Perfusion Levels Research Articles

Dynamic conditioning of porcine kidney grafts with extracellular vesicles derived from urine progenitor cells: A proof-of-concept study.

: Among strategies to limit ischemia/reperfusion (IR) injuries in transplantation, cell therapy using stem cells to condition/repair transplanted organs appears promising. We hypothesized that using a cell therapy based on extracellular vesicles (EVs) derived from urine progenitor cells (UPCs) during hypothermic and normothermic machine perfusion can prevent IR-related kidney damage. We isolated and characterized porcine UPCs and their extracellular vesicles (EVs). Then these were used in an ex vivo porcine kidney preservation model. Kidneys were subjected to warm ischemia (32min) and then preserved by hypothermic machine perfusion (HMP) for 24h before 5h of normothermic machine perfusion (NMP). Three groups were performed (n=5-6): Group 1 (G1): HMP/vehicle + NMP/vehicle, Group 2 (G2): HMP/EVs + NMP/vehicle, Group 3 (G3): HMP/EVs + NMP/EVs. Porcine UPCs were successfully isolated from urine and fully characterized as well as their EVs which were found of expected size/phenotype. EVs injection during HMP alone, NMP alone, or both was feasible and safe and did not impact perfusion parameters. However, cell damage markers (LDH, ASAT) were decreased in G3 compared with G1, and G3 kidneys displayed a preserved tissue integrity with reduced tubular dilatation and inflammation notably. However, renal function indicators such as creatinine clearance measured for 5h of normothermic perfusion or NGAL perfusate's level were not modified by EVs injection. Regarding perfusate analysis, metabolomic analyses and cytokine quantification showed an immunomodulation signature in G3 compared with G1 and highlighted potential metabolic targets. In vitro, EVs as well as perfusates from G3 partially recovered endothelial cell metabolic activity after hypoxia. Finally, RNA-seq performed on kidney biopsies showed different profiles between G1 and G3 with regulation of potential IR targets of EVs therapy. We showed the feasibility/efficacy of UPC-EVs for hypothermic/normothermic kidney conditioning before transplantation, paving the way for combining machine perfusion with EVs-based cell therapy for organ conditioning. HIGHLIGHTS: ·UPCs from porcine urine can be used to generate a cell therapy product based on extracellular vesicles (pUPC-EVs). ·pUPC-EVs injection during HMP and NMP decreases cell damage markers and has an immunomodulatory effect. ·pUPC-EVs-treated kidneys have distinct biochemical, metabolic, and transcriptomic profiles highlighting targets of interest. ·Our results pave the way for combining machine perfusion with EV-based cell therapy for kidney conditioning.

Abstract 4119926: Inadequate calorie and macronutrient intake in a population with congestive heart failure in a non-cardiovascular tertiary hospital.

Introduction: Chronic Heart Failure (HF) is a clinical syndrome that as a consequence of the compensatory mechanisms to maintain an adequate level of perfusion, causes dyspnea, peripheral edema, fatigue, lack of appetite, changes in body weight, cachexia, sarcopenia, among others. The presence of these signs and symptoms, with other factors such as restrictions on salt and water consumption, early satiety, and poor mobility, producing changes in the patient's nutritional status that can indirectly increase the risk of inadequate dietary intake, which over a prolonged period will lead to the development of nutritional deficiencies. Objective: To analyze the dietary intake of energy, macronutrients, and micronutrients of patients with chronic HF in outpatient care. Methods: Cross-sectional study, including 75 outpatients with HF, who attended a Heart Failure Clinic. Data collection on dietary intake was obtained using a multi-step 24-hour recall. The ESHA Food Processor program was used to calculate the energy, macronutrient, and micronutrient intake. The presence of congestion was evaluated by bioelectrical impedance vectorial analysis and VEXUS. Results: The baseline characteristics of the population are shown in Table 1. Of the total population, 34% presented with deficient caloric intake, and the subjects who presented congestion also ingested significant fewer calories compared with those who do not present congestion (p= 0.031). Only 15% of patients had an adequate protein intake that resulted in lower NYHA class; among those subjects with a deficient protein intake, 72% had congestion measured by VExUS or bioelectrical impedance. For the sodium intake in the subjects' diet, 45% exceeded the recommendation stated in the guidelines of less than 2,400 mg of sodium per day which was not statistically significant (p=0.077). Discussion and Conclusions: The inadequate intake of calorie or macronutrients in patients with CHF led the patients to more congestion and higher NYHA class, this provide a perspective on the importance of adequate nutritional advice by an expert in the area, which is also essential to improve the clinical course of heart failure. Likewise, future studies are deeded to investigate whether this poor dietary intake is inversely related to some clinical manifestations such as congestion, suggesting that improving these conditions could positively impact patients' volume status and improve functional class.

