Total Ischemia Research Articles

MITOCHONDRIA RESPIRATION IN RAT BRAIN NEURONS UNDER CEREBRAL ISCHEMIA OF VARYING SEVERITY

The knowledge of the mechanisms of energy deficiency development in ischemic lesions is necessary to specify the pathogenesis and assess the damage/compensation ratio.
 The aim of the paper is to study respiration indices of mitochondria of rat brain homogenates in total and subtotal cerebral ischemia.
 Materials and Methods. The experiments were carried out on 88 male outbred white rats weighing 260±20 grams in compliance with the Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.
 Results. In 1-hour subtotal cerebral ischemia, V2 increased by 24 (18; 27) % (p<0.05), in the presence of malate/glutamate, if compared with the control, while the acceptor control coefficient and the phosphorylation coefficient decreased by 25 (17; 29) % (p<0.05). Other indices (V1, V3, V4, respiratory control coefficient) did not change (p>0.05). In the presence of malate/glutamate under 1-hour SCI, mitochondrial respiration rates V1, V2, V3, and V4 were higher than under 1-hour TCI 89 (82; 93), 58 (55; 63), 24 (21; 29) and 32 (27; 37) % respectively (p<0.05). Decrease in V1, V2, and V3 indices under 24-hour SCI is a consequence of the decrease in oxygen content for mitochondrial respiration. The inhibition of energy processes is more pronounced than under 1-hour SCI, which reflects the extremely low phosphorylation coefficient. Changes in V1, V2, and V3 indices under 1-hour SCI and 1-hour TCI are multidirectional. Their increase under SCI is associated with uncoupling between oxidation and phosphorylation, while their decrease under TCI is associated with a lack of substrates for mitochondrial respiration.
 Conclusion. The most pronounced decrease in respiration indices of the mitochondrial fraction of brain homogenates occurs under total cerebral ischemia due to the complete cessation of neuron blood supply.

Changes in the Content of Neuroglobin in the Neurons of the Cerebral Cortex of Rats with Ischemia

Introduction: Neuroglobin is a metalloprotein of the family globin, which contains protoporphyrin with an iron atom in the center, forming six coordination bonds. Due to its ability to bind oxygen, Ngb enhances the supply of oxygen to the mitochondria of metabolically active neurons. Objectives: To assess the content of neuroglobin in the brain of rats with cerebral ischemia of varying severity. Materials and methods: The experiments were performed on 60 male outbred white rats weighing 260±20 g in compliance with the requirements of the Directive of the European Parliament and of the Council No. 2010/63/EU of September 22, 2010 on the protection of animals used for scientific purposes. Modeling of the cerebral was carried out under conditions of intravenous thiopental anesthesia (40-50 mg/kg). The studies used models of total, subtotal, stepped subtotal, and partial cerebral ischemia. Conclusion: The most pronounced disorders of the prooxidant-oxidant balance, as well as a decrease in the content of neuroglobin, were observed during cerebral ischemia lasting 1 day. During cerebral ischemia with ligation of both common carotid arteries with an interval of 7 days, an increase in the content of neuroglobin was noted, as a manifestation of the activation of compensatory mechanisms.

L-citrulline supplementation reduces systolic arterial pressure and myocardial infarct size in a rat model of sleep apnea syndrome

Sleep apnea syndrome is characterized by intermittent hypoxia (IH), leading to an increase in blood pressure (BP) and infarct size. Independently, IH has been demonstrated to alter arginine (Arg) metabolism. As Arg availability directly impacts nitric oxide production, we speculate that plasmatic Arg deficiency during IH may contribute to cardiovascular alterations induced by IH. Knowing that citrulline (Cit) is a better precursor of Arg than Arg itself, we propose to assess the impact of chronic Cit supplementation on IH-induced an increase in BP and infarct size. Four groups of rats ( n = 11–14), were submitted to normoxia (N) or IH [14 days (d), 8 h per d, 30 s-O2 21%/30 s-O2 5%] and supplemented or not with Cit (1 g.kg −1 .d −1 ). After 14 d, BP was measured by carotid catheterization; hearts were perfused by the Langendorff method and submitted to global and total ischemia (30 min)-reperfusion (120 min) before measuring infarct size related to left ventricle area (I/V) by colorimetry and planimetry. Another set of rats was added ( n = 5–6) in order to collect the heart and aorta for histological and biochemical analyses. IH increases systolic BP (144.5 ± 3.5 vs. 165.1 ± 4.2 mmHg in N and IH respectively, n = 11–14, P < 0.01) and I/V (33.7 ± 4.4 vs. 46 ± 2.5% in N and IH, respectively, n = 10–12, P < 0.05). Cit abolishes IH-induced increase in both systolic BP (139.8 ± 4. vs. 155.6 ± 6.6 mmHg NCit and IHCit, respectively) and I/V (35.7 ± 3.3 vs. 38.2 ± 2.1% in NCit and IHCit). Preliminary western blot results show that IH decreases T495P-eNOS in heart whereas it did not affect S1177P-eNOS. Interestingly, Cit supplementation seems to decrease even more the T495P-eNOS in the IHCit group compared to IH and NCit groups. Cit supplementation abolishes the deleterious effects of IH in terms of BP and infarct size. This suggests that citrulline could be a complementary or alternative treatment to the current sleep apnea standard treatment that is not fully efficient. However, biochemical and histological studies (NOx, oxidative stress, S-nitrosylation…) are ongoing to enlighten the specific mechanisms involved in cardiovascular protection induced by citrulline chronic supplementation during IH.

