Changes in Blood Potassium after Reperfusion during Living-Donor Liver Transplantation: An Exploratory Study

The incidence of hyperkalemia (> 5.5 mEq/L) or high blood potassium (5–5.5 mEq/L) during living-donor liver transplantation (LDLT) is reported to be more than 10%. It occurs more frequently in the early post-reperfusion period and is a major cause of post-reperfusion arrhythmia and cardiac arrest. Unlike deceased-donor liver transplantation, the pattern of blood potassium changes immediately after reperfusion has not been described in LDLT. From January 2021 to March 2021, fifteen consecutive patients were enrolled. Baseline blood potassium was measured from blood samples obtained 10-min (T-10) and immediately before (T0) reperfusion. During the first 5 min after reperfusion, blood potassium measurements were conducted every one minute (T1–T5). The blood potassium levels at T-10 and T0 were 3.8 ± 0.4 and 3.9 ± 0.4 mEq/L, respectively. After reperfusion, mean increases (95% CI) in blood potassium from T-10 and T0 were 0.5 (0.4–0.6) and 0.4 (0.3–0.5) mEq/L, respectively. Blood potassium peaked at T1, returned to baseline at T3, and fell below the baseline at T5. Peak blood potassium after reperfusion showed strong correlations with blood potassium measured at T-10 (p < 0.001) and T0 (p < 0.0001). These findings can support the establishment of future research plans and perioperative management of blood potassium in LDLT.

EFFECTS OF MELATONIN AND CURCUMIN TREATMENTS ON THE OVARIUM IN KIDNEY ISCHEMIA-REPERFUSION INJURY: A HISTOPATHOLOGICAL INVESTIGATION

Aim: We aimed to investigate how bilateral renal ischemia-reperfusion (I/R) damage affects the ovaries as a distant organ and the effects of melatonin (MEL), curcumin (CUR) and melatonin+curcumin (MEL+CUR) treatments on I/R damage. Material and Method: 42 female Wistar rats were used in the study. Rats were divided into 6 groups and study was designed as follows: Control group (G1) – opening and closing the abdomen only (sham surgery group) –, I/R group (G2) – 45 min ischemia followed by 2 h reperfusion –, I/R+MEL group (G3) – 45 min ischemia, intraperitoneal (i.p) 20 mg/kg MEL injection 5 min before reperfusion, followed by 2 h reperfusion –, I/R+CUR group (G4) – 45 min ischemia, 5 min before reperfusion i.p 200 mg/kg CUR injection and then 2 hours reperfusion –, I/R+MEL+CUR group (G5) – 45 min ischemia, 5 min before reperfusion i.p 20 mg/kg MEL and 200 mg/kg CUR injection, followed by 2 hours reperfusion –. At the end of the reperfusion period, the rats were sacrificed. Right ovaries were removed from the peritoneum and fixed. After fixation and follow-up, tissue sections were stained with hematoxylin&eosin (H&E), Periodic acid-Schiff (PAS)+Hematoxylin (PAS+H) and Masson’s trichrome stains. Pathological changes were scored and statistically evaluated. Results: Compared to the control group, there was a decrease in hemorrhage, vascular congestion, follicular degeneration, inflammation, interstitial edema, vasodilation and growing follicle numbers in all groups; these changes were severe in the G2 group; Mild to moderate severity was observed in the G3, G4 and G5 groups. Conclusion: Renal I/R damage significantly affects the ovaries histopathologically. MEL, CUR, and MEL+CUR partially preserve the histological structure, but MEL treatment seems to be more effective than CUR treatment.

