Protective effect of Guanxin Danshen formula on myocardial ischemiareperfusion injury in rats

Purpose: Myocardial ischemia/reperfusion injury (MIRI) leads to myocardial tissue necrosis, which will increase the size of myocardial infarction. The study examined the protective effect and mechanism of the Guanxin Danshen formula (GXDSF) on MIRI in rats. Methods: MIRI model was performed in rats; rat H9C2 cardiomyocytes were hypoxia-reoxygenated to establish a cell injury model. Results: The GXDSF significantly reduced myocardial ischemia area, reduced myocardial structural injury, decreased the levels of interleukin (IL-1ß, IL-6) in serum, decreased the activity of myocardial enzymes, increased the activity of superoxide dismutase (SOD), and reduced glutathione in rats with MIRI. The GXDSF can reduce the expression of nucleotide- binding oligomerization domain, leucine-rich repeat and pyrin domain containing nod-like receptor family protein 3 (NLRP3), IL-1ß, caspase-1, and gasdermin D (GSDMD) in myocardial tissue cells. Salvianolic acid B and notoginsenoside R1 protected H9C2 cardiomyocytes from hypoxia and reoxygenation injury and reduced the levels of tumor necrosis factor α (TNF-α) and IL-6 in the cell supernatant, decreasing the NLRP3, IL-18, IL-1ß, caspase-1, and GSDMD expression in H9C2 cardiomyocytes. GXDSF can reduce the myocardial infarction area and alleviate the damage to myocardial structure in rats with MIRI, which may be related to the regulation of the NLRP3. Conclusion: GXDSF reduces MIRI in rat myocardial infarction injury, improves structural damage in myocardial ischemia injury, and reduces myocardial tissue inflammation and oxidative stress by lowering inflammatory factors and controlling focal cell death signaling pathways.

Naringin attenuates acute myocardial ischemia-reperfusion injury via miR126/GSK-3ß/ß-catenin signaling pathway

Introduction: Myocardial ischemia-reperfusion (I/R) injury is one of the mechanisms contributing to the high mortality rate of acute myocardial infarction. Purpose: This study intended to study the role of naringin in cardiac I/R injury. Methods: AC16 cells (human cardiomyocyte cell line) were subjected to oxygen-glucose deprivation/recovery (OGD/R) treatment and/or naringin pretreatment. Then, the apoptosis was examined by flow cytometry and Western blotting. The concentration of IL-6, IL-8 and TNF-α was measured by enzyme-linked immunosorbent assay (ELISA) kits. How naringin influenced microRNA expression was examined by microarrays and quantitative real-time polymerase chain reaction (qRT-PCR). Dual luciferase reporter assay was employed to evaluate the interaction between miR-126 and GSK-3ß. The GSK-3ß/ß-catenin signaling pathway was examined by Western blotting. Finally, rat myocardial I/R model was created to examine the effects of naringin in vivo. Results: Naringin pretreatment significantly decreased the cytokine release and apoptosis of cardiomyocytes exposed to OGD/R. Bioinformatical analysis revealed that naringin upregulated miR-126 expression considerably. Also, it was found that miR-126 can bind GSK-3ß and downregulate its expression, suggesting that naringin could decrease GSK-3ß activity. Next, we discovered that naringin increased ß-catenin activity in cardiomyocytes treated with OGD/R by inhibiting GSK-3ß expression. Our animal experiments showed that naringin pre-treatment or miR-126 agomir alleviated myocardial I/R. Conclusions: Naringin preconditioning can reduce myocardial I/R injury via regulating miR-126/GSK-3ß/ß-catenin signaling pathway, and this chemical can be used to treat acute myocardial infarction.

Tanshinone IIA ameliorates myocardial ischemia/reperfusion injury in rats by regulation of NLRP3 inflammasome activation and Th17 cells differentiation

Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion

Purpose: To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. Methods: Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion. Results: It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%). Conclusion: These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.(AU)

Unexpectedly prolonged fasting and its consequences on elderly patients undergoing spinal anesthetics. A prospective observational study

Purpose:To measure the preoperative fasting durations with respect to time of the day and its effect on vital parameters and electrocardiogram in elderly patients undergoing surgery under spinal anesthesia.Methods:This study investigated 211 patients older than 60 years undergoing elective surgery under spinal anesthesia. Patients scheduled for surgery in morning hours (AM) and afternoon hours (PM) were compared. Patients fasting hours and repeated measurements of mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (Sp02) and the type and number of ischemic electrocardiogram (ECG) signs were recorded and compared [preoperative, zeroth, 2nd,5th,15th,30th minutes following spinal anesthesia(SA)].Results:Mean fasting durations were 12±2.8 and 9.5±2.1 hours in AM group and 15.5±3.4 12.7±4.4 hours in PM group for foods and liquids respectively. ECG changes were significantly more frequent in PM group and body temperatures were significantly higher in AM group patients.Conclusion:Our study has shown that fasting times in our population is far longer than recommended and fasting prolonged>15 hours is related to a transiently increased cardiac stress and mild hypothermia.(AU)

Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion

Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.(AU)

Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats

Purpose:To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats.Methods:Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed.Results:Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats.Conclusion:These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.(AU)