Melanoma: Morphological essays of energetic tumor death under the influence of live mitochondria.

e21561 Background: Global trials form a new mitochondrial paradigm for suppressing the growth of malignant tumors. The unique role of mitochondria (MC) in the processes of metabolism, proliferation, and cell death was proven by the establishment of signaling pathways and critical conditions for the self-organization and degradation of MC. There are still many unsolved problems in the development of a new strategy, including the absence of an integral picture of morphological changes in the tumor under the influence of mitochondrial therapy (MCT), and this determined the purpose of the study. Methods: The study included male and female Balb/c Nude mice weighing 21-22 g. B16/F10 melanoma was transplanted to mice subcutaneously, and suspension of live liver MC was injected intraperitoneally. MC were isolated by differential centrifugation (Avanti J-E high-speed centrifuge, BECKMAN COULTER, USA). After an MCT cycle, the melanoma structure was examined with hematoxylin and eosin staining and light microscopy (LEICA DM LS2). Results: Control samples of melanoma (without MCT) showed abundant vascularization with dense growth of epithelial-like cells with branched cytoplasm, an eccentric nucleus and a moderate content of melanin pigment. Massive hypoxic death, autolysis and autoxidation of tumor cells were registered in male mice after MCT, as well as matrix hyalinosis, pronounced subcutaneous tissue edema with segregation and necrotization of fat accumulations. The formation of a large cavity filled with detritus indicated signs of total tumor necrosis and ischemia. The accumulation of hyperchromic granules indicated the activation of granulocytic and phagocytic elements in the mechanism of tumor regression. Female mice showed rare small areas of necrosis, as well as pronounced fragmentation of nuclei and cytoplasm of cells in most fields of view induced by bioenergetic hypoxia, with the formation of apoptotic bodies. Along the edge of the cells subjected to autophagocytosis, melanin accumulated as it left the cells and accumulated as large granules, while small ones filled the space of the vessels. The process of melanoma regression was confirmed by a significant increase in free fibrous areas, where only faint cell shadows remained. Conclusions: The initial state of melanoma degrades under the influence of MCT inducing bioenergetic hypoxia in male and female Balb/c Nude mice in different ways. Gender, in fact, hormonal differences determine the dominance of different ways of cell death, necrosis (in males) and apoptosis (in females), while maintaining the MCT access to the processes of preventing tumor growth.

Exogenous growth differentiation factor 15 (GDF15) exerts direct cardioprotective properties towards myocardial ischemia reperfusion injury

Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine which can be produced under certain pathological situations, mainly related to inflammatory stress, aging and disease. While clinical data suggest that GDF15 is a powerful risk factor in several high-risk cardiovascular situations such as myocardial infarction and coronary artery disease, experimental studies rather consider this cytokine as a cardioprotective molecule. We aimed to clarify the direct cardiac effects of GDF15 during ischemia-reperfusion (I-R) injury, at concentrations found in patients with high cardiovascular risk, such as these of patients presenting with acute myocardial infarction or stroke. Wistar male rats (200–400 g) were used for both in vivo and ex vivo ischemia-reperfusion and anesthetized with isoflurane. In vivo rats were intubated before a left thoracotomy was performed between the 3rd and the 4th intercostal space. Rats were injected with either saline (Control groups) or 2.5 μg/kg of GDF15 (GDF15 groups), 20 minutes before the transient ligation of the left anterior descending artery for 30 min followed by 24 h of reperfusion. Ex vivo rat's hearts were isolated and perfused on a Langendorff model with either saline (Control groups) or 2000 ng/L of GDF15 upstream the coronary bed (GDF15 groups) for 10 minutes, then subjected to either 20 or 30 minutes of global normothermic total ischemia, followed by 2 h of reperfusion. GDF15 decreased the infarct size in vivo as well as in ex vivo. Moreover, in our ex vivo model, GDF15 induced a better recovery of most contractile parameters after ischemia ( P < 0.05 for all parameters). These results demonstrate for the first time that exogenous preischemic short-term administration of GDF15 decreased cardiac cell death in vivo but also ex vivo, the latter situation involving that inflammatory, endocrine, and nervous systems are not interfering. These original results suggest that GDF15 exerts direct cardioprotective properties towards ischemia-reperfusion injury.

