Association of soluble ST2 Level with 6-month Mortality and/or Recurrent Cardiovascular-Related Hospitalization in Pulmonary Embolism. / Associação do Nível de ST2 Solúvel com Mortalidade em 6 Meses e/ou Hospitalização Recorrente Relacionada a Doenças Cardiovasculares em Embolia Pulmonar.

BACKGROUND: The association of soluble suppression of tumorigenesis-2 (sST2) levels with prognosis in pulmonary embolism (PE) is unknown. OBJECTIVE: This study aimed to investigate the relationship between sST2 levels in patients with acute PE and 6-month mortality and recurrent hospitalizations. METHODS: This prospective study included 100 patients with acute PE. Patients were classified into two groups according to 6-month mortality and the presence of recurrent Cardiovascular-Related hospitalizations. Two groups were compared. A p-value of 0.05 was considered statistically significant. RESULTS: Soluble ST2 levels were significantly higher in the group with mortality and recurrent hospitalizations. (138.6 ng/mL (56.7-236.8) vs. 38 ng/mL (26.3-75.4); p<0.001) The best cut-off threshold for sST2 levels in the prediction of a composite outcome of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization was found to be >89.9 with a specificity of 90.6% and a sensitivity of 65.2%, according to the receiver operating characteristic curve (area under the curve = 0.798; 95% CI, 0.705-0.891; p <0.0001). After adjusting for confounding factors that were either statistically significant in the univariate analysis or for the variables correlated with the sST2 levels, sST2 level (OR = 1.019, 95% CI: 1.009-1.028, p 0.001) and C-reactive protein (CRP ) (OR = 1.010, 95% CI: 1.001-1.021, p = 0.046) continued to be significant predictors of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in the multiple logistic regression model via backward stepwise method. CONCLUSION: Soluble ST2 level seems to be a biomarker to predict 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in patients with acute PE.

FUNDAMENTO: A associação de supressão solúvel da tumorigênese-2 (sST2) com prognóstico em embolia pulmonar (EP) é desconhecida. OBJETIVO: Este estudo teve como objetivo investigar a relação entre os níveis de sST2 em pacientes com EP aguda e mortalidade em 6 meses e hospitalizações recorrentes. MÉTODOS: Este estudo prospectivo incluiu 100 pacientes com EP aguda. Os pacientes foram classificados em dois grupos de acordo com a mortalidade em 6 meses e a presença de hospitalizações recorrentes relacionadas a doenças cardiovasculares. Dois grupos foram comparados. Um valor de p de 0,05 foi considerado estatisticamente significativo. RESULTADOS: Os níveis de ST2 solúvel foram significativamente maiores no grupo com mortalidade e internações recorrentes. (138,6 ng/mL (56,7-236,8) vs. 38 ng/mL (26,3-75,4); p<0,001) O melhor limite de corte para níveis de sST2 na previsão de um desfecho composto de mortalidade em 6 meses e/ou a hospitalização recorrente relacionada a doenças cardiovasculares foi >89,9, com especificidade de 90,6% e sensibilidade de 65,2%, de acordo com a curva Receiver Operating Characteristic (área sob a curva = 0,798; IC 95%, 0,705­0,891; p <0,0001). Após ajuste para fatores de confusão que foram estatisticamente significativos na análise univariada ou para as variáveis correlacionadas com os níveis de sST2, nível de sST2 (OR = 1,019, IC 95%: 1,009-1,028, p 0,001) e proteína C reativa (PCR). (OR = 1,010, IC 95%: 1,001-1,021, p = 0,046) continuaram a ser preditores significativos de mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares no modelo de regressão logística múltipla através do método backward stepwise. CONCLUSÕES: O nível de ST2 solúvel parece ser um biomarcador para prever mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares em pacientes com EP aguda.

Efficacy of boric acid used to treat experimental vascular graft infection by methicillin-resistant Staphylococcus aureus.

