Low Perfusion Research Articles

Yaşlı Acil Servis Hastaları Sonuçlarının Tahmininde Ulusal Erken Uyarı Skoru ve Perfüzyon İndeksinin Kullanımı

Objectives: Vitals are the most important parameters for assessing a patient’s status and the National Early Warning Score helps to assess vitals to predict how urgent a patient’s condition is. The perfusion index is the ratio of the pulsatile blood flow to the non-pulsatile/static blood flow in a patient’s peripheral tissue. We aimed to investigate the relationship between the National Early Warning Score and perfusion index in the courses and evaluate whether NEWS and PI are useful in predicting outcomes of older patients in an Emergency Department. Method: In this prospective cross-sectional study, we evaluated non-traumatized older patients admitted to an Emergency Department. National Early Warning Score, perfusion index, and patients’ Emergency Department outcomes were recorded. Results: A total of 967 patients (55% female, mean age=74.8) were enrolled. The initial National Early Warning Score of the patients had a significant, negative correlation with perfusion index (p < 0.001). Patients admitted to the hospital had higher National Early Warning Score and lower perfusion index values than those discharged (both p < 0.001). Patients admitted to an ICU had significantly higher National Early Warning Score and lower perfusion index values than those admitted to the medical floor (both p < 0.001). Conclusion: The National Early Warning Score and the perfusion index are useful instruments to distinguish critically ill older patients in an Emergency Department.

Association of Epicardial Adipose Tissue With Left Ventricular Strain and MR Myocardial Perfusion in Patients With Known Coronary Artery Disease.

Epicardial adipose tissue (EAT) may have a paracrine effect on coronary microcirculation and myocardium. However, it is unclear whether EAT is linked to cardiac function and perfusion. To investigate the association of EAT with left ventricular (LV) strain and myocardial perfusion in patients with coronary artery disease (CAD). Retrospective. A total of 78 patients with CAD and 20 healthy controls. The patients were further divided into high (n=39) and low EAT volume (n=39) groups according to median EAT volume. A 1.5 T, balanced steady-state free precession, inversion recovery prepared echo-planar, and segmented-turbo fast low-angle shot (FLASH) phase-sensitive inversion recovery (PSIR) sequences. EAT volume was measured by manually tracing the epicardial border and the visceral layer of pericardium on the short-axis cine stacks. LV strain parameters included global radial (GRS), circumferential (GCS), and longitudinal peak strain (GLS). Perfusion indices included upslope, perfusion index, time-to-maximum signal intensity (TTM), and maximum signal intensity (MaxSI). One-way analysis of variance or Kruskal-Wallis rank tests, Chi-squared or Fisher exact tests. Multivariate linear regression analyses. A P value < 0.05 was considered statistically significant. The parameters of GRS GCS, GLS, upslope, perfusion index, and MaxSI were significantly lower in the patients when compared to the controls. Moreover, the high EAT volume group presented significantly longer TTM values and lower GRS, GCS, GLS, upslope, perfusion index, and MaxSI than the low EAT volume group. Multivariate linear regression analyses demonstrated that EAT was independently associated with GRS, GCS, GLS, upslope, perfusion index, TTM, and MaxSI in patients. EAT and upslope were independently associated with GRS, while EAT and perfusion index were both independently associated with GCS and GLS. EAT was associated with parameters of LV function and perfusion, and myocardial perfusion was independently associated with LV strain in patients with CAD. 3. Stage 3.

Blood flow perfusion in visual pathway detected by arterial spin labeling magnetic resonance imaging for differential diagnosis of ocular ischemic syndrome.

