Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

The Impact of Revascularisation on Quality of Life in Chronic Mesenteric Ischemia.

Background: Chronic mesenteric ischemia (CMI) is characterized by long-standing abdominal symptoms due to insufficient mesenteric circulation. Data on the effect of revascularisation on quality of life (QoL) for CMI are scarce. This study is the first to evaluate the impact of revascularisation on quality of life. Methods: Seventy-nine patients with CMI or acute-on-chronic mesenteric ischemia (AoCMI) underwent an intervention of one or more mesenteric arteries between January 2010 and July 2012. QoL before and after intervention was measured with the EuroQol-5D. Preintervention questionnaires were of standard care. Postintervention data were obtained by resending a questionnaire to the patients between February and May 2013. To investigate the clinical relevance of our findings, the minimal clinically important difference (MCID) was used. Since there is no established MCID for CMI, we used the literature reference MCID of inflammatory bowel syndrome (IBS) of 0.074. Results: Fifty-five (69.6%) of 79 patients returned their questionnaire and 23 (29.1%) were completely filled out. There was a significant increase of the median EQ-index score from 0.70 to 0.81 (p=0.02) and a significant reduction of symptoms in the domains usual activities (34.4%) and pain/discomfort (32.3%). There was a significant improvement of 17% in overall current health condition (VAS) (p=0.001). The MCID between baseline and postoperative EQ-5D index score was 0.162, indicating a clinically relevant improvement of quality of life after revascularisation. Conclusion: Quality of life of CMI patients is improved after mesenteric artery revascularisation.

Culture results from wound biopsy versus wound swab: does it matter for the assessment of wound infection?

OBJECTIVES: The aim of this study was to determine whether assessment of wound infection differs when culture results from wound biopsy versus wound swab are available in clinical practice. METHODS: For 180 eligible patients, a swab and biopsy were taken from one wound during a regular appointment at a wound care facility in eastern Netherlands. Culture results from both methods were supplemented with clinical information and provided to a panel of six experts who independently assessed each wound as infect or not, separately for swab and biopsy. Assessments for biopsy and swab were compared for the complete expert panel, and for individual experts. RESULTS: The complete expert panel provided the same wound assessment based on (clinical information and) culture results from wound biopsy and wound swab in 158 of 180 wounds (87.8%, kappa 0.67). For individual experts, agreement between biopsy and swab varied between 77% and 96%. However, there were substantial differences between experts: the same assessment was provided in 62 (34.4%) to 76 (42.2%) wounds for swab and biopsy respectively. CONCLUSIONS: Assessment of infection does not significantly differ when culture results from swabs or biopsies are available. The substantial variability between individual experts indicates non-uniformity in the way wounds are assessed. This complicates accurate detection of infection and comparability between studies using assessment of infection as reference standard.

Endovascular treatment of ruptured abdominal aortic aneurysm: is there a long-term benefit at follow-up?

