Jean-Louis Saumet

Transcutaneous Oxygen Pressure Measurements on the Buttocks During Exercise to Detect Proximal Arterial Ischemia Comparison With Arteriography

Background—We sought to identify whether transcutaneous oxygen tension (tcPo2) measurements could be used to noninvasively detect lesions in the arterial network supplying blood flow to the hypogastric circulation. Methods and Results—A study was undertaken in vascular patients with suspected (PC, n=43) and not with suspected (NPC, n=34) proximal ischemia. TcPo2 was measured on both buttocks and with a chest reference electrode. Arteriography on the right or left side was positive for stenoses (≥75%) or occlusion of one or more of the following arteries: the aorta, the common iliac arteries, or the internal iliac arteries. The arteriography was compared with the resting tcPo2 values (REST) and with the minimal value (MIN) and maximal change from rest normalized to eventual chest changes (DROP) recorded during or after a treadmill test. REST, MIN, and DROP were, respectively, as follows in positive versus negative arteriograms (mean±SD; in mm Hg): 80.2±10.9 versus 78.6±11.5 (P >0.05), 55.2±20.0 versus 69.9±15.8 (P <0.001), and −31.8±17.6 versus −9.5±6.4 (P <0.0001) in PC and 78.9±14.0 versus 80.5±14.3 (P >0.05), 64.4±21.0 versus 75.1±14.6 (P <0.02), and −24.1±13.5 versus −8.7±4.8 (P <0.0001) in NPC. In PC and NPC respectively, with a cutoff point of −16 and −15 mm Hg, DROP showed, respectively, 83%/82% and 79%/86% sensitivity/specificity in the diagnosis of positive arteriograms. Conclusions—Proximal ischemia is a frequent finding in vascular patients. TcPo2 measurement on the buttocks during exercise is a sensitive and specific indicator for lesions in the arterial tree toward the hypogastric circulation. Potentially it could objectively assess the response to endovascular or surgical approaches to iliac lesions.

Non-nociceptive capsaicin-sensitive nerve terminal stimulation allows for an original vasodilatory reflex in the human skin

A significant increase of cutaneous laser Doppler flowmetry was found before blood flow decreases with increasing pressure during a 5 mmHg min-1 increase of pressure strain on the finger. Pre-treatment with a local anaesthetic or chronically applied capsaicin, resulted in the disappearance of the vasodilatory response. These results suggest an original vasodilatory axon reflex response to non-noxious pressure strain which is initiated by capsaicin-sensitive nerve terminals in the human skin.

Mechanisms of the cutaneous vasodilator response to local external pressure application in rats: involvement of CGRP, neurokinins, prostaglandins and NO

Local pressure‐induced vasodilation (PIV) is a neural vasodilator response to non‐nociceptive externally applied pressure in the skin, previously described in humans. We first determined whether PIV exists in rats and depends on capsaicin‐sensitive fibres as it does in humans. We then examined the mediators involved in the efferent pathway of PIV. Cutaneous blood flow was measured by laser Doppler flowmetry during 11.1 Pa s−1 increases in local applied pressure in anaesthetized rats. The involvement of capsaicin‐sensitive fibres in PIV was tested in rats treated neonatally with capsaicin. To antagonize CGRP, neurokinin‐1, −2, or −3 receptors, different groups of rats were treated with CGRP8–37, SR140333, SR48968 or SR142801, respectively. Prostaglandins involvement was tested with indomethacin treatment. To inhibit nitric oxide synthase (NOS) activity or specific neuronal NOS, rats were treated with NG‐nitro‐L‐arginine or 7‐nitroindazole, respectively. PIV was found in rats, as in humans. PIV was abolished by neonatal treatment with capsaicin and by administration of CGRP8–37 but remained unchanged with SR140333, SR48968 and SR142801 treatments. Prostaglandin inhibition resulted in a significant decrease in PIV. Inhibition of NOS abolished PIV, whereas inhibition of neuronal NOS caused a diminution of PIV. These data suggest that PIV depends on capsaicin‐sensitive fibres in rats, as in humans. It appears that CGRP plays a major role in the PIV, whereas neurokinins have no role. Furthermore, PIV involves a contribution from prostaglandins and depends on endothelial NO, whereas neuronal NO has a smaller role.