Myocardial ischemic post-conditioning protects the lung against myocardial ischemia/reperfusion-induced damage by activating GSK-3

Purpose: To investigate whether modulating GSK-3 could attenuate myocardial ischemia reperfusion injury (MIRI) induced acute lung injury (ALI) and analyze the underlying mechanism. Methods: Male SD rats were subjected to MIRI with or without myocardial ischemic post-conditioning in the presence or absence of GSK-3 inhibitor. GSK-3 inhibitor was injected peritoneally 10min before MIRI. Lung W/D weight ratio, MPO, PMNs, histopathological changes, TUNEL, Bax, Bcl-2, IL-6, IL-8, IL-10, GSK-3, and caspase-3 were evaluated in the lung tissues of all rats. Results: After MIRI, lung injury was significantly increased manifested as significant morphological changes and increased leukocytes in the interstitial capillaries, Lung W/D ratio, MPO, and PMN in BALF, which was associated with enhanced inflammation evidenced by increased expressions of IL-6, IL-8 and reduced expression of IL-10. MIRI significantly increased cell apoptosis in the lung as increased levels of apoptotosis, Bax, cleaved caspase-3, and reduced expression of Bcl-2 was observed, which was concomitant with reduced p-GSK-3. All these changes were reversed/prevented by ischemic post-conditioning, while these beneficial effects of ischemic post-conditioning were abolished by GSK-3 inhibition. Conclusion: Myocardial ischemia reperfusion injury induces acute lung injury by induction of inflammation and cell apoptosis. Ischemic post-conditioning protects the lung from ALI following MIRI by increasing p-GSK-3.(AU)

AVALIAÇÃO DOS NÍVEIS SÉRICOS DE CK-MB E TROPONINA I EM OVINOS (Ovis aries) SUBMETIDOS A DIFERENTES PRESSÕES DE PNEUMOPERITÔNIO INDUZIDO CIRURGICAMENTE

Procedimentos cirúrgicos por videolaparoscopia são amplamente utilizados, por possuírem vantagens em relação à laparotomia. A insuflação da cavidade peritoneal com gás carbônico (CO2), empregado para facilitar a realização do procedimento laparoscópico, muitas vezes leva a efeitos deletérios sobre os sistemas orgânicos, principalmente no cardiovascular, respiratório e nas vísceras abdominais, dependendo da pressão exercida e do tempo de exposição. Com objetivo de avaliar a presença de lesão miocárdica no pós-operatório, o presente trabalho avaliou os marcadores CK-MB e troponina I em amostras de sangue. Foram utilizados 10 ovinos adultos, fêmeas, em modelo "cross-over", submetidos a um tempo fixo de 60 minutos e pressões intra-abdominais (PIA) de 0mmHg (G1), 10mmHg (G2), 12 mmHg (G3) e 15mmHg (G4) para a realização de videolaparoscopia sob anestesia geral inalatória. Os níveis séricos de CK-MB foram avaliados em um tempo préoperatório (T0), 24 horas (T1) e 72 horas após o procedimento (T2). Os níveis de CK-MB no T1 foram significativamente maiores do que no T0 e no T2 (p<0,05), porém não houve diferença significativa entre os grupos. Para a análise de troponina I, foram utilizados testes qualitativos para este biomarcador no tempo pré-operatório (T0), 24 horas (T1), 72 horas (T2) e sete dias (T3) após o procedimento. Não foi observada associação entre os resultados de troponina I cardíaca de acordo com os tempos de mensuração para os grupos G1, G2, G3 e G4 (p>0,05). Também não houve associação entre os resultados de troponina I de acordo com os grupos (p>0,05). O aumento dos níveis de CK-MB no T1 pode indicar lesão miocárdica, porém esse impacto não foi diferente entre os grupos. O modelo qualitativo de troponina I não foi significativo para indicar lesão miocárdica.

Surgical procedures by laparoscopy are widely used, as they have advantages over laparotomy. Insufflation of the peritoneal cavity with carbon dioxide (CO2), used to facilitate the performance of the laparoscopic procedure, often leads to deleterious effects on the organic systems, mainly in the cardiovascular, respiratory and abdominal viscera, depending on the pressure exerted and the time of exposure. In order to assess the presence of myocardial injury in the postoperative period, the present study evaluated the markers CK-MB and troponin I in blood samples. Ten adult female sheep were used, in a cross-over model, submitted to a fixed time of 60 minutes and intra-abdominal pressures (IAP) of 0mmHg (G1), 10mmHg (G2), 12 mmHg (G3) and 15mmHg (G4) for the performance of videolaparoscopy under general inhalation anesthesia. Serum CK-MB levels were assessed at preoperative time (T0), 24 hours (T1) and 72 hours after the procedure (T2). CK-MB levels at T1 were significantly higher than at T0 and T2 (p <0.05), but there was no significant difference between groups. For the analysis of troponin I, qualitative tests for this biomarker were used in the preoperative time (T0), 24 hours (T1), 72 hours (T2) and seven days (T3) after the procedure. There was no association between cardiac troponin I results according to measurement times for groups G1, G2, G3 and G4 (p>0,05). There was also no association between troponin I results according to groups (p>0,05). The increase in CK-MB levels