Various Techniques and Outcomes of Arterial Anastomosis in Live Renal Transplant: An Institutional Experience.

IntroductionRenal transplantation with multiple arteries is associated with a major index of surgical complications. Relevant papers and meta-analyses have shown relatively more vascular and urological complications in transplant of donor kidneys with multiple arteries. In live donor grafts due to the unavailability of a carrel patch, several techniques for bench and in situ reconstruction have been described in order to reduce the incidence of these vascular complications. In this study, the short and long-term results of living donor kidney transplants with multiple renal arteries (MRAs) versus single renal artery (SRA) were compared retrospectively.MethodsThis is a retrospective study done on patients who received a living donor kidney between January 2012 and January 2018 at the Institute of Urology, Madras Medical College, Chennai. We have excluded deceased donor kidney transplants and ABO-incompatible cases done in the same time period. The study was approved by the Institutional Ethics Committee (Approval No: IES-MMC-008) and performed in accordance with the guidelines of the Declaration of Helsinki. Open live donor nephrectomy was performed through an extra-peritoneal flank incision in all cases. In the SRA group, the renal artery was anastomosed end to end to the Internal iliac artery, while the renal vein was anastomosed to the external iliac vein in the end to side fashion. Urinary tract reconstruction was accomplished by the Gregoir technique in both groups. We looked at recipient complications, baseline and postoperative serum creatinine, total ischemia time, mean operating time, and short- and long-term graft and patient survival as postoperative outcomes.ResultsIn a six-year period (2012-2018) at our institute, 256 living donor transplantations were performed; 36 (14%) kidneys had two or more renal arteries which were anastomosed using various techniques. Cold ischemia time was relatively longer in the MRA group (45 mins vs 28 mins in the SRA group) (p-value <0.05). while warm ischemia time was comparable in both groups (2.5 vs 2.9 mins) serum creatinine was comparable in both groups at the 30th postoperative day (1.4 in SRA group vs 1.2 in MRA group) (p-value >0.05). Incidence of surgical complications in SRA and MRA groups was: vascular - 3.6% and 2.7%; urological - 3.2% and 2.7%; the incidence of lymphocele was 4.5% and 5.5% and delayed graft function 4.5% and 5.5% respectively.ConclusionMultiple renal arteries are no longer a relative contraindication with advanced surgical techniques. in renal grafts with multiple arteries, all techniques of vessel anastomosis are comparable in terms of post-surgical complications.

Impact of the Total Ischemia Time on No-Reflow Phenomenon in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BackgroundNo-reflow phenomenon after primary percutaneous coronary intervention is a common condition affecting the outcomes; therefore, studying its predictive factors is helpful in identifying patients at high risk. Our objective was to investigate the impact of the total ischemia time on no-reflow phenomenon and its correlation to thrombolysis in myocardial infarction flow grade after primary percutaneous coronary intervention.MethodsThis study was conducted on 545 patients with ST-elevation myocardial infarction who underwent PPCI; the patients were divided into two groups according to the incidence of no-reflow, TIMI flow ≤2 was considered no-reflow. The time interval from chest pain onset to balloon dilatation was assessed and correlated to thrombolysis in myocardial infarction flow grade.ResultsThe incidence of no-reflow was 13.9%; thrombolysis in myocardial infarction flow ≤2 occurred in 76 patients. Multivariate regression analysis showed that advanced age >65 years, the total ischemia time ˃6 h, high thrombus burden, and cardiogenic shock were the independent predictors of no-reflow phenomenon. Spearman’s correlation analysis showed a significant negative correlation between the total ischemia time and thrombolysis in myocardial infarction flow grade (r = −351 and P-value = .001).ConclusionThe time delay is the main limitation of achieving thrombolysis in myocardial infarction 3 flow after primary percutaneous coronary intervention. The total ischemia time has a significant negative correlation with thrombolysis in myocardial infarction flow grade after primary percutaneous coronary intervention.

Comparison of Open and Robot-Assisted Kidney Transplantation in terms of Perioperative and Postoperative Outcomes.

