DEcrease STress through RESilience training for Students (DESTRESS) Study: Protocol for a randomized controlled trial nested in a longitudinal observational cohort study.

INTRODUCTION: Chronic stress and burnout are highly prevalent among academically trained healthcare professionals, negatively affecting their well-being and capacity to engage in their work. Resilience to stress develops early in one's career path, hence offering resilience training to university students in these professions is one approach to fostering well-being and mental health. The aim of this study is to assess whether offering mindfulness-based resilience training to university students in healthcare professions reduces their perceived chronic stress. METHODS AND ANALYSIS: The study has a hybrid design combining a longitudinal observational cohort with a nested randomized controlled trial (RCT) with sequential multiple assignment and multistage adaptive interventions while taking participants' preferences into account. All students in healthcare related programmes at the Erasmus University Rotterdam are invited to participate. Within the observational cohort, students with a score of 14 or higher on the Perceived Stress Scale (PSS) are invited to take part in the RCT (n = 706). Eligible participants are randomized to control or active intervention in a ratio of 1:6. Those randomized to the control group and non-randomized participants in the cohort receive passive web-based psychoeducation about chronic stress and burnout through referral to specific websites. Participants randomized to the intervention group receive one of 8 active mindfulness-based interventions. They select a rank order of 4 preferred interventions and are randomized across these with equal probability. Non-response to the intervention is followed by sequential randomized assignment to another intervention, for a total maximum of 3 sequential interventions. All participants receive questionnaires at baseline, before and after each 8-week intervention period, and at 1- and 2-year follow-up. The primary outcome is perceived chronic stress measured with the PSS. Secondary outcomes include mental well-being, burnout, quality of life, healthcare utilization, drug use, bodyweight, mental and physical stress-related symptoms, resilience, and study progress. ETHICS AND REGISTRATION: Approval from the Medical Ethics Review Committee was obtained under protocol number MEC-2018-1645. The trial is registered in the Netherlands National Trial Register by registration number NL7623, 22/03/2019, https://www.trialregister.nl/.

Inflammation and TGF-ß Signaling Differ between Abdominal Aneurysms and Occlusive Disease.

Abdominal aortic aneurysms (AAA), are usually asymptomatic until rupture causes fatal bleeding, posing a major vascular health problem. AAAs are associated with advanced age, male gender, and cardiovascular risk factors (e.g. hypertension and smoking). Strikingly, AAA and AOD (arterial occlusive disease) patients have a similar atherosclerotic burden, yet develop either arterial dilatation or occlusion, respectively. The molecular mechanisms underlying this diversion are yet unknown. As this knowledge could improve AAA treatment strategies, we aimed to identify genes and signaling pathways involved. We compared RNA expression profiles of abdominal aortic AAA and AOD patient samples. Based on differential gene expression profiles, we selected a gene set that could serve as blood biomarker or as pharmacological intervention target for AAA. In this AAA gene list we identified previously AAA-associated genes COL11A1, ADIPOQ, and LPL, thus validating our approach as well as novel genes; CXCL13, SLC7A5, FDC-SP not previously linked to aneurysmal disease. Pathway analysis revealed overrepresentation of significantly altered immune-related pathways between AAA and AOD. Additionally, we found bone morphogenetic protein (BMP) signaling inhibition simultaneous with activation of transforming growth factor ß (TGF-ß) signaling associated with AAA. Concluding our gene expression profiling approach identifies novel genes and an interplay between BMP and TGF-ß signaling regulation specifically for AAA.

An MRI-based method to register patient-specific wall shear stress data to histology.