Minimizing Acute Kidney Injury in Pediatric Cardiac Surgery: Incidence, Early Detection, and Preemptive Measures.

Background Acute kidney injury (AKI) poses a significant challenge in pediatric cardiac surgery, having a profound impact on patient morbidity and mortality. This study aims to determine the incidence of AKI, explore novel biomarkers for early detection,assess potential risk factors along with preemptive strategies to minimize its incidence and compare the results with similar studies that did not use these interventions. Methods This prospective observational cohort study, conducted from October 2022 to June 2024 at a tertiary care center, involved 44 pediatric patients, aged three months to 15 years, undergoing cardiac surgery. Kidney function was assessed through preoperative and postoperative measurements of serum creatinine, urine output, blood urea, and newer biomarkers such as cystatin C and urine neutrophil gelatinase-associated lipocalin (NGAL). AKI was defined and classified using the Acute Kidney Injury Network (AKIN) criteria, based on increases in serum creatinine or reductions in urine output within the first three days post surgery. To reduce the risk of AKI, a low-dose vasopressin infusion and blood transfusion were administered to maintain renal perfusion and optimal hematocrit levels. The incidence of AKI was calculated and compared with other studies that did not utilize these strategies Results AKI occurred in 31.8% (n=14) of the pediatric patients undergoing cardiac surgery. To reduce the risk of AKI, preemptive low-dose vasopressin was used as a preventive strategy. Patients who developed AKI exhibited significant elevations in serum creatinine, blood urea, and cystatin C, with postoperative NGAL levels exceeding 50 ng/ml. The study found a strong correlation between lower intraoperative hematocrit levels (<30%) and a higher incidence of AKI (100% vs. 6.2%, p<0.001). Conclusions Effective management of intraoperative hematocrit levels and the preemptive use of vasopressin are promising strategies for reducing AKI risk by optimizing renal perfusion and function during cardiac surgery.Early detection through biomarkers like cystatin C and NGAL offers the potential for timely intervention and better patient outcomes. These findings contribute to improving risk assessment and perioperative management in pediatric patients vulnerable to AKI.

Peculiarities of the body component composition and microcirculation of qualified divers

One of the important aspects of improving the effectiveness of training qualified divers is understanding the peculiarities of body component composition and the state of microcirculation. The aim of this study was to investigate the component body composition and microcirculation peculiarities of qualified divers diving from different types of gymnastic equipment. The study sample included 30 qualified divers, consisting of 17 girls and 13 boys aged 13 to 18 years. Body composition was assessed using bioimpedance analysis, and the functional state of the microcirculatory system was evaluated through laser Doppler flowmetry. The results indicated that divers who utilized the 10-meter tower exhibited a statistically significant decrease in adipose tissue content and an increase in fat-free mass and relative muscle mass compared to athletes in other diving disciplines. Additionally, a high level of tissue perfusion and microvascular reactivity was observed among the athletes. These findings are crucial for assessing and enhancing the training effectiveness of qualified diving athletes.

Effects of veno-arterial extracorporeal membrane oxygenation return cannula side hole structure on aortic hemodynamic features under different perfusion levels.

The interaction between primary left ventricular output and Veno-arterial extracorporeal membrane pulmonary oxygenation (VA ECMO) flow may impede the perfusion of aortic vessels with hyperoxic blood, leading to differential oxygenation. ECMO return cannula design significantly influences the perfusion level of blood supplied via ECMO. This study aimed to investigate the impact of various cannula designs (side hole number) on intravascular flow patterns under different blood perfusion conditions. Six return cannula models with different side hole number and three cardiac output waveforms were designed based on clinical data for comparative analysis. The position of the blood mixing zone (MZ) was influenced by the flow-volume ratio of the heart output (CO/(CO+Qec)) and cannula design. As the CO/(CO+Qec) and the number of side holes in the cannula increased, the MZ shifted from the ascending aorta to the descending aorta. Concurrently, aortic wall and scalar shear stress on the impact side of ECMO cannulation reduced progressively. Return cannula with side holes effectively mitigated discrepancies in the perfusion of the renal artery and inadequate perfusion of the lower limb vessels on the cannula side while simultaneously reducing damage to the vessel walls and blood. However, increasing the number of side holes in the return cannulas resulted in diminished perfusion of the aortic arch bifurcation vessels by hyperoxic blood supplied via ECMO. Increasing the number of return cannula side holes for VA ECMO femoral artery cannulation improves hypoxic perfusion in the lower limb and reduces vascular endothelial injury, but may also lead to inadequate hypoxic perfusion in the upper body.