Ocular ischemic syndrome (OIS), attributable to chronic hypoperfusion caused by marked carotid stenosis, is one of the important factors that cause ocular neurodegenerative diseases such as optic atrophy. The current study aimed to detect blood flow perfusion in a visual pathway by arterial spin labeling (ASL) and magnetic resonance imaging (MRI) for the differential diagnosis of OIS. This diagnostic, cross-sectional study at a single institution was performed to detect blood flow perfusion in a visual pathway based on 3D pseudocontinuous ASL (3D-pCASL) using 3.0T MRI. A total of 91 participants (91 eyes) consisting of 30 eyes with OIS and 61 eyes with noncarotid artery stenosis-related retinal vascular diseases (39 eyes with diabetic retinopathy and 22 eyes with high myopic retinopathy) were consecutively included. Blood flow perfusion values in visual pathways derived from regions of interest in ASL images, including the retinal-choroidal complex, the intraorbital segments of the optic nerve, the tractus optics, and the visual center, were obtained and compared with arm-retinal circulation time and retinal circulation time derived from fundus fluorescein angiography (FFA). Receiver operating characteristic (ROC) curve analyses and the intraclass correlation coefficient (ICC) were performed to evaluate the accuracy and consistency. Patients with OIS had the lowest blood flow perfusion values in the visual pathway (all p < 0.05). The relative intraorbital segments of optic nerve blood flow values at post-labeling delays (PLDs) of 1.5 s (area under the curve, AUC = 0.832) and the relative retinal-choroidal complex blood flow values at PLDs of 2.5 s (AUC = 0.805) were effective for the differential diagnosis of OIS. The ICC of the blood flow values derived from the retinal-choroidal complex and the intraorbital segments of the optic nerve between the two observers showed satisfactory concordance (all ICC > 0.932, p < 0.001). The adverse reaction rates of ASL and FFA were 2.20 and 3.30%, respectively. 3D-pCASL showed that the participants with OIS had lower blood flow perfusion values in the visual pathway, which presented satisfactory accuracy, reproducibility, and safety. It is a noninvasive and comprehensive differential diagnostic tool to assess blood flow perfusion in a visual pathway for the differential diagnosis of OIS.

Revealing the Protective Effect of Topically Applied Cymbopogon citratus Essential Oil in Human Skin through A Contact Model

Preparations of the Cymbopogon citratus leaves are used in folk medicine for the treatment of inflammatory processes. The present study investigated the proposed anti-inflammatory properties of C. citratus essential oil (EOCC) in human skin in vivo using the methylnicotinate (MN) microinflammation skin model. Skin exposure to MN causes a disturbance that triggers the production of reactive oxygen species and evokes a short duration microinflammatory reaction that might be explored to meet this objective. Fourteen participants of both sexes were selected after providing informed consent. Three areas (3 cm × 3 cm) were drawn on both forearms. One randomly chosen area was treated for 14 days, twice a day, with a polyacrylic acid gel containing 5% EOCC. Remaining areas were used as controls. Results revealed a clear protective effect at the EOCC-treated site. The MN reaction showed significantly lower transepidermal water loss, blood perfusion, erythema, and edema when compared with the other areas. Furthermore, the methodology here proposed is an innovative approach to study the clinical impact of these substances on human skin, contributing to an evidence-based support regarding the interest of using these products in human health.

