Organ Perfusion Research Articles

Surgical treatment of a newborn with critical aortic coarctation using palliative stenting: a case report

Introduction. Coarctation of the aorta (CoA) is a congenital severe narrowing of the aortic isthmus, which in turn is often accompanied by impaired organ perfusion or even cardiogenic shock. In newborns with critical CoA in the case of patent ductus arteriosus (PDA) closure, the clinical condition of patients with this congenital heart defect (CHD) sharply worsens and leads to multiple organ failure. In this group of children, mortality ranges from 30 to 50% of infant mortality from CHD. This case demonstrates the positive effect of palliative stenting of a narrowed section of the aorta, which made it possible to safely perform radical surgery for CHD.Case description. Nine-year-old male patient with body weight of 3,5 kg and body length of 53 cm was admitted to the clinic with a diagnosis of CHD: Critical CoA. Secundum atrial septal defect. PDA. Multiple organ failure. Taking into account the severe comorbidity status in the form of multiple organ failure, the high risk of necrotizing enterocolitis, case conference decided to perform a step-by-step CHD treatment as follows: palliative endovascular stenting of critical CoA, followed by radical surgery after stabilization of the patient's condition. The plan was successfully implemented.Conclusion. Сritical CoA stenting can be used as a bridge to radical surgery of the defect in newborns with multiple organ failure. This palliative intervention helps to stabilize the child for up to 3 weeks and more safely perform radical surgery of CoA.

Spectral characterization of intraoperative renal perfusion using hyperspectral imaging and artificial intelligence

Accurate intraoperative assessment of organ perfusion is a pivotal determinant in preserving organ function e.g. during kidney surgery including partial nephrectomy or kidney transplantation. Hyperspectral imaging (HSI) has great potential to objectively describe and quantify this perfusion as opposed to conventional surrogate techniques such as ultrasound flowmeter, indocyanine green or the subjective eye of the surgeon. An established live porcine model under general anesthesia received median laparotomy and renal mobilization. Different scenarios that were measured using HSI were (1) complete, (2) gradual and (3) partial malperfusion. The differences in spectral reflectance as well as HSI oxygenation (StO2) between different perfusion states were compelling and as high as 56.9% with 70.3% (± 11.0%) for “physiological” vs. 13.4% (± 3.1%) for “venous congestion”. A machine learning (ML) algorithm was able to distinguish between these perfusion states with a balanced prediction accuracy of 97.8%. Data from this porcine study including 1300 recordings across 57 individuals was compared to a human dataset of 104 recordings across 17 individuals suggesting clinical transferability. Therefore, HSI is a highly promising tool for intraoperative microvascular evaluation of perfusion states with great advantages over existing surrogate techniques. Clinical trials are required to prove patient benefit.

Normothermic Regional Perfusion in Controlled Donation After the Circulatory Determination of Death: Understanding Where the Benefit Lies.

Controlled donation after the circulatory determination of death (cDCDD) has emerged as a strategy to increase the availability of organs for clinical use. Traditionally, organs from cDCDD donors have been subject to standard rapid recovery (SRR) with poor posttransplant outcomes of abdominal organs, particularly the liver, and limited organ utilization. Normothermic regional perfusion (NRP), based on the use of extracorporeal membrane oxygenation devices, consists of the in situ perfusion of organs that will be subject to transplantation with oxygenated blood under normothermic conditions after the declaration of death and before organ recovery. NRP is a potential solution to address the limitations of traditional recovery methods. It has become normal practice in several European countries and has been recently introduced in the United States. The increased use of NRP in cDCDD has occurred as a result of a growing body of evidence on its association with improved posttransplant outcomes and organ utilization compared with SRR. However, the expansion of NRP is precluded by obstacles of an organizational, legal, and ethical nature. This article details the technique of both abdominal and thoracoabdominal NRP. Based on the available evidence, it describes its benefits in terms of posttransplant outcomes of abdominal and thoracic organs and organ utilization. It addresses cost-effectiveness aspects of NRP, as well as logistical and ethical obstacles that limit the implementation of this innovative preservation strategy.

Acute kidney injury and cardiogenic shock severity for mortality risk stratification in patients supported with VA ECMO.

