Peripheral Arterial Occlusive Disease Stage Research Articles

Topicality of the fundamental and determining importance of chronic critical ischemia of the extremities and its restorative treatment using crural/pedal bypasses in Germany and in Saxony-Anhalt

Currently, there is an increase in severe stages of peripheral arterial occlusive disease (PAOD) with critical ischemia. This seems to correspond to the general demographic change as well as aconsequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of the last 3years. The now established and accepted interventional/endovascular approach for severe lower leg PAOD in experienced hands is still considered the first-line treatment but from the authors' perspective crural/pedal venous bypass is experiencing arenaissance. Compact narrative review of the current state of crural/pedal bypass surgery in Germany and Saxony-Anhalt (SA) combined with selective references from the current scientific medical literature and own clinical experiences. The current statistics of case-related diagnosis-related groups (DRG) data show that, especially with the occurrence of the corona pandemic, adecrease in inpatient case numbers of patients with PAOD stage IIB can be observed nationwide and also in SA. The severe PAOD stages have remained approximately the same in case numbers but increased in SA. The risk stratification based on the wound, ischemia and foot infection (WIFI) classification offers the possibility to be able to make statements about the risk of amputation, benefits and type of revascularization measures. The length of the occlusion, occlusion site of the affected vessels and degree of calcification are taken into account in the global limb anatomic staging system (GLASS) to assess the prognosis. The evaluation of the case-based hospital statistics from 2015 to 2020 showed aconstant use of femorocrural/femoropedal bypass surgery in Germany as well as aslight increase in reconstruction using femorocrural bypasses in SA, which seems to correlate with the tendency for an increase in the number of cases of severe PAOD. Parameter-based objectification of the severity of critical limb ischemia should be included in the indications for placement of a crural/pedal bypass. The WIFI classification and GLASS are suitable for this purpose as arelative prognosis of success is also possible. The treatment of critical limb ischemia by crural/pedal bypass surgery continues to find aconstant application in Germany and SA.

The In-Hospital Care of Patients With Peripheral Arterial Occlusive Disease.

Studies from Denmark and the USA have shown differences in treatment outcomes for patients with peripheral arterial occlusive disease (PAOD) between hospitals of different size and certification status. For Germany, it is not known whether certification as a specialist center for vascular diseases or hospital size is associated with differences in the primary treatment outcome. Using data from the German Federal Statistical Office, all hospitalizations due to PAOD of Fontaine stage IIb or higher were included in our study and the hospitals were classified according to their size and certification status. PAOD stage, age, sex, and comorbidities were documented for each hospitalization. Univariate and multivariate logistic regressions were performed to identify independent variables that predict various treatment endpoints. A total of 558 785 hospitalizations were included for analysis, of which 29% were in hospitals with certified vascular centers. In multivariate analysis, admissions to certified hospitals were associated with lower rates of major amputation (odds ratio [OR] 0.95, 95% confidence interval [0.92; 0.98], p = 0.003) and higher rates of minor amputation (OR 1.04 [1.01; 1.06], p = 0.004) with no difference observed in mortality (OR 0.99 [0.96; 1.03], p = 0.791). Admissions to larger hospitals were associated with more comorbidities, longer hospital stays, and higher rates of mortality and amputations. Treatments in certified hospitals are associated with fewer major and more minor amputations. This may reflect intensification of therapy targeting preservation of functional limbs.

Antinociceptive effect of garlic, garlic preparations and derivative compounds.

The antinociceptive effects of garlic have shown promise in treating different chronic diseases in humans, such as knee osteoarthritis, rheumatoid arthritis and peripheral arterial occlusive disease stage II. The most common garlic products are garlic powder (dried garlic), steam distilled garlic oils, garlic oil macerate and aged garlic extract. These commercial products contain organosulphur compounds (OSCs) that have been extensively evaluated in preclinical models and some clinical assays to treat different diseases against pain. In this review, we describe the importance of some bioactive compounds found in garlic and their role in treating pain. A systematic search of the literature in Dimensions, PubMed, Scopus, and Web of Science was performed. Terms and preselected keywords relating to garlic, its derivatives and organusulphure compounds in acute, chronic and neuropathic pain, were used to perform a systematic literature search. Two independent reviewers screened the papers for inclusion and assessed the methodological quality. The antinociceptive activity of garlic and its OSC is related to its antioxidant and anti-inflammatory properties, which may be explained by the ability to block the synthesis of PGs, pro-inflammatory cytokines and interferon-γ, by the reduction COX-2 activity and increasing the levels of anti-inflammatory cytokines. Besides, garlic extract is an activator of TRPA1 and TRPV1, where the principal responsible for this activation are OSC. The relationship between these pathways allows a better understanding how garlic and its derivates could be carrying out its pharmacological action over the management of acute and chronic pain and provide a base by further investigations. Antinociceptive effect of garlic and its OSCs has been extensively evaluated in preclinical models and clinical assays to treat different diseases, contributing to the modulation of inflammation as an essential factor in reducing pain. The current review emphasizes the potential therapeutic effect of garlic and its derivatives in treatment of pain and related mechanisms of action. Moreover, it provides information about the potential clinical use in patients with painful conditions.