Comparison of deep learning-based denoising methods in cardiac SPECT

BackgroundMyocardial perfusion SPECT (MPS) images often suffer from artefacts caused by low-count statistics. Poor-quality images can lead to misinterpretations of perfusion defects. Deep learning (DL)-based methods have been proposed to overcome the noise artefacts. The aim of this study was to investigate the differences among several DL denoising models.MethodsConvolution neural network (CNN), residual neural network (RES), UNET and conditional generative adversarial neural network (cGAN) were generated and trained using ordered subsets expectation maximization (OSEM) reconstructed MPS studies acquired with full, half, three-eighths and quarter acquisition time. All DL methods were compared against each other and also against images without DL-based denoising. Comparisons were made using half and quarter time acquisition data. The methods were evaluated in terms of noise level (coefficient of variation of counts, CoV), structural similarity index measure (SSIM) in the myocardium of normal patients and receiver operating characteristic (ROC) analysis of realistic artificial perfusion defects inserted into normal MPS scans. Total perfusion deficit scores were used as observer rating for the presence of a perfusion defect.ResultsAll the DL denoising methods tested provided statistically significantly lower noise level than OSEM without DL-based denoising with the same acquisition time. CoV of the myocardium counts with the different DL noising methods was on average 7% (CNN), 8% (RES), 7% (UNET) and 14% (cGAN) lower than with OSEM. All DL methods also outperformed full time OSEM without DL-based denoising in terms of noise level with both half and quarter acquisition time, but this difference was not statistically significant. cGAN had the lowest CoV of the DL methods at all noise levels. Image quality and polar map uniformity of DL-denoised images were also better than reduced acquisition time OSEM’s. SSIM of the reduced acquisition time OSEM was overall higher than with the DL methods. The defect detection performance of full time OSEM measured as area under the ROC curve (AUC) was on average 0.97. Half time OSEM, CNN, RES and UNET provided equal or nearly equal AUC. However, with quarter time data CNN, RES and UNET had an average AUC of 0.93, which was lower than full time OSEM’s AUC, but equal to quarter acquisition time OSEM. cGAN did not achieve the defect detection performance of the other DL methods. Its average AUC with half time data was 0.94 and 0.91 with quarter time data.ConclusionsDL-based denoising effectively improved noise level with slightly lower perfusion defect detection performance than full time reconstruction. cGAN achieved the lowest noise level, but at the same time the poorest defect detection performance among the studied DL methods.

Abstract WP141: The Combined Effect Of Blood Pressure And Translesional Pressure Ratio Impacts The Stroke Mechanisms Of Intracranial Atherosclerosis

Introduction: ICAS confers the greatest risk of stroke, but the pathophysiology of stroke mechanismremains unclear. Essentially, plaque rupture is a physical process of structural failuredue to destructive biomechanics, and hypoperfusion is due to low perfusion pressure,which act as 2 major stroke mechanisms in sICAS. Notably, blood pressure (BP)plays key role in determining both biomechanics and perfusion of ICAS. Hypothesis: ICAS could result in significant BP change which may further influence strokemechanism. High local pressure gradient across ICAS may cause plaque rupture andthe subsequent artery-to-artery embolism, whereas low perfusion pressure atpost-stenosis area may restrict perfusion and induce the subsequent borderzoneinfarcts (Fig) . Method: A total of 339 sICAS patients due to 50-99% stenosis in MCA or ICA were includedfrom CNSR3. By Newton-Krylov-Schwarz method, CFD models were built based onTOF-MRA (Fig) . Translesional pressure ratio (PR) across ICAS was calculated as:pressurepoststenotic/pressureprestenotic. SBP gradient was calculated as: SBPх(1-PR),indicating the SBP drop across ICAS. Perfusion pressure at post-stenosis area wascalculated as: MAPхPR. Results: After adjustment, high SBP gradient and low perfusion pressure was shown tocorrelate with cortical infarcts (p=0.041) and borderzone infarcts (borderlinesignificant, p=0.059) (Fig) . Between the 2 parameters, Pearson correlation coefficient=-0.854, p &lt;.0001. The cutoff of SBP gradient and perfusion pressure for the above 2stroke mechanisms was 14.4mmHg and 94.4mmHg, respectively. Conclusions: We demonstrated the hemodynamic hypothesis of stroke mechanism in sICAS thatartery-to-artery embolism and hypoperfusion could be attributed to the combinedeffect of blood pressure and translesional PR. Accordingly, a double-edged role of high BP level in sICAS may further surface, which can induce destructivebiomechanics but relieve hypoperfusion simultaneously.

Rapid Eye Movement Sleep, Neurodegeneration, and Amyloid Deposition in Aging.