Influence of Age and Sex on Stability Indicators of the Right-Left Hemodynamic Balance of Skin Microcirculation in Symmetrical Areas of the Human Head.

Indicators (markers) of microcirculation stability (MCR) of the skin in symmetric areas of the head were studied in young (18-19-years-old) and elderly (60-80-years-old) male and female subjects. We performed synchronous MCR measurements of symmetrical areas of the head using laser Doppler flowmetry in 40 healthy volunteers (10 men and 10 women in each age group). Numerical values of stability markers (T1, T2, and ζ) and indicators of the right-left hemodynamic balance of the MCR (regression coefficients a1, a2, b1, b2) were obtained using the previously developed computational and experimental methods. The coefficients a2 and b2 that determine the contribution of the right MCR bed to the right-left hemodynamic balance were higher in elderly men than in young men, while in young and elderly women, no significant differences in the values of these coefficients were revealed. In young men, coefficients a2 and b2 were lower than in young women, while in elderly subjects, the sex differences in these coefficients were leveled. Young men have lower stability markers than women, while in elderly subjects, these stability markers were similar in men and women. No significant age and sex differences in the level of perfusion of the symmetrical temporal regions were found. The results attest to low stability of MCR in young men in comparison with young women and similar stability in old age, which, apparently, can be explained by the influence of sex hormones on the regulation of human cardiovascular functions.

Arterial hypoperfusion as a negative predictive marker for primary hepatic malignancies treated with Y-90 glass microsphere transarterial radioembolization.

Radioembolization with yttrium-90 (Y-90) is utilized to treat primary liver malignancies. The efficacy of this intra-arterial therapy in arterially hypoperfused tumors is not known. We reviewed data of patients with primary liver tumors treated with Y-90 prescription doses of at least 150 Gy. Baseline patient characteristics, treatment history, imaging-based tumor response assessments, and clinical outcome metrics were recorded. Tumors were classified as arterially hyperperfused versus hypoperfused on post-TARE Y-90 SPECT/CTs or pre-TARE hepatic perfusion SPECT/CTs. Perfusion status was correlated with tumor response assessments and clinical outcomes. Cox proportional hazards models were utilized to compare survival and progression-free survival. Inverse probability weighting was utilized to account for clinical factors and adjusted multivariable proportional hazards analyses to examine the relationship of quantitative perfusion and cancer outcomes. Of 400 Y-90 treatments, 88 patients received a prescribed dose of at least 150 Gy and had pre- or post-treatment SPECT/CT images. 11 and 77 patients had arterially hypoperfused and hyperperfused lesions, respectively. On dedicated liver MRI or CT at 3 months after Y-90, the complete response rates were 5.6% and 16.5% in the hypoperfused and hyperperfused cohort, respectively (P = 0.60). When controlling for various clinical features, including tumor histology, patients with arterially hypoperfused tumors had significantly shorter progression-free survival (HR 1.87, 95% CI - 1.03 - 3.37, P = 0.039) and greater elsewhere liver (HR 3.36, 95% CI = 1.23 - 9.20, P = 0.019) and distant failure (HR 7.64 (2.71 - 21.54, P < 0.001). In inverse probability weighted analysis, patients with arterially hypoperfused tumors had worse overall survival (P = 0.032). In the quantitative analysis, lower levels of lesion perfusion were also associated with worse clinical outcomes, again controlling for tumor histology. Compared to arterially hyperperfused tumors, hypoperfused primary liver tumors treated with Y-90 may have worse clinical outcomes.

Altered brain perfusion and oxygen levels relate to sleepiness and attention in post-COVID syndrome.

