Effects of local and remote ischemic postconditioning methods on ischemiareperfusion injury in a young animal model of acute mesenteric ischemia

Purpose: Acute mesenteric ischemia (AMI) is a condition in pediatric surgery that ranges from intestine necrosis to death. Ischemic postconditioning (IPoC) methods were developed to reduce the damage caused by revascularization. This study aimed to evaluate the efficacy of these methods in an experimental weaning rat model. Methods: Thirty-two 21-day-old Wistar rats were allocated into four groups according to the surgical procedure performed: control, ischemia-reperfusion injury (IRI), local (LIPoC) and remote IPoC (RIPoC). At euthanasia, fragments of the intestine, liver, lungs, and kidneys were submitted to histological, histomorphometric, and molecular analyses. Results: In the duodenum, intestines, and kidneys histological alterations promoted by IRI were reversed by remote postconditioning method. In the distal ileum, the histomorphometric alterations could be reversed by the postconditioning methods with more evident effects promoted by the remote method. The molecular analysis found that the levels of expression of Bax (proapoptotic) and Bcl-XL (antiapoptotic) genes in the intestine were increased by IRI. These alterations were equally reversed by the postconditioning methods, with more evident effects of the remote method. Conclusions: IPoC methods positively reduced the damage caused by IRI in weaning rats.

Reperfusion Strategies in Acute Myocardial Infarction: State of the Art

Abstract ST elevation myocardial infarction (STEMI) is a highly prevalent condition worldwide. Reperfusion therapy is strongly associated with the prognosis of STEMI and must be performed with a high standard of quality and without delay. A systematic review of different reperfusion strategies for STEMI was conducted, including randomized controlled trials that included major cardiovascular events (MACE), and systematic reviews in the last 5 years through the PRISMA ( Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology. The research was done in the PubMed and Cochrane Central Register of Controlled Trials databases, in addition to a few manual searches. After the exclusion criteria were applied, 90 articles were selected for this review. Despite the reestablishment of IRA patency in PCI for STEMI, microvascular lesions occur in a significant proportion of these patients, which can compromise ventricular function and clinical course. Several therapeutic strategies - intracoronary administration of nicorandil, nitrates, melatonin, antioxidant drugs (quercetin, glutathione), anti-inflammatory substances (tocilizumab [an inhibitor of interleukin 6], inclacumab, P-selectin inhibitor), immunosuppressants (cyclosporine), erythropoietin and ischemic pre- and post-conditioning and stem cell therapy - have been tested to reduce reperfusion injury, ventricular remodeling and serious cardiovascular events, with heterogeneous results: These therapies need confirmation in larger studies to be implemented in clinical practice

Protective effects of ischemic postconditioning on skeletal muscle following crush syndrome in the rat

ABSTRACT Purpose To investigate the effect of ischemic postconditioning (IPostC) on skeletal muscle and its optimal protocol. Methods This article is about an animal study of rat model of crush syndrome. Sixty rats were randomized into nine different IPostC intervention groups and a control group. The anesthetized rats were subjected to unilateral hindlimb 3-kg compression with a compression device for 6 h, followed by nine different IPostC intervention protocols. Results Serum levels of creatine kinase (CK) at 3 h post-crush became 2.3-3.9 times among all 10 groups after crush. At 72 h post-crush, serum CK level was reduced to 0.28-0.53 time in all intervention groups. The creatinine (CREA) level in the control group was elevated to 3.11 times at 3 h post-crush and reduced to1.77 time at 72 h post-crush. The potassium (K+) level in the control group was elevated to 1.65 and 1.41 time at 3 and 72 h post-crush, respectively. Conclusions Our IPostC intervention protocols can effectively protect rats from crush-induced elevation of serum CK, CREA, and K+ levels. The timing of IPostC intervention should be as early as possible, to ensure the protective effect.

