Human ocular surface microcirculation quantified by in vivo computer assisted video microscopy and diffuse reflectance spectroscopy.

Non-invasive imaging techniques are increasingly used to objectively quantify anterior segment structures of the eye. In this study, we apply the novel oxygen delivery index (ODIN) concept that, quantifies microvascular capacity for oxygen delivery, to the ocular surface in healthy humans. The purpose of the study was to test the applicability of the technologies used for data acquisition from the human ocular surface. We also validated whether the ODIN concept has sufficient sensitivity to detect and differentiate between microvascular structure and function in limbal and bulbar conjunctiva. Multiple ocular surface measurements using computer-assisted video microscopy (field of view: 1.6 mm × 0.9 mm) and diffuse reflectance spectroscopy (measuring volume: ∼0.1 mm3) were obtained from limbal and bulbar conjunctiva in 20 healthy volunteers. Three parameters were extracted during analyses: Functional capillary density, capillary flow velocity, and microvascular oxygen saturation. Functional capillary density was higher at limbus than in bulbar conjunctiva (11.2 ± 1.8 c/mm versus 5.2 ± 1.2 c/mm, p < 0.01), and microvascular oxygen saturation was lower at limbus (77 ± 8%) as compared to bulbar conjunctiva (89 ± 6%), p < 0.01. More than 80% of scored capillaries had continuous blood flow and no difference was seen between the recording sites (p = 0.68). In conclusion, the ODIN concept is applicable for the assessment of human ocular surface microvascular function and has sufficient sensitivity to detect increased capillary density and oxygen extraction at limbus as compared with bulbar conjunctiva.

Microvascular remodeling following skin injury.

OBJECTIVE: The aim of this study was to describe possible remodeling (i.e., dilatation and elongation) of papillary capillaries induced by increased oxygen demand for the repair process following a skin wound. METHODS: Computer-assisted video microscopy was used to examine 10 healthy volunteers before (baseline) and after (≈1 h and ≈24 h) an incision (5 mm long and 1 mm deep) on the forearm, 0-1 mm and 30 mm (control site) from the incision. We defined categories from 0 (low) to 3 (high) to grade dilatation and elongation of the nutritive papillary capillaries, as well as the visibility of the superficial vascular plexus. Approximately 10 000 capillaries from 200 films were scored. RESULTS: The nutritive papillary capillaries were dilated and elongated (p < 0.01) after ≈24 h; that is, elongation (score 1.9 ± 0.9) vs baseline (score 0.9 ± 0.6), p < 0.01 and dilatation (score 2.2 ± 0.7) vs baseline (score 0.3 ± 0.3), p < 0.01. Superficial plexus visibility increased (p < 0.01) after ≈1 h (score 2.0 ± 0.7) and ≈24 h (score 2.7 ± 0.3) vs baseline (score 0.8 ± 0.4). CONCLUSION: The superficial vascular skin plexus showed enhanced visibility already ≈1 h after the skin trauma. Morphological remodeling in the nutritive papillary capillaries-dilatation and elongation after ≈24 h-facilitate increased O2  supply.

Ocular surface microcirculation is better preserved with pulsatile versus continuous flow during cardiopulmonary bypass-An experimental pilot.

BACKGROUND: Non-pulsatile cardiopulmonary bypass (CPB) may induce microvascular dysregulation. In piglets, we compared ocular surface microcirculation during pulsatile versus continuous flow (CF) bypass. METHODS: Ocular surface microcirculation in small tissue volumes (~0.1 mm3 ) at limbus (high metabolic rate) and bulbar conjunctiva (low metabolic rate) was examined in a porcine model using computer assisted video microscopy and diffuse reflectance spectroscopy, before and after 3 and 6 h of pulsatile (n = 5 piglets) or CF (n = 3 piglets) CPB. Functional capillary density, capillary flow velocity and microvascular oxygen saturation were quantified. RESULTS: At limbus, velocities improved with pulsatility (p < 0.01) and deteriorated with CF (p < 0.01). In bulbar conjunctiva, velocities were severely reduced with CF (p < 0.01), accompanied by an increase in capillary density (p < 0.01). Microvascular oxygen saturation decreased in both groups. CONCLUSION: Ocular surface capillary densities and flow patterns are better preserved with pulsatile versus CF during 6 h of CPB in sleeping piglets.