To assess the stage of acute kidney injury (AKI), as an index of organ perfusion, combined with shock severity, measured by the Society for Cardiovascular Angiography and Interventions (SCAI) shock stage classification, to stratify the risk of mortality in patients diagnosed with cardiogenic shock (CS) and supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). From January 2018 to December 2020, consecutive adult patients diagnosed with CS and received VA ECMO were retrospectively evaluated. The highest AKI stage within 48h after ECMO initiation was assessed using the Kidney Disease: Improving Global Outcomes criteria. We included 216 patients with a mean age of 58.8years and 31.0% were females. 88.4% of patients received ECMO for postcardiotomy, while 11.6% for medical CS. The total in-hospital mortality was 53.2%. AKI occurred in 182 (84.3%) patients receiving ECMO for CS. AKI stage 0, 1, 2, and 3 were present in 15.7%, 17.6%, 18.1%, and 48.6% of patients with in-hospital mortality of 26.5%, 26.3%, 61.5%, and 68.6%, respectively (P<0.001). The AKI stage (P<0.001), SCAI shock stage before ECMO (P=0.008), and NYHA ≥ Class III on admission (P=0.044) were independent predictors of in-hospital mortality. The area under the receiver operating characteristic curve of 0.754 (95% confidence interval: 0.690 to 0.811) for AKI stage combined with SCAI shock stage was better than those for AKI stage (0.676), SCAI shock stage (0.657), serum lactate level (0.682), SOFA score (0.644), SVAE score (0.582), and VIS score (0.530) prior to ECMO. In this single-center CS population who received VA ECMO for circulatory support, predominantly postcardiotomy cases, AKI occurred in 84.3% of the patients. AKI stage, as an index of organ perfusion combined with shock severity measured by the SCAI shock classification, demonstrates a good correlation with in-hospital mortality.

Nitroglycerin versus milrinone for low central venous pressure in patients undergoing laparoscopic hepatectomy: a double-blinded randomized controlled trial

BackgroundConventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients’ recovery.MethodsIn total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2–0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2–0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome.ResultsBlood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05).ConclusionOur findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin.Trial registrationChiCTR2200056891,first registered on 22/02/2022.

Protocol description and initial experience in kidney graft perfusion using infrared thermography.

Protocol description for renal perfusion study using thermographic technology and description of the thermographic and clinical behavior of the transplanted kidneys before and after unclamping. Infrared thermographic images of renal grafts are obtained before kidney reperfusion, 10min after and just before closing the surgical wound. Thermographic data is evaluated together with the type of graft and donor, cold ischemia time, hypovascularized areas determined by the surgeon during surgical intervention, alterations in vascular flow in postoperative echo-Doppler, time at the beginning of graft function and serum creatinine monitoring during postoperative follow-up. 17 grafts were studied. The mean temperature of the grafts before reperfusion, 10min after and at the end of the surgery were 18.7°C (SD 6.27), 32.36°C (SD1.47) and 32.07°C (SD1.78) respectively. 4 grafts presented hypoperfused areas after reperfusion. These areas presented a lower temperature compared to the well perfused parenchyma surface using thermographic images. The study of the usefulness and applicability of thermography can allow the development of tools that provide additional objective information on organ perfusion in real time and non-invasive manner. Our protocol and initial results can contribute to provide new evidence. Further analyses should be developed to shed light on the role of this technology.

1087 Factors That Impact Cold Ischaemia Time for Deceased Donor Kidney Transplants: Results of a National Transplant Access to Theatre Audit (NTACT)

Abstract Aim Deceased donor kidney utilisation confronts challenges leading to prolonged cold ischemia time (CIT), affecting graft survival. Despite these challenges, an understanding of the obstacles remains unclear. This audit aims to identify the factors that prolong CIT. Method A multicentre, prospective audit of adult deceased donor kidney-only transplants spanned 14 UK transplant centres from February to September 2022. Data, encompassing time intervals between important checkpoints pre-transplantation and perceived reasons for delays, were collected through RedCap. Descriptive statistics was used for analysis. Results Data from 476 kidney-only transplants were gathered (29 excluded for incomplete/incorrect data). Of these, 230 were donations after brainstem death (DBD) organs, and 202 were donations after circulatory death (DCD) organs. Median CIT was 10:55 (IQR:08:11-15:13) for DBD organs and 11:19 (IQR:08:31-15:10) for DCD organs, with 42% of DCD and 15% of DBD organs surpassing national CIT recommendations. Median time from organ arrival to knife to skin was 04:02 (IQR:02:35-07:35). Full and virtual crossmatches constituted 35% and 65%, respectively, with 16% of results arriving after the organ arrives at centre. Anaesthetic time had a median duration of 00:55 (IQR:00:39-01:10) and Knife to skin to organ perfusion was 01:25 (01:10-01:51). Delays reported in 34% of transplant cases, most common causes were the availability of surgical and anaesthetic teams, porters, and the operating theatre. Conclusions This audit allowed us to uncover the factors that prolong CIT at each stage of the transplantation post-arrival. These findings will guide the establishment of realistic targets for optimizing processes in the future.