Rapid eye movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, gray matter volume, and perfusion in aging. We included 121 cognitively unimpaired older adults (76 women, mean age 68.96 ± 3.82 years), who underwent a polysomnography, T1-weighted magnetic resonance imaging, early and late Florbetapir positron emission tomography scans to evaluate gray matter volume, perfusion, and amyloid deposition. We computed indices reflecting REM sleep macro- and microstructural integrity (ie, normalized electroencephalographic spectral power values). Voxel-wise multiple regression analyses were conducted between REM sleep indices and neuroimaging data, controlling for age, sex, education, the apnea-hypopnea index, and the apolipoprotein E ε4 status. Lower perfusion in frontal, anterior and posterior cingulate, and precuneus areas was associated with decreased delta power and electroencephalographic slowing (slow/fast frequencies ratio), and increased alpha and beta power. To a lower extent, similar results were obtained between gray matter volume and delta, alpha, and beta power. In addition, lower REM sleep theta power was more marginally associated with greater diffuse amyloid deposition and lower gray matter volume in fronto-temporal and parieto-occipital areas. These results suggest that alterations of REM sleep microstructure are associated with greater neurodegeneration and neocortical amyloid deposition in older adults. Further studies are warranted to replicate these findings, and determine whether older adults exhibiting REM sleep alterations are more at risk of cognitive decline and belonging to the Alzheimer's continuum. ANN NEUROL 2023;93:979-990.

Effect of Buerger Allen Exercise on Lower Extremity Perfusion among Patients with Type 2 Diabetes Mellitus

Effect of Buerger Allen Exercise on Lower Extremity Perfusion among Patients with Type 2 Diabetes Mellitus

The Effects of Different Doses of Sildenafil on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts.

The dose-response relationship of sildenafil effects on cardiac function is not completely elucidated. The aim of this study was to assess the effects of different doses of sildenafil on coronary flow and oxidative stress in isolated rat hearts. Coronary flow and markers of oxidative stress, including nitrite outflow, and superoxide anion production in coronary effluent, were determined for isolated rat hearts. The experiments were performed during control conditions and in the presence of sildenafil (10, 20, 50, 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 μM). Sildenafil was shown to result in a significant increase in coronary flow at lower coronary perfusion pressure (CPP) values at all administered doses, whereas, with an increase in CPP, a reduction in coronary flow was observed. An increase in nitric oxide (NO) was most pronounced in the group treated with the lowest dose of sildenafil at the highest CPP value. After the inhibition of the NO-cyclic guanosine monophosphate (cGMP) signaling (NOS) system by L-NAME, only a dose of 200 nM sildenafil was high enough to overcome the inhibition and to boost release of O2-. That effect was CPP-dependent, with statistical significance reached at 80, 100 and 120 mmHg. Our findings indicate that sildenafil causes changes in heart vasculature in a dose-dependent manner, with a shift from a vasodilatation effect to vasoconstriction with a pressure increase. The highest dose administered is capable of producing superoxide anion radicals in terms of NOS system inhibition.

Experience with clinical cerebral autoregulation testing in children hospitalized with traumatic brain injury: Translating research to bedside.

To report our institutional experience with implementing a clinical cerebral autoregulation testing order set with protocol in children hospitalized with traumatic brain injury (TBI). After IRB approval, we examined clinical use, patient characteristics, feasibility, and safety of cerebral autoregulation testing in children aged <18 years between 2014 and 2021. A clinical order set with a protocol for cerebral autoregulation testing was introduced in 2018. 25 (24 severe TBI and 1 mild TBI) children, median age 13 years [IQR 4.5; 15] and median admission GCS 3[IQR 3; 3.5]) underwent 61 cerebral autoregulation tests during the first 16 days after admission [IQR1.5; 7; range 0-16]. Testing was more common after implementation of the order set (n = 16, 64% after the order set vs. n = 9, 36% before the order set) and initiated during the first 2 days. During testing, patients were mechanically ventilated (n = 60, 98.4%), had invasive arterial blood pressure monitoring (n = 60, 98.4%), had intracranial pressure monitoring (n = 56, 90.3%), brain-tissue oxygenation monitoring (n = 56, 90.3%), and external ventricular drain (n = 13, 25.5%). Most patients received sedation and analgesia for intracranial pressure control (n = 52; 83.8%) and vasoactive support (n = 55, 90.2%) during testing. Cerebral autoregulation testing was completed in 82% (n = 50 tests); 11 tests were not completed [high intracranial pressure (n = 5), high blood pressure (n = 2), bradycardia (n = 2), low cerebral perfusion pressure (n = 1), or intolerance to blood pressure cuff inflation (n = 1)]. Impaired cerebral autoregulation on first assessment resulted in repeat testing (80% impaired vs. 23% intact, RR 2.93, 95% CI 1.06:8.08, p = 0.03). Seven out of 50 tests (14%) resulted in a change in cerebral hemodynamic targets. Findings from this series of children with TBI indicate that: (1) Availability of clinical order set with protocol facilitated clinical cerebral autoregulation testing, (2) Clinicians ordered cerebral autoregulation tests in children with severe TBI receiving high therapeutic intensity and repeatedly with impaired status on the first test, (3) Clinical cerebral autoregulation testing is feasible and safe, and (4) Testing results led to change in hemodynamic targets in some patients.

