Biomedical subjects

Dominique Sigaudo-Roussel

Publications and source records attributed to Dominique Sigaudo-Roussel.

13 recordsLinked to original sources

PubMed2006

Neuroendocrine pathway involvement in the loss of the cutaneous pressure-induced vasodilatation during acute pain in rats.

Pain is regarded as a risk factor in pressure ulcer development by contributing to immobility. Pressure-induced vasodilatation (PIV) is a mechanism whereby cutaneous blood flow increases in response to progressive locally applied pressure, thereby delaying the occurrence of ischaemia and appearing to be a protective response to local pressure. When the interaction between nervous and vascular systems is deregulated, PIV, which relies on both systems, is absent. We thus hypothesized that acute pain could alter PIV. This study investigated the effects on PIV of acute pain triggered by noxious heat (50 degrees C) applied to the tail of anaesthetized rats. To address the mechanisms underlying these effects, chronic sympathectomy was performed using guanethidine, and the plasma concentrations of pituitary adrenocorticotrophin (ACTH) and catecholamines were measured. Our results show that acute pain induces a loss of PIV associated with an increase of ACTH. Direct involvement of hypertensive effects and peripheral sympathetic nervous system are excluded in the loss of PIV, whereas the activation of brain structures that have descending inhibitory control cannot be excluded. A low dose of systemic morphine prevented this loss of PIV and maintained the ability of the cutaneous microcirculation to adapt to the applied pressure. The loss of a protective response to local pressure (PIV) induced by acute pain lends physiological support to the direct involvement of pain in pressure ulcer development. Therefore, an adequate evaluation and treatment of pain is crucial.

Acute Disease↗

PubMed2006

Aldose reductase pathway inhibition improved vascular and C-fiber functions, allowing for pressure-induced vasodilation restoration during severe diabetic neuropathy.

Pressure-induced vasodilation, a neurovascular mechanism relying on the interaction between mechanosensitive C-fibers and vessels, allows skin blood flow to increase in response to locally nonnociceptive applied pressure that in turn may protect against pressure ulcers. We expected that severe neuropathy would dramatically affect pressure-induced vasodilation in diabetic mice, and we aimed to determine whether pressure-induced vasodilation alteration could be reversed in 8-week diabetic mice. Control and diabetic mice received no treatment or sorbinil, an aldose reductase inhibitor, or alagebrium, an advanced glycation end product breaker, the last 2 weeks of diabetes. Laser Doppler flowmetry was used to evaluate pressure-induced vasodilation and endothelium-dependent vasodilation after iontophoretic delivery of acetylcholine (ACh). We assessed the nervous function with measurements of motor nerve conduction velocity (MNCV) as well as the C-fiber-mediated nociception threshold. Pressure-induced vasodilation, endothelial response, C-fiber threshold, and MNCV were all altered in 8-week diabetic mice. None of the treatments had a significant effect on MNCV. Although sorbinil and alagebrium both restored ACh-dependent vasodilation, sorbinil was the sole treatment to restore the C-fiber threshold as well as pressure-induced vasodilation development. Therefore, the inhibition of aldose reductase pathway by sorbinil improved vascular and C-fiber functions that allow pressure-induced vasodilation restoration that could limit neuropathic diabetic cutaneous pressure ulcers.

Acetylcholine↗

PubMed2005

Preservation of pressure-induced cutaneous vasodilation by limiting oxidative stress in short-term diabetic mice.

