Artery Clamping Research Articles

Effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats

Objective: To investigate the effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats and its possible mechanism. Methods: Twenty-one adult male SD rats were enrolled and their right kidneys were excised. After two weeks, they were randomly assigned to 3 groups, with 7 rats in each group, namely sham-operated group (Group S), ischemia-reperfusion group (Group I/R), and normobaric hyperoxia+ischemia-reperfusion group (Group NBHO+I/R). In group S, only the left renal pedicle was isolated, but no ischemic treatment was performed. However, in group I/R and group NBHO+I/R, left renal pedicles were separated and left renal ischemia was induced by noninvasive arterial clamp for 45 min, and after 24 h of reperfusion, rats in group S and group I/R inhaled regular concentration of oxygen (21%), while rats in group NBHO+I/R inhaled high concentration of oxygen (60%), 2 h at each time, once a day for 7 days. On the 7th day after surgery, blood urea nitrogen (BUN) and creatinine (Cr) levels were measured by taking blood from the orbital veins of rats. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) was detected from the left kidney tissues. The mRNA and protein contents of Keap1 and Nrf2 gene in kidney tissues were determined by qPCR and Western Blotting, respectively. Hematoxylin-eosin staining (HE) was employed to observe the pathological changes of kidney tissue. Immunohistochemical staining was used to measure the protein expression of Keap1 and Nrf2 in kidney tissues. Results: Compared with group S, the serum BUN [(10.7±1.7) mmol/L, (8.4±1.0) mmol/L vs (6.1±1.3) mmol/L, both P<0.05] and Cr [(81.0±3.7) μmol/L, (62.9±3.4) μmol/L vs (48.3±2.9) μmol/L, both P<0.05] levels of rats in the group I/R and group NBHO+I/R increased, and the I/R group had the most significant increase. Compared with group S, the MDA content of kidney tissue in the rats of group I/R and NBHO+I/R increased [(10.5±1.0) μmol/L, (8.6±0.8) μmol/L vs (6.5±0.5) μmol/L, both P<0.05], but the MDA content in group NBHO+I/R was lower than that of group I/R (P<0.05). Compared with group S, the SOD content in the kidney tissues of rats in both group I/R and group NBHO+I/R decreased. However, the SOD content of group NBHO+I/R was higher than that of group I/R (P<0.05). Compared with group S, the mRNA and protein contents of Keap1 gene in kidney tissues of group I/R and group NBHO+I/R decreased, and group NBHO+I/R had the most significant decrease (P<0.05). However, compared with group S, mRNA and protein expressions of Nrf2 gene increased in kidney tissues of group I/R and group NBHO+I/R, and NBHO+I/R group had the most significant increase (P<0.05). Postoperative pathological results suggested that compared with group S, the pathological damage of kidney tissues in group I/R and group NBHO+I/R increased, but the degree of damage in group NBHO+I/R was lower than that in group I/R. Conclusion: Normobaric hyperoxia intervention may have protective effects on renal ischemia-reperfusion injury in rats by activating Keap1-Nrf2 signaling pathway.

The Effect of Remote Ischemic Preconditioning on Serum Creatinine in Patients Undergoing Partial Nephrectomy: A Randomized Controlled Trial.

Renal function declines after partial nephrectomy due to ischemic reperfusion injury induced by surgical insult or renal artery clamping. The effect of remote ischemic preconditioning (RIPC) on reducing renal injury after partial nephrectomy has not been studied regarding urinary biomarkers. Eighty-one patients undergoing partial nephrectomy were randomly assigned to either RIPC or the control group. RIPC protocol consisted of four cycles of five-min inflation and deflation of a blood pressure cuff to 250 mmHg. Serum creatinine levels were compared at the following time points: preoperative baseline, immediate postoperative, on the first and third days after surgery, and two weeks after surgery. The incidence of acute kidney injury, other surgical complication rates, and urinary biomarkers, including urine creatinine, β-2 microglobulin, microalbumin, and N-acetyl-beta-D-glucosaminidase were compared. Split renal functions measured by renal scan were compared up to 18 months after surgery. There was no significant difference in the serum creatinine level on the first postoperative day (median (interquartile range) 0.87 mg/dL (0.72–1.03) in the RIPC group vs. 0.92 mg/dL (0.71–1.12) in the control group, p = 0.728), nor at any other time point. There was no significant difference in the incidence of acute kidney injury. Secondary outcomes, including urinary biomarkers, were not significantly different between the groups. RIPC showed no significant effect on the postoperative serum creatinine level of the first postoperative day. We could not reveal any significant difference in the urinary biomarkers and clinical outcomes. However, further larger randomized trials are required, because our study was not sufficiently powered for the secondary outcomes.