Initial experience with del Nido cardioplegia solution at a Pediatric and Congenital Cardiac Surgery Program in Brazil

Objective: The aim of this study was to evaluate outcome measures between our standard multidose cardioplegia protocol and a del Nido cardioplegia protocol in congenital heart surgery patients. Methods: Retrospective single-center study including 250 consecutive patients that received del Nido cardioplegia (DN group) with a mandatory reperfusion period of 30% of cross clamp time and 250 patients that received a modified St. Thomas’ solution (ST group). Groups were matched by age, weight, gender, and Risk Adjustment for Congenital Heart Surgery (RACHS-1) scores. Preoperative hematocrit and oxygen saturation were also recorded. Outcomes analyzed were the vasoactive inotropic score (VIS), lactate, ventilation time, ventricular dysfunction with low cardiac output syndrome (LCOS), intensive care unit (ICU) length of stay (LOS), hospital LOS, bypass and aortic cross-clamp times, and in-hospital mortality. Results: Both groups were comparable demographically. Statistically significant differences (p ⩽ 0.05) were noted for cardiac dysfunction with LCOS, hematocrit at end of surgery (p = 0.0038), VIS on ICU admission and at end of surgery (p = 0.0111), and ICU LOS (p = 0.00118) with patients in the DN group having more desirable values for those parameters. Other outcome measures did not reach statistical significance. Conclusion: In our congenital cardiac surgery population, del Nido cardioplegia strategy was associated with less ventricular dysfunction with LCOS, a lower VIS and decreased ICU LOS compared with patients that received our standard myocardial protection using a modified St. Thomas’ solution. Despite the limitation of this study, including its retrospective nature and cohort size, these data supported our transition to incorporate del Nido cardioplegia solution with a mandatory reperfusion period as the preferred myocardial protection method in our program.

Early Graft Dysfunction Following Kidney Transplantation: Can Thermographic Imaging Play a Predictive Role?

The shortage of organs and the growing need for them over recent years have led to the adoption of less stringent donor acceptance criteria, resulting in the approval of marginal organs for transplant, especially from elderly donors. This implies a higher risk of graft dysfunction, a higher frequency of immunological and vascular complications, and shorter graft survival. Several strategies have been implemented in clinical practice to assess graft quality and suitability for transplantation. We have started to test the prospective intraoperative use of thermo-vision cameras during graft reperfusion. Images were acquired using the FLIR One Pro thermo-vision camera for android devices. We hypothesized that thermal images would give a better perspective about the quality of arterial perfusion and graft revascularization of the renal cortex. Thermo-vision cameras provide an easy-to-use, noninvasive, cost-effective tool for the global assessment of kidney graft cortical microcirculation in the immediate post-reperfusion period, providing additional data on the immediate viability and function of a graft.

DSIP-Like KND Peptide Reduces Brain Infarction in C57Bl/6 and Reduces Myocardial Infarction in SD Rats When Administered during Reperfusion

A structural analogue of the DSIP, peptide KND, previously showed higher detoxification efficacy upon administration of the cytotoxic drug cisplatin, compared to DSIP. DSIP and KND were investigated using the model of acute myocardial infarction in male SD rats and the model of acute focal stroke in C57Bl/6 mice. A significant decrease in the myocardial infarction area was registered in KND-treated animals relative to saline-treated control animals (19.1 ± 7.3% versus 42.1 ± 9.2%). The brain infarction volume was significantly lower in animals intranasally treated with KND compared to the control saline-treated animals (7.4 ± 3.5% versus 12.2 ± 5.6%). Injection of KND in the first minute of reperfusion in the models of myocardial infarction and cerebral stroke reduced infarction of these organs, indicating a pronounced cardioprotective and neuroprotective effect of KND and potentiality for the treatment of ischemia-reperfusion injuries after transient ischemic attacks on the heart and brain, when administered during the reperfusion period. A preliminary pilot study using the model of myocardial infarction with the administration of DSIP during occlusion, and the model of cerebral stroke with the administration of KND during occlusion, resulted in 100% mortality in animals. Thus, in the case of ischemia-reperfusion injuries of the myocardium and the brain, use of these peptides is only possible during reperfusion.