Wall shear stress (WSS), the frictional force exerted on endothelial cells by blood flow, is hypothesised to influence atherosclerotic plaque growth and composition. We developed a methodology for image registration of MR and histology images of advanced human carotid plaques and corresponding WSS data, obtained by MRI and computational fluid dynamics. The image registration method requires four types of input images, in vivo MRI, ex vivo MRI, photographs of transversally sectioned plaque tissue and histology images. These images are transformed to a shared 3D image domain by applying a combination of rigid and non-rigid registration algorithms. Transformation matrices obtained from registration of these images are used to transform subject-specific WSS data to the shared 3D image domain as well. WSS values originating from the 3D WSS map are visualised in 2D on the corresponding lumen locations in the histological sections and divided into eight radial segments. In each radial segment, the correlation between WSS values and plaque composition based on histological parameters can be assessed. The registration method was successfully applied to two carotid endarterectomy specimens. The resulting matched contours from the imaging modalities had Hausdorff distances between 0.57 and 0.70 mm, which is in the order of magnitude of the in vivo MRI resolution. We simulated the effect of a mismatch in the rigid registration of imaging modalities on WSS results by relocating the WSS data with respect to the stack of histology images. A 0.6 mm relocation altered the mean WSS values projected on radial bins on average by 0.59 Pa, compared to the output of original registration. This mismatch of one image slice did not change the correlation between WSS and plaque thickness. In conclusion, we created a method to investigate correlations between WSS and plaque composition.

[A girl with a cold foot]. / Een meisje met een koude voet.

A 14-year-old girl presented with a progressively cold, pale foot. Pedal pulses were absent and there was sensory and motor loss. CT angiography revealed a thromboembolic occlusion of the crural arteries and a popliteal artery entrapment. Following thromboembolectomy with popliteal artery patch angioplasty and release of the gastrocnemius muscle, the girl fully recovered.

Low Socioeconomic Status is an Independent Risk Factor for Survival After Abdominal Aortic Aneurysm Repair and Open Surgery for Peripheral Artery Disease.

OBJECTIVE/BACKGROUND: The association between socioeconomic status (SES), presentation, and outcome after vascular surgery is largely unknown. This study aimed to determine the influence of SES on post-operative survival and severity of disease at presentation among vascular surgery patients in the Dutch setting of equal access to and provision of care. METHODS: Patients undergoing surgical treatment for peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), or carotid artery stenosis between January 2003 and December 2011 were retrospectively included. The association between SES, quantified by household income, disease severity at presentation, and survival was studied using logistic and Cox regression analysis adjusted for demographics, and medical and behavioral risk factors. RESULTS: A total of 1,178 patients were included. Low income was associated with worse post-operative survival in the PAD cohort (n = 324, hazard ratio 1.05, 95% confidence interval [CI] 1.00-1.10, per 5,000 Euro decrease) and the AAA cohort (n = 440, quadratic relation, p = .01). AAA patients in the lowest income quartile were more likely to present with a ruptured aneurysm (odds ratio [OR] 2.12, 95% CI 1.08-4.17). Lowest income quartile PAD patients presented more frequently with symptoms of critical limb ischemia, although no significant association could be established (OR 2.02, 95% CI 0.96-4.26). CONCLUSIONS: The increased health hazards observed in this study are caused by patient related factors rather than differences in medical care, considering the equality of care provided by the study setting. Although the exact mechanism driving the association between SES and worse outcome remains elusive, consideration of SES as a risk factor in pre-operative decision making and focus on treatment of known SES related behavioral and psychosocial risk factors may improve the outcome of patients with vascular disease.

Differences in mortality, risk factors, and complications after open and endovascular repair of ruptured abdominal aortic aneurysms.

OBJECTIVE/BACKGROUND: Endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA) has faced resistance owing to the marginal evidence of benefit over open surgical repair (OSR). This study aims to determine the impact of treatment modality on early mortality after rAAA, and to assess differences in postoperative complications and long-term survival. METHODS: Patients treated between January 2000 and June 2013 were identified. The primary endpoint was early mortality. Secondary endpoints were postoperative complications and long-term survival. Independent risk factors for early mortality were calculated using multivariate logistic regression. Survival estimates were obtained by means of Kaplan-Meier curves. RESULTS: Two hundred and twenty-one patients were treated (age 72 ± 8 years, 90% male), 83 (38%) by EVAR and 138 (62%) by OSR. There were no differences between groups at the time of admission. Early mortality was significantly lower for EVAR compared with OSR (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.21-0.97). Similarly, EVAR was associated with a threefold risk reduction in major complications (OR: 0.33, 95%CI: 0.15-0.71). Hemoglobin level <11 mg/dL was predictive of early death for patients in both groups. Age greater than 75 years and the presence of shock were significant risk factors for early death after OSR, but not after EVAR. The early survival benefit of EVAR over OSR persisted for up to 3 years. CONCLUSION: This study shows an early mortality benefit after EVAR, which persists over the mid-term. It also suggests different prognostic significance for preoperative variables according to the type of repair. Age and the presence of shock were risk factors for early death after OSR, while hemoglobin level on admission was a risk factor for both groups. This information may contribute to repair-specific risk prediction and improved patient selection.

