Blood pressure targets after successful reperfusion in mechanical thrombectomy for acute ischemic stroke: an updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: This study sought to determine whether intensive blood pressure (BP) control for patients with successful reperfusion following acute ischemic stroke (AIS) is beneficial, compared to conventional BP management. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) on the subject. The studied outcomes included dependency or death at 90 days (modified Rankin Scale [mRS] 3-6); severe disability at 90 days (mRS 3-5); mortality at 90 days; and symptomatic intracranial hemorrhage. Odds ratios (OR) with 95% confidence intervals were used to compare the treatment effects for categorical outcomes. We employed a fixed-effect model for analyses with low heterogeneity (I2 < 25%) and a random-effects model for analyses with higher heterogeneity. RESULTS: A total of 1519 patients were included, with 50% (n = 760) receiving intensive BP control (systolic BP < 140 mmHg). Functional disability or death at 90 days was significantly higher in the intensive group (54.9%) compared to the conventional treatment group (44.1%) (OR = 1.51; 95% Confidence Interval [CI]: 1.15-1.96; p = 0.003; I2 = 29%). Severe functional disability (mRS 3-5) was significantly higher in the intensive group (30.6% vs. 43.5%, OR = 1.75; 95%CI = 1.36-2.25; p < 0.0001; I2 = 0%). There was no difference in symptomatic intracranial hemorrhage (OR = 1.13; 95%CI = 0.76-1.67) or mortality (OR = 1.22; 95%CI = 0.9-1.64). CONCLUSIONS: Intensive BP control is harmful in patients who underwent EVT for AIS and achieved successful reperfusion. It yields higher rates of functional dependence, with no differences in mortality or symptomatic intracranial hemorrhage.

Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling.

BACKGROUND: Acute renal failure (ARF) following renal ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown. METHODS: We examined intracellular Ca2+ dynamics in adult ventricular cardiomyocytes isolated from C57BL/6 mice 7 or 15 days following unilateral renal I/R. RESULTS: After 7 days of I/R, the cell contraction was significantly lower in cardiomyocytes compared to sham-treated mice. It was accompanied by a significant decrease in both systolic Ca2+ transients and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) activity measured as Ca2+ transients decay. Moreover, the incidence of pro-arrhythmic events, measured as the number of Ca2+ sparks, waves or automatic Ca2+ transients, was greater in cardiomyocytes from mice 7 days after I/R than from sham-treated mice. Ca2+ mishandling related to systolic Ca2+ transients and contraction were recovered to sham values 15 days after I/R, but Ca2+ sparks frequency and arrhythmic events remained elevated. CONCLUSIONS: Renal I/R injury causes a cardiomyocyte Ca2+ cycle dysfunction at medium (contraction-relaxation dysfunction) and long term (Ca2+ leak), after 7 and 15 days of renal reperfusion, respectively.

Device size selection can enhance Y-stentrieving efficacy and safety as a rescue strategy in stroke thrombectomy.

BACKGROUND: Despite advancements in stroke treatment, refractory clots are relatively common, prompting the exploration of alternative techniques. Bifurcation occlusions pose specific intraprocedural challenges, occasionally dealt with by two stentrievers deployed in Y-configuration. Previous studies have portrayed this strategy as feasible, yet little is known about its safety and efficacy, and how to best select retrievers. OBJECTIVE: To determine whether device selection influences the efficacy and safety of Y-stentrieving. METHODS: We performed a multicentric, retrospective analysis of patients undergoing Y-stentrieving rescue for bifurcation occlusions. Demographics, devices, procedural metrics, neurological severity, reperfusion, disability, and safety were assessed. RESULTS: Y-configuration stents were used as a rescue maneuver after 2.16±1.5 failed attempts with other techniques in 20 patients. Successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3) was achieved in 70% of patients after the first Y-stentrieving attempt. The first stentriever more often had a larger diameter (5.15±0.92 vs 3.67±0.57 mm, p=0.017) and longer length (33.12±5.78 vs 20.67±1.15 mm, p=0.002) in successfully reperfused cases. Also, the diameter of the first device was associated with both any parenchymal (6.0 vs 4.71±0.99 mm, p=0.045) and symptomatic (6.0 vs 4.86±1.02 mm, p<0.001) hemorrhages. Exact logistic regression demonstrated that a longer length first stentriever independently predicted better angiographic outcomes (OR=1.26, p=0.036), and a 6 mm diameter first stentriever independently predicted more intracranial hemorrhages (OR=15.28, p=0.044). No periprocedural mortality was recorded. CONCLUSION: Y-stentrieving is an effective and safe bail-out strategy for refractory bifurcation clots. Longer stents may promote better angiographic outcomes, whereas avoidance of disproportionately large retrievers may mitigate intracranial hemorrhage. Future studies should account for these factors when evaluating alternative stentriever techniques.

Evaluation of pharmacoinvasive strategy versus percutaneous coronary intervention in patients with acute myocardial infarction with ST-segment elevation at the National Institute of Cardiology (PHASE-MX).

