PERIPHERAL ARTERIOSCLEROSIS—Present Concepts of Management

Three hundred patients with clinical manifestations of ischemia due to peripheral arteriosclerosis were studied. An accurate demonstration of the extent of the arterial occlusive process by means of aortography was of major importance in determining therapy and prognosis.The results from thromboendarterectomy to restore the arterial lumen in cases of segmental thrombosis or stenosis greatly exceeded those obtained from other methods of therapy for peripheral arteriosclerosis. The indications for and the limitations of lumbar sympathectomy as a palliative procedure are described. Medical treatment, except for the use of specific protective measures, was of little value in altering either the symptoms or prognosis.     

MANAGEMENT OF PERIPHERAL ARTERIAL OCCLUSIVE DISEASE

The proper use of medical therapeutic agents in the management of peripheral arterial occlusive disease must be based upon a thorough understanding of the factors controlling vasomotor tone and vasospasm, mechanisms regulating blood flow in skin and muscle, factors favoring nutritional and shunt flow, effects of the diversion of blood from one vascular bed to another, muscle contraction as a factor which may limit the blood flow to a part, epinephrine sensitivity after sympathectomy, and the effects of vasodilator drugs on the local and total circulations.There are six major classes of therapy for peripheral arteriosclerosis: General medical care, administration of vasodilator drugs and administration of anticoagulants, sympathectomy, direct vascular operation and amputation. In many cases the most successful treatment is a combination of medical and surgical therapy.     

Age-related arterial calcification in rats

In man, i) arteries calcify with age and ii) age-linked arterial calcification is amplified by vascular pathology such as hypertension or arteriosclerosis. Age-linked arterial calcification has a bad prognosis but drugs to prevent it are lacking. This is partially due to the lack of appropriate animal models. This paper looks at the extent to which arteries calcify with age in the rat and whether hypertension or arteriosclerosis amplifies such calcification. Total calcium levels were determined by acid digestion and flame spectrophotometry and intracellular calcium levels ([Ca2+]i) by the intracellular calcium-sensitive dye, fura-2. Arteries contained up to 5 times more calcium than other soft tissues. Arteries progressively calcified with age whereas other soft tissues did not. Accumulation of calcium with age was essentially extracellular. Hypertension had no effect on age-related arterial calcification. Calcification of the same order as in man was produced in a rat model of arteriosclerosis (vitamin D plus nicotine treatment). In conclusion, as in man, age-linked, organ-specific arterial calcification does occur in rats but its intensity is far less. Arterial calcification of a similar degree to that observed in man can be obtained in rats by hypervitaminosis D plus nicotine.     

SUPRACONDYLAR AMPUTATION IN THE AGED

Of 105 consecutive supracondylar amputations done at the San Diego County General Hospital during the five-year period, 1953-58, 88 were in patients more than 60 years of age. Occlusive arterial disease was the reason for operation in 85 of the 88 cases.Presenting complaints at the time of amputation were gangrene in 45 cases, pre-gangrene associated with severe pain in 34. Acute arterial occlusion as a cause of thigh amputation was infrequent.The average age of patients requiring thigh amputation from complications of arteriosclerosis obliterans was 78.3 years; for those with diabetic arteriosclerosis or embolism it was about seven and a half years less.Supracondylar amputation was considered the procedure of choice in the elderly debilitated patients with far-advanced occlusive diffuse arteriosclerosis, complicated by gangrene, ulcer and infection of the toes or feet. Sympathectomy and direct arterial operation if done early in the course of the disease may postpone or prevent subsequent amputation.The surgical mortality rate (first two weeks) for supracondylar amputation was 12.5 per cent. More than two-thirds of the deaths were due to bronchopneumonia.     