Long-term clinical effectiveness of supervised exercise therapy versus endovascular revascularization for intermittent claudication from a randomized clinical trial.

BACKGROUND: Long-term comparisons of supervised exercise therapy (SET) and endovascular revascularization (ER) for patients with intermittent claudication are scarce. The long-term clinical effectiveness of SET and ER was assessed in patients from a randomized trial. METHODS: Consenting patients with intermittent claudication were assigned randomly to either SET or ER. Outcome measures on functional performance (pain-free and maximum walking distance, ankle : brachial pressure index), quality of life (QoL) and number of secondary interventions were measured at baseline and after approximately 7 years of follow-up. Repeated-measurement and Kaplan-Meier methods were used to analyse the data on an intention-to treat-basis. RESULTS: A total of 151 patients were randomized initially to either SET or ER. After 7 years, functional performance (P < 0.001) and QoL (P ≤ 0.005) had improved after both SET and ER. Long-term comparison showed no differences between the two treatments, except in the secondary intervention rate, which was significantly higher after SET (P = 0.001). Nevertheless, the total number of endovascular and surgical interventions (primary and secondary) remained higher after ER (P < 0.001). CONCLUSION: In the longer term, SET-first or ER-first treatment strategies were equally effective in improving functional performance and QoL in patients with intermittent claudication. The substantially higher number of invasive interventions in the ER-first group supports a SET-first treatment strategy for intermittent claudication. REGISTRATION NUMBER: NTR199 (http://www.trialregister.nl).

Vitamin D deficiency may be an independent risk factor for arterial disease.

OBJECTIVES: The aim of this study was to assess the vitamin D status in patients with occlusive or aneurysmatic arterial disease in relation to clinical cardiovascular risk profiles and markers of atherosclerotic disease. METHODS: We included 490 patients with symptomatic peripheral arterial disease (PAD, n = 254) or aortic aneurysm (n = 236). Cardiovascular risk factors and comorbidities carotid intima-media thickness (CIMT), ankle-brachial index (ABI), serum high-sensitive C-reactive protein (hs-CRP) and vitamin D were assessed. Patients were categorised into severely (≤25 nmol l(-1)) or moderately (26-50 nmol l(-1)) vitamin D deficient, vitamin D insufficient (51-75 nmol l(-1)) or vitamin D sufficient (>75 nmol l(-1)). RESULTS: Overall, 45% of patients suffered from moderate or severe vitamin D deficiency. The prevalence of vitamin D deficiency was similar in patients with PAD and those with an aortic aneurysm. Low levels of vitamin D were associated with congestive heart failure and cerebrovascular disease. Adjusting for clinical cardiovascular risk factors, multivariable regression analyses showed that low vitamin D status was associated with higher CIMT (P = 0.001), lower ABI (P < 0.001) and higher hs-CRP (P = 0.022). CONCLUSIONS: The current study shows a strong association between low vitamin D status and arterial disease, independent of traditional cardiovascular risk factors and irrespective of the type of vascular disease, that is, occlusive or aneurysmatic disease.

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.

In treatment of popliteal artery cystic adventitial disease, primary bypass graft not always first choice: two case reports and a review of the literature.