Twenty-four hour blood pressure variability and the prevalence and the progression of cerebral white matter hyperintensities

Blood pressure variability (BPV) is related to cerebral white matter hyperintensities (WMH), but longitudinal studies assessing WMH progression are scarce. Patients with cardiovascular disease and control participants of the Heart-Brain Connection Study underwent 24-hour ambulatory blood pressure monitoring and repeated brain MRI at baseline and after 2 years. Using linear regression, we determined whether different measures of BPV (standard deviation, coefficient of variation, average real variability (ARV), variability independent of the mean) and nocturnal dipping were associated with WMH and whether this association was mediated or moderated by baseline cerebral perfusion. Among 177 participants (mean age: 65.9 ± 8.1 years, 33.9% female), the absence of diastolic nocturnal dipping was associated with higher WMH volume at baseline (β = 0.208, 95%CI: 0.025–0.392), but not with WMH progression among 91 participants with follow-up imaging. None of the BPV measures were associated with baseline WMH. Only 24-hour diastolic ARV was significantly associated with WMH progression (β = 0.144, 95%CI: 0.030–0.258), most profound in participants with low cerebral perfusion at baseline (p-interaction = 0.042). In conclusion, absent diastolic nocturnal dipping and 24-hour diastolic ARV were associated with higher WMH volume. Whilst requiring replication, these findings suggest that blood pressure patterns and variability may be a target for prevention of small vessel disease.

The Clinical Experience of 22 Years Analysis of Therapeutic and Surgical Treatment of the Early Glaucoma

The article presents the clinical case of a 22-year follow-up of a patient with early glaucoma whose visual functions were stabilized during the first 12 years after trabeculectomy and during the next 10 years of therapeutic treatment due to poor compliance the disease progressed to advanced glaucoma. As a result, in 2021 there were pronounced changes in the visual field of the left eye, the main cause, probably, was a vascular accident against the background of low perfusion pressure and uncompensated IOP. After a thorough analysis and scrupulous selection of eyedrops, IOP was compensated with laser and instillation of Dortimol Antiglau, which showed the best results of tolerability and achievement of tolerant pressure. This article presents data from clinical and instrumental studies and analyzes factors reflecting the importance of assessing the level of compliance in reducing the glaucoma progression.

A low peripheral perfusion index can accurately detect prolonged capillary refill time during general anesthesia: A prospective observational study.