Objective: The objective of PHASE-MX registry is to validate the efficacy and safety of the pharmacoinvasive strategy in comparison with percutaneous coronary intervention (PCI) in patients with acute myocardial infarction with ST segment elevation (STEMI) in a metropolitan region of Mexico. The primary outcome will consist of the composite of cardiovascular death, re-infarction, stroke and cardiogenic shock. Methods: The PHASE-MX registry will include a prospective cohort of patients with STEMI who received reperfusion treatment (mechanical of pharmacological) in the first 12 h after the onset of symptoms. The registry is designed to compare the efficacy and safety of primary PCI and pharmacoinvasive strategy. The simple size was calculated in 344 patients divided into two groups, with an estimated loss rate of 10%. Patients included in the PHASE-MX cohort will be followed for up to one year. Conclusion: In Mexico, only 5 out of 10 patients with STEMI have access to reperfusion therapy. Pharmacoinvasive strategy is takes advantage of the accessibility of fibrinolysis and the effectiveness of PCI. The present research protocol aims to provide information that serves as a link between information derived from controlled clinical trials and records derived from real world experience.

Objetivo: El objetivo del registro PHASE-MX es validar la eficacia y seguridad de la estrategia farmacoinvasiva en comparación con la angioplastia coronaria transluminal percutánea primaria (ACTPp) en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en una región metropolitana de México. El desenlace primario es el compuesto de muerte cardiovascular, reinfarto, accidente vascular cerebral y choque cardiogénico. Métodos: El registro PHASE-MX es una cohorte prospectiva de pacientes con IAMCEST que recibieron tratamiento de reperfusión (mecánico o farmacológico) en las primeras 12 horas desde el inicio de los síntomas, atendidos en el Instituto Nacional de Cardiología Ignacio Chávez. El análisis estadístico se basa en la no inferioridad de la estrategia farmacoinvasiva en comparación con la ACTPp. Se calcula un tamaño de muestra de 344 pacientes divididos en dos grupos (angioplastia primaria y estrategia farmacoinvasiva), considerada una tasa de pérdidas de 10%. Los pacientes incluidos en la cohorte PHASE-MX se seguirán durante un año. Discusión: En México, sólo 5 de cada 10 pacientes con IAMCEST tienen acceso al tratamiento de reperfusión. La estrategia farmacoinvasiva aprovecha la accesibilidad de la fibrinólisis y la efectividad de la ACTPp, por lo que podría resultar el método de elección en el tratamiento del IAMCEST en la mayoría de los casos. El presente protocolo de investigación pretende aportar información que sirva como enlace entre la información derivada de los estudios clínicos controlados y los registros derivados de la experiencia del mundo real.

Evaluation of pharmacoinvasive strategy versus percutaneous coronary intervention in patients with acute myocardial infarction with ST-segment elevation at the National Institute of Cardiology (PHASE-MX) / Evaluación de la estrategia farmacoinvasiva versus angioplastia coronaria transluminal percutánea primaria en pacientes con infarto agudo de miocardio con elevación del segmento ST en el Instituto Nacional de Cardiología (PHASE-MX)

Abstract Objective: The objective of PHASE-MX registry is to validate the efficacy and safety of the pharmacoinvasive strategy in comparison with percutaneous coronary intervention (PCI) in patients with acute myocardial infarction with ST segment elevation (STEMI) in a metropolitan region of Mexico. The primary outcome will consist of the composite of cardiovascular death, re-infarction, stroke and cardiogenic shock. Methods: The PHASE-MX registry will include a prospective cohort of patients with STEMI who received reperfusion treatment (mechanical of pharmacological) in the first 12 h after the onset of symptoms. The registry is designed to compare the efficacy and safety of primary PCI and pharmacoinvasive strategy. The simple size was calculated in 344 patients divided into two groups, with an estimated loss rate of 10%. Patients included in the PHASE-MX cohort will be followed for up to one year. Conclusion: In Mexico, only 5 out of 10 patients with STEMI have access to reperfusion therapy. Pharmacoinvasive strategy is takes advantage of the accessibility of fibrinolysis and the effectiveness of PCI. The present research protocol aims to provide information that serves as a link between information derived from controlled clinical trials and records derived from real world experience.

Resumen Objetivo: El objetivo del registro PHASE-MX es validar la eficacia y seguridad de la estrategia farmacoinvasiva en comparación con la angioplastia coronaria transluminal percutánea primaria (ACTPp) en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en una región metropolitana de México. El desenlace primario es el compuesto de muerte cardiovascular, reinfarto, accidente vascular cerebral y choque cardiogénico. Métodos: El registro PHASE-MX es una cohorte prospectiva de pacientes con IAMCEST que recibieron tratamiento de reperfusión (mecánico o farmacológico) en las primeras 12 horas desde el inicio de los síntomas, atendidos en el Instituto Nacional de Cardiología Ignacio Chávez. El análisis estadístico se basa en la no inferioridad de la estrategia farmacoinvasiva en comparación con la ACTPp. Se calcula un tamaño de muestra de 344 pacientes divididos en dos grupos (angioplastia primaria y estrategia farmacoinvasiva), considerada una tasa de pérdidas de 10%. Los pacientes incluidos en la cohorte PHASE-MX se seguirán durante un año. Discusión: En México, sólo 5 de cada 10 pacientes con IAMCEST tienen acceso al tratamiento de reperfusión. La estrategia farmacoinvasiva aprovecha la accesibilidad de la fibrinólisis y la efectividad de la ACTPp, por lo que podría resultar el método de elección en el tratamiento del IAMCEST en la mayoría de los casos. El presente protocolo de investigación pretende aportar información que sirva como enlace entre la información derivada de los estudios clínicos controlados y los registros derivados de la experiencia del mundo real.