2型糖尿病患者肝损伤标志物与下肢动脉病变的相关性分析

目的：探讨2型糖尿病患者肝损伤标志物水平与其下肢动脉病变的相关性,为2型糖尿病并发症的防治提供参考依据。方法：选取我院收治的2型糖尿病患者946例,根据下肢动脉内膜中层厚度分为以下3组,即无动脉硬化组（276例）、单纯性动脉硬化组（598例）和动脉硬化伴管腔狭窄或闭塞组（72例）。分析和比较三组之间肝损伤标志物谷丙转氨酶（ALT）、谷草转氨酶（AST）、γ-谷氨酰转肽酶（GGT）水平的差异,及其与2型糖尿病患者下肢动脉硬化程度的相关性。结果：随着动脉硬化程度的加重,2型糖尿病患者的ALT水平逐渐升高,三组之间两两比较差异均有统计学意义（P〈0．05）。动脉硬化伴管腔狭窄或闭塞组AST水平显著高于非动脉硬化组和单纯性下肢动脉硬化组,而动脉硬化组和非动脉硬化组之间AsT水平比较无显著差异（P〉0．05）。三组之间γ-谷氨酰转肽酶水平比较无显著性差异（P〉0．05）。Spearman等级相关分析显示ALT与糖尿病下肢动脉硬化的相关系数为0．30484。结论：2型糖尿病患者ALT水平与其下肢动脉硬化程度显著相关。     

2 型糖尿病患者肝损伤标志物与下肢动脉病变的相关性分析

目的：探讨2 型糖尿病患者肝损伤标志物水平与其下肢动脉病变的相关性,为2 型糖尿病并发症的防治提供参考依据。方 法：选取我院收治的2 型糖尿病患者946 例,根据下肢动脉内膜中层厚度分为以下3 组,即无动脉硬化组(276 例)、单纯性动脉硬 化组(598 例)和动脉硬化伴管腔狭窄或闭塞组(72 例)。分析和比较三组之间肝损伤标志物谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)水平的差异,及其与2型糖尿病患者下肢动脉硬化程度的相关性。结果：随着动脉硬化程度的加重,2 型糖尿病患者的ALT 水平逐渐升高,三组之间两两比较差异均有统计学意义(P<0.05)。动脉硬化伴管腔狭窄或闭塞组AST 水平显著高于非动脉硬化组和单纯性下肢动脉硬化组,而动脉硬化组和非动脉硬化组之间AST 水平比较无显著差异(P>0.05)。三组之间γ-谷氨酰转肽酶水平比较无显著性差异(P>0.05)。Spearman 等级相关分析显示ALT 与糖尿病下肢动脉硬化的相关系数为0.30484。结论：2型糖尿病患者ALT 水平与其下肢动脉硬化程度显著相关。     

Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats: blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthesis.

Monocyte chemoattractant protein-1 (MCP-1) may play an essential part in the formation of arteriosclerosis by recruiting monocytes into the arterial wall. Thus, we devised a new strategy for anti-MCP-1 gene therapy against arteriosclerosis by transfecting an amino-terminal deletion mutant (missing the amino-terminal amino acids 2 to 8) of the human MCP-1 gene into a remote organ (skeletal muscles). Intramuscular transduction with the mutant MCP-1 gene blocked monocyte recruitment induced by a subcutaneous injection of recombinant MCP-1. In a rat model in which the chronic inhibition of endothelial nitric oxide synthesis induces early vascular inflammation as well as subsequent coronary vascular remodeling, this strategy suppressed monocyte recruitment into the coronary vessels and the development of vascular medial thickening, but did not reduce perivascular fibrosis. Thus, MCP-1 is necessary for the development of medial thickening but not for fibrosis in this model. This new strategy may be a useful and feasible gene therapy against arteriosclerosis.     

Influence of pulsing electromagnetic field therapy on resting blood pressure in aging adults

This double-blind study tested the effects of pulsating electromagnetic field (PEMF) therapy sessions on the changes in peripheral cardiovascular function in a group of aging adults after 12 weeks of treatment. Each therapy session involved 15 min of exposure to low-frequency PEMF with asymmetrical waveforms emitted by the Impulser? Pro mattress. The treatment was provided 5 days per week for a total of 60 sessions. Resting blood pressure and arterial stiffness index were determined for peripheral cardiovascular function. Fifty-four older men and women (mean age 59.8 ± 3.5 yrs) completed the entire protocol involving either the PEMF or a sham treatment. The results include statistically significant reductions in systolic and pulse blood pressure, while no significant difference in diastolic pressure or the index of arterial stiffness was observed. These findings suggest that the PEMF treatment might be linked to improvements in peripheral resistance or circulation.     