Value of T2 Mapping in the Dynamic Evaluation of Renal Ischemia-Reperfusion Injury

To explore the value of T2 mapping in the dynamic quantitative evaluation of renal ischemia- reperfusion injury (IRI). Forty-eight healthy New Zealand rabbits were randomly divided into IRI group (n = 40) and control group (n = 8). Rabbits in the IRI group underwent left renal artery clamping for 60 minutes. Rabbits underwent MRI examinations (T2WI and T2 mapping) before and 1, 12, 24, and 48 hours after IRI. The inter-observer and intra-observer reproducibility of the T2 values were assessed using the intraclass correlation coefficient (ICC) with 95% confidence interval (CI). Correlations between the T2 value of the renal outer medulla and injury scores were assessed by Spearman correlation analysis. The repeated measures analysis of variance was used to compare the differences in T2 values of the IRI and control group across the different time points. Both of the intra-observer (ICC = 0.97, 95% CI 0.95-0.99) and inter-observer reproducibility (ICC = 0.92, 95% CI 0.86-0.96) were excellent for T2 values. The T2 value of the renal outer medulla was moderately positive correlated with tubular epithelial edema (ρ = 0.686, p < 0.001). In IRI group, T2 values of the renal outer medulla were increase at 1 h after IRI (p = 0.001) and were decrease from 1 h to 12 h (p = 0.002). At 1 h after IRI, the T2 values of the renal outer medulla for the IRI group were higher than those for the control group (p < 0.001). T2 mapping can reflect the dynamic changes of renal parenchyma in an animal model of IRI and be used to assess the early renal IRI.

EARLY EFFECTS OF EXTRACELLULAR VESICLES SECRETED BY ADIPOSE TISSUE MESENCHYMAL CELLS IN RENAL ISCHEMIA FOLLOWED BY REPERFUSION: MECHANISMS RELY IN THE RESTORATION OF THE REDOX TISSULAR ENVIRONMENT

<h3>Background</h3> The acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is one of the more frequent and severe processes, which, with very high mortality, affects renal structures and function. The first hours of lesion are critical for organ recovery, but the mechanisms of lesions to support early beneficial therapeutic actions are not well understood. AKI is characterized by intense production of anion superoxide (O2•-) and oxidative damage. In this study we investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administrated at the moment of reperfusion, suppresses the exacerbated mitochondrial O2•- formation in the first 24 h after I/R. <h3>Methods</h3> Rats were submitted to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received subcapsularly EVs (I/R+EVs group) or saline (I/R group). The 3rd group was of the false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and immediately used. EVs were characterized by cytometry (CD9, TSG101, CD63, CD81) and transmission electron microscopy. The probe Amplex Red™ was used to measure mitochondrial O2•- formation and MitoTracker® Orange to evaluate the mitochondrial electrical potential (Δψ). In vitro studies were carried out by using human renal cells (HK-2) co-cultured or not with EVs under hypoxia conditions. <h3>Results</h3> Administration of EVs to I/R rats restored O2•- formation to SHAM levels in all mitochondrial functional conditions: non-phosphorylating, phosphorylating, with ATP synthesis blocked and uncoupled. Proton leak was not modified. During this period, AKI remained active, as demonstrated by qRT-PCR analysis of the lesion biomarkers Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocaline. Tubular catalase and superoxide dismutase mRNA remained low. Heme oxygenase-1 (HO-1) was intensely upregulated. The co-cultures of HK-2 cells with EVs revealed decrease of apoptosis. <h3>Conclusions</h3> These findings provide evidence that the mechanisms in which rely the early recovery by EVs of the renal structure and function after I/R are those related with the normalization of the mitochondrial redox environment and open new vistas for the acellular treatment of AKI.