Intensive Rehabilitation Program in Arterial Occlusive Disease Patients

Peripheral arterial occlusive disease (PAOD) limits walking efficiency and distance. The main disabling symptom is vasculopathy that leads to claudicatio intermittens and limits walking efficiency. Stretching techniques are effective in treatments for retractions and are used to improve flexibility of triceps surae and range of motion of the ankle. The aim of this study is to evaluate the effects of a combined walking and stretching program on walking efficiency in elderly PAOD patients. Seventy patients with PAOD stage II of the Leriche–Fontaine classification were randomly assigned into a stretching group (SG) or conditioning group (CG). Both groups participated in an eleven-day intensive rehabilitation program based on walking and strength training, while the SG performed five extra sessions of stretching. Walking autonomy was assessed through treadmill and overground tests with the recording of initial and absolute pain. A univariate ANOVA analysis was applied for the differences between the initial and final outcomes. Walking autonomy improved in both groups (p < 0.01), while only the SG improved flexibility (from −14.0 ± 8.1 to −10.3 ± 8.3 cm; p < 0.01). An intensive eleven-day rehabilitation program based on walking, strength, and stretching exercises is effective to improve the onset and the delay of pain during walking in patients with PAOD.

Efficacy and safety of a new pneumatic compression device for peripheral arterial disease with intermittent claudication

SummaryBackground: The primary objective of the study was to demonstrate that Intermittent Pneumatic Compression (IPC) with the new ANGIO PRESS™ IPC device can significantly improve the walking distance, i.e. pain free initial intermittent claudication distance (ICD) and the absolute claudication distance (ACD) in patients with stage II peripheral arterial occlusive disease (PAD) compared to control treatment.Patients and methods: A total of 67 patients were screened and randomized into the study in four clinical centers based in Israel and Germany. Patients were randomized to one of the two study groups: 1. Medication treatment with ASS / Clopidogrel and standardized walking exercise with additional IPC treatment, two times per day for 1.5 hours for three months. 2. Medication treatment and standardized walking exercise alone. The safety and efficacy of the ANGIO PRESS™ device was determined for the treatment of symptoms of PAD Fontaine stage IIb by measuring the pain free walking distance, the absolute walking distance, the ankle-brachial-index (ABI) and the walking pain. Additionally the quality of life (QOL) of each subject was assessed according to the SF-36 questionnaire. Subjects were followed up at six weeks and 3 months.Results: No statistical differences were observed in any of the demographic characteristics and baseline scores. A significant difference was found between the treatment and control group in the ACD and the walking pain scale. Subjects in the treatment group improved their total walking distance in 54 meters, an improvement of 40% compared to their baseline distance. The walking pain improved by 1.89 points in the treatment group. Despite the fact that the difference in the ICD between the study groups were not found significantly different, the mean change from baseline in ICD score at the three month visit in the treatment group of 37 m was found statistically significant (p=0.0002), whereas the mean change of 20.7 m in the control group was not found significantly different. No changes were found between the study groups in the ABI and the QOL. The treatment was easy to tolerate and most patients suffered no side-effects, nor complained of any significant discomfort. Two subjects suffered from SAEs which were determined as not related to the study treatment.Conclusion: The ANGIO PRESS™ is a non-invasive, easy to use, home treatment which is safe and moderately effective for the treatment of intermittent claudication. The ability of subjects to improve their absolute walking distance and reduce the walking pain on the same time may offer a significant value for patients at early stages of PAD who are not indicated for an invasive treatment.

