AB0439 CAPILLAROSCOPIC PATTERNS IN PATIENTS WITH SYSTEMIC SCLEROSIS-POLYMYOSITIS/DERMATOMYOSITIS (SSc-PM/DM) OVERLAP SYNDROME

Background:Impaired microcirculation is one of the leading factors in local and general pathogenesis of SSc. Widefield nail-fold video-capillaroscopy (NFVC) stands as the most informative and at the same time simple method used for evaluation of capillary circulation.Objectives:To identify characteristic and specific for SSc– PM/DM capillaroscopic features.Methods:Both hand II – V fingers of 68 pts with SSc-PM/DM were subjected to widefield NFC, evaluated using a binocular 20x magnification Olympus microscope and analyzed in view of specific skin lesions discriminating diffuse and limited SSc forms.Results:SSc-specific dilatations of capillary loops were the most common for SSc-PM/DM and were found in all pts; 50% of them had signs of active scleroderma pattern, such as capillary loss or “avascular areas” (50%) and hemorrhages (51.5%), associated with generalized microvascular spasm in early disease and capillary sclerosis in advanced disease. The morphological capillary abnormalities such as varying degrees of capillary loops tortuosity/vascular inhomogeneity were present in 63% of examined nailfolds, branching bushy behavior of capillary loops and mega-capillaries predominated; architectural disorientation/disarrangement of capillary loops with formation of subcutaneous plexus was seen in more than 50% of them. Capillaroscopic changes consistent with active scleroderma pattern were present in 54 % and were associated with lab signs of inflammatory muscle syndrome and immunological disorders: giant capillaries (p<0.02), disorientation of capillary loops (p<0.02) and ramified/bushy capillaries (p<0.04) were significantly more frequent in patients with severe muscle syndrome, increased CPK, ANF -positivity and hemorrhages (p<0.03).Conclusion:Thus, widefield NFVC revealed a “mixed” nature of capillaroscopic changes, combining features specific for SSc (capillary dilation, avascular areas, hemorrhages) and for PM/DM (bushy and giant capillaries, disorientation of capillary loops of the nailfold with formation of subcutaneous plexuses.)Disclosure of Interests:None declared

Swept-source OCTA quantification of capillary closure predicts ETDRS severity staging of NPDR

PurposeTo test whether a single or composite set of parameters evaluated with optical coherence tomography angiography (OCTA), representing retinal capillary closure, can predict non-proliferative diabetic retinopathy (NPDR) staging according to the gold standard ETDRS grading scheme.Methods105 patients with diabetes, either without retinopathy or with different degrees of retinopathy (NPDR up to ETDRS grade 53), were prospectively evaluated using swept-source OCTA (SS-OCTA, PlexElite, Carl Zeiss Meditec) with 15×9 mm and 3×3 mm angiography protocols. Seven-field photographs of the fundus were obtained for ETDRS staging. Eyes from age-matched healthy subjects were also imaged as control.ResultsIn eyes of patients with type 2 diabetes without retinopathy or ETDRS levels 20 and 35, retinal capillary closure was in the macular area, with predominant alterations in the parafoveal retinal circulation (inner ring). Retinal capillary closure in ETDRS stages 43–53 becomes predominant in the retinal midperiphery with vessel density average values of 25.2±7.9 (p=0.001) in ETDRS 43 and 23.5±3.4 (p=0.001) in ETDRS 47–53, when evaluating extended areas of 15×9 protocol. Combination of acquisition protocols 3×3 mm and 15×9 mm, using SS-OCTA, allows discrimination between eyes with mild NPDR (ETDRS 10, 20, 35) and eyes with moderate-to-severe NPDR (ETDRS grades 43–53).ConclusionsRetinal capillary closure, quantified by SS-OCTA, can identify NPDR severity progression. It is located mainly in the perifoveal retinal capillary circulation in the initial stages of NPDR, whereas the retinal midperiphery is predominantly affected in moderate-to-severe NPDR.

