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Braz. J. Pharm. Sci. (Online) ; 58: e191062, 2022. graf
Article in English | LILACS | ID: biblio-1394040


Abstract The aim of this study was to assess the effects of methanol extract of G. verum on redox status of isolated heart of spontaneously hypertensive rats after ischemia. Twenty-four Wistar albino rats were divided into three groups: untreated control rats and rats that received 125 and 250 mg/kg G. verum extract for 4 weeks per os. Index of lipid peroxidation (measured as TBARS) and parameters of antioxidative defence system such as level of reduced glutathione (GSH) and activities of catalase (CAT) and superoxide dismutase (SOD) were spectrophotometrically determined in heart homogenate. The index of lipid peroxidation in heart tissue was lower in both treated groups compared to the control group. On the other hand, the activity of SOD was significantly higher after consumption of both doses, while the activity of CAT was significantly higher only after treatment with a higher dose of extract. Based on our results we might conclude that 4-week treatment with methanol extracts of G. verum has the potential to modulate myocardial redox signaling after ischemia, thus significantly alleviating cardiac oxidative stress and exerting dose-dependent antioxidant properties. Future studies are certainly necessary to fully clarify the role of this plant species in myocardial I-R injury.

Animals , Male , Rats , Rats, Inbred SHR , Plant Extracts/adverse effects , Galium/adverse effects , Wounds and Injuries/classification , Oxidative Stress/immunology , Heart , Ischemia/pathology , Antioxidants/adverse effects
Rev. chil. cardiol ; 39(1): 24-33, abr. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1115446


INTRODUCCIÓN: Los ratones SR-B1 KO/ApoER6 1h/h que son alimentados con una dieta rica en grasas saturadas, desarrollan enfermedad coronaria aterosclerótica severa, complicaciones isquémicas e insuficiencia cardíaca, con alta mortalidad. Los estudios con este modelo se han enfocado fundamentalmente en la enfermedad coronaria y menos en el remodelado cardíaco. El OBJETIVO del trabajo ha sido caracterizar el remodelado miocárdico, evaluar la evolución temporal de la función ventricular izquierda y la sobrevida asociada a enfermedad cardíaca por ateromatosis. MÉTODO: Ratones homocigotos SR-B1 KO/ApoER6 1h/h fueron alimentados por 8 semanas con dieta aterogénica o dieta normal y se comparó la sobrevida en ambos grupos. A las 4 semanas se realizó un ecocardiograma bidimensional. En los ratones eutanasiados se evaluó en la pared cardíaca fibrosis miocárdica y tamaño de los cardiomiocitos por morfometría, apoptosis con técnica de TUNEL e infiltración por células inflamatorias mononucleares (ED1) por inmunohistoquímica. RESULTADOS: En el grupo que recibió dieta aterogénica la sobrevida se redujo en 46,7% (p < 0.001), debido a muerte súbita y a falla cardíaca progresiva. En este grupo, a las 4 semanas se observó dilatación de cavidades izquierdas y disminución de la fracción de eyección del ventrículo izquierdo en comparación con el grupo control (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01). También se observó aumento de la masa cardíaca relativa de 2.1 veces (p<0,001) y del peso pulmonar relativo en 80% (p<0,001), sin cambios en las dimensiones de los cardiomiocitos. En el miocardio de los ratones que recibieron dieta aterogénica hubo un aumento de la fibrosis cardíaca de 7.9 veces (p < 0.01) y del número de cardiomiocitos apoptóticos en 55.9 veces (p < 0.01), junto a un aumento del número de células inflamatorias mononucleares ED1. CONCLUSIONES: En el modelo de falla cardíaca severa de etiología isquémica con alta mortalidad en el ratón homocigoto SR-B1 KO/ApoER6 1h/h sometido a una dieta aterogénica, con falla cardíaca izquierda por disfunción sistólica, el remodelado patológico del miocardio está dado fundamentalmente por apoptosis y fibrosis. También se observa un aumento discreto de macrófagos en la pared cardíaca. Es posible que el edema parietal también pueda ser un mecanismo de remodelado relevante en este modelo.

Abstract: SR-B1 KO/ApoER6 1h/h mice fed a high saturated fat diet develop severe coronary atheromatosis, and cardiac failure with a high mortality rate. Cardiac remodeling under these conditions has not been well studied. AIM: To evaluate the time course of left ventricular function, cardiac remodeling and survival associated to the administration of an atherogenic diet. METHOD: Homozygote SR-B1 KO/ApoER6 1h/h mice received an atherogenic diet for 8 weeks. Mice receiving a normal diet served as controls. Survival rate, myocardial fibrosis, cardiomyocyte size, apoptosis and infiltration by inflammatory or mononuclear cells were compared between groups. A TUNEL technique was used to evaluate apoptosis. RESULTS: A 46.7% survival reduction compared to controls was observed in the experimental group (p<0.01), due to left ventricular and atrial dilatation associated to a decrease in ejection fraction (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01, respectively). Also, an increased cardiac weight, 2.6 times greater was observed in the experimental group, compared to controls. Mice receiving the atherogenic diet showed an 80% increased lung weight. There was no evident change in cardiomyocytes, but there was more (7.9 times) cardiac fibrosis (p<0.01) and 55.9 times more apoptotic cells. (p<0.01), along with a greater number of inflammatory cells and ED1 mononuclear cells. CONCLUSION: Mice receiving an atherogenic diet develop heart failure and reduced survival rate. This is associated with cardiac remodeling with underlying apoptosis an ventricular wall fibrosis. It is posible that wall edema might contribute to the observed cardiac remodeling.

