Abstract P21: Free Radicals Mediate Post-shock Contractile Impairment in Cardiomyocytes

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Min S Tsai ◽  
Shijie Sun ◽  
Giuseppe Ristagno ◽  
Carlos Castillo ◽  
Max H Weil ◽  
...  

Background Previous studies demonstrated myocardial dysfunction after electrical shock and indicated that it may be related to the generation of free radicals. Whether the free radicals are generated after electrical shock has not been documented at the cellular level and its effect on post-shock contractile function has not been clarified. Hypothesis : Electrical shock generates intracellular free radicals inside cardiomyocytes. Reducing intracellular free radicals by pre-treatment of ascorbic acid (AA) would reduce the contractile dysfunction following electrical shock. Methods : Cardiomyocytes isolated from adult male rats were divided into 4 groups, (1) electrical shock alone, (2) electrical shock pre-treated with AA, (3) pre-treated with AA alone and (4) control. AA was administered in an amount of 0.2 mM into the perfusate of the AA + electrical shock and AA groups. Electrical shock of 2 J was delivered in the electrical shock and AA+ electrical shock groups. Results : DCFH-DA loaded cardiomyocytes showed increased intracellular free radicals after electrical shock. The length shortening and Ca 2+ transients were recorded optically with fura-2 loading. Within 4 minutes following electrical shock in the electrical shock group, the length shortening decreased from 8.4±2.5% to 5.6±3.4% ( P =0.000) and the Ca 2+ transient decreased from 1.15±0.13 au to 1.08±0.1 au ( P =0.038). Compared with control, a significant difference in length shortening ( P =0.001) and Ca 2+ transient ( P =0.052) was observed. In the presence of AA, electrical shock did not affect length shortening and Ca 2+ transient. Conclusion: Electrical shock generates intracellular free radicals inside the cardiomyocyte. This is associated with contractile impairment and decrease of Ca 2+ transient. Administering AA may decrease such damage by eliminating free radicals.

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240669
Author(s):  
Armond Daci ◽  
Lorenzo Da Dalt ◽  
Rame Alaj ◽  
Shpejtim Shurdhiqi ◽  
Burim Neziri ◽  
...  

Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study was to investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute vascular inflammatory response. Male rats were treated with 5 mg/kg RVX (oral gavage) followed by 10 mg/kg LPS i.p injection. Circulating levels of IL-6, MCP-1, VCAM-1, and ICAM-1 were measured in plasma 6 and 24 hours after LPS injection, while isolated aorta was used for gene expression analysis, immunohistochemistry, and vascular tone evaluation. RVX pre-treatment significantly reduced LPS mediated increase after 6h and 24h for IL-6 (4.4±2.2 and 2.8±1.7 fold), MCP-1 (1.4±1.5 and 1.3±1.4 fold) VCAM-1 (1.8±2.0 and 1.7±2.1 fold). A similar trend was observed in the aorta for iNOS (5.5±3.3 and 3.3±1.9 folds reduction, P<0.01 and P<0.001, respectively), VCAM-1 (1.3±1.2 and 1.4±1.3 fold reduction, P<0.05), and MCP-1 (3.9±2.2 and 1.9±1.6 fold reduction, P<0.01). Moreover, RVX pre-treatment, improved LPS-induced PE contractile dysfunction in aortic rings (Control vs LPS, Emax reduction = 35.4 and 31.19%, P<0.001; Control vs LPS+RVX, Emax reduction = 10.83 and 11.48%, P>0.05, respectively), resulting in 24.5% and 19.7% change in maximal constriction in LPS and LPS+RVX respectively. These data indicate that RVX pre-treatment attenuates LPS-induced acute vascular inflammation and contractile dysfunction.


2014 ◽  
Vol 2 (2) ◽  
pp. 41-46
Author(s):  
Elida Soviana ◽  
Banundari Rachmawati ◽  
Nyoman Suci Widyastiti

