[Use of prolonged-release nicotinic acid in patients treated with statins as a secondary prevention and a persistently low HDL-cholesterol level in France]. / Etude d'utilisation de l'acide nicotinique a libération prolongée en France chez des patients en prévention secondaire sous statine avec persistance d'un taux bas de HDL-c.

UNLABELLED: HDL-c is a potent predictor of cardiovascular risk in all epidemiologic studies, especially as secondary prevention, regardless of LDL-c level obtained on statin treatment. The objective of this longitudinal observational study was to investigate the effects of prolonged-release nicotinic acid in high cardiovascular risk patients on statin treatment and with low HDL-c. METHOD: The selected patients of both genders, aged over 18 years patients showed primary hypercholesterolemia or mixed hyperlipidemia, received statin treatment as secondary prevention and had a HDL-c level

Analysis of ambulatory heart failure management and its incidence on one-year survival.

AIM: To assess in a daily practice survey one-year survival in a cohort of patients with heart failure (HF) according to their clinical profiles and the way they were managed by cardiologists. METHODS AND RESULTS: A prospective observational survey was conducted in 1941 patients with HF followed up for one year. Results show high rates of prescription for ACE inhibitors, indicating that cardiologists take into account international recommendations. ACE inhibitors are prescribed at dosage levels approaching those recommended by the guidelines. However, beta-blocker prescription still shows a significant deficit and the prescribed doses are much lower than those currently recommended. The multifactorial modeling analysis showed that global heart failure (P=0.004), advanced NYHA class (P<0.001), renal failure (P<0.001) were predictive of poor outcome whereas an increased survival likelihood was observed in patients given ACE-inhibitor/beta-blocker combination compared with beta-blocker alone or ACE-inhibitor alone. CONCLUSION: The results from this study should enhance the prescription of ACE inhibitors and beta-blockers at effective doses in compliance with the guidelines. They also suggest that a synergic positive effect of the combination of these two therapeutic classes is observed in real life situations.

[First-intent monotherapy: persistence rate of antihypertensive treatment is better with angiotensin receptor blockers. Ol'métrise Cardio survey results]. / Monothérapie de première intention: le traitement antihypertenseur est plus souvent poursuivi, seul ou combiné, quand il s'agit d'un ARA II. Enquête Ol'métrise Cardio.

OBJECTIVES: To describe, according to the type of first-line antihypertensive monotherapy (FLAM) the persistence rate and the cumulative probability of its potential given up to the advantage of another antihypertensive class (rotation) in the following 3 years. METHODS: retrospective survey (to avoid any "survey effect" undertaken by 551 French cardiologists, in treated hypertensive patients. The survey described the FLAM, patients characteristics when FLAM was introduced, when given up in case of rotation and at the inclusion visit, as well as the dates of introduction, rotation and visit. STATISTICAL ANALYSIS: Kaplan Meier's method, Cox model. RESULTS: One thousand nine hundred and fifty five patients (62 +/- 11 years, males 57%, diabetes 13%, coronary disease 11%, LVH 20%) were analysed. At the end of 2.1 +/- 0.7 years, 1407 patients (72%) continued the FLAM alone (N=738, 52%) or combined (N=669, 48%). Survival analysis shows i) that the probability of rotation is roughly constant over time whatever the FLAM ii) that the probability of rotation against time is different according to the FLAM (p<0.0001, log rank) and lesser with ARB. These results are confirmed by the multivariate analysis (Cox model adjusted on age, sex and comorbidities).

[Evolution of secondary prevention medication prescriptions after myocardial revascularisation: the ANCOR survey]. / Evolution de la prescription de prévention secondaire chez les coronariens après revascularisation: enquête ANCOR (analyse nationale de la prise en charge de la maladie coronaire avant et après revascularisation).