Animals , Mice , Ventricular Remodeling , Diet, Atherogenic , Heart Failure/etiology , Hyperlipidemias/pathology , Ischemia/etiology , Fibrosis , Survival Analysis , Ventricular Function, Left , Apoptosis , Mice, Knockout , Ventricular Dysfunction , Disease Models, Animal , Heart Failure/physiopathology , Heart Failure/mortality , Heart Failure/pathology , Ischemia/physiopathology , Ischemia/mortality , Ischemia/pathology
Acta cir. bras ; 35(5): e202000503, 2020. tab
Article in English | LILACS | ID: biblio-1130645


Abstract Purpose To investigate the effect of hyperbaric oxygen therapy on colonic anastomosis healing with and without ischemia in rats. Methods Forty female rats underwent segmental resection of 1 cm of the left colon followed by end-to-end anastomosis. They were randomly assigned to four groups (n=10 each), a sham group; two groups were submitted to Hyperbaric Oxygen therapy (HBOT) with and without induced ischemia and the induced ischemia group without HBOT. The HBOT protocol evaluated was 100% O2 at 2.4 Atmosphere absolute pressure (ATA) for 60 minutes, two sessions before as a preconditioning protocol and three sessions after the operation. Clinical course and mortality were monitored during all experiment and on the day of euthanasia on the fourth day after laparotomy. Macroscopic appearance of the abdominal cavity were assessed and samples for breaking strength of the anastomosis and histopathological parameters were collected. Results There was no statistically significant difference in mortality or anastomosis leak between the four experimental groups. Anastomosis breaking strength was similar across groups. Conclusion The HBOT protocol tested herein at 2.4 ATA did not affect histopathological and biomechanical parameters of colonic anastomotic healing, neither the clinical outcomes death and anastomosis leak on the fourth day after laparotomy.

Animals , Female , Wound Healing , Colon/surgery , Colon/blood supply , Ischemic Preconditioning/methods , Hyperbaric Oxygenation/methods , Ischemia/pathology , Postoperative Period , Rats, Inbred Lew , Time Factors , Severity of Illness Index , Anastomosis, Surgical , Reproducibility of Results , Treatment Outcome , Colon/pathology , Ischemia/prevention & control
Acta cir. bras ; 35(2): e202000205, 2020. graf
Article in English | LILACS | ID: biblio-1130618


Purpose To investigate the effects of induction of selective liver hypothermia in a rodent model. Methods Seven male Wistar rats were subjected to 90 minutes of partial 70% liver ischemia and topic liver 26°C hypothermia (H group). Other seven male Wistar rats were subjected to 90 minutes of partial 70% normothermic liver ischemia (N group). Five additional rats underwent a midline incision and section of liver ligaments under normothermic conditions and without any liver ischemia (sham group). All animals were sacrificed 24-h after reperfusion, and livers were sampled for analyses. Pathology sections were scored for sinusoidal congestion, ballooning, hepatocelllular necrosis and the presence of neutrophilic infiltrates. Results At the end of the experiment, liver tissue expressions of TNF-ɑ, IL-1β, iNOS and TNF-ɑ/IL-10 ratio were significantly reduced in the H group compared to N group, whereas IL-10 and eNOS were significantly increased in H group. Histopathological injury scores revealed a significant decrease in ischemia/reperfusion (I/R) injuries in H group. Conclusion Selective liver hypothermia prevented I/R injury by inhibiting the release of inflammatory cytokines, preserves microcirculation, prevents hepatocellular necrosis and leukocyte infiltration, allowing maintenance of the liver architecture.

Animals , Male , Rats , Reperfusion Injury/prevention & control , Acute Lung Injury/prevention & control , Hypothermia, Induced/methods , Liver/blood supply , Body Temperature , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Cytokines/metabolism , Tumor Necrosis Factor-alpha , Rats, Wistar , Inflammation Mediators/metabolism , Nitric Oxide Synthase/metabolism , Disease Models, Animal , Acute Lung Injury/pathology , Ischemia/pathology , Liver/pathology , Necrosis/pathology , Nitric Oxide/metabolism
Int. braz. j. urol ; 45(4): 754-762, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019881


ABSTRACT Purpose This study aimed to study morphological and renal structural changes in relation to different ischemic times and types of renal vascular pedicle clamping. Methods Sixteen pigs were divided into two groups (n = 8): Group AV - unilateral clamping of the renal artery and vein and Group A - unilateral clamping of the renal artery only, both with the contralateral kidney used as control. Serial biopsies were performed at 0, 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after clamping. Results there is a correlation between the occurrence of renal damage as a function of time (p <0.001), with a higher frequency of Group A lesions for cellular alterations (vascular congestion and edema, interstitial inflammatory infiltrate, interstitial hemorrhage and cell degeneration), with the exception of in the formation of pigmented cylinders that were evidenced only in the AV Group. Conclusion the number of lesions derived from ischemia is associated with the duration of the insult, there is a significant difference between the types of clamping, and the AV Group presented a lower frequency of injuries than Group A. The safety time found for Group A was 10 minutes and for Group AV 20 minutes.

Animals , Female , Renal Artery/pathology , Renal Veins/pathology , Ischemia/pathology , Kidney/blood supply , Kidney/pathology , Nephrectomy/methods , Reference Values , Swine , Time Factors , Biopsy , Reproducibility of Results , Constriction
Rev. Col. Bras. Cir ; 46(5): e20192260, 2019. tab, graf
Article in Portuguese | LILACS | ID: biblio-1057172