Hemodynamic evaluation of a new pulsatile blood pump during low flow cardiopulmonary bypass support.

BACKGROUND: The VentriFlo® True Pulse Pump (VentriFlo, Inc, Pelham, NH, USA) is a new pulsatile blood pump intended for use during short-term circulatory support. The purpose of this study was to evaluate the feasibility of the VentriFlo and compare it to a conventional centrifugal pump (ROTAFLOW, Getinge, Gothenberg, Sweden) in acute pig experiments. METHODS: Pigs (40-45 kg) were supported by cardiopulmonary bypass (CPB) with the VentriFlo (n = 9) or ROTAFLOW (n = 5) for 6 h. Both VentriFlo and ROTAFLOW circuits utilized standard CPB components. We evaluated hemodynamics, blood chemistry, gas analysis, plasma hemoglobin, and microcirculation at the groin skin with computer-assisted video microscopy (Optilia, Sollentuna, Sweden). RESULTS: Pigs were successfully supported by CPB for 6 h without any pump-related complications in either group. The VentriFlo delivered an average stroke volume of 29.2 ± 4.8 ml. VentriFlo delivered significantly higher pulse pressure (29.1 ± 7.2 mm Hg vs. 4.4 ± 7.0 mm Hg, p < 0.01) as measured in the carotid artery, with mean aortic pressure and pump flow comparable with those in ROTAFLOW. In blood gas analysis, arterial pH was significantly lower after five hours support in the VentriFlo group (7.30 ± 0.07 vs. 7.43 ± 0.03, p = 0.001). There was no significant difference in plasma hemoglobin level in both groups after six hours of CPB support. In microcirculatory assessment, VentriFlo tended to keep normal capillary flow, but it was not statistically significant. CONCLUSIONS: VentriFlo-supported pigs showed comparable hemodynamic parameters with significantly higher pulse pressure compared to ROTAFLOW without hemolysis.

Skin trauma rapidly induces thermoregulatory plexus hyperemia, while an increased nutritive papillary capillary function can be detected after 24 h.

OBJECTIVE: Clinical assessments and laser Doppler perfusion measurements (LDPM) of skin microcirculation have limited value, as they fail to capture events regulated by local metabolic needs at a papillary capillary level. This study aimed to examine the ability of computer-assisted video microscopy (CAVM) and diffuse reflectance spectroscopy (DRS) to assess skin nutritive perfusion-compared to LDPM. METHODS: Healthy volunteers (n = 10) were examined after (≈1 and ≈24 h) an incision (5 × 1 mm) on the forearm, at 0.1 mm (only with CAVM), 2-3 mm, and 30 mm from the trauma. RESULTS: No changes were detected by CAVM after ≈1 h. After ≈24 h, 0-1 mm from the trauma, both CAVM parameters were increased: functional capillary density (capillary crossings/mm, 11.8 ± 1.4 vs. 7.3 ± 1.2, p < .01) and capillary flow velocities (CFV, %capillaries with brisk flow, 10 ± 6.8 vs. 1 ± 1, p < .01). At a distance of 2-3 mm, only CFV was increased (6.2 ± 6.1 vs. 1 ± 1, p < .05). DRS and LDPM measurements increased 2-3 mm from the trauma line in relation to baseline after both ≈1 and ≈24 h, that is, with DRS (%microvascular oxygen saturation): 45.8 ± 7.4% (baseline), 70.0 ± 12.5% (≈1 h), and 73.1 ± 10.4% (≈24 h), p < .01 and with LDPM (a.u.): 7.2 ± 2.5 (baseline), 28.3 ± 18.7 (≈1 h), and 45.9 ± 16.3 (≈24 h), p < .01. CONCLUSIONS: ≈24 h after skin trauma, an increased function of the nutritive papillary capillaries can be detected by CAVM.

Intraperitoneal microdialysis detects intestinal leakage earlier than hemodynamic surveillance and systemic inflammation in a pig model.

