Microvascular Perfusion Research Articles

Biventricular Impairment and Ventricular Interdependence in Patients With Alcoholic Cardiomyopathy: Insights Through Cardiac Magnetic Resonance Imaging.

Alcoholic cardiomyopathy (ACM) can lead to progressive cardiac dysfunction and heart failure, but little is known about biventricular impairment and ventricular interdependence (VI) in ACM patients. To use cardiac MRI to investigate biventricular impairment and VI in ACM patients. Retrospective. Forty-one male patients with ACM and 45 sex- and age-matched controls. 3.0 T/balanced steady-state free precession sequence, inversion recovery prepared echo-planar imaging sequence and phase-sensitive inversion recovery sequence. Biventricular structure, function, and global strain (encompassing peak strain [PS], peak systolic, and diastolic strain rate), PS of interventricular septal (IVS), microvascular perfusion (including upslope and time to maximum signal intensity [TTM]), late gadolinium enhancement (LGE), and baseline characteristics were compared between the controls and ACM patients. Student's t-test, Mann-Whitney U test, Pearson's correlation, and multivariable linear regression models with a stepwise selection procedure. A two-tailed P value <0.05 was deemed as statistically significant. Compared to control subjects, ACM patients showed significantly biventricular adverse remodeling, reduced left ventricle (LV) global upslope and prolonged global TTM, and the presence of LGE. ACM patients were characterized by a significant decline in all global strain within the LV, right ventricle (RV), and IVS compared with the controls. RV global PS was significantly associated with LV global PS and IVS PS in radial, circumferential, and longitudinal directions. Multivariable analyses demonstrated the longitudinal PS of IVS was significantly correlated with RV global radial PS (β = 0.614) and circumferential PS (β = 0.545). Additionally, RV global longitudinal PS (GLPS) was significantly associated with radial PS of IVS (β = -0.631) and LV GLPS (β = 1.096). ACM patients exhibited biventricular adverse structural alterations and impaired systolic and diastolic function. This cohort also showed reduced LV microvascular perfusion, the presence of LGE, and unfavorable VI. 3 TECHNICAL EFFICACY: Stage 3.

Microvascular Perfusion Imaging in Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide and significantly impacts the essential functions of daily life and social activities. Research on AD has found that its pathogenesis is related to the extracellular accumulation of amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles in the cortical and limbic areas of the human brain, as well as cerebrovascular factors. The detection of Aβ or tau can be performed using various probes and methodologies. However, these modalities are expensive to implement and often require invasive procedures, limiting accessibility on a large scale. While magnetic resonance imaging (MRI) and computed tomography (CT) are generally used for morphological and structural brain imaging, they show wide variability in their accuracy for the clinical diagnosis of AD. Several novel imaging modalities have emerged as alternatives that can accurately and vividly display the changes in blood flow and metabolism in each brain area and enable physicians and researchers to gain insights into the generation and progression of the cerebro-microvascular pathologies of AD. In this review, we summarize the current knowledge on microvascular perfusion imaging modalities and their application in AD, including MRI (dynamic susceptibility contrast-MRI, arterial spin labeling-MRI), CT (cerebral CT perfusion imaging), emission computed tomography (positron emission tomography (PET), single-photon emission computed tomography (SPECT)), transcranial doppler ultrasonography (TCD), and retinal microvascular imaging (optical coherence tomography imaging, computer-assisted methods for evaluating retinal vasculature).

Anthocyanins attenuate vascular and inflammatory responses to a high fat high energy meal challenge in overweight older adults: A cross-over, randomised, double-blind clinical trial

Postprandial metabolic imbalances are important indicators of later developing cardiovascular disease (CVD)(1). This study investigated the effects of food anthocyanins on vascular and microvascular function, and CVD associated biomarkers following a high fat high energy (HFHE) meal challenge in overweight older adults. Sixteen subjects (13 female, 3 male, mean age 65.9 SD 6.0 and body mass index 30.6 kg/m 2 SD 3.9) participated in a crossover, randomised, controlled, double-blind clinical trial (Australian New Zealand Clinical Trials Registry # ACTRN12620000437965). Participants consumed a HFHE breakfast meal (65g total fat; 33g saturated fat) together with a 250 mL dose of either intervention (Queen Garnet Plum providing 201 mg anthocyanins) or control (apricot) juice. A wash-out period of 14 days occurred between meal challenges, with a 4-day run-in period for juice consumption before each challenge. Blood samples and blood pressure measures were collected at baseline, 2 h and 4 h following the HFHE meal. Vascular function, assessed using flow mediated dilatation (FMD), and microvascular cutaneous vascular reactivity, measured using Laser Speckle Contrast Imaging (LSCI), were evaluated at baseline and 2 h after the HFHE meal. Participants had a higher 2 h postprandial FMD (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P = 0.019 and P = 0.049, respectively). C-reactive protein was lower 4 h postprandially in the anthocyanins (1.80 mg/L, IQR 0.90) vs control arm (2.30 mg/L, IQR 1.95) (P = 0.026), accompanied by a trend for lower concentrations of interleukin-6 (P = 0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor α, interleukin-1 β, or maximum microvascular perfusion following iontophoresis of acetylcholine. Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat ‘Western’ meal.