INTRODUCTION: We aimed to investigate the efficacy of local boric acid (BA) and teicoplanin in prosthetic vascular graft infection (PVGI) caused by methicillin-resistant Staphylococcus aureus (MRSA) in a rat model. METHODOLOGY: Fourty rats were divided into five groups. Group 1 received no treatments (control group); group 2 was uncontaminated polytetrafluoroethylene (PTFE) graft group; group 3 was untreated and the PTFE graft was contaminated with 2×107 CFU/mL MRSA; group 4 received local BA (8 mg/kg) and was contaminated with with 2×107 CFU/mL MRSA; group 5 received local BA (8 mg/kg) and intraperitoneal teikoplanin (10 mg/kg), and was contaminated with 2×107 CFU/mL MRSA; On the 3rd day, grafts and serums were removed for microbiological, histological and serological tests. RESULTS: The amounts of culture growth in groups 4 and 5 were significantly lower compared to group 3 (p < 0.001). TNF-α was significantly higher in Group 3 than the other groups (p = 0.001). There was no significant difference between the groups in serum IL-1 levels (p = 0.138). Monocyte chemotactic protein-1 (MCP-1) was not significantly different between groups 3, 4, and 5, but it was significantly higher than groups 1 and 2 (p < 0.001). The severity of inflammation was significantly higher in group 3 than the other groups, and fibroblastic proliferation, granulation tissue and collagen synthesis were significantly lower (p < 0.05). CONCLUSIONS: Our study showed that local BA and combined teicoplanin treatment is effective in preventing PVGI.

Lycopene hampers lung injury due to skeletal muscle ischemia-reperfusion in rat model.

This study investigates lycopene's preventive efficacy in skeletal muscle ischemia-reperfusion (I/R) induced lung injury. Thirty-two rats were randomly assigned to control group, lycopene group, I/R group and I/R + lycopene group. In the lycopene and I/R + lycopene groups, the rats initially received 10 mg/kg/day lycopene orally for 15 days. Then, dissection around the abdominal aorta was performed in all rats under general anesthesia. The aorta was clamped at the infrarenal level in the I/R group and I/R + lycopene group for two hours before two hours of reperfusion. The mean serum levels of malondialdehyde (53.0 ± 20.14 nmol/mL) and superoxide dismutase (1.03 ± 0.16 U/mL) were higher and lower in the I/R group than the other three groups, respectively (p < 0.001). The mean serum IMA level of I/R + lycopene group (0.42 ± 0.04 abs/u) was lower than the I/R group (0.47 ± 0.04 abs/u) (p = 0.015). The mean tissue malondialdehyde levels of I/R group (69.10 ± 11.55 nmol/mL) and I/R + lycopene group (68.36 ± 21.17 nmol/mL) were high compared to the control group (49.87 ± 6.52 nmol/mL) and lycopene group (47.82 ± 4.44 nmol/mL) (p = 0.002). The mean tissue glutathione peroxidase (p < 0.001) and superoxide dismutase (p = 0.001) levels of I/R group (121.81 ± 43.59 nmol/mL and 25.17 ± 8.69 U/mL) were low compared to the control group (236.12 ± 18.01 nmol/mL and 46.30 ± 5.17 U/mL), lycopene group (227.52 ± 16.92 nmol/mL and 45.82 ± 4.02 U/mL), and I/R + lycopene group (176.02 ± 24.27 nmol/mL and 35.20 ± 4.85 U/mL). The histopathological analyses of I/R + lycopene group indicated less significant changes than the control group. Tissue damage in the I/R + lycopene group was less prominent than the I/R group. These findings suggest oral lycopene supplementation as a promising prevention against skeletal muscle I/R caused lung injury.

Effect of mechanical ventilation during cardiopulmonary bypass on oxidative stress: a randomized clinical trial.

