[Comparison of efficacy of rivaroxaban and warfarin after open operations on the infrainguinal segment]. / Sravnenie éffektivnosti rivaroksabana i varfarina posle otkrytykh operatsii na infraingvinal'nom segmente.

The authors analysed oral anticoagulant agents prescribed in the postoperative period to patients after endured reconstructive operative intervention on arteries of the femorotibial segment. The study included a total of 104 patients subjected to femoropopliteal or femorotibial bypass grafting using an autologous vein or a prosthesis. Depending on the prescribed anticoagulation agent, the patients were subdivided into two groups. Group One patients (n=43) in the postoperative period received rivaroxaban, and Group Two patients (n=61) took warfarin. Efficacy of therapy was evaluated by the frequency of haemorrhage and thromboses in the early and remote postoperative periods. The findings of the immediate postoperative period demonstrated comparable rates of haemorrhagic complications, early thromboses and redo interventions in both Groups (p=0.7). The duration of long-term postoperative period varied from 3 months to 5 years. No statistically significant differences in patency of the performed reconstructions were revealed between the groups. The 3-year primary assisted patency rate in the rivaroxaban group and warfarin group amounted to 89 and 80%, respectively. The incidence of haemorrhagic complications in the postoperative period was insignificant in the studied groups. Hence, rivaroxaban may be prescribed in the early and remote postoperative period to patients who underwent open reconstructive operative intervention on arteries of the infrainguinal zone.

The Effect of Nitroglycerin on Arterial Stiffness of the Aorta and the Femoral-Tibial Arteries.

AIM: The effect of nitroglycerin on proper arterial stiffness of the arterial tree has not been fully clarified. The cardio-ankle vascular index (CAVI), which is an application of the stiffness parameter ß theory on the arterial tree from the origin of the aorta to the ankle, was developed recently. Furthermore, the stiffness of the aorta (heart-thigh ß (htBeta)) and of the femoral-tibial arteries (thigh to ankle ß (taBeta)) could be monitored by applying the same theory. The effects of nitroglycerin on CAVI, htBeta, and taBeta were studied comparing the values of healthy people and those of arteriosclerotic patients. METHODS: The subjects were healthy people (CAVI ＜7.5, n=25) and arteriosclerotic patients (CAVI ＞9, n=25). Nitroglycerin (0.3 mg) was administrated sublingually, and various arterial stiffness indices were measured at one-minute intervals for a period of 20 minutes using Vasera VS-1500 (Fukuda Denshi, Tokyo). RESULTS: After the administration of nitroglycerin in healthy people, CAVI decreased significantly after 5 min. [from 6.76(6.32-7.27) to 5.50(4.70-6.21), P＜0.05], and recovered after 15 min. htBeta [from 5.10(4.76-5.76) to 3.96(3.35-4.79), P＜0.05], and taBeta [from 14.41(10.80-16.33) to 10.72 (9.19-13.01), P＜0.05] also decreased significantly. In arteriosclerotic patients, CAVI decreased after 5 min. [from 10.47(9.67-11.29) to 9.71(8.74-10.57), P＜0.05] and recovered after 15 min. htBeta did not significantly change [from 12.00(11.46-13.21) to 11.81(10.14-13.83), ns], but taBeta decreased significantly [from 18.55(12.93-23.42) to 12.37(9.68-16.99), P＜0.05]. CONCLUSION: These results indicate that a nitroglycerin-induced decrease of arterial stiffness is more prominent in muscular arteries than in elastic arteries, and this effect was preserved much more prominently in arteriosclerotic patients than in healthy people.

Paclitaxel-coated balloons and aneurysm formation in peripheral vessels.

We report two cases of early aneurysmal vessel dilatation after a paclitaxel-coated balloon (PCB) was used for angioplasty of the peripheral vessels. The first case refers to a failing vein bypass with a tight proximal anastomotic stenosis, whereas the second refers to a distal tibial artery occlusion. A PCB was used to treat both patients. Aneurysmal dilatation of the previously treated segment was noted in both patients during subsequent follow-up imaging. In the absence of other causal factors, we attribute both cases to PCB application. The aneurysms that formed had no detrimental effect on the patients' health and required no further treatment; however, it is important to bear in mind this potential risk of presumed paclitaxel toxicity.

Measurement of tibial endothelial cell function after cigarette smoking, cessation of smoking and hyperbaric oxygen therapy.