The ANCOR survey was designed to assess the evolution of the prescription of secondary prevention medications in patients undergoing myocardial revascularisation, from the preoperative period to 3-6 months post-procedure. A total of 1535 patients (mean age: 64 years, 79% men), 321 after coronary surgery and 1214 after percutaneous coronary intervention, were included. Of them 37% still described anginal symptoms (Canadian class 1 in 80% of them); 38% still had elevated blood pressure (> or = 140 mm HG systolic and/or > or = 90 mmHg diastolic) and 27% of previous smokers still smoked after the procedure. All classes of secondary prevention medications were more often prescribed after than before intervention, antiplatelet agents (63.5 to 89%), beta-blockers (53 to 73.5%), statins (51 to 3%), ACE inhibitors (27 to 39%) and nicorandil (14 to 21%). Factors associated with the prescription of the different classes of medications were both expected (such as hypertension for ACE inhibitors or statins in hyperlipidemic patients) or unsupported by scientific evidence (less beta-blockers in diabetic patients). Overall this survey shows that myocardial revascularisation constitutes a key point in the management of patients with coronary disease, and that cardiologists consider that treatment of the atherosclerotic process is as important as the treatment of focal coronary artery stenoses.

[Factors predicting blood pressure normalization in hypertensive patients treated with a fixed-dose combination of bisoprolol 2.5 mg/hydrochlorothiazide/6.25 mg]. / Facteurs de prédiction d'une normalisation de la pression artérielle chez des hypertendus traités par la combinaison fixe bisoprolol 2,5 mg/hydrochlorothiazide 6,25 mg.

It is not clear which duration of treatment is needed to achieve complete efficacy with fixed low dose antihypertensive therapy. The aim of this study was to compare blood pressure control rate in patients treated with bisoprolol 2.5 mg/HCTZ 6.25 mg, not controlled after 4 weeks, but treated at the same dosage for one more month to patients not controlled after 4 weeks, and uptitrated to bisoprolol 5 mg/HCTZ 6.25 mg for one month. The 641 patients who entered the study had a mean age of 58 +/- 12 with SBP/DBP at baseline of 165 +/- 12/96 +/- 7 mmHg. After 4 weeks, 252 (39%) where normalized (< 140/90) with SBP/DBP reductions of -27/-15 mmHg. In uncontrolled patients, 19% of those randomized to B 2.5 mg/H 6.25 mg and 33% of those treated with B 5 mg/H 6.25 mg where normalized at the end of the study (p < 0.001). Multivariate analysis indicates determinants of blood pressure normalisation after 4 weeks with B2.5 mg/HCTZ 6.25 mg as female gender, initial BP < 175/105 mmHg, previously untreated hypertension, age < 50 years. In conclusion, when the initial therapy with bisoprolol 2.5 mg/HCTZ 6.25 mg is not sufficient to control blood pressure, continuation with the same dosage 4 weeks longer increases the rate of blood pressure control. However, up-titration to bisoprolol 5 mg/6.25 mg is more efficacious to increase the number of patients with a final blood pressure < 140/90 mmHg.

Naftidrofuryl-driven regulation of endothelial ICAM-1 involves nitric oxide.

Naftidrofuryl is a selective inhibitor of the 5-HT2 receptor expressed on human endothelial cells. This drug has been used over the years to cope with cerebral or peripheral ischemic accidents; however, no clear mechanism of action of this molecule has been highlighted to explain its vascular effects. In the present work, we demonstrate that the involvement of nitric oxide can account for the effects of naftidrofuryl. Indeed, naftidrofuryl potently inhibited the TNF-alpha-triggered increase of intercellular adhesion molecule-1 (ICAM-1) expression as well as stress fiber formation in human umbilical vein endothelial cells (HUVEC). Moreover, naftidrofuryl induced the expression of type II nitric oxide synthase (NOS II) messenger and protein, leading to a noticeable increase in nitric oxide synthesis. Furthermore, using the specific NOS II inhibitor 1400W, we verified that the observed effects of naftidrofuryl were NOS II-dependent. The biology of nitric oxide accounts for the reduction of the vasospasm associated with stroke and the strong inhibition of platelet aggregation. In conclusion, our work provides evidence for the inhibition of leukocyte recruitment by downregulation of CD54/ICAM-1, an additional key factor to be dealt with during thrombotic accidents. Importantly, it also highlights a novel NOS II-dependent mechanism of action for naftidrofuryl.