Effects of simvastatin, pentoxifylline and spironolactone on hepatic fibrosis and portal hypertension in rats with bile duct ligation

AIMS/METHODS Our aim was to study the antifibrotic and hemodynamic effects of simvastatin (SMV), pentoxifylline (PTX) and spironolactone (SPN), three drugs which may have antifibrotic and/or portal hypotensive properties, in a model of hepatic fibrosis and portal hypertension induced in rats by bile duct ligation. A blind study was performed in five groups of 53 Sprague-Dawley rats: sham, placebo (PL), SMV (2.5 mg x kg(-1) x J(-1)), PTX (50 mg x kg(-1) x J(-1)) and SPN (100 mg x kg(-1) x J(-1)). Drugs were administered by daily gavage over a 4-week period as soon as bile duct ligation was performed. At day 28, the following parameters were evaluated: area of hepatic fibrosis by image analysis after staining collagen with picrosirius and plasma concentrations of hyaluronate, splanchnic and systemic hemodynamics (radiolabeled microspheres). RESULTS Portal venous pressure (PL: 15.5+/-1.5, SMV: 15.8+/-2.5, PTX: 15.9+/-1.8, SPN: 13.5+/-2.1 mmHg, p<0.05) and porto-systemic shunts (PL: 30+/-31, SMV: 18+/-27, PTX: 25+/-24, SPN: 5+/-4%, p<0.05) were significantly reduced in the SPN group; other hemodynamic parameters were not significantly altered. There was a significant correlation between portosystemic shunts and portal pressure (r(s)=0.47, p<0.01). The area of fibrosis was not significantly different among the four groups of bile duct ligated rats (PL: 8.7+/-3.9, SMV: 7.1+/-3.6, PTX: 7.8+/-2.7, SPN: 6.6+/-3.3%) but was higher than in sham rats (1.5+/-0.5%, p<0.001). Hyaluronate was significantly higher in bile duct ligated rats (from 374+/-162 to 420+/-131 microg/l, among the four groups) than in sham rats (52+/-16 microg/l, p<0.0001). CONCLUSIONS In this model, none of the drugs prevented hepatic fibrosis. On the other hand, spironolactone decreased portal pressure and prevented porto-systemic shunts. Therefore, this drug may have beneficial effects in patients with early portal hypertension.

Time-frequency analysis of laser Doppler flowmetry signals recorded in response to a progressive pressure applied locally on anaesthetized healthy rats.

The laser Doppler flowmetry technique has recently been used to report a significant transient increase of the cutaneous blood flow signal, in response to a local non-noxious pressure applied progressively on the skin of both healthy humans and rats. This phenomenon is not entirely understood yet. In the present work, a time-frequency analysis is applied to signals recorded on anaesthetized healthy rats, at rest and during a cutaneous pressure-induced vasodilation (PIV). The comparison, at rest and during PIV, of the scalogram relative energies and scalogram relative amplitudes in five bands, corresponding to five characteristic frequencies, shows an increased contribution for the endothelial related metabolic activity in PIV signals, till 400 s after the beginning of the progressive pressure application. The other subsystems (heart, respiration, myogenic and neurogenic activities) contribute relatively less during PIV than at rest. The differences are statistically significant for all the relative activities in the interval 0-200 s following the beginning of the pressure. These results and others obtained on patients, such as diabetics, could increase the understanding of some cutaneous pathologies involved in various neurological diseases and in the pathophysiology of decubitus ulcers.

Echography of external iliac artery endofibrosis in cyclists

Forty-eight cyclists were studied for suspected external iliac artery endofibrosis with ultrasound B-mode imag ing. In highly trained competition cyclists, symptoms of external iliac artery endofibrosis were characterized by lower limb claudication during maximal effort that was caused by fibrosis thickening of the intima of the exter nal iliac arterial wall. Typical ultrasound imaging aspects consisted of parietal thickening, enhanced echogenicity of the arterial wall, straightness of the abnormal arterial segment, and mild narrowing of the arterial diameter of the proximal or medial segment of the diseased external iliac artery. Although ultrasound B-mode imaging study seems to be useful in the diagnosis of external iliac artery endofibrosis, results with this technique must be compared with results of clinical examination, physio logic tests, and arteriography.