Capillary refill time (CRT) is the gold standard for evaluating peripheral organ perfusion; however, intraoperative CRT measurement is rarely used because it cannot be conducted continuously, and it is difficult to perform during general anesthesia. The peripheral perfusion index (PI) is another noninvasive method for evaluating peripheral perfusion. The PI can easily and continuously evaluate peripheral perfusion and could be an alternative to CRT for use during general anesthesia. This study aimed to determine the cutoff PI value for low peripheral perfusion status (prolonged CRT) by exploring the relationship between CRT and the PI during general anesthesia. We enrolled 127 surgical patients. CRT and the PI were measured in a hemodynamically stable state during general anesthesia. A CRT >3 s indicated a low perfusion status. Prolonged CRT was observed in 27 patients. The median PI values in the non-prolonged and prolonged CRT groups were 5.0 (3.3-7.9) and 1.5 (1.2-1.9), respectively. There was a strong negative correlation between the PI and CRT (r = -0.706). The area under the receiver operating characteristic curve generated for the PI was 0.989 (95% confidence interval, 0.976-1.0). The cutoff PI value for detecting a prolonged CRT was 1.8. A PI <1.8 could accurately predict a low perfusion status during general anesthesia in the operating room. A PI <1.8 could be used to alert the possibility of a low perfusion status in the operating room. University Hospital Medical Information Network (UMIN000043707; retrospectively registered on March 22, 2021, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno = R000049905).

Use of the Allgöwer-Donati Suture Technique for Wound Closure Following Transmetatarsal Amputation

Introduction. The Allgöwer-Donati suture technique reportedly has lower incision perfusion impairment compared with other suture techniques. The authors of the present case series hypothesized that suture technique selection to achieve lower incision perfusion impairment may result in improved healing rates and decreased incidence of wound complications in partial foot amputations, specifically TMAs. Objective. To evaluate the efficacy of TMA with skin closure completed using the Allgöwer-Donati suture technique. Materials and Methods. The records of 7 patients (8 limbs) who underwent closure with the Allgöwer-Donati suture technique after TMA between March 2021 and March 2022 were retrospectively reviewed. Only patients with a diagnosis of gangrene were included. Results. Five of 8 limbs (62.5%) healed uneventfully, with an average time to healing of 3.3 weeks. Six of 8 limbs (75%) healed within 4 weeks, and 1 limb was lost to follow-up. Conclusions. The results of this small case series suggest that use of the Allgöwer-Donati suture technique may result in decreased incidence of wound complications by allowing improved perfusion at the amputation site.

Lower Body Perfusion Reduces the Morbidity of Postoperative Acute Kidney Injury in Type A Dissection: A Propensity-Matched Analysis.

Lower body perfusion (LBP) is a technique used to provide blood perfusion to distal organs and spinal cord during circulatory arrest. However, the effect of LBP on the prognosis of aortic arch surgery, especially on postoperative renal function, remains unclear. A total of 304 patients with acute type A aortic dissection who underwent total aortic arch replacement combined with frozen elephant trunk implantation between May 2016 and December 2021 were retrospectively analyzed. The patients were divided into LBP group (group L, n=85) and non-LBP group (group NL, n=219). Routine lower body circulatory arrest was applied during operation in group NL, and antegrade LBP combined was applied during operation in group L. Perioperative data were recorded. Propensity score matching was used for statistical analysis. After propensity score matching, 85 pairs of patients were successfully matched. Two groups significantly differed in circulatory arrest time (six minutes vs. 30 minutes, P=0.000), cross-clamping time (101 minutes vs. 92 minutes, P=0.010), minimum nasopharyngeal temperature (29.4ºC vs. 27.2ºC, P=0.000), and highest lactate value during cardiopulmonary bypass (2.3 μmol/L vs. 4.1 μmol/L, P=0.000). Considering the postoperative indicators, the drainage volume (450 mL vs. 775 mL, P=0.000) and the incidence of level I acute kidney injury (23.5% vs. 32%, P=0.046) in group L was lower than those in group NL. LBP resulted as a safe and feasible approach in aortic arch surgery, as it could significantly shorten the circulatory arrest time, which might reduce the incidence of postoperative level I acute kidney injury.

