A functional model of microvascular thrombosis

A new model of microvascular thrombosis is presented, with the evaluation of single-dose heparin in the prevention of microvascular thrombosis. The technique, which involves arterial crushing and an arteriotomy with intimal abrasion, was performed on the superficial femoral artery of the rat. The model was applied to a series of 30 consecutive rat superficial femoral arteries. A 100 percent thrombosis rate was seen immediately and at 24 hours in 10 nonheparinized animals. An operator control group of 10 vessels without intimal abrasion had a patency rate of 100 percent immediately and at 24 hours. Ten vessels following single-dose heparin and intimal abrasion were all patent initially, with 7 remaining patent at 24 hours. Reproducibility of the model was documented by a second operator with similar results. Utilizing this model, single-dose heparin was effective in maintaining vessel patency.     

Operations on large arteries; application of recent advances

With the use of anticoagulants to prevent recurrence of thrombosis it is now possible to open a major artery which has been occluded by a thrombus, remove the thickened lining with the clot and restore the continuity of the vessel. Free vein grafts have been used successfully to replace arterial segments in the extremities. Vein inlay grafts are preferred in dealing with aneurysms of the abdominal aorta. The aneurysmal wall can be used to support the venous segments. It has been possible to by-pass aneurysms of the abdominal aorta by anastomosing the splenic artery to the left iliac artery. The use of the left superficial femoral artery as a by-pass to supply blood to the right leg is described.     

OPERATIONS ON LARGE ARTERIES—Application of Recent Advances

With the use of anticoagulants to prevent recurrence of thrombosis it is now possible to open a major artery which has been occluded by a thrombus, remove the thickened lining with the clot and restore the continuity of the vessel. Free vein grafts have been used successfully to replace arterial segments in the extremities. Vein inlay grafts are preferred in dealing with aneurysms of the abdominal aorta. The aneurysmal wall can be used to support the venous segments.It has been possible to by-pass aneurysms of the abdominal aorta by anastomosing the splenic artery to the left iliac artery. The use of the left superficial femoral artery as a by-pass to supply blood to the right leg is described.     

EVERSION ENDARTERECTOMY: A NEW APPLICATION OF AN OLD TECHNIQUE

Restoration of arterial flow to a severely ischemic extremity remains a major challenge in vascular surgery. The procedure of choice for limb salvage is a bypass utilizing reversed saphenous vein. When the saphenous vein is unsuitable or unavailable, the surgeon must turn to endarterectomy of the femoral and popliteal systems or synthetic, composite, heterologous, autologous, or homologous grafts. To avoid the problems associated with these techniques and to improve the results of limb salvage, we have revived and modified the technique of superficial femoral artery eversion endarterectomy and combined it with other reconstructive techniques in an effort to salvage the severely ischemic lower extremity. Of 38 patients treated for incapacitating claudication or severe limb ischemia during a one-year period, six patients had an unsuitable saphenous vein for the proposed reconstruction. Five of these patients underwent superficial femoral eversion endarterectomy. These six patients have 100% patency at follow-up seven months to one year postoperatively. Our experience with these six patients, including angiographic follow-up, will be presented.     

Heterogeneity in conduit artery function in humans: impact of arterial size

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men (n = 20; 31 +/- 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response (r = -0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial (r = -0.66, P = 0.001), brachial (r = -0.55, P = 0.01), and popliteal artery (r = -0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size (r = -0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size (r = -0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.     

Effects of posture on shear rates in human brachial and superficial femoral arteries