Transplantation of donor hearts after circulatory death using normothermic regional perfusion and cold storage preservation.

Hearts donated after circulatory determination of death are usually preserved with normothermic machine perfusion prior to transplantation. This type of preservation is costly, requires bench time adding to warm ischaemia, and does not provide a reliable evaluation of the unloaded donor heart. We report on 4 successful donation after circulatory death (category III) hearts transplanted after thoraco-abdominal normothermic regional perfusion (NRP) and static cold storage. After life sustaining therapy was withdrawn and death was declared, perfusion to thoraco-abdominal organs was restored using extracorporeal circulation via cannulas in the femoral artery and vein and clamping of supra-aortic vessels. After weaning from extracorporeal circulation, cardiac function was assessed. Once approved, the heart was retrieved and stored using classic static cold storage. Data are expressed as median [min-max]. Donor and recipient ages were 44 years [12-60] (n = 4) and 53 years [14-64] (n = 4), respectively. Time from the withdrawal of life sustaining therapy to start of NRP was 22 min [18-31]. Cold storage time was 72 min [35-129]. Thirty-day survival was 100% with a left ventricle ejection fraction of 60% [50-60]. Donation after circulatory death heart transplantation using thoraco-abdominal NRP and subsequent cold storage preservation for up to 129 min was safe for 4 procedures and could be a way to expand the donor heart pool while avoiding costs of machine preservation.

Alveolar Recruitment Maneuver Reduces Cerebral Oxygen Saturation and Cerebral Blood Flow Velocity in Patients During Carotid Endarterectomy.

BackgroundThis study aimed to determine the effects of alveolar recruitment maneuver (RM) on cerebral oxygen saturation and cerebral blood velocity in patients undergoing carotid endarterectomy (CEA) before clamping of the carotid artery.Material/MethodsIn this crossover exploratory study, all patients were randomized to undergo an RM (30 cmH2O of continuous airway pressure for 30 s) and a “sham” maneuver (SM; 5 cmH2O for 30 s), followed by an alternative intervention after a 5-min equilibration period. Near-infrared spectroscopy (NIRS) was used to monitor regional cerebral oxygen saturation (rSO2), and transcranial Doppler ultrasonography (TCD) to evaluate blood velocity of the middle cerebral artery (V-MCA). Changes in rSO2, V-MCA, mean arterial pressure (MAP), and heart rate (HR) in response to the 2 interventions were compared.ResultsA total of 59 patients underwent the study procedure. RM reduced rSO2, V-MCA, MAP, and HR, but these variables slightly changed during SM. A significant drop in rSO2 was observed immediately after RM compared with the baseline value (68.51±4.4% vs 64.12±5.15%; P<0.001). The decrease in rSO2 was higher during the RM than during the SM (−6±4% vs 1±2%; P<0.001). Similarly, change in V-MCA was more significant in response to RM than SM (−26±19% vs 19±16%; P<0.001). The V-MCA value changed from 39 cm/s to 29 cm/s after RM. In addition, V-MCA of the ipsilateral to the surgical side decreased more obviously than the contralateral side (−26±19% vs −20±17%; P=0.001).ConclusionsAn RM at 30 cmH2O of continuous airway pressure for 30 s decreased rSO2 and V-MCA. In addition, MAP and HR were affected.

Protective Role of ECMO on Reperfusion Injury and Acute Rejection in Lung Transplantation: A Pathological Analysis