Protective effects of NF-κB inhibitor and continuous perfusion of pulmonary arteries on pulmonary injury in piglet models of deep hypothermia low flow

Deep hypothermia with low flow perfusion (DHLF) is a common cardiopulmonary bypass (CPB) technique. The associated lung ischemia/reperfusion injury is a major cause of postoperative morbidity and mortality in patients undergoing DHLP; we aimed to investigate the effects of nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) with continuous perfusion of pulmonary arteries (CPP) on DHLF-induced lung injury and the related molecular mechanisms. Twenty-four piglets were randomly divided into the DHLF (control), CPP (with DHLF), or CPP+PDTC (intravenous PDTC before CPP with DHLF) groups. Lung injury was evaluated by respiratory function measurement, lung immunohistochemistry, and serum levels of TNF, IL-8, IL-6, and NF-κB before CPB, at CPB completion, and at 1 h post-CPB. Western blot was used to detect NF-κB protein expression in lung tissues. After CPB, decreased parcial pressure of oxygen (PaO2) and increased parcial pressure of carbon dioxide (PaCO2) and serum levels of TNF, IL-8, IL-6, and NF-κB were observed in the DHLF group. Both CPP and CPP+PDTC groups showed better indices of lung function, decreased levels of TNF, IL-8, and IL-6, and less severe pulmonary edemas and injuries. PDTC with CPP further improved pulmonary function and mitigated pulmonary injury than did CPP alone. PDTC with CPP better attenuates DHLF-induced lung injury than does CPP alone.

Early Stent Patency After Endovascular Therapy for Tandem or Isolated Carotid Steno-Occlusive Disease

Early Stent Patency After Endovascular Therapy for Tandem or Isolated Carotid Steno-Occlusive Disease

Chronic nicotine impairs the angiogenic capacity of human induced pluripotent stem cell-derived endothelial cells in a murine model of peripheral arterial disease

ObjectiveLifestyle choices such as tobacco and e-cigarette use are a risk factor for peripheral arterial disease (PAD) and may influence therapeutic outcomes. The effect of chronic nicotine exposure on the angiogenic capacity of human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) was assessed in a murine model of PAD. MethodsMice were exposed to nicotine or phosphate-buffered saline (PBS) for 28 days, followed by induction of limb ischemia and iPSC-EC transplantation. Cells were injected into the ischemic limb immediately after induction of hindlimb ischemia and again 7 days later. Limb perfusion was assessed by laser Doppler spectroscopy, and transplant cell survival was monitored for 14 days afterward using bioluminescence imaging, followed by histological analysis of angiogenesis. ResultsTransplant cell retention progressively decreased over time after implantation based on bioluminescence imaging, and there were no significant differences in cell survival between mice with chronic exposure to nicotine or PBS. However, compared with mice without nicotine exposure, mice with prior nicotine exposure had had an impaired therapeutic response to iPSC-EC therapy based on decreased vascular perfusion recovery. Mice with nicotine exposure, followed by cell transplantation, had significantly lower mean perfusion ratio after 14 days (0.47 ± 0.07) compared with mice undergoing cell transplantation without prior nicotine exposure (0.79 ± 0.11). This finding was further supported by histological analysis of capillary density, in which animals with prior nicotine exposure had a lower capillary density (45.9 ± 4.7 per mm2) compared with mice without nicotine exposure (66.5 ± 8.1 per mm2). Importantly, the ischemic limbs mice exposed to nicotine without cell therapy also showed significant impairment in perfusion recovery after 14 days, compared with mice that received PBS + iPSC-EC treatment. This result suggested that mice without chronic nicotine exposure could respond to iPSC-EC implantation into the ischemic limb by inducing perfusion recovery, whereas mice with chronic nicotine exposure did not respond to iPSC-EC therapy. ConclusionsTogether, these findings show that chronic nicotine exposure adversely affects the ability of iPSC-EC therapy to promote vascular perfusion recovery and angiogenesis in a murine PAD model.