Shear rate is significantly lower in the superficial femoral compared with the brachial artery in the supine posture. The relative shear rates in these arteries of subjects in the upright posture (seated and/or standing) are unknown. The purpose of this investigation was to test the hypothesis that upright posture (seated and/or standing) would produce greater shear rates in the superficial femoral compared with the brachial artery. To test this hypothesis, Doppler ultrasound was used to measure mean blood velocity (MBV) and diameter in the brachial and superficial femoral arteries of 21 healthy subjects after being in the supine, seated, and standing postures for 10 min. MBV was significantly higher in the brachial compared with the superficial femoral artery during upright postures. Superficial femoral artery diameter was significantly larger than brachial artery diameter. However, posture had no significant effect on either brachial or superficial femoral artery diameter. The calculated shear rate was significantly greater in the brachial (73 +/- 5, 91 +/- 11, and 97 +/- 13 s(-1)) compared with the superficial femoral (53 +/- 4, 39 +/- 77, and 44 +/- 5 s(-1)) artery in the supine, seated, and standing postures, respectively. Contrary to our hypothesis, our current findings indicate that mean shear rate is lower in the superficial femoral compared with the brachial artery in the supine, seated, and standing postures. These findings of lower shear rates in the superficial femoral artery may be one mechanism for the higher propensity for atherosclerosis in the arteries of the leg than of the arm.     

Relationship between upper and lower limb conduit artery vasodilator function in humans

Brachial artery flow-mediated dilation (FMD) is a strong predictor of future cardiovascular disease and is believed to represent a "barometer" of systemic endothelial health. Although a recent study [Padilla et al. Exp Biol Med (Maywood) 235: 1287-1291, 2010] in pigs confirmed a strong correlation between brachial and femoral artery endothelial function, it is unclear to what extent brachial artery FMD represents a systemic index of endothelial function in humans. We conducted a retrospective analysis of data from our laboratory to evaluate relationships between the upper (i.e., brachial artery) vs. lower limb (superficial femoral n = 75; popliteal artery n = 32) endothelium-dependent FMD and endothelium-independent glyceryl trinitrate (GTN)-mediated dilation in young, healthy individuals. We also examined the relationship between FMD assessed in both brachial arteries (n = 42). There was no correlation between brachial and superficial femoral artery FMD (r(2) = 0.008; P = 0.46) or between brachial and popliteal artery FMD (r(2) = 0.003; P = 0.78). However, a correlation was observed in FMD between both brachial arteries (r(2) = 0.34; P < 0.001). Brachial and superficial femoral artery GTN were modestly correlated (r(2) = 0.13; P = 0.007), but brachial and popliteal artery GTN responses were not (r(2) = 0.08; P = 0.11). Collectively, these data indicate that conduit artery vasodilator function in the upper limbs (of healthy humans) is not predictive of that in the lower limbs, whereas measurement of FMD in one arm appears to be predictive of FMD in the other. These data do not support the hypothesis that brachial artery FMD in healthy humans represents a systemic index of endothelial function.     

The erect posture as an aid to the circulation in the feet in the presence of arterial obstruction

When the main artery in the lower limb is occluded and narrow collateral vessels by-passing the obstruction offer the limiting resistance to blood flow, the increase in arterial pressure at the ankle on assuming the erect posture is greater than would be predicted by consideration of the hydrostatic factors. In seven patients with femoral artery occlusion the pressure at the ankle was greater than expected in all and on the average by 8.0 mm. Hg±1.5 S.E. when sitting, (P<0.01) and in the four patients tested, by 12.4 mm. Hg±0.5 S.E. when standing (P<0.01). Rate of blood flow in subdermal tissue of the forefoot estimated by xenon-133 clearance was an average of 21% less when sitting than when supine in five limbs of four normal subjects while in five limbs with occlusion or severe stenosis of the superficial femoral artery the rate of flow was an average of 44% greater.     

Effect of Ilizarov tibial lengthening on limb blood flow

The experiment in 23 adult dogs was based on the study of volumetric blood flow velocity in the superficial femoral artery and femoral vein, pulse changes in blood filling of the m. gastrocnemius in the conditions of tibial lengthening to 17.5-23% from the initial length. Complex changes in the blood flow parameters were revealed after surgical intervention and within 7 distraction days. When the distraction ended, the volumetric blood flow velocity in the femoral artery was reduced by 19% and the blood flow out of the vessel was improved by 17%. When fixation was over, the volumetric blood flow velocity in the vessel increased by 37% and the improved outflow preserved. At each experimental stage, there was an increased volumetric blood flow velocity in the femoral vein as compared to its value in the control group, its correspondence to the superficial femoral artery as well as similar dynamics in blood flow changes in the femoral vessels and m. gastrocnemius. The findings show that the vascular system of bone regeneration provides accelerated arterial blood transportation into the venous system during organotypical bone area formation.     