Dynamics of violations the absorption function of the small intestine in conditions of acute blood loss complicated by ischemia-reperfusion of the limbs and their correction

Introduction. In the structure of modern injuries in wartime and peacetime the share of gunshot wounds increased significantly. The timeliness of applying a tourniquet is one of the main methods of saving lives on the battlefield. The patterns of formation of enteral insufficiency syndrome in conditions of acute blood loss complicated by ischemia-reperfusion of the limb have not been studied enough. There are no data on the features of violations of the absorption function of the small intestine in these conditions and the effectiveness of correction with Carbacetam, which is able to reduce the manifestations of acute hemic hypoxia and ischemic-reperfusion syndrome.The objective of research: To establish the peculiarities of the absorption function of the small intestine in the pathogenesis of acute blood loss, ischemia-reperfusion of the limb and their combination. To evaluate the effectiveness of Carbacetam in the correction of identified abnormalities.Materials and methods. The experimental studies were conducted on 108 white nonlinear male rats weighing 200-220 g, which were housed in standard vivarium conditions. All animals were divided into five groups: control and four experimental. Under thiopental-sodium anesthesia in the first experimental group was simulated ischemia-reperfusion of the limb, in the second group – acute blood loss, and in the third group – these injuries were combined. In the fourth experimental group, animals with acute blood loss and ischemia-reperfusion of the limb were intraperitoneally administered Carbacetam at a dose of 5 mg per kilogram of animal weight. After 1 and 2 hours, as well as after 1, 7 and 14 days studied the absorption function of the intestines by D-xylose test.The results and discussion. Simulation of limb ischemia-reperfusion compared with the control group causes a decrease in the content of D-xylose in the urine after 1 day of the reperfusion period. Also, acute blood loss is accompanied by a significant decrease in this indicator after 1 day. Until the end of the experiment the rate increases, but up to 14 days does not reach the level of control. The combination of acute blood loss and ischemia-reperfusion of the limb causes a decrease in the content of D-xylose in the urine starting from 1 hour of the experiment, which reaches a minimum after 1 day and remains at the same level until 14 days. In these terms the rate was the lowest compared to other studied groups. The use of Carbacetam for corrective purposes in rats with acute blood loss complicated by ischemia-reperfusion of the limb, compared with animals without correction significantly reduces the detected abnormalities after 7 days and more after 14 days of use.Conclusions. Complications of acute blood loss by ischemia-reperfusion of the limb causes a significant decrease in the absorption function of the small intestine after 1 day of the experiment. The intensity of disorders was significantly higher compared to other experimental groups. The use of Сarbacetam for 7-14 days in the reperfusion period in animals with acute blood loss complicated by limb ischemia-reperfusion, compared with animals without correction, causes a significant increase in the absorption function of the small intestine. This indicates the protective effect of the drug under the conditions of simulated pathology.

EARLY AND REMOTE RESPONSE OF HIF-1Α PROTEIN IN THE HIPPOCAMPUS FIELDS TO ISCHEMIA-REPERFUSION IN RATS WITH DIABETES MELLITUS

The role of the transcription factor Hif-1α in pathogenesis of hypoxic lesions and diabetes mellitus (DM) has been confirmed, though molecular mechanisms underlying dysfunctions of the factor in the association of DM with ischemic-reperfusion lesion of the brain remain unknown. Objective: the investigation of Hif-1α protein content in the neurons of the hippocampus fields of rats with experimental DM in the dynamics of ischemic-reperfusion lesion of the brain. The study was conducted on 60 6-month rats with DM simulated at the age of 2 months by means of a single administration of streptozotocin (60 mg/kg of the body weight) (Sigma, USA). Disorders of the cerebral circulation were simulated by means of occlusion of both carotid arteries for 20 minutes. The content of Hif1-α protein was determined by means of fluoroimmunoassay after 20-minute ischemia with one hour reperfusion, and on the 12th day of the post-ischemic period in the hippocampus fields: СА1, СА2, СА3, СА4. In rats without DM 20-minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the hippocampus fields. On the 12th day of ischemic-reperfusion period in СА2-СА4 hippocampus fields the values of certain examined activity indices of the transcription factor Hif-1α continue to increase, and in СА1 field they are normalized or come closer to the values of animals from the control group. In rats with DM at the early post-ischemic period changes of Hif-1α protein content are lacking in СА1 field, the signs of its reduced activity are found in СА2 field, in СА3 field they are limited by the response of one index, and in СА4 field they are similar to those of the control rats under the experimental conditions. On the 12th day of ischemic-reperfusion period all the activity indices of the transcription factor Hif-1α increase in СА1 filed. They are higher than the corresponding indices in animals from the control group by absolute values under similar experimental conditions; changes of the examined parameters are limited in СА2 and СА3 fields in comparison with those from the control group; the parameters, which increased in the control group of animals, decreased in СА4 field. DM restricts Hif-1α protein response to ischemia-reperfusion in the neurons of СА1-СА3 field at the early ischemic-reperfusion period and in the neurons of СА2-СА4 fields — on the 12th day of the observation.