Persisting neurological symptoms after COVID-19 affect up to 10% of patients and can manifest in fatigue and cognitive complaints. Based on recent evidence, we evaluated whether cerebral hemodynamic changes contribute to post-COVID syndrome (PCS). Using resting-state functional magnetic resonance imaging, we investigated brain perfusion and oxygen level estimates in 47 patients (44.4 ± 11.6 years; F:M = 38:9) and 47 individually matched healthy control participants. Group differences were calculated using two-sample t-tests. Multivariable linear regression was used for associations of each regional perfusion and oxygen level measure with cognition and sleepiness measures. Exploratory hazard ratios were calculated for each brain metric with clinical measures. Patients presented with high levels of fatigue (79%) and daytime sleepiness (45%). We found widespread decreased brain oxygen levels, most evident in the white matter (false discovery rate adjusted-p-value (p-FDR) = 0.038) and cortical grey matter (p-FDR = 0.015). Brain perfusion did not differ between patients and healthy participants. However, delayed patient caudate nucleus perfusion was associated with better executive function (p-FDR = 0.008). Delayed perfusion in the cortical grey matter and hippocampus were associated with a reduced risk of daytime sleepiness (hazard ratio (HR) = 0.07, p = 0.037 and HR = 0.06, p = 0.034). Decreased putamen oxygen levels were associated with a reduced risk of poor cognitive outcome (HR = 0.22, p = 0.019). Meanwhile, lower thalamic oxygen levels were associated with a higher risk of cognitive fatigue (HR = 6.29, p = 0.017). Our findings of lower regional brain blood oxygen levels suggest increased cerebral metabolism in PCS, which potentially holds a compensatory function. These hemodynamic changes were related to symptom severity, possibly representing metabolic adaptations.

Dye-less quantification of tissue perfusion by laser speckle contrast imaging is equivalent to quantified indocyanine green in a porcine model.

Subjective surgeon interpretation of near-infrared perfusion video is limited by low inter-observer agreement and poor correlation to clinical outcomes. In contrast, quantification of indocyanine green fluorescence video (Q-ICG) correlates with histologic level of perfusion as well as clinical outcomes. Measuring dye volume over time, however, has limitations, such as it is not on-demand, has poor spatial resolution, and is not easily repeatable. Laser speckle contrast imaging quantification (Q-LSCI) is a real-time, dye-free alternative, but further validation is needed. We hypothesize that Q-LSCI will distinguish ischemic tissue and correlate over a range of perfusion levels equivalent to Q-ICG. Nine sections of intestine in three swine were devascularized. Pairs of indocyanine green fluorescence imaging and laser speckle contrast imaging video were quantified within perfused, watershed, and ischemic regions. Q-ICG used normalized peak inflow slope. Q-LSCI methods were laser speckle perfusion units (LSPU), the base unit of laser speckle imaging, relative perfusion units (RPU), a previously described methodology which utilizes an internal control, and zero-lag normalized cross-correlation (X-Corr), to investigate if the signal deviations convey accurate perfusion information. We determine the ability to distinguish ischemic regions and correlation to Q-ICG over a perfusion gradient. All modalities distinguished ischemic from perfused regions of interest; Q-ICG values of 0.028 and 0.155 (p < 0.001); RPU values of 0.15 and 0.68 (p < 0.001); and X-corr values of 0.73 and 0.24 (p < 0.001). Over a range of perfusion levels, RPU had the best correlation with Q-ICG (r = 0.79, p < 0.001) compared with LSPU (r = 0.74, p < 0.001) and X-Corr (r = 0.46, p < 0.001). These results demonstrate that Q-LSCI discriminates ischemic from perfused tissue and represents similar perfusion information over a broad range of perfusion levels comparable to clinically validated Q-ICG. This suggests that Q-LSCI might offer clinically predictive real-time dye-free quantification of tissue perfusion. Further work should include validation in histologic studies and human clinical trials.

Exploring laser-induced acute and chronic retinal vein occlusion mouse models: Development, temporal in vivo imaging, and application perspectives.

Photodynamic venous occlusion is a commonly accepted method for establishing mouse models of retinal vein occlusion (RVO). However, existing model parameters do not distinguish between acute and chronic RVO subtypes. Large variations in laser energy seem to correlate with fluctuating retinopathy severity and high rates of venous recanalization during the acute phase, along with the variable levels of retinal perfusion during the chronic phase. After optimizing the modeling procedure and defining success and exclusion criteria, laser energy groups of 80mW, 100mW, and 120mW were established. Multimodal imaging confirmed that higher energy levels increased the incidence of retinal cystoid edema and intraretinal hemorrhage, exacerbated the severity of exudative retinal detachment, and reduced the venous recanalization rate. For the acute model, 100mW was considered an appropriate parameter for balancing moderate retinopathy and venous recanalization. Continuous imaging follow-up revealed that day 1 after RVO was the optimal observation point for peaking of retinal thickness and intensive occurrence of retinal cystic edema and intraretinal hemorrhage. After excluding the influence of venous recanalization on retinal thickness, acute retinal edema demonstrated a positive response to standard anti-vascular endothelial growth factor therapy, validating the clinical relevance of the acute RVO model for further study in pathogenic mechanisms and therapeutic efficacy. For the chronic model, the 120mW parameter with the lowest venous recanalization rate was applied, accompanied by an increase in both photocoagulation shots and range to ensure sustained vein occlusion. Imaging follow-up clarified non-ischemic retinopathy characterized by tortuosity and dilation of the distal end, branches, and adjacent veins of the occluded vein. These morphological changes are quantifiable and could be combined with electrophysiological functional assessment for treatment effectiveness evaluation. Moreover, the stable state of venous occlusion may facilitate investigations into response and compensation mechanisms under conditions of chronic retinal hypoperfusion.