BACKGROUND: Cardiopulmonary bypass (CPB) causes systemic oxidative stress response and endothelial damage in systemic organs. We investigated the effects of positive end-expiratory pressure (PEEP) and mechanical ventilation (MV) applications on oxidative stress in CPB. METHODS: Seventy-one patients were recruited and 60 completed the study. Randomized groups: MV off (Group 1); MV on, tidal volume (TV) at 3-4 mL.kg-1 (Group 2); MV on, TV at 3-4 mL.kg-1, PEEP at 5 cmH2O (Group 3), n = 20 in each group. As oxidative stress markers, we used glutathione peroxidase (GPx), total antioxidant status (TAS), total oxidant status (TOS), total and native thiol (TT, NT), malondialdehyde (MDA), and catalase. We also investigated the correlation between oxidative stress and postoperative intubation time. RESULTS: The postoperative GPx levels in Group 2 were higher than Group 3 (p = 0.017). In groups 2 and 3, TAS levels were higher postoperatively than intraoperatively (p = 0.001, p = 0.019, respectively). In Group 2, the TT levels were higher postoperatively than preoperatively and intraoperatively (p = 0.008). In Group 3, the postoperative MDA levels were higher than preoperatively (p = 0.001) and were higher than both postoperative levels of Group 1 and 2 (p = 0.043, p = 0.003). As the preoperative TAS (Group 2) decreased and the postoperative NT (Group 2) and catalase (Group 3) increased, the postoperative intubation time lengthened. CONCLUSION: MV ( 3-4 mL.kg-1) alone seems to be the most advantageous strategy. Prolonged postoperative intubation time was associated with both increased NT and catalase levels.

Comparison of the operative and postoperative effects of del Nido and blood cardioplegia solutions in cardiopulmonary bypass surgery.

OBJECTIVE: Our goal was to compare the operative and postoperative effects of del Nido cardioplegia (DN group) and blood cardioplegia (BC group) performed in cardiac surgery. METHODS: A total of 83 patients were included, separated into DN group and BC group. The operative and postoperative effects of the two groups were compared for the first 24 hours until extubation. The operative and postoperative complete blood count (CBC), biochemical values and clinical parameters were compared. RESULTS: The first control activated clotting time (ACT) levels in DN group patients were lower (P=0.003) during the operation. The amount of cardioplegia in DN group were lower than that in BC group (P=0.001). The pump outflow and postoperative lactate level of DN group were lower than those of BC group (P=0.005, P=0.018, respectively), as well as the amounts of NaHCO3 (P=0.006) and KCl (P=0.001) used during the operation. The same occurred with the first monocytes (Mo) and mean corpuscular volume (MCV) levels in the postoperative intensive care unit (P=0.006, P=0.002). However, the first glucose level and the eosinophil (Eo) level were higher in DN group (P=0.011, P=0.047, respectively). CONCLUSION: In the operative evaluation, the amount of cardioplegia, the first ACT levels, the pump outflow lactate level and the amounts of NaHCO3 and KCl in DN group were lower. In postoperative evaluation, measured level of lactate, Mo and MCV in DN group were all lower; their glucose and Eo levels were higher.

Comparison of the operative and postoperative effects of del Nido and blood cardioplegia solutions in cardiopulmonary bypass surgery

Abstract Objective: Our goal was to compare the operative and postoperative effects of del Nido cardioplegia (DN group) and blood cardioplegia (BC group) performed in cardiac surgery. Methods: A total of 83 patients were included, separated into DN group and BC group. The operative and postoperative effects of the two groups were compared for the first 24 hours until extubation. The operative and postoperative complete blood count (CBC), biochemical values and clinical parameters were compared. Results: The first control activated clotting time (ACT) levels in DN group patients were lower (P=0.003) during the operation. The amount of cardioplegia in DN group were lower than that in BC group (P=0.001). The pump outflow and postoperative lactate level of DN group were lower than those of BC group (P=0.005, P=0.018, respectively), as well as the amounts of NaHCO3 (P=0.006) and KCl (P=0.001) used during the operation. The same occurred with the first monocytes (Mo) and mean corpuscular volume (MCV) levels in the postoperative intensive care unit (P=0.006, P=0.002). However, the first glucose level and the eosinophil (Eo) level were higher in DN group (P=0.011, P=0.047, respectively). Conclusion: In the operative evaluation, the amount of cardioplegia, the first ACT levels, the pump outflow lactate level and the amounts of NaHCO3 and KCl in DN group were lower. In postoperative evaluation, measured level of lactate, Mo and MCV in DN group were all lower; their glucose and Eo levels were higher.

