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Lack of effect of ischemia and dipyridamole on prostacyclin production in arteriosclerosis obliterans.

Six patients with advanced arteriosclerosis obliterans in the lower extremities were subjected to an exercise test on a tread mill with and without dipyridamole treatment. Prostacyclin (PGI2) release was measured by the concentration of its stable metabolite, 6-keto-prostaglandin F1 alpha in plasma. All the patients suffered from ischemic pain during both tests, but no changes were seen in plasma 6-keto-PGF1 alpha. Dipyridamole did not affect the physical performance. Our results suggest that atherosclerotic vessels do not increase PGI2 production in response to ischemia and that a single dose of dipyridamole does not change PGI2 production.

6-Ketoprostaglandin F1 alpha↗

Arteriosclerosis obliterans in Japanese diabetic patients.

Arteriosclerosis obliterans (ASO) of the lower extremities was found in 32 cases (1.9%) among 1673 Japanese diabetic patients. Comparison with age-and sex-matched control patients revealed that male sex, older age, hypertension and neglect of treatment of diabetes were positively correlated with ASO, but obesity, smoking and hyperlipidemia were not correlated with ASO. Proteinuria, cerebral vascular disease and myocardial infarction were significantly associated with ASO. The arterial pulses of the foot were examined in 451 diabetic patients. The pulse of A. dorsalis pedis was absent in 29 (6.4%) and was significantly related to the clinical signs and symptoms of ASO. The loss of the pulse of A. dorsalis pedis increased with age and was more frequent in men than in women. The results indicate a lower frequency of ASO in Japanese than in Western diabetic patients.

Aged↗

[General anesthesia for a patient on hemodialysis with arteriosclerosis obliterans].

A 48-year-old man with arteriosclerosis obliterans was scheduled for axillofemoral bypass. He had chronic renal failure and on hemodialysis (HD) for 22 years. On the morning of the day of surgery he received HD and two hours later anesthesia was induced with fentanyl 300 micrograms and midazolam 6 mg, and maintained with fentanyl, nitrous oxide and intermittent isoflurane. The common carotid artery was cannulated to measure arterial blood pressure because arteries in extremities were not available. Internal jugular vein at the other side of the arterial catheterization was cannulated to measure central venous pressure. Crystalloid and blood transfusion was performed to adjust hemodynamics and central venous pressure. Hemodynamics were stable during surgery and no complication occurred regarding the common carotid arterial line. The common carotid artery was useful for blood pressure monitoring in a patient whose extremities were not available. Midazolam and fentanyl could give stable hemodynamics to a patient with arteriosclerosis obliterans and chronic renal failure.

Anesthesia, General↗

Coronary artery disease in patients with arteriosclerosis obliterans of the lower extremities or aortic aneurysm.

Routine coronary angiography was performed in order to determine the incidence and clinical condition of coronary artery disease in 37 patients with arteriosclerosis obliterans or aortic aneurysm. Coronary angiography demonstrated significant stenosis in 12 (57%) of 21 patients with arteriosclerosis obliterans and in 7 (44%) of 16 patients with aortic aneurysm. The prevalence of risk factors for arteriosclerosis was similar for patients with arteriosclerosis obliterans and those with aortic aneurysm, and similar for patients with and without coronary artery stenosis. But coronary artery disease is often silent in patients with arteriosclerosis obliterans.

Aged↗

Fibrinolytic activity and the effects of beta-pyridylcarbinol (Ronicol) in patients with arteriosclerosis obliterans.

Twenty-one patients with arteriosclerosis obliterans of lower extremities were treated with beta-pyridylcarbinol (Ronicol) for five weeks. The long-term therapy with beta-pyridylcarbinol did not influence platelet aggregability. Activation of the fibrinolytic system was observed. This fibrinolytic effect of Ronicol was abolished in patients treated with aspirin. In most cases a slight clinical improvement was seen, manifested by elongation of pain-free walking distance and increased blood flow in affected limbs. It is concluded that the therapeutic effect of Ronicol in humans may be partly mediated by the release of endogenous prostacyclin.