RESUMO Objetivo: avaliar o uso do curativo de filme e gel de biopolímero de celulose bacteriana no tratamento de pacientes com feridas isquêmicas submetidos à revascularização dos membros inferiores. Métodos: ensaio clínico randomizado realizado no ambulatório de Angiologia e Cirurgia Vascular do Hospital das Clínicas da Universidade Federal de Pernambuco, entre janeiro de 2017 e dezembro de 2018. Foram acompanhados 24 pacientes após revascularização de membros inferiores, divididos em dois grupos: Experimental, tratado com filme e gel de biopolímero de celulose bacteriana, e Controle, tratado com ácidos graxos essenciais. Os pacientes foram acompanhados em consultas semanais para troca dos curativos e o processo de cicatrização das feridas foi avaliado em um período de 90 dias. Resultados: a redução da área das feridas isquêmicas no período de 30 dias foi de 4,3cm2 (55%), em média, para o grupo experimental, e de 5,5cm2 (48,5%) para o grupo controle (p>0,05). A taxa de cicatrização completa, em 90 dias, foi de 34,8%, sendo 50% no grupo experimental e 18,2% no grupo controle (p=0,053). Conclusão: o filme de biopolímero de celulose bacteriana associada a gel pode ser utilizado como curativo no tratamento de feridas isquêmicas de pacientes submetidos à revascularização de membros inferiores

ABSTRACT Objective: to evaluate the use of a bacterial cellulose biopolymer film and gel dressing in the treatment of patients with ischemic wounds submitted to lower limb revascularization. Methods: we conducted a randomized clinical trial in the Angiology and Vascular Surgery outpatient clinic of the Clinics Hospital of the Federal University of Pernambuco, between January 2017 and December 2018. We followed 24 patients after lower limb revascularization, divided into two groups: Experimental, treated with bacterial cellulose biopolymer film and gel, and Control, treated with essential fatty acids. Patients attended weekly appointments to change dressings and had their wound healing processes evaluated over a period of 90 days. Results: the reduction of the ischemic wounds' areas after 30 days was 4.3cm2 (55%) on average for the experimental group, and the 5.5cm2 (48.5%) for the control group (p>0.05). The complete healing rate at 90 days was 34.8%, 50% in the experimental group and 18.2% in the control group (p=0.053). Conclusion: the bacterial cellulose biopolymer film associated with gel can be used as a dressing in the treatment of ischemic wounds of patients undergoing revascularization of the lower limbs.

Humans , Male , Female , Aged , Aged, 80 and over , Bandages , Wound Healing/drug effects , Biopolymers/therapeutic use , Cellulose/therapeutic use , Lower Extremity/pathology , Ischemia/complications , Ischemia/therapy , Time Factors , Treatment Outcome , Angioplasty , Lower Extremity/blood supply , Gels/therapeutic use , Ischemia/pathology , Middle Aged
Acta cir. bras ; 33(11): 964-974, Nov. 2018. tab, graf
Article in English | LILACS | ID: biblio-973473


Abstract Purpose: To evaluate the hepatic changes associated with gastric ischemia. Methods: Thirty male rabbits were studied, distributed in 3 groups (n=10). Group 1: ligature and section of the gastric vasculature and removal of the liver after three hours; Group 2: ligature and section of the gastric vasculature and removal of the liver after 6 hours; Group 3: ligature and section of the gastric vasculature and removal of the liver after 12 hours. Blood samples were collected immediately before surgery and after the determined time of ischemia in each group to evaluate the hepatic function. After the death of the rabbits, the liver was removed for macro and microscopic study. Results: An increase in aminotransferases and bilirubin occurred in groups 2 and 3. Total protein and albumin diminished in all of the animals. All of the rabbits from groups 2 and 3 presented hepatocellular necrosis. Conclusion: The devascularization of the stomach for a period of above three hours is associated with hepatic morphological and functional disorders.

Animals , Male , Rabbits , Stomach/blood supply , Stomach/pathology , Ischemia/complications , Liver/pathology , Aspartate Aminotransferases , Reference Values , Time Factors , Bilirubin/blood , Serum Albumin/analysis , Reperfusion Injury/pathology , Random Allocation , Alanine Transaminase , Alkaline Phosphatase , gamma-Glutamyltransferase , Ischemia/pathology , Liver/blood supply , Liver Diseases/etiology , Liver Diseases/pathology , Necrosis
Acta cir. bras ; 33(10): 924-934, Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-973470


Abstract Purpose: To develop a new 24 hour extended liver ischemia and reperfusion (LIR) model analyzing the late biochemical and histopathological results of the isolated and combined application of recognized hepatoprotective mechanisms. In addition, we used a new stratification with zoning to classify the histological lesion. Methods: A modified animal model of severe hepatic damage produced through 90 minutes of segmental ischemia (70% of the organ) and posterior observation for 24 hours of reperfusion, submitted to ischemic preconditioning (IPC) and topical hypothermia (TH) at 26ºC, in isolation or in combination, during the procedure. Data from intraoperative biometric parameters, besides of late biochemical markers and histopathological findings, both at 24 hours evolution time, were compared with control (C) and normothermic ischemia (NI) groups. Results: All groups were homogeneous with respect to intraoperative physiological parameters. There were no losses once the model was stablished. Animals subjected to NI and IPC had worse biochemical (gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, direct bilirubin, and total bilirubin) and histopathological scores (modified Suzuki score) compared to those of control groups and groups with isolated or associated TH (p < 0.05). Conclusion: The new extended model demonstrates liver ischemia and reperfusion at 24 hour of evolution and, in this extreme scenario, only the groups subjected to topical hypothermia, combined with ischemic preconditioning or alone, had better outcomes than those subjected to only ischemic preconditioning and normothermic ischemia, reaching similar biochemical and histopathological scores to those of the control group.