Ferroptosis Inhibition with Deferoxamine Alleviates Radiation-Induced Fibrosis.

Background Radiation-induced fibrosis (RIF) is a debilitating sequelae of radiation therapy that has been shown to improve with topical treatment with the iron chelator deferoxamine (DFO). We investigated whether DFO exerts this effect through attenuation of ferroptosis, a recently described iron-dependent pathway of cell death. Methods Adult C57BL/6J mice were treated with topical DFO or ferrostastin-1 (Fer-1) and irradiated with 30 Grays of ionizing radiation to the dorsal skin to promote development of chronic RIF. Immunofluorescent staining with 4-hydroxynonenal (4-HNE) antibody was carried out directly following irradiation to assess ferroptosis activity. Perfusion testing with laser Doppler was performed throughout the healing interval. Eight weeks following radiation, dorsal skin was harvested and analyzed histologically and biomechanically. Results Immunohistochemical staining demonstrated lower presence of 4-HNE in non-irradiated skin, DFO-treated skin, and Fer-1-treated skin compared to irradiated, untreated skin. DFO resulted in histological measurements (dermal thickness and collagen content) that resembled normal skin, while Fer-1 treatment yielded less significant improvements. These results were mirrored by analysis of extracellular matrix ultrastructure and biomechanical testing, which recapitulated the ability of topical DFO treatment to alleviate RIF across these parameters while Fer-1 resulted in less notable improvement. Finally, perfusion levels in DFO treated irradiated skin were similar to measurements in normal skin, while Fer-1 treatment did not impact this feature. Conclusions Ferroptosis contributes to the development of RIF and attenuation of this process leads to reduced skin injury. DFO further improves RIF through additional enhancement of perfusion not seen with Fer-1.

Advancements in non-invasive hyperspectral imaging: Mapping blood oxygen levels and vascular health for clinical and research applications

Oxygen content is crucial for the functioning of human body organs, as it plays a vital role in cellular respiration, which generates energy necessary for life-sustaining functions. The absence of adequate oxygen leads to cellular dysfunction and eventual organismal death due to energy deprivation.In this study, we designed a rapid, non-invasive, and non-contact custom hyperspectral imaging system to assess blood perfusion in arteries, capillaries, and veins across various human organs, including the arm, eye, and leg. The system recorded cube images consisting of multispectral image ranges, capturing spectral information in both the visible and infrared spectra. Segmentation of the visible spectrum (400 to 700 nm) and the infrared spectrum (700 to 1000 nm) facilitated the mapping of blood oxygen levels in the investigated samples.The estimated oxygen levels were calculated using the custom hyperspectral imaging system and associated algorithm, with validation and calibration performed against the gold standard pulse oximeter. Our results demonstrate that the custom hyperspectral imaging system accurately mapped blood perfusion and oxygen levels in organs, showing strong agreement with pulse oximeter measurements.This study underscores the utility of custom hyperspectral imaging in non-invasively assessing blood oxygenation and perfusion in human organs, offering a promising avenue for clinical diagnostics and monitoring of vascular health.

Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Quantitative analysis of intestinal perfusion with indocyanine green (ICG) and methylene blue (MB) using a single clinically approved fluorescence imaging system: a demonstration in a porcine model