Two new cutaneous free flaps: the medial and lateral thigh flaps

Two new cutaneous free-flap donor areas are described on the medial and lateral sides of the thigh. The medial thigh flap is supplied by an unnamed artery from the superficial femoral artery and is drained by the accompanying venae comitantes. Its nerve supply is from the medial femoral cutaneous nerve. The lateral thigh flap has its vascular pedicle from the third perforating artery of the profunda femoral artery and its accompanying vein. The lateral femoral cutaneous nerve provides sensation over the area. These flaps provide a large surface area of both skin and subcutaneous tissue without the usual bulk of subcutaneous fat and muscle. Their desirable features include long vascular pedicles with large vessel diameters and potential of being neurovascular flaps with specific sensory nerve supply and predictable anatomy. The principal disadvantage is that the donor site may leave a slight contour defect with primary closure or require grafting when a large flap is taken. We predict that these flaps will become important donor sites for reconstructive problems requiring resurfacing of cutaneous defects in various anatomic areas.     

Hemodynamic response to LBNP during the 14 month MIR spaceflight (94-95)

Lower body negative pressure (LBNP) was used during the Mir spaceflight in a study of orthostatic tolerance. Hemodynamic responses were measured including heart rate, blood pressure, cerebral artery blood flow, and lower limb vascular resistance. Results showed that femoral flow volume decreased, which may be due to hypovolemia and reduced cardiac output. Additional changes in femoral vascular response and cerebral to femoral blood flow are discussed.     

Changes in hemodynamics of tibial diaphysis in case of blood flow disorder in superficial femoral artery

Changes in tibial hemodynamics have been studied experimentally after applying a clamp (n=41) and resection of superficial femoral artery (n=22) in 63 adult dogs. It has been revealed with the help ofrheovasography that, in case of blood flow disorders in the superficial femoral artery, anastomoses with deep femoral artery branches contribute to maintenance of blood circulation in tibia, and in this connection the parameters of tibial blood flow may significantly differe from those of circulation in the leg soft tissues. Preservation of intraosseous pressure all along tibial diaphyseal cavity demonstrates a possibility of using its driving force to compensate for the circulatory insufficiency in the leg soft tissues and, moreover, in that part of the bone the environment of which in ischemia is involved.     

Effect of Externally Applied Pressure on Femoral Vein Blood Flow

The effect of incremental increases in external pressure, applied to the leg, on blood volume flow in the femoral vein was studied in dogs. Clinical investigation of external pressure increases was also carried out on nine patients undergoing surgery for varicose veins. An external pressure between 5 and 15 mm. Hg caused a sustained increase in mean femoral vein flow both in a control and in the compressed limb. Above 15 mm. Hg external pressure flow decreased in the compressed limb but was maintained at an increased level in the control limb.If external compression is to be used to prevent and treat deep vein thrombosis its application must be carefully controlled.     

Distally based vastus lateralis muscle flap for coverage of wounds about the knee

The blood supply to the vastus lateralis muscle has been evaluated by dye injection techniques in fresh cadaver dissections. The main dominant blood supply is the descending branch of the lateral femoral circumflex artery. Vascular contributions from distal perforators of the superficial femoral artery, the superior geniculate artery, fill the main vascular pedicle in a retrograde fashion. Latex staining is observed consistently in the proximal third of the muscle. Five patients are presented in whom the distally based vastus lateralis muscle flap was successfully used to cover defects above the knee. Superficial muscle necrosis is a complication of this operation but has not precluded its usefulness. It is anticipated that this flap will be useful in the armamentarium of reconstructive surgeons treating such problematic patients.     