Background The gold standard treatment method for end-stage renal disease (ESRD) is renal transplantation (RT). RT can be done with open or minimally invasive surgical methods. We aimed to compare the outcomes between patients who underwent robot-assisted renal transplantation (RART) and open renal transplantation (ORT). Methods Data of the patients who underwent ORT or RART in two institutions between June 2015 and February 2020 were retrospectively reviewed. Patients who underwent live donor RT were included, and all donor nephrectomy procedures were performed by the laparoscopic technique. Demographic data, ischemia times, anastomosis times, operation times, and postoperative complications were recorded. Results 98 patients were included in the ORT group, while 91 patients were included in the RART group. There was a significant difference between the two groups regarding mean patient age. While total ischemia time was 86.9 ± 7 minutes in the RART group, it was calculated as 71.2 ± 3.3 minutes in the ORT group, with a significant difference. The anastomosis time was significantly shorter in the ORT group than in the RART group. The incision length and duration of hospital stay were significantly shorter, visual analogue scores were significantly lower, and estimated blood loss was less in the RART group than in the ORT group. Conclusion Both ORT and RART are effective and safe methods for treating ESRD. According to our study, RART is associated with relatively longer ischemia times but lower complication rates and higher patient comfort.

V13-02 INTRAOPERATIVE RECOGNITION &amp; MANAGEMENT OF AN IATROGENIC CLIPPING OF THE SUPERIOR MESENTERIC ARTERY DURING ROBOTIC LEFT CYTOREDUCTIVE NEPHRECTOMY

You have accessJournal of UrologyCME1 May 2022V13-02 INTRAOPERATIVE RECOGNITION & MANAGEMENT OF AN IATROGENIC CLIPPING OF THE SUPERIOR MESENTERIC ARTERY DURING ROBOTIC LEFT CYTOREDUCTIVE NEPHRECTOMY Brijesh Patel, Daniel Roadman, Mark Biebel, Alexander Chow, and Robert Figenshau Brijesh PatelBrijesh Patel More articles by this author , Daniel RoadmanDaniel Roadman More articles by this author , Mark BiebelMark Biebel More articles by this author , Alexander ChowAlexander Chow More articles by this author , and Robert FigenshauRobert Figenshau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002646.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ligation of the superior mesenteric artery (SMA) is a very rare, and often fatal complication of minimally invasive left nephrectomy (MILN). Despite its rare occurrence, urologists must be cautious when dissecting the left renal artery (RA) and vein (RV) in cases where surgical planes and vascular anatomy are distorted. We present a case of a 77 year old male with metastatic renal cell carcinoma who underwent a robotic left nephrectomy following immunotherapy. METHODS: The patient was placed in standard right decubitus position with the left flank flexed. Pneumoperitoneum was achieved with a Veress needle, and 4 robotic 8 mm ports were placed in a straight line along the lateral edge of the rectus with a 12 mm assistant port in the midline. After the colon was medialized, hilar dissection started with identifying the RV. A pulsation was seen cephalad and parallel to the RV. This vessel was dissected and presumed to be the RA. After the RA was ligated with one clip, the distal part of the vessel continued to pulsate. The left kidney and hilar region behind this clipped vessel continued pulsating, raising suspicion that we clipped the SMA. Adding to this suspicion was the anterior location of the artery, in contrast to the normal posterior location relative to the RV. Immediately, two needle drivers were inserted and the clip prongs were pulled in opposite directions to dislodge the locking mechanism. Total ischemia time was less than ten minutes, and the rest of the case was completed without incident. RESULTS: Procedure time was 4 hours and 2 minutes. Pathology revealed clear cell RCC, Furhman grade 4 with rhabdoid features and negative surgical margins. On the evening of POD#0, the patient’s pain was well controlled, vital signs were stable, and abdominal exam was reassuring. On POD#1, the patient remained stable with no clinical deterioration. He was monitored and discharged on POD#2. CONCLUSIONS: Ligation of the SMA during MILN is exceedingly rare, but can occur in several scenarios: post-systemic therapy operative fields, cytoreductive settings, and large tumors distorting anatomy via mass effect. In such cases, the path of the SMA can be distorted and appear to head laterally towards the kidney. We favor clip placement over stapling to permit removal of the clips should such a complication arise. Urologists must know techniques to remove clips, including using the laparoscopic clip remover, cutting the locking mechanism off the clip, and pulling the prongs of the clip in opposite directions to dislodge the locking mechanism. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1031 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brijesh Patel More articles by this author Daniel Roadman More articles by this author Mark Biebel More articles by this author Alexander Chow More articles by this author Robert Figenshau More articles by this author Expand All Advertisement PDF DownloadLoading ...