BackgroundNear-infrared fluorescence (NIRF) angiography with intraoperative administration of indocyanine green (ICG) has rapidly disseminated in clinical practice. Another clinically approved, and widely available dye, methylene blue (MB), has up to now not been used for this purpose. Recently, we demonstrated promising results for the real-time evaluation of intestinal perfusion using this dye. The primary aim of this study was to perform a quantitative analysis of bowel perfusion assessment for both ICG and MB.MethodsFour mature female Landrace pigs underwent laparotomy under general anesthesia. An ischemic bowel loop with five regions of interest (ROIs) with varying levels of perfusion was created in each animal. An intravenous (IV) injection of 0.25 mg/kg–0.50 mg/kg MB was administered after 10 min, followed by NIRF imaging in MB mode and measurement of local lactate levels in all corresponding ROIs. This procedure was repeated in ICG mode (IV dose of 0.2 mg/kg) after 60 min. The quest spectrum fluorescence camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging of both MB and ICG.ResultsIntraoperative NIRF imaging of bowel perfusion assessment with MB and ICG was successful in all studied animals. Ingress (i/s) levels were calculated and correlated with local lactate levels. Both MB and ICG ingress values showed a significant negative correlation (r = − 0.7709; p = < 0.001; r = − 0.5367, p = 0.015, respectively) with local lactate levels. This correlation was stronger for MB compared to ICG, although ICG analysis showed higher absolute ingress values.ConclusionOur fluorescence quantification analysis validates the potential to use MB for bowel perfusion assessment besides the well-known and widely used ICG. Further human studies are necessary to translate our findings to clinical applications.

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) improves lipid utilization but not survival following prolonged hemorrhagic shock

Hemorrhagic shock induces insulin resistance and cellular ATP depletion, the initial step for cell death and organ injury. AMPK is a fuel-sensing enzyme that maintains ATP production by facilitating glucose and fatty acid uptake and oxidation. Using a previously developed rat model of AKI induced by prolonged hemorrhagic shock, we tested the hypothesis that AICAR, an AMPK activator, can enhance fuel consumption, delay onset of AKI, and increase survival following prolonged hemorrhagic shock. Additionally, we hypothesized that AICAR requires 7.5% polyethylene glycol-20k (PEG) to elicit the catabolism effect, as PEG enhances the capillary perfusion in the absence of resuscitation, and thus, in theory, facilitates AICAR delivery into ischemic tissues. Rats were randomized into 4 groups (n=8/group) based on treatment: saline (vehicle), AICAR, PEG, and AICAR+PEG. Trauma was induced in (Inactin) anesthetized rats with muscle injury and fibula fracture, followed by pressure-controlled hemorrhagic shock (MAP = 55 mmHg) for 45 minutes. Animals then received an intravenous injection of saline (vehicle), AICAR, PEG, or AICAR+PEG. MAP, blood gases, RBF, renal oxygen delivery, capillary perfusion and tissue oxygen levels in the skeletal muscle were monitored for another 2 hours. GFR and mortality were recorded at the end of the experiment. The saline group exhibited impaired tissue perfusion and GFR with 100% mortality. AICAR alone showed no effect on hemodynamics, renal function, or mortality (100%). PEG and AICAR+PEG similarly improved MAP, capillary perfusion in the skeletal muscle, renal blood flow, renal oxygen delivery, and GFR. Compared to PEG, free FA levels were further decreased in AICAR+PEG, which was concomitant with elevated lactate levels and blunted oxygen partial pressure in the skeletal muscle despite the improved capillary perfusion. The mortality was 12.5% in PEG and 50% in AICAR+PEG. Our results suggest that AICAR+PEG does enhance fuel utilization but fails to further improve the tolerance to hemorrhagic shock, possibly due to a shift of oxygen consumption from vital organs to peripheral tissue. Importantly, the catabolism effect of AICAR relies on suffcient tissue perfusion, suggesting that PEG might be potentially considered as a routine therapeutic tool to optimize drug delivery during hemorrhagic shock. DoD disclaimer: The views expressed in this article are those of the author(s) and do not reflect the offcial policy or position of the U.S. Army Medical Department, Department of the Army, DoD, or the U.S. Government. Funding: This study was funded by US Army Medical Research and Development Command. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Parameter Identification Approach towards Hemodynamics based on Capnography

Research question Pulse detection decisions during cardiopulmonary resuscitation (CPR) are commonly augmented by end-tidal CO2-concentration (etCO2) levels and trend as etCO2 is a surrogate measure of systemic blood flow during (CPR)1. However, ventilatory and circulatory parameters influence the interpretability of etCO2 heavily. Recently developed methods of continuous cardiac output measurement based on capnography are not applicable during CPR due to the required controlled ventilation settings2. In this study, a parameter identification for a model of CO2 transport during resuscitation is used to estimate cardiac output based on capnography and tidal flow. Methodology After development of a compartmental ordinary differential equation (ODE) model to represent CO2 transport during CPR, parameters such as airway dead space and the level of systemic perfusion are estimated by a multishooting parameter identification approach3. To evaluate the method, tests are conducted on experimental data from a porcine model (approved by an ethics committee vote of the Austrian Federal Ministry of Education, Science and Research (GZ: 2021-0.895.386)). The estimated level of systemic perfusion is compared visually to invasively measured mean arterial pressure due to a lack of continuous cardiac output measurements as a ground truth. Results For exemplary data from a female pig (weight 50.4 kg), airway resistance was estimated to 20.8 hPa s /L, compliance: 25.2 mL/hPa, and dead space: 109 mL. Changes in cardiac output can be identified qualitatively as shown in Fig. 1. Conclusion A validated, simple ODE model for CO2 extraction during CPR could contribute quantifying the impact of ventilatory parameters on etCO2 and elucidate CO2 production, storage and transport during cardiac arrest. Assumptions on CO2 production during cardiac arrest and redistribution in the body, and the lacking cardiac output measurements complicate the analysis. Conflicts of Interest All authors have no conflict of interest to declare.