Comparison of remote and local postconditioning against hepatic ischemic-reperfusion injury in rats

ABSTRACT Purpose: The aim of this study is to compare the hepatic protective effect of both remote and local postconditioning (POS). Methods: Twenty-eight Wistar rats were assigned into four groups: sham group(SHAM), ischemia-reperfusion group (IR), local ischemic POS group (lPOS) and remote ischemic POS group (rPOS). Animals were subjected to liver ischemia for 30 min. Local ischemic POS group consisted of four cycles of 5 min liver ischemia, followed by 5 min reperfusion (40 min). Remote ischemic POS group consisted of four cycles of 5 min hind limb ischemia, followed by 5 min hind limb perfusion after the main liver ischemia period. After 190 minutes median and left liver lobes were harvested for biochemical and histopathology analysis. Results: All the conditioning techniques were able to increase the level of bothglutathione reductase and peroxidase, showing higher values in the rPOS group when compared to the lPOS. Also, thiobarbituric acid reactive substances were higher in all intervention groups when compared to SHAM, but rPOS had the lower rates of increase, showing the best result. The histopathology analysis showed that all groups had worst injury levels than SHAM, but rPOS had lower degrees of damage when compared to the lPOS, although it was not statistically significant. Conclusion: Remote postconditioning is a promising technique to reduce liver ischemia-reperfusion injury, once it increased antioxidants substances and reduced the damage.

Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation

Abstract Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.

Role of adiponectin in diabetes myocardial ischemia-reperfusion injury and ischemic postconditioning

Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P <0.05). IPO significantly attenuated myocardial injury and up-regulated plasma APN content and cardiac p-Akt expression in non-diabetic rats but not in diabetic rats. Linear correlation analysis showed that the expression of adiponectin was positively correlated with p-Akt and negatively correlated with myocardial infarction area ( P <0.01). Conclusion Protective effect of IPO was tightly correlated with the expression of adiponectin, exacerbation of I/R injury and ineffectiveness of IPO was partially due to the decline of adiponectin and inactivation of Akt in diabetes mellitus.

Beneficios perioperatorios por condicionamiento isquémico a distancia en la revascularización coronaria / Perioperative benefits of distant ischemic conditioning in coronary revascularization

Introducción: Una serie de breves periodos de isquemias a distancia pueden limitar el daño miocárdico producido por la isquemia/reperfusión. Objetivo: Analizar las diferencias entre los dos grupos (control y estudio) teniendo en cuanta el consumo de inotrópicos y/o vasopresores durante los períodos intra y posoperatorio, así como, incidencia de eventos adversos cardiacos mayores y mortalidad en el postoperatorio. Métodos: Se realizó un estudio cuasiexperimental, explicativo, comparativo con control histórico, en dos grupos de 247 pacientes, propuestos para revascularización coronaria. Se colocó un torniquete en el brazo derecho, en el grupo estudio, alternando 3 insuflaciones con 3 desinsuflaciones con una presión de 200 mmHg, manteniéndola 5 min cada una. Este proceder se realizó previo, durante y después del evento isquémico mayor, provocado por el pinzamiento de la arteria coronaria. Resultados: Se logró una disminución significativa del consumo de drogas inotrópicas y vasoactivas. Se comprobó además, la disminución en la incidencia de bajo gasto cardiaco reversible, fibrilación ventricular, nuevo infarto agudo de miocardio. Conclusiones: El condicionamiento isquémico a distancia es una importante herramienta a tener en cuenta para la protección cardiaca perioperatoria en la revascularización coronaria(AU)

Introduction: A series of brief distant ischemia periods can limit myocardial damage produced by ischemia or reperfusion. Objective: To analyze the differences between the two groups (control and study) taking into account the consumption of inotropics and/or vasopressors during the intraoperative and postoperative periods, as well as the incidence of major cardiac adverse events and mortality in the postoperative period. Methods: A quasiexperimental, explanatory and comparative study with historical control was conducted on two groups of 247 patients proposed for coronary revascularization. A tourniquet was placed to the right arm, in the study group, alternating three insufflations with three dessufflations with a pressure of 200 mmHg, keeping each for five minutes. This procedure was performed before, during and after the major ischemic event, caused by pinching of the coronary artery. Results: A significant decrease in the consumption of inotropic and vasoactive drugs was achieved. The decrease in the incidence of low reversible cardiac output, ventricular fibrillation, and new acute myocardial infarction was also proven. Conclusions: Distant ischemic conditioning is an important tool to be taken into account for perioperative cardiac protection in coronary revascularization(AU)