OBJECTIVE: Pressure-induced vasodilation (PIV) allows skin blood flow to increase in response to locally applied pressure and may be protective against pressure ulcers. We previously showed that PIV was absent in 1-week diabetic mice exhibiting no neuropathy. Our aim was to determine whether the diabetes-induced PIV alteration could be prevented. METHODS AND RESULTS: Diabetic mice received no treatment or a daily treatment with either sorbinil, alagebrium or alpha-lipoic acid (LPA) for 1 week. Laser Doppler flowmetry was used to evaluate PIV as well as endothelium-dependent vasodilation following iontophoretic delivery of acetylcholine (ACh). The effect of each treatment on oxidative stress was examined by plasma 8-isoprostane assay. LPA was the sole treatment to prevent both PIV and ACh vasodilation alterations, with a significant reduction of oxidative stress in diabetic mice. Both PIV and ACh-vasodilation were abolished in LPA-treated diabetic mice following injection of Nomega-nitro-L-arginine (p<0.05). In contrast, alagebrium and sorbinil prevented neither diabetes-induced PIV abolition nor endothelial alteration. CONCLUSIONS: LPA treatment significantly reduced the oxidative stress and was able to preserve endothelial nitric oxide availability in the cutaneous microcirculation and then to preserve the PIV response in diabetic mice. LPA treatment could play a key role in limiting the risk of pressure-induced cutaneous ulcer during diabetes.

Acetylcholine↗

PubMed2005

Cellular mechanisms underlying cutaneous pressure-induced vasodilation: in vivo involvement of potassium channels.

In the skin of humans and rodents, local pressure induces localized cutaneous vasodilation, which may be protective against pressure-induced microvascular dysfunction and lesion formation. Once activated by the local pressure application, capsaicin-sensitive nerve fibers release neuropeptides that act on the endothelium to synthesize and release nitric oxide (NO) and prostaglandins, leading to the development of the cutaneous pressure-induced vasodilation (PIV). The present study was undertaken to test in vivo the hypothesis that PIV is mediated or modulated by differential activation of K+ channels in anesthetized rats using pharmacological methods. Local pressure was applied at 11.1 Pa/s. Endothelium-independent and -dependent vasodilation were tested using iontophoretic delivery of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively, and was correlated with PIV response. PIV was reduced after systemic administration of tetraethylammonium (a nonspecific K+ channel blocker), iberiotoxin [a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker], and glibenclamide [a specific ATP-sensitive K+ (KATP) channel blocker], whereas PIV was unchanged by apamin (a specific small-conductance Ca2+-activated K+ channel blocker) and 4-aminopyridine (a specific voltage-sensitive K+ channel blocker). The responses to SNP and ACh were reduced by iberiotoxin but were unchanged by glibenclamide. We conclude that the cellular mechanism of PIV in skin involves BKCa and KATP channels. We suggest that the opening of BKCa and KATP channels contributes to the hyperpolarization of vascular smooth muscle cells to produce PIV development mainly via the NO and prostaglandin pathways, respectively.

Acetylcholine↗

PubMed2005

Carotid endarterectomy impairs blood pressure homeostasis by reducing the physiologic baroreflex reserve.