(PM-17) THE ROLE OF PHOSPHODIESTERASE-5 INHIBITORS IN THE TREATMENT OF COMPLEX PENILE WOUNDS: A CASE REPORT AND LITERATURE REVIEW

Abstract Introduction/Objective Phosphodiesterase-5 inhibitors (PDE5i) are traditionally employed for the management of erectile dysfunction and lower urinary tract symptoms. However, their role in the healing of complex penile wounds remains scarcely discussed. This study aims to describe the case of a 27-year-old man who suffered from penile strangulation, treated with sildenafil. Additionally, a literature review concerning the use of PDE5i for the treatment of complex penile injuries will be conducted. Methods A 27-year-old man presented to the emergency room after a self-induced penile strangulation using a ring placed at the base of the penis. Extensive necrosis of the corpus cavernosum was identified through magnetic resonance imaging. Considering the psychosocial implications of penile amputation, organ preservation was chosen, and conservative treatment with sildenafil and daily local dressings was initiated. Thirty days after admission, Doppler ultrasound revealed symmetrical corpus cavernosum with normal echogenicity and usual blood flow patterns. Subsequently, the patient underwent superficial necrotic tissue debridement followed by partial skin grafting in a second stage, leading to hospital discharge after 55 days of hospitalization. Results PDE5 inhibitors enhance nitric oxide bioavailability, promoting vasodilation and improved tissue oxygenation, thereby facilitating various phases of the healing process. Evidence indicates their benefit in microvascular perfusion in skin and soft tissues. Reports suggest satisfactory outcomes of topical PDE5i application in radiation-induced lesions, implying their role in epidermal cell expansion, reduction of inflammatory infiltrates, enhanced vascularization, and decreased collagen deposition. Conclusion This study presents a successful case of sildenafil use in treatment of a complex penile wound, shedding light on an unconventional application of PDE5i. Financing No conflict.

The relationship of serum sodium and albumin levels on the severity of intracerebral hemorrhage

Background: Hyponatremia causes complications and increases the severity of Intracerebral Hemorrhage (ICH) patients. Plasma albumin can be a neuroprotector against ICH by reducing brain volume and edema, increasing blood flow to the brain experiencing a perfusion crisis, and increasing microvascular perfusion. ICH patients with hypoalbuminemia have a 2-fold increased risk of worse outcomes and in-hospital death. This research was conducted to see the relationship between sodium and serum albumin levels on the severity of ICH patients. Methods: This research is a cross sectional study where the number of research subjects was 69 people who met the inclusion criteria. Low serum sodium levels had a significant relationship with the severity of ICH patients as assessed by the NIHSS. Data were analyzed using SPSS version 27.0 for Windows. Results: Admissions showed severe severity in 44 subjects (91.7%) with a value of 0.000 (&lt;0.05). Low serum albumin levels have a significant relationship with the severity of ICH patients, showing severe severity in 50 subjects (96.2%) with a p-value of 0.000 (&lt;0.05). Low serum sodium and albumin levels had the highest proportion of 97.6% with a severe severity level, while normal sodium and albumin levels were only 18.2% with a severe severity level. From the statistical test results, it was obtained that the p-value (0.000) &lt; 0.05. Conclusion: There is a relationship between the combination of serum sodium-albumin levels and the severity of ICH.