FEATURES OF CAPILLARY BLOOD FLOW IN PATIENTS WITH PATHOLOGY OF INTRANASAL STRUCTURES AND NASAL BREATHING DISORDERS

The investigation of the vascular microcirculation system is important for diagnosis, assessment of the severity and nature of pathological processes in human body, monitoring the effectiveness of treatment. Monitoring the state of microcirculation in impaired respiratory function of the nose helps to study the subtle mechanisms of regulation of vascular−tissue relations. To do this, there were used the biomicroscopic methods to study capillary blood flow, one of the most relevant and promising is optical capillaroscopy of the nail bed. This method makes it possible to identify at the evidence level the peculiarities of the functioning of the peripheral circulatory system by the state of the capillary system and to evaluate the effectiveness of treatment by the rheological properties of blood in hematological practice. There were examined 145 patients by means of computer capillaroscopy to study the rate of capillary circulation in the patients with pathology of intranasal structures and nasal breathing disorders. All patients underwent a complete clinical examination, routine instrumental examinations, and computer capillaroscopy using a video capillaroscope with a visual magnification of up to 550 times. The obtained images were stored and processed according to a special software. During the characterization of the capillaroscopic picture there were evaluated: pathological tortuosity, change in the caliber of arterioles and venules, disorganization of the capillary network, the number of functioning capillaries. Changes in the speed and nature of capillary blood flow (accelerated, slow, stasis) were observed. The optical capillaroscopy method allows not only to visually assess the condition of microvessels, but also to determine such an important parameter as blood circulation, actually, it can replace the study of laser Doppler. Such data will be important in the diagnosis of respiratory and olfactory disorders and the formation of adequate tactics for their treatment. Key words: microcirculation, microcirculatory tract, capillary circulation, nasal obstruction, nasal breathing disorders, pathology of intranasal structures, computer capillaroscopy.

P1012NAIL CAPILLARY DENSITY DURING POSTOCCLUSIVE REACTIVE HYPEREMIA AND VENOUS CONGESTION IS MORE IMPAIRED IN DIABETIC COMPARED TO NON-DIABETIC CKD PATIENTS

Background and Aims Αlterations in endothelial function and capillary circulation have been associated with increased cardiovascular events and overall mortality. Both diabetes mellitus (DM) and chronic kidney disease (CKD) have been associated with microcirculatory damage. Nailfold video-capillaroscory can provide a thorough assessment of capillary density and microcirculation changes. This is the first study examining in comparison microcirculatory function parameters in diabetic and non-diabetic patients with CKD. Method We included 48 diabetic and 48 non-diabetic adult patients (&gt;18 years) with CKD (eGFR: &lt;90 and ≥15mL/min/1.73m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia) and at the end of a 2-minute venous occlusion (congestion phase). Results Baseline demographic, anthropometric and laboratory characteristics were similar between patients with and without diabetes in total and in CKD stages. Overall, no significant differences at baseline capillary density were observed between groups; however diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3±3.8 vs 38.3±4.3 capillaries/mm2, p=0.022) and at venous congestion (37.8±4.0 vs 39.8±4.2 capillaries/mm2, p=0.015). When stratified according to CKD stages, the between-group differences in parameters of interest were not significant in stages 2, 3a and 4. In stage 3b, capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline (31.1±2.8 vs 33.4±3.4 capillaries/mm2, p=0.044), during postocclusive hyperemia (36.8±2.7 vs 40.0±4.3 capillaries/mm2, p=0.037) and venous congestion (38.3±2.8 vs 41.5±3.5 capillaries/mm2, p=0.022). Conclusion Capillary density during postocclusive reactive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory functional impairment in CKD. These differences are more prominent in CKD stage 3b, and less prominent in earlier and later stages.

Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury: A hyperacute role for neutrophils in persistent traffic jams

Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in salvageable penumbra after reperfusion. These stalls, which are different from permanent cellular plugs of no-reflow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling slowly through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments under reperfused conditions. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. Decreased number and duration of stalls were associated with improvement in penumbral blood flow within 2–24 h after reperfusion along with increased capillary oxygenation, decreased cellular damage and improved functional outcome. Thereby, dynamic microcirculatory stall phenomenon can be a contributing factor to ongoing penumbral injury and is a potential hyperacute mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke.

Behavior of oxygen saturation and blood filling in the venous capillary system of the biceps brachii muscle during a fatiguing isometric action

The objective of the study is to develop a better understanding of the capillary circulation in contracting muscles. Ten subjects were measured during a submaximal fatiguing isometric muscle action by use of the O2C spectrophotometer. In all measurements the capillary-venous oxygen saturation of hemoglobin (SvO2) decreases immediately after the start of loading and levels off into a steady state. However, two different patterns (type I and type II) emerged. They differ in the extent of deoxygenation (–10.37 ±2.59 percent points (pp) vs. –33.86 ±17.35 pp, P = .008) and the behavior of the relative hemoglobin amount (rHb). Type I reveals a positive rank correlation of SvO2 and rHb (ρ = 0.735, P <.001), whereas a negative rank correlation (ρ = –0.522, P <.001) occurred in type II, since rHb decreases until a reversal point, then increases averagely 13% above the baseline value and levels off into a steady state. The results reveal that a homeostasis of oxygen delivery and consumption during isometric muscle actions is possible. A rough distinction in two types of regulation is suggested.