Cystic adventitial disease (CAD) is a rare cause of unilateral intermittent claudication of unknown aetiology, which is characterized by the formation of multiple mucin-filled cysts in the adventitial layer of the arterial wall resulting in obstruction to blood flow. The disease predominantly presents in young otherwise healthy males and most commonly affects the popliteal artery. CAD can be diagnosed by magnetic resonance imaging, computed tomographic angiography, or duplex ultrasound. Surgery is the primary mode of treatment, including exarterectomy, or replacement of the affected vascular segment by venous or synthetic interposition graft. Alternatively, the cysts can be drained by percutaneous ultrasound-guided needle aspiration. We provide a literature update on the aetiology and treatment of this uncommon condition and present two cases supporting patient tailored treatment without primary bypass grafting.

Aortic surgery complications evaluated by an implanted continuous electrocardiography device: a case report.

INTRODUCTION: Cardiac arrhythmias are a major cause for morbidity and mortality in patients undergoing non-cardiac vascular surgery. REPORT: An implantable loop recorder (Reveal(®) XT) was used for continuous heart rhythm monitoring to detect perioperative arrhythmias in a 69-year-old man undergoing major vascular surgery for an infected aortobifemoral prosthesis. The Reveal(®) detected several episodes of asymptomatic new-onset atrial fibrillation postoperatively, associated with elevated serum levels of troponin-T and N-terminal pro-B-type natriuretic peptide NT-proBNP). DISCUSSION: Continuous heart rhythm monitoring with assessment of serum cardiac biomarkers may allow early identification and treatment of patients at high risk of perioperative cardiovascular complications, in particular, cardiac arrhythmias.

Decision-making in type-B dissection: current evidence and future perspectives.

Aortic dissection is a devastating cardiovascular condition with an incidence of 3,5:100 000. It is classified according to anatomic extent, mechanism of lesion, duration from index event and course (uncomplicated vs. complicated). Intramural hematoma and penetrating aortic ulcers share many of the features of classic dissections, but tend to occur in older patients with advanced atherosclerosis. In uncomplicated type-B dissection, conservative treatment with tight blood pressure and heart rate control is safe and effective. Early stent-graft implantation may, however, result in more favorable aortic remodeling and reduced late complications. For acute complicated cases intervention is usually required. Stent-graft coverage of the entry tear frequently resolves malperfusion, but the role of the false lumen in organ perfusion must be assessed and endovascular revascularization performed if necessary. In chronic type-B dissections, coverage of the entry tear likely results in continued pressurization of the false lumen due to rigidity of the dissecting membrane and distal fenestrations. Better understanding of the different disease mechanisms involved, imaging advances and introduction of dedicated stent-grafts are expected to further improve patient outcomes in the future. Primary and secondary pharmacological prevention, stricter follow-up protocols and screening of family members may also prove valuable. Better patient selection will allow preventive treatment with low morbidity for those at higher risk of complications.

Hypoxia disturbs fetal hemodynamics and growth.

Low-birth-weight babies have an increased risk of cardiovascular disease (CVD) in later life. The authors hypothesize that fetal hypoxia alters the structure and function of the developing cardiovascular system resulting in CVD. They investigated the effects of chronic hypoxia on cardiac performance, hemodynamic control, and growth during the second half of embryonic chick development. Three stages of hemodynamic adaptations were identified in hypoxic chick embryos. At embryonic day 13 (E13), heart rate and blood pressure were higher in hypoxic embryos. At E17, this was followed by sympathetic hyperinnervation of peripheral arteries, resulting in increased vasoconstriction during a chemoreflex. This was accompanied by dilatation of the left ventricle and a 50% reduction in cardiac contractility. E19 hypoxic embryos had a 33% higher baseline vascular tone, but failed to maintain blood pressure during acute stress, indicating cardiac failure. Reduced body, heart, and liver weights followed the hemodynamic changes. Chronic hypoxia induces dilated cardiomyopathy and sympathetic hyperinnervation of the peripheral vasculature leading to aberrant fetal hemodynamics and fetal growth restriction. This study identifies that alterations in fetal hemodynamic regulation are in the causal pathway between disturbances in fetal environment, restricted fetal growth and CVD, and establishes fetal hypoxia as a novel risk factor for cardiovascular disease.

Hypoxia induces aortic hypertrophic growth, left ventricular dysfunction, and sympathetic hyperinnervation of peripheral arteries in the chick embryo.