3D Single Vessel Fractional Moving Blood Volume (3D-svFMBV): Fully Automated Tissue Perfusion Estimation Using Ultrasound.

Power Doppler ultrasound (PD-US) is the ideal modality to assess tissue perfusion as it is cheap, patient-friendly and does not require ionizing radiation. However, meaningful inter-patient comparison only occurs if differences in tissue-attenuation are corrected for. This can be done by standardizing the PD-US signal to a blood vessel assumed to have 100% vascularity. The original method to do this is called fractional moving blood volume (FMBV). We describe a novel, fully-automated method combining image processing, numerical modelling, and deep learning to estimate three-dimensional single vessel fractional moving blood volume (3D-svFMBV). We map the PD signals to a characteristic intensity profile within a single large vessel to define the standardization value at the high shear vessel margins. This removes the need for mathematical correction for background signal which can introduce error. The 3D-svFMBV was first tested on synthetic images generated using the characteristics of uterine artery and physiological ultrasound noise levels, demonstrating prediction of standardization value close to the theoretical ideal. Clinical utility was explored using 143 first-trimester placental ultrasound volumes. More biologically plausible perfusion estimates were obtained, showing improved prediction of pre-eclampsia compared with those generated with the semi-automated original 3D-FMBV technique. The proposed 3D-svFMBV method overcomes the limitations of the original technique to provide accurate and robust placental perfusion estimation. This not only has the potential to provide an early pregnancy screening tool but may also be used to assess perfusion of different organs and tumors.

Non-invasive pulse arrival time is associated with cardiac index in pediatric heart transplant patients with normal ejection fraction

Objective. Cardiac Index (CI) is a key physiologic parameter to ensure end organ perfusion in the pediatric intensive care unit (PICU). Determination of CI requires invasive cardiac measurements and is not routinely done at the PICU bedside. To date, there is no gold standard non-invasive means to determine CI. This study aims to use a novel non-invasive methodology, based on routine continuous physiologic data, called Pulse Arrival Time (PAT) as a surrogate for CI in patients with normal Ejection Fraction (EF). Approach. Electrocardiogram (ECG) and photoplethysmogram (PPG) signals were collected from beside monitors at a sampling frequency of 250 samples per second. Continuous PAT, derived from the ECG and PPG waveforms was averaged per patient. Pearson’s correlation coefficient was calculated between PAT and CI, PAT and heart rate (HR), and PAT and EF. Main Results. Twenty patients underwent right heart cardiac catheterization. The mean age of patients was 11.7 ± 5.4 years old, ranging from 11 months old to 19 years old, the median age was 13.4 years old. HR in this cohort was 93.8 ± 17.0 beats per minute. The average EF was 54.4 ± 9.6%. The average CI was 3.51 ± 0.72 l min−1 m−2, with ranging from 2.6 to 4.77 l min−1 m−2. The average PAT was 0.31 ± 0.12 s. Pearson correlation analysis showed a positive correlation between PAT and CI (0.57, p < 0.01). Pearson correlation between HR and CI, and correlation between EF and CI was 0.22 (p = 0.35) and 0.03 (p = 0.23) respectively. The correlation between PAT, when indexed by HR (i.e. PAT × HR), and CI minimally improved to 0.58 (p < 0.01). Significance. This pilot study demonstrates that PAT may serve as a valuable surrogate marker for CI at the bedside, as a non-invasive and continuous modality in the PICU. The use of PAT in clinical practice remains to be thoroughly investigated.