Functional state of dermal circulation in patients with lichen planus

Lichen planus belongs to the group of the most common dermatoses. The etiology and mechanisms of development of lichen planus are not fully understood. This dermatosis is characterized by a variety of clinical forms, as well as a chronically relapsing course, and a fairly frequent resistance to traditional therapies. The chronically relapsing course and susceptibility to complications and deterioration in the quality of life of patients with lichen planus give this dermatosis the status of a medical and social problem. Objective — to investigate the state of blood circulation in the areas of skin lesions of patients with lichen planus, depending on the stage of the clinical course of dermatosis. Materials and methods. We observed 37 patients with lichen planus with a typical (classical) clinical form (22 men and 15 women) aged 20 to 44 years. The comparison group consisted of 30 apparently healthy individuals, comparable by sex and age. In 19 patients, the progressive stage of dermatosis was diagnosed, in 18 — the stationary stage. The duration of the course of the disease in the subjects ranged from two weeks to six months. In all the examined patients, the microcirculation index (MI), the mean quadratic deviation of the microcirculation indicators, the coefficient of variation (KV), as well as maximum amplitude of slow oscillations (ALF), maximum amplitude of rapid oscillations (AHF), maximum amplitude of pulse oscillations (ACF) were determined. The first component of the active mechanism of regulation of tissue circulation was calculated according to the formula ALF/PM; the second component — according to the formula σ/ALF; the first component of the passive mechanism of modulation of tissue circulation was calculated according to the formula ACF/σ; the second component — according to the formula AHF/σ. In addition, the intravascular resistance ACF/PM · 100 % and the microcirculation efficiency coefficient ALF/(AHF + ACF) were studied. The study was carried out on a Doppler flowmeter Vingmed SD-100 (Sweden). Results and discussion. The obtained results indicate a low level of tissue perfusion, insufficient functioning of tissue blood circulation modulation mechanisms and reduced vasomotor activity of microvessels in the areas of affected skin of patients with lichen planus. It was also established that the modulation of tissue blood circulation was redistributed in the direction of reducing the passive mechanism, that is, in the direction of disturbances of cardiac and respiratory rhythms of fluctuations. Conclusions. In the examined patients with a typical (classical) form of the clinical course of lichen planus, a stagnant­static type of hemodynamics in the dermis was established during the examination by laser Doppler flowmetry in the skin areas affected by a specific papular rash.It has also been proved that in patients with lichen planus, in particular, in skin areas with specific lichenoid lesions, there is a redistribution of modulation of tissue blood circulation towards a decrease in the passive mechanism, that is, towards cardiac and respiratory rhythm disorders of fluctuations.The established disorders of dermal vascularization in the areas of skin lesions of patients with lichen planus expand the understanding of the pathogenesis of this dermatosis and need to be taken into account when developing the tactics of its complex, individualized therapy, which will contribute to increasing the effectiveness of treatment.

Comparison of Intact Fish Skin Graft and Allograft as Temporary Coverage for Full-Thickness Burns: A Non-Inferiority Study.