Peritoneal dialysis

Peritoneal dialysis is achieved by repeated cycles of instillation and drainage of dialysis fluid within the peritoneal cavity, with the two main functions of dialysis—solute and fluid removal—occurring due to the contact between dialysis fluid and the capillary circulation of the parietal and visceral peritoneum across the peritoneal membrane. It can be used to provide renal replacement therapy in acute kidney injury or chronic kidney disease. Practical aspects—choice of peritoneal dialysis as an effective modality for renal replacement in the short to medium term (i.e. several years) is, for most patients, a lifestyle issue. Typically, a patient on continuous ambulatory peritoneal dialysis will require three to four exchanges of 1.5 to 2.5 litres of dialysate per day. Automated peritoneal dialysis and use of the glucose polymer dialysis solution icodextrin enables flexibility of prescription that can mitigate the effects of membrane function (high solute transport). Peritonitis—this remains the most common complication of peritoneal dialysis, presenting with cloudy dialysis effluent, with or without abdominal pain and/or fever, and confirmed by a leucocyte count greater than 100 cells/µl in the peritoneal fluid. Empirical antibiotic treatment, either intraperitoneal or systemic, with cover for both Gram-positive and Gram-negative organisms, should be commenced immediately while awaiting specific cultures and sensitivities. Long-term changes in peritoneal membrane function influence survival on peritoneal dialysis if fluid removal is less efficient (ultrafiltration failure), especially in the absence of residual kidney function. This is the main limitation of treatment, along with avoiding the risk of encapsulating peritoneal sclerosis—a life-threatening complication of peritoneal dialysis, particularly if of long duration (15–20% incidence after 10 years), that is characterized by severe inflammatory thickening, especially of the mesenteric peritoneum, resulting in an encapsulation and progressive obstruction of the bowel.

Accidental hypothermia as a factor of microcirculatory disorders

Aim. To study the dynamics of indicators of microcirculation during a single episode of hypothermia of moderate degree in rats, both immediately after cessation of cooling, and in different periods of posthypothermia. Methods. The study was performed on 25 Wistar rats. The animals were subjected to a single immersion cooling in water at a temperature of 5 °C until reaching a rectal temperature of 27-30 °C. Analysis of the microvasculature was carried out immediately upon reaching a moderate degree of hypothermia, 2, 5, 10 and 14 days after the cooling. The microcirculation parameters were estimated using a laser analyzer of capillary circulation LAKK-02 (SMO «Lazma», Russia) at a wavelength of 0.63 μm. The main parameters of microcirculation were recorded, and the amplitude-frequency spectrum of blood flow oscillations was analyzed. Results. Immediately after reaching a moderate degree of hypothermia, vasospasm was recorded, which was confirmed by a decrease in the rate of perfusion and wave amplitudes of all frequency ranges. 2 days after stopping the cooling perfusion index returned to baseline, a decrease in amplitude of endothelial, vasomotor and respiratory waves was observed with an increase in pulse waves. On day 5, perfusion increased by 5 times was observed along with decreased amplitudes of the waves of all ranges. By day 10, the level of blood flow returned to its original values, and the wave amplitudes of all frequency ranges remained at the same low level. By day 14, a progressive decrease of the factors of bloodflow modulation was associated by the decrease of perfusion. Conclusion. Single cooling to a moderate degree of hypothermia leads to a progressive decrease of tissue perfusion and deep inhibition of active and passive factors of bloodflow modulation.

Neutrophil-mediated dynamic capillary stalls in ischemic penumbra: persistent traffic jams after reperfusion contribute to injury

Ever since the introduction of thrombolysis and the subsequent expansion of endovascular treatments for acute ischemic stroke, it remains to be identified why the actual outcomes are less favorable despite recanalization. Here, by high spatio-temporal resolution imaging of capillary circulation in mice, we introduce the pathological phenomenon of dynamic flow stalls in cerebral capillaries, occurring persistently in the salvageable penumbra after recanalization. These stalls, which are distinct from permanent cellular plugs that can lead to no-flow, were temporarily and repetitively occurring in the capillary network, impairing the overall circulation like small focal traffic jams. In vivo microscopy in the ischemic penumbra revealed leukocytes traveling through capillary lumen or getting stuck, while red blood cell flow was being disturbed in the neighboring segments, within 3 hours after stroke onset. Stall dynamics could be modulated, by injection of an anti-Ly6G antibody specifically targeting neutrophils. By decreasing the number and duration of stalls, we were able to improve the blood flow in the penumbra within 2-24 hours after reperfusion, increase capillary oxygenation, decrease cellular damage and improve functional outcome. Thereby the dynamic microcirculatory stall phenomenon contributes to the ongoing penumbral injury and is a potential hyperacute stage mechanism adding on previous observations of detrimental effects of activated neutrophils in ischemic stroke.SignificanceThis work provides in vivo evidence that, even in perfused capillaries, abnormal capillary flow patterns in the form of dynamic stalls can contribute to ongoing tissue injury in the salvageable penumbra in very early hours of cerebral ischemia. These events resembling micro traffic jams in a complex road network, are mediated by passage of neutrophils through the microcirculation and persist despite recanalization of the occluded artery.