Sheet-based extrusion bioprinting: a new multi-material paradigm providing mid-extrusion micropatterning control for microvascular applications

As bioprinting advances into clinical relevance with patient-specific tissue and organ constructs, it must be capable of multi-material fabrication at high resolutions to accurately mimick the complex tissue structures found in the body. One of the most fundamental structures to regenerative medicine is microvasculature. Its continuous hierarchical branching vessel networks bridge surgically manipulatable arteries (∼1–6 mm) to capillary beds (∼10 µm). Microvascular perfusion must be established quickly for autologous, allogeneic, or tissue engineered grafts to survive implantation and heal in place. However, traditional syringe-based bioprinting techniques have struggled to produce perfusable constructs with hierarchical branching at the resolution of the arterioles (∼100-10 µm) found in microvascular tissues. This study introduces the novel CEVIC bioprinting device (i.e. Continuously Extruded Variable Internal Channeling), a multi-material technology that breaks the current extrusion-based bioprinting paradigm of pushing cell-laden hydrogels through a nozzle as filaments, instead, in the version explored here, extruding thin, wide cell-laden hydrogel sheets. The CEVIC device adapts the chaotic printing approach to control the width and number of microchannels within the construct as it is extruded (i.e. on-the-fly). Utilizing novel flow valve designs, this strategy can produce continuous gradients varying geometry and materials across the construct and hierarchical branching channels with average widths ranging from 621.5 ± 42.92% µm to 11.67 ± 14.99% µm, respectively, encompassing the resolution range of microvascular vessels. These constructs can also include fugitive/sacrificial ink that vacates to leave demonstrably perfusable channels. In a proof-of-concept experiment, a co-culture of two microvascular cell types, endothelial cells and pericytes, sustained over 90% viability throughout 1 week in microchannels within CEVIC-produced gelatin methacryloyl-sodium alginate hydrogel constructs. These results justify further exploration of generating CEVIC-bioprinted microvasculature, such as pre-culturing and implantation studies.

Alveolar membrane and capillary function in COVID-19 convalescents: insights from chest MRI

ObjectivesTo investigate potential presence and resolution of longer-term pulmonary diffusion limitation and microvascular perfusion impairment in COVID-19 convalescents.Materials and methodsThis prospective, longitudinal study was carried out between May 2020 and April 2023. COVID-19 convalescents repeatedly and age/sex-matched healthy controls once underwent MRI including hyperpolarized 129Xe MRI. Blood samples were obtained in COVID-19 convalescents for immunophenotyping. Ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP), and gas phase (GP) as well as lung surface-volume ratio were quantified and correlations with CD4+/CD8+ T cell frequencies were assessed using Pearson’s correlation coefficient. Signed-rank tests were used for longitudinal and U tests for group comparisons.ResultsThirty-five participants were recruited. Twenty-three COVID-19 convalescents (age 52.1 ± 19.4 years, 13 men) underwent baseline MRI 12.6 ± 4.2 weeks after symptom onset. Fourteen COVID-19 convalescents underwent follow-up MRI and 12 were included for longitudinal comparison (baseline MRI at 11.5 ± 2.7 weeks and follow-up 38.0 ± 5.5 weeks). Twelve matched controls were included for comparison. In COVID-19 convalescents, RBC-TP was increased at follow-up (p = 0.04). Baseline RBC-TP was lower in patients treated on intensive care unit (p = 0.03) and in patients with severe/critical disease (p = 0.006). RBC-TP correlated with CD4+/CD8+ T cell frequencies (R = 0.61/ − 0.60) at baseline. RBC-TP was not significantly different compared to matched controls at follow-up (p = 0.25).ConclusionImpaired microvascular pulmonary perfusion and alveolar membrane function persisted 12 weeks after symptom onset and resolved within 38 weeks after COVID-19 symptom onset.Clinical relevance statement129Xe MRI shows improvement of microvascular pulmonary perfusion and alveolar membrane function between 11.5 ± 2.7 weeks and 38.0 ± 5.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease.Key Points• The study aims to investigate long-term effects of COVID-19 on lung function, in particular gas uptake efficiency, and on the cardiovascular system.• In COVID-19 convalescents, the ratio of 129Xe in red blood cells/tissue plasma increased longitudinally (p = 0.04), but was not different from matched controls at follow-up (p = 0.25).• Microvascular pulmonary perfusion and alveolar membrane function are impaired 11.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease at 38.0 weeks.

Clinical outcomes of spinal cord stimulation in patients with intractable leg pain in Japan.