The extent and depth of burn injury may mandate temporary use of cadaver skin (allograft) to protect the wound and allow the formation of granulation tissue while split-thickness skin grafts (STSGs) are serially harvested from the same donor areas. However, allografts are not always available and have a high cost, hence the interest in identifying more economical, readily available products that serve the same function. This study evaluated intact fish skin graft (IFSG) as a temporary cover to prepare the wound bed for STSG application. Thirty-six full-thickness (FT) 5 × 5 cm burn wounds were created on the dorsum of six anesthetized Yorkshire pigs on day -1. To mimic the two-stage clinical situation, on day 0, wounds were excised down to a bleeding wound bed and a temporary cover (either IFSG or cadaver porcine skin) was applied; then, on day 7, wounds were debrided to a viable wound bed prior to the application of autologous 1.5:1 meshed STSG (mSTSG). Rechecks were performed on days 14, 21, 28, 45, and 60 with digital images, non-invasive measurements, and punch biopsies. The IFSG created a granulated wound bed receptive to the application of an mSTSG. FT burn wounds treated with an IFSG had similar outcome measures, including contraction rates, trans-epidermal water loss (TEWL) measurements, hydration, and blood perfusion levels, compared to cadaver skin-treated burn wounds. Pathology scoring indicated significant differences between the allograft- and IFSG-treated wounds on day 7, with the IFSG having increased angiogenesis, granulation tissue formation, and immune cells. Pathology scoring indicated no significant differences once mSTSGs were applied to wounds. The IFSG performed as well as cadaver skin as a temporary cover and was not inferior to the standard of care, suggesting the potential to transition IFSGs into clinical use for burns.

Comparison of computed tomography perfusion and magnetic resonance dynamic susceptibility contrast perfusion-weighted imaging in canine brain.

Brain perfusion allows for the evaluation of cerebral hemodynamics, particularly in brain infarcts and tumors. Computed tomography (CT) perfusion (CTP) provides reliable data; however, it has a limited scan field of view and radiation exposure. Magnetic resonance (MR) perfusion provides detailed imaging of small structures and a wide scan field of view. However, no study has compared CTP and MR perfusion and assessed the correlation between the perfusion parameters measured using CTP and MR perfusion. The aim of the present study was to assess the correlation and agreement of the cerebral perfusion derived from dynamic susceptibility contrast (DSC)-MRI and CTP in dogs. In this crossover design study, the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time, and time to peak were measured in the temporal cerebral cortex, caudate nucleus, thalamus, piriform lobe, and hippocampus using CTP and DSC-MRI in six healthy beagle dogs and a dog with a pituitary tumor. On the color map of healthy beagles, blood vessels and the perivascular brain parenchyma appeared as red-green, indicating high perfusion, and the areas distant from the vessels appeared as green-blue, indicating low perfusion levels in CTP and DSC-MRI. CTP parameters were highest in the piriform lobe (CBF = 121.11 ± 12.78 mL/100 g/min and CBV = 8.70 ± 2.04 mL/100 g) and lowest in the thalamus (CBF = 63.75 ± 25.24 mL/100 g/min and CBV = 4.02 ± 0.55 mL/100 g). DSC-MRI parameters were also highest in the piriform lobe (CBF = 102.31 ± 14.73 mL/100 g/min and CBV = 3.17 ± 1.23 mL/100 g) and lowest in the thalamus (CBF = 37.73 ± 25.11 mL/100 g/min and CBV = 0.81 ± 0.44 mL/100 g) although there was no statistical correlation in the quantitative perfusion parameters between CTP and DSC-MRI. In a dog with a pituitary tumor, the color map of the tumor appeared as a red scale, indicating high perfusion and higher CBF and CBV on CTP (149 mL/100 g and 20 mL/100 g/min) and on DSC-MRI (116.3 mL/100 g and 15.32 mL/100 g/min) compared to those measured in healthy dogs. These findings indicate that DSC-MRI and CTP maps exhibit comparability and interchangeability in the assessment of canine brain perfusion.

Insights into hippocampal perfusion using high-resolution, multi-modal 7T MRI

We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 tesla arterial spin labeling (ASL) data, we generated robust perfusion maps and observed significant variations in perfusion among hippocampal subfields, with CA1 exhibiting the lowest perfusion levels. Notably, these perfusion differences were robust and already detectable with 50 perfusion-weighted images per subject, acquired in 5 min. To understand the underlying factors, we examined the influence of image quality metrics, various tissue microstructure and morphometric properties, macrovasculature, and cytoarchitecture. We observed higher perfusion in regions located closer to arteries, demonstrating the influence of vascular proximity on hippocampal perfusion. Moreover, ex vivo cytoarchitectonic features based on neuronal density differences appeared to correlate stronger with hippocampal perfusion than morphometric measures like gray matter thickness. These findings emphasize the interplay between microvasculature, macrovasculature, and metabolic demand in shaping hippocampal perfusion. Our study expands the current understanding of hippocampal physiology and its relevance to neurological disorders. By providing in vivo evidence of perfusion differences between hippocampal subfields, our findings have implications for diagnosis and potential therapeutic interventions. In conclusion, our study provides a valuable resource for extensively characterizing hippocampal perfusion.