OBJECTIVE: Anastomotic leakage is a common complication following large abdominal surgery, often developing to life-threatening abdominal sepsis due to late diagnosis. Currently, diagnostics rely on systemic hemodynamic and infection monitoring. We hypothesized that intraperitoneal microdialysis allows detection of peritonitis prior to changes in standard clinical parameters in a pig model. MATERIALS AND METHODS: We included six pigs; five underwent intraperitoneal fecal contamination, one had sham surgery for a total of 10 h. Microdialysis was established in four intraabdominal quadrants and two hepatic lobes. All pigs were hemodynamically monitored with pulmonary artery and femoral artery catheters. Blood samples were assessed for inflammatory markers, terminal complement complex (TCC), interleukin (IL)-6, IL-10, and plasminogen activator inhibitor-1 (PAI-1). RESULTS: Microdialysis showed intraperitoneal lactate increase during the first two hours after fecal contamination, which remained elevated throughout the observation time with concurrent decrease of glucose. Arterial lactate remained within reference range (<1,6mM). Systemic inflammatory markers TCC, IL-6, IL-10 and PAI-1 increased significantly after minimum four hours. Mean arterial pressure, stroke volume variation and cardiac output were not compromised the first five hours. Sham surgery did not influence any of the parameters. CONCLUSION: Intraperitoneal fecal contamination leads to a rapid and pronounced intraperitoneal increase in lactate, decrease in glucose while pyruvate and glycerol levels remain unchanged. This distinct metabolic pattern of peritoneal inflammation can be easily detected by microdialysis. Observation of this pattern may minimize time to safe diagnosis of intestinal perforations after intraperitoneal fecal contamination.

Quantification of ocular surface microcirculation by computer assisted video microscopy and diffuse reflectance spectroscopy.

In piglets we tested the applicability of digital video microscopy and diffuse reflectance spectroscopy for non-invasive assessments of limbal and bulbar conjunctival microcirculation. A priori we postulated that the metabolic rate is higher in limbal as compared to bulbar conjunctiva, and that this difference is reflected in microvascular structure or function between the two locations. Two study sites, Oslo University Hospital (OUH), Norway and Cleveland Clinic (CC), USA, used the same video microscopy and spectroscopy techniques to record limbal and bulbar microcirculation in sleeping piglets. Recordings were analyzed with custom-made software to quantify functional capillary density, capillary flow velocity and microvascular oxygen saturation in measuring volumes of approximately 0.1 mm3. The functional capillary density was higher in limbus than in bulbar conjunctiva at both study sites (OUH: 18.1 ± 2.9 versus 12.2 ± 2.9 crossings per mm line, p < 0.01; CC: 11.3 ± 3.0 versus 7.1 ± 2.8 crossings per mm line, p < 0.01). Median categorial capillary blood flow velocity was higher in bulbar as compared with limbal recordings (CC: 3 (1-3) versus 1 (0-3), p < 0.01). Conjunctival microvascular oxygen saturation was 88 ± 5.9% in OUH versus 94 ± 7.5% in CC piglets. Non-invasive digital video microscopy and diffuse reflectance spectroscopy can be used to obtain data from conjunctival microcirculation in piglets. Limbal conjunctival microcirculation has a larger capacity for oxygen delivery as compared with bulbar conjunctiva.

Acute skin trauma induces hyperemia, but superficial papillary nutritive perfusion remains unchanged.

OBJECTIVES: Superficial skin papillary capillaries with blood supply from a superficial vascular plexus and regulated by local metabolic needs supply oxygen and nutrients for epithelial cell proliferation. A deep vascular plexus regulated by autonomous nerves serves body thermoregulation. In healthy volunteers, we assessed circulatory effects of a standardized skin trauma by CAVM, DRS, and LDPM to assess the measuring depth of the three techniques and to describe the acute trauma effects on nutritive and thermoregulatory perfusion. METHODS: Volunteers (n=12) were examined at baseline and after induction of a 5.0 mm×1.0 mm incision on the forearm; 30 minutes after the trauma induction, data were collected at 0-1, 2-3 and 30 mm distances. RESULTS: LDPM showed hyperemia at 2-3 mm distance (35.8±15.2 a.u.), but not at 30 mm distance (7.4±2.5 a.u.) compared to baseline (8.8±1.8 a.u.). The DRS saturation increased at 2-3 mm (71.2±4.8%), but not at 30 mm (49.8±7.9%) compared to baseline (45.8±7.4%). Capillary density and flow velocities were unaffected at all distances. CONCLUSIONS: The results indicate that skin nutritive papillary capillary function can be assessed by CAVM and DRS, but not with LDPM because of its dependence of the deep plexus perfusion.