Regular transient limb ischemia prevents atherosclerosis progression in hypercholesterolemic rabbits / 中华医学杂志(英文版)

BACKGROUND@#Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits.@*METHODS@#Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test.@*RESULTS@#Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049).@*CONCLUSION@#In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.

Garlicin Post-Conditioning Suppresses Adhesion Molecules in a Porcine Model of Myocardial Ischemia-Reperfusion Injury / 中国结合医学杂志

OBJECTIVES@#To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction (AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31).@*METHODS@#Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin (1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion.@*RESULTS@#Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflflow area (P<0.05 respectively).@*CONCLUSIONS@#Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the mRNA expression of CD29 and CD31.

Ischemic postconditioning improves longitudinal contractile function of the reperfused myocardium in patients with anterior wall acute myocardial infarction / 中南大学学报(医学版)

To investigate whether ischemic postconditioning (IPTC) can promote the recovery of left ventricular impaired regional or global longitudinal systolic function.
 Methods: The trial was divided into a percutaneous coronary intervention (PCI) group, an PCI+IPTC group and a control group. Thirty-two patients with anterior acute anterior wall ST-segment elevation myocardial infarction (STEMI) underwent the first emergency PCI in the PCI group, 28 patients with anterior acute STEMI underwent the combination of PCI and IPTC in the PCI+IPTC group, while 30 patients underwent coronary angiography in the control group. Two-dimensional dynamic echocardiography was collected before operation, 0.5 h, 1 day, 3 days, 1 week, 1 month and 6 months after operation, respectively. The longitudinal strain parameters at different time points were analyzed and compared in the 3 groups.
 Results: The regional longitudinal strain of infracted segments in the PCI+IPTC group after the operation within 1 week was higher than that in the PCI group (P0.05). There was no significant difference in the long-term regional and global longitudinal strains of left ventricle between the PCI+IPTC group and the PCI group (both P>0.05).
 Conclusion: The IPTC can improve the short-term longitudinal systolic function of the reperfused myocardium in patients with acute anterior wall STEMI after PCI.

Cardioprotective effect of preconditioning is more efficient than postconditioning in rats submitted to cardiac ischemia and reperfusion

Abstract Purpose: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. Methods: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis. Results: After reestablishment of coronary blood flow, we observed variations of the ECG trace with increased incidence of ventricular arrhythmia (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%) in cardiac I/R group. The comparison between I/R + preIC group with I/R group demonstrated significant reduction in VA incidence to 28%, AVB to 0% and lethality to 14%. The comparison of I/R + postIC group with I/R group was observed significance reduction in AVB incidence to 25% and lethality to 25%. Conclusion: The preconditioning strategies produce cardioprotection more efficient that postconditioning against myocardial dysfunctions and lethality by cardiac ischemia and reperfusion.

Effect of ischemic postconditioning and atorvastatin in the prevention of remote lung reperfusion injury

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.

Evaluation of the effects of atorvastatin and ischemic postconditioning preventing on the ischemia and reperfusion injury: experimental study in rats