[Effect of naftidrofuryl on physiological walking distance in patients with intermittent claudication]. / Effet du naftidrofuryl sur la distance de marche physiologique chez des patients au stade de claudication intermittente.

PURPOSE: To evaluate the physiological walking distance measured with the Peripheral Arterial Disease Holter Control device (PADHOC) after 12 months of treatment with naftidrofuryl in a double blind placebo controlled, parallel group study, in patients presenting with intermittent claudication. MATERIAL AND METHODS: The outpatients selected were of both sexes, aged 40 to 80, with a chronic, stable intermittent claudication and an ankle brachial index between 0.60 and 0.90. They received naftidrofuryl 200 mg tid or placebo for 12 months. Outcome measures included physiological painfree and maximal walking distances using the PADHOC device. The principle of this device is the measurement of the intermalleolar distances using ultrasound telemetry. The PADHOC measures the walking distance and the speed profile in an ambulatory subject. RESULTS: 182 patients were randomised and 168 entered the intention to treat analysis. The two groups were well matched for demographic variables, risk factors and history of vascular disease. After 12-month treatment, patients who received naftidrofuryl had a 107% improvement of geometric physiological pain-free walking distance versus 12% in the placebo group (P < 0.001) and 74% improvement of geometric maximal physiological walking distance versus 1% in the placebo group (P < 0.001). CONCLUSION: This study demonstrates the efficacy of naftidrofuryl versus placebo in patients with intermittent claudication using a new device measuring the walking distances of the patients in a more physiological way than the treadmill test.

[Deleterious cardiac effects of serotonin in myocardial ischemia: role of naftidrofuryl]. / Analyse des effets délétères cardiaques de la sérotonine lors de l'ischémie myocardique: place du naftidrofuryl.

It is now accepted that serotonin can either initiate or aggravate myocardial ischaemia through a vasoconstrictor action and platelet activation. It is therefore possible that substances likely to neutralize the effects of serotonin could be used, without any danger, in humans with ischaemic heart disease. This type of action may therefore be exerted by 5-HT2 antagonists, such as naftidrofuryl. A recent double-blind clinical study has in fact shown that administration of naftidrofuryl versus placebo leads to better exercise tolerance, with an increase in the maximum level and delay in ST segment shift (increase in the threshold of onset of ischaemia). The purpose of this study was therefore to evaluate, in an animal model (pig) of acute myocardial ischaemia (occlusion of the proximal section of the left anterior descending coronary artery), the action of serotonin, naftidrofuryl and a combination of both substances on the following parameters: 1) electrophysiological (sinus heart rate, ST segment shift, T-wave amplitude, duration of monophasic action potentials, intraventricular conduction time); 2) haemodynamic (systolic, diastolic and mean blood pressure, first derivative of rate of increase of left ventricular pressure with time: LV dP/dt max); and 3) biochemical (malonedialdehyde concentration as an index, cell peroxidation index, creatine phosphate and adenosine triphosphate). It was found that co-infusion of serotonin aggravated the myocardial ischemia and that naftidrofuryl exerted beneficial effects on the serotonin-mediated aggravation of myocardial ischaemia.

Effect of naftidrofuryl on platelet aggregation in plasma from aspirin treated patients: an in vitro study.

This study concerns an in vitro evaluation of the effect of naftidrofuryl on platelet aggregation in plasma of 15 diabetic patients, who were being treated with aspirin, and who were suffering from chronic arterial disease of the lower limbs. Platelet aggregation, induced either spontaneously or by aggregating agents, was measured in platelet-rich plasma (PRP). The results show that serotonin (5-HT)- and adenosine 5'-diphosphate (ADP)-induced platelet aggregation significantly decreased after addition of naftidrofuryl. Decreases were achieved with naftidrofuryl at a low dose (0.06 microM) and became more marked with naftidrofuryl at higher concentrations. In contrast, naftidrofuryl did not appear to modify routinely spontaneous platelet aggregation. These results show an in vitro antiaggregating effect of naftidrofuryl on platelets of aspirinized patients. However, the clinical interest of a such coadministration of naftidrofuryl and aspirin in patients, has still to be confirmed in a double blind randomized trial.