Synergistic effect of angiopoietin-1 and vascular endothelial growth factor on neoangiogenesis in hypercholesterolemic rabbit model with acute hindlimb ischemia

Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are essential for vascular integrity and development. The purpose of the study was to test the hypothesis that Ang1 will promote angiogenic response to VEGF in the spontaneous Watanabe heritable hypercholesterolemic (WHHL) rabbit model of acute hindlimb ischemia. Immediately after the ligation of the external iliac artery and the excision of the common and superficial femoral artery in one female WHHL rabbit, 250 microg of phVEGF(165) (n = 8), 500 microg of pAng1* (n = 8), or 250 microg of phVEGF(165) plus 500 microg of pAng1* (n = 8) was injected intramuscularly into the ischemic hindlimb muscles. Gross appearance of ischemic limb, collateral vessel formation and limb perfusion were assessed 30 days after treatment. The incidence of ischemic limb necrosis was higher in the animals treated by phVEGF(165) or by pAng1* than in those treated by phVEGF(165) plus pAng1* (100%, 75% and 14.3%, respectively; P = 0.002). Animals in the combination therapy group had a significantly higher calf blood pressure ratio at day 30 (VEGF plus Ang1* = 0.84 +/- 0.06; VEGF = 0.54 +/- 0.01; Ang1* = 0.59 +/- 0.05; P < 0.01). A combination therapy of VEGF plus Ang*1 had a significantly higher (P < 0.01) angiographic score than either therapy alone. Capillary density (P < 0.05) and capillary/muscle fiber ratio (P < 0.01) of the combination therapy group were also significantly higher than that of either therapy alone. In conclusion, Ang1 can potentiate the angiogenic response to VEGF in the hyperlipidemic rabbit model of acute hindlimb ischemia. Intramuscular administration of cytokines on revascularization of the ischemic hindlimb model of hyperlipidemic rabbit is feasible.     

Whole bone marrow transplantation induces angiogenesis following acute ischemia

Several recent studies have shown that purified subsets of bone marrow (BM) cells can differentiate into endothelial, cardiac, and other cell types. During coronary artery bypass graft (CABG) surgery, sternal BM is routinely discarded. To determine if this BM can be used to induce angiogenesis and augment perfusion of the cardiac tissues after CABG, a simplified and more practical approach of using whole BM extract was tried to determine whether it would be adequate for the induction of BM-derived angiogenesis in experimental acute limb ischemia. BM was prepared from FVB/N-TgN(TIE2 lacZ)182 Sato (Tie2-lacZ) or B6.129S7-Gtrosa 26 (Rosa 26) mice that express beta-galactosidase (beta-gal) in endothelial cells and most adult tissues, respectively. Acute limb ischemia was induced in either C57BL6/J or FVB/N mice by double ligation of the left femoral artery just distal to the profunda femoral artery branch. Occlusion of the ligated artery was verified by angiography. The study group (n = 31) received an intramuscular injection of 50 micro l containing 1 x 10(6) BM cells, 5 mm proximal to the site of ligation. Experimental controls (n = 21) had an intramuscular injection of 50 micro l of saline. Angiogenesis in the mice was assessed by histological analysis. BM-derived beta-gal(+) cells were observed to aggregate in the vicinity of the ligated artery and not in the injected musculature BM-derived endothelial cells were incorporated within capillaries and small size blood vessels near the site of ligation. Generation of BM-derived blood vessels in experimental acute limb ischemia does not require purification of specific subset of cells. The elimination of cell purification will enhance the ease of using BM transplantation in generating blood vessels.     

Sympathetic nervous system contributes to the age-related impairment of flow-mediated dilation of the superficial femoral artery