Effect of subchronic use of sodium nitrite on the functional parameters of an isolated rat heart

Introduction. The active development of agriculture with the widespread use of nitrogen-containing fertilizers, increased consumption of processed meat products containing sodium nitrite as a preservative, inevitably leads to an increase in the nitrogen load on the human body and can cause the development of cardiovascular diseases. Materials and methods. The cardiotoxic effect of sodium nitrite was evaluated on a model of an isolated rat heart with subchronic intragastric administration for 28 days at doses of 0.03; 0.3; 3.0 mg/kg. Results. The use of sodium nitrite leads to dilation of the coronary vessels and myocardium, inhibition of the contractile activity of the heart, disruption of its electrical activity in the form of a shortening of the QT interval associated with an increased risk of ventricular fibrillation, and a tendency to increase the amplitude of the T wave, which indicates myocardial ischemia. In a stress test with total ischemia, it was revealed that the magnitude of the change in the parameters characterizing the restoration of myocardial function under reperfusion conditions is inversely proportional to the dose of sodium nitrite used. Limitations. The study was performed only on male white rats more prone to the development of cardiovascular pathology. Conclusion. With subchronic administration, sodium nitrite has cardiotoxicity at a dose of 0.028 mg/kg, which is twice lower than the WHO-established permissible daily intake for humans (0.06 mg/kg).

Reconsidering treatment guidelines for acute myocardial infarction during the COVID-19 pandemic

BackgroundCOVID-19 affects healthcare resource allocation, which could lead to treatment delay and poor outcomes in patients with acute myocardial infarction (AMI). We assessed the impact of the COVID-19 pandemic on AMI outcomes.MethodsWe compared outcomes of patients admitted for acute ST-elevation MI (STEMI) and non-STEMI (NSTEMI) during a non-COVID-19 pandemic period (January–February 2019; Group 1, n = 254) and a COVID-19 pandemic period (January–February 2020; Group 2, n = 124).ResultsFor STEMI patients, the median of first medical contact (FMC) time, door-to-balloon time, and total myocardial ischemia time were significantly longer in Group 2 patients (all p < 0.05). Primary percutaneous intervention was performed significantly more often in Group 1 patients than in Group 2 patients, whereas thrombolytic therapy was used significantly more often in Group 2 patients than in Group 1 patients (all p < 0.05). However, the rates of and all-cause 30-day mortality and major adverse cardiac event (MACE) were not significantly different in the two periods (all p > 0.05). For NSTEMI patients, Group 2 patients had a higher rate of conservative therapy, a lower rate of reperfusion therapy, and longer FMC times (all p < 0.05). All-cause 30-day mortality and MACE were only higher in NSTEMI patients during the COVID-19 pandemic period (p < 0.001).ConclusionsCOVID-19 pandemic causes treatment delay in AMI patients and potentially leads to poor clinical outcome in NSTEMI patients. Thrombolytic therapy should be initiated without delay for STEMI when coronary intervention is not readily available; for NSTEMI patients, outcomes of invasive reperfusion were better than medical treatment.

Single Lung Transplantation for Pulmonary Fibrosis Secondary to COVID-19

IntroductionAs of April 2021, 78 lung transplants (LTx) were performed for a diagnosis of COVID-19: 50 for COVID-19 ARDS and 28 for pulmonary fibrosis. Bilateral LTx has been recommended as many patients develop significant pulmonary hypertension. Additionally, native lung explants may include cavitary areas of pneumonia, which could serve as a nidus for infection. Single LTx (SLTx) can be considered in patients who have chronic pulmonary fibrosis secondary to COVID-19 with a short window to receive a transplant, or who would otherwise be considered for a single lung. There have been no published cases of a single lung transplant for COVID-19 pulmonary fibrosis. We present a case of a patient with pulmonary fibrosis from COVID-19 who underwent SLTx.Case ReportA 70yo male with O+ blood type was hospitalized 8/2020 to 10/2020 with COVID-19 pneumonia, treated with Remdesivir and Tocilizumab. He had hypoxia but never required intubation. His course was complicated by bilateral pneumothoraces requiring chest tubes. He developed pulmonary fibrosis requiring 6 L of oxygen at rest. CT scan of his chest showed multifocal, peripheral prominent ground glass opacities and interlobal septal thickening with traction bronchiectasis. Ventilation-perfusion scan demonstrated 22% perfusion to the left lung and 78% to the right lung. Right heart catheterization showed pulmonary artery pressures of 36/12 mmHg. His pulmonary function test was suggestive of restrictive disease (FEV 0.81 L [30%], FVC 0.96 L [27%], and FEV1/FVC 85%) that had worsened over time. He was presented at multidisciplinary review board with recommendation to list for left SLTx, which was activated August 2021. The patient was admitted in September 2021 and underwent left single lung transplant via left anterolateral thoracotomy, off cardiopulmonary bypass. Total ischemia time was 3:54. Explant pathology showed end stage pulmonary fibrosis. The patient was extubated on postoperative day 1 with an uneventful postoperative course. He was discharged to skilled nursing facility on postoperative day 26 for rehabilitation.SummarySLTxp is safe and feasible for COVID-19 related pulmonary fibrosis in well-selected patients who have a short window to receive a transplant.

