Impaired endothelial function in isolated human uremic resistance arteries

BACKGROUND: Patients with chronic renal failure (CRF) face a markedly increased risk of cardiovascular death. CRF is frequently complicated by hypertension and changes in both the heart (left ventricular hypertrophy) and the vasculature (endothelial dysfunction and accelerated atherosclerosis). The mechanisms underlying changes in vascular function and specifically endothelial dysfunction are unclear. This present study therefore examined subcutaneous resistance artery function in vitro, comparing adult uremic patients and controls using wire myography. METHODS: Subcutaneous fat biopsies were obtained from 12 patients with CRF (median serum creatinine 735 micromol/L) at the time of renal transplantation or peritoneal dialysis catheter insertion, and from eight controls without renal disease at the time of abdominal surgery. Resistance arteries were mounted on a wire myograph. Their contractile ability was tested with high potassium depolarization, and endothelial integrity was tested by relaxation to acetylcholine. Cumulative concentration-response curves were then constructed for norepinephrine, endothelin-1, acetylcholine, and sodium nitroprusside (SNP). RESULTS: Following preconstriction with norepinephrine, vessels from uremic patients vasodilated less well to acetylcholine compared with vessels from controls [maximum % relaxation 77% (range 41, 97) vs. 98% (78, 100), P < 0.001]. The vasodilation to SNP was similar [95% (63, 100) vs. 94% (71, 100), P = 0.751]. There was a trend toward increased maximum pressure (kPa) achieved with both norepinephrine and endothelin-1 in vessels from uremic patients, and the contractions to both of these agents were more prolonged in the uremic vessels. CONCLUSIONS: The pattern of normal vasodilation to SNP but reduced vasodilation to acetylcholine is consistent with endothelial dysfunction due to impaired nitric oxide (NO) production in uremic vessels. Similar results have been demonstrated in vivo in uremia, one suggested mechanism being accumulation of endogenous inhibitors of NO synthase such as asymmetric dimethylarginine (ADMA). This in vitro study suggests that a short-lived circulating factor is not entirely responsible and that there may be an inherent abnormality in endothelial function in uremia, although the exact pathophysiology remains unclear. Endothelial dysfunction may predispose the patient to accelerated atherosclerosis and may be involved in the pathogenesis of hypertension in end-stage renal failure.     

Flow waveform assessment of polytetrafluoroethylene grafts for reconstruction of lower extremity arteries. A preliminary report

On the basis of our findings that the outcome of reconstructive surgery for lower limbs could well be predicted by flow waveform analysis, we reviewed femoropopliteal arterial bypass operations involving the use of polytetrafluoroethylene (PTFE) grafts for 35 patients. Of 38 grafts, 26 were PTFE alone, and 12 were PTFE/vein composite grafts. Neither ankle pressure index nor angiographic distal runoff was of predictive value as a prognostic indicator. The cumulative patency rate, calculated by the life-table method, revealed the usefulness of flow waveform analysis for prediction of the outcome of PTFE grafts. In type 0 or I flow, the patency rate was 94% at 1 and 2 years and 79% at 3 years. In contrast, in type II flow, the patency rate was 74% at 1 year, 66% at 2 years, and 49% at 3 years, with a statistical significance at 2 and 3 years (p less than 0.05). Comparison of the result of PTFE grafts with that of PTFE/vein composite grafts showed superior results of composite grafts at 3 years after implantation (42% vs. 83%, p less than 0.05). These findings indicate that flow waveform analysis is useful for prediction of the outcome of PTFE grafts and that PTFE/vein composite grafts should probably be used, particularly in cases of abnormal blood flow.     

Noninvasive assessment of lower extremity arterial disease

Although angiography is the accepted "gold standard" for demonstrating the presence of arterial occlusive disease, it is less accurate for grading the associated hemodynamic consequences and is prohibitively invasive and expensive to be used as a first-line investigation. Currently available noninvasive tests allow not only for the detection of perfusion abnormalities, but for an appreciation of their severity as well as their likely location. This information is invaluable for predicting the need for revascularization, guiding the choice of reconstructive procedure, and predicting the likelihood of healing of amputation wounds and ischemic lesions. Although some obstructive lesions are easily detected, others require more in-depth testing to reveal and quantify. Consequently, a thorough understanding of available noninvasive diagnostic modalities, including both their capabilities as well as their pitfalls, is paramount to the effective practice of vascular surgery.     