Arteriosclerosis Obliterans↗

Effects of selective LDL apheresis on plasma concentrations of ICAM-1, VCAM-1 and P-selectin in diabetic patients with arteriosclerosis obliterans and receiving maintenance hemodialysis.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a serious complication in patients with end-stage renal disease (ESRD) caused by diabetic nephropathy. Adsorption of low-density lipoprotein (LDL) has been performed to treat ASO. While efficacy of this treatment has been reported in limb ischemia, the mechanism underlying the benefit remains unclear. We investigated how LDL adsorption affected soluble adhesion molecules; P-selectin, an endothelial and platelet activation marker; inflammatory cytokines such as interleukin (IL)-1beta, IL-6 and tissue necrosis factor (TNF)-alpha; and lipids in serum. METHODS: Selective LDL adsorption by dextran sulfate columns (LDL apheresis) was performed weekly for 10 weeks to treat eight hemodialysis patients with ASO, ESRD, and type 2 diabetes mellitus. Serum was sampled before and immediately after apheresis. RESULTS: LDL apheresis was performed safely. After LDL apheresis lipid concentrations were significantly reduced and clinical findings, such as Fontaine's classification and ankle brachial pressure index values, were improved. Pretreatment concentrations of soluble intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1) and also P-selectin were higher in patients than healthy controls. After apheresis these decreased, especially P-selectin. IL-1beta, IL-6, and TNF-alpha concentrations before apheresis were similar to those in controls and were unaffected by treatment. CONCLUSION: Effectiveness of LDL apheresis against ASO may involve decreased endothelial cell and platelet activation.

Aged↗

Thromboxane B2, 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 plasma levels in arteriosclerosis obliterans: relationship to clinical manifestations, risk factors, and arterial pathoanatomy.

Current concepts of atherogenesis based on animal and human investigations indicate prostaglandins as a key factor in atherosclerotic lesions. The plasma profiles of thromboxane B2 (TXB2), 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 were investigated by means of a sensitive radioimmunoassay technique in 40 patients with arteriosclerosis obliterans and in 30 healthy control subjects. Abnormally high levels of TXB2 and PGE2 (222.97 +/- 320.86 pg/ml, mean +/- SD, vs 20 +/- 2.1 and 352.66 +/- 235.54 vs 24.4 +/- 3, p less than 0.01) were detected in arteriosclerosis obliterans patients. The ratio between TXB2 and 6-keto-PGF1 alpha was increased from 1.2 in control subjects to 6.0 in patients. In arteriosclerosis obliterans TXB2 increased in relation to clinical manifestations and to the extension of the vascular damage. In addition, TXB2 was positively related to serum triglyceride content (r = 0.562, p less than 0.05) and inversely related to platelet count (r = 0.727, p less than 0.001). The marked imbalance between the stable metabolites of thromboxane and prostacyclin in arteriosclerosis obliterans patients provides biologic evidence which fits well with the thrombogenic theory of atherosclerosis. These results further support the theory that prostaglandins may be heavily involved in atherosclerosis.

6-Ketoprostaglandin F1 alpha↗

Prevalence of severe arteriosclerosis obliterans in patients with diabetes mellitus. Relation to smoking and form of therapy.

Noninvasive methods were used to determine the prevalence and severity of arteriosclerosis obliterans associated with diabetes in 674 subjects including 153 recruited as controls. A resting ankle systolic blood pressure that was less than 90% of the arm pressure indicated severe arteriosclerosis obliterans. Of the 71 subjects with severe disease, 64 (90%) had a history of smoking, which is significantly greater than the 60% overall smoking rate (p less than 0.001). In non-insulin-dependent diabetic smokers, the diet-treated subjects had 2.5 times the prevalence of severe arteriosclerosis obliterans as those treated with insulin (p = 0.01); the sulfonylurea-treated subjects had twice the prevalence of severe disease as those treated with insulin (p = 0.015).

Adult↗

Systemic arterial compliance in patients with arteriosclerosis obliterans of the lower limbs. Observations on the effect of intravenous propranolol.

Hemodynamic parameters and systemic arterial compliance were measured in patients with arteriosclerosis obliterans of the lower limbs before and after acute administration of propranolol. Arterial compliance was evaluated from a simple viscoelastic model, enabling the calculation of diastolic drainage and diastolic blood flow as indices of the reservoir role of the larger arteries in overall circulation. In comparing basal conditions with normal subjects of the same age, patients with arteriosclerosis obliterans exhibited a significant decrease in arterial compliance (p less than 0.01) and heart rate (p less than 0.02) with a significant increase in systolic pressure (p less than 0.001). Diastolic drainage was increased (p less than 0.01) and was positively correlated with diastolic time (r = 0.73, p less than 0.001). Diastolic blood flow remained within normal ranges (52 +/- 2 vs 49 +/- 3 ml/m2/sec). After acute propranolol intravenous administration, heart rate and stroke volume decreased (p less than 0.001), while total peripheral resistance increased (p less than 0.001). Systemic arterial compliance and diastolic blood flow significantly decreased (p less than 0.01). The study provided evidence that in patients with arteriosclerosis obliterans, the diastolic blood flow was maintained in basal conditions despite the observed reduction in arterial compliance, and that intravenous propranolol administration decreased systemic arterial compliance and diastolic blood flow.