Anastomosis Time and Outcomes after Donation after Circulatory Death Kidney Transplantation.

At every stage in the transplantation process for a deceased-donor kidney, time means ischemia. Donation after circulatory death (DCD) kidneys are already subject to warm ischemia in the donor, but another underappreciated component of warm ischemia time is the time required for anastomosis prior to reperfusion. We studied the effect of anastomosis time (AT) on outcomes after DCD kidney transplantation. This is a retrospective study of the Scientific Registry of Transplant Recipients, including all US adult DCD kidney transplantation recipients from 2009 to 2015 (N = 6,397). Our exposure was AT (time out of cold storage until reperfusion, quartiles). Outcomes included delayed graft function (DGF), death-censored graft survival, and overall patient survival. Multivariable logistic and Cox regression quantified the association of AT with outcomes, adjusting for donor and recipient factors (including donor warm ischemia time). AT accounted for 67% of total warm ischemia time on average, with a median AT of 38 minutes (median total warm ischemia 56 minutes). Longer AT (fourth [≥48min] vs first quartile [≤30min]) was associated with increased DGF (odds ratio = 1.19, p = 0.024) and increased graft failure (hazard ratio = 1.21, p = 0.043) but was not associated with patient survival. Comparing patients with the longest vs shortest AT, adjusted DGF incidence was 44.0% vs 36.7% (p = 0.024), and 5-year graft survival was 84.8% vs 88.2% (p = 0.004). Prolonged AT is associated with worse graft outcomes in DCD kidney transplant recipients. Efforts to minimize rewarming during implantation and optimize AT may improve graft outcomes.

Kidney Transplants From Donors on Extracorporeal Membrane Oxygenation Prior to Death Are Associated With Better Long-Term Renal Function Compared to Donors After Circulatory Death.

Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical characteristics. Primary non function (PNF) and delayed graft function (DGF) rates, dialysis need, hospitalization duration, and patient and graft survival rates were compared. The estimated glomerular filtration rate (eGFR) was measured throughout the follow-up. Better clinical outcomes were achieved with EPD than with DCD despite similar graft and patient survival rates The total warm ischemia time (WIT) was longer in the DCD group than in the EPD group. Pure WIT was the highest in the class II group. The DGF rate was higher in the DCD group than in the EPD group. PNF rate was similar in the groups. Dialysis need was the greatest and hospitalization the longest in the class II DCD group. eGFR was lower in the class II DCD group than in the EPD group. Our results indicate good clinical outcomes of kidney transplants from DCD despite the long “no-touch period” and show that ECMO in the procurement phase improves graft outcome, suggesting EPD as a source for pool expansion.

The content of ATP Synthase in Cerebral Ischemia of Varying Severity Comparative Analysis

Objective. Evaluation of changes in the content of ATP synthase in the parietal cortex and hippocampus of the brain of rats with ischemia of varying severity in a comparative aspect. Methods. The experiments were performed on 88 male outbred white rats weighing 260 ± 20 g. Brain ischemia was modeled under conditions of intravenous thiopental anesthesia (40-50 mg / kg). Total cerebral ischemia was modeled by decapitation of animals. The brain sampling was carried out 1 hour and 24 hours after decapitation - to study tissue respiration of mitochondria, as well as 1 hour later to determine the content of ATP synthase. Subtotal cerebral ischemia was modeled by simultaneous ligation of both common carotid arteries. The material was taken after 1 hour to determine the content of ATP synthase. Stepwise subtotal cerebral ischemia was performed by sequential ligation of both common carotid arteries with an interval of 7 days. The sampling was carried out 1 hour after ligation of the second common carotid artery in each of the subgroups. Partial cerebral ischemia was modeled by ligation of one common carotid artery on the right. The sampling was carried out 1 hour after the operation. Determination of the content of ATP synthase was carried out by immunohistochemical method using monoclonal antibodies. For this purpose, after decapitation, the brain was quickly removed from the rats, pieces of the cerebral cortex were fixed in zinc-ethanol-formaldehyde at + 4 ° C (overnight), then embeddedвinвparaffin. Results. In the group of stepwise subtotal cerebral ischemia, the smallest decrease in the content of ATP synthase was observed in the 1st subgroup with an interval between dressings of 7 days, while the greatest decrease in the content of the enzyme was noted in the 3rd subgroup with the minimum interval between the dressings of the common carotid artery (1 day). Modeling of more severe types of ischemic damage led to pronounced morphological changes in neurons in the parietal cortex and hippocampus of the rat brain - a decrease in their size, deformation of the perikarya, an increase in the degree of neuronal chromatophilia with their simultaneous wrinkling and subsequent death. These disorders were most pronounced in the 3rd subgroup of stepwise subtotal cerebral ischemia with the shortest interval between dressings, which was 1 day, and in the group of total cerebral ischemia. Conclusion. Thus, the most pronounced decrease in the content of ATP synthase was observed in the groups of total cerebral ischemia, subtotal cerebral ischemia and in the 3rd subgroup of stepwise subtotal cerebral ischemia, with a minimal time interval between the ligation of the common carotid artery. In stepwise subtotal cerebral ischemia with an interval between ligation of the common carotid artery of 7 days, the suppression of the ATP synthase content was not so significant.