Neuromodulation through spinal cord stimulation (SCS) is a therapeutic option for relieving leg pain and improving the chances of limb salvage in patients with intractable chronic limb-threatening ischemia (CLTI); however, there is no consensus on its indications. The aim of this study was to assess the clinical outcomes of SCS in patients with intractable leg pain caused by various diseases treated in the department of cardiovascular medicine in Japan. This was a retrospective study of patients who underwent SCS for pain management. Patients were considered eligible for the therapy if they met the following criteria: (1) intractable leg pain (numerical rating scale [NRS] score of 10), (2) no revascularization option, and (3) no septicemia. Twenty patients (mean age: 77 years; men/women: 11/9) were included in this study. The NRS score of the patients significantly reduced from 10 ± 0 before procedure to 4 ± 3 at discharge (p < 0.001). The clinical response rate of the entire cohort was 65% (13/20) at 17 ± 14 months after implantation; however, patients with intractable CLTI showed a low response rate (45%), whereas those with subacute limb ischemia showed a high response rate (100%). A multivariable regression analysis showed that hemoglobin level was significantly associated with treatment response, even after adjusting for age and sex (p = 0.026). The area under the receiver operating characteristic curve for the correlation between hemoglobin level (cutoff, 11.4 g/dL) and clinical response to SCS was 0.824 (0.619-1). SCS can reduce clinical symptoms in majority of patients with intractable leg pain. Although implantation of an SCS device has been shown to improve microvascular perfusion insufficiency, the correlation between hemoglobin level and the clinical effect of SCS indicates that a preserved microcirculatory vascular bed is essential for the therapy to be effective.

Skin perfusion and oxygen saturation after mastectomy and radiation therapy in breast cancer patients

The pathophysiological mechanism behind complications associated with postmastectomy radiotherapy (PMRT) and subsequent implant-based breast reconstruction are not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion and saturation in the skin after mastectomy and assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate – MN).Skin microvascular perfusion and oxygenation >2 years after PMRT were measured using white light diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) in the irradiated chest wall of 31 women with the contralateral breast as a control. In the non-irradiated breast, the perfusion after application of MN (median 0.84, 25th–75th centile 0.59–1.02 % RBC × mm/s) was higher compared to the irradiated chest wall (median 0.51, 25th–75th centile 0.21–0.68 % RBC × mm/s, p < 0.001). The same phenomenon was noted for saturation (median 91 %, 25th–75th centile 89–94 % compared to 89 % 25th–75th centile 77–93 %, p = 0.001). Eight of the women (26%) had a ≥10 % difference in skin oxygenation between the non-irradiated breast and the irradiated chest wall.These results indicate that late microvascular changes caused by radiotherapy of the chest wall significantly affect skin perfusion and oxygenation.

Effect of Intraorbital Mechanical Compression on Retinal Microvascular Perfusion in Quiescent Thyroid-Associated Ophthalmopathy Based on Ocular Biomechanics Measured by Corvis ST.

To analyze the correlation between orbital compliance and retinal vessel density (VD) based on dynamic Scheimpflug analyzer (Corvis ST) and optical coherence tomographic angiography (OCT-A). In this prospective observational study, 65 eyes of 44 patients with thyroid-associated ophthalmopathy (TAO) in quiescent stage were included (15 males and 29 females). The whole eye movement (WEM) was detected by Corvis ST. The superficial capillary plexus VD (SCP-VD) and deep capillary plexus VD (DCP-VD) were obtained by scanning the 3 × 3mm area around the fovea using OCT-A, while the peripapillary vessel density (ppVD) was obtained by scanning the 4.5 × 4.5mm area around the optic disk. Covariances including biomechanically corrected intraocular pressure (bIOP), axial length, age and gender were adjusted during data analysis. The mean WEM of the participants was 0.235 ± 0.066mm. The mean SCP-VD and DCP-VD in whole image were 46.20% ± 3.77% and 50.51% ± 3.96%; the mean whole pp-VD was 49.75% ± 2.01%. WEM was positively correlated with SCP-VD (r = 0.327, p = 0.01) and the whole pp-VD (r = 0.394, p < 0.01) after adjusting by gender, axial length (AL), age and bIOP, but it was not significantly correlated with DCP-VD (r = 0.072 p = 0.581). Increase in orbital pressure might reduce retinal microvascular perfusion. Our data suggest orbital mechanical compression may be an important cause of retinal VD changes in quiescent patients with TAO.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

Ultrasound Targeted Microbubble Cavitation (UTMC) for the treatment of Myocardial Microvascular Obstruction (MVO)