Adult↗

Successful therapy of advanced arteriosclerosis obliterans with prostacyclin.

Five patients with advanced arteriosclerosis obliterans of the lower extremities, as evidenced by resting pain, ischaemic ulcers, and focal necrosis, received intra-arterial infusions of prostacyclin at doses of 5--10 ng/kg/min for 72 h. Within 2 days of termination of the infusion, pain at rest had disappeared in all patients. In three of the five, the necrosis had completely regressed and the ischaemic ulcers healed within 2 months. The other two patients showed considerable improvement. Prostacyclin therapy was not associated with changes in the radiographic appearance of the major blood-vessels. However, muscle blood-flow, as measured by xenon-133 clearance, was significantly increased both during prostacyclin infusion and for the 6 weeks of measurement after its termination.

Aged↗

Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities.

Treatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 micro g/day) for 5 consecutive days. On day 5, PBSCs were collected, sorted from blood circulation of patients, and then intramuscularly injected into their ischemic lower limbs. A significant improvement of clinical manifestations including severe pain, skin temperature and ulcer, was observed, without obvious adverse effect. The patient's limb was successfully saved. Satisfactory remission was obtained 3 months after transplantation as shown by significant improvement in ankle-brachial pressure index (ABI), blood flow in personal vascular laboratory (PVL), laser Doppler blood perfusion, and the angio-graphic scores. Our data suggest for the first time that autologous transplantation of mobilized PBSCs provides a practical, safe, and effective method of treatment for lower limb ischemia.

Aged↗

Beneficial results of pentoxifylline ('Trental') therapy in arteriosclerosis obliterans: possible mechanism of action.

A study was carried out in 17 patients with arteriosclerosis obliterans to assess the effectiveness of treatment with pentoxifylline ('Trental') and to investigate its possible mechanism of action. Patients received pentoxifylline on a combined intravenous/oral dosage regimen for 3 weeks and then were maintained on 800 mg orally for a further 2 weeks. The results showed that there was clinical improvement in 16 patients which was evident as a significant increase in the pain-free walking distance and blood flow in ischaemic legs, and the disappearance of rest pain. These changes were seen as soon as 1 week after the start of treatment. At the same time, an increase was observed in platelet sensitivity to the anti-aggregatory action of endogenous PGI2, as well as an activation of fibrinolysis in blood. After 5 weeks of treatment, further improvement was observed; however, platelets were no more hypersensitive to PGI2, and fibrinolytic activity of blood returned to the previous value. In experiments ex vivo, no release of a disaggregatory substance into blood was observed after a single bolus intravenous injection of pentoxifylline in patients with arteriosclerosis obliterans. It is concluded that the beneficial results of pentoxifylline therapy in such patients may be explained partially by a potentiation of the action of endogenous PGI2.

Adenosine Diphosphate↗

Percutaneous transluminal angioplasty against arteriosclerosis obliterans in dialysis patients.

The incidence of peripheral arteriosclerosis is on the increase in chronic hemodialysis patients. Recently, the intervention (IV) treatment is conducted to deal with this problem. IV was performed in 4 dialysis patients against the complication of arteriosclerosis obliterans (ASO) but the result was unsuccessful in 3 of them. These 3 failure cases were investigated to find the problems associated with percutaneous transluminal angioplasty (PTA). Cases 1, 2 and 3 had intermittent claudication while case 4 had gangrenous toes as the major complaint. The symptoms in these cases were attributable to 90-100% stenosis and occlusion of superficial femoral artery, bilateral iliac arteries, bilateral superficial femoral-popliteal artery, branch of right iliac artery and left iliac artery region, respectively. IV was successful in case 1 but failed in cases 2 and 4 because the catheter itself did not go through due to the severe stenosis of vessel or the procedure of forcefully dilating the vessel caused dispersion of minute thrombi. In case 3, acute myocardial infarction occurred at 10 h after successful IV, resulting in sudden death. In view of the extent of invasion, IV is a treatment method selected against ASO in dialysis patients. However, the method has a high risk of causing thrombus formation, vessel rupture and organ failure. In this regard, it is advisable to evaluate the systemic condition and conduct IV if the extent of stenosis is mild.

Aged↗