Advantages and Limitations of Clinical Scores for Donation After Circulatory Death Liver Transplantation.

Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally.Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems.Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not.Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.

Surgical Outcomes of Hepatectomy with Vascular Resection for Colorectal Liver Metastases

Introduction: Liver resection combined with vascular reconstruction is a curative option for hepatic metastases with vascular invasion. However, vascular surgery during major liver resection significantly increases morbidity and mortality. This study aims to assess the results of vascular resection and reconstruction during hepatectomy for colorectal liver metastases (CLM). Methods: We conducted a descriptive study to evaluate surgical outcomes of CLM patients who underwent hepatectomy with vascular resection. A prospectively collected database was reviewed from January 2019 to May 2021. Results: Overall, 10 hepatectomies in 9 CLM patients were included in the study (3 female and 6 male). The median age was 57 (IQR: 53-61) years. Performed procedures included 4 right hepatectomies, 2 right extended hepatectomies, 2 left extended hepatectomies, 1 central hepatectomy, and 1 segmentectomy of 4B liver segment. Vascular surgery involved 3 portal vein resections, 6 hepatic vein resections, and 1 simultaneous portal vein and hepatic artery resection. Median total liver ischemia time was 50 (IQR: 21-84) min. Median operative time was 375 (IQR: 225-585) min. Median blood loss was 900 (IQR: 250-2000) mL and 4 patients (40%) required blood transfusions. R0 rate was 90%. The 90-day major morbidity (Clavien-Dindo grade III-V) and mortality were 80% and 33%. Median ICU and hospital stays were 3 (IQR: 1-5) and 18 (IQR: 9-33) days. Conclusion: Hepatectomy with vascular resection is feasible for CLM with vascular invasion and demonstrates outcomes comparable with available data from high-volume centers.Tabled 1EP01C-017No.SexAge (years)Type of hepatectomyType of VRLiver ischemia time (min)Operating time (min)Blood loss (mL)Morbidity (CD grade)Death cause1M55RHLPV756701,500IIIbNA2M59CHLHV110350800IIIaNA3F61LEHRHV21290600Vsmall-for-size syndrome4M53REHRHV844003,500IIIaNA5F49RHMHV30200250IIIbNA6F72RHPVC15225250INA7F72SMHV20180100INA8M52REHLHA, PV605854,000Vmassive bleeding9M57LEHLHV, MHV1076602,000Vliver failure10M57RHPV404101,000IIIbNABMI, body mass index; CD, Clavien-Dindo; CH central hepatectomy; F, female; LEH, left extended hepatectomy; LHA, left hepatic artery; LHV, left hepatic vein; LPV, left portal vein; M, male; MHV, middle hepatic vein; NA, not applicable; OR, operating room; PV, portal vein; PVC, portal vein confluence; REH, right extended hepatectomy; RH, right hepatectomy; RHV, right hepatic vein; S, segmentectomy; VR, vascular resection and reconstruction Open table in a new tab BMI, body mass index; CD, Clavien-Dindo; CH central hepatectomy; F, female; LEH, left extended hepatectomy; LHA, left hepatic artery; LHV, left hepatic vein; LPV, left portal vein; M, male; MHV, middle hepatic vein; NA, not applicable; OR, operating room; PV, portal vein; PVC, portal vein confluence; REH, right extended hepatectomy; RH, right hepatectomy; RHV, right hepatic vein; S, segmentectomy; VR, vascular resection and reconstruction