Efficacy of naftidrofuryl in patients with vascular or mixed dementia: results of a multicenter, double-blind trial.

BACKGROUND: Dementia is a cerebral disorder resulting in a progressive deterioration of intellectual function that compromises the patient's ability to function. The diagnostic criteria for dementia are primarily clinical and are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Hachinski score and computed tomography of the brain help distinguish between degenerative and vascular dementias. OBJECTIVE: This study examined the efficacy of naftidrofuryl in patients with vascular or mixed dementia. METHODS: This multicenter, randomized, double-blind study compared naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed dementia. A preliminary 2-month washout period allowed selection of patients who were compliant with treatment. The end point was change in the scores on the Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State Examination. RESULTS: Eighty-four patients were assessable on an intent-to-treat basis, and 74 were assessable for the per-protocol analysis (on-treatment). Statistically significant improvements in cognitive and global function were observed in patients receiving naftidrofuryl. Naftidrofuryl was well tolerated, and produced no clinically significant abnormalities in laboratory test results. CONCLUSION: The results of this study suggest that naftidrofuryl is effective and well tolerated in treating the symptoms of vascular and mixed dementia.

[Survey on adherence to hygiene and dietary rules in patients with arterial occlusive disease]. / Enquête sur les conditions de suivi des règles hygiéno-diététiques chez l'artériopathe.

OBJECTIVE: Chronic arterial occlusive disease of the lower limbs, a common (800,000 patients in France) invalidating condition, can involve one or more arterial territories. In 90% of the cases, it is related to a more general disease, atherosclerosis. The risk factors are the same as for atherosclerosis and can be classed into three distinct groups: pathological conditions, constitutional characteristics, and lifestyle. Besides age and gender, smoking habits are by far the most predominant vascular risk factor for chronic arterial occlusive disease. Other factors include diabetes, known to play a particular role in diabetic arteriopathy, generally with more distal and quite severe lesions, high blood pressure, a less evident but certain risk factor, and hyperlipidemia, whole role in the pathogenesis of chronic arterial occlusive disease is well recognized though not predominant. These different data led us to analyze a cohort of patients with chronic arterial occlusive disease of the lower limbs to ascertain the cause of success or failure of hygiene and diet counseling. PATIENTS AND METHODS: The study protocol included three steps. We first established the profile of a typical arteriopathy patient based on demographic data, history of the arterial disease, personal and familial medical history and lifestyle: smoking habits, physical exercise, diet. The second step was to estimate the proportion of patients following hygiene and dietary rules. Finally, we looked for the reasons why the patients succeeded or failed in following these rules. This cross-sectional study involved 1,500 practitioners. Each physician selected 3 patients, men or women aged 40 to 80 years whose arteriopathy had reached the stage of intermittent claudication. Evaluation criteria were based on the demographic data and conditions of adherence to advice as well as conditions leading to success or failure: personal motivation, familial support, the patient's knowledge of the disease, its pathophysiological mechanisms, and the way the risk factors contribute to its genesis and aggravation. RESULTS: The sex ratio of the 3,294 recruited patients was 4.3 (2,672 men and 622 women). Disease duration and walking distance were 8.6 +/- 6 years and 418 +/- 297 meters respectively. Thirty-eight percent of the patients had undergone surgery of the lower limbs. One thousand four hundred ninety-four patients (45%) had undergone surgery for their arterial disease (lower limbs, coronary or cerebral arteries). Forty-nine percent were aware of the risk of amputation. Overall adherence to drug therapy was good for 82% of the patients. Patients were treated basically with vasoactive and platelet antiaggregates (95 and 82% of the patients respectively). Seventy-nine percent of the patients were former smokers (38% continued to smoke). Fifty-six percent had a specific regular physical activity compared with 42% prior to their disease. Seventeen percent of the patients had already tried a Mediterranean type diet (with a success rate of 69%). Among the 3, 294 patients, 950 (28.8%) followed hygiene and dietary rules well. The main reasons and/or conditions differentiating those who were successful and those who were not were, for each item: personal motivation, family support, and perception of the influence of lifestyle on disease course. These differences were highly significant (p <0.001). CONCLUSION: Considering the importance of following good hygiene and dietary rules for secondary prevention of chronic arterial occlusive disease of the lower limbs, it was interesting to assess with precision the percentage of diseased patients who follow such rules. Only about 30% of the patients were successful in correcting all behaviors.