AIM: Several studies have shown the feasibility of endovascular repair of ruptured abdominal aortic aneurysms (rEVAR). However, the role and value of rEVAR remains controversial due to selection bias and lack of long-term results. In the present study we describe our short- and long-term results of treating patients with rEVAR irrespective of hemodynamic condition and challenging anatomy. METHODS: In April 2006 we started the single centre prospective non-randomised Ruptured Aneurysm Study (RASA). During a four year enrolment period all consecutive patients presenting with infrarenal ruptured AAA (rAAA, N.=117) were assessed for preferential rEVAR treatment. A rAAA was defined as extravasation of blood or hematoma outside the AAA due to transmural tear in the infrarenal abdominal aorta wall documented by preoperative computed tomography (CT) angiography examination or during open repair. Patients with challenging anatomy (infrarenal neck length below 15 mm and neck angulation above 60 degrees) were included as part of a damage control concept. Complication and mortality rates were studied at 30 days and yearly afterwards. RESULTS: Thirty-five patients (33% of all admitted rAAA) were treated with rEVAR and 42% of them were considered hemodynamically unstable (systolic blood pressure <100 mmHg) and 30% had challenging AAA anatomy. The mortality rate at 30 days in the rEVAR group was 17%, in the open repair group 31%, and in the entire rAAA group (including abstained patients) 36%. During the first 30 days, 18 rEVAR patients experienced complications with nine re-interventions as a result. Long-term mortality of the rEVAR patients was 34% after a median follow-up of 3.4 years. All deaths after one year follow-up were non-AAA related. Multivariate analysis shows that Hardman index, presence of peripheral arterial obstructive disease and lowest systolic blood pressure during surgery are independently associated with long-term survival. Challenging rAAA anatomy was not associated with impaired survival. CONCLUSION: Our study shows that rEVAR is feasible irrespective of hemodynamic condition and that it is associated with relative low mortality rates. Challenging rAAA anatomy may not affect overall long-term survival, but six out of ten patients remain unsuitable for rEVAR because of inappropriate anatomy.

Final results of the prospective European trial of the Endurant stent graft for endovascular abdominal aortic aneurysm repair.

OBJECTIVES: The Endurant Stent Graft System (Medtronic Vascular, Santa Rosa, CA) is specifically designed to treat patients with abdominal aortic aneurysm, including those with difficult anatomies. This is the 1-year report of a prospective, non-randomised, open-label trial at 10 European centres. METHODS: Between November 2007 and August 2008, 80 patients were enrolled for elective endovascular aneurysm repair (EVAR) with the Endurant; 71 with moderate (≤ 60°) and nine with high (60-75°) infrarenal aortic neck angulation. Safety and stent-graft performance were assessed throughout a 1-year follow-up period. RESULTS: The device was successfully delivered and deployed in all cases. All-cause mortality was 5% (4/80), with one possibly device-related death. Serious adverse events were comparable between the high and moderate angulation groups. There were no device migrations, stent fractures, aortic ruptures or conversions to open repair. Maximal aneurysm diameter decreased >5 mm in 42.7% of cases. A total of 28 endoleaks were observed (26 type II, two undetermined). Three secondary endovascular procedures were performed for outflow vessel stenosis, graft limb occlusion and iliac extension, resulting in a secondary patency rate of 100%. No re-interventions were required in the high angulation group. CONCLUSIONS: The Endurant Stent Graft was successfully delivered and deployed in all cases and performed safely and effectively in all patients, including those with unfavourable proximal neck anatomy.

Leucocyte and platelet adhesion in different layers of the small bowel during experimental total warm ischaemia and reperfusion.

BACKGROUND: Ischaemia and reperfusion (IR) of the small bowel is involved in many clinical conditions. A key component in IR-induced tissue damage is microvascular dysfunction. The aim was to investigate the role of leucocytes and platelets in capillary flow impediment and tissue damage. METHODS: Anaesthetized rats were subjected to 30 min warm ischaemia of the small bowel, followed by 1 h reperfusion. To elucidate the influence of leucocytes on platelet adhesion, leucocyte-vessel wall interactions induced by IR were prevented by anti-platelet activating factor (PAF) or anti-intercellular adhesion molecule (ICAM)-1. Intravital videomicroscopy was performed and tissue injury was evaluated histologically. RESULTS: In submucosal venules, IR induced an increase in the median number of interacting leucocytes from 3 to 10 and 20 leucocytes per 100-microm venule segment after 10 and 60 min reperfusion respectively. Anti-PAF or anti-ICAM-1 completely attenuated this increase, resulting in an eightfold improvement in submucosal capillary flow and reduced tissue injury. Shedding of villi no longer occurred. Platelet-vessel wall interactions occurred particularly in submucosal venules, but were not affected by anti-PAF or anti-ICAM-1. CONCLUSION: Small bowel IR initiated an inflammatory and thrombotic response in the submucosal layer only. Attenuation of leucocyte adhesion improved submucosal capillary perfusion, preventing shedding of mucosal villi.