Physiologic variations in lower extremity venous valvular function

We conducted this study to investigate the physiologic variations in venous valvular function and calf muscle pump function that occur in normal limbs after prolonged stationary standing. Twenty-two limbs from 11 healthy volunteers were studied after a brief period of activity and after 4 to 6 hours of stationary standing. Vein diameter, peak reflux flow velocity (PRFV), and valve closure time (VCT) were measured with duplex scanning in the standing position in the common femoral vein (CFV), superficial femoral vein (SFV), popliteal vein (POP), proximal greater saphenous vein (GSV), and greater saphenous vein at the knee (kGSV). Pneumatic rapid inflation-deflation cuffs were used to elicit reflux. Vein cross-sectional area (VA) and peak reflux volume (PRVol) were calculated. Venous volume (W), venous filling index (VFI), ejection fraction (EF), residual volume fraction (RVF), and outflow fraction (OF) were measured with air plethysmography in all limbs. After stationary standing, there was no significant change or trend toward an increase in diameter or VA in any of the deep veins and there was no change in the PRFV or VCT. In the proximal GSV there was a significant increase in diameter (p=0.0001)and VCT (p=0.048)without a change in PRFV. No significant changes were noted in the kGSV. In the GSV the PRFV was significantly lower (p <0.05) and the VCT significantly shorter (p <0.05)compared with the SFV and POP but values were no different from those in the CFV. The PRFV was significantly higher in the SFV (p < 0.0001)and the POP (p <0.002)compared with that in the CFV. The VCT was significantly shorter in the CFV (p <0.004)and the POP (p <0.01)compared with the SFV. VCTs in the greater saphenous and deep veins remained <333 msec in 97.5% of all measurements. No significant change in W, VFI, EF, or OF occurred after prolonged standing. Prolonged standing does not produce a significant dilatation or deterioration in valvular function in the large veins of the deep system but does produce a significant dilatation and delayed valve closure in the proximal GSV. VCT in normal lower extremity veins rarely exceeds 1/3 second. Prolonged standing does not produce significant changes in valvular competence or calf muscle pump function in the lower extremities of normal persons as assessed by air plethysmography.Supported in part by grants from The Research Council of The University of North Carolina at Chapel Hill and by a Junior Faculty Development Award from The University of North Carolina at Chapel Hill.Presented at the Nineteenth Annual Meeting of the Peripheral Vascular Surgery Society, Seattle, Wash., June 5, 1994.     

Syndrome of diabetic foot and atherosclerosis of the lower extremity arteries

Obstructive damages of the peripheral arteries in diabetes mellitus patients are known to occur 4 times more often than in patients not having diabetes. For the recent 10 years 390 patients with serious decompensated diabetes mellitus and diabetic foot have been examined and treated. The atherosclerotic process in the low extremity arteries in diabetes mellitus patients was found to be more distally located, symmetrical and the ischemia signs were quickly progressing and badly answered to treatment. As a rule, sympathectomy and restoring operations were ineffective, often followed by necrotic alterations of the foot skin and gangrene. Our data have shown that even young patients with the main type of blood flow having the diabetic foot syndrome have certain signs of atherosclerotic affection of the low extremity arteries. It must be taken into consideration in their treatment.     

介入性再通术治疗下肢动脉平齐闭塞病变

目的探讨介入性再通术治疗下肢动脉平齐闭塞病变的方法和疗效。方法17例经CT血管造影（CTA）或MR血管造影（MRA）诊断的下肢主要动脉起始部平齐闭塞患者,病变分别位于髂总动脉（4例）、髂外动脉（2例）、股浅动脉（8例）、胫后或胫前动脉（3例）,临床表现为静息痛等下肢严重缺血症状。经同侧、对侧股动脉或右肱动脉等途径,主要使用内膜下血管成形方法对平齐闭塞端血管进行顺行开通治疗。结果17例患者中,12例成功使导丝和导管经平齐闭塞端进入并通过闭塞端,完成再通治疗,其中11例（11/12）使用了内膜下血管成形技术,在髂、股动脉共植入支架19枚;1例髂总动脉、2例股浅动脉和2例胫（胫前、胫后）动脉平齐闭塞病变因无法使导管导丝嵌入闭塞起始部而终止再通操作,再通成功率为70.59%（12/17）。未发生与介入操作相关的并发症。再通术后临床症状明显改善或消失,踝臂指数（ABI）平均值从0.47上升至0.71。6个月近期随访无症状复发,8、12和24个月各有1例患者症状加重,其中1例复查CAT显示支架内完全闭塞。结论使用内膜下血管成形术对下肢动脉平齐闭塞病变进行再通治疗可以获得安全而良好的临床疗效,拓展了介入治疗对于复杂、严重下肢缺血病变的适用范围。     

Quantitative assessment of outflow resistance in lower extremity arterial reconstructions