The physiological aging process is associated with endothelial dysfunction, as assessed by flow-mediated dilation (FMD). Aging is also characterized by increased sympathetic tone. Therefore, the aim of the present study is to assess whether acute changes in sympathetic activity alter FMD in the leg. For this purpose, the FMD of the superficial femoral artery was determined in 10 healthy young (22 +/- 1 yr) and 8 healthy older (69 +/- 1 yr) men in three different conditions: 1) at baseline, 2) during reduction of sympathetic activity, and 3) during sympathetic stimulation. Reduction of sympathetic activity was achieved by performing a maximal cycling exercise, leading to postexercise attenuation of the sympathetic responsiveness in the exercised limb. A cold pressor test was used to increase sympathetic activity. Nitroglycerin (NTG) was used to assess endothelium-independent vasodilation in all three conditions. Our results showed that, in older men, the FMD and NTG responses were significantly lower compared with young men (P = 0.001 and P = 0.02, respectively). In older men, sympathetic activity significantly affected the FMD response [repeated-measures (RM) ANOVA: P = 0.01], with a negative correlation between the level of sympathetic activity and FMD (R = -0.41, P = 0.049). This was not the case for NTG responses (ANOVA; P = 0.48). FMD and NTG responses in young men did not differ among the three conditions (RM-ANOVA: P = 0.32 and P = 0.31, respectively). In conclusion, in older men, FMD of the femoral artery is impaired. Local attenuation of the sympathetic responsiveness partly restores the FMD in these subjects. In contrast, in young subjects, acute modulation of the sympathetic nervous system activity does not alter flow-mediated vasodilation in the leg.     

患肢加压溶栓治疗下肢深静脉血栓形成的临床疗效及护理效应

目的:探讨止血带结扎患肢,从足背浅静脉推注尿激酶治疗下肢深静脉血栓形成的临床疗效及护理效应。方法:对62例下肢深静脉血栓患者经患肢足背静脉穿刺,踝关节上用止血带阻断浅静脉后,推注中等剂量尿激酶.通过测量腿围和彩超结果来评价是否有效。并采用多种护理辅助手段辅助治疗。结果:临床症状迅速改善,有效率22.5%,显效率77.5%。结论:此方法操作简单,所用材料价格便宜,临床效果明显,值得推广应用。     

Vascular adaptation to 4 wk of deconditioning by unilateral lower limb suspension

Physical inactivity or deconditioning is an independent risk factor for atherosclerosis and cardiovascular disease. In contrast to exercise, the vascular changes that occur as a result of deconditioning have not been characterized. We used 4 wk of unilateral lower limb suspension (ULLS) to study arterial and venous adaptations to deconditioning. In contrast to previous studies, this model is not confounded by denervation or microgravity. Seven healthy subjects participated in the study. Arterial and venous characteristics of the legs were assessed by echo Doppler ultrasound and venous occlusion plethysmography. The diameter of the common and superficial femoral artery decreased by 12% after 4 wk of ULLS. Baseline calf blood flow, as measured by plethysmography, decreased from 2.1 +/- 0.2 to 1.6 +/- 0.2 ml.min(-1).dl tissue(-1). Both arterial diameter and calf blood flow returned to baseline values after 4 wk of recovery. There was no indication of a decrease in flow-mediated dilation of the superficial femoral artery after ULLS deconditioning. This means that functional adaptations to inactivity are not simply the inverse of adaptations to exercise. The venous pressure-volume curve is shifted downward after ULLS, without any effect on compliance. In conclusion, deconditioning by 4 wk of ULLS causes significant changes in both the arterial and the venous system.     

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. While these therapies lead to the rapid restoration of blood flow, these technologies remain limited by restenosis in the case of bare metal stents and angioplasty, or reduced healing and possibly enhanced risk of thrombosis in the case of drug eluting stents. A key pathophysiological mechanism in the formation of restenosis is intimal hyperplasia caused by the activation of vascular smooth muscle cells and inflammation due to arterial stretch and injury. Surgeries that induce arterial injury in genetically modified mice are useful for the mechanistic study of the vascular response to injury but are often technically challenging to perform in mouse models due to the their small size and lack of appropriate sized devices. We describe two approaches for a surgical technique that induces endothelial denudation and arterial stretch in the femoral artery of mice to produce robust neointimal hyperplasia. The first approach creates an arteriotomy in the muscular branch of the femoral artery to obtain vascular access. Following wire injury this arterial branch is ligated to close the arteriotomy. A second approach creates an arteriotomy in the main femoral artery that is later closed through localized cautery. This method allows for vascular access through a larger vessel and, consequently, provides a less technically demanding procedure that can be used in smaller mice. Following either method of arterial injury, a degradable drug delivery patch can be placed over or around the injured artery to deliver therapeutic agents.