Protective Effects of Adrenomedullin on Rat Cerebral Tissue After Transient Bilateral Common Carotid Artery Occlusion and Reperfusion.

OBJECTIVE: We aimed to investigate the protective effect of adrenomedullin (ADM) on cerebral tissue of rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Thirty-two Wistar rats were randomized into four groups (n=8). In the I/R Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, reperfused for 120 minutes. In the ADM Group, rats received 12 µg/kg of ADM. In the I/R+ADM Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, the rats received 12 µg/ kg of ADM. Then, reperfusion was performed for 120 minutes. The Control Group underwent no procedure. Blood and brain tissue samples were collected for biochemical and histopathological analysis. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were analysed. Brain tissue was evaluated histopathologically and neuronal cells were counted in five different fields, at a magnification of ×400. RESULTS: Brain MDA in I/R Group was significantly higher than in ADM Group. Brain GPx and SOD in I/R+ADM Group were significantly higher than in I/R Group. The number of neurons was decreased in I/R Group compared to the Control Group. The number of neurons in I/R+ADM Group was significantly higher than in I/R Group, and lower than in Control Group. Apoptotic changes decreased significantly in I/R+ADM Group and the cell structure was similar in morphology compared to the Control Group. CONCLUSION: We demonstrated the cerebral protective effect of ADM in the rat model of cerebral I/R injury after bilateral carotid artery occlusion.

Protective effects of adrenomedullin on rat cerebral tissue after transient bilateral common carotid artery occlusion and reperfusion

Abstract Objective: We aimed to investigate the protective effect of adrenomedullin (ADM) on cerebral tissue of rats with cerebral ischemia/reperfusion (I/R) injury. Methods: Thirty-two Wistar rats were randomized into four groups (n=8). In the I/R Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, reperfused for 120 minutes. In the ADM Group, rats received 12 µg/kg of ADM. In the I/R+ADM Group, bilateral common carotid arteries were clamped for 30 minutes and, subsequently, the rats received 12 µg/ kg of ADM. Then, reperfusion was performed for 120 minutes. The Control Group underwent no procedure. Blood and brain tissue samples were collected for biochemical and histopathological analysis. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were analysed. Brain tissue was evaluated histopathologically and neuronal cells were counted in five different fields, at a magnification of ×400. Results: Brain MDA in I/R Group was significantly higher than in ADM Group. Brain GPx and SOD in I/R+ADM Group were significantly higher than in I/R Group. The number of neurons was decreased in I/R Group compared to the Control Group. The number of neurons in I/R+ADM Group was significantly higher than in I/R Group, and lower than in Control Group. Apoptotic changes decreased significantly in I/R+ADM Group and the cell structure was similar in morphology compared to the Control Group. Conclusion: We demonstrated the cerebral protective effect of ADM in the rat model of cerebral I/R injury after bilateral carotid artery occlusion.

The protective effects of lycopene on ischemia/reperfusion injury in rat hind limb muscle model.