OBJECTIVE: To assess the impact of carotid endarterectomy on blood pressure homeostasis and baroreflex function, with particular reference to the presence or absence of significant contralateral carotid artery disease, we conducted a prospective study in 80 patients with symptomatic extracranial carotid disease undergoing carotid endarterectomy in a regional teaching hospital over 2 years. METHODS: Patients were divided into two groups: the control group (n = 37) had no significant contralateral carotid disease; patients in the diseased group (n = 23) had either >70% stenosis or occlusion of the contralateral carotid artery. Seventeen patients with abnormal heart rhythms, poor quality recordings, or with intermediate degrees of contralateral carotid stenosis were excluded. Three patients who had previously undergone contralateral carotid endarterectomy were separately evaluated. Atheromatous plaque was removed from carotid lumen and the baroreflex mechanism received direct intraoperative stimulation before and after carotid endarterectomy. The main outcome measures were (1) the hemodynamic response to the carotid endarterectomy, baroreflex sensitivity, and operating set point (the resting blood pressure, which the baroreflex mechanism maintains) before and after removal of the atheromatous plaque, and (2) the responsiveness of the ipsilateral baroreceptor mechanism to direct stimulation. The impact of the presence of contralateral carotid stenosis on these variables was also evaluated. RESULTS: Patients in the two groups were comparable for preoperative demographic, medication, and hemodynamic variables. Carotid endarterectomy led to a rise in mean arterial pressure from 81.3 +/- 3.9 mm Hg to 103.5 +/- 4.6 mm Hg ( P < .00001) and from 87.6 +/- 4.3 mm Hg to 94.0 +/- 4.5 mm Hg ( P < .003) in the diseased and control groups, respectively. The magnitude of blood pressure response was significantly greater in the diseased group than in the control group ( P < .00001). This hypertensive shift was not accompanied by the expected fall in heart rate. Direct baroreflex stimulation prior to carotid endarterectomy caused a significantly greater response in the diseased group, suggesting sensitization of the ipsilateral carotid baroreceptor in the presence of contralateral carotid disease. Furthermore, the baroreflex response was obliterated after endarterectomy. There were significant reductions in baroreflex sensitivity and a hypertensive shift in the operating set point, the magnitude of which was significantly greater in patients with contralateral carotid disease. CONCLUSIONS: Carotid endarterectomy impairs blood pressure homeostasis through surgical destruction of the ipsilateral carotid baroreflex mechanism. Patients with contralateral carotid stenosis have a reduced baroreflex reserve and show greater baroreflex dysfunction and hemodynamic instability after endarterectomy. These patients are at greater risk of postendarterectomy complications and should be monitored closely.

Aged↗

PubMed2004

Effect of lignocaine injection in carotid sinus on baroreceptor sensitivity during carotid endarterectomy.

OBJECTIVES: This study was undertaken to test the hypothesis that there is a neural basis for baroreceptor deterioration during carotid endarterectomy (CEA), by investigating intraoperative hemodynamic changes induced by intraluminal carotid stretch stimulation, before and after application of local anesthetic to the adventitial layer of the carotid sinus region. METHODS: This was a prospective study of 20 patients undergoing elective CEA. During CEA, before removal of the atheroma, intraluminal stretch simulation of the carotid baroreceptors (rub test) was performed before and after injection of 1% lignocaine into adventitial tissue of the artery in the region of the carotid sinus. Continuous measurements of mean arterial blood pressure (MAP), electrocardiographic r-r intervals (R-R), heart rate, cardiac vagal tone, and carotid sinus baroreflex were recorded to determine alterations in baroreceptor function. RESULTS: Rub test before injection of lignocaine was associated with a decrease in MAP and heart rate and an increase in R-R, cardiac vagal tone, and carotid baroreflex response, indicating a functioning baroreflex. After lignocaine injection and repetition of the rub test, no significant change was seen in MAP, heart rate, R-R, cardiac vagal tone, or carotid baroreflex response, indicating a nonfunctioning baroreflex. Comparing the peak responses to the rub test stimulus before and after lignocaine injection showed significant differences for all variables (P <.05), with carotid baroreflex response and heart rate being highly significant (P <.0005). CONCLUSIONS: The baroreflex response to intraluminal stretch stimulation of the carotid sinus area is operational in patients undergoing CEA, and this response is abolished by infiltration of local anesthetic into the periadventitial tissue around the carotid sinus.

Aged↗

PubMed2004

Low skin temperature impairs the cutaneous vasodilator response to local progressive pressure strain.

A pressure-induced vasodilation (PIV) was recently reported as a putative protective response in human skin. Therefore, we examined the influence of skin temperatures on cutaneous blood flow responses to local progressive pressure strain. Ten healthy volunteers were studied at different ambient temperatures leading to low (29.0 +/- 0.3 degrees C), intermediate (32.6 +/- 0.1 degrees C), high (33.9 +/- 0.1 degrees C) and very high (36.0 +/- 0.1 degrees C) skin temperatures. We measured cutaneous blood flow using laser Doppler flowmetry on the foot in response to a local progressive pressure increase of 5.0 mm Hg min(-1). Progressive pressure strain led to an almost linear cutaneous laser Doppler flow decrease at both low and intermediate skin temperatures (-40.1 +/- 6.6% and -31.2 +/- 6.5% from baseline at 30 +/- 1.25 mm Hg), whereas at both high and very high skin temperatures, subjects responded with a transient cutaneous vasodilation (+33.6 +/- 10.6% and +50.6 +/- 15.4% from baseline at 30 +/- 1.25 mm Hg). These findings suggest that high skin temperatures are required for the PIV to develop.