Abstract Introduction: Reperfusion injury leads to systemic morphological and functional pathological alterations. Some techniques are already estabilished to attenuate the damage induced by reperfusion. Ischemic preconditioning is one of the standard procedures. In the last 20 years, several experimental trials demonstrated that the ischemic postconditioning presents similar effectiveness. Recently experimental trials demonstrated that statins could be used as pharmacological preconditioning. Methods: 41 Wistar rats (Rattus norvegicus albinus) were distributed in 5 groups: Ischemia and Reperfusion (A), Ischemic Postconditioning (B), Statin (C), Ischemic Postconditioning + Statins (D) and SHAM (E). After euthanasia, lungs, liver, kidneys and ileum were resected and submitted to histopathological analysis. Results: The average of lung parenchymal injury was A=3.6, B=1.6, C=1.2, D=1.2, E=1 (P=0.0029). The average of liver parenchymal injury was A=3, B=1.5, C=1.2, D=1.2, E = 0 (P<0.0001). The average of renal parenchymal injury was A=4, B=2.44, C=1.22, D=1.11, E=1 (P<0.0001). The average of intestinal parenchymal injury was A=2, B=0.66, C=0, D=0, E=0 (P=0.0006). The results were submitted to statistics applying Kruskal-Wallis test, estabilishing level of significance P<0.05. Conclusion: Groups submitted to ischemic postconditioning, to pre-treatment with statins and both methods associated demonstrated less remote reperfusion injuries, compared to the group submitted to ischemia and reperfusion without protection.

Diverse Ischemic Postconditioning Protocols Affect the Infarction Size in Focal Ischemic Stroke

OBJECTIVE: Ischemic postconditioning (IPostC), consisted of transient brain ischemia/reperfusion cycles, is considered to have neuroprotective effect. However, there is no best single protocol of IPostC, because varied factors like species tested and characteristics of the tissue may affect the efficacy of IPostC. Thus, we investgated whether different protocols of IPostC affect neuroprotective effects in experimental animal models. MATERIALS AND METHODS: Through occlusion of middle cerebral artery (MCA) with intraluminal suture, stroke was induced in a transient focal ischemia model in mice. We conducted IPostC via brief and repeated MCA occlusion, 2 minutes after reperfusion, followed by different ischemia and reperfusion protocols. After procedure, functional neurological score and histological examination were evaluated. RESULTS: IPostC with different protocols resulted in diverse effects. Among them, a protocol that consists of 3 cycle of IPostC significantly reduced the infarction size 3 days after stroke. CONCLUSION: IPostC was confirmed to reduce infarction size. The effects of IPostC are definitely affected by differences in the protocol used, including the number of cycles, the duration of individual ischemia/reperfusion episode and the entire duration of the IPostC stimuli.

Remote Ischemic Postconditioning for Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中华医学杂志(英文版)

<p><b>Background</b>Remote ischemic postconditioning (RIPostC) appears to protect distant organs from ischemia-reperfusion injury (IRI). However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC.</p><p><b>Methods</b>CNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated.</p><p><b>Results</b>A total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks (RR = 0.37; 95% CI: 0.26-0.55; P < 0.00001). Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score (MD: 1.96; 95% CI: 2.18-1.75; P < 0.00001), modified Rankin Scale score (MD: 0.73; 95% CI: 1.20-0.25; P = 0.00300), and high-sensitivity C-reactive protein (MD: 4.17; 95% CI: 4.71-3.62; P < 0.00001) between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration.</p><p><b>Conclusion</b>The present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI.</p>

Effect of postconditioning and atorvastatin in preventing remote intestinal reperfusion injury / Efeito do pós-condicionamento e da atorvastatina na prevenção de lesão de reperfusão intestinal remota

ABSTRACT Objective: To evaluate the capacity of ischemic postconditioning and atorvastatin in prevent or minimize reperfusion injury in small bowel of rats subjected to ischemia and reperfusion by abdominal aorta clamping. Methods: 41 Wistar norvegic rats were distributed into 5 groups: ischemia and reperfusion, ischemic postconditioning, postconditioning + statin, statin and Sham. After anesthesia, laparotomy and dissection of the infra-renal abdominal aorta were performed; except the Sham group, all others were subjected to aorta clamping for 70 min (ischemia) and withdrawal of clamp for 70 min (reperfusion). In the IPC and IPC + S groups, four cycles of postconditioning were performed between the phases of ischemia and reperfusion lasting 30 s each. In IPC + S and S groups, 3.4 mg/day of atorvastatin was given for seven days per gavage; 1 cm of the ileum were removed for histological study and the results were subjected to statistical treatment considering significant p < 0.05. Results: The average of intestinal lesion was 2 in the I/R group, 0.66 in the IPC group, 0 in the IPC + S group, 0 in the S group, and 0 in the SHAM group. Conclusion: The ischemic postconditioning and atorvastatin were capable of minimizing intestinal reperfusion injury, either alone or in combination.