BACKGROUND: Acute ischemia/reperfusion (I/R) injury of skeletal muscle, an important mortality and morbidity cause, is associated with oxidative stress. Lycopene is a carotenoid pigment with potent antioxidant activity and is found in vegetables and fruits. This study aims to investigate the protective effects of lycopene against I/R injury in rat hind limb muscle model. METHODS: Thirty-two Wistar-albino rats were randomly allocated to control, lycopene, I/R and I/R+lycopene groups. In lycopene and I/R+lycopene groups, the rats received 10 mg/kg/day lycopene orally for 15 days before the experiment. Dissection around abdominal aorta at the infrarenal level was performed in all rats under general anesthesia. The aorta was clamped at the infrarenal level in the I/R and I/R+lycopene groups for two hours. Then, reperfusion was allowed for two hours in these groups. Samples were obtained from the hind limb muscles of rats after sacrifice for biochemical and histopathological analyses. RESULTS: Serum and tissue malondialdehyde and ischemia-modified albumin levels were significantly lower in the I/R+lycopene group compared to I/R group (p<0.001). Serum glutathione peroxidase (GSH-Px) levels were significantly lower in the I/R group compared to those in control and I/R+lycopene groups (p<0.05). Tissue GSH-Px levels were significantly lower in the I/R group compared to the Lycopene group (p=0.003). Serum superoxide dismutase (SOD) levels were significantly lower in the I/R group compared to three groups (p<0.001). Tissue SOD levels were significantly lower in the I/R group compared to those in control and Lycopene groups (p=0.005). Histopathological assessments revealed that inflammatory changes following I/R injury were significantly reduced in the I/R+lycopene group. CONCLUSION: The findings obtained in this study show lycopene's cytoprotective activity against I/R injury in rat skeletal muscle model.

Evaluation of the cardioprotective effects of crystalloid del Nido cardioplegia solution via a rapid and accurate cardiac marker: heart-type fatty acid-binding protein

Background/aim: Our aim in this study was to compare the efficacy and safety of crystalloid del Nido solution and cold blood cardioplegia solution on clinical and laboratory parameters. Materials and methods: Sixty patients who underwent elective coronary bypass operation between July 2019 and January 2020 were included in our study. Patients were divided into 2 groups of 30 patients using del Nido solution (DNS) and cold blood cardioplegia solution (CBCS), which were given for cardiac arrest. Demographic data, preoperative, postoperative 0th h, 6th h and 4th day creatine kinase myocardial band (CK-MB) and troponin I values were compared with a specific cardiac enzyme heart-type fatty acid-binding protein (H-FABP). Results: We found that aortic cross clamp duration and cardiopulmonary bypass (CPB) time were shorter in patients using del Nido solution than cold blood cardioplegia solution (57.30 ± 23.57 min, 76.07 ± 27.18 min, P = 0.006) (95.07 ± 23.06 min, 114.13 ± 33.93, P = 0.014). Total cardioplegia solution volume was higher in the cold blood cardioplegia solution group (1426.67 ± 416.00 vs. 1200 ± 310.73 P = 0.02). Preoperative and postoperative levels of cardiac enzymes including CK-MB, troponin I and H-FABP were comparable in del Nido solution and cold blood cardioplegia solution groups. Conclusion: According to these results, when we compare both demographic data and CK-MB, troponin I and H-FABP levels, both cardioplegia solutions were comparable regarding safety and efficacy in terms of myocardial protection.

Effect of picroside II on hind limb ischemia reperfusion injury in rats.

INTRODUCTION: Many structural and functional damages are observed in cells and tissues after reperfusion of previously viable ischemic tissues. Acute ischemia reperfusion (I/R) injury of lower extremities occurs especially when a temporary cross-clamp is applied to the abdominal aorta during aortic surgery. Research regarding the treatment of I/R injury has been increasing day-by-day. In this study, we aimed to investigate the effect of picroside II on skeletal muscle of rats experiencing simulated I/R. MATERIALS AND METHODS: Twenty-four male Wistar albino rats weighing between 210 and 300 g were used in this study. Rats were randomly divided into 4 groups of 6 rats each (control, I/R, control + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R group. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg kg-1) was administered intraperitoneally to the animals in control + picroside II and I/R + picroside II groups. At the end of the study, skeletal muscle tissue was obtained for the determination of total oxidant status (TOS) and total antioxidant status (TAS) levels. Apoptosis was evaluated by TUNEL experiment. RESULTS: TOS levels were significantly higher in I/R group than that of control and I/R + picroside II groups (P=0.014, P=0.005, respectively). TAS levels were significantly higher in I/R group than that of control and I/R + picroside II groups (P=0.007 P=0.005, respectively). TUNEL assay revealed that picroside II reduced cell necrosis. CONCLUSION: The results of this study demonstrated that picroside II plays a critical role to prevent I/R injury. Even though our results were found to be satisfactory, it should be encouraging to those who want to conduct future research on this topic.