Noninvasive assessments of oxygen delivery from the microcirculation to skin in hypothermia-treated asphyxiated newborn infants.

BACKGROUND: Therapeutic hypothermia (TH) has become standard treatment for severe and moderate hypoxic-ischemic neonatal encephalopathy (HIE). Our group has developed an optically based, noninvasive concept of assessing the capacity for oxygen delivery from the microcirculation to the cells of a tissue under investigation. The hypothesis was that mechanisms of reduced oxygen delivery due to reduced metabolism in cooled asphyxiated neonates could be characterized with this concept. METHODS: The skin of 28 asphyxiated newborn infants was studied on days 1 and 3 during TH and on day 4 following rewarming with laser Doppler perfusion measurements (LDPM), computer-assisted video microscopy (CAVM), and diffuse reflectance spectroscopy (DRS). Twenty-five healthy neonates served as a control group. RESULTS: The LDPM decreased during cooling (P < 0.01). Functional capillary density was higher both during and following TH compared with control infants (P < 0.01). Capillary flow velocities were reduced during TH (P < 0.05). The heterogeneity of the flow velocities was larger in the HIE infants than in the control infants. Tissue oxygen extraction was higher during TH (P < 0.01). CONCLUSION: This study indicates that assessments of skin microvascular density, capillary flow velocity, and oxygen extraction can be used to characterize reduced oxygen delivery to cells during TH.

Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7.

Seven patients diagnosed with erythromelalgia (EM) were investigated by microneurography to record from unmyelinated nerve fibers in the peroneal nerve. Two patients had characterized variants of sodium channel Nav1.7 (I848T, I228M), whereas no mutations of coding regions of Navs were found in 5 patients with EM. Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the patients with EM showed spontaneous activity. In the patient with mutation I848T, all nociceptors, but not sympathetic efferents, displayed enhanced early subnormal conduction in the velocity recovery cycles and the expected late subnormality was reversed to supranormal conduction. The larger hyperpolarizing shift of activation might explain the difference to the I228M mutation. Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the patient carrying the I848T mutation, confirming in human subjects that the presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant channels. The characteristic pattern of changes in conduction velocity observed in the patient with the I848T gain-of function mutation in Nav1.7 could be explained by axonal depolarization and concomitant inactivation of Nav1.7. If this were true, activity-dependent hyperpolarization would reverse inactivation of Nav1.7 and account for the supranormal CV. This mechanism might explain normal pain thresholds under resting conditions.

Skin microcirculation in healthy term newborn infants--assessment of morphology, perfusion and oxygenation.

UNLABELLED: Despite microcirculation's fundamental role, assessments of its function are limited. We explored the applicability of Computer Assisted Video Microscope (CAVM), Laser Doppler Perfusion Measurements (LDPM) and Diffuse Reflectance Spectroscopy (DRS) to study skin microvascular morphology, perfusion and oxygen saturation in twenty-five healthy newborns day 1-3 of life. RESULTS: Day 1-3 (mean (SD)): Microvascular density (CAVM; number of microvessels crossing a grid of lines/mm line, c/mm): Chest: 11.3 (1.5), 11.0 (1.7), 10.7 (1.6). Hand: 13.2 (2.0), 13.2 (1.9), 12.4 (1.6). Capillary density was significantly higher in the hand than in the chest each day (p <  0.001). Perfusion (LDPM; arbitrary units): Chest: 109.1 (26.0), 101.4 (24.6), 100.8 (25.3). Hand: 58.9 (17.5), 54.3 (15.8), 46.9 (14.8). Perfusion was significantly higher in the chest than in the hand each day (p <  0.01). Microvascular oxygen saturation (DRS; %): Chest: 88.1 (5.2), 87.8 (10.0), 86.7 (9.0). Hand: 79.9 (15.2), 82.7 (11.8), 82.2 (12.1) (p <  0.05). Capillary flow velocities (CAVM) were similar in the chest and hand: 60-70% capillaries had "continuous high flow" and 30-40% "continuous low flow".Multimodal skin microvascular assessments with CAVM, LDPM and DRS are feasible with reproducible data in newborns. The hand has lower perfusion, higher capillary density and higher oxygen extraction than the chest.