超声引导下外周神经阻滞对老年下肢动脉硬化闭塞症截肢术患者循环系统和疼痛的影响

目的:研究超声引导下外周神经阻滞对老年下肢动脉硬化闭塞症截肢术患者循环系统和疼痛的影响。方法:选择我院2016年2月～2019年11月收治的82例老年下肢动脉硬化闭塞症患者为研究对象,所有患者均接受下肢截肢术治疗,对照组采用硬膜外麻醉,研究组采用超声引导下外周神经阻滞。对比两组感觉神经、运动神经阻滞情况、阻滞效果,循环功能,疼痛指标和不良反应。结果:研究组感觉神经及运动神经阻滞起效时间较对照组短,感觉神经及运动神经阻滞维持时间较对照组长,差异比较有统计学意义(P0.05)。两组优良率差异比较无统计学意义(P0.05)。手术开始30 min时,对照组心率、平均动脉压均下降,研究组无明显改变,差异比较有统计学意义(P0.05)。术后24h时,两组疼痛指标浓度均较入室时增加,研究组低于对照组,差异比较有统计学意义(P0.05)。研究组不良反应总发生率低于对照组(P0.05)。结论:老年下肢动脉硬化闭塞症截肢术患者予以超声引导下外周神经阻滞的起效时间更快,能够减轻围术期疼痛,保持术中循环功能的稳定。     

Successes, failures and complications in thrombolytic therapy in peripheral, arterial and venous occlusions]

Thrombocytic therapy in peripheral arterial and venous vessel occlusion represents a clearly described alternative towards the surgery of vessels. A success rate of 36.5% can be found in subacute peripheral arterial thrombosis and 46.3% in subacute thrombotic occlusion of a bypass-graft. Contrary to that, a rate of 29.8% can be found in complications or side-effects respectively. In cases of peripheral deep venous thrombosis, a partial or full success can be found in 72%. However, the rate of complication amounting to 44.2% is comparatively high. The longer thrombolytic therapy with streptokinase or urokinase will last, the more frequently and more serious will be the complications, such as bleedings of different kind as well as increase of temperature to mention the most frequent ones. The application of urokinase is absolutely possible today, however, the use of urokinase seems to be only justified, if a thrombolytic therapy with streptokinase was carried out successfully and a subsequent surgical therapy was not possible. The present costs of this preparation are far too high for urokinase to be applied routinely. A thrombolytic therapy with SK as well as with UK has to be followed by an anticoagulant treatment.     

Study of dynamic microcirculatory problems in ‘blackfoot disease’ -emphasizing its differences from arteriosclerosis

The cutaneous microcirculation can be divided into thermoregulatory shunt vessels and nutritive skin capillaries. Flux in nonnutritional shunt vessels dominates the signal recorded by the laser Doppler flowmeter. Computerized videophotometric capillaroscopy is a sensitive method for assessing cutaneous nutritive microcirculation. Using patients with blackfoot disease and arteriosclerosis as disease models, we evaluated the sensitivity and clinical usefulness of these relatively new techniques for peripheral vascular disorders. In blackfoot disease, blood flux measured by the laser Doppler flowmeter in the affected toe was lower than that in the nonaffected toe. In symptom-free fingers, blood flow was not significantly different between blackfoot disease and arteriosclerosis. However, blood flow in both diseases was lower than that of the control group. Patients who had the same status of thermoregulatory flow and eyeground arteriosclerotic classification underwent a 1-min arterial occlusion of the digits. The postocclusive reactive hyperemia response (PRH) of nailfold capillary loops was evaluated. All parameters for PRH for the cutaneous nutrient microcirculation including resting capillary blood cell velocity (rCBV), peak capillary blood cell velocity (pCBV) and time to pCBV were more significantly disturbed in the blackfoot disease group than in the arteriosclerotic group. On the basis of the results of this study, dynamic capillaroscopy provides a new approach for the early detection of circulatory disturbances resulting from different mechanisms.     

The Recognition and Management of Peripheral Arterial Injuries

Early recognition of limb ischemia may allow prompt, effective therapy for peripheral arterial injuries. A review of cases of peripheral arterial trauma at the Toronto General Hospital since 1953 revealed that 50% of the injuries were not immediately recognized. An expanding hematoma, pulsatile hemorrhage or the onset of a bruit and thrill signifies arterial damage in penetrating wounds. Ischemia may be difficult to recognize in patients with soft tissue or skeletal trauma, but the presence of distal pallor, coolness, paresis, cyanosis, anesthesia, poor capillary refill and disproportionate pain indicates significant arterial damage and necessitates surgical exploration. The diagnosis of arterial “spasm” in such instances is untenable and can only be made after direct inspection, or on the return of pulses after reduction of a fracture or release of a tight cast. Restoration of arterial continuity by end-to-end anastomosis is the recommended technique for all arterial injuries, since after ligation of even minor vessels, ischemia may ensue, and amputation may occasionally be necessary.     