Total warm ischemia and reperfusion impairs flow in all rat gut layers but increases leukocyte-vessel wall interactions in the submucosa only.

OBJECTIVE: To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte-vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes. SUMMARY BACKGROUND DATA: Gut injury as a result of I/R plays a pivotal role in a variety of clinical conditions, such as small bowel transplantation, heart or aortic surgery, and (septic) shock. The precise mechanism behind I/R injury and the role of microvascular changes remain unclear. The influence of warm I/R of the gut on microvascular parameters in the different gut layers has not been studied before. METHODS: Anesthetized Lewis rats were either subjected to 30 minutes of ischemia and 1 hour of reperfusion or sham-treated as controls. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Intravital video microscopic measurements were obtained at intervals. Tissue injury of the small bowel and other organs was histologically evaluated afterward. In addition, plasma levels of I-FABP were determined to measure enterocyte damage. RESULTS: After ischemia, mean red blood cell velocity decreased significantly in all layers of the small bowel, but no diameter changes were observed. Leukocyte-vessel wall interactions increased in the submucosa but not in the muscle layers. Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward. The intestinal mucosa was severely injured; no histologic damage was detected in other tissues. CONCLUSIONS: This is the first in vivo study showing that total warm ischemia of the rat gut impairs perfusion in the whole small bowel, whereas leukocyte-vessel wall interactions increase in the submucosal layer only. Therefore, the early inflammatory response to I/R seems to be limited to the submucosa. Both microvascular effects may have contributed to the severe morphologic and functional mucosal injury observed after I/R.

Effect of repetitive asphyxia on leukocyte-vessel wall interactions in the developing chick intestine.

BACKGROUND/PURPOSE: Information on leukocyte-vessel wall interactions (LVWI) during development of the immature intestine is scarce. The authors designed an experimental model for studying the microcirculation in the developing intestine of chick fetuses at days 13 (n = 12), 15 (n = 17), and 17 (n = 19) of incubation (0.6, 0.7, and 0.8 of the incubation time, respectively) using intravital microscopy. METHODS: The authors investigated whether episodes of asphyxia increase LVWI and induce tissue damage in the developing intestine. Asphyxia was induced by clamping of the chorioallantoic vein for 6 periods of 5 minutes each, with 5-minute intervals, whereas in sham groups a sham procedure was performed. Video recordings were made before as well as 10, 20, and 30 minutes after the end of the asphyxia or sham protocol. RESULTS: Baseline number of rolling leukocytes per minute significantly increased (P < .001) from 0 at 0.6 incubation to 1.5 and to 4 at 0.7 and 0.8 incubation time, respectively. At 0.6 and 0.7 incubation no adherent leukocytes were observed under baseline conditions, whereas at 0.8 incubation single leukocytes adhered to the venular wall. LVWI variably increased during the course of the experiments. Asphyxia neither enhanced LVWI nor induced histological damage in the intestine. CONCLUSIONS: These findings indicate that (1) leukocyte-vessel wall interactions mature during fetal development, and (2) repetitive episodes of asphyxia induce neither an inflammatory response nor histological tissue injury in the developing intestine from 0.6 to 0.8 incubation. The authors hypothesize that immaturity of leukocyte-vessel wall interactions, as part of the nonspecific host defense to invading bacteria, might play a role in the development of necrotizing enterocolitis in premature neonates.

Skin blood flow abnormalities in a rat model of neuropathic pain: result of decreased sympathetic vasoconstrictor outflow?