Animals , Male , Rats , Reperfusion Injury/pathology , Ischemic Preconditioning , Ischemia/pathology , Time Factors , Reperfusion Injury/etiology , Rats, Wistar , Disease Models, Animal , Hypothermia, Induced , Ischemia/etiology , Liver/physiopathology , Liver/blood supply , Liver/pathology
Rev. bras. cir. cardiovasc ; 33(2): 115-121, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-958394


Abstract Objective: The aim of the present study was to evaluate the ability of ischemic postconditioning, atorvastatin and both associated to prevent or minimize reperfusion injury in the lung of rats subjected to ischemia and reperfusion by abdominal aortic clamping. Methods: We used 41 Wistar norvegic rats, which were distributed into 5 groups: ischemia and reperfusion (I/R), ischemic postcondictioning (IPC), postconditioning + atorvastatin (IPC+A), atorvastatin (A) and SHAM. It was performed a medium laparotomy, dissection and isolation of the infra-renal abdominal aorta; except for the SHAM group, all the others were submitted to the aortic clamping for 70 minutes (ischemia) and posterior clamp removal (reperfusion, 70 minutes). In the IPC and IPC+A groups, postconditioning was performed between the ischemia and reperfusion phases by four cycles of reperfusion and ischemia lasting 30 seconds each. In the IPC+A and A groups, preceding the surgical procedure, administration of 3.4 mg/day of atorvastatin was performed for seven days by gavage. After the surgical procedure, the right caudal lobe was removed from the lung for histological study, using tissue injury score ranging from grade 1 (normal tissue) to grade 4 (intense lesion). Results: The mean lung injury was 3.6 in the I/R group, 1.6 in the IPC group, 1.2 in the IPC+A group, 1.2 in the A group, and 1 in the SHAM group (P<0.01). Conclusion: Ischemic postconditioning and atorvastatin were able to minimize lung reperfusion injury, alone or in combination.

Animals , Male , Reperfusion Injury/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Ischemic Postconditioning/methods , Atorvastatin/therapeutic use , Lung/blood supply , Aorta, Abdominal , Time Factors , Reperfusion Injury/pathology , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Combined Modality Therapy , Ischemia/pathology , Ischemia/prevention & control , Lung/pathology
Rev. Assoc. Med. Bras. (1992) ; 64(1): 22-31, Jan. 2018. tab, graf
Article in English | LILACS | ID: biblio-896419


Summary Objective: Ovarian torsion must be diagnosed and treated as early as possible. The aim of the present study was to investigate the effects of intraperitoneal administration of nanocurcumin on ischemia-reperfusion injury in ovaries. Method: Thirty-five (35) healthy female Wistar rats weighing approximately 250 g were randomized into seven experimental groups (n=5): Group SSG - The rats underwent only laparotomy. Group I: A 3-hour ischemia only. Group I/R: A 3-hour ischemia and 3-hour reperfusion. Group I/C: A 3-hour ischemia only, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion, and 1 mg/kg intraperitoneal administration of curcumin 2.5 hours after induction of ischemia. Group I/NC: A 3-hour ischemia only and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia. Group I/R/C: A 3-hour ischemia, 3-hour reperfusion and 1 mg/kg intraperitoneal administration of nanocurcumin 2.5 hours after induction of ischemia. Results: Nanocurcumin-treated animals showed significantly improved development of ischemia and reperfusion tissue injury compared to those in the other groups (p<0.05). Significant higher values of SOD, tGSH, GPO, GSHRd and GST were observed in I/R/NC animals compared to those in the other groups (p<0.05). The damage indicators (NOS, MDA, MPO and DNA damage level) were significantly lower in I/R/NC animal compared to those of other groups (p<0.05). Conclusion: Intraperitoneal administration of nanocurcumin can be helpful in minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia.

Humans , Animals , Female , Rats , Ovary/blood supply , Reperfusion Injury/drug therapy , Curcumin/administration & dosage , Nanoparticles/administration & dosage , Ischemia/drug therapy , Antioxidants/administration & dosage , Administration, Cutaneous , Reperfusion Injury/pathology , Rats, Wistar , Disease Models, Animal , Injections, Intraperitoneal , Ischemia/pathology
Acta cir. bras ; 31(11): 759-764, Nov. 2016. tab, graf
Article in English | LILACS | ID: biblio-827667


ABSTRACT PURPOSE: To analyze the influence of chlorpromazine on renal histology of rats submitted to ischemia and reperfusion injury. METHODS: Sixteen Wistar rats - split in two groups - have been used: control group, receiving 3 mg/kg isotonic saline solution through caudal vein, and, the chlorpromazine group, receiving 3 mg/kg-IV of such medication. The nephrectomy of the left kidney lower third was carried out; immediately, the test-drug was administrated. After 15 minutes of test-drug administration, the renal pedicle was clamped; in 60 minutes of ischemia it was released. After 24 hours of the renal reperfusion, the rats were, once more, anesthetized and submitted to total left nephrectomy, and, afterwards, to euthanasia. Histological findings regarding ischemia have been evaluated and compared between the groups. RESULTS: There was no statistical difference related to inferior renal pole histological analysis. Regarding 60-minute renal ischemia, chlorpromazine has statistically reduced the accrual of leucocytes within the vasa recta renis (p=0.036) and the congestion of peritubular capillaries (p=0.041). When conducting joint analysis of histological patterns, the control group showed a median score of 11 and chlorpromazine group of 5.5 (p=0.036). CONCLUSION: Chlorpromazine significantly reduced the occurrence of secondary damage to ischemia and reperfusion process in the overall histological analysis.

Animals , Male , Rats , Reperfusion Injury/pathology , Chlorpromazine/pharmacology , Ischemic Preconditioning/methods , Kidney/blood supply , Kidney Diseases/pathology , Rats, Wistar , Disease Models, Animal , Ischemia/pathology , Kidney/pathology
Int. braz. j. urol ; 42(5): 1028-1032, Sept.-Oct. 2016. graf
Article in English | LILACS | ID: lil-796899


ABSTRACT Report case (s) relevant aspects: Man, 27 years old, complaining of acute testicular pain by 2 hours in the remaining left testicle. Denies fever, lower urinary tract symptoms such as dysuria, urinary frequency, concommitant or prior urethral discharge to the painful condition. He underwent right orchiectomy 13 years ago by testicular torsion. He is a chronic user of cocaine for 15 years and during the last three days the drug use was continuous and intense. Proposed premise substantiating case (s) description: Initial diagnostic hypothesis: Syndromic: Acute Scrotum Syndrome (SEA) Main Etiologic (testicular torsion) Secondary Etiologic (acute orchiepididymitis) Briefly delineates what might it add? Lines of research That Could be Addressed: In this challenging clinical case we presented an alternative and new etiologic diangosis for the acute scrotum which the main etiologic factor remains testicular torsion. This new diangosis is acute testicular ischemia as a complication of cocaine abuse.