Acclimatization↗

PubMed2004

Impaired pressure-induced vasodilation at the foot in young adults with type 1 diabetes.

Vascular and neurological mechanisms are both likely to be involved in foot ulcer. We recently reported a pressure-induced vasodilation (PIV), relying on unmyelinated afferent excitation. We previously found that cutaneous blood flow in response to locally applied pressure might be impaired in diabetic patients because of the combined effects of low cutaneous temperature and alterations in microcirculatory function. Therefore, we aimed to analyze whether, at a relatively high cutaneous temperature, PIV is present in type 1 diabetes and to assess endothelial-dependent vasodilation and endothelium-independent vasodilation. We measured cutaneous blood flow using laser Doppler flowmetry on the head of the first metatarsus in response to applied pressure at 5.0 mmHg/min in warm conditions (29.5 +/- 0.2 degrees C). Responses to iontophoresis of acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) were measured using laser Doppler flowmetry in the forearm. The data indicate that PIV exists at the foot level in normal subjects, whereas it was not found in diabetic patients. In diabetic patients, the nonendothelial-mediated response to sodium nitroprusside was preserved, whereas the endothelial-mediated response to acetylcholine was impaired. These findings might be relevant to the high prevalence of foot ulcer that occurs in diabetic patients.

Adult↗

PubMed2004

Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice.

Pressure-induced vasodilation (PIV) is a mechanism whereby skin blood flow increases in response to progressive locally applied pressure. Skin blood flow in response to applied pressure decreased early in diabetic patients as a result of vascular and/or neural impairment. This study was designed to determine the effect of vascular changes on PIV in 1-week streptozotocin-induced diabetic mice. We assessed cutaneous microvascular response to local increasing pressure application measured by laser Doppler flowmetry (LDF) and endothelium-dependent and -independent vasodilation by iontophoretic delivery of acetylcholine and sodium nitroprusside and sciatic motor nerve conduction velocity and morphometry. In control mice, LDF increased 34% from baseline to 0.2 kPa external pressure, showing PIV response. In contrast, diabetic mice had no LDF increase in response to progressive external pressure. Moreover, after iontophoretic delivery of acetylcholine, endothelium-dependent vasodilation was largely attenuated in diabetic mice (25%) compared with control mice (81%), whereas vasodilation to sodium nitroprusside was not different between groups. Nerve function as assessed by sciatic nerve conduction velocity and morphometry did not differ between groups. These findings suggest that endothelial impairment is sufficient to severely alter PIV response, which seems to be highly sensitive to endothelial nitric oxide levels. PIV suppression could favor diabetes complications such as diabetic foot ulcers.

Animals↗

PubMed2003

Evidence for the involvement of VPAC1 and VPAC2 receptors in pressure-induced vasodilatation in rodents.