Loose ligation of a sciatic nerve in rats provokes signs and symptoms like those observed in human conditions of neuropathic pain. Some of these have been associated with sympathetic dysfunction. Since the skin microcirculation in the rat is strongly influenced by sympathetic tone, abnormalities in skin blood flow may be used as an indirect measure of sympathetic dysfunction. We measured, by means of laser Doppler flowmetry, skin blood flow at the plantar surface of the rat hind paw before and after ipsilateral loose sciatic nerve ligation. We assessed basal skin blood flow as well as the vasoconstrictor response which follows cooling of the rat abdomen. The effectiveness of this response may be used as a measure of sympathetic vasoconstrictor outflow. As compared to the values obtained before ligation (= 100%): (1) the vasoconstrictor response was impaired (65%, P < 0.01) from day 1 onwards, whereas (2) basal skin blood flow was increased (171%; P < 0.01) from day 3 until day 5, and decreased (51%, P < 0.0001) from day 7 until day 28. At day 28, blockade of impulse propagation in the loosely ligated sciatic nerve (by means of lidocaine) did not increase the lowered level of skin blood flow. These findings suggest that in the chronic construction injury model loose ligation of a sciatic nerve reduces sympathetic vasoconstrictor outflow, which, in turn may induce supersensitivity of skin microvessels to catecholamines.

Effects of different durations of total warm ischemia of the gut on rat mesenteric microcirculation.

BACKGROUND: Gut injury due to ischemia and reperfusion (I/R) plays a pivotal role in many clinical conditions, such as small bowel transplantation, heart or aortic surgery in adults, and necrotizing enterocolitis in neonates. The influence of ischemic events on microcirculatory mechanisms is not well understood. Therefore, we studied, in vivo, local perfusion and leukocyte-vessel wall interactions before and after different periods of total warm ischemia of the whole gut and subsequent reperfusion in mesenteric microvessels. MATERIALS AND METHODS: Groups of pentobarbital-anaesthetized Lewis rats were subjected to 15 (n = 9), 30 (n = 12), or 60 min (n = 5) of total warm gut ischemia and 2 h reperfusion. As control a sham group (n = 10) was included. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Before and at different time periods after start of reperfusion intravital video microscopic measurements were performed. RESULTS: Rats subjected to 60 min ischemia died during the early reperfusion phase. Fifteen, 30, and 60 min ischemia induced in venules a significant decrease in blood flow, while diameter changes were not observed. This flow decrease was severe in the 15- and 30-min ischemia groups, dropping to 40 and 25% of control, respectively. Following 60 min ischemia blood flow did not exceed 10% of control. The total number of interacting leukocytes, a parameter which includes both leukocyte rolling and adhesion in venules, increased up to 5 or 10 times its control value following 15 or 30 min ischemia, respectively. Leukocyte-vessel wall interactions could not be studied in the 60-min ischemia group, due to the low blood flow. CONCLUSIONS: Even short periods of total warm ischemia of the whole gut induce severe attenuation of venular blood flow with an increase in leukocyte-vessel wall interactions. These changes increase with prolongation of the ischemic period. A 60-min period of total warm ischemia is fatal during the early reperfusion phase.

Ischemia/reperfusion injury in rat mesenteric venules: red blood cell velocity and leukocyte rolling.

The authors determined the effects of 15 (n = 9) and 30 (n = 12) minutes of warm ischemia on the rat mesentery and compared the results with those of a sham-operated group (n = 10). Red blood cell velocity and number of rolling leukocytes were assessed before ischemia as well as 10, 20, 30, 60, 90, and 120 minutes after the start of reperfusion. Leukocyte rolling is considered to be an early step of the inflammatory process. Leukocytes roll along the vessel wall at a velocity that is clearly lower than that of the other blood cells. The preischemic values of red blood cell velocity and number of rolling leukocytes in the 15- and 30-minute ischemia groups did not differ from those of the sham group. In the sham group, no significant changes in red blood cell velocity and number of rolling leukocytes were observed over time. Compared with the sham group, the red blood cell velocity of the 15-minute ischemia group was significantly lower at 30, 60, 90, and 120 minutes after the start of reperfusion the number of rolling leukocytes did not differ significantly. For the 30-minute ischemia group, red blood cell velocity also was significantly lower at 20, 30, 60, 90, and 120 minutes after the start of reperfusion, and the number of rolling leukocytes was higher at 10, 20, and 30 minutes after the start of reperfusion. The results of this study indicate that short periods of total warm ischemia of the rat small bowel and subsequent reperfusion result in a significantly impaired microcirculatory blood flow in the mesentery. However, a prolonged period of ischemia is required to increase leukocyte-vessel wall interactions. In the future, this model will enable us to study the effect of pharmacological interventions during an early stage of the inflammatory response to ischemia/reperfusion in the gut.