SUMMARY: Cigarette smoking is hazardous to a range of human tissues. For instance, cigarette smoke inhalation has been proven to delay bone healing. This study analysed the effects of cigarette smoking on tibial vascular endothelium and blood flow using the bone-chamber model. The effects of smoking cessation and hyperbaric oxygen (HBO) on the damage caused by smoking were also compared. 54 adult New Zealand rabbits were divided into three groups. Group 1: control, Group 2: 1 week smoking, and Group 3: 6 weeks' smoking. This study on rabbits confirmed that both short-term and long-term cigarette smoking is dangerous to the bony vascular endothelium of the tibia. The vasodilatation caused by nitric oxide production was significantly attenuated in Group 2 and 3's tibia. Long-term smoking damaged the vascular endothelium more severely than short-term smoking (P<.01). Cessation of smoking effectively reduces the adverse effects of smoking when the cessation time equals the smoking time. HBO also effectively reduces the adverse effects of smoking.

Hypoxia attenuates insulin-induced proliferation and migration of human diabetic infrapopliteal vascular smooth muscle cells.

The proliferative effects of insulin on infrapopliteal vascular smooth muscle cells (VSMCs) have been established. We examined the effect of hypoxia in the presence and absence of insulin on the proliferation and migration of human diabetic infrapopliteal VSMCs in vitro. VSMCs isolated from the infrapopliteal arteries of male diabetic patients of identical disease and clinical patterns undergoing below-knee amputation were harvested and grown to subconfluence. Cells were then exposed to control medium (M199/1% fetal bovine serum/2% antibiotic-antimycotic) or control medium with 100 ng/mL insulin in oxygen concentrations of 17% (normoxia), 5%, and 1%. Cellular proliferation was assayed using [methyl-3H]-thymidine incorporation. Migration assays were performed using the Corning Costar Transwell system. Lactate dehydrogenase was assayed and compared among groups as a marker for cytotoxicity. VSMCs in normoxic conditions (17%) had a significant increase in both proliferation (100 +/- 6.5% vs. 124 +/- 4.7%, p = 0.007) and migration [73.2 +/- 9.3 vs. 118.1 +/- 14.9 cells/4 high-power fields (HPF), p = 0.03] when exposed to insulin. Of cells exposed to insulin, those at both 5% (75.9 +/- 7.9%, p = 0.0001) and 1% (73.6 +/- 4%, p < 0.0001) hypoxia proliferated at a significantly decreased rate compared with cells at normoxia (124 +/- 4.7%). Migration of these insulin-exposed cells was significantly decreased at 1% hypoxia (63.1 +/- 9.0 cells/4HPF) compared to those at normoxia (118.1 +/- 14.9 cells/4HPF, p = 0.006) and 5% hypoxia (101.2 +/- 10.0 cells/4HPF, p = 0.01). There were no significant differences in migration between cells at normoxia and 5% hypoxia. Finally, hypoxia and insulin exerted no significant effect on cytotoxicity. The proliferative and promigratory effects of insulin on diabetic VSMCs are attenuated in hypoxic conditions in a manner unrelated to cytotoxicity.

Multicenter randomized prospective trial comparing a pre-cuffed polytetrafluoroethylene graft to a vein cuffed polytetrafluoroethylene graft for infragenicular arterial bypass.

Poor patency of synthetic grafts for infragenicular revascularization has led to use of distal vein patches or cuffs. The aim of this study was to compare the distally widened Distaflo PTFE graft, which mimics a vein cuff, with a PTFE graft with distal vein modification. In this prospective, randomized, multicenter trial we compared use of a precuffed PTFE graft wit that of PTFE grafts with distal vein modification for infragenicular revascularization in patients with critical limb ischemia without saphenous vein. Study end points were primary and secondary patency and limb salvage rates at 2 years. From January 28,1999 to November 1, 2000, 104 patients were enrolled in 10 North American centers. Thirteen were excluded for protocol violation. Ninety-one bypasses were performed in 89 patients with a mean age of 73 years (range 47-90). By randomization, 47 bypasses were done with the precuffed graft and 44 with PTFE graft with vein cuff. Both groups were comparable for comorbidities and operative variables, except for a higher incidence of acute ischemia in the precuffed group (19% vs. 4.5%, p = 0.03). Bypass was a redo procedure in 53% and was performed at the infrapopliteal vessels in 79%. Operative mortality was 2.2% (2/91). Mean follow-up was 14 months (range 1-30). At 1 and 2 years, primary patency was 52% and 49% for the precuffed group and 62% and 44% for the vein cuffed group, respectively (p = 0.53). At 1 year and 2 years, the limb salvage rate was 72% and 65% for the precuffed group and 75% and 62% in the vein cuffed group (p = 0.88). Although numbers are small and follow-up short, this midterm analysis shows similar results for the Distaflo precuffed grafts and PTFE grafts with vein cuff. A precuffed graft is a reasonable alternative conduit for infragenicular reconstruction in the absence of saphenous vein and provides favorable limb salvage.