Evaluation of pharmacoinvasive strategy versus percutaneous coronary intervention in patients with acute myocardial infarction with ST segment elevation at the National Institute of Cardiology (PHASE-MX).

Objective: The objective of PHASE-MX registry is to validate the efficacy and safety of the pharmacoinvasive strategy in comparison with percutaneous coronary intervention (PCI) in patients with acute myocardial infarction with ST segment elevation (STEMI) in a metropolitan region of Mexico. The primary outcome will consist of the composite of cardiovascular death, re-infarction, stroke and cardiogenic shock. Methods: The PHASE-MX registry will include a prospective cohort of patients with STEMI who received reperfusion treatment (mechanical of pharmacological) in the first 12 h after the onset of symptoms. The registry is designed to compare the efficacy and safety of primary PCI and pharmacoinvasive strategy. The simple size was calculated in 344 patients divided into two groups, with an estimated loss rate of 10%. Patients included in the PHASE-MX cohort will be followed for up to one year. Conclusion: In Mexico, only 5 out of 10 patients with STEMI have access to reperfusion therapy. Pharmacoinvasive strategy is takes advantage of the accessibility of fibrinolysis and the effectiveness of PCI. The present research protocol aims to provide information that serves as a link between information derived from controlled clinical trials and records derived from real world experience.

Objetivo: El objetivo del registro PHASE-MX es validar la eficacia y seguridad de la estrategia farmacoinvasiva en comparación con la angioplastia coronaria transluminal percutánea primaria (ACTPp) en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en una región metropolitana de México. El desenlace primario es el compuesto de muerte cardiovascular, reinfarto, accidente vascular cerebral y choque cardiogénico. Métodos: El registro PHASE-MX es una cohorte prospectiva de pacientes con IAMCEST que recibieron tratamiento de reperfusión (mecánico o farmacológico) en las primeras 12 horas desde el inicio de los síntomas, atendidos en el Instituto Nacional de Cardiología Ignacio Chávez. El análisis estadístico se basa en la no inferioridad de la estrategia farmacoinvasiva en comparación con la ACTPp. Se calcula un tamaño de muestra de 344 pacientes divididos en dos grupos (angioplastia primaria y estrategia farmacoinvasiva), considerada una tasa de pérdidas de 10%. Los pacientes incluidos en la cohorte PHASE-MX se seguirán durante un año. Discusión: En México, sólo 5 de cada 10 pacientes con IAMCEST tienen acceso al tratamiento de reperfusión. La estrategia farmacoinvasiva aprovecha la accesibilidad de la fibrinólisis y la efectividad de la ACTPp, por lo que podría resultar el método de elección en el tratamiento del IAMCEST en la mayoría de los casos. El presente protocolo de investigación pretende aportar información que sirva como enlace entre la información derivada de los estudios clínicos controlados y los registros derivados de la experiencia del mundo real.

Mechanical thrombectomy for reperfusion of acute ischemic stroke in a Stroke Unit in Argentina.

OBJECTIVE: Stroke is an important cause of morbidity and mortality worldwide. Reperfusion therapy with intravenous tissue plasminogen activator (IV-tPA) was first implemented in 1996. More recently, endovascular reperfusion with mechanical thrombectomy (MT) demonstrated a robust beneficial effect, extending the 4.5 h time window. In our country, there are difficulties to achieve the implementation of both procedures. Our purpose is to report the early experience of a Comprehensive Stroke Center in the use of MT for acute stroke. METHODS: Analysis of consecutive patients from January 2015 to September 2018, who received reperfusion treatment with MT. Demographic data, treatment times, previous use of IV-tPA, site of obstruction, recanalization, outcomes and disability after stroke were assessed. RESULTS: We admitted 891 patients with acute ischemic stroke during this period. Ninety-seven received IV-tPA (11%) and 27 were treated with MT (3%). In the MT group, mean age was 66.0±14.5 years. Median NIHSS before MT was 20 (range:14‒24). The most prevalent etiology was cardioembolic stroke (52%). Prior to MT, 16 of 27 patients (59%) received IV-tPA. Previous tPA treatment did not affect onset to recanalization time or door-to-puncture time. For MT, door-to-puncture time was 104±50 minutes and onset to recanalization was 289±153 minutes. Successful recanalization (mTICI grade 2b/3) was achieved in 21 patients (78%). At three-month follow-up, the median NIHSS was 5 (range:4‒15) and mRS was 0‒2 in 37%, and ≥3 in 63%. CONCLUSIONS: With adequate logistics and strict selection criteria, MT can be implemented in our population with results like those reported in large clinical trials.