Congestive heart failure following acute myocardial infarction is increasing due to microvascular obstruction (MVO), for which there is no effective therapy. We have been developing ultrasound-targeted microbubble cavitation (UTMC) as a potential treatment. Rapacz familial hypercholesterolemic (RFH) pigs were used in this study. MVO was created in the left anterior descending (LAD) microcirculation. UTMC therapy was applied during infusion of Definity®. Left ventricular (LV) segmental wall motion and microvascular perfusion were assessed with ultrasound. Cardiac MRI was obtained to measure infarct size and area of MVO; ultrasound imaging and coronary angiography were performed at 48h. LAD angiographic flow was improved at 48 h post-treatment in comparison to control. UTMC treatment significantly improved echo-based LV systolic performance. UTMC was also found to significantly enhance LAD blood volume at 48h versus control. MRI-derived LV segmental wall motion and ejection fraction also improved post-treatment. Infarct size was reduced as assessed by both Evans Blue/TTC staining and MRI. In conclusion, we demonstrated that UTMC significantly reduced infarct size, enhanced LAD microvascular perfusion and improved LV systolic performance.

Establishment of CME Mouse Model Based on Autologous Thrombotic Particles and the Effect of Shexiang Tongxin Dropping Pill on the Coronary Microvascular Blood Flow in This Model

Coronary microvascular disease poses significant clinical harm and is closely associated with major cardiovascular adverse events. Existing research has highlighted coronary microvascular embolism (CME) as an important factor. Previous studies have utilized microspheres to construct a mouse model of CME, which can partially simulate coronary microvascular disease. However, there are notable discrepancies from the clinical reality. Shexiang Tongxin Dropping Pill (SXDP), a traditional Chinese patent medicine, is widely used in Chinese hospitals for treating coronary heart disease. Our preliminary research has indicated that SXDP effectively alleviates chest pain symptoms and improves coronary thrombolysis in myocardial infarction (TIMI) blood flow in patients with angina pectoris. Nonetheless, the specific mechanism remains unclear. To address this, the current study aimed to explore the size and concentration of autologous thrombotic particles to construct a CME mouse model, taking reference from previous studies on microsphere parameters (size: 9 µm; concentration: 500 000/50 µl). Additionally, we aimed to observe the effect of SXDP on coronary microvascular blood flow in this model. The experiments revealed that the average size of 400-mesh thrombus particles closely approximated 9 µm, and the concentration suspension at a ratio of 1 : 0.15, with a volume of 50 µl, contained approximately 500 000 particles. Concurrently, we observed that 400-mesh blood clot particles induced T-wave elevation in the electrocardiogram, decreased region of interest value in laser speckle examination, downregulated CD31 and Lectin in vascular endothelium, caused thrombosis in coronary microvessels, and led to myocardial infarction. Moreover, a decrease in serum nitric oxide levels and an increase in endothelin-1 (ET-1) were observed. Furthermore, we investigated the effects of SXDP on this animal model and identified potential mechanisms underlying its ability to reverse the aforementioned pathological changes. The research findings suggest that 400-mesh blood clot particles can successfully establish a CME mouse model, and SXDP can improve coronary microvascular blood perfusion, potentially through the improvement of endothelial function.

Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia-reperfusion injury and repair.

Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia-reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5 dyn/cm2 for 6 h and subsequently restored to physiological fluid shear stress level (2 dyn/cm2) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood-brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia-reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI.

Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance

Context Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection. Objective To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality. Materials and methods A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1’s safe dosage. Groups for each model were: in vivo—a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro—a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 μM for 30 min). NGR1’s effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated. Results Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 μM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis. Discussion and conclusions Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1’s efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Microcirculatory changes in the skin after postmastectomy radiotherapy in women with breast cancer

Postmastectomy radiotherapy (PMRT) increases the risk for complications after breast reconstruction. The pathophysiological mechanism underlying this increased risk is not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion in the skin directly after, and at 2 and 6 months after PMRT and to assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate—MN) after PMRT. Skin microvascular responses after PMRT were measured on two sites in the irradiated chest wall of 22 women before, immediately after, and at 2 and 6 months after unilateral PMRT with the contralateral breast as a control. A significant increase in basal skin perfusion was observed in the irradiated chest wall immediately after RT (p < 0.0001). At 2 and 6 months after RT, there was no longer a difference in basal skin perfusion compared to the contralateral breast and compared to baseline. Similarly, the blood flow response in the skin after application of MN was stronger immediately after RT compared to before RT (p < 0.0001), but there was no difference at later time points. These results indicate that the increased risk for complications after surgical procedures are not directly related to changes in skin perfusion and microvascular responsiveness observed after postmastectomy RT.