Critical evaluation of endovascular surgery for limb salvage

Rest pain, tissue loss, and gangrene are manifestations of critical limb ischemia caused by peripheral arterial disease and define a patient subgroup at highest risk for major limb amputation. Patients with nonhealing lower extremity wounds should be screened for the risk factors for peripheral arterial disease and offered noninvasive vascular testing. The diagnosis of critical limb ischemia mandates prompt institution of medical and surgical management to achieve the best chance of limb salvage. Surgical intervention has evolved from primary amputation to open bypass to the present era of endovascular therapy. The goals of surgical bypass and endovascular therapy are to improve perfusion sufficiently to permit healing. Despite poorer patency rates and the more frequent need for reintervention, endovascular therapy has been shown in multiple retrospective studies to achieve limb salvage similar to open bypass. Only one large, prospective, randomized controlled trial exists comparing open bypass with endovascular therapy: The Bypass versus Angioplasty in Severe Limb Ischemia of the Leg (BASIL) trial. Close clinical surveillance and serial monitoring of limb perfusion by means of noninvasive arterial studies are needed to determine the need for further vascular intervention. Limb salvage patients suffer from multiple comorbidities and benefit from a multidisciplinary, team approach to care.     

Expanding the horizons in treatment of severe peripheral vascular disease using microsurgical techniques

The use of microvascular tissue transfer as an adjunct to arterial reconstruction has begun to have a positive impact on limb salvage in patients with advanced arteriosclerosis and nonhealing ischemic wounds. However, many patients with severe peripheral vascular insufficiency not amenable to conventional arterial reconstructive procedures eventually require limb amputation. We have treated 12 patients with advanced peripheral vascular disease and nonhealing ischemic wounds by three different methods. These included distal bypass alone, distal bypass done in conjunction with free-tissue transfer, and free-tissue transfer alone. All bypass grafts were done to vessels at or below the ankle using a reversed saphenous vein. In each case, the distal anastomosis was performed, using the operating microscope and standard microvascular technique. Mean follow-up for these patients is 18 months. Distal bypass alone resulted in limb salvage in three of five patients. In the combined bypass and free-flap group, three of five patients had salvage of their threatened extremity at a 1-year follow-up. Two patients with ischemic ulcers, rest pain, and unsuitable distal vessels for bypass were treated with free-tissue transfer alone. This resulted in healed wounds, limb salvage, and complete resolution of the rest pain symptoms in both patients. When advanced ischemia is complicated by large areas of tissue loss, combined bypass and microvascular free-issue transfer, performed in stages or simultaneously, is safe and can often result in limb salvage. In the rare instance of a completely obliterated distal runoff bed, free-tissue transfer alone may provide not only a healed wound, but also a means of "indirect" revascularization of the extremity and limb salvage.     

Increased endogenous nitric oxide production induced by physical exercise in peripheral arterial occlusive disease patients

The effects of 14-day physical exercise or iloprost treatment (0.5-2 ng/Kg/min) on endogenous nitric oxide production and neutrophil adhesion were evaluated in 20 patients with peripheral arterial occlusive disease (Fontaine Stage II). Peripheral venous blood samples and 4-h urine samples were collected before, immediately after 14 days of therapy and 7-10 days after therapy in order to evaluate neutrophil adhesion, nitrite/nitrate and cGMP excretion rates. A longer pain free walking distance was observed after exercise, compared to iloprost (>500 m in 3/10 subjects). Urinary nitrite/nitrate, as well as cGMP concentrations, significantly increased after exercise. Nitrite/nitrate excretion rate inversely correlated to neutrophil adhesion. No variations were observed in these parameters in iloprost treated patients. The improvement in claudication and the transient increase in urinary nitrite/nitrate suggest a possible nitric oxide-dependent mechanism for the clinical efficacy of physical exercise. The results from the present and previous observations indicate that, besides pharmacological treatments, a regular aerobic exercise improves peripheral arterial occlusive disease.     