CONTRIBUTION OF TRANSCUTANEOUS OXYMETRY IN DIABETIC FOOT SYNDROME

Four major complications are participating in tissue damage in diabetic foot syndrome – diabetic angiopathy, neuropathy, osteoarthropathy and inflammation. Low ankle-brachial pressure index (ABI) is a well-known indicator for ischemia of lower limbs, but in patients with diabetes mellitus is common also a high ABI (over 1.3) as reliable predictor of the presence of arterial calcification – medial calcinosis. Aim of the study is to determine the degree of ischemia using transcutaneous oximetry in patients with diabetic foot syndrome - with clinical manifestations of peripheral arterial occlusive disease (PAOD) and medial calcinosis. We investigated three groups: first consisted of 46 members in IInd stage of PAOD according to Fontaine classification, in second group were 30 members in IIIrd stage of PAOD and third had 29 members in IVth stage of PAOD. The ABI was determined with Doppler ultrasound examination. Transcutaneous oxygen tension (TcPO2) was measured with Oxykapnomonitor Hellige SMK Germany equipment with sensing probe – transoxode. Resting values of TcPO2 were obtained in lying patient on the foot in first metatarsal space. Subsequently leg was passively elevated into 30 degree angle for 3 minutes and then reimposed into primary position. One minute exercise – plantar and dorsal feet flexion was performed and after the TcPO2 values stabilization the patient hung his shin from the edge of the bed touching the floor. TcPO2 values were continuously recorded by analog waveform. In more severe stages of PAOD according to Fontaine stage III and IV we detected lower levels of TcPO2 under basal resting conditions: 20 respectively 5 mmHg. Patients with IInd stage of PAOD had basal TcPO2 values of 40 mmHg. Conclusions of the study are: TcPO2 values are not affected by the presence of medial calcinosis and sothis method is particularly beneficial in patients where Doppler ultrasound examination shows artificial high pressure values on lower limbs. In the third and fourth stage of PAOD passive leg elevation is as effective in determination of ischemia as working test.

Simultaneous MR Arteriography and Venography With Blood Pool Contrast Agent Detects Deep Venous Thrombosis in Suspected Arterial Disease

The purpose of this study was to investigate the prevalence of incidental deep venous thrombosis (DVT) in patients with clinically suspected peripheral arterial occlusive disease (PAOD) using contrast-enhanced MR angiography (MRA) with a blood pool contrast agent. Two hundred fifty-nine MRA examinations with blood pool contrast agent in 245 consecutive patients (161 men; age range, 36-92 years), yielding a total of 4102 assessable arterial and venous vessel segments, were assessed with regard to the rate of incidentally observed acute and organized DVT and arterial stenosis grades. Incidental DVT was confirmed using duplex ultrasound. Contralateral nondiseased veins served as internal controls. The relationship between PAOD stages and acute and organized DVT was investigated using chi-square tests and a Mann-Whitney U test. Arterial stenosis grading using MRA with blood pool contrast agent revealed less than 50% luminal stenosis in 78% of segments (3199/4102), 50% or greater stenosis in 8% of segments (317/4102), and occlusion in 14% of segments (586/4102). Incidental DVT was observed in 26 of 245 patients (11%) (acute DVT was seen in 10 patients and 26 segments; organized DVT was seen in 17 patients and 35 segments; and one patient had both acute and organized DVT). All incidentally diagnosed cases of DVT were confirmed by duplex ultrasound. Internal controls revealed no false-positive or -negative findings (26 patients and 172 segments). Incidental acute DVT was significantly more common among patients without arterial stenosis greater than 50% (p < 0.05). Otherwise, there was no significant relationship between Fontaine PAOD stages and the occurrence of acute (p = 0.688) or organized (p = 0.995) DVT. Incidental DVT was prevalent in 11% of patients with clinically suspected PAOD. MRA with blood pool contrast agent has a potential role in the simultaneous assessment of arteries and veins and can detect concomitant venous disease affecting therapeutic management.

Epidurale Rückenmarkstimulation zur Therapie chronischer Schmerzen

Epidural spinal cord stimulation (SCS) is a reversible but invasive procedure which should be used for neuropathic pain, e.g. complex regional pain syndrome I (CRPS) and for mostly chronic radiculopathy in connection with failed back surgery syndrome following unsuccessful conservative therapy. Epidural SCS can also successfully be used after exclusion of curative procedures and conservative therapy attempts for vascular-linked pain, such as in peripheral arterial occlusive disease stages II and III according to Fontaine and refractory angina pectoris. Clinical practice has shown which clinical symptoms cannot be successfully treated by epidural SCS, e.g. pain in complete paraplegia syndrome or atrophy/injury of the sensory pathways of the spinal cord or cancer pain. A decisive factor is a critical patient selection as well as the diagnosis. Epidural SCS should always be used within an interdisciplinary multimodal therapy concept. Implementation should only be carried out in experienced therapy centers which are in a position to deal with potential complications.