BACKGROUND: Low birth weight is associated with an increased incidence of cardiovascular diseases, including hypertension, later in life. This suggests that antenatal insults program for fetal adaptations of the circulatory system. In the present study, we evaluated the effects of mild hypoxia on cardiac function, blood pressure control, and arterial structure and function in near-term chick embryos. METHODS AND RESULTS: Chick embryos were incubated under normoxic (21% O2) or hypoxic (15% O2) conditions and evaluated at incubation day 19 by use of histological techniques, isolated heart preparations, and in vivo measurements of sympathetic arterial tone and systemic hemodynamics. Chronic hypoxia caused a 33% increase in mortality and an 11% reduction in body weight in surviving embryos. The lumen of the ascending aorta in hypoxic embryos was 23% smaller. Left ventricular systolic pressure was 22% lower, and heart weight/body weight ratio was 14% higher. In resistance arteries of hypoxic embryos, in vivo baseline tone was 23% higher, norepinephrine sensitivity was similar, and norepinephrine release from sympathetic nerves increased 2-fold, indicating sympathetic hyperinnervation. Mean arterial pressure and heart rate were similar under resting conditions, but chronically hypoxic embryos failed to maintain blood pressure during acute stress. CONCLUSIONS: This study indicates that mild hypoxia during embryonic development induces alterations in cardiac and vascular function and structure and affects hemodynamic regulation. These findings reveal that antenatal insults have profound effects on the control and design of the circulatory system that are already established at birth and may program for hypertension and heart failure at a later age.

Effects of experimental lower-limb ischaemia-reperfusion injury on the mesenteric microcirculation.

BACKGROUND: Ischaemia-reperfusion (I-R) of the leg is associated with functional and structural changes in the intestine. This study assessed whether acute hind-limb I-R in rats induced a reduction in perfusion and/or signs of an inflammatory response in the intestine. METHODS: Rats were subjected to 2 h of unilateral hind-limb ischaemia followed by 2 h of reperfusion (I-R group, n = 9) or to a sham procedure (control group, n = 9). Mesenteric microvascular diameters, red blood cell velocity, blood flow and leucocyte-vessel wall interactions during reperfusion were measured using intravital microscopy. RESULTS: Blood pressure and heart rate decreased from 30 min of reperfusion onwards in the I-R group compared with controls. From 15 min after the start of reperfusion, mesenteric arteriolar and venular red blood cell velocity and blood flow decreased by 40-50 per cent. Microvascular diameters and leucocyte-vessel wall interactions did not change. CONCLUSION: Restoration of blood flow to an acutely ischaemic hind limb led to a significant decline in the splanchnic microcirculatory blood flow. There were, however, no signs of an early inflammatory response in the gut.

Development of vasomotor responses in fetal mesenteric arteries.

Changes in mesenteric arterial diameters were studied using intravital microscopy in chick fetuses at days 13 and 17 of incubation, corresponding to 0.6 and 0.8 fetal incubation time, both during 5 min of hypoxia followed by 5 min of reoxygenation and after topical administration of increasing concentrations (10(-6)-10(-2) M) of norepinephrine (NE) and acetylcholine (ACh). Baseline diameters of second-order mesenteric arteries increased from 56 microm at 0.6 incubation to 75 microm at 0.8 incubation. Acute hypoxia induced a reduction in arterial diameter to 87 +/- 4.4% of baseline at 0.6 incubation and to 44 +/- 6.7% at 0.8 incubation (P < 0.01). During reoxygenation, mesenteric arteries dilated to 118 +/- 6.5% and 121 +/- 7.5% of baseline at 0.6 and 0.8 fetal incubation time, respectively. Phentolamine did not affect the vasoconstriction during hypoxia at 0.6 incubation, whereas this alpha-adrenergic antagonist significantly attenuated the vasoconstrictor response at 0.8 incubation (to 93 +/- 2.7% of baseline, P < 0.01). Topical NE induced maximal vasoconstriction to 71 +/- 3% of baseline at 0.6 incubation and to 35 +/- 3.8% at 0.8 incubation (P < 0.01). Maximal vasodilation to topical ACh was 113 +/- 4.4% and 122 +/- 4.8% of baseline at 0.6 and 0.8 incubation, respectively. These in vivo findings show that fetal mesenteric arteries constrict in response to acute hypoxia and that the increase in magnitude of this vasoconstrictor response from 0.6 to 0.8 of fetal development results from an increase in adrenergic constrictor capacity.