Humans , Male , Adult , Scrotum/blood supply , Testicular Diseases/etiology , Testis/blood supply , Cocaine-Related Disorders/complications , Acute Pain/etiology , Ischemia/etiology , Scrotum/pathology , Spermatic Cord Torsion/pathology , Testicular Diseases/pathology , Testis/pathology , Vasoconstrictor Agents/poisoning , Cocaine/poisoning , Diagnosis, Differential , Ischemia/pathology
Clinics ; 71(7): 412-419, graf
Article in English | LILACS | ID: lil-787431


OBJECTIVES: Necrotizing enterocolitis is a severe multifactorial intestinal disorder that primarily affects preterm newborns, causing 20-40% mortality and morbidity. Intestinal fatty acid-binding protein has been reported to be a biomarker for the detection of intestinal injuries. Our aim was to assess intestinal tissue injury and the molecular expression of intestinal fatty acid-binding protein over time in a necrotizing enterocolitis model. METHODS: A total of 144 Newborn rats were divided into two groups: 1) Control, which received breastfeeding (n=72) and 2) Necrotizing Enterocolitis, which received formula feeding and underwent hypoxia and hypothermia (n=72). A total of six time points of ischemia (2 times a day for 3 days; 12 pups for each time point) were examined. Samples were collected for analysis of body weight, morphological and histological characteristics, intestinal weight, intestinal weight/body weight ratio, injury grade, and intestinal fatty acid-binding protein levels. RESULTS: Body and intestinal weights were lower in the Necrotizing Enterocolitis group than in the Control group (p<0.005 and p<0.0005, respectively). The intestinal weight/body weight ratio was higher in the Necrotizing Enterocolitis group than in the Control group (p<0.005) only at the sixth ischemia time point. The Necrotizing Enterocolitis group displayed higher expression of intestinal fatty acid-binding protein (p<0.0005) and showed greater tissue damage than the Control group. CONCLUSION: Intestinal fatty acid-binding protein was an efficient marker of ischemic injury to the intestine and a good correlation was demonstrated between the time of ischemic injury and the grade of intestinal injury.

Animals , Enterocolitis, Necrotizing/metabolism , Enterocolitis, Necrotizing/pathology , Fatty Acid-Binding Proteins/metabolism , Ileum/pathology , Reference Values , Time Factors , Severity of Illness Index , Body Weight , Immunohistochemistry , Biomarkers/analysis , Random Allocation , Blotting, Western , Rats, Sprague-Dawley , Disease Models, Animal , Fatty Acid-Binding Proteins/analysis , Ileum/blood supply , Ischemia/pathology , Animals, Newborn , Hypoxia/pathology
Int. j. morphol ; 33(4): 1313-1318, Dec. 2015. ilus
Article in English | LILACS | ID: lil-772314


The purpose of this study, ischemia reperfusion injury in rats, Potentilla fulgens is to investigate the protective effects. Wistar albino rats (n= 30) weighing 180-220 g were used in the experiment. Group 1 animals underwent sham laparotomy without ischemia-reperfusion injury. Group 2 animals underwent laparotomy and occlusion of superior mesenteric arteries for 30 min followed by 20 min of reperfusion without pretreatment. The Potentilla fulgens group received 400 mg/kg/day Potentilla fulgens intraperitoneally 5 days before Ischemia-reperfusion injury. There was a significant difference between the group with ischemia-reperfusion group Potentilla fulgens (p<0.0001). In statistical analysis of the MDA level, data were obtained after a respective measurement in all groups. Potentilla fulgens group with ischemia-reperfusion group was a significant decrease in MDA (p<0.001). In the period after ischemia-reperfusion, marked PCNA immunoreactivities were observed in the nuclei of crypt and villus cell. In ischemia reperfusion group, the number of PCNA immunoreactivity is quite advanced and they extended throughout the middle part of the intestine folds. The number of TUNEL-positive nuclei were also developed. In ischemia-reperfusion plus P. fulgens group, the intestinal epithelium with only a few PCNA immunoreactive nuclei. TUNEL positive nuclei were noted in the gut lumen and mucosal close differentiated goblet cells. We showed that Potentilla fulgens extract significantly prevented mucosal lesions caused by intestinal ischemia-reperfusion.

El objetivo fue investigar los efectos protectores de Potentilla fulgens sobre la lesión por isquemia-reperfusión en ratas albinas Wistar (n= 30) con un peso de 180 g. En el grupo 1, los animales fueron sometidos a laparotomía simulada sin lesión por isquemia-reperfusión. En el Grupo 2, los animales fueron sometidos a laparotomía y oclusión de las arteria mesentérica superior durante 30 min seguido de 20 min de reperfusión sin pretratamiento. El grupo Potentilla fulgens recibió 400 mg/kg/día de P. fulgens por vía intraperitoneal 5 días antes de la lesión por isquemia-reperfusión. Hubo diferencias significativas entre el grupo de grupo con isquemia-reperfusión y el tratado con Potentilla fulgens (p<0,0001). En el análisis estadístico del nivel de malondialdehído (MDA), los datos se obtuvieron después de una medición respectiva en todos los grupos. Los grupos Potentilla fulgens y con isquemia-reperfusión tuvieron una disminución significativade MDA (p<0,0001). En el periodo después de la isquemia-reperfusión, se observó inmunorreactividad del marcador PCNA en los núcleos de las células de las criptas y vellosidades. En el grupo de isquemia-reperfusión, la inmunoreactividad a PCNA fue bastante avanzada y se extendió a lo largo de la parte media de los plieges intestinales. También aumentó el número de núcleos positivos a TUNEL. En el grupo isquemia-reperfusión tratado con P. fulgens, el epitelio intestinal mostró pocos núcleos inmunorreactivos a PCNA; núcleos positivos a TUNEL se observaron en el lumen intestinal y la mucosa, cerca de las células caliciformes diferenciadas. Demostramos que el extracto de P. fulgens disminuye significativamente lesiones de la mucosa intestinal causadas por la isquemia-reperfusión.