Comparable outcome of acute unplanned peritoneal dialysis and haemodialysis

The impact of dialysis modality on outcome, especially on infection early in the course of dialysis, in unplanned acute dialysis initiation has not been well evaluated. The aim of the study was to compare the rates and causes of mortality and morbidity in incident dialysis patients started unplanned acute peritoneal dialysis (PD) or haemodialysis (HD). In this observational cohort study, incident dialysis patients with initiation of unplanned and acute PD (n = 66) or HD (n = 57) at a single centre from March 2005 to June 2010 were included and followed up for 6 months (0-183 days, mean follow-up time 4.72 months). For PD, surgically placed Tenckhoff catheters were used. All HD patients were dialysed with a central venous catheter (non-tunnelled or tunnelled). There were no significant differences in terms of gender, age and prevalence of diabetes mellitus in either group. The prevalence of heart failure [New York Heart Association (NYHA) Stage III-IV] was significantly higher in the PD group (73 versus 46% in HD group, P < 0.01). The population was stratified to PD and HD comparing mortality, infection, bacteraemia and hospitalization. Of the 123 patients who commenced acute and unplanned dialysis, n = 44 (35.8%) died during the follow-up period of 0-183 days. There were no significant difference in half-year mortality in n = 20 PD patients (30.3%) versus n = 24 HD patients (42.1%) (P = 0.19). The cardiovascular mortality in PD and HD patients were 9.1 and 10.5%, respectively (P = 1.00). Overall mortality due to infection was higher in the HD (17.5%) versus in the PD group (9.1%), however, not significant (P = 0.19). HD patients had significantly higher probability of bacteraemia in the first 183 days compared to PD patients (21.1 versus 3.0%, P < 0.01). Group comparison by Poisson regression analyses showed that the relative risk of bacteraemia in the PD group versus HD group was 0.16 (95% confidence interval, 0.05-0.57, P = 0.005). The significant difference was not affected by the confounder's patient age at time of dialysis, male sex, heart failure (NYHA III-IV), diabetes, malignancy and peripheral arterial occlusive disease Stage IV. There were high proportions of hospitalization after the initiation of dialysis in both groups (PD 75.0% and HD 67.3%, P = 0.40). Univariate and multiple regression analyses revealed only age at initiation of dialysis to be significantly associated with overall mortality (P < 0.05). Dialysis modality (PD versus HD) in an acute unplanned dialysis setting showed, in our population, no significant influence on survival. HD patients had a significantly higher risk of bacteraemia, perhaps due to central venous dialysis catheter. PD seems to be a safe and efficient, at least comparable, alternative to HD in acute unplanned dialysis settings.

Peripheral Bolus-Chase MR Angiography: Analysis of Risk Factors for Nondiagnostic Image Quality of the Calf Vessels—A Combined Retrospective and Prospective Study

The objective of our study was to evaluate the influence of endogenous and exogenous risk factors on the rate of nondiagnostic examinations of the calves in peripheral bolus-chase MR angiography (MRA). Peripheral bolus-chase MRA runoff studies in 177 patients with peripheral arterial occlusive disease (PAOD) were retrospectively assessed with regard to the rate of nondiagnostic image quality due to substantial venous overlay in the calf arteries requiring repeated MRA examinations. Logistic regression was used to analyze the rate of nondiagnostic MRA examinations as a function of several endogenous and exogenous risk factors and of the stage of PAOD. To probe the retrospective data, 22 consecutive patients were prospectively included and underwent a standard peripheral MRA examination if the probability of a nondiagnostic examination was less than 50% based on the results of logistic regression; otherwise, a hybrid MRA examination was ordered. Nondiagnostic image quality of the calf arteries was found in 53 patients (30%). The incidence increased with each stage of PAOD up to 39% for stage IV. For each increase in the stage of PAOD, the probability of nondiagnostic image quality increased by a factor of 1.5561 (p = 0.0024). With an increasing number of risk factors, a significantly (p = 0.0074) higher rate of nondiagnostic images was found. Based on the retrospective statistical analysis of PAOD stages and risk factors, selected patients can be triaged to undergo a specific hybrid MRA technique and thus circumvent the occurrence of nondiagnostic images and the need for repeated MRA examinations.