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.

Influence of partial nerve injury in the rat on efferent function of sympathetic and antidromically acting sensory nerve fibers.

OBJECTIVE: To investigate how partial injury of a large peripheral nerve affects efferent (vasomotor) function of sympathetic and antidromically acting sensory nerve fibers. DESIGN: Randomized animal study. MATERIALS AND METHODS: We assessed, by laser Doppler flowmetry, skin blood flow (SBF) in the hindpaw of male Lewis rats before partial injury of the ipsilateral sciatic nerve (through loose ligation) as well as at an early stage (day 4) and at a later stage (day 21) after this procedure. This procedure has been reported to induce signs and symptoms like those observed in patients with causalgia. At the two time points after nerve injury, SBF was assessed before and after (chemical) blockade of sensory and nonsensory (sympathetic) sciatic nerve fibers. Furthermore, at day 21 we measured the density of sympathetic nerve fibers in footpad arteries. MEASUREMENTS AND MAIN RESULTS: At day 4, compared with preligation values, we observed an increase in SBF that was reduced by blockade of sensory nerve fibers. Subsequent blockade of nonsensory nerve fibers further reduced SBF. At day 21, SBF was decreased compared with preligation values. Blockade of sensory nerve fibers further reduced SBF, and subsequent blockade of nonsensory nerve fibers did so as well. The density of sympathetic nerve fibers was lower on the ligated side than on the nonligated side. CONCLUSIONS: Partial injury of the rat sciatic nerve causes an ipsilateral increase in SBF at an early stage, which is followed by a decrease at a later stage. At both stages, antidromically acting sensory and orthodromically acting nonsensory (sympathetic) nerve fibers are involved in the vasodilator response. At a later stage, however, neurogenic vasodilator mechanisms are overruled by a nonneurogenic vasoconstrictor mechanism. The latter may consist of supersensitivity of skin microvessels to catecholamines consequent to reduced neurogenic disposition of catecholamines.

Skin blood flow disturbances in the contralateral limb in a peripheral mononeuropathy in the rat.

Electrical excitation of nociceptive afferents in an extremity has been demonstrated to increase skin blood flow in the contralateral extremity. Hence, one would expect that loose sciatic nerve ligation, which induces an experimental painful peripheral neuropathy, may also provoke a vasodilator response in the contralateral hindpaw. On the non-ligated side, such a response may involve inhibited skin vasoconstrictor activity as well as neurogenically mediated active vasodilation. We studied skin blood flow changes in the rat hindpaw consequent to contralateral loose sciatic nerve ligation. After ligation, we also investigated whether blockade of afferent input from the ligated sciatic nerve to the spinal cord, by means of lidocaine, overrules the vasodilator response in the non-ligated paw. On the non-ligated side, we assessed the vasoconstrictor response of skin microvessels to cooling of the rat abdomen as a measure of skin vasoconstrictor activity in this paw. In order to investigate the involvement of sensory and/or non-sensory nerve fibers in the non-ligated sciatic nerve on skin blood flow abnormalities in the non-ligated paw, we studied the influence of blockade of these fibers through successive capsaicin and lidocaine application. We show that loose ligation of the sciatic nerve induces a vasodilator response in the contralateral hindpaw, which is completely abolished by blockade of afferent input from the ligated sciatic nerve. From day 1 after ligation, skin vasoconstrictor activity in the non-ligated paw was reduced, as indicated by an impaired vasoconstrictor response to cooling of the rat abdomen. Besides, blockade of sensory but not of non-sensory nerve fibers on the non-ligated side attenuated the vasodilator response in this paw. The data presented here indicate that loose ligation of the rat sciatic nerve induces a vasodilator response in the contralateral hindpaw. On the non-ligated side, this vasodilator response may involve inhibition of skin vasoconstrictor activity, as well as antidromically acting sensory nerve fibers.