Animals , Rats , Intestines/drug effects , Ischemia/drug therapy , Plant Extracts/pharmacology , Potentilla/chemistry , Reperfusion Injury/drug therapy , Disease Models, Animal , In Situ Nick-End Labeling , Intestines/blood supply , Intestines/pathology , Ischemia/pathology , Proliferating Cell Nuclear Antigen , Rats, Wistar , Reperfusion Injury/pathology
J. vasc. bras ; 14(4): 305-310, out.-dez. 2015. tab
Article in English | LILACS | ID: lil-767708


Contexto A calcificação da camada média arterial pode tornar o Índice Tornozelo-Braquial (ITB) falsamente elevado em diabéticos, dificultando a avaliação da doença arterial. Objetivo Comparar os valores do ITB de diabéticos e não diabéticos com isquemia crítica. Métodos Foram incluídos 140 pacientes (60% de diabéticos) acompanhados no Serviço de Cirurgia Vascular do Complexo Hospitalar Universitário Professor Edgard Santos com isquemia crítica por DAOP infra-inguinal. Comparou-se a média dos valores do ITB dos dois grupos de pacientes, correlacionando o ITB com a gravidade da isquemia, segundo a Classificação de Rutherford. A análise estatística foi realizada pelo EPI-INFO. Resultados A maioria dos 140 pacientes (77%) se encontrava na Categoria 5 da Classificação de Rutherford, 6% na 4 e 17% na 6. Nove diabéticos (11%) e um não diabético (2%) apresentaram ITB > 1,15 (p = 0,02), sendo excluídos da análise das médias do ITB. Considerando os 130 pacientes, os 75 doentes diabéticos apresentaram média do ITB na artéria tibial posterior de 0,26 versus 0,28 dos 55 doentes não diabéticos (p = 0,6); e no ITB da artéria pediosa aqueles apresentaram média de 0,32 versus 0,23 desses (p = 0,06). Estratificando os doentes nas categorias da Classificação de Rutherford, não houve diferença nas médias do ITB nas categorias 4 e 5. Apenas em relação à artéria pediosa e em pacientes na Categoria 6, a média do ITB foi significativamente maior em diabéticos (0,44 versus 0,16; p = 0,03). Conclusão Os diabéticos apresentaram maior prevalência de ITB falsamente elevado. Porém, excluindo-se esses casos, a média dos valores de ITB são semelhantes aos não diabéticos, exceto na artéria pediosa, nos pacientes com isquemia na categoria 6.

Calcification of the arterial tunica media can falsely elevate the Ankle-Brachial Index (ABI) in diabetics, making it difficult to assess arterial disease. Objective To compare ABI values in diabetics and non-diabetics with critical ischemia. Methods A total of 140 patients (60% diabetics) with critical ischemia due to infrainguinal peripheral arterial obstructive disease were recruited from the vascular surgery service at the Complexo Hospitalar Universitário Professor Edgard Santos. Mean ABI values for the two groups of patients were compared and correlated with severity of ischemia, according to the Rutherford Classification. Statistical analysis was conducted using EPI-INFO. Results A majority of the 140 patients (77%) were classified as Rutherford Category 5, 6% as Category 4 and 17% as Category 6. Nine diabetics (11%) and one non-diabetic (2%) exhibited ABI > 1.15 (p = 0.02) and were excluded from the comparative analysis of mean ABIs. For the 130-patient sample, the 75 diabetic patients had a mean ABI for the posterior tibial artery of 0.26, vs. 0.28 for the 55 non-diabetic patients (p = 0.6); while mean ABIs for the dorsalis pedis artery were 0.32 vs. 0.23 respectively (p = 0.06). When the patients were stratified by Rutherford categories, there were no differences in mean ABIs in categories 4 or 5. Only mean ABI for the dorsalis pedis artery in Category 6 patients was significantly higher among diabetics (0.44 vs. 0.16; p = 0.03). Conclusions The diabetic patients had a higher prevalence of falsely elevated ABI, but when these cases were excluded, mean ABI values were similar to those of non-diabetic patients, with the exception of ABI measured at the dorsalis pedis artery in patients with category 6 ischemia.

Humans , Atherosclerosis/complications , Diabetes Mellitus/metabolism , Ischemia/pathology , Ankle Brachial Index/methods , Prevalence , Retrospective Studies
Acta cir. bras ; 30(11): 756-761, Nov. 2015. graf
Article in English | LILACS | ID: lil-767601


PURPOSE: To investigate the effects of remifentanil as an antioxidant and analyze the histopathologic, biochemical changes in experimental ischemia-reperfusion (I/R) exposed rat uteri. METHODS: Wistar albino rats were assigned to three groups (n = 7). 2h period of ischemia was followed by 1h of reperfusion in the I/R and the I/R-remifentanil groups. After ischemia, no drug was administered in the sham and I/R groups. In the I/R-remifentanil group, remifentanil infusion (2 μg/kg/min) was started in the ischemia period, and continued until the end of reperfusion. After the ischemic and reperfusion period, the ischemic uterine horns were removed surgically for biochemical and histopathologic examination. Tissue damage scores (endometrial epithelial glandular leukocytosis, degeneration, and endometrial stromal changes) were examined. Malondialdehyde levels and catalase, superoxide dismutase enzyme activities in tissue were measured. RESULTS: We found significantly lower epithelial leukocytosis and cell degeneration in the I/R-remifentanil group (p<0.05). Remifentanil administration significantly decreased concentrations of malondialdehyde, and increased catalase and superoxide dismutase enzyme activities (p<0.05). CONCLUSION: Remifentanil appears to protect the uterine tissue against ischemia-reperfusion and can be used safely in uterus transplantation.