Association of Preexisting Medical Conditions with In-Hospital Mortality in Multiple-Trauma Patients

Mortality after trauma has been shown to be influenced by host factors, such as age and preexisting medical conditions (PMCs). The independent predictive value of specific PMCs for in-hospital mortality after adjustment for injury severity, injury pattern, age, and presence of other PMCs has not been fully elucidated. Records of 11,142 trauma patients (18 years of age or older, Injury Severity Score > or = 16, years 2002 to 2007) documented in the Trauma Registry of the German Society for Trauma Surgery were analyzed to assess the association of PMCs with in-hospital mortality. Multiple logistic regression models were used for this analysis. PMCs were affirmed for 3,836 of the 11,142 patients studied (34.4%). An independent statistical association with increased in-hospital mortality was found for 6 of 14 analyzed PMCs after adjustment for age and the Revised Injury Severity Classification score, respectively, ie, heart disease, obesity, hepatitis/liver cirrhosis, malignancies, coagulation disorder, and peripheral arterial occlusive disease stage IV. The association with mortality varied with different injury patterns. Specific PMCs were associated with increased mortality after trauma independent from injury severity and age. Knowledge of the identified relevant PMCs could help the medical team to be able to assess the mortality risk profile of trauma patients in a more detailed and quantifiable way.

The Effect of Selected Health, Demographic and Psychosocial Aspects on Quality of Life in Patients with Peripheral Arterial Occlusive Disease – a Prospective Analysis

Peripheral arterial occlusive disease (PAOD) is a prevalent atherosclerotic disorder characterized by exertional limb pain, loss of limb, and a high mortality rate. Because of its chronic nature, it often has a negative impact on a patient quality of life (QoL). Aims. To evaluate the effect of selected health, demographic and psychosocial aspects on QoL in respondents with PAOD. The study is a prospective and cross-sectional. It was carried out at the 2nd Department of Medicine of Charles University Hospital at the Faculty of Medicine in Hradec Králové, Czech Republic. Forty two respondents with PAOD (28 male, 14 female) were evaluated. All the respondents had involvement of femoral and popliteal arterial circulation. The number of all respondents in accordance with Fontaine classification was as follows: intermittent claudication: stage IIa - 4, stage IIb (<200 m) - 16, stage IIb (<50 m) - 9, chronic limb ischaemia: stage III - 6, stage IV - 7. The average age of all respondents was 65,4 years old (age range 45-79 years old). The study evaluates the effect of health aspects (stage of PAOD in accordance with Fontaine classification, diabetes mellitus, arterial hypertension, hyperlipidaemia, obesity, smoking), demographic (age, sex) and psychosocial aspects (level of education, marital status, religion) on QoL in respondents with PAOD. The Czech version of the International Generic European Quality of Life Questionnaire - EQ-5D was used. The statistical evaluation presents statistically a significant dependence of QoL in respondents with PAOD on age (p < 0,01) and the stage of PAOD in accordance with the Fontaine classification (p < 0,01). The effect of other health, demographic and psychosocial aspects was statistically insignificant. The results had shown that with an increasing age and with a serious stage of PAOD in accordance with Fontaine classification, the QoL declines. The global QoL in respondents with PAOD is low.