Statin therapy is associated with improved patency of autogenous infrainguinal bypass grafts.

OBJECTIVE: HMG-CoA reductase inhibitors (statins) broadly reduce cardiovascular events, effects that are only partly related to cholesterol lowering. Recent studies suggest important anti-inflammatory and antiproliferative properties of these drugs. The purpose of this study was to determine the influence of statin therapy on graft patency after autogenous infrainguinal arterial reconstructions. METHODS: A retrospective analysis of consecutive patients (1999-2001) who underwent primary autogenous infrainguinal reconstructions with a single segment of greater saphenous vein was performed. Patients were categorized according to concurrent use of a statin. Graft lesions (identified by duplex surveillance) and interventions were tabulated. Comparisons between groups were made by using the Fisher exact test for categorical variables and the Student t test for continuous variables. Patency, limb salvage, and survival were compared by log rank test. A stepwise Cox proportional hazards analysis was then employed to ascertain the relative importance of factors influencing graft patency. RESULTS: A total of 172 patients underwent 189 primary autogenous infrainguinal arterial reconstructions (94 statin, 95 control) during the study period. The groups were well matched for age, indication, and atherosclerotic risk factors. Procedures were performed primarily for limb salvage (92%), with 65% to an infrapopliteal target. Perioperative mortality (2.6%) and major morbidity (3.2%) were not different between groups. There was no difference in primary patency (74% +/- 5% vs 69% +/- 6%; P =.25), limb salvage (92% +/- 3% vs 90% +/- 4%; P =.37), or survival (69% +/- 5% vs 63% +/- 5%; P =.20) at 2 years. However, patients on statins had higher primary-revised (94% +/- 2% vs 83% +/- 5%; P <.02) and secondary (97% +/- 2% vs 87% +/- 4%; P <.02) graft patency rates at 2 years. Of all factors studied by univariate analysis, only statin use was associated with improved secondary patency (P =.03) at 2 years. This was confirmed by multivariate analysis. The risk of graft failure was 3.2-fold higher (95% confidence interval, 1.04-10.04) for the control group. Perioperative cholesterol levels (available in 47% of patients) were not statistically different between groups. CONCLUSIONS: Statin therapy is associated with improved graft patency after infrainguinal bypass grafting with saphenous vein.

Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations.

INTRODUCTION: Diabetes mellitus is a significant risk factor for atherosclerotic peripheral vascular disease. Hyperglycemia and hyperinsulinemia, as encountered in patients with type II diabetes, have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation, a paramount feature in atherosclerosis. Female sex hormones, such as estrogen, have been suggested to inhibit VSMC proliferation. However, the role of progesterone, particularly in patients with diabetes mellitus, has not been examined. Therefore, we studied the effect of progesterone on VSMCs exposed to various concentrations of glucose and insulin. METHODS: Human infragenicular VSMCs isolated from the tibial arteries of five male patients with diabetes undergoing lower extremity amputation were used. Immunocytochemical studies with confocal microscopy were performed for progesterone receptor identification in these VSMCs. Cells were grown to subconfluence, followed by exposure to deprived media with various glucose (100 and 200 mg/dL) and insulin (no insulin and 100 ng/mL) concentrations. Cells were then additionally exposed to physiologic progesterone (10 ng/mL, progesterone group) and compared with a no-progesterone group. Cell count and methyl-(3)H-thymidine incorporation were used to determine cellular proliferation. Cell count with hemocytometry was performed on day 6. DNA synthesis as reflected through methyl-(3)H-thymidine incorporation was measured at 24 hours. RESULTS: Immunocytochemical studies with confocal microscopy showed cytosolic progesterone receptors. The no-progesterone group showed a significant rise in cell count (P <.05) at all concentrations of glucose or insulin compared with the control group containing 100 mg/dL glucose concentration. The no-progesterone group also showed a significant rise in thymidine incorporation (P <.05) in the 100 mg/dL glucose-100 ng/mL insulin group and the 200 mg/dL glucose-100 ng/mL insulin group compared with the 100 mg/dL glucose group. In the cell count studies, progesterone significantly inhibited cellular proliferation in several settings. All cell groups cultured with insulin or an elevated glucose concentration showed a significant (P <.05) antiproliferative effect when exposed to progesterone. With thymidine incorporation, progesterone showed a similar antiproliferative effect in cells stimulated with glucose or insulin. CONCLUSION: Significant reductions in cell proliferation as determined with both cell count and thymidine incorporation suggest that progesterone is an inhibitor of VSMC proliferation induced by our in vitro models of hyperglycemia and hyperinsulinemia. Therefore, progesterone may have a protective role against the atherosclerotic changes associated with type II diabetes.