[Assessment of the prevalence of atherosclerotic lower limb arteriopathy in France as a systolic index in a vascular risk population]. / Appréciation de la prévalence de l'artériopathie oblitérante des membres inférieurs en France à l'aide de l'index systolique dans une population à risque vasculaire.

OBJECTIVE: Obliterative arteriopathy of the lower limbs is a severe disease. History taking often underestimates prevalence. In studies using the Rose questionnaire and examining the prevalence of symptomatic arteriopathy defined by the presence of intermittent claudication, prevalence has been rather constant, around 2% in the general population in industrialized countries. A more clinical approach searching for physical anomalies (absence of distal pulse) generally gives higher rates. The most recent data led us to conduct a study focusing on screening for arterial disease using the systolic index (the systolic index is the ratio between the ankle and humeral systolic pressure). A systolic index below 0.90 would be a sign of defective perfusion, increasing in severity with poorly compensated arterial lesions. METHOD: A survey was performed in a random sample of 150 practitioners using an allocation procedure to the nearest colleague in case of refusal. A data sheet containing demographic data and the main risk factors was established for each consulting patient aged from 40 to 80 years. The systolic index was measured in each patient with at least one vascular risk or who consulted for pain in the lower limbs. A simple sequential non-randomized patient recruitment scheme was used. RESULTS: The survey population included nearly 9,000 patients (8,987), 46% men and 54% women, mean age 64 years (table I). Patient risk factors including smoking, diabetes, hypertension, and physical exercise were adjusted for sex and age (table II-VI, IX). The systolic index was recorded in 41% of the population who had a vascular risk factor. Among these patients, nearly one-fourth had a systolic index under 0.90, giving a prevalence in the sample population of 11% (table VII). This rate was also assessed by age and sex (table VIII). Logistic regression evidenced a prognostic value (fig. 1) for smoking, hypertension and sedentary activity, and to a lesser extent, for age and sex. There was a significant difference by latitude, patients living in northern France having a higher risk than those living in southern France (table X). In addition, there was a relationship between the systolic index and spontaneous complaint, showing that this complaint is poorly specific for arterial disease (table XI, XII). CONCLUSION: This epidemiological approach to arteriopathy implemented by general practitioners searching for patients with a vascular profile and measuring systolic index is a novel method. It gave an estimation of prevalence at 11% in the French population, a rate compatible with that reported by other international teams. The method also allowed an analysis of factors affecting the rate.

[Evaluation of the efficacy and tolerance of naftidrofuryl in patients presenting with exertional angina. Multicenter double-blind versus placebo study]. / Evaluation de l'efficacité et tolérance du naftidrofuryl chez des patients présentant un angor d'effort. Etude multicentrique double-aveugle versus placebo.