Impact of universal health insurance on total ischemia time and door-to-balloon time in STEMI: A single-center study from a geographical adverse region

We studied the impact of a Universal Health Insurance (UHI) Scheme introduced in India on total ischemia time (an important determinant of ST-elevation myocardial infarction [STEMI] outcome). This is a retrospective hospital-based comparative study which evaluated the total ischemia time (min) of all the patients presenting with STEMI and undergoing primary angioplasty before (Group A) and after (Group B) implementation of this scheme. A total of 221 patients (mean age: 54.18 ± 13.02 years in Group A and 57.59 ± 11.42 years in Group B) were included in the study. Median pain to first medical contact time was 300 and 360 min (P = 0.49), whereas the median first medical contact to percutaneous coronary intervention PCI center time was 330 and 210 min (P = 0.32), for Groups A and B, respectively. A statistically significant difference was noted in the mean door-to-device time between two groups (67.46 ± 33.10 min in Group A vs. 58.48 ± 12.99 min in Group B; P = 0.02). A significant difference in door-to-balloon time was found after implementation of UHI, but total ischemia time was no different. It emphasizes the importance of establishing a system of STEMI care that can decentralize the benefits of early reperfusion like hub-and-spoke model.

Delay in presentation and reperfusion therapy in ST-segment elevation myocardial infarction: Gaps between practice and the guidelines

Developing an efficient regional ST-segment elevation myocardial infarction (STEMI) network in our country has become a challenging priority. In our study, we aimed to assess the factors associated with prolonged delays to reperfusion in STEMI patients treated with Primary PCI or rescue PCI. Patients with STEMI treated with PCI from 2018 until 2019 were prospectively enrolled. Subjects were classified according to the presence of diabetes and according to the origin of the referral. Delays from chest pain onset to the diagnosis of STEMI as well as delays from the diagnosis of STEMI to reperfusion therapy were analyzed. Our population consisted of 225 patients. Baseline characteristics were similar. Diabetes was not associated with longer delays to reperfusion while the source of referral was significantly associated with longer patient delays. In fact, patients out of Sousse had received lytic therapy 5,77 ± 4,12 hours after chest pain onset versus 3,76 ± 2,5 hours for patients in Sousse; P = 0,03. Also, it took 13,09 ± 6,44 hours for patients out of Sousse to diagnose STEMI and thus, decide to perform a primary PCI versus 5,36 ± 4,84 hours for patients in Sousse; P < 0,001. For the system delays, there was no significant difference in the delay from the failure of the lytic therapy to the rescue PCI for patients in Sousse compared to patients out of Sousse (4,5 ± 4,68 hours vs. 6,5 ± 4,34 hours; P = 0,069). However, the delay from the diagnosis of STEMI in the emergency department to the primary PCI was significantly longer for patients out of Sousse (0,76 ± 0,81 hours vs. 2,5 ± 0,64 hours; P < 0,001). Shortening the time from symptoms to reperfusion is a great challenge in STEMI care. To improve the overall care of patients with STEMI particularly in our country, improvements should be focusing on how to minimize the total ischemia time.

Simultaneous Pancreas Kidney Transplant at Hospital Guillermo Almenara Irigoyen from Lima Peru 2009 to 2021

Introduction: Simultaneous pancreas kidney transplantation is a surgical procedure that consists of placing a healthy pancreas and kidney from a deceased donor in a patient with diabetes mellitus and kidney failure in order to improve their quality of life. In Peru, this procedure has been carried out since 2009 with the Guillermo Almenara Irigoyen Hospital as its precursor center. The objective of this study is to describe the symptoms and evolution of cases of simultaneous pancreas-kidney transplants performed to date. Method: The type of study was descriptive, retrospective. Clinical data was collected from the medical records of patients who underwent pancreas kidney transplantation from 2009 to 2021. The data were expressed in tables of frequency and percentage. Results: We were able to identify 9 patients who underwent transplantation. 4 women and 5 men. Ages at the time of transplantation between 29 to 36 years. Most frequent complications: Hemorrhage after transplantation. Graft thrombosis, Graft pancreatitis. Operative technique: Pancreas graft with systemic venous drainage and enteric endocrine drainage. Average operative time: 12 hours. Average total ischemia time: 12 hours Hospital stay: 1 to 8 weeks. Mortality 0% during outpatient follow-up until the end of 2021. Conclusions: Simultaneous kidney pancreas transplantation is the ideal treatment option for patients with diabetes mellitus and end-stage renal failure. It allows the recovery of insulin-independence and avoids the need for dialysis. Simultaneous kidney pancreas transplantation has proven to be an effective and safe surgery in our institution, achieving a better quality of life in our patients.