Mechanical thrombectomy for reperfusion of acute ischemic stroke in a Stroke Unit in Argentina / Trombectomía mecánica para la reperfusión en el accidente cerebrovascular agudo en una Unidad Cerebrovascular de Argentina

Abstract Stroke is an important cause of morbidity and mortality worldwide. Reperfusion therapy with intravenous tissue plasminogen activator (IV-tPA) was first implemented in 1996. More recently, endovascular reperfusion with mechanical thrombectomy (MT) demonstrated a robust beneficial effect, extending the 4.5 h time window. In our country, there are difficulties to achieve the implementation of both procedures. Objective: Our purpose is to report the early experience of a Comprehensive Stroke Center in the use of MT for acute stroke. Methods: Analysis of consecutive patients from January 2015 to September 2018, who received reperfusion treatment with MT. Demographic data, treatment times, previous use of IV-tPA, site of obstruction, recanalization, outcomes and disability after stroke were assessed. Results: We admitted 891 patients with acute ischemic stroke during this period. Ninety-seven received IV-tPA (11%) and 27 were treated with MT (3%). In the MT group, mean age was 66.0±14.5 years. Median NIHSS before MT was 20 (range:14‒24). The most prevalent etiology was cardioembolic stroke (52%). Prior to MT, 16 of 27 patients (59%) received IV-tPA. Previous tPA treatment did not affect onset to recanalization time or door-to-puncture time. For MT, door-to-puncture time was 104±50 minutes and onset to recanalization was 289±153 minutes. Successful recanalization (mTICI grade 2b/3) was achieved in 21 patients (78%). At three-month follow-up, the median NIHSS was 5 (range:4‒15) and mRS was 0‒2 in 37%, and ≥3 in 63%. Conclusions: With adequate logistics and strict selection criteria, MT can be implemented in our population with results like those reported in large clinical trials.

Resumen El accidente cerebrovascular isquémico (ACVi) es una importante causa de morbi-mortalidad a nivel mundial. La reperfusión con trombólisis endovenosa es utilizada desde 1996. Más recientemente, la reperfusión con trombectomía mecánica (TM) ha demostrado un beneficio consistente extendiendo la ventana terapéutica. En nuestro país existen dificultades para que su implementación sea una práctica habitual. Objetivo: Reportamos la experiencia de un Centro Integral de Neurología Vascular en el uso de TM como tratamiento del ACVi agudo. Métodos: Análisis retrospectivo de pacientes consecutivos desde enero 2015 a septiembre 2018, que recibieron reperfusión con TM. Se registraron datos demográficos, tiempos de tratamiento, uso de rtPA, sitio de obstrucción, recanalización, severidad del evento y discapacidad. Resultados: Se evaluaron 891 pacientes con ACVi en este periodo. 97 recibieron rtPA (11%) y 27 recibieron TM (3%). En el grupo TM, la edad promedio fue 66 años (±14.5). Mediana de NIHSS previo a TM: 20 (RIC 14‒24). La etiología más frecuente fue cardioembolia (52%). Previo a TM, 16 pacientes (59%) recibieron rtPA endovenoso. No hallamos efecto del rtPA en tiempo de recanalización por TM o tiempo puerta-punción. Para la TM, el tiempo puerta-punción fue 104±50 minutos y el tiempo entre inicio de síntomas-recanalización fue 289±153 minutos. En 21 pacientes (78%) se logró recanalización exitosa (TICI 2B/3). En el seguimiento a tres meses, el mRS fue 0‒2 en el 37% y ≥3 en el 63%. Conclusión: Una logística adecuada y un estricto criterio de selección ha posibilitado el uso de TM en nuestra población, obteniendo resultados similares a aquellos reportados en los estudios clínicos publicados.

Efeito da infusão da solução M& G na proteção do tecido renal de ratos Wistar submetidos a isquemia e reperfusão programada / Effect of infusion of M& G solution for protection of renal tissue in Wistar rats subjected to programmed ischemia-reperfusion

Resumo Contexto A isquemia e reperfusão (I/R) renal está envolvida diretamente com insuficiência renal aguda, ocorrendo em casos como infarto por embolização ou trombose, quadros de septicemia e transplante renal. Esse processo é complexo, envolvendo respostas imunes inatas e adaptativas, presença de infiltrado celular, produção e liberação de citocinas e quimiocinas. Também desencadeia respostas celulares e liberação de espécies reativas de oxigênio, além de resultar em apoptose e, em alguns casos, necrose celular. Nesse contexto, é imprescindível a avaliação dos mecanismos de proteção ao tecido renal. Objetivos O objetivo foi testar a solução desenvolvida M&G, avaliando sua capacidade protetora no rim por meio de análise morfométrica e presença e expressão de citocinas inflamatórias (TNF-alfa, VEGF, HIF e IL-8). Métodos Foram selecionados 18 ratos Wistar, divididos em três grupos: Sham (S), Controle (C) e Estudo (E). O grupo S foi submetido ao processo cirúrgico sem o clampeamento arterial. No grupo C, foi clampeada a aorta acima e abaixo da artéria renal esquerda, sem a infusão de solução preservadora. No grupo E, além do clampeamento, realizou-se a punção da aorta e a infusão contínua da solução M&G por 20 minutos a 15 °C. Realizou-se a avaliação morfológica e imuno-histoquímica com os marcadores. Resultados Identificaram-se diferenças morfológicas entre o grupo S comparado aos grupos C e E. Na análise dos marcadores, houve redução na intensidade de expressão do TNF e na expressão do VEGF no grupo E. Não houve diferenças com HIF e IL-8 entre os grupos. Conclusões A solução M&G apresentou redução da presença e expressão de TNF-alfa e tendência de redução do VEGF.