Skin microvascular dysfunction in systemic lupus erythematosus patients with and without cardiovascular risk factors

Objectives Patients with SLE have increased cardiovascular mortality. Alterations in both macro- and micro-circulation have been associated with cardiovascular disease. We sought to assess skin microvascular function by using laser speckle contrast analysis (LASCA) in patients with SLE, with and without cardiovascular disease and risk factors. Methods Continuous blood flow was recorded using a LASCA device during baseline, a 5-min arterial occlusion and a 5-min reperfusion period. Results Thirty-five patients with SLE (85.7% women) with a median disease duration 12.0 (6.5–17.5) years and a mean age of 46.3 (8.6) years and 31 controls matched for age, sex and BMI were enrolled. During reperfusion, SLE patients exhibited a smaller peak magnitude compared with controls (161.0 (47.1) vs 197.2 (41.4)%, respectively, P =0.002). Results remained unchanged among 24 SLE patients without cardiovascular disease compared with the control group (169.2 (48.1) vs 195.6 (34.0)%, respectively, P =0.002). Conclusion Our study shows, for the first time, that patients with SLE, even without overt cardiovascular disease or risk factors, exhibit a blunted microvascular reactivity during reperfusion compared with controls. These results show that skin microvascular dysfunction is present in SLE independently of the CV burden that these patients bear and may represent an early sign of vascular damage.

State of the antioxidant protection system of rat liver in ischemia and reperfusion

Purpose: determination of the state of the antioxidant protection system of the cytosolic fraction and suspension of rat liver mitochondria after experimental ischemia and reperfusion. Materials and methods: the study was conducted using white mature rats, divided into 3 groups: the control group (n = 15); The 2nd group of animals (n = 15), from which the liver was taken after 15 minutes of liver ischemia; the 3rd group of rats (n = 15), from which the liver was taken after a 15-minute reperfusion period, followed by a 15-minute ischemic period. Mitochondrial suspension and cytosolic fraction were isolated from liver tissue. Results: the obtained research results showed the presence of certain pathobiochemical changes in the suspension of mitochondria and the cytosolic fraction after ischemia or reperfusion. In the mitochondrial suspension during the reperfusion period it was found an adaptive increase in the activity of glutathione peroxidase by 39% and glutathione reductase by 61%. In the cytosolic fraction, it was the most remarkable increase of the total antioxidant capacity by 38% already during ischemia and a progressive decrease in the level of reduced glutathione form by 26% in ischemic and 55% in reperfusion period. The change in the state of the antioxidant system occurred against the background of an increase in the number of products of oxidative modifications of biomolecules by 40% during ischemia and 2.2 times after reperfusion. Conclusion: The results indicate the need to develop not only a mitochondria-oriented correction of oxidative disorders, but also active support for the components of the cytosol, which provide the main accumulation of free radical damage products and their subsequent removal from the cell, which is essential for survival.