Exercise-Induced Weakness of the Leg Muscles - Cycling

HISTORY: A 40 year old hobby cyclist (annual training volume 10,000 km, regular participation in cycling marathons) with a history of weakness, numbness and “pins/needles” sensation of both lateral buttocks, thighs, calves and feet over the past two years. The discomfort occurred during cycling, especially uphill and most recently when walking quickly after at least 200 meters. The discomfort disappeared immediately at rest. Due to the discomfort he had to substantially reduce cycling-training. PHYSICAL EXAMINATION: 40 year old healthy, in good general health, the examination of the heart and the lungs produced no pathological findings, blood pressure was normal, and a supraumbilical systolic murmur could be heard at the abdomen. Examination of the pulses revealed a weak but symmetrical finding in both legs and feet. No muscular atrophy, no paresis and no loss of sensation. The reflexes were normal. Examination of cranial nerve status revealed no pathological findings. DIFFERENTIAL DIAGNOSIS: Central or peripheral neurological disease Myopathy Disease of the spinal column Vascular disease TEST AND RESULTS: Before admission to our clinic, preceding neurological examination including electroneurography, EMG and MR tomography of the spinal column revealed only a mild prolapsed intervertebral disc L¾ und L4/5. Exercise testing: Continuous walking at 6 km/h induced pain in both legs after 1 min. Calf muscle (CF) oxygenation as measured by Near-infrared spectroscopy (NIRS) showed a persistent decrease of StO2 from 60 to 27 %. Ultrasound of the abdomen: 10x7 mm large flap valve structure at the infrarenal abdominal aorta with luminal constriction and pronounced turbulent flow in the duplex scan. The Doppler scan revealed an acceleration of the flow to more than 6 m/sec in the stenosis. Angiography: High grade short focal stenosis of the infrarenal aorta with collateral circulation through lumbal arteries and the A. mesenterica inferior. FINAL WORKING DIAGNOSIS: Peripheral arterial occlusive disease stage IIb, due to the high grade short focal stenosis of the infrarenal aorta. TREATMENT AND OUTCOMES: Angioplasty and stenting with a self-expanding Nitinol Stent Secondary prophylaxis: Platelet aggregation inhibitor, statin therapy, advice to quit smoking, continue the aerobic exercise. The patient returned to cycling, starting with basic endurance training. No recurrence of prior symptoms and return to a good physical performance. Using the walking protocol as mentioned above, oxygenation kinetics (NIRS) in CF normalized with an initial smaller decrease in StO2 from 62 to 52%, followed by an increase to 72% until the end of exercise.

Sympathetic skin response in patients with peripheral arterial occlusive disease

Objective The current study aimed to assess the viability of sympathetic sudomotor fibers in patients suffering from mild peripheral arterial occlusive disease (PAD). Methods Sympathetic skin response (SSR) from the hand (electrical stimulation) and sole (electrical and magnetic stimulation) of 25 patients with PAD (19 males and 6 females with mean age 62.7±10.2 years) was recorded unilaterally depending on the side of the affected limb (18 right side, 7 left side). Electrophysiological data were also collected and correlated with the SSR results. Twenty-five, age- and gender-matched healthy volunteers served as controls. Results No evidence of nerve conduction abnormalities was recorded from the group of patients. Intact SSR recordings were obtained from the upper limb of patients. Nine patients (36%) had absent SSR in the lower limb following electrical stimulation, whilst the same 9 patients had absent SSR following magnetic stimulation. Significant differences occurred between groups in the SSR latency scores recorded from the lower limb. Following electrical stimulation the mean SSR latency in patients was significantly prolonged, compared to that of controls ( P=0.000), whilst the same applied following magnetic stimulation ( P=0.000). There was no correlation between SSR abnormalities and nerve conduction measurements. The manifestation of intermittent claudication at a walking distance of 250 m was strongly correlated with absent lower limb SSR ( r=0.71, P=0.035). Conclusions SSR abnormalities appeared to be an early and independent finding of neural impairment in our patients. Significance SSR study, performed at an early stage of PAD may prove useful in differentiating PAD-induced neuropathy from other neuropathic processes.

Mechanisms of anti-ischemic action of prostaglandin E1 in peripheral arterial occlusive disease.

The mechanisms of anti-ischemic effects of PGE1 in patients with peripheral arterial occlusive disease (PAD) are probably complex and clearly not limited to a direct vasodilator action. In addition to the known effects on blood flow, viscosity, fibrinolysis and platelet aggregation, the compound also inhibits monocyte and neutrophil function, suggesting that PGE1 will also have anti-inflammatory effects. Recent research has detected additional actions of PGE1 and prostacyclin analogs which might be relevant to its clinical efficacy. This includes inhibition of expression of adhesion molecules (E-selectin, ICAM-1, and VCAM-1), release of inflammatory cytokines (TNFalpha, MCP-1), matrix components and generation and release of growth factors (CYR61, CTGF). These actions may also contribute to the long-term effects of PGE1, particularly in more advanced stages of PAD. Gene-expression experiments with chemically stable prostacyclins and PGE1 suggest that several genes in vascular smooth muscle cells and fibroblasts are modified by prostaglandins at the transcriptional level. This includes TNFalpha-induced VCAM expression in vascular smooth muscle cells which appears to be inhibited via the prostaglandin EP2 receptor as well as IL-1-induced expression of the type-1 collagen gene in fibroblasts. Thus, regulation of gene transcription by PGE1 may contribute to tissue protection in critical ischemia of the lower limbs.