Purpose The routine utilization of intraoperative extracorporeal membrane oxygenation (ECMO) in lung transplantation is recently extensively investigated for its protective role, especially on reperfusion injury. The purpose of this study is to compare pathological features on pre and post-reperfusion biopsies and on 30 and 90-days surveillance trans-bronchial biopsies in lung transplantations performed with or without ECMO support to assess its protective role on the graft Methods 51 patients (13 with ECMO support, 38 without ECMO support) underwent bilateral lung transplantation at our Institution between 2012 and 2019. Only patients on ECMO at time of anesthetic induction or before the first clamping of the pulmonary artery were included. Patients submitted to graft volume reduction before lung reperfusion were excluded from the analysis.Intra-operative pre and post-reperfusion biopsies were collected to analyze edema, leucocyte margination and congestion/extravasation (score 0-3). The presence of acute rejection (grade A0-3, grade B0-2) diffuse alveolar damage (DAD), organizing pneumonia (OP) on 30 and 90-days trans-bronchial surveillance biopsies was also compared in the two groups. Results No significant differences were found between the two groups in terms of edema, leucocyte margination and congestion in pre reperfusion biopsies. On post reperfusion biopsies, leucocyte margination was significantly less frequent in ECMO group (46% vs 76%; p=0.043). A lower frequency of acute rejection (grade A0-3) was also found in the ECMO group on 30-days biopsies (25% vs 58%, p=0.047). Conclusion In conclusion, this analysis does not show significant differences between the two groups except for a lower frequency of leucocyte margination at post-reperfusion biopsies and acute rejection at 30-days biopsies in the ECMO group. Other studies, with a larger population, are needed in order to evaluate whether the positive clinical impact of using ECMO as a prevention of reperfusion edema after lung transplantation can also be explained by a defined pathological picture

Blood Lactate Level Evolution during Lung Transplantation

<h3>Purpose</h3> Lactic acidosis has been recently propose as independently associated with longer intubation times and length of stay in lung transplantation(1). However, there is no data on the association between elevated blood lactate concentration (BLC) and grade 3 primary graft dysfunction at day 3 after lung transplantation (PGD3). The purpose of the study was to investigate the profile of BLC during double-lung transplantation and it association with PGD3. <h3>Methods</h3> We performed a retrospective observational study of all bilateral lung transplantations at the Foch Hospital from January 2012 to December 2019, excluding those on bridge-to-transplantation, under cardiopulmonary bypass, and multiple-organ transplantation. BLC was measured at every key time of the invention: initially, at every pulmonary artery clamping or declamping, and at end-surgery stage. The ethical committee of the French Society of Anesthesia and Critical Care (SFAR) approved the study. The evolution of intraoperative BLC was evaluated with a paired T-test with Holm correction to compare lactate. AUC was constructed to determine Sp and Se. The optimal threshold of lactates variable used for separation of PGD3 was calculated using the Youden-index. <h3>Results</h3> Over 478 patients were included, 83 (17.3%) had a PGD3. BLC evolution during surgery is illustrated in figure 1. The median of BLC at end-surgery was 2 [1.5 - 3.1] and 3.3 [2.4 - 4.9] mmol/L in no PGD3 and PGD3 groups respectively, p = 0.02. BLC kinetic illustrated by its variability was the best predictive factor of PGD3 (AUC=0.84, Se=77.03, Sp=79.82%). <h3>Conclusion</h3> Hyperlactatemia reflects anaerobic metabolism during peroperative hemodynamic unstable conditions and poor oxygen exchange after implantation of the grafts. Blood lactate variability during surgery is associated with PGD3.1. Worrell SG, et al. Is Lactic Acidosis After Lung Transplantation Associated With Worse Outcomes The Annals of Thoracic Surgery. 2020 Aug;110(2):434-40.

Time from Start of Agonal Phase to Pulmonary Artery Cross Clamp in Donor Cardiac Death Donors Does Not Correlate with Diminished Recipient Lung Function or Survival