Abstract Background Renal ischemia-reperfusion (I/R) is directly associated with acute renal failure and can occur in conditions such as infarction caused by embolization or thrombosis, septicemia, and kidney transplantation. The process is complex, involving innate and adaptive immune responses, presence of cellular infiltrate, and production and release of cytokines and chemokines. It also triggers cell responses and release of reactive oxygen species, in addition to causing apoptosis and, in some cases, cell necrosis. Against this background, evaluation of renal tissue protection mechanisms is essential. Objectives The objective of this study was to test the M&G solution, developed in prior research, evaluating its capacity to protect the kidneys using morphometric analysis and by assaying the presence and expression of inflammatory cytokines (TNF-alpha, VEGF, HIF, and IL-8). Methods Eighteen Wistar rats were divided into three groups: Sham (S), Control (C), and Experimental (E). The S group underwent the surgical operation, but without arterial clamping. In group C, the aorta was clamped above and below the left renal artery, without infusion of the preservation solution. In group E, in addition to clamping, the aorta was punctured and M&G solution was infused continuously for 20 minutes at 15o C. Morphological analysis and immunohistochemical assessment of markers were then conducted. Results Morphological differences were identified in group S compared with groups C and E. Analysis of markers revealed reduced intensity of expression of TNF and of VEGF in group E. There were no differences in HIF or IL-8 between groups. Conclusions The M&G solution was associated with a reduction in presence and expression of TNF-alpha and a trend to reduced VEGF.

Splenic ischemic preconditioning attenuates oxidative stress induced by hepatic ischemia-reperfusion in rats

Purpose: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. Methods: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. Results: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH-Rd were significantly higher in sIPC group than in IRI group. Conclusion: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.(AU)

N-acetyl-l-cysteine exacerbates kidney dysfunction caused by a chronic high-sodium diet in renal ischemia and reperfusion rats.

AIMS: To investigate the effect of long-term N-acetyl-l-cysteine (NAC) treatment in Wistar rats subjected to renal ischemia and reperfusion (IR) and a chronic high­sodium diet (HSD). MAIN METHODS: Adult male Wistar rats received an HSD (8.0% NaCl) or a normal­sodium diet (NSD; 1.3% NaCl) and NAC (600 mg/L) or normal drinking water starting at 8 weeks of age. At 11 weeks of age, the rats from both diet and NAC or water treatment groups underwent renal IR or Sham surgery and were followed for 10 weeks. The study consisted of six animal groups: NSD + Sham + water; NSD + IR + water; NSD + IR + NAC; HSD + Sham + water; HSD + IR + water; and HSD + IR + NAC. KEY FINDINGS: Tail blood pressure (tBP) increased with IR and NAC treatment in the NSD group but not in the HSD group. The serum creatinine level was higher after NAC treatment in both diet groups, and creatinine clearance was decreased in only the HSD + IR + NAC group. Albuminuria increased in the HSD + IR + water group and decreased in the HSD + IR + NAC group. Kidney mass was increased in the HSD + IR group and decreased with NAC treatment. Renal fibrosis was prevented with NAC treatment and cardiac fibrosis was decreased with NAC treatment in the HSD + IR group. SIGNIFICANCE: NAC treatment promoted structural improvements, such as decreased albuminuria and fibrosis, in the kidney and heart. However, NAC could not recover kidney function or blood pressure from the effects of IR associated with an HSD. Therefore, in general, long-term NAC treatment is not effective and is deleterious to recovery of function after kidney injury.

α-lipoic acid reduces postreperfusion syndrome in human liver transplantation - a pilot study.

A double-blind randomized controlled trial was performed to compare the safety and efficacy of α-lipoic acid (ALA) in liver transplantation (LT). The grafts were randomized to receive ALA or placebo before the cold ischemia time. Furthermore, patients transplanted with the ALA-perfused graft received 600 mg of intravenous ALA, while patients with the nonperfused graft received the placebo just before graft reperfusion. Hepatic biopsy was performed 2 h postreperfusion. Blood samples were collected before, during and 1 and 2 days after reperfusion. Quantitative polymerase chain reaction (qPCR) analysis was performed on biopsies to assess genes involved in the response to hypoxia, apoptosis, cell growth, survival and proliferation, cytokine production and tissue damage protection. Nine of 40 patients developed postreperfusion syndrome (PRS), but seven of them belonged to the control group. There was a decrease in PHD2 and an increase in alpha subunit of hypoxia-inducible factor-1 (HIF-1α) and baculoviral IAP repeat containing 2 (Birc2) transcript levels in the biopsies from the ALA-treated versus the control group of patients. Additionally, plasma levels of alarmins were lower in ALA-treated patients than control patients, which suggests that ALA-treated grafts are less inflammatory than untreated grafts. These results showed that ALA is safe for use in LT, induces gene changes that protect against hypoxia and oxidative stress and reduces the appearance of PRS.

Predictors of Outcomes after Correction of Acute Type A Aortic Dissection under Moderate Hypothermic Circulatory Arrest and Antegrade Cerebral Perfusion.