Due to its vascular and platelet 5-HT2 receptor antagonist properties and its metabolic properties, naftidrofuryl specifically counteracts local ischaemic phenomena. One of its major indications is the treatment of intermittent claudication, but it is well known that peripheral arterial disease is the sign of diffuse arterial disease, associated with particularly lethal coronary disease. Recent studies increasingly implicate serotonin (5-HT) in coronary ischaemic processes. In view of the similarities between these pathophysiological data and the characteristics of this molecule, we decide to evaluate the coronary protection afforded by naftidrofuryl and its safety. This multicentre double-blind placebo-controlled study was conducted in 51 patients over a period of one month. Inclusion criteria were stable angina with an electrically positive stress test, despite antianginal treatment either by beta-blocker or by calcium channel blocker. Follow-up comprised clinical assessment and a stress test on inclusion and at 1 month. The groups were comparable on inclusion. Overall, the results showed a greater improvement with naftidrofuryl than with reference treatment for all parameters studied. Significant differences were observed in favour of the verum group for time to onset of ST depression, the maximum level reached, the number of stress tests which became negative and the patient's global assessment. No problems of interaction with concomitant treatments, particularly beta-blockers, calcium channel blockers or antiarrhythmics was observed. This study shows that naftidrofuryl allows improvement of ergometric parameters and especially elevation of the ischaemic threshold on exertion.

Protection against light-induced retinal degeneration with naftidrofuryl (Praxilene) in the rat.

The purpose of this work was to investigate the ability of Naftidrofuryl (Praxilene, Lipha-Santé, France) to produce light-induced retinal degeneration in the rat. Fisher male rats were injected intraperitoneally with 30 mg/kg Naftidrofuryl in 0.9% NaCl. The first injection took place 30 minutes before the beginning of the constant light exposure (90 fc) and was repeated at days 2 and 4. The animals were sacrificed at day 7. Controls treated or not with Naftidrofuryl were exposed to a regular cyclic light environment (20 fc). Eyes were fixed in 4% paraformaldehyde and embedded in Historesin. Whole median 5 microns sections of the retina were analyzed by measurement of the thickness of the retinal photoreceptor nuclear and inner and outer segment layers with a Biocom image analyzer. After one week of constant illumination, the photoreceptor nuclear layer thickness decreased in all regions of the retina, more in the superior than in the inferior region. In animals treated with Naftidrofuryl, a significant rescue from degeneration was observed throughout all retinal regions. An average rescue of 66% (compared with the retina from constantly illuminated rats) was observed. Naftidrofuryl had no effect on cyclic light-raised rats. Naftidrofuryl partially protects against the degeneration of photoreceptors induced by constant light illumination of the rat retina.

[Evaluation of the analgesic effect of naftidrofuryl in permanent ischemia in patients with arterial diseases. Double-blind versus placebo study]. / Evaluation de l'effet antalgique du naftidrofuryl dans l'ischémie permanente chez l'artériopathe. Etude double-aveugle contre placebo.

Ischemic rest pain, with or without trophic disorders and occurring very frequently at night, is responsible for insomnia and complications such as positional oedema. The pathophysiological mechanisms underlying the analgesic effect of naftidrofuryl led us to evaluate the efficacy of this treatment. 37 selected patients were given 2 daily infusions of 400 mg of naftidrofuryl for 8 days, under double-blind conditions. Evaluation criteria were pain assessment using a visual analogue scale, analgesic consumption considering both the power (WHO scale: level I paracetamol, level II dextropropoxyphene, level III morphine) and the dosage of the analgesic used (analgesic score), index of therapeutic success including the level of pain reduction and the absence of analgesic use. The results showed a significant difference in favour of naftidrofuryl for: reduction of pain, difference in the course of the analgesic score, the distribution of the population according to the index of therapeutic success. Three patients discontinued treatment due to inefficacy, but all 3 belonged to the placebo group. This study demonstrates the benefit of naftidrofuryl in pain reduction which was assessed, in particular, by the reduction of analgesic consumption.

Experimental and clinical study of the effect of naftidrofuryl on the recovery from peripheral nerve lesions.

After primary repair of lesions of nerves and vessels, patients who were administered a vasoactive drug, naftidrofuryl, postoperatively, had a better functional recovery than untreated patients. Evidence for the favourable effect of the drug on nerve regeneration was first obtained from experiments in the rat. The sciatic nerve was transected and repaired with standard microsurgical techniques. Results were evaluated by electromyography and histology. Data indicated that treated animals had better motor responses and distal latency than untreated rats. Fibre counts showed a greater number of nerve fibres in the distal stump of treated animals. The clinical study was undertaken in cases of carpal tunnel syndrome with muscle atrophy. Assessment was performed by electrophysiology: motor and sensory conduction was studied. Data showed that all treated patients recovered totally or partially from the thenar atrophy they presented before operation, whereas thenar atrophy persisted in 37% of the patients receiving placebo. In conclusion, naftidrofuryl has an experimentally and clinically favourable effect on nerve regeneration and on muscle trophicity, but the mechanism of action of this drug is not known.