Lower Extremity Arterial Disease in Sports

The recent description of exercise-induced intimal fi brosis affecting mainly the iliac artery (and therefore usually described as external iliac artery endofibrosis) has dramatically changed the diagnostic approach of unexplained recurrent lower limb exercise pain, espe cially in cyclists. Because arterial disease is often as sociated with the aftereffect of various concomitant musculotendinous lesions, several months may pass before an arterial origin is suspected. The arterial origin of the pain must not be eliminated on normal ankle-to- arm index or normal Doppler velocity profiles at rest. Ultrasound examinations taken at rest may show the lesions in 80% of endofibrotic patients and allow for the diagnosis of popliteal entrapment syndrome during dorsiflexion of the foot. However, the hemodynamic consequences of a stenosis on the aortoiliofemoral axis can only be proved by measurement of the ankle- to-arm index after exercise. A cutoff of this index <0.5 provides an 85% sensitivity in the detection of endofi brosis. Invasive investigations (arteriography or an gioscopy) will confirm the diagnosis before surgery is discussed. Although long-term results in endofibrosis are unknown, most of the surgically treated patients return to competition.

Progressive calibrated pressure device to measure cutaneous blood flow changes to external pressure strain

The present methodological paper describes a simple and useful device for local, external pressure application. The mechanical devices, the difficulties, the time required, the possibilities and limitations of the technique to apply a progressive calibrated pressure and to measure cutaneous blood flow with a laser Doppler probe at the same site are discussed. This technique was used to study the effects of local pressure on the cutaneous blood flow with laser Doppler technique. Use of this protocol has provided evidence for a transient cutaneous vasodilation in the human hand during progressive externally applied pressure strain. Results from our laboratory thus far suggest that this vasodilator response is mediated by small sensory nerve fibres in the skin.

Spectral components of laser Doppler flowmetry signals recorded in healthy and type 1 diabetic subjects at rest and during a local and progressive cutaneous pressure application: scalogram analyses

A significant transient increase in laser Doppler flowmetry (LDF) signals is observed in response to a local and progressive cutaneous pressure application in healthy subjects. This reflex may be impaired in diabetic patients. The work presents a signal processing providing the clarification of this phenomenon. Scalogram analyses of LDF signals recorded at rest and during a local and progressive cutaneous pressure application are performed on healthy and type 1 diabetic subjects. Three frequency bands, corresponding to myogenic, neurogenic and endothelial related metabolic activities, are studied. The results show that, at rest, the scalogram energy of each frequency band is significantly lower for diabetic patients than for healthy subjects, but the scalogram relative energies do not show any statistical difference between the two groups. Moreover, the neurogenic and endothelial related metabolic activities are significantly higher during the progressive pressure than at rest, in healthy and diabetic subjects. However, the relative contribution of the endothelial related metabolic activity is significantly higher during the progressive pressure than at rest, in the interval 200-400 s following the beginning of the pressure application, but only for healthy subjects. These results may improve knowledge on cutaneous microvascular responses to injuries or local pressures initiating diabetic complications.

Past, Present and Future of Arterial Endofibrosis in Athletes A Point of View

Exercise-induced arterial endofibrosis (EIAE) is now a 20-year-old concept. Initially observed in highly trained cyclists, it has been found in many other male and female endurance athletes. Most stenoses are located on the first centimetres of the external iliac artery but other localisation may be found. The disease is defined by specific histological findings showing fibrosis of the intimal and medial wall of the artery. Ankle pressure measurement plays a key role in the diagnosis of EIAE provided that the exercise tests reproduce symptoms and are performed with the subject being highly trained, and that pressure measurements are performed early following exercise. Various cut-off values have been proposed in the literature.Magnetic resonance imaging or arteriography or ultrasound imaging should be performed by trained operators only. Surgical ‘endofibrosectomy’ is preferable in young cyclists generally associated with a saphenous enlargement patch. We do not recommend angioplasty. Athletes are generally allowed to return to competition within 3–4 months following surgery. Many unanswered questions remain, specifically about the pathophysiology of this disease. Mechanical and pressure strain play a central role in the development of EIEA, but nutritional and haemorrheological factors, hormonal changes and a genetic predisposition are likely to contribute. New techniques could facilitate the diagnosis of EIAE.