The spinal component to skin blood flow abnormalities in reflex sympathetic dystrophy.

OBJECTIVE: To determine whether the mechanisms of reflex sympathetic dystrophy, a neuropathic pain syndrome characterized by skin blood flow abnormalities associated with sympathetic vasoconstrictor and antidromic vasodilator mechanisms, are solely of peripheral origin or have an additional spinal component and act exclusively through neural or also involve humoral pathways. PATIENTS: The 54 patients with unilateral reflex sympathetic dystrophy were divided into the following three stages according to their perception of skin temperature in the clinically affected hand: stage I, stationary warmth sensation; stage II, intermittent warmth and cold sensation; and stage III, stationary cold sensation. METHODS: Investigation of basal skin blood flow and vasoconstrictive response to dependency of skin microvessels in the clinically unaffected hand and the clinically affected hand of patients with reflex sympathetic dystrophy and the left hand of 16 control subjects. Microcirculation was investigated at the predominantly neurally controlled thermoregulatory level (Doppler laser flowmetry) and at the predominantly humorally controlled nutritive level (capillary microscopy). RESULTS: In the clinically unaffected hand, at the thermoregulatory level of the microcirculation: (1) basal skin blood flow was increased at stage I compared with the control subjects, whereas no differences could be observed at this stage compared with the clinically affected hand; (2) the vasoconstrictive response to dependency (defined as skin blood flow at heart level divided by skin blood flow in the dependent position) was attenuated at stage I compared with the control subjects, whereas no differences could be observed at this stage compared with the clinically affected hand; and (3) basal skin blood flow and the vasoconstrictive response to dependency did not differ from the control subjects at stages II and III. In the clinically unaffected hand, at the nutritive level, no differences could be observed at any stage of the syndrome compared with the control subjects. CONCLUSIONS: This study indicates that there is a spinal component to microcirculatory abnormalities at stage I of the reflex sympathetic dystrophy syndrome that most likely acts through neural (antidromic vasodilator) mechanisms and that may be initiated by traumatic excitation of a peripheral nerve on the clinically affected side.

The influence of local skin heating and reactive hyperaemia on skin blood flow abnormalities in patients with reflex sympathetic dystrophy (RSD).

Skin blood flow in reflex sympathetic dystrophy (RSD) patients has been reported to develop from an increase at an early stage to a decrease at later stages. So far, it remains unclear whether these abnormalities are solely of microcirculatory origin, and result from functional vasospasm or structural vessel wall changes. Eighty-seven RSD patients were categorized as follows: stage I in case of a stationary warmth sensation; stage II in case of an intermittent warmth and cold sensation; and stage III in case of a stationary cold sensation. Laser Doppler flowmetry (LDF) was used as a measure of total skin blood flow and transcutaneous oximetry (TCPO2) as a measure of vascular reactivity in the more superficial skin layers. Local skin heating and reactive hyperaemia were used to study the relative reserve capacity of skin microvessels. Finapres was used to assess digital arterial pressures. As compared to healthy volunteers (n = 16), LDF under control conditions demonstrated an increase in skin blood flow at stage I (P < 0.01). A decrease in skin blood flow under control conditions was seen at stages II (P < 0.05) and III (P < 0.05), but the relative flow reserve capacity, as measured with LDF, was not impaired at these stages. Regression analysis did not show a relation between LDF parameters and duration of the syndrome. TCPO2 revealed no differences between patient groups and controls. Regression analysis did not demonstrate a relation between TCPO2 parameters and duration of the syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex sympathetic dystrophy: evolution of microcirculatory disturbances in time.