Background : Hyperglycemia on diabetes mellitus can cause increasing of free radicals production. Free radicals caused lipid peroxidation reaction by forming malondialdehyde (MDA). β-carotene has antioxidant activity may inhibit the formation of ROS.Objective : To prove the effect of multilevel doses β-carotene 1 mg/kg BW, 20 mg/kg BW and 20 mg/kg BW on alternate days within 30 days orally supplementation on blood glucose level and MDA level on Sprague Dawley male rats induced by streptozotocin (STZ). Methods : Thirty rats were randomly divided into 5 groups: X1=Negative control/diabetic, X2 (STZ 40 mg/kg BW + BC 1 mg/kg BW), X3 (STZ 40 mg/kg BW + BC 10mg/kg BW), X4 (STZ 40 mg/kg BW + BC 20 mg/kg BW), X5 (technic control/non diabetic). β-Carotene supplementation was given by nasogastric tube on alternate days within thirty days. Blood glucose level was measured by GOD-PAP and MDA level by ELISA with TBARS methods. Data was analized using paired t-test, wilcoxon, one way anova and post hoc bonferroni. Results : there was a significant difference of blood glucose level (p = 0,0001) and MDA level (p = 0,0001) after suplementation β-carotene on alternate days within 30 days orally. β-carotene 10 mg/kg BW was the most effective and efficient dose to lowering blood glucose, while 20 mg/kg BW to lowering MDA level. Conclusion : The multilevel doses β-carotene (1 mg/kg BW, 10 mg/kg BW and 20 mg/kg BW) on alternate days within 30 days orally supplementation can decrease blood glucose and MDA level. β-carotene 10 mg/kg BW is the most effecetive and efficient to decrease blood glucose and β-carotene 20 mg/kg BW to decrease MDA level.


Author(s):  
П.А. Ермолаев ◽  
Т.П. Храмых ◽  
Л.О. Барская

Цель - оценить роль холемии в генезе миокардиальной дисфункции после субтотальной резекции печени у крыс. Методика. Эксперименты выполнены на 48 беспородных белых крысах-самцах. 38 животным проводили субтотальную атипичную резекцию 80% печени оригинальным способом, 10 интактных животных составили контрольную группу. Определение общей концентрации желчных кислот в сыворотке крови проводили энзиматическим колориметрическим методом у интактных животных и в 1-е, 3-и и 7-е сут после резекции печени. Прямую оценку сократительной функции и метаболизма миокарда интактных животных проводили на спонтанно сокращающихся изолированных сердцах. При перфузии сердец с добавлением в перфузат желчи, рассчитывали комплекс силовых и скоростных показателей сократимости, определяли содержание глюкозы, лактата, активность аспартатаминотрасферазы в коронарном протоке. Результаты. Выявлено повышение общего содержания желчных кислот в сыворотке крови оперированных животных. Добавление желчи в раствор для перфузии изолированных сердец вызывало развитие брадикардии, снижение силовых и скоростных показателей сократительной функции. При этом происходило увеличение потребления глюкозы, выделения лактата и аспартатаминотрансферазы в коронарный перфузат. Заключение. Полученные данные свидетельствуют о значимой роли холемии, развивающейся после субтотальной резекции печени, в генезе функционально-метаболических нарушений в миокарде. Aim. To assess the role of cholemia in development of myocardial dysfunction following the subtotal hepatic resection in rats. Methodology. Experiments were conducted on 48 white mongrel male rats. Subtotal atypical 80% liver resection was performed on 38 animals using an original method; the control group consisted of 10 intact animals. Total serum concentration of bile acids was measured using the enzymatic colorimetric method in intact animals and on days 1, 3, and 7 after the liver resection. Myocardial contractile function and metabolism were directly evaluated on spontaneously contracting isolated hearts of intact animals. During the heart perfusion with added bile, a set of contractile force and velocity indices was calculated; glucose and lactate concentrations and aspartate aminotransferase activity were measured in the coronary perfusate. Results. The total serum content of bile acids was increased in operated animals at all study points. When bile was added to the perfusion solution, the isolated hearts developed bradycardia, decreases in force and speed indices of the contractile function, increased glucose consumption, and release of lactate and aspartate aminotransferase into the coronary perfusate. Conclusion. The study showed the importance of cholemia following the subtotal liver resection for the development of functional and metabolic disorders of the myocardium.


1987 ◽  
Vol 252 (3) ◽  
pp. H566-H577 ◽  
Author(s):  
M. I. Charlat ◽  
P. G. O'Neill ◽  
J. M. Egan ◽  
D. R. Abernethy ◽  
L. H. Michael ◽  
...  

Recent evidence suggests that postischemic myocardial dysfunction (or myocardial “stunning”) may be mediated by oxygen free radicals, but the mechanism for their production remains unknown. To explore the role of xanthine oxidase as a potential source of free radicals, open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received intravenously either allopurinol (50 mg/kg 48 h, 20 h, and 30 min before occlusion, 10 mg/kg 1 min before REP, and 6.25 mg X kg-1 X h-1 throughout REP, n = 13) or saline (n = 14). The two groups were similar with respect to occluded bed size (postmortem perfusion) and collateral flow (radioactive microspheres). In controls, the transcardiac difference in plasma uric acid (great cardiac vein - arterial concentration) increased 199 +/- 70% (means +/- SE) during ischemia (P less than 0.02) and remained elevated for 5 min after REP; no increase was observed in treated dogs. Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. Following REP, however, recovery of contractile function (expressed as percent of preocclusion values) was considerably greater in allopurinol-treated as compared with control dogs: 57 +/- 14 vs. -22 +/- 16 (P less than 0.01) at 1 h, 70 +/- 13 vs. -15 +/- 15 (P less than 0.001) at 2 h, 65 +/- 14 vs. -28 +/- 13 (P less than 0.001) at 3 h, and 68 +/- 13 vs. -17 +/- 14 (P less than 0.001) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that xanthine oxidase is a source of the oxygen free radicals responsible for myocardial stunning following a brief episode of reversible regional ischemia.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1061
Author(s):  
Gusbakti Rusip ◽  
Syafrudin Ilyas ◽  
I. Nyoman Ehrich Lister ◽  
Chrismis N. Ginting