Animals , Female , Analgesics, Opioid/pharmacology , Ischemia/prevention & control , Piperidines/pharmacology , Reperfusion Injury/prevention & control , Uterus/blood supply , Antioxidants/pharmacology , Catalase/drug effects , Ischemia/pathology , Malondialdehyde/analysis , Random Allocation , Rats, Wistar , Reproducibility of Results , Reperfusion Injury/pathology , Superoxide Dismutase/drug effects , Time Factors , Uterus/pathology
Acta cir. bras ; 30(11): 749-755, Nov. 2015. tab, graf
Article in English | LILACS | ID: lil-767602


PURPOSE: To evaluate the underlying mechanisms by which sevoflurane protects the liver against ischemia/reperfusion injury evaluate the mechanism by which sevoflurane exerts this protective effect. METHODS: Twenty-six rats were subjected to partial ischemia/reperfusion injury for 1h: one group received no treatment, one group received sevoflurane, and sham group of animals received laparotomy only. Four hours after reperfusion, levels of alanine and aspartate aminotransferases, tumor necrosis factor-a, and interleukins 6 and 10 were measured. Analyses of mitochondrial oxidation and phosphorylation, malondialdehyde content, histology, and pulmonary vascular permeability were performed. RESULTS: Serum levels of alanine and aspartate aminotransferases were significantly lower in the sevoflurane group compared to untreated controls (p<0.05). The sevoflurane group also showed preservation of liver mitochondrial function compared to untreated controls (p<0.05). Sevoflurane administration did not alter increases in serum levels of tumor necrosis factor-a, and interleukins 6 and 10. Sevoflurane treatment significantly reduced the coagulative necrosis induced by ischemia/reperfusion (p<0.05). Pulmonary vascular permeability was preserved in the sevoflurane group compared to untreated controls. CONCLUSION: Sevoflurane administration protects the liver against ischemia/reperfusion injury, via preservation of mitochondrial function, and also preserves lung vascular permeability.

Animals , Male , Anesthetics, Inhalation/pharmacology , Ischemia/prevention & control , Liver/blood supply , Methyl Ethers/pharmacology , Mitochondria, Liver/drug effects , Reperfusion Injury/prevention & control , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Capillary Permeability/drug effects , Cytokines/blood , Ischemia/pathology , Lipid Peroxidation , Liver/pathology , Mitochondria, Liver/physiology , Necrosis , Phosphorylation , Rats, Wistar , Reproducibility of Results , Reperfusion Injury/pathology , Time Factors
ABCD arq. bras. cir. dig ; 28(3): 167-170, July-Sept. 2015. tab, graf
Article in English | LILACS | ID: lil-762819


BACKGROUND: Despite the rich vascular arcade of the stomach, gastric ischemia represents an important medical challenge and can be the consequence of obstructive or non-obstructive vascular processes of pathological or iatrogenic origin.AIM: To assess the effects of acute gastric ischaemia on the different regions of the stomach.METHOD: Fifteen New Zeland rabbits were divided into three groups: group 1, animals were observed during 3 h; group 2, during 6 h; group 3, during 12 h. Rabbit stomachs were subjected to devascularization of the greater and lesser curvatures. After predetermined time, the stomachs were removed for macro and microscopic studies.RESULTS: Haemorrhagic necrosis was more marked in the gastric fundus and body. In contrast, the antropylorus remained preserved in 80% of the animals. Necrosis of the gastric body and fundus mucosa were observed in all animals after 6 h and 12 h of ischaemia.CONCLUSION: Acute gastric ischaemia in rabbits produces haemorrhagic necrosis of the gastric fundus and body even in a short period of time. Beside this, the antropyloric region was significantly more resistant to ischaemia.

RACIONAL: Isquemia gástrica representa importante desafio médico e geralmente é decorrente de processos vasculares obstrutivos ou não-obstrutivos. Apesar da rica arcada vascular do estômago, lesões de isquemia gástrica têm sido observadas. Quando a isquemia progride, pode culminar em necrose do órgão.OBJETIVO: Avaliar os efeitos dos diferentes tempos de isquemia gástrica sobre os tecidos da parede do estômago de coelhos mediante desvascularização total de ambas as curvaturas gástricas.MÉTODO: Foram utilizados 15 coelhos machos da raça Nova Zelândia. Os animais foram distribuídos nos seguintes grupos: grupo 1, observados por 3 h; grupo 2, por 6 h; grupo 3, por 12 h. A técnica cirúrgica foi a mesma em todos os animais e consistiu na ligadura e secção de todas as veias e artérias da parede gástrica. Após o período pré-determinado de observação, o estômago foi removido por completo para estudo macro e microscópico.RESULTADOS: As alterações macroscópicas e histológicas tornaram-se mais intensas com o aumento do tempo de isquemia e foram mais evidentes nas regiões do fundo e do corpo. Por outro lado, o antro manteve-se preservado na maioria dos animais operados. Necrose de mucosa do corpo e do fundo foi observada em todos os animais estudados, e foi acompanhada por hemorragia em 60% dos coelhos dos grupos 2 e 3.CONCLUSÃO: O modelo experimental de isquemia gástrica foi eficaz para produzir necrose hemorrágica de fundo e corpo do estômago de coelhos mesmo em curto tempo. Por outro lado, a região do antro pilórico desses animais mostrou-se significativamente mais resistente à isquemia do que as demais regiões.