Purpose Donor cardiac death (DCD) donors could expand the field of lung donors, but the acceptably safe time interval between the onset of agonal phase and application of the pulmonary artery clamp is controversial. The purpose of this study was to determine if the time from the beginning of the agonal phase to placement of the pulmonary artery cross clamp in DCD donors is associated with worse recipient lung function or long-term survival. Methods The Scientific Registry for Transplant Research database (2008-2019) was queried for lung transplants performed from DCD donors (N=227) excluding pediatric, multi-organ, and redo lung transplants. Time from the beginning of agonal phase to the time of pulmonary artery cross clamp placement was determined, and donor and recipient characteristics and outcomes were examined for 3 groups: 0-30 minutes (N=178), 30-45 minutes (N=25), and over 45 minutes (N=21). Eight DCD donor lungs had an agonal phase to pulmonary artery cross clamp time between 75 and 120 minutes. The primary endpoints were forced expiratory volume in 1 second (FEV1) at 1 and 2 years and overall survival using Kaplan Meier analysis. Results There were no significant differences in donor age, gender or body mass index between the three groups. Recipient characteristics were comparable between the three groups, and there was no difference in recipient FEV1 at 1 (80.47+/-22.45%, 79.81+/-16.60%, and 76.67+/-13.30%, p=0.840) and 2 years (76.23+/-27.13%, 76.11+/-24.31%, 82.17+/-17.58%, p=0.868) for the three groups (0-30 minutes, 30-45 minutes, and over 45 minutes, respectively) . There was no difference in long term survival out to 10 years between the three groups using Kaplan Meier analysis. Conclusion Lung transplant recipient lung function and survival is similar for recipients of DCD donor lungs regardless of the time from start of the agonal phase to application of the pulmonary artery transplant out to and beyond 45 minutes.

Retroperitoneoscopic partial nephrectomy using a 980/1470-nm dual-diode laser for small exophytic renal tumors

Laser-supported laparoscopic partial nephrectomy is a promising new technique, but remains under experiment. We presented our single institutional experience of laparoscopic partial nephrectomy using the 980/1470-nm dual-diode laser system to investigate its feasibility, and oncological and functional outcomes. The study retrospectively evaluated 25 patients with small exophytic renal tumors, who underwent laparoscopic partial nephrectomy using a 980/1470-nm dual-diode laser. The demographics, surgical data, complications, pathological variables, oncological, and functional outcomes were reviewed. The changes in hemoglobin and estimated glomerular filtration rate (eGFR) before and after surgery were statistically analyzed. The investigators operated on a total of 25 patients. The off-clamping technique was performed for 23 cases, while the other two cases required renal artery clamping due to unsatisfactory hemostasis. The tumor diameter was 24.6± 6.2 mm, and the mean operative time was 104.4± 23.4 min. The median estimated intraoperative blood loss (EBL) was 100 ml (range 50-600 ml). No major complications (Clavien-Dindo >II) occurred perioperatively. The mean change in hemoglobin before and after the operation was 9 g/l, with a P value of <0.001. The mean decrease in eGFR from before the surgery to the 6-month follow-up was 1.4 ml/min, with a P value of 0.463. The postoperative histopathology evaluation did not demonstrate a positive surgical margin. No recurrence or metastasis was found during the follow-up (mean 24 months). Laparoscopic partial nephrectomy using a 980/1470 nm dual-diode laser appears to be a feasible and oncological satisfactory technique for the treatment of small renal mass (SRM), with the advantages of reducing warm ischemia time.

How to improve outcome in nephron-sparing surgery: the impact of new techniques.

Nephron-sparing partial nephrectomy is the state of the art for localized small renal mass and it is gaining attention also for more advanced cases. In the present narrative review, we discuss the new developments that have occurred in the advancement of this approach over the past few years. Off-clamp, selective/superselective clamp and early-unclamping techniques are safe and feasible approaches, with potentially superior functional outcomes, and noninferior complications rate and oncological outcomes, when compared with main artery clamping. Renorrhaphy must preserve the physiological vascularization of residual parenchyma. Running sutures, particularly using barbed wires, shorten the operating and ischemia times. A further advantage could derive from avoiding a double-layer suture. Transperitoneal robot-assisted partial nephrectomy (RAPN) and retroperitoneal RAPN can be considered equivalent in terms of perioperative morbidity, functional and oncologic outcomes, regardless of tumor's location, thus the choice of the approach should be driven by the surgeon's expertise. Future improvements should be introduced by the single-port robotic surgery, which seems to be safe and feasibly also in an off-clamp manner. Significant advances have recently been achieved in nephron-sparing surgery technique. However, future studies with standardized reporting of these new techniques are needed to assess the real impact of them on early and long-term functional outcomes.

The tryptophan pathway and nicotinamide supplementation in ischaemic acute kidney injury.