A transient increase in skin blood flow in response to an innocuous local pressure application, defined as pressure-induced vasodilatation (PIV), delays the occurrence of ischaemia, suggesting a protective feature against applied pressure. The PIV response depends on capsaicin-sensitive nerve fibres and calcitonin gene-related peptide (CGRP) has been shown to be involved. In these fibres, CGRP coexists with pituitary adenylate cyclase-activating polypeptide (PACAP). Three distinct receptors mediate the biological effects of PACAP: VPAC1 and VPAC2 receptors binding with the same affinity for PACAP and vasoactive intestinal peptide and PAC1 receptors showing high selectivity for PACAP. Because the receptors are widely expressed in the nervous system and in the skin, we hypothesized that at least one of them is involved in PIV development. To verify this hypothesis, we used [D-p-Cl-Phe(6),Leu(17)]-VIP (nonspecific antagonist of VPAC1/VPAC2 receptors), PG 97-269 (antagonist of VPAC1 receptors), PACAP(6-38) (antagonist of VPAC2/PAC1 receptors) and Max.d.4 (antagonist of PAC1 receptors) in anaesthetized rodents. The blockade of VPAC1/VPAC2, VPAC1 or VPAC2/PAC1 receptors eliminated the PIV response, whereas PAC1 blockade had no effect, demonstrating an involvement of VPAC1/VPAC2 receptors in PIV development. Moreover, endothelium-independent and -dependent vasodilator responses were unchanged by the VPAC1/VPAC2 antagonist. Thus, the absence of a PIV response following VPAC1/VPAC2 blockade cannot be explained by any dysfunction of the vascular smooth muscle or endothelial vasodilator capacity. The involvement of VPAC1/VPAC2 receptors in the development of PIV seems to imply a series relationship in which each receptor type (CGRP, VPAC1, VPAC2) is necessary for the full transmission of the response.

Animals↗

PubMed2003

Effect of isoflurane on skin-pressure-induced vasodilation.

Since general anesthesia has been shown to attenuate endothelium-dependent vasodilation, it was of interest to verify whether general anesthesia would modify skin vasodilation in response to local pressure application, which is endothelium dependent. To study the effect of general anesthesia on pressure-induced vasodilation development, we examined the effects of low- and high-dose isoflurane. Skin blood flow was measured by laser Doppler flowmetry during 11.1 Pa s(-1) increases in locally applied pressure in anesthetized rats treated with low or high doses of isoflurane. Following the administration of low doses of isoflurane, skin blood flow increased from baseline, with increasing local pressure application (+37 +/- 10% at 2.0 kPa). The increase in skin blood flow was absent in rats treated with high doses (-20 +/- 5% at 2.0 kPa), even when the anesthesia-induced hypotension was corrected by gelofusine infusion (-20 +/- 10% at 2.0 kPa). Whereas sodium-nitroprusside-induced vasodilation developed following low and high doses of isoflurane, acetylcholine-induced vasodilation was impaired with high doses compared to low doses. These data show that pressure-induced vasodilation is abolished with high doses of anesthetics. It is not the anesthesia-induced hypotension, but the depth of anesthesia, which can lead to the disappearance of pressure-induced vasodilation by an alteration in endothelial function.

Acetylcholine↗

PubMed2003

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 (> or =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.

Angiography↗

PubMed2002

Heart rate variability after prolonged spaceflights.

Astronauts returning from spaceflight often experience post-flight orthostatic intolerance. This study was designed to determine whether cosmonauts with post-flight syncope could be distinguished from those with no post-flight syncope. The autonomic function was determined in a group of ten subjects, with no previous history of syncope, during a stand test before and after a long-term spaceflight (90 to 198 days). Heart rate (HR) and systolic blood pressure (SBP) were measured beat-by-beat, pre- and post-flight and the spontaneous baroreflex sensitivity and HR variability were studied. Individuals were categorized according to their ability to remain standing for 5 min the day after landing. Three of the ten cosmonauts failed to finish the standing test performed the day after landing (nonfinishers). The spontaneous baroreflex slope was reduced in both groups after the spaceflight. The non-finisher group had a lower SBP (P < 0.05) at rest in pre-flight tests than the group that completed the test (finisher group). The non-finisher group also had higher indicators of parasympathetic activity when supine, both pre- and post-flight, but this difference disappeared with standing. At the end of the stand test, SBP and HR were lower in non-finisher cosmonauts than the finishers, while HR did not increase compared to early measurements in the stand test of the finisher group. These results suggest an impairment in autonomic control of HR, which might contribute to the fainting response.

Adult↗