Correlation Between Serum Transaminase Levels and Estimated Glomerular Filtration Rate After Living-Donor Kidney Transplantation

BackgroundThere is a risk of hypoperfusion during kidney transplantation surgery owing to patients’ underlying disease and ischemia-reperfusion injury; further, hypoperfusion may cause injury to major organs. We hypothesized that the decrease in blood pressure after ischemia-reperfusion injury during kidney transplantation may be associated with indicators of liver injury and kidney graft function. MethodsData regarding living-donor kidney transplantations performed at our institution between 2018 and 2022 were retrospectively evaluated. Exclusion criteria included pediatric recipients or donors aged <18 years, multiple organ transplantation, and elevated postoperative serum transaminase levels. Correlations among blood pressure, serum transaminase levels on postoperative days 3 to 5, and estimated glomerular filtration rate (eGFR) on postoperative days 7 and 14 were analyzed. Further, a subgroup analysis was performed based on eGFR. ResultsA total of 276 patients were included in the final analysis. Serum transaminase levels were significantly negatively correlated with eGFR (partial correlation coefficient—0.26, P < .001). The postreperfusion decrease in blood pressure was not correlated with serum transaminase levels. However, the postreperfusion decrease in blood pressure and baseline blood pressure correlated with the eGFR (partial correlation coefficient = −0.18, P = .004). ConclusionThese findings indicate a correlation between intraoperative liver injury and kidney graft function, suggesting the importance of intraoperative management of organ perfusion. Since postreperfusion blood pressure changes did not significantly correlate with liver injury indicators, it is important to consider other causative factors for hypoperfusion in major organs during living-donor kidney transplantation, including microcirculatory failure and organ congestion-related ischemia/reperfusion.

Effects of General Anesthesia on Noninvasively Measured Central and Peripheral Blood Pressure: A Prospective, Observational-based Cross-over Study

Abstract Background: Blood pressure (BP) monitoring is the basic hemodynamic parameter necessary to monitor the hemodynamic changes occurring under general anesthesia (GA) to maintain adequate perfusion to major organs such as the heart, brain, and kidneys. Physicians heavily rely upon peripheral hemodynamic measurements despite availability of devices suitable for measurement of central blood pressure through non-invasive manner paving a gap in the literature concerning the effects of GA on central pressure. Aims and Objective: In this comparative cross-over study, authors have aimed to find out the degree of changes in central and peripheral BP after the introduction of GA among adult patients of different age groups scheduled for routine surgical procedures with an objective to maintain vital functions more precisely – considering the fact that vital organ perfusions (heart, brain etc.,) depend more on the required values of CBP than that of PBP. Material &amp; Methods: Following approval from IEC, sixty adult patients with ASA physical status 1 or 2 undergoing routine surgical procedures under general anesthesia were enrolled in this prospective cross-over study where each patient was case as well control for measurement and comparison of his/her central and peripheral blood pressure. Patients, being divided into three groups as per age range - 20-40 years (Group A), 40-60 years (Group B), and 60-80 years (Group C) had their normal Riva Rocci BP cuff (Space Lab Inc. USA) placed in one arm for peripheral BP measurement and special Riva Rocci (Uscom Ltd., Australia).) BP cuff for on another arm for Central BP measurement. After patient’s arrival into operation theatre, baseline hemodynamic parameters were taken followed by sequential measurements of CBP and PBP with an interval of 2 minutes till 30-40 mins of operation. There were alternative measurements of these pressures with recording of data from either of the devices as mentioned for further comparison and analysis. Results: From baseline values, it was found that all the three groups were comparable in respect of age, height, weight, PBP and CBP. When measured pressure of all groups combined, that there was a fall in both Central and Peripheral SBP as well as DBP after giving intravenous induction agent (propofol) and rise in both central and peripheral SBP and DBP after laryngoscopy and intubation. Degree of systolic blood pressure change in both peripheral &amp; central that is fall of BP in 3rd reading &amp; rise of BP in 5th reading was greatest in group C, followed by group B, then group A [p - 0.005]. While comparing three subgroups, the baseline Augmentation Index (AI) was highest in group C and lowest in group A. Following the administration of general anesthesia (GA), the change in Augmentation Index (ΔAI), was most pronounced in the third reading corresponding to the time after the administration of the induction agent. Conclusion: Measurement of CBP through peripheral placement of cuff is a unique feasible method to detect real changes of circulation with actual pressure in vital organs. Thus, the study suggests that central blood pressure measurements can provide a more accurate reflection of hemodynamic changes during general anesthesia, especially in older individuals or those with different cardiovascular conditions allowing better vital management of body circulation.

Engineering Low Volume Resuscitants for the Prehospital Care of Severe Hemorrhagic Shock

AbstractGlobally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time‐sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR – correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non‐coagulopathic resuscitant has profound potential for application in trauma medicine.

Engineering Low Volume Resuscitants for the Prehospital Care of Severe Hemorrhagic Shock.