ABSTRACTBackgroundDown-regulation of the enzymes involved in tryptophan-derived nicotinamide (NAM) adenine dinucleotide (NAD+) production was identified after acute kidney injury (AKI), leading to the hypothesis that supplementation with NAM may increase the kidney NAD+ content, rescuing tryptophan pathways and subsequently improving kidney outcomes.MethodsUrinary measurement of tryptophan and kynurenin using liquid chromatography–mass spectrometry metabolomics was used in a cohort of 167 cardiac bypass surgery patients along with tests for correlation to the development of postoperative AKI. A mouse model of ischaemic AKI using ischaemia–reperfusion injury (bilateral clamping of renal arteries for 25 min) was also used.ResultsWe identified a significant decrease in urinary tryptophan and kynurenin in patients developing AKI, irrespective of the Kidney Disease: Improving Global Outcomes (KDIGO) stage. Although a significant difference was observed, tryptophan and kynurenin moderately discriminated for the development of all AKI KDIGO stages {area under the curve [AUC] 0.82 [95% confidence interval (CI) 0.75–0.88] and 0.75 [0.68–0.83], respectively} and severe KDIGO Stages 2–3 AKI [AUC 0.71 (95% CI 0.6–0.81) and 0.66 (0.55–0.77), respectively]. Sparked by this confirmation in humans, we aimed to confirm the potential preventive effect of NAM supplementation in wild-type male and female C57BL/6 mice subjected to ischaemic AKI. NAM supplementation had no effect on renal function (blood urea nitrogen at Day 1, sinistrin–fluorescein isothiocyanate glomerular filtration rate), architecture (periodic acid–Schiff staining) and injury or inflammation (kidney injury molecule 1 and IL18 messenger RNA expression). In addition, NAM supplementation did not increase post-AKI NAD+ kidney content.ConclusionNotwithstanding the potential role of NAM supplementation in the setting of basal NAD+ deficiency, our findings in mice and the reanalysis of published data do not confirm that NAM supplementation can actually improve renal outcomes after ischaemic AKI in unselected animals and probably patients.

Robotic anatomical resection of liver segment 4 with glissonian approach and selective hepatic artery clamping

Robotic anatomical resection of liver segment 4 with glissonian approach and selective hepatic artery clamping

Urinary Cyclophilin A as Marker of Tubular Cell Death and Kidney Injury.

Background: Despite the term acute kidney injury (AKI), clinical biomarkers for AKI reflect function rather than injury and independent markers of injury are needed. Tubular cell death, including necroptotic cell death, is a key feature of AKI. Cyclophilin A (CypA) is an intracellular protein that has been reported to be released during necroptosis. We have now explored CypA as a potential marker for kidney injury in cultured tubular cells and in clinical settings of ischemia-reperfusion injury (IRI), characterized by limitations of current diagnostic criteria for AKI. Methods: CypA was analyzed in cultured human and murine proximal tubular epithelial cells exposed to chemical hypoxia, hypoxia/reoxygenation (H/R) or other cell death (apoptosis, necroptosis, ferroptosis) inducers. Urinary levels of CypA (uCypA) were analyzed in patients after nephron sparing surgery (NSS) in which the contralateral kidney is not disturbed and kidney grafts with initial function. Results: Intracellular CypA remained unchanged while supernatant CypA increased in parallel to cell death induction. uCypA levels were higher in NSS patients with renal artery clamping (that is, with NSS-IRI) than in no clamping (NSS-no IRI), and in kidney transplantation (KT) recipients (KT-IRI) even in the presence of preserved or improving kidney function, while this was not the case for urinary Neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, higher uCypA levels in NSS patients were associated with longer surgery duration and the incidence of AKI increased from 10% when using serum creatinine (sCr) or urinary output criteria to 36% when using high uCypA levels in NNS clamping patients. Conclusions: CypA is released by kidney tubular cells during different forms of cell death, and uCypA increased during IRI-induced clinical kidney injury independently from kidney function parameters. Thus, uCypA is a potential biomarker of kidney injury, which is independent from decreased kidney function.

Altered lung metabolism and mitochondrial DAMPs in lung injury due to acute kidney injury.