RESUMO Objetivo: Avaliar a capacidade do pós-condicionamento isquêmico e da atorvastatina para prevenir ou minimizar a lesão de reperfusão no intestino Delgado de ratos submetidos à isquemia e reperfusão por pinçamento de aorta abdominal. Métodos: 41 ratos noruegueses Wistar foram distribuídos em 5 grupos: isquemia e reperfusão, pós-condicionamento isquêmico, pós-condicionamento + estatina, estatina e simulacro. Depois da anestesia, procedeu-se à laparotomia e dissecação da aorta abdominal infrarrenal; exceto no grupo de simulacro, todos os demais grupos foram submetidos ao pinçamento da aorta durante 70 minutos (isquemia) e à retirada do pinçamento também durante 70 minutos (reperfusão). Nos grupos PCI e PCI + E, foram efetuados quatro ciclos de pós-condicionamento entre as fases de isquemia e de reperfusão, com duração de 30 segundos cada. Nos grupos PCI + E e E, foram administrados 3,4 mg/dia de atorvastatina durante 7 dias por gavagem; procedemos à remoção de 1 cm do íleo para o estudo histológico, e os resultados foram estatisticamente tratados. Consideramos p < 0,05 como estatisticamente significativo. Resultados: As médias para as lesões intestinais foram 2 no grupo I/R, 0,66 no grupo PCI, 0 no grupo PCI + E, 0 no grupo E, e 0 no grupo S. Conclusão: O procedimento de pós-condicionamento e atorvastatina demonstraram capacidade de minimizar a lesão de reperfusão intestinal, tanto isoladamente como em conjunto.

Atorvastatin can prevent hepatic remote reperfusion injury / Atorvastatina é capaz de prevenir a lesão de reperfusão remota no fígado

ABSTRACT Background: Some studies have shown that statins have a promising effect on protection against reperfusion injury. Aim: To evaluate the ability of ischemic postconditioning, statins and both associated to prevent or minimize reperfusion injury in the liver of rats subjected to ischemia and reperfusion by abdominal aorta clamping. Method: Were used 41 Wistar rats, which were distributed into five groups: ischemia and reperfusion (I/R), ischemic postcondictioning (IPC), postconditioning + statin (IPC+S), statin (S) and Sham. It was performed a medium laparotomy, dissection and isolation of the infra-renal abdominal aorta; excepting Sham group, all the others were submitted to the aorta clamping for 70 min (ischemia) and posterior clamping removing (reperfusion, 70 min). In the IPC and IPC+S groups, postconditioning was performed between the ischemia and reperfusion phases by four cycles of reperfusion and ischemia lasting 30 s each. In IPC+S and S groups, preceding the surgical procedure, administration of 3.4 mg/day of atorvastatin was performed for seven days by gavage. The left hepatic lobe was removed for histological study and euthanasia was performed. Results: The mean hepatic injury was 3 in the I/R group, 1.5 in the IPC group, 1.2 in the IPC+S group, 1.2 in the S group, and 0 in the SHAM group. The I/R group had a higher degree of tissue injury compared to the others in the statistical analysis and there was no difference between the others (p<0.01). Conclusion: Ischemic postconditioning and atorvastatin were able to minimize hepatic reperfusion injury, either alone or in combination.