Effect of picroside II on erythrocyte deformability and lipid peroxidation in rats subjected to hind limb ischemia reperfusion injury.

BACKGROUND: Ischemia reperfusion injury (I/R) in hind limb is a frequent and important clinical phenomenon. Many structural and functional damages are observed in cells and tissues in these kinds of injuries. In this study, we aimed to evaluate the effect of picroside II on lipid peroxidation and erythrocyte deformability during I/R in rats. METHODS: Rats were randomly divided into four groups - each containing six animals (sham, I/R, sham + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R groups. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg·kg(-1)) was administered intraperitoneally to the animals in the appropriate groups (sham + picroside II, I/R + picroside II groups). All rats were euthanized by intraperitoneal administration of ketamine (100 mg·kg(-1)) and taking blood from the abdominal aorta. Erythrocytes were extracted from heparinized complete blood samples. Buffer (PT) and then erythrocytes (PE) were passed through the filtration system and the changes in pressure were measured to investigate the role of serum malondialdehyde and nitric oxide (NO) in lipid peroxidation and erythrocyte deformability index. RESULTS: Deformability index was significantly increased in the I/R group compared to groups sham, sham + picroside-II, and I/R + picroside-II (P<0.0001, P<0.0001, and P=0.007). Malondialdehyde (MDA) and NO levels were evaluated. MDA level and NO activity were also higher in the I/R group than in the other groups. Picroside II treatment before hind limb I/R prevented these changes. CONCLUSION: These results support that deformability of erythrocytes is decreased in I/R injury and picroside II plays a critical role to prevent these alterations. Further experimental and clinical studies are needed to evaluate and clarify the molecular mechanisms of action and clinical importance of these findings.

Effects of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in skeletal muscle in rats.

BACKGROUND: In this study we investigated the effects of adrenomedullin (AM) and vascular endothelial growth factor (VEGF) on skeletal muscle ischemia/reperfusion (I/R) injury in a rat model. MATERIALS AND METHODS: Thirty-six Wistar rats were randomized into six groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Nothing else was done in Group S (Sham). The Group I/R underwent I/R performed by clamping and declamping of the infrarenal abdominal aorta for 120 min, respectively. Group VEGF and Group AM received intravenous infusion of VEGF (0.8 µg/kg) or AM (12 µg/kg) respectively, without I/R. Group I/R + VEGF and Group I/R + AM received intravenous infusion of VEGF (0.8 µg/kg) or AM (12 µg/kg) immediately after 2 h period of ischemia, respectively. At the end of reperfusion period, skeletal muscle samples of lower extremity were taken from all groups for biochemical and histopathologic examinations. RESULTS: Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and hypoxia inducible factor 1 alpha (HIF 1α) were found to be significantly higher in Group I/R than the levels in Group S (P < 0.05). Tissue levels of MDA, SOD, NO, and HIF 1α were significantly lower in Group I/R + AM compared with the levels in Group I/R (P < 0.05). In Group I/R + VEGF, tissue levels of MDA and NO were significantly lower than the levels in Group I/R (P < 0.05). No statistically significant difference was found in the tissue levels of catalase among the groups. Histologic examination revealed a larger central muscular necrosis than the peripheral necrosis, red blood cells in the lumens of capillary vessels, and a stronger atrophy and elliptical or round shape in muscle fibers in Group I/R. Terminal deoxynucleotidyl transferase mediated dUPT nick end labeling (TUNEL)-positive cell count was significantly lower in groups I/R + AM and I/R + VEGF than Group I/R (P < 0.0001, P < 0.0001, respectively). CONCLUSIONS: These results indicate that AM and VEGF have protective effects on I/R injury in skeletal muscle in a rat model.