Acute respiratory distress syndrome (ARDS) is a common cause of mortality in patients with acute kidney injury (AKI). Inflammatory crosstalk from the kidney to the lung has been shown to contribute to lung injury after AKI, but anti-inflammatory therapies have not been proven beneficial in human studies. Recently, AKI was shown to alter mitochondria and related metabolic pathways in the heart, but the impact of AKI on lung metabolism has not been investigated to our knowledge. In this study, we evaluated the metabolomic profile of the lung following renal ischemia and reperfusion to identify novel pathways that may be modifiable. We randomized C57BL/6 mice to 20 minutes of bilateral renal arterial clamping or sham operation under ketamine/xylazine anesthesia. At 4 hours after reperfusion, we found a significant increase in markers of lung injury, as well as significant metabolomic changes across lung, kidney, plasma and bronchoalveolar lavage fluid (BALF) compared to shams. Comparative analyses revealed that the fatty acid oxidation pathway was the most significantly altered metabolic pathway, a finding which is consistent with mitochondrial dysfunction systemically and in the lung. These metabolomic changes correlated with the extracellular accumulation of the mitochondrial damage associated molecular patterns (mtDAMPs), mitochondrial DNA (mtDNA) and transcription factor A, mitochondria (TFAM). Finally, we found that intraperitoneal injection of renal mtDAMPs caused metabolomic changes consistent with mitochondrial dysfunction in the lung in vivo. Mitochondrial function and mtDAMPs warrant further investigation as potential therapeutic targets in preventing lung injury because of AKI.

Application of neuroendoscopy combined with fluorescence angiography in anterior circulation aneurysm clipping

Objective: To explore the value of neuroendoscopy combined with fluorescence angiography in anterior circulation aneurysm clipping. Methods: A total of 15 patients with anterior circulation aneurysm from Department of Neurosurgery, Zhongnan Hospital of Wuhan University between October 2018 and January 2019 were enrolled. Neuroendoscopy combined with indocyanine green fluorescence angiography (ICGA) was used to determine the shape of the aneurysm, the specific location of the aneurysm neck and its relationship with the aneurysm-bearing artery during anterior circulation aneurysm clipping. Meanwhile, Neuroendoscopy combined with ICGA can be employed to observe whether there was stenosis and incomplete clamping of the aneurysm-bearing artery after clipping the aneurysm, and whether there was misclamping of the perforating branches hidden under the posterior wall of the aneurysm. Results: The success rate of aneurysm clipping in 15 cases was 15/15. After aneurysm clipping, ICGA and neuroendoscopy were performed. The residual aneurysm neck was detected in 3 cases, and the position of aneurysm clip was adjusted or aneurysm clips were added. In one case, the anterior choroidal aneurysm was found to be mistakenly clipped. After adjusting the aneurysm clip, ICGA and neuroendoscopy showed that the anterior choroidal artery was normal. In another case, the A1 segment aneurysm was clipped. ICGA and neuroendoscopy found that the perforating branch blood vessels were mistakenly clipped. After the adjustment of the aneurysm clip, the blood vessels recovered their patency. There were no surgical-related deaths, disability and coma cases in the study. Conclusions: During aneurysm clipping, neuroendoscopy combined with ICGA can reduce cerebral vasospasm, decrease the misclipping rate of perforation of blood vessels, and avoid residual neck of aneurysm, stenosis or occlusion of aneurysm-bearing artery by using neuroendoscopy to observe whether misclipping of the perforating branch vessels exist and whether the aneurysm is clipped. Therefore, it can reduce postoperative complications.

A Chemomechanobiological Model of the Long-Term Healing Response of Arterial Tissue to a Clamping Injury.