Changes of biochemical indicators of blood serum and the skeletal muscle homogenate of the hind limbs of the rats in acute ischemia-reperfusion and in the condition of using of the carbacetam

Annotation. Simulation of ischemia-reperfusion causes the biochemical disorders and changes in the prooxidant-antioxidant system, both in the serum and skeletal muscles of the affected limb. The severity of local and systemic postischemic imbalance decreases in with correction with medicine from the group of nootropics – carabacetam. The aim of the study was determining the degree of metabolic disorders based on the analysis of changes in serum biochemical parameters and muscle homogenate in ischemic-reperfusion disorders caused by the imposition of an arterial tourniquet and under conditions of correction with carbacetam. Materials and methods. A biochemical study of blood serum and muscle homogenate of 60 rats was performed. Ischemia was simulated by applying SWAT rubber tourniquets on the hind limbs of the rats, on the inguinal fold, for 2 hours, and reperfusion was modeled by removing the tourniquet and restoring of blood circulation through 2 hours after its application. Observations of the animals were carried out during for 14 days. 30 rats in the reperfusion period were intraperitoneally administered the carbacetam at a dose of 5 mg per kilogram of body weight 1 time a day for 14 days of the reperfusion period. The Blood serum was separated and the soft tissue samples were taken below the turniquet site for the biochemical studies. Statistical processing of the material was performed using the package of programs “Microsoft Excel”. The largest deviations in serum were observed after 1 day of the reperfusion: an increase in creatinine by 28.16 % (p<0.005), total bilirubin by 20.75 % (p<0,005), ALT by 96.14 % (p<0,005), AST by 147.27 % (p<0.005) and alkaline phosphatase by 70.84 % (p<0.005), as well as an increase in prooxidant activity of CD by 77.27 % (p<0.005), CT 147.47 % (p<0,005) and TBC-AL by 82.52 % (p<0,005) against the background of a decrease in SOD activity by 9.77 % (p<0.005) and an increase in catalase levels by 15.37 % (p<0.005) relative to the value of the control group. The development of ischemia and reperfusion was accompanied by the largest increase in the level of prooxidants (CD – by 27.55 % (p<0.005), CT – by 47.34 % (p<0.05), TBC-AL – by 62.09 %) (p<0.005)) in the homogenate of the skeletal muscles after 2 hours after restoration of the blood supply. Antioxidant activity, on the other hand, decreased by 15.06 % (p<0.005) SOD and by 8.96 % (p<0.005) catalase after 1 day. After 14 days, a gradual increase and return of most of the studied values to the level of the control group. Under the influence of the carbacetam, the biochemical parameters of blood serum most significantly decreased in relative to the value of the groups without correction after 7 days of the experiment. The level of total bilirubin was lower by 29.65 % (p˂0.05), ALT by 14.95 % (p˂0.05), AST by 19.84 % (p˂0.05), alkaline phosphatase by 25.53 % (p˂0.05), and the difference in the content of diene, triene conjugates and TBC-LP was the largest after 1 day – by 17.09 % (p<0.005), 20,41 % (p<0.05) and 11.24 % (p<0.05), respectively. Under the conditions of correction, the indicators of SOD and catalase activity increased, being significantly higher than in the groups of the animals without correction, especially after 7 days of reperfusion – by 29.41 % (p<0.005) and by 15.71 % (p<0.05) in accordance. The content of the diene, triene conjugates and TBC-LP muscle homogenate was statistically significantly lower in the groups with the introduction of the carbacetam than in the groups of the animals without correction. The largest difference between the groups was found after 1 day with a difference of 9.16 % (p<0.05), 7.35 % (p<0.005) and 16.05 % (p<0.05), respectively. Antioxidant activity of SOD and catalase after 1 day was higher by 27.41 % (p<0.005) and by 25.13 % (p<0.005), compared with the group of the animals without introduction of the carbacetam. Thus, simulated ischemia-reperfusion is accompanied by the greatest biochemical disorders in the serum – after 1 day, and in the muscle homogenate – after 2 hours of the reperfusion. After 14 days of the experiment, most indicators still do not return to the level of the control group. The application of the correction helps to reduce the severity of biochemical disorders at the systemic and local levels, especially during periods of their greatest deviations.