RESUMO Racional: Alguns estudos têm demonstrado que as estatinas apresentam efeito promissor contra a lesão de reperfusão. Objetivo: Avaliar a capacidade do pós-condicionamento, estatina e ambos associados em prevenir ou minimizar a lesão de reperfusão à distância no fígado em ratos submetidos à isquemia e reperfusão por clampeamento aórtico. Método: Foram utilizados 41 ratos Wistar distribuídos em cinco grupos: isquemia e reperfusão (I/R), pós-condicionamento isquêmico (PCI), pós-condicionamento + estatina (PCI+E), estatina (E) e SHAM. Os animais foram anestesiados, submetidos à laparotomia, dissecção e isolamento da aorta abdominal infrarrenal; exceto o grupo SHAM, todos os outros foram submetidos ao clampeamento aórtico por 70 min (isquemia) e posterior retirada do clampe (reperfusão). Nos grupos PCI e PCI+E o pós-condicionamento foi realizado entre as fases de isquemia e reperfusão por quatro ciclos de reperfusão e isquemia durando 30 s cada. Nos grupos PCI+E e E, previamente ao procedimento cirúrgico foi realizada a administração de 3,4 mg/dia de atorvastatina durante sete dias por gavagem. Resultados: A média de lesão hepática foi 3 no grupo I/R, 1,5 no grupo PCI, 1,2 no grupo PCI+E, 1,2 no grupo E e 0 no grupo SHAM. O grupo I/R teve maior grau de lesão tecidual (p<0,01). Conclusão: O pós-condicionamento isquêmico e atorvastatina foram capazes de minimizar a lesão hepática de reperfusão remota, isoladamente e em associação.

The influence of allopurinol and post-conditioning on lung injuries induced by lower-limb ischemia and reperfusion in Wistar rats

Abstract Purpose: To analyze the effects of allopurinol and of post-conditioning on lung injuries induced by lower-limb ischemia and reperfusion. Methods: Thirty rats were used. They were divided in 5 groups: (1) group A: abdominal aortic dissection only, (2) group B: ischemia and reperfusion, (3) group C: administered allopurinol (100mg/Kg) a few hours before procedure, (4) group D: post-conditioned and (5) group E: administered allopurinol and post-conditioned. With the exception of group A, all groups were submitted to infrarenal aortic ischemia for 2 hours, and reperfusion for 72 hours. After euthanasia, lungs were removed for histological analysis. They were graded under two scores: pulmonary injury (neutrophil infiltration, interstitial edema, vascular congestion, and destruction of lung architecture) and lymphocytic score (neutrophil infiltration, lymphoid aggregate and secondary follicle). Results: On the pulmonary injury score, the degree of injury was smaller than in groups D and E, when compared to group B, p<0.05. Group C did not obtain the same result (p>0,05). On the lymphocytic score, there was no statistic difference among groups, p>0.05. Conclusion: Both post-conditioning and the combination of allopurinol and post-conditioning were effective in remote lung protection induced by lower-limbs I/R. When used in isolation, allopurinol showed no protective effect.

Perconditioning combined with postconditioning on kidney ischemia and reperfusion

Abstract Purpose: To evaluate if combination of perconditioning and postconditioning provides improved renal protection compared to perconditioning alone in a model of renal reperfusion injury. Methods: Thirty rats were assigned into 6 groups: normality; sham; ischemia and reperfusion; postconditioning; perconditioning; perconditioning + postconditioning. Animals were subjected to right nephrectomy and left renal ischemia for 30 minutes. Postconditioning consisted of 3 cycles of 5 min renal perfusion followed by 5 min of renal ischemia after major ischemic period. Perconditioning consisted of 3 cycles of 5 min hindlimb ischemia followed by 5 min of hindlimb perfusion contemporaneously to renal major ischemic period. After 24 hours, kidney was harvested and blood collected to measure urea and creatinine. Results: Perconditioning obtained better values for creatinine and urea level than only postconditioning (p<0.01); performing both techniques contemporaneously had no increased results (p>0.05). Regarding tissue structure, perconditioning was the only technique to protect the glomerulus and tubules (p<0.05), while postconditioning protected only the glomerulus (p<0.05). Combination of both techniques shows no effect on glomerulus or tubules (p>0.05). Conclusions: Perconditioning had promising results on ischemia and reperfusion induced kidney injury, enhanced kidney function and protected glomerulus and tubules. There was no additive protection when postconditioning and perconditioning were combined.