Skin microvascular morphology and hemodynamics during treatment with veno-arterial extra-corporeal membrane oxygenation.

OBJECTIVES: To explore the potentials of microcirculatory assessments for predicting outcome of patients treated with extra corporeal membrane oxygenation for cardiogenic shock. METHODS: Eight patients with acute cardiogenic shock treated with ECMO and eight healthy controls were examined with skin vital microscopy and laser Doppler perfusion measurements. RESULTS: Three patients died on ECMO (group 1). Five patients were successfully weaned off ECMO (group 2). Four patients were discharged from hospital and one died after successful weaning from bleeding complications. Patients surviving ECMO (group 2) had microcirculatory findings comparable with healthy controls. Patients in group 1 showed major skin microvascular pathology: pericapillary bleedings (n = 1), pericapillary dark haloes (n = 2) and capillary micro thrombi (n = 1). As compared with survivors they had lower functional capillary density (FCD) (n = 3), higher heterogeneity of functional capillary density (n = 3) and significantly reduced capillary mean flow-categorical velocity (n = 2). Laser Doppler measurements in group 1 had non-significant lower laser Doppler flux values as compared with survivors and controls. CONCLUSION: Skin microvascular pathology as detected with video microscopy (pericapillary bleedings or haloes, micro-thrombi/capillaries with "no flow", low FCD with high spatial distribution heterogeneity or low mean flow-categorial velocity) seems to be associated with poor prognosis.

Nonspecific capillary proliferation and vasculopathy indicate skin hypoxia in erythromelalgia.

OBJECTIVE: To report on the histopathologic findings of affected skin in consecutively collected biopsy specimens from 49 patients with erythromelalgia (EM). DESIGN: Skin biopsy specimens were obtained from the foot arch and analyzed by light microscopy, immunofluorescence microscopy, and electron microscopy. SETTING: Oslo University Hospital-Gaustad, University of Oslo, Oslo, Norway. PARTICIPANTS: Thirty-one patients had primary EM, 17 patients had secondary EM, and 1 patient had erythromelalgic syndrome. MAIN OUTCOME MEASURE: Evidence of microvascular abnormalities in skin biopsy specimens. RESULTS: Light microscopy showed evidence of capillary proliferation in 10 of 31 patients with primary EM and in 1 of 17 patients with secondary EM. The biopsy specimen from the patient with erythromelalgic syndrome showed numerous capillary nests with endothelial cell defects and a slight perivascular inflammatory reaction. Among the 17 secondary EM cases, sparse perivascular lymphocyte infiltrations were observed in the biopsy specimens from 2 patients with chronic myelogenous leukemia and 1 patient with diabetes mellitus. Eleven patients also had signs of vasculopathy based on findings of immunodeposits of C3 and fibrin. Six of 30 patients with primary EM showed endothelial abnormalities on electron microscopy. All 3 investigations showed unremarkable biopsy results in 16 cases. CONCLUSIONS: Histopathologic analysis is not useful as a routine diagnostic tool in EM because no morphological changes are specific to EM. The capillary proliferation and vasculopathy are assumed to be a consequence of intermittent skin hypoxia (vascular hypothesis of pathogenesis). Whether the proliferation is a consequence of EM or a pathogenic factor in the development of the disease is uncertain.

Pain in primary erythromelalgia--a neuropathic component?