The introduction of economic criteria into the management of arterial disease: an illustration with regard to the socioeconomic consequences of peripheral occlusive arterial disease of the lower limbs.

A survey of studies was used to investigate the economic repercussions of arterial disease; these repercussions included the cost of the disease and its management, and cost/efficacy, cost/utility, and cost/benefit studies of preventive, diagnostic, and therapeutic strategies. The study presented is an evaluation of the socio-economic consequences of peripheral occlusive arterial disease of the lower limbs (POADLL). The cost of health care was measured by means of a prospective 6-month study of 85 patients recruited in 6 centers. The average cost over the 6-month period was 15,735 FF (1991 francs) ($2,760 U.S.). The 85 patients were classified by age, sex, risk factors, concomitant disease, and how the illness was managed, notably in terms of hospitalization and vascular surgery. The four-group classification was used to calculate an annual management cost for POADLL, which ranged from 9,500 FF ($1,667 U.S.) for a stage II patient (mean age, 66 years) with no major risk factors and not presenting any complication requiring admission to hospital, to 35,000 FF ($6,140 U.S.) for patients (mean age, 62 years) who presented major risk factors and who required vascular surgery during the year.

[Histochemical quantification of muscular ischemia: effect of treatment with naftidrofuryl]. / Quantification histochimique l'ischémie musculaire: effets d'un traitement par le naftidrofuryl.

Evaluation of degree of muscle ischemia of a limb and its reversibility is a poorly resolved practical problem, and it has not been clarified whether vasodilatory and circulatory spasmolytic substances possess, in addition to an effect of increasing irrigation, any direct action on muscle cell energy metabolism. An experimental study used histochemical techniques to evaluate oxidative enzyme activity of tissues. The compound tetrazolium nitro-blue (NBT), when reduced by tissue dehydrogenases, has the property of producing a dense non-crystalline blue pigment designated "formazan". During muscle ischemia, the time of appearance of this reaction increases with degree of ischemia through the bias of the decrease or disappearance of succinate-dehydrogenases. Transient ischemia of hindpaw, over 3, 6, 9, 12, 15 and 18 hours, was provoked by tourniquet in 49 rats treated with a vasodilator (naftidrofuryl) and 21 untreated (control) rats. Spontaneous revascularization occurred after removal of the tourniquet. Muscles were studied by microsurgical removal of specimens on removal of tourniquet and 1 and 12 hours and 3, 7 and 14 days after its removal (fig. 1 and 2). Times for staining of muscles with tetrazolium were measured and curves of comparative times established (fig. 3 and 4). Histopathologic specimens were also obtained at the same periods (fig. 5, 6, 7). Results of histochemical studies with tetrazolium and with quantitative determination of degree of cellular anoxia showed the action of naftidrofuryl to be related to mitochondrial metabolism of skeletal muscle, specifically for succinate-dehydrogenase. Clinical application in the determination of therapy and of functional prognosis of an ischemic limb is a possibility by the use of the NBT test in vascular surgery.

tcpO2, arterial blood flow and lactate/pyruvate modifications induced by a single dose of naftidrofuryl IV during stage III lower-limb arteriopathies.

A single dose of 600 mg of naftidrofuryl perfused IV during three hours in 12 stage III arteriopathic patients did not modify the average blood flow at the calf but did significantly increase transcutaneous oxygen pressure (33 vs 52 mmHg) and also improved lactates (1.44 vs 0.88 mmol/liter), pyruvate (59 vs 79 mumol/liter), and lactates-pyruvates ratio (33.48 vs 20.92).