Effect of Hypotension and Dobutamine on Gastrointestinal Microcirculations of Healthy, Anesthetized Horses.

Horses undergoing abdominal exploratory surgery are at risk of hypotension and hypoperfusion. Normal mean arterial pressure is used as a surrogate for adequate tissue perfusion. However, measures of systemic circulation may not be reflective of microcirculation. This study measured the mean arterial pressure, cardiac index, lactate, and four microcirculatory indices in six healthy, anesthetized adult horses undergoing elective laparotomies. The microcirculatory parameters were measured at three different sites along the gastrointestinal tract (oral mucosa, colonic serosa, and rectal mucosa) with dark-field microscopy. All macro- and microcirculatory parameters were obtained when the horses were normotensive, hypotensive, and when normotension returned following treatment with dobutamine. Hypotension was induced with increases in inhaled isoflurane. The horses successfully induced into hypotension did not demonstrate consistent, expected changes in systemic perfusion or microvascular perfusion parameters at any of the three measured gastrointestinal sites. Normotension was successfully restored with the use of dobutamine, while the systemic perfusion and microvascular perfusion parameters remained relatively unchanged. These findings suggest that the use of mean arterial pressure to make clinical decisions regarding perfusion may or may not be accurate.

Dual-exposure temporal laser speckle imaging for simultaneously accessing microvascular blood perfusion and angiography.

Laser speckle contrast imaging (LSCI) has gained significant attention in the biomedical field for its ability to map the spatio-temporal dynamics of blood perfusion in vivo. However, LSCI faces difficulties in accurately resolving blood perfusion in microvessels. Although the transmissive detecting geometry can improve the spatial resolution of tissue imaging, ballistic photons directly transmitting forward through tissue without scattering will cause misestimating in the flow speed by LSCI because of the lack of a quantitative theoretical model of transmissvie LSCI. Here, we develop a model of temporal LSCI which accounts for the effect of nonscattered light on estimating decorrelation time. Based on this model, we further propose a dual-exposure temporal laser speckle imaging method (dEtLSCI) to correct the overestimation of background speed when performing traditional transmissive LSCI, and reconstruct microvascular angiography using the scattered component extracted from total transmitted light. Experimental results demonstrated that our new method opens an opportunity for LSCI to simultaneously resolve the blood vessels morphology and blood flow speed at microvascular level in various contexts, ranging from the drug-induced vascular response to angiogenesis and the blood perfusion monitoring during tumor growth.

Monitoring coronary blood flow by laser speckle contrast imaging after myocardial ischaemia reperfusion injury in adult and aged mice.

Investigating coronary microvascular perfusion responses after myocardial infarction (MI) would aid in the development of flow preserving therapies. Laser speckle contrast imaging (LSCI) is a powerful tool used for real-time, non-contact, full-field imaging of blood flow in various tissues/organs. However, its use in the beating heart has been limited due to motion artifacts. In this paper, we report the novel use of LSCI, combined with custom speckle analysis software (SpAn), to visualise and quantitate changes in ventricular perfusion in adult and aged mice undergoing ischaemia-reperfusion (IR) injury. The therapeutic benefit of inhibiting the actions of the pro-inflammatory cytokine interleukin-36 (IL-36) was also investigated using an IL-36 receptor antagonist (IL-36Ra). Imaging from uncovered and covered regions of the left ventricle demonstrated that whilst part of the LSCI flux signal was derived from beating motion, a significant contributor to the flux signal came from ventricular microcirculatory blood flow. We show that a biphasic flux profile corresponding to diastolic and systolic phases of the cardiac cycle can be detected without mathematically processing the total flux data to denoise motion artifacts. Furthermore, perfusion responses to ischaemia and postischaemia were strong, reproducible and could easily be detected without the need to subtract motion-related flux signals. LSCI also identified significantly poorer ventricular perfusion in injured aged mice following IR injury which markedly improved with IL-36Ra. We therefore propose that LSCI of the heart is possible despite motion artifacts and may facilitate future investigations into the role of the coronary microcirculation in cardiovascular diseases and development of novel therapies.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.