INTRODUCTION: Hypothermic circulatory arrest is widely used for correction of acute type A aortic dissection pathology. We present our experience of 45 consecutive patients operated in our unit with bilateral antegrade cerebral perfusion and moderate hypothermic circulatory arrest. METHODS: Between January 2011 and April 2015, 45 consecutive patients were admitted for acute type A aortic dissection and operated emergently under moderate hypothermic circulatory arrest and bilateral antegrade cerebral perfusion. RESULTS: Mean age was 58±11.4 years old. Median circulatory arrest time was 41.5 (30-54) minutes while the 30-day mortality and postoperative permanent neurological deficits rates were 6.7% and 13.3%, respectively. Unadjusted analysis revealed that the factors associated with 30-day mortality were: preoperative hemodynamic instability (OR: 14.8, 95% CI: 2.41, 90.6, P=0.004); and postoperative requirement for open sternum management (OR: 5.0, 95% CI: 1.041, 24.02, P=0.044) while preoperative hemodynamic instability (OR: 8.8, 95% CI: 1.41, 54.9, P=0.02) and postoperative sepsis or multiple organ dysfunction (OR: 13.6, 95% CI: 2.1, 89.9, P=0.007) were correlated with neurological dysfunction. By multivariable logistic regression analysis, postoperative sepsis and multiple organ dysfunction independently predicted (OR: 15.9, 95% CI: 1.05, 96.4, P=0.045) the incidence of severe postoperative neurological complication. During median follow-up of 6 (2-12) months, the survival rate was 86.7%. CONCLUSION: Bilateral antegrade cerebral perfusion and direct carotid perfusion for cardiopulmonary bypass, in the surgical treatment for correction of acute aortic dissection type A, is a valuable technique with low 30-day mortality rate. However, postoperative severe neurological dysfunctions remain an issue that warrants further research.

Predictors of outcomes after correction of acute type a aortic dissection under moderate hypothermic circulatory arrest and antegrade cerebral perfusion

Abstract Introduction: Hypothermic circulatory arrest is widely used for correction of acute type A aortic dissection pathology. We present our experience of 45 consecutive patients operated in our unit with bilateral antegrade cerebral perfusion and moderate hypothermic circulatory arrest. Methods: Between January 2011 and April 2015, 45 consecutive patients were admitted for acute type A aortic dissection and operated emergently under moderate hypothermic circulatory arrest and bilateral antegrade cerebral perfusion. Results: Mean age was 58±11.4 years old. Median circulatory arrest time was 41.5 (30-54) minutes while the 30-day mortality and postoperative permanent neurological deficits rates were 6.7% and 13.3%, respectively. Unadjusted analysis revealed that the factors associated with 30-day mortality were: preoperative hemodynamic instability (OR: 14.8, 95% CI: 2.41, 90.6, P=0.004); and postoperative requirement for open sternum management (OR: 5.0, 95% CI: 1.041, 24.02, P=0.044) while preoperative hemodynamic instability (OR: 8.8, 95% CI: 1.41, 54.9, P=0.02) and postoperative sepsis or multiple organ dysfunction (OR: 13.6, 95% CI: 2.1, 89.9, P=0.007) were correlated with neurological dysfunction. By multivariable logistic regression analysis, postoperative sepsis and multiple organ dysfunction independently predicted (OR: 15.9, 95% CI: 1.05, 96.4, P=0.045) the incidence of severe postoperative neurological complication. During median follow-up of 6 (2-12) months, the survival rate was 86.7%. Conclusion: Bilateral antegrade cerebral perfusion and direct carotid perfusion for cardiopulmonary bypass, in the surgical treatment for correction of acute aortic dissection type A, is a valuable technique with low 30-day mortality rate. However, postoperative severe neurological dysfunctions remain an issue that warrants further research.

Cerebral microvascular dysfunction in metabolic syndrome is exacerbated by ischemia-reperfusion injury.

BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia. Microvascular dysfunction is an important feature underlying the pathophysiology of cerebrovascular diseases. In this study, we aimed to investigate the impacts of ischemia and reperfusion (IR) injury on the cerebral microvascular function of rats with high-fat diet-induced MetS. RESULTS: We examined Wistar rats fed a high-fat diet (HFD) or normal diet (CTL) for 20 weeks underwent 30 min of bilateral carotid artery occlusion followed by 1 h of reperfusion (IR) or sham surgery. Microvascular blood flow was evaluated on the parietal cortex surface through a cranial window by laser speckle contrast imaging, functional capillary density, endothelial function and endothelial-leukocyte interactions by intravital videomicroscopy. Lipid peroxidation was assessed by TBARs analysis, the expression of oxidative enzymes and inflammatory markers in the brain tissue was analyzed by real-time PCR. The cerebral IR in MetS animals induced a functional capillary rarefaction (HFD IR 117 ± 17 vs. CTL IR 224 ± 35 capillary/mm2; p < 0.05), blunted the endothelial response to acetylcholine (HFD IR -16.93% vs. CTL IR 16.19% from baseline inner diameter p < 0.05) and increased the endothelial-leukocyte interactions in the venules in the brain. The impact of ischemia on the cerebral microvascular blood flow was worsened in MetS animals, with a marked reduction of cerebral blood flow, exposing brain tissue to a higher state of hypoxia. CONCLUSIONS: Our results demonstrate that during ischemia and reperfusion, animals with MetS are more susceptible to alterations in the cerebral microcirculation involving endothelial dysfunction and oxidative stress events.