Animals , Male , Rabbits , Ischemia/pathology , Stomach/blood supply , Stomach/pathology , Acute Disease , Tissue Survival
Acta cir. bras ; 30(6): 414-421, 06/2015. tab, graf
Article in English | LILACS | ID: lil-749644


PURPOSE: To investigate the protective effect of dexmedetomidine (Dex) on testicular damage induced by ischemia-reperfusion injury in rats. METHODS: Sham group underwent left scrotal exploration only (group 1). The ischemia-reperfusion only group underwent left testicular torsion and detorsion (group 2). The ischemia-reperfusion plus Dex group underwent left testicular torsion, received 50 µg/kg Dex (group 3) and 100 µg/kg Dex (group 4) intraperitoneally at minute 180 of ischemia and then underwent detorsion. We determined histopathological findings and performed specific biochemical analyses. RESULTS: Increasing doses of Dex significantly increased TAS, and significantly decreased OSI. Analyzing the antioxidant effects of increasing doses of Dex in torsion and contrlateral testicles: Dex 100 µg/kg statistically significant increased the tissue total antioxidant status (TAS) and oxidative stress index (OSI) when compared with Dex 50 µg/kg but not found significantly change on the tissue total oxidant status (TOS). However, Dex did not significantly improve these histological alterations. CONCLUSION: The antioxidant effects of dexmedetomidine on testicular ischemia-reperfusion injury in ipsilateral and contrlateral testis, but in the histopathological level, there was no difference statistically according to Johnsen's scoring system between groups at both sides. .

Animals , Male , /pharmacology , Antioxidants/pharmacology , Dexmedetomidine/pharmacology , Reperfusion Injury/prevention & control , Spermatic Cord Torsion/prevention & control , Testis/blood supply , /therapeutic use , Dexmedetomidine/therapeutic use , Immunohistochemistry , Ischemia/pathology , Ischemia/prevention & control , Oxidative Stress/drug effects , Prospective Studies , Random Allocation , Rats, Wistar , Reference Values , Reperfusion Injury/pathology , Severity of Illness Index , Spermatic Cord Torsion/pathology , Time Factors , Testis/pathology
Braz. j. pharm. sci ; 51(1): 127-141, Jan-Mar/2015. graf
Article in English | LILACS | ID: lil-751371


Tetramethylpyrazine (TMP), a major active ingredient of Ligusticum wallichi Franchat extract (a Chinese herb), exhibits neuroprotective properties in ischemia. In this study, we assessed its protective effects on Schwann cells (SCs) by culturing them in the presence of oxygen glucose deprivation (OGD) conditions and measuring cell survival in cold ischemic rat nerves. In the OGD-induced ischemic injury model of SCs, we demonstrated that TMP treatment not only reduced OGD-induced cell viability losses, cell death, and apoptosis of SCs in a dose-dependent manner, and inhibited LDH release, but also suppressed OGD-induced downregulation of Bcl-2 and upregulation of Bax and caspase-3, as well as inhibited the consequent activation of caspase-3. In the cold ischemic nerve model, we found that prolonged cold ischemic exposure for four weeks was markedly associated with the absence of SCs, a decrease in cell viability, and apoptosis in preserved nerve segments incubated in University of Wisconsin solution (UWS) alone. However, TMP attenuated nerve segment damage by preserving SCs and antagonizing the decrease in nerve fiber viability and increase in TUNEL-positive cells in a dose-dependent manner. Collectively, our results indicate that TMP not only provides protective effects in an ischemia-like injury model of cultured rat SCs by regulating Bcl-2, Bax, and caspase-3, but also increases cell survival and suppresses apoptosis in the cold ischemic nerve model after prolonged ischemic exposure for four weeks. Therefore, TMP may be a novel and effective therapeutic strategy for preventing peripheral nervous system ischemic diseases and improving peripheral nerve storage.

Tetrametilpirazina (TMP), o principal componente do extrato de Ligusticum wallichi Franchat (erva chinesa), apresenta propriedades neuroprotetoras na isquemia. Nesse estudo, avaliamos seus efeitos protetores nas células de Schwann (SC), cultivando-as na presença de condições de depleção de oxigênio da glicose (OGD) e medindo a sobrevivência dos nervos de ratos isquêmicos pelo resfriamento. No modelo de lesão isquêmica em SC induzida por OGD, demonstramos que o tratamento com TMP não somente reduziu as perdas de viabilidade celular induzida por OGD, a morte celular, a apoptose de SC dose-dependente e inibiu a liberação de LDH, mas, também, suprimiu a infra-regulação do Vcl-2 e a supra-regulação de Bax e caspase-3, e inibiu a consequente ativação da caspase-3. No modelo de nervo isquêmico por resfriamento, observamos que a exposição prolongada ao resfriamento por quatro semanas estava, marcadamente, associada com a ausência de SC, com o decréscimo da viabilidade celular e a apoptose em segmentos de nervo incubados na solução da Universidade de Wisconsin apenas. Entretanto, a TMP atenuou o dano no segmento do nervo preservando SC e antagonizando a diminuição da viabilidade da fibra nervosa e o aumento das células TUNEL-positiva de modo dose-dependente. De forma conjunta, nossos resultados indicam que o TMP não só fornece efeitos protetores em um modelo de dano semelhante à isquemia de SC de ratos cultivados pela regulação de BCl-2, Bax e caspase 3, mas, também, aumenta a sobrevivência celular e suprime a apoptose no modelo de isquemia por resfriamento por exposição prolongada por quatro semanas. Então, TMP pode ser uma estratégia terapêutica eficaz para prevenir doenças isquêmicas do sistema nervoso periférico e melhora a armazenagem do nervo periférico.

Ischemia/pathology , Rats , Schwann Cells/classification , Thymidine Monophosphate/analysis , Peripheral Nerve Injuries/prevention & control , Peripheral Nervous System