Vascular clamping often causes injury to arterial tissue, leading to a cascade of cellular and extracellular events. A reliable in silico prediction of these processes following vascular injury could help us to increase our understanding thereof, and eventually optimize surgical techniques or drug delivery to minimize the amount of long-term damage. However, the complexity and interdependency of these events make translation into constitutive laws and their numerical implementation particularly challenging. We introduce a finite element simulation of arterial clamping taking into account acute endothelial denudation, damage to extracellular matrix, and smooth muscle cell loss. The model captures how this causes tissue inflammation and deviation from mechanical homeostasis, both triggering vascular remodeling. A number of cellular processes are modeled, aiming at restoring this homeostasis, i.e., smooth muscle cell phenotype switching, proliferation, migration, and the production of extracellular matrix. We calibrated these damage and remodeling laws by comparing our numerical results to in vivo experimental data of clamping and healing experiments. In these same experiments, the functional integrity of the tissue was assessed through myograph tests, which were also reproduced in the present study through a novel model for vasodilator and -constrictor dependent smooth muscle contraction. The simulation results show a good agreement with the in vivo experiments. The computational model was then also used to simulate healing beyond the duration of the experiments in order to exploit the benefits of computational model predictions. These results showed a significant sensitivity to model parameters related to smooth muscle cell phenotypes, highlighting the pressing need to further elucidate the biological processes of smooth muscle cell phenotypic switching in the future.

Real-time identification of aberrant left hepatic arterial territories using near-infrared fluorescence with indocyanine green during gastrectomy for gastric cancer.

An aberrant left hepatic artery is frequently encountered during upper gastrointestinal surgery, and researchers have yet to propose optimal strategies with which to address this arterial variation. The objective of this study was to determine whether the areas perfused by an aberrant left hepatic artery can be visualized in real-time using near-infrared fluorescence imaging with indocyanine green. Patients with gastric adenocarcinoma who underwent minimally invasive radical gastrectomy from May 2018 to August 2019 were enrolled and retrospectively analyzed at a single-center. Patients with an aberrant left hepatic artery and normal preoperative liver function were examined. After the clamping of an aberrant left hepatic artery, indocyanine green was administered via a peripheral intravenous route during surgery. Fluorescence at the liver was visualized under near-infrared fluorescence imaging. In 31 patients with aberrant left hepatic arteries, near-infrared fluorescence imaging was used without adverse events associated with indocyanine green. Six (19%) patients were reported to have an aberrant left hepatic artery upon preoperative CT imaging, while all other instances were detected during surgery. Fluorescence excitation on the liver was, on average, visible after 43s (range, 25-65). Fluorescence across the entire surface of the liver was noted in 20 (65%) patients in whom the aberrant left hepatic artery could be ligated. Aberrant left hepatic arteries were safely preserved in 10 (32%) patients who showed areas of no or partial fluorescence excitation. Guided by near-infrared fluorescence imaging, ligation of aberrant left hepatic arteries elicited no significant changes in postoperative liver function. Near-infrared fluorescence imaging facilitates the identification of aberrant left hepatic arterial territories, guiding decisions on the preservation or ligation of this arterial variation.

Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury.

Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood. To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20. After recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups. In this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.

Effect of unilateral renal ischemia on the contralateral kidney assessed by Caspase 3 expression.

BackgroundStudies have demonstrated with histological analysis and Doppler flow measurement analysis that unilateral renal ischemia, which is performed in some surgeries, interfered with the contralateral kidney, identifying the phenomenon of kidney-kidney crosstalk.ObjectivesTo identify the effects on the ischemic and contralateral kidney of renal ischemia induced by two types of clamping technique by analyzing the volume of kidney cells positive for Caspase 3.MethodsSixteen pigs were divided into 2 groups, as follows: A (n = 8) – clamping of left renal artery only and AV (n = 8) – clamping of left renal artery and vein. Immunohistochemical analyses (anti Caspase 3) were conducted with biopsy specimens collected from the ischemic and contralateral kidney at 0, 30, 60, and 90 minutes of ischemia and morphometric analysis was performed, taking the mean to represent the volume of the Caspase 3 positive area (%).ResultsMorphometric analysis of specimens collected at 30, 60, and 90 minutes of ischemia showed that the mean area marked for Caspase 3 was statistically larger in the contralateral kidney than the ischemic kidney in both groups: clamped renal artery (A) and clamped renal artery and vein (AV). Comparing the ischemic and contralateral kidney, there was no statistically significant difference in the area marked for Caspase 3 between the two types of clamping.ConclusionsIn the experimental model of unilateral renal ischemia, the non-ischemic kidney exhibited cell damage, demonstrated by Caspase 3 expression. The type of hilum clamping does not appear to influence the area marked for Caspase 3.