Individual assessment of arteriosclerosis by empiric clinical profiling

Background

Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient.

Methodology/Principal Findings

269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient''s disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125).

Conclusions/Significance

Empiric clinical profiling and the disease activity score that are based on accessible, available and affordable clinical data are valid markers for symptomatic arteriosclerosis.     

跨病灶压力梯度检测在下肢动脉硬化闭塞症腔内治疗的应用价值

摘要 目的：探讨跨病灶压力梯度（TLPG）检测在下肢动脉硬化闭塞症腔内治疗中的应用价值。方法：选取2018年1月~2019年6月于长沙市第一医院住院并进行腔内治疗的73例下肢动脉硬化闭塞症患者,造影证实管腔病灶,并通过管腔真径测量记录其狭窄程度。予导丝通过病灶后,进行病灶前-后的管腔压力的测定并记录干预前压力梯度值。根据患者临床表现、术前病灶影像学检查及压力梯度值,决定是否进行球囊扩张和/或支架植入干预治疗。完成所有干预后再次进行病灶近-远端测压,并记录干预后压力梯度值,分析干预前TLPG与Fontaine分期、踝肱指数（ABI）、疼痛评分的相关性,分析TLPG与管腔狭窄程度的相关性,并分析干预前后压力梯度值差值与ABI指数差值、疼痛评分差值的相关性。结果：Spearman相关分析结果显示,干预前TLPG与Fontaine分期、ABI指数、疼痛评分呈正相关（P<0.05）,TLPG与管腔狭窄程度未见明显相关性（P>0.05）,干预前后压力梯度值差值与ABI指数差值呈正相关（P<0.05）,与疼痛评分差值未见明显相关性（P>0.05）。结论：在腔内治疗过程中进行TLPG测定,可能成为指导下肢动脉硬化病变评估的客观精确指标,可能有助于临界性病变的干预指征把握,可能有助于客观评估干预的即时效果,从而为下肢动脉硬化闭塞症的规范腔内治疗,提供一定的指导和帮助。     

Basic study on radon effects and thermal effects on humans in radon therapy

Because most of the diseases to which radon (222Rn) therapy is applied are related to activated oxygen, in this study the effect of the radioactivity of radon and the thermal effect were compared under a room or a hot spring condition with the same chemical component using as the parameters the activity of superoxide dismutase (SOD), which is an oxidation inhibitor, and lipid peroxide and low density lipoprotein (LDL)-cholesterol, which are closely involved in arteriosclerosis. Results show that the SOD activity was significantly increased, and the lipid peroxide and LDL-cholesterol levels were significantly decreased on days 6 and 7 of study. The results were about 2-fold larger in the radon group than in the thermo group. This suggests that the anti-oxidation function was more enhanced by radon therapy than by thermo therapy, and suggests that radon therapy may help to prevent the causes of life style-related diseases such as arteriosclerosis. These findings are important in understanding the mechanism of diseases in which radon therapy is used as treatment, and most of which are called activated oxygen-related diseases.     

Pathogenesis of Lethal Shock After Intravenous Staphylococcal Enterotoxin B in Monkeys

The pathogenesis of shock in the rhesus monkey given intravenous staphylococcal enterotoxin B (SEB) is not understood. Several cardiovascular changes produced by a highly purified preparation of SEB were studied after administration of doses ranging from 50 to 1,000 mug/kg. Irreversible arterial hypotension was found consistently at the higher doses. Arterial blood pressure and cardiac output declined substantially as shock developed. Total peripheral vascular resistance did not rise at any time, but showed a significant fall during the late stages of shock. Portal and central venous pressures remained essentially unchanged. Venous O(2) content and pO(2) declined gradually throughout the period of toxemia, but arterial O(2) content remained constant until just prior to death, when a slight fall was noted in some monkeys. These changes were consistent with a pooling of blood in the peripheral vascular beds and seemed to resemble cardiovascular responses reported to occur in monkeys during shock due to bacterial endotoxin. Epinephrine, administered in the late stages of shock, caused arterial pressure to increase almost immediately and cardiac output to return to normal about 1 min later. Although life could occasionally be prolonged for several hours by continuous or intermittent epinephrine infusions, this therapy never succeeded in reversing the lethal effects of high doses of SEB.