Microcirculation and tolerability following i.v. infusion of PGE 1 and iloprost: a randomized cross-over study in patients with critical limb ischemia

In a randomized cross-over study, the effect of PGE 1 and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE 1 and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE 1: first hour 20 μg, next 2 h 30 μg each. Iloprost: first hour 0.5 ng/kg/min, next 2 h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tc PO 2) values increased much more with PGE 1. Median tc PO 2 increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE 1 and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE 1) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE 1.

Influence of Fibrinogen and Hematocrit on the Early Outcome of Angioplasty in Patients With PAOD

To evaluate any correlation of fibrinogen and hematocrit with the early success of balloon angioplasty for peripheral arterial occlusive disease (PAOD) and compare the outcomes of angioplasty in diabetic and nondiabetic patients. From November 1997 through October 2000, 330 patients (246 men; mean age 63.6+/-10.9 years; 221 nondiabetic, 109 diabetic) with known PAOD were treated with percutaneous procedures. The majority of patients (239, 72.4%) were Fontaine stage IIa or IIb; the remaining (91, 27.6%) had critical limb ischemia (Fontaine stages III and IV). Fibrinogen and hematocrit assays were performed on all patients upon admission, and the results were then correlated with early angioplasty success. With advancing PAOD stage, fibrinogen concentrations increased significantly in both nondiabetic (p<0.006) and diabetic (p<0.02) patients, while angioplasty success rates declined by a factor of 3 in nondiabetics and 2 in diabetics. There was a significantly stronger association between low fibrinogen values and successful interventions relative to unsuccessful interventions (p<0.048). Interestingly, compared with nondiabetics, the angioplasty success rate in diabetics was associated with significantly higher fibrinogen levels (p<0.044) and lower hematocrit (p<0.022). Our findings appear to indicate that hemorheological factors, such as fibrinogen and hematocrit, can affect early angioplasty success. Moreover, high fibrinogen concentrations appear to be detrimental to early angioplasty success. Interestingly, low hematocrit levels in diabetics may partially offset the negative effects of hyperfibrinogenemia.

Autoantibodies and peripheral arterial occlusive disease

In patients with early manifestation of peripheral arterial occlusive disease (PAOD) and a less classical atherosclerotic risk profile, vasculitis is presumed to be the underlying disease. We performed a prospective study of the importance of determination of autoantibodies used for the diagnosis of vasculitis and collagen diseases in patients with symptomatic PAOD. 698 consecutive patients (mean age +/- SD: 68 +/- 10 years) were included who were referred from 1998 to 1999 for interventional treatment of PAOD. In 121 PAOD-patients (61 +/- 12 years) with a less pronounced atherosclerotic risk profile, or rarefied distal arteries without sclerosis of the media, or elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) independent from the stage IV of PAOD, the following autoantibodies were investigated: antinuclear antibodies (ANA), antibodies against extractable nuclear antigens (ENA): SCL 70, RNP, SS-A, SS-B, Jo-1, SM), double-stranded DNA antibodies (ds-DNA), antineutrophil cytoplasmatic antibodies (c- and p-ANCA), antiphospholipid antibodies [phosphatidylserine (APSA) and beta(2)-glycoprotein], smooth (SMA) and striated muscle (StrMA). ANA, SMA and StrMA were estimated by indirect immunofluorescence technique, ENA by Western-blot and the others by enzyme linked immunoassay. 38 PAOD-patients (35%) had increased autoantibody concentrations. The rate of different PAOD stages and localization did not differ between the group of patients with increased autoantibody concentrations and the group of patients without. But the group of patients with increased autoantibody concentrations had higher rates of elevated ESR [p-value of 0.0043, odds ratio of 7.1 (95% CI: 1.49-33.81)]. ANA were the most frequent autoantibodies detected in 17 (14%) of the 121 patients followed by APSA and autoantibodies directed against beta(2)-glycoprotein. During follow-up of 24 +/- 6 months no vasculitis or collagen diseases associated with the elevated autoantibody concentrations became clinically manifest in the 38 patients. Two patients died due to coronary heart disease. Four patients had a worsening of their PAOD but no amputation was performed. Out of the 83 patients without elevated concentrations of autoantibodies, eight patients died and three amputations were carried out. All in all, increased autoantibody concentrations in patients suffering from peripheral atherosclerosis are not a rare finding. A systematic determination of autoantibodies, especially in patients with a low atherosclerotic risk profile, does not increase the number of manifest or developing vasculitis of collagen disease.