Isquemia e reperfusão por circulação retrógrada: estudo comparativo experimental / Ischemia and reperfusion by retrograde flow: experimental comparative study

Contexto: Isquemia crítica de membro inferior sem leito distal tem opções restritas para tratamento. Desviar o fluxo de maneira retrógrada através da circulação venosa é alternativa amparada em evidências de inúmeros trabalhos publicados. Objetivos: Comparar o comportamento de variáveis clínicas e laboratoriais em extremidades de suínos submetidas a isquemia e a isquemia com reperfusão por circulação retrógrada entre si e em relação e a um grupo controle. Métodos: Dez suínos foram separados em dois grupos. No grupo 1 (n=5), controle, avaliaram-se padrões fisiológicos de variáveis como fluxo ao Doppler, temperatura, gasometria, lactato, creatinoquinase (CK) e pressão arterial. No grupo 2 (n=5), após um período médio de isquemia de 27 minutos e 30 segundos, consequente à interrupção do fluxo nas artérias femorais, os animais foram submetidos a arterialização venosa no membro posterior esquerdo e a manutenção da isquemia no direito. As variáveis foram analisadas separadamente durante momentos 0, 2, 3, 4 e 6 horas após a reperfusão para efeito de comparação entre si e com o grupo controle. Resultados: A análise das variáveis mostrou, em ambos os procedimentos, queda de BE e pO2 , com elevação significativa de lactato e CK em relação ao grupo controle. Nos membros isquêmicos arterializados, encontramos fluxo ao Doppler e maiores pressões arteriais e temperaturas quando comparadas ao membro em isquemia. Conclusões: A análise comparativa das extremidades em isquemia e isquemia arterializada mostrou, em relação ao grupo controle, um quadro de acidose metabólica, com significativo aumento de lactato e CK, que sugerem dano celular e sinais de reperfusão retrógrada nas extremidades arterializadas

Background: There are few options for treating critical ischemia in limbs with no distal patency. Diverting flow through the venous circulation is an option supported by evidence from numerous published studies. Objectives: To compare the behavior of clinical and laboratory variables between the hind limbs of pigs subjected to ischemia and to ischemia with reperfusion by retrograde circulation and between these intervention groups and a control group. Methods: Ten pigs were divided into 2 groups. In group 1 (n=5), controls, patterns of physiological variables such as flow according to Doppler ultrasound, temperature, blood gas analysis results, lactate, creatine kinase, and blood pressure were evaluated. In group 2 (n=5), after an initial ischemia period with mean duration of 27 minutes and 30 seconds, provoked by interrupting flow through the femoral arteries, the animals were subjected to venous arterialization of the left hind limb while the right hind limb was maintained in ischemia. Variables were analyzed separately for each hind leg at 0, 2, 3, 4, and 6 hours after reperfusion and compared against each other and the control group. Results: Analysis of variables from both procedures showed decreases in BE and PO2 and significant increases in lactate and creatine kinase, in relation to the control group. In arterialized ischemic limbs, we observed flow on Doppler ultrasound, and arterial pressures and temperatures were higher than in the ischemic limbs. Conclusions: Comparative analysis of the extremities in ischemia and arterialized ischemia showed, in relation to the control group, metabolic acidosis with significant increases in lactate and creatine kinase, suggesting cellular damage, and there were signs of retrograde reperfusion in arterialized extremities.

DIFFERENT PROTOCOLS OF POSTCONDITIONING DOES NOT ATTENUATE MESENTERIC ISCHEMIA-REPERFUSION INJURY AFTER SHORT-TERM REPERFUSION.

Background: Mesenteric ischemia is a challenging diagnosis. Delay in diagnosis can lead to extent bowel necrosis and poor outcomes. Ischemia and reperfusion syndrome plays an important role in this scenario. Aim: To access effects of different post-conditioning cycles on mesenteric ischemia-reperfusion syndrome. Method: Twenty-five rats were assigned into five groups: Sham, used to establish normal parameters; control group, submitted to mesenteric ischemia for 30 min; in groups GP3, GP1 and GP30, ischemia was followed by post-conditioning protocol, which consisted of 1 cycle of 3 min (GP3), 3 cycles of 1 min (GP1) or 6 cycles of 30 s (GP30), respectively. Ileum samples were harvested after one hour of reperfusion. Intestinal mucosal injury was evaluated through histopathological analysis. Results: The average of mesenteric injury degree was 0 in the sham group, 3.6 in the control group, 3.4 in GP3, 3.2 in GP1, and 3.0 in GP30; villous length average was 161.59 in sham group, 136.27 in control group, 135.89 in GP3, 129.46 in GP1, and 135.18 in GP30. Was found significant difference between sham and other groups (p<0.05); however, there was no difference among post-conditioning groups. Conclusion: Post-conditioning adopted protocols were not able to protect intestinal mucosa integrity after mesenteric ischemia and short term reperfusion.

Racional: O desfecho satisfatório na abordagem cirúrgica da obesidade deve contemplar, além da perda de peso, alteração significativa nas comorbidades preexistentes e na qualidade de vida dos pacientes. Objetivo: Avaliar a qualidade de vida no pós-operatório tardio de pacientes submetidos à cirurgia de gastrectomia vertical por videolaparoscopia. Métodos: Foi aplicado o questionário "Bariatric Analysis and Reporting Outcome System" (BAROS) em pacientes submetidos à gastrectomia vertical por videolaparoscopia. Resultados: Foram avaliados 47 pacientes, entre 21 e 60 anos de idade. O IMC médio antes da operação era 43,06±5,87 kg/m². A média percentual de redução do excesso de peso após foi de 85,46±23,6%. A pontuação obtida pelos pacientes no questionário sobre a melhora na qualidade de vida evidenciou resultado excelente (36,17%), ótimo (40,43%), bom (21,28%) e razoável (2,13%). Houve melhora clínica após a operação em todas as comorbidades investigadas. Conclusão: A perda de peso foi fundamental para a melhoria na qualidade de vida e proporcionou resolução ou a melhora clínica em todas as comorbidades investigadas.