Graft patency is thought to correlate with resistance in the runoff bed or outflow resistance. However, accurate measurement of this parameter has been difficult. A simple and reproducible method for direct measurement of outflow resistance following completion of the distal anastomosis of a bypass graft has been developed. This method employs injection of a fixed amount of normal saline through the proximal end of the graft and measurement of the resulting integrated pressure increment by an analog computer. Division of this pressure integral by the volume injected is a measure of the outflow resistance expressed in resistance units (mm Hg/ml/min). The median outflow resistance in 31 femoropopliteal bypasses was 0.29 units with a range of 0.08-1.38 units. The median outflow resistance in 33 femorodistal bypasses was 0.7 units with a range of 0.18-2.34 units. All bypasses with an outflow resistance of 1.1 units or less remained patent for 3 months. There were 51 grafts in this group (30 femoropopliteal; 21 femorodistal) and their outflow resistance ranged from 0.08 to 1.1 units. All bypasses with an outflow resistance of 1.2 units or higher thrombosed within the first postoperative month. There were 13 grafts in this group (1 femoropopliteal; 12 femorodistal) and their outflow resistance ranged from 1.2 to 2.38 units. Eight of the 13 grafts that failed originally were subjected to thrombectomy, which was uniformly unsuccessful. Although this method does not yet allow bypass surgery to be denied to any patient, it does define a group of patients in whom thrombectomy will not be effective and should not be attempted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Partial denervation in complex treatment of occlusive diseases of the lower extremity arteries

The interventions efficacy, conducted on a nervous structures in 198 patients for occlusive diseases of the lower extremities arteries, in 68 of whom a femoral and sciatic nerves blockade were performed together with epidural anesthesia and open alcoholizing of sciatic nerve, was estimated. Efficacy of partial denervation in complex treatment of patients, suffering chronic ischemia of the lower extremities stages II - IlIA, was established, when performance of a direct revascularization is impossible because of a secured functional reserve present.     

A review of methods currently used for assessment of in vivo endothelial function.

An intact vascular endothelium is critical to the maintenance of normal arterial tone and coagulation status. Endothelial injury leading to dysfunction is thought to be a precursor to most if not all vascular disease, and has been implicated as a critical event in atherosclerosis. At present there are several methods available for detection of in vivo endothelial function, and the aim of this study was to critically review these methods. Five distinct methods were identified and studied in detail. These methods are diverse and each assesses a different vascular bed. Importantly there is no uniformity among investigators over choice of method and protocol, making it difficult to compare in vivo enothelial dysfunction between groups. These issues need to be addressed in large scale comparative analyses so that investigators can agree a common approach to endothelial function assessment.     

Noninvasive methods of the examination in surgery of obliterating atherosclerosis of lower extremity arteries

The purpose of the study was to determine surgical policy in atherosclerotic lesions of aorta and lower extremities arteries on the basis on non-invasive diagnostic methods--duplex scanning (DS) and computer tomographic angiography (CTA). From 1998 to 1999 47 patients were examined on this program (DS + CTA). At the first stage of the study, 17 patients underwent translumbal aorto-arteriography at the same time with DS and CTA. Analysis of the angiograms revealed that sensitivity of angiography for detection of lesions in aorto-iliac segment was 94%, in femoro-popliteal segment--78%. Diagnostic mistakes were associated with partial thrombosis of aneurysm's lumen, as a result of which the aorta looked non-dilated in angiograms. Femoral arteries contrasted unsatisfactory in 4 patients because of low collateral blood velocity distal to occlusion of iliac arteries. Initial segments of deep and superficial femoral arteries closed each other in angiograms on anterior-posterior projection, and it also led to low potential of angiography in assessment of femoral arteries state. Complex of non-invasive diagnostic methods (DS + CTA) allowed to correct diagnosis in each case. The methods complemented one another: CTA permitted to make three-dimensional reconstruction of vascular tree and to study its on various projections; DS--to study the vascular wall's state and hemodynamical parameters of blood flow. At the second stage of the study, high sensitivity of DS and CTA allowed to reject traditional angiography in preoperative period. Intraoperative findings confirmed the provisional diagnosis completely.     

Amputation. Preoperative assessment and lower extremity surgical techniques

Amputation surgery is an important part of the treatment for severe limb disorders. The decision-making process must be done thoughtfully, remembering that blood flow is not the only issue. Many factors enter into the decision to perform a partial foot amputation or to perform a more proximal level amputation. Adherence to good surgical principles, proven techniques, and gentle soft tissue handling can make the difference between a successful and durable amputation or continued complications and frustrations.     

Immediate and late outcomes of endovascular therapy for lower extremity arteries in Buerger disease

Objective

Buerger disease is a rare inflammatory vasculopathy presenting with severe claudication or critical limb ischemia. In this study, we sought to evaluate the feasibility and clinical outcomes of endovascular therapy for Buerger disease involving arteries in the lower extremities.

Improved assessment of lower extremity alignment using new roentgenographic techniques

Accurate assessment of total hip and knee alignment requires a single-exposure weight-bearing roentgenogram of the involved limb. The problem with single-exposure technique is that a good exposure of the hip overexposes the lower leg. This problem is solved by using leaded acrylic wedges, which, when placed in front of the X-ray tube (collimator), block excessive radiation to the lower limb and create an evenly exposed film of the entire lower extremity. The development of these collimator wedge filters and the advent of newer fast-speed film and screens have reduced the amount of radiation absorbed by the patient by eight times or more. Guided by a chart to interchange and choose between film/screen combinations, the method and technique provides the surgeon with an exact alignment of the limb and joints for all kinds of operations.