Erythromelalgia is a condition characterized by attacks of red, hot, painful extremities with relief of symptoms by cooling and aggravation by warmth. Although the main emphasis has been on pathophysiological mechanisms related to circulatory changes, recent reports have focused on an involvement of efferent small nerve fibers indicating a neuropathic component. Since the symptoms resemble those described in neuropathic pain, we wanted to investigate the possible affection of afferent nerve fibers. Twenty-five patients with primary erythromelalgia were examined by neurological testing, neurography and quantitative sensory testing. Thresholds for heat, cold, heat-pain and cold-pain detection were compared with those of a group of 29 healthy controls. The patients had significantly higher median heat (39.5 (36.1-40.8) and cold (29.3 (27.1-30.8)-detection thresholds at the dorsal aspects of their feet compared to the controls (37.0 (35.4-37.7) and 31.2 (30.3-31.5) respectively). These findings show an impaired small fiber function inside or close to the symptomatic area in this group of erythromelalgia patients. Seven patients had brush-evoked allodynia and fourteen had punctate hyperalgesia inside or close to the symptomatic areas in their feet. When comparing the individual results, there is a tendency to clustering of patients in two separate groups; reduced small fiber input/no hyperalgesia and normal thermal thresholds/hyperalgesia. Our results showing an affection of afferent small nerve fibers together with the nature of the symptoms, suggest that the pain experienced by erythromelalgia patients could have a neuropathic component.

The prostaglandin E1 analog misoprostol reduces symptoms and microvascular arteriovenous shunting in erythromelalgia-a double-blind, crossover, placebo-compared study.

Based on previous experience with parenteral prostanoids, we studied the effect of misoprostol treatment, an orally administered prostaglandin E1 analog, in patients with erythromelalgia. Treatment with placebo was followed by treatment with misoprostol (0.4-0.8 mg per d), both for 6 wk. The patients (n=21) and a study nurse who administered the trial were blinded. The endpoints were change in pain and need for cooling and global assessment of the treatment. Following central body heat provocation, global skin perfusion, capillary morphology, and change in pain were also recorded before and after each treatment period. Results were compared with data from healthy control subjects (n=11) that did not undergo treatment. Clinical safety and tolerability evaluation included physical examinations, clinical laboratory tests, and monitoring of adverse events. All clinical outcome measures were significantly better after treatment with misoprostol (p<0.01) as compared with placebo treatment and after a 3- mo follow-up without treatment. The heat-induced increase in global perfusion after misoprostol treatment was similar to the control group and significantly lower when compared with baseline (p<0.01) and placebo treatment (p<0.05), respectively. This study demonstrates that misoprostol is clinically superior to placebo in patients with erythromelalgia. The results of the perfusion studies may imply that the mechanism of action of the beneficial effect of misoprostol is reduced microvascular arteriovenous shunting in affected skin.

Prostacyclin reduces symptoms and sympathetic dysfunction in erythromelalgia in a double-blind randomized pilot study.

Sympathetic dysfunction and skin microvascular arteriovenous shunting with insufficient nutritive perfusion and tissue hypoxia have been reported in patients with erythromelalgia. The objective of this study was to determine whether iloprost, a synthetic prostacyclin analogue--primarily a vasodilator and inhibitor of platelet activation--improves symptoms and sympathetic function in patients with erythromelalgia. Erythromelalgia is a rare condition, but we managed to collect 12 primary cases for a double-blind, randomized, parallel-group pilot trial evaluating the effect of iloprost (n = 8) and placebo (n = 4). The treatment effect was determined by the need for cooling of affected skin and by vasoconstrictor tests following Valsalva's manoeuvre and contralateral cooling. The results show a significant reduction in symptoms (p < 0.05) and sympathetic dysfunction (p < 0.05) in the iloprost group. Further studies with oral prostacyclins or analogues are suggested.

Reduced skin capillary density during attacks of erythromelalgia implies arteriovenous shunting as pathogenetic mechanism.