Reflex sympathetic dystrophy (RSD) is a pain syndrome that is characterised by autonomic, motor and sensory disturbances. The syndrome has often been associated with sympathetic dysfunction. Therefore, we investigated whether there are disturbances in the sympathetic function of skin microcirculation in the various clinical stages of RSD. Laser Doppler flowmetry (LDF) was used to obtain information about total (mainly thermoregulatory) skin blood flow (TSBF), since blood flow in arteriovenous anastomoses and subpapillary plexus, which are richly innervated by sympathetic nerve endings, contributes predominantly to the flow signal as obtained by LDF. Capillary microscopy was used to appraise whether the trophic changes, as observed in RSD, result from an impaired nutritive skin blood flow (NSBF). Transcutaneous oximetry (TCPO2) was employed as a measure of the oxygenation of superficial skin layers. Skin temperature (ST) was also determined. Patients were divided into 3 clinical stages: stage I in case of a chronic warmth sensation, stage II in case of an intermittent warmth and cold sensation, and stage III in case of a chronic cold sensation. As compared to controls: (1) TSBF was increased (P < 0.05) at stage I and decreased at stages II (P < 0.05) and III (P < 0.001), (2) NSBF was decreased at stages II (P < 0.05) and III (P < 0.001), (3) TCPO2 was not impaired at any stage, (4) ST was increased (P < 0.01) at stage I and decreased (P < 0.05) at stage III. The present study is the first to report an increase of TSBF at stage I of RSD, which may be caused by a decrease in efferent sympathetic nerve impulses. At stages II and III both TSBF and NSBF were decreased which may reflect increased sensitivity of skin microvessels to (circulating) catecholamines.

Reflex sympathetic dystrophy: result of autonomic denervation?

1. To investigate the nature of sympathetic dysfunction in the pathogenesis of reflex sympathetic dystrophy, the microcirculatory vasoconstrictive responses to dependency were investigated in the skin of the hand of 76 reflex sympathetic dystrophy patients with unilateral disease by means of laser Doppler flowmetry (in perfusion units) and capillary microscopy. The patients were divided into three stages according to their perception of skin temperature (stage I in the case of a stationary warmth sensation, stage II in the case of an intermittent warmth and cold sensation, and stage III in the case of a stationary cold sensation). The vasoconstrictive responses were induced by lowering of the affected hand. 2. As compared to controls, the mainly sympathetically mediated vasoconstrictive response at thermoregulatory level of the skin microcirculation, as measured by laser Doppler flowmetry, was attenuated at stage I (1.82 versus 1.41, P < 0.05), stage II (1.82 versus 1.09, P < 0.0001) and stage III (1.82 versus 1.14, P < 0.01), suggesting the involvement of sympathetic denervation at all stages of the reflex sympathetic dystrophy syndrome. This sympathetic denervation may also account for the observed increase in thermoregulatory skin blood flow at stage I as compared to controls (152 versus 81, P < 0.01). 3. Since sympathetic denervation has been reported to cause increased sensitivity of vascular structures to catecholamines, the decrease in thermoregulatory skin blood flow at stages II (54 versus 81, P < 0.05) and III (31 versus 81, P < 0.05), both as compared to controls, may result from hypersensitivity to catecholamines of skin microvessels. 4. The sympathetically independent vasoconstrictive response at the nutritive level of skin microcirculation, as measured by capillary microscopy, was impaired only at stage III as compared to controls (1.04 versus 2.06, P < 0.05). This divergence in microvascular reactivity upon dependency of the nutritive and thermoregulatory subsystems also supports the hypothesis of sympathetic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)