Prostanoids for intermittent claudication.

Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity in the general population. While numerous studies have established the efficacy of prostanoids in PAOD stages III and IV the question of the role of prostanoids as an alternative or additive treatment in patients suffering from claudicatio intermittens (PAOD II) has not yet been clearly answered. The aim of this review was to evaluate effects of prostanoids in patients with intermittent claudication. Computerised searches of the Cochrane Peripheral Vascular Diseases Specialised Register (last searched April 2003), The Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2003), MEDLINE and EMBASE were undertaken. In addition relevant journals were hand-searched. Randomized clinical trials describing the effects of prostanoids in the treatment of patients suffering from intermittent claudication have been considered for inclusion. All reviewers assessed the quality of studies and extracted data unblinded. Statistical analysis including tests for heterogeneity and overall effect were performed by using MetaView of Review Manager 4.2. All numeric values are expressed as mean +/- Standard deviation (SD). Eighteen studies were included for analysis. A significant heterogeneity between the included studies was detected in most of the subgroup analysis. Five studies compared the effects of prostaglandin E1 (PGE1) versus placebo, and reported in their individual results significant increases in walking distances after the administration of PGE1. The attained increase in walking distances appears to be not merely a short-term effect because several studies reported that walking capacity remained increased even after termination of treatment. On the other hand, oral or intravenous prostacyclin did not increase the walking distances significantly. At least one adverse reaction was reported from 23.6% of the patients treated with prostacyclin (PGI2), and its analogues and from 13.7% of the patients treated with PGE1. Because of the heterogeneity between most of the included studies, we did not pool relevant parts of the data by meta-analysis. Based on the individual results of the published literature, patients with intermittent claudication seem to benefit from administration (intravenous or intra-arterial) of PGE1 by a significant improvement of their walking capacity. Further well-conducted randomized, double blinded trials, with a sufficient number of patients to provide statistical powerful information, should be performed to confirm the results of this review.

EFFECTS OF TRAINING AFTER ANGIOPLASTY ON PERFORMANCE, BLOOD FLOW AND MUSCLE HSP70 EXPRESSION IN PERIPHERAL ARTERIAL OCCLUSIVE DISEASE

Successful therapeutic interventions should improve blood supply and muscle function in peripheral arterial occlusive disease (PAOD). Muscular stress induced expression of heat-shock/stress proteins (HSPs) may increase the survival of ischemic-reperfused muscle. OBJECTIVE To evaluate the effects of a four week walking training after angioplasty (PTA) on blood flow and HSP70 expression in skeletal muscle. METHODS 30 patients with PAOD stage II were randomly assigned into two groups: controls (CON, n=16) and training (TR). In TR, four week supervised training was performed 1h/d, 6 d/wk, CON conducted self guided training. Recorded parameters were painfree walking distance (WD), Doppler-ankle pressure (DAP) and post-exercise perfusion measured by transcutaneous PO2 (TcPO2). Fine needle biopsies of the m. gastrocnemius were taken before and after the training. HSP70 was quantified by SDS-PAGE using western-blot with reference to a series of standard HSP70. HSP70 mRNA was determined through real time quantitative PCR. RESULTS DAP increased in both groups after PTA. WD in CON augmented from 47.5 m to 128 m and in TR from 60 to 185 m. TcPO2 remained unchanged. After the 4 week training period WD further increased in TR (650 m; p < 0.05) while it decreased in CON (90 m). TcPO2 increased significantly in TR while no change could be observed in CON. No significant difference was detected in regard to DAP after training. Angioplasty did not reveal any changes in HSP70 expression neither on protein nor on mRNA level in both groups. After 4 weeks training, HSP70 expression increased slightly on protein level (30.2 to 36.2 ng/2.5 μg protein) and significantly on mRNA level (27.2 to 307.9% of control) in CON while in TR there were no changes. CONCLUSION The functional effect of angioplasty on painfree walking distance was augmented by 4 weeks of walking training but not maintained in controls which is related to microperfusion and changes in skeletal muscle tissue. Increased HSP70 expression on protein and mRNA level in CON may be related to remodelling and reperfusion damage.