Globally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time-sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR - correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non-coagulopathic resuscitant has profound potential for application in trauma medicine.

Intestinal mucosal perfusion and integrity are maintained in hypotensive brain dead mice.

Brain death (BD) leads to complex hemodynamic and inflammatory alterations which may compromise organ perfusion and induce morphologic and functional damage in various organs. The intestine is particularly sensitive to hypoperfusion and donor hypotension usually precludes intestinal donation. Previous studies reported inflammatory intestinal changes following BD but information on mucosal integrity and perfusion are lacking. BD was induced in mice by inflating an epidural balloon catheter. Controls underwent only anesthesia and tracheostomy. Intestinal perfusion was assessed using laser Doppler flowmetry (LDF). Intestinal injury was assessed after 2h of BD by the Chiu-Park score and morphometry. Intestinal tight junction (TJ) proteins (claudin-1, claudin-3, occludin, tricellulin) as well as inflammatory activation (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) were also analysed and compared with a sham group. Although blood pressure decreased in BD mice, intestinal perfusion remained similar between BD and sham mice. Histologically, mucosal injury was absent/minimal and TJs appeared well maintained in both groups. BD may trigger intrinsic, autoregulatory mechanisms to preserve microvascular tissue perfusion and mucosal integrity in spite of mild hypotension.

Cerebral Oxygen Saturation Associates with Changes in Oxygen Transport Parameters during Cardiopulmonary Bypass.

(1) Background: Adequate organ perfusion during cardiopulmonary bypass (CPB) requires accurate estimation and adjustment of flow rates which conventional methods may not always achieve. Perioperative monitoring of cerebral oxygen saturation (ScO2) may detect changes in oxygen transport. This study aims to compare estimated and measured perfusion flow rates and assess the capacity of ScO2 to detect subtle changes in oxygen transport during CPB. (2) Methods: This observational study included 50 patients scheduled for elective coronary artery bypass grafting (CABG) surgery, all of whom provided written informed consent. Perfusion flow rates were estimated using the DuBois formula and measured using echocardiography and a flow probe in the arterial line of the CPB system. ScO2 was continuously monitored, alongside intermittent measurements of oxygen delivery and extraction ratios. (3) Results: Significant discrepancies were found between estimated flow rates (5.2 [4.8-5.5] L/min) and those measured at the start of the surgery (4.6 [4.0-5.0] L/min). These discrepancies were flow rate-dependent, being more pronounced at lower perfusion rates and diminishing as rates increased. Furthermore, ScO2 showed a consistent correlation with both oxygen delivery (r = 0.48) and oxygen extraction ratio (r = 0.45). (4) Conclusions: This study highlights discrepancies between estimated and actual perfusion flow rates during CPB and underscores the value of ScO2 monitoring as a continuous, noninvasive tool for maintaining adequate organ perfusion, suggesting a need for improved, patient-tailored perfusion strategies.

Graphene Oxide Significantly Modifies Cardiac Parameters and Coronary Endothelial Reactivity in Healthy and Hypertensive Rat Hearts Ex Vivo.

Interactions of graphene oxide (GO) with an ex vivo rat heart and its coronary vessels have not been studied yet. Moreover, the conflicting data on the "structure-properties" relationships do not allow for biomedical applications of GO. Herein, we study the impact of GO on the ex vivo isolated rat heart, normotensive and hypertensive, under the working heart and the constant-pressure perfusion (Langendorff) regimes. Four structural GO variants of the following initial morphology were used: few-layer (below 10-layer) GO1, O < 49%; predominantly single-layer GO2, O = 41-50%; 15-20-layer GO3, O < 11%; and few-layer (below 10-layer) NH4 +-functionalized GO4, O < 44%, N = 3-6%. The aqueous GO dispersions, sonicated and stabilized with bovine serum albumin in Krebs-Henseleit-like solution-uniformized in terms of the particle size-were eventually size-monodisperse as revealed by dynamic light scattering. To study the cardiotoxicity mechanisms of GO, histopathology, Raman spectroscopy, analysis of cardiac parameters (coronary and aortic flows, heart rate, aortic pressure), and nitric oxide (NO-)-dependent coronary flow response to bradykinin (blood-vessel-vasodilator) were used. GO1 (10 mg/L) exerted no effects on cardiac function and preserved an increase in coronary flow in response to bradykinin. GO2 (10 mg/L) reduced coronary flow, aortic pressure in normotensive hearts, and coronary flow in hypertensive hearts, and intensified the response to bradykinin in normal hearts. GO3 (10 mg/L) reduced all parameters in hypertensive hearts and coronary response to bradykinin in normal hearts. At higher concentrations (normotensive hearts, 30 mg/L), the coronary response to bradykinin was blocked. GO4 (10 mg/L) reduced the coronary flow in normal hearts, while for hypertensive hearts, all parameters, except the coronary flow, were reduced and the coronary response to bradykinin was blocked. The results showed that a low number of GO layers and high O-content were safer for normal and hypertensive rat hearts. Hypertensive hearts deteriorated easier upon perfusion with low-O-content GOs. Our findings support the necessity of strict control over the GO structure during organ perfusion and indicate the urgent need for personalized medicine in biomedical applications of GO.