Системная гипотония и низкое перфузионное давление как факторы прогрессирования первичной открытоугольной глаукомы

Glaucoma progression is still a relevant issue in up-to-date ophthalmology. An important prerequisite for stabilizing glaucoma is the achievement of the target intraocular pressure (IOP). However, many patients with primary open-angle glaucoma (POAG) continue to suffer vision loss despite IOP reduction. Additional factors are also important for glaucoma progression, e.g., blood pressure (BP) and ocular perfusion pressure (OPP). Multiple published data have shown a decrease in blood flow velocity in the retrobulbar vessels, choroid, retina, and optic nerve in patients with glaucoma. A decrease in OPP is a predictor of insufficient intraocular blood supply. Systemic BP has a strong effect on OPP. Intensive treatment for hypertension significantly reduces BP, decreases OPP, and prevents the progression of glaucomatous optic neuropathy. A new paradigm shift that implies a personalized approach to the choice of diagnostic and treatment strategy for glaucoma is emerging. This paper reviews current published data on the effect of systemic hypotension and low OPP on POAG progression. KEYWORDS: glaucoma, intraocular pressure, blood pressure, hypertension, hypotension, perfusion pressure. FOR CITATION: Мyakonkaya O.S., Sarkisyan A.S., Seleznev A.V., Kuroyedov A.V., Brezhnev A.Yu. Systemic hypotension and low perfusion pressure as risk factors for primary open-angle glaucoma progression. Russian Journal of Clinical Ophthalmology. 2023;23(4):202–206 (in Russ.). DOI: 10.32364/2311-7729-2023-23-4-5.

PS-C12-4: OPEN-ANGLE GLAUCOMATOUS OPTIC DAMAGE ASSOCIATED WITH DAYTIME AND NOCTURNAL DIPS IN BLOOD PRESSURE

Background: Impaired ocular perfusion pressure via systemic hypoperfusion plays a pivotal role in the pathogenesis of open-angle glaucoma (OAG). Extreme dips in mean arterial pressure (MAP) during 24-h are associated with OAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of OAG damage with daytime and nocturnal dips in MAP. Methods: We conducted a retrospective longitudinal study that included 110 primary OAG patients who underwent 24-h ambulatory blood pressure monitoring. OAG damage was defined as changes in mean deviation (MD) of visual field tests during follow-up. MAP variability independent of the mean (VIMmap) was computed for daytime and nighttime. Dips were the five daytime and three nighttime lowest drops in MAP. We also calculated the night-to-day ratio and defined low diurnal and nocturnal MAP levels. We applied mixed models to evaluate changes in MD (expressed as decibels [dB]) during follow-up in relation to diurnal and nocturnal variability and dips in MAP. Results: The mean age was 64.0y (53% women). The median follow-up was nine years. In adjusted mixed models, every + 3 mmHg increase in daytime VIMmap was associated with a -2.57 dB longitudinal change in MD (P &lt; 0.001). The longitudinal changes in MD associated with daytime dip measures ranged from -2.56 dB (95% confidence interval [CI], -3.61 to -1.51; P &lt; 0.001) to -3.19 dB (95% CI, -4.53 to -1.84; P &lt; 0.001). For nighttime measures, the MD changed -0.71 dB (CI, -1.24 to -0.17; P = 0.009) per every -5 decrease in the nighttime MAP level. Nocturnal MAP level &lt; 74 mmHg and every 0.05 decrease in the night-to-day ratio were related to -7.23 (P = 0.003) and -0.96 (P = 0.011) changes in MD. Nighttime VIMmapP and nocturnal dips were not associated with changes in MD (P &gt; 0.097). Conclusions: Extreme daytime dips in MAP relate to OAG damage independently of the MAP level. Whereas, the association between OAG damage and nocturnal measures is driven by the nocturnal MAP level rather than variability or dips in MAP. The assessment of diurnal patterns in MAP might offer an opportunity to understand the pathogenesis of OAG. This is also critical as the perfusion pressure to the eyes is physiological 30% lower than at the brachial level in the standing or sitting positions. Therefore, a physiological lower perfusion pressure combined with extreme diurnal dips in MAP would exacerbate the hypoperfusion state in the optic nerve, leading to further glaucoma damage.