: VEGF production by leukocytes correlates temporally and spatially with cautery-induced angiogenesis in the rat cornea. Both inflammatory products and hypoxia appear to sufficiently increase VEGF expression near the cautery lesion to increase vascular permeability of limbal vessels and induce endothelial cell migration and proliferation. (+info)
Vitamin E and vascular homeostasis: implications for atherosclerosis.
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Considerable epidemiologic data suggest that dietary consumption of vitamin E reduces the incidence of cardiovascular disease. The precise mechanisms are not clear, but emerging data indicate that vitamin E has numerous activities that may, in part, explain its effect on vascular disease. In particular, vitamin E enhances the bioactivity of nitric oxide, inhibits smooth muscle proliferation, and limits platelet aggregation. One common mechanism to account for these effects of vitamin E is the inhibition of protein kinase C stimulation. In the setting of atherosclerosis, inhibition of protein kinase C by vitamin E would be expected to maintain normal vascular homeostasis and thus reduce the clinical incidence of cardiovascular disease. (+info)
The effects of lithium on vascular development in the chick area vasculosa.
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The effects of lithium on vascular development were examined using the chick embryo area vasculosa in shell-less culture as an experimental model. Embryos were explanted after 48 h in ovo and LiC1 (50, 100, 150 and 200 microg in 10 microl water) was applied to the centre of the blastodisc. Controls were untreated or given equimolar amounts of NaCl. At 24 h and 48 h after treatment, untreated and NaCl controls were identical, having well developed extraembryonic vessels. At doses of 100 microg and greater, LiCl significantly inhibited normal vascular development and expansion of the area vasculosa in the majority of explants. In many specimens blood islands continued to form but their assembly into primitive vessels was prevented, indicating that lithium affects the mechanism regulating the assembly of vascular endothelium. At the same time the embryos were alive but retarded in development compared with controls. When LiCl (150 microg) was applied to cultures explanted after 72 h in ovo (when the primary vascular network had already formed through vasculogenesis) no adverse effects were seen. This suggests that lithium affects vasculogenesis but not angiogenesis. Treatment with myo-inositol completely reversed the effects of lithium in a time dependent manner indicating that the phosphatidylinositol second messenger cycle may be involved in the cellular events of vasculogenesis. Finally the results of this study show that the yolk sac vasculature is particularly vulnerable to lithium and the consequent effects of this interference on embryonic development are discussed. (+info)
Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro.
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BACKGROUND: Restenosis after percutaneous coronary intervention remains a serious clinical problem. Progress in local gene therapy to prevent restenosis has been hindered by concerns over the safety and efficacy of viral vectors and the limited efficiency of nonviral techniques. This study investigates the use of adjunctive ultrasound to enhance nonviral gene delivery. METHODS AND RESULTS: Cultured porcine vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) were transfected with naked or liposome-complexed luciferase reporter plasmid for 3 hours. Ultrasound exposure (USE) for 60 seconds at 1 MHz, 0.4 W/cm2, 30 minutes into this transfection period enhanced luciferase activity 48 hours later by 7.5-fold and 2. 4-fold, respectively. Luciferase activity after lipofection of ECs was similarly enhanced 3.3-fold by adjunctive USE. USE had no effect on cell viability, although it inhibited VSMC but not EC proliferation. CONCLUSIONS: Adjunctive USE was associated with enhanced transgene expression in VSMCs and ECs and reduced VSMC but not EC proliferation in vitro, which suggests that ultrasound-assisted local gene therapy has potential as an antirestenotic therapy. (+info)
What guides early embryonic blood vessel formation?
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Survival of vertebrate embryos depends on their ability to assemble a correctly patterned, integrated network of blood vessels to supply oxygen and nutrients to developing tissues. The arrangement of larger caliber intraembryonic vessels, specification of arterial-venous identity, and proper placement of major branch points and arterial-venous connections are all precisely determined. A number of recent studies in both mammalian and nonmammalian vertebrate species, reviewed here, have now begun to reveal the major role played by genetically predetermined extrinsic cues in guiding the formation of early embryonic blood vessels and determining the global pattern of the vasculature. (+info)
Immunohistochemical study of rabbit choroidal innervation.
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Immunocytochemical methods with antibodies to the light (68 kDa), medium (160 kDa), and heavy (200 kDa) chain subunits of the neurofilament triplet have been used to visualize neuronal structures in rabbit choroids. Choroidal nerve fibers were present in the suprachoroid and vascular laminae and absent in the choriocapillary layer. These fibers may be classified as perivascular and intervascular. Perivascular fibers surround all arterial and venous blood vessels and form a network; these fibers were labeled with the three NF antibodies, although they were more easily visualized with anti NF-160 and anti NF-200 than anti NF-68. Intervascular fibers formed two groups. The first group consisted of fibers situated between the blood vessels and parallel to the blood vessel wall surface (paravascular fibers); these fibers were better observed using anti NF-160 and NF-200 than anti NF-68. The second group consisted of fibers which travel the entire length of the choroid until they reach the nerve plexus of the ciliary body (long tract fibers). The plexus was observed with anti NF-68, anti NF-160 and anti NF-200; however, the long tract fibers were more clearly visualized with anti NF-160 and anti NF-200 than with anti NF-68. Two types of choroidal cell were also labeled: ganglion cells and melanocytes. Ganglion cells are small, scarce neurons situated in the peripheral choroid; they were labeled with anti NF-160 and anti NF-200. The melanocytes were only labeled with anti NF-200 and they were the only non neuronal structure visualized using antibodies against neurofilaments. (+info)