Vascular endothelium, a promising target for effectively treating fulminant diquat intoxication?

Following the withdrawal of paraquat, diquat (DQ) has emerged as the predominant herbicide. When people come into contact with or ingest DQ, may lead to poisoning and potentially fatal outcomes. Reports suggest that the mortality of DQ poisoning can be as high as 50%. DQ poisoning can be categorized as mild, moderate or severe. In cases of severe poisoning, victims often succumb to multiple organ failure within 48 h. This presents a significant challenge in the clinical management. Scholars have discovered that oxidative stress, inflammatory injury, and cell apoptosis play crucial roles in the DQ poisoning. However, the underlying connection of the extensive organ damage remains unknown. The abnormal function and activity of endothelial cells (EC) should play a crucial role in tissue damage caused by DQ due to rich microcirculation and high sensitivity to perfusion in the vulnerable organs. However, reports on DQ-induced EC injury is rare. We made a significant discovery-the presence of severe vascular endothelial damage in the kidneys and lungs affected by DQ. Therefore, we hypothesize that DQ poisoning may be attributed to oxidative stress damage and cell apoptosis in EC, ultimately resulting in multiple organ failure.

Real time organ hypoperfusion detection using Indocyanine Green in a piglet model

BackgroundPreserving sufficient oxygen supply to the tissue is fundamental for maintaining organ function. However, our ability to identify those at risk and promptly recognize tissue hypoperfusion during abdominal surgery is limited. To address this problem, we aimed to develop a new method of perfusion monitoring that can be used during surgical procedures and aid surgeons’ decision-making.MethodsIn this experimental porcine study, thirteen subjects were randomly assigned one organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3), and spleen (n = 3)]. After baseline perfusion recordings, using high-frequency, low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG, organ-supplying arteries were manually and completely occluded leading to hypoperfusion of the target organ. Continuous organ perfusion monitoring was performed throughout the experimental conditions.ResultsAfter manual occlusion of pre-selected organ-supplying arteries, occlusion of the peripheral arterial supply translated in an immediate decrease in oscillation signal in most organs (3/3 ventricle, 3/3 ascending colon, 3/3 rectum, 2/3 spleen). Occlusion of the central arterial supply resulted in a further decrease or complete disappearance of the oscillation curves in the ventricle (3/3), ascending colon (3/3), rectum (3/3), and spleen (1/3).ConclusionContinuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real-time.

Inhibition of circulating dipeptidyl-peptidase 3 by procizumab in experimental septic shock reduces catecholamine exposure and myocardial injury

BackgroundDipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock.MethodsIn this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65–75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin–angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples.ResultsPCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression.ConclusionsIn an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling.Graphical

Surgical Perfusion and Isolation of the Porcine Pancreas for Islet Isolation.

Pancreatic islet transplantation is an emerging treatment for type I diabetes; however, it is limited by donor matching and availability. Porcine islet xenotransplantation offers a promising alternative to allotransplantation, with the potential for large-scale production of on-demand, functional islets. The yield and viability of isolated islets is highly susceptible to the quality of the donor pancreas and the method of procurement, particularly the duration of warm-ischemia time. To improve organ preservation and subsequent islet yield and viability, we have developed a protocol for surgical perfusion and resection of the porcine pancreas. This protocol employs direct infrarenal aortic cannulation and organ perfusion to both minimize warm-ischemia time and simplify the procedure for operators who do not have extensive surgical expertise. Subsequent arterial perfusion of the pancreas via the aorta flushes stagnant blood from the microvasculature, thereby reducing thrombosis and oxidative damage to the tissue. This manuscript provides a detailed protocol for surgical perfusion and resection of the porcine pancreas, followed by islet isolation and purification.