Claudication Time Research Articles

Ciprostene in patients with peripheral vascular disease (PVD). An open-label, tolerance trial

Epoprostenol (Prostacyclin) has been studied with various success in patients with peripheral vascular disease (PVD). We investigated the tolerance of a new, stable prostacyclin derivative ciprostene (9-beta-methyl carbacyclin) in 9 PVD patients. The drug was infused intravenously for 8 hours a day, once a week for 4 consecutive weeks, at a dose of 120 ng/kg/min. There were 6 men and 3 women with a mean age of 63 years (42–78). The PVD was verified by arteriography (9 patients) and by clinical findings. Patient #9 was lost to follow up after the first infusion and, consequently, was excluded from further evaluation. In patient #5 with a history of arrhythmias, the last ciprostene infusion had to be discontinued at 4.5 hours due to arrhythmias but his data were included into the evaluation. The cardiac disturbances were not judged to be ciprostene-related. Patients were followed monthly for 3 months after last infusion. Ciprostene was well tolerated although it produced adverse medical events (AMEs); most of them were rated as mild. The most frequent were those typical of prostacyclin: headache, facial flushing and warmth, body warmth, jaw pain and sleepiness. No consistent changes in blood pressure and heart rate were observed. One paitent who initially had 9 ischemic ulcers underwent transmetatarsal amputation at month 4. The absolute and relative claudication time was measured by treadmill. As compared to baseline, the absolute claudication time increased significantly at week 3 and 4 of the infusion period and also at the end of month 3, but not at the end of month 4. There was a tendency for relative claudication to improve also and a significant increase was achieved at week 3. Two patients had rest pain at the beginning of the study and both of them reported improvement of this symptom during the study. No changes in ankle/brachial index from baseline were observed. Seven out of 8 patients felt that ciprostene increased their walking time and decreased their symptoms; 7 of them requested additional treatment with ciprostene. These data warrant conduct of a placebo-controlled, double-blind trial with ciprostene in PVD patients.

Effects of venesection on leg blood flow in claudicants with high-normal haematocrit.

Patients with intermittent claudication frequently have high-normal levels of haematocrit and hence blood viscosity, which may contribute to decreased calf blood flow on exercise, and hence to the symptom of claudication. Reduction in haematocrit and viscosity by serial venesection in eight patients with stable claudication and high-normal haematocrit (mean 0.50) was performed, and the effects on claudication, calf blood flow, and calf oxygen delivery were studied. Following reduction in haematocrit to low-normal levels (mean 0.44), resting calf blood flow was unchanged; peak flow after ischaemic exercise increased slightly (+17%), but peak oxygen delivery (peak flow X haemoglobin concentration) was unchanged. Hence any increase in calf blood flow in the symptomatic leg is balanced by a decrease in oxygen-carrying capacity after venesection. No increase in claudication time would therefore be expected, and none was observed in the present study.

Clinical pharmacologic evaluation of the antiatherosclerotic agent, pyridinolcarbamate. A double-blind crossover trial in the treatment of atherosclerosis obliterans

The antiatherosclerotic effect of pyridinolcarbamate in man has been subjected to the present controlled clinical trial in 43 patients suffering from atherosclerosis obliterans with relatively stable signs and short claudication times (101 ± 8 sec.). To isolate individual factors such as age, sex, constitution, social condition, and spontaneous fluctuations of symptoms from the drug effect, a double-blind crossover technique (within-subject comparison) has been applied. After the initial 3 weeks of placebo wash out, a 10 week regimen of placebo or pyridinolcarbamate (1.5 Gm. daily) and another 10 weeks of alternative regimens were given successively. After drug regimen the prolonged crest time in plethysmography was shortened (p < 0.01) and claudication time prolonged with a statistically significant correlation (p < 0.05). The statistically significant preference for pyridinolcarbamate over placebo has been established by the effect on crest time alone, claudication time alone, and also major symptoms including ischemic ulcer, cyanosis, pain, and paresthesia of affected legs (p < 0.001). The relatively slow-acting and persistent effect of pyridinolcarbamate on the clinical signs observed in these patients encourages further histologic analysis of its effect on atheromatous lesions in man.

Controlled ergometric studies of effect of heparin on intermittent claudication.

Clinical experience has demonstrated the need for an accurate method for the determination of claudication time.^*The subjective report of the patient with intermittent claudication is frequently extremely variable and has proved unsatisfactory for the evaluation of therapy in occlusive vascular disease. The time of onset of claudication pain may be influenced by the rate of walking,¹the gradient of the incline on which the walking is done, and psychological factors. Patients frequently report variations in claudication time apparently related to environmental temperature or humidity. Interest in this subject was renewed following the report of Graham and co-workers,²later confirmed by Engelberg,³suggesting that intermittent heparin administration resulted in relief of angina pectoris in patients with coronary arteriosclerosis. Recognizing the difficulty in evaluating the effect of any treatment for angina as well as the basic similarity of angina and claudication,⁴we have endeavored to determine objectively

Deproteinated pancreatic extract (depropanex): 1. Effect in the treatment of intermittent claudication due to arteriosclerosis obliterans

(1) We have described an apparatus to measure claudication time. (2) Following one injection of deproteinated pancreatic extract, twenty-three of a series of twenty-seven patients with arteriosclerosis obliterans showed an improvement (prolongation) of their claudication time. This initial response was in most instances temporary. (3) Following ten or more injections of deproteinated pancreatic extract, nineteen patients showed improvement in their claudication time. (4) After a series of ten or more treatments, the claudication time was, in this series, prolonged to an average of more than three times that of the control tests. (5) Physiologic saline failed to produce an increase in claudication time under identical conditions (6) Further studies will be necessary to determine the extent to which improvement may be advanced, and the duration of the favorable effects after cessation of the treatment.