Later Evaluation of Ischemia and Reperfusion by the Pringle Maneuver in Wistar Rats, Demonstrating That Hepatic Lesions Can Be Reversible.

OBJECTIVE: There has been much research on hepatic ischemia and reperfusion by means of short or longer interruption of the portal triad. The aim of this work was to evaluate the mitochondrial respiratory activity and liver histology at 2 different times after the Pringle maneuver. METHODS: Twenty-eight male Wistar rats, weighing ∼308 g, with histologic and mitochondrial study: immediate ischemic group (IIG; 40 minutes; 9 animals) and late ischemic group (LIG; 28 days; 9 animals). The rats were anesthetized and underwent a U-incision in the abdomen. In a simulated operation, manipulation of the hepatic pedicle was performed (5 animals immediate [ISG] and 5 late [LSG]). The hepatic pedicle was clamped for 20 minutes of ischemia foloowed by 20 minutes of reperfusion. The animals were killed under anesthesia. RESULTS: Mitochondria when stimulated by adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone had a significant respiratory reduction (P < .001). The respiratory control ratio in the LIG was altered (P < .02) compared with IIG. In the resting state, there was no change in the velocity of respiration between ischemic groups. Histopathologic findings showed 55.5% sinusoidal dilatation in IIG and 66.6% in LIG; 77.7% ballooning in IIG and 55.5% in LIG; and 11.1% focal necrosis in both IIG and LIG. CONCLUSIONS: The oxidative phosphorylation system recovered with improvement in mitochondrial respiration; however, morphologic recovery was associated with the type and intensity of injury.

Mistura de Ácido Gálico e Ciclosporina e seus Efeitos sobre a Disfunção Cardíaca Induzida pela Isquemia / Reperfusão e Expressão de eNOS/iNOS / Gallic Acid and Cyclosporine Mixture and their Effects on Cardiac Dysfunction Induced by Ischemia/Reperfusion and eNOS/iNOS Expression

Fundamento: Embora muitas pesquisas tenham sido conduzidas com um determinado antioxidante ou mPTP individualmente, pouca atenção tem sido dada para os efeitos da co-administração de um antioxidante e um inibidor de mPTP sobre a disfunção cardíaca após a lesão de I/R. Objetivos: Este estudo objetiva determinar os efeitos do ácido gálico (como antioxidante) combinado com a ciclosporina A (CsA) (como inibidor de mPTP) na função cardíaca e endotelial na disfunção induzida por I/R (função de NO). Métodos: Ratos Wistar machos foram pré-tratados com ácido gálico (7,5, 15 ou 30 mg.kg-1 de peso corporal, diariamente) por um período de 10 dias. Em seguida, o coração foi isolado e exposto a isquemia de 30 minutos e perfundido por CsA (0,2 µM) 20 min durante o período de reperfusão. Resultados: Os dados mostraram que o tamanho do infarto foi significativamente diminuído por CsA e ácido gálico sozinho (p < 0,05, ANOVA unidirecional seguido de teste LSD). A combinação de ambos os fármacos, entretanto, apresentou efeitos de melhora mais significativos (p < 0,001). A combinação destes dois fármacos melhorou mais significativamente a taxa máxima de aumento e de queda da pressão ventricular (± dp.dt-1 máx), o duplo produto (DP), a pressão ventricular esquerda desenvolvida (PVED), a frequência cardíaca e o fluxo coronário quando comparada à aplicação de apenas um deles (p < 0,05, medidas repetidas ANOVA seguidas de teste de LSD). Conclusões: Em conclusão, o benefício de um antioxidante concomitante com um inibidor da mPTP poderia ter efeitos mais benéficos sobre a disfunção cardíaca induzida pela lesão I/R

Background: Although many researches have been conducted on either a certain antioxidant or mPTP individually, little attention has been drawn to the effects of co-administration of an antioxidant and mPTP inhibitor together on cardiac dysfunction after I/R injury. Objectives: This study aims at determining the effects of gallic acid (as Antioxidant) combined with cyclosporine A (CsA) (as mPTP inhibitor) on I/R induced cardiac and endothelial (role of NO) dysfunction. Methods: Male Wistar rats were pretreated with gallic acid (7.5, 15, or 30mg.kg-1 body weight, daily) for a period of 10 days. Then, the heart was isolated and exposed to 30-minute ischemia and perfused by CsA (0.2 µM) 20 min during reperfusion period. Results: The data have shown that infarct size was decreased significantly by CsA and gallic acid alone (p < 0.05, one way ANOVA followed by LSD test), however the combination of both drugs had more significant improving effects (p < 0.001). The combination of these two drugs improved more significantly maximum rate of rise and fall of ventricular pressure (±dp.dt-1 max), rate pressure product (RPP), left ventricular developed pressure (LVDP), heart rate and coronary flow rather than applying each one alone (p < 0.05, repeated measurement ANOVA followed by LSD test). Conclusion: In conclusion, benefiting from an antioxidant concomitant with an mPTP inhibitor could have more improving effects on the cardiac dysfunction induced by I/R injury