Erythromelalgia is characterized by burning pain, erythema, and increased temperature in acral skin. The pain is aggravated by warming and relieved by cooling. Increased microvascular arteriovenous shunting in deep dermal plexa has been hypothesized as the pathogenetic mechanism of pain in affected skin, inducing hypoxia during pain attacks. The aim of this study was to quantify skin capillary density in erythromelalgic patients before and after heat provocation, as increased skin temperature should increase the need for nutritive blood supply by the capillaries. Fourteen patients and 10 healthy control subjects were studied using an enhanced technique of computer-assisted analysis of capillary bed morphology and temperature measurements before and after central body heating. The increase in acral skin temperature was significantly higher (p < 0.05) in the eight patients where symptoms were induced after heat provocation, compared to asymptomatic patients and healthy control subjects. The number of visible capillaries in a field of view (1.7 mm2) decreased significantly (p = 0.01) in erythromelalgia patients from 105 (62-137) (median with total range) to 89 (49-118) after warming in areas with numerous arteriovenous anastomoses (nail bed region). In symptomatic patients an even more significant reduction was observed (p = 0.01). The capillary size was also significantly reduced (p < 0.05) from 41.0 (31.5-50.5) (arbitrary units) to 37.3 (33.0-46.0) in symptomatic patients. The change in capillary density in the nail bed area was significantly larger in erythromelalgia patients -17 (-49 to 39) compared to controls 0 (-47 to 13) (p < 0.05), and in symptomatic patients -19 (-49 to -12) compared to asymptomatic patients -8 (-48 to 39) (p < 0.05) and controls (p < 0.01). The reduced skin capillary density after heating is compatible with increased microvascular arteriovenous shunting of blood and a corresponding relative deficit in nutritive perfusion (steal phenomenon) with skin hypoxia, causing the symptoms in erythromelalgia.

Impaired neurogenic control of skin perfusion in erythromelalgia.

Erythromelalgia is a clinical diagnosis characterized by erythema, increased temperature and burning pain in acral skin. The pain is relieved by cooling and aggravated by warming. The symptoms have been hypothesized to be caused by skin hypoxia due to increased arteriovenous shunting. We examined skin microvascular perfusion in response to vasoconstrictory and vasodilatory stimuli, to characterize local and central neurogenic reflexes as well as vascular smooth muscle and vascular endothelial function, using laser Doppler perfusion measurements in 14 patients with primary erythromelalgia and healthy control persons. Skin perfusion preceding provocative stimuli was significantly reduced in patients with erythromelalgia (p < 0.01). The laser Doppler flowmetry signal after sympathetic stimulation of reflexes mediated through the central nervous system, was significantly diminished in patients with erythromelalgia as compared with healthy controls (Valsalva's maneuver p < 0.01; contralateral cooling test p < 0.05). Local neurogenic vasoconstrictor (venous cuff occlusion and dependency of the extremity) and vasodilator reflexes (local heating of the skin), as well as tests for vascular smooth muscle and vascular endothelial function (postocclusive hyperemic response) were maintained. These results indicate that postganglionic sympathetic dysfunction and denervation hypersensitivity may play a pathogenetic role in primary erythromelalgia, whereas local neurogenic as well as endothelial function is unaffected.

[Preoperative expectations and clinical outcome of transmyocardial laser treatment in patients with angina pectoris]. / Preoperativ forventning og klinisk effekt ved transmyokardial laserbehandling mot angina pectoris.

BACKGROUND: The aims of this study were to evaluate the effect of transmyocardial laser treatment on quality of life and to assess the correlation between preoperative expectations and clinical improvement after one year. MATERIAL AND METHODS: 13 patients (median age 56 years) with disabling angina pectoris were subjected to transmyocardial holmium: YAG laser. Quality of life was assessed preoperatively and at three and 12 months by Hospital Anxiety and Depression Scale (HAD), Physical Symptom Distress Index (PSDI) and Life Satisfaction Index (LSI). Expectations were evaluated by Leedham's scale. RESULTS: A significant improvement in Canadian Cardiovascular Society Score (CCS) from 3.4 +/- 0.5 (mean +/- SD) preoperatively to 1.6 +/- 1.0 and 1.7 +/- 0.8 three and 12 months after treatment was observed (p < 0.01). Quality of life (PSDI and LSI) improved. No significant changes in ejection fraction or exercise performance were found. Preoperative expectations were generally high, but did not correlate significantly with improvements in CCS or quality of life. INTERPRETATION: Although no changes in objective parameters were found, the lack of significant correlations between preoperative expectation and subjective clinical improvement indicate that the improvement of angina pectoris only partly can be explained by placebo effects.