Vascular dysfunction after repair of coarctation of the aorta: impact of early surgery.

BACKGROUND: Patients with repaired coarctation are at increased risk of hypertension and cardiovascular disease despite successful repair. We studied the function of conduit arteries in upper and lower limbs of patients late after successful coarctation repair and its relation to age at surgery. METHODS AND RESULTS: Flow-mediated dilatation (FMD) and the dilatation after sublingual nitroglycerin (NTG, 25 microgram) were measured by using high-resolution ultrasound in the brachial artery in 64 coarctation patients (44 males and 20 females, aged 19+/-10 years; median age at operation 4 months) and 45 control subjects (28 males and 17 females, aged 19+/-10 years) and in the posterior tibial artery in 37 patients and 22 control subjects. Arterial stiffness was determined by pulse-wave velocity (PWV) of the brachioradial and femoral-dorsalis pedis tracts. Patients, compared with control subjects, had lower brachial FMD (7.16+/-3.4% versus 8.62+/-2.3%, respectively; P=0.02) and NTG (11.46+/-4.3% versus 13.21+/-4.6%, respectively; P=0.046) and higher brachioradial PWV (9.17+/-3.1 versus 8.06+/-1.9 m/s, respectively; P=0.05). In contrast, posterior tibial FMD, NTG, and lower limb PWV were comparable. Age (months) at the time of repair was related to brachioradial PWV (r=0.42, P=0.002) but not to brachial FMD or NTG. CONCLUSIONS: Patients with repaired aortic coarctation have impaired conduit artery function, with abnormal responses to flow and NTG, and increased vascular stiffness confined to the upper part of the body. Early repair is associated with preserved elastic properties of conduit arteries, but reduced reactivity remains.

Phenotypic characterization of human smooth muscle cells derived from atherosclerotic tibial and peroneal arteries.

PURPOSE: The vascular smooth muscle cell plays a pivotal role in the development of atherosclerosis. The objectives of this study were to characterize smooth muscle cells from the human atherosclerotic tibial artery to determine their phenotypic properties and to examine the contractile reactions of these cells to physiologic and pharmacologic stimuli. METHODS: After below-knee amputations were performed, vascular smooth muscle cells were harvested and cultivated from tibioperoneal source. Characterization was done with transmission electron microscopy and immunocytochemistry. The contractile properties were determined by observing the response to various stimuli. In addition, segments of vessels harvested were submitted to electron microscopy studies for comparison with the cultured cells. RESULTS: Immunofluorescent labeling was positive for alpha-smooth muscle actin. Electron microscopy revealed the presence of a thickened basal laminae and large intracellular lipid vacuoles. The earlier passages revealed cells with a large number of microfilaments characteristic of a contractile cell. As later passages were examined, there was a notable change in character with an increasing amount of rough endoplasmic reticulum and Golgi complexes. The increased thickness of the basal lamina in the cultured cells resembled that found in vessel segments studied by electron microscopy. A rapid contraction response was seen when the cells were incubated with angiotensin II, bradykinin, or endothelin. No response was seen with the addition of isoproterenol, nitroglycerin, or nitroprusside, known smooth-muscle relaxants. CONCLUSION: This model demonstrates the apparent inability of these smooth muscle cells from atherosclerotic tibial arteries to relax to pharmacologic and physiologic stimuli. In addition, as seen by transmission electron microscopy, these cells maintain their atherosclerotic phenotype after multiple passages.