Background: Prolonged activation of skeletal muscles causes a decrease in the production of fatigue. Exercise with strenuous intensity causes an increase in Reactive Oxygen Species (ROS). An increase in free radicals causes oxidative stress resulting in damage to cell function to mitochondrial dysfunction, and fatigue. This study aimed to determine the antioxidant potential of red dragon fruit (RDF) to delay fatigue due to oxidative stress, which improves cell function in mitochondria. Methods: 25 male rats (Rattus norvegicus) aged three months were divided into five groups: Group K1 was N.A. (No Activity) but drinking and eating; Group K2 performed strenuous exercise without RDF treatment; Groups 3, 4, and 5 (P1, P2 and P3, respectively) performed strenuous exercise and were treated with 75 mg kg-1.bw, 150 mg kg-1.bw, and 300 mg kg-1.bw of RDF extract, respectively. The exercise for the rats involved intense swimming for 20 minutes every day, four days a week for 31 days.  Malondialdehyde (MDA) was measured with the ELISA and histopathology for muscle soleus and lung tissue. Results: Strenuous exercise followed by RDF extract ingestion was compared for fatigue in terms of duration and time; before (24.55±1.38 minute) and after (95.31±7.82 minute) and led to a significant difference of 39% (p<0.01). The study also compared MDA before and after RDF extract ingestion in the K2 vs. the P1 group (p<0.05). At the same time, P2 differed more significantly (p<0.01). This indicated a spread of free radicals and featured histopathological damage of muscle cells. However, ingestion of RDF extract leads to improvement of soleus muscle cells; thus, repairs cell function, delaying fatigue. Conclusion: This study confirmed that strenuous exercise, which causes an increase in ROS, intensifies free radicals with RDF extract ingestion and declines oxidative stress, repairing cell function and delaying fatigue.


Author(s):  
P Han ◽  
A Turpie ◽  
E Genton ◽  
M Gent

Platelets play a role in the development and complications of coronary artery disease (CAD) and a number of abnormalities of platelet function which can be corrected by antiplatelet drugs have been described. Betathromboglobulin (BTG), a platelet-specific protein which is released from α-granules during platelet activation is significantly elevated in patients with angiographically demonstrated CAD (51.0 ± 31.0 ng/ml., n = 50) compared to normal (28.0 ± 8.0 ng/ml., n = 70) p < 0.001. The effect of sulphinpyrazone (800 mg.) or aspirin (1200 mg.)/dipyridamole (200 mg.) on plasma BTG in CAD was studied in a blind prospective crossover trial in 25 patients. Mean BTG concentration pre-treatment was 52.3 ng/ml. and after 1 month’s treatment with placebo, sulphinpyrazone or aspirin/dipyridamole mean plasma BTG concentrations were 53.5, 49.6 and 56.7 ng/ml. respectively. Analysis of variance showed no significant difference between the means (p > 0.1) . This study confirms increased plasma BTG concentrations in patients with CAD and indicates that therapeutic doses of these antiplatelet drugs do not significantly effect the BTG level and thus appear not to prevent α-granule release in CAD.


1960 ◽  
Vol XXXV (III) ◽  
pp. 381-396 ◽  
Author(s):  
Sven Almqvist

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.


2017 ◽  
Vol 17 (1) ◽  
pp. 93-98
Author(s):  
Zheng Yue ◽  
Zhang Wen-Cheng ◽  
Wu Ze-Yu ◽  
Fu Chuan-Xiang ◽  
Gao Han ◽  
...  

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.


Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1569
Author(s):  
Tomislav Šušnjar ◽  
Ivana Kuzmić Prusac ◽  
Ivan Švagelj ◽  
Anđela Jurišić ◽  
Tomislav Šušnjar ◽  
...  

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Annarita Perillo ◽  
Valeria Landoni ◽  
Alessia Farneti ◽  
Giuseppe Sanguineti

Abstract Purpose The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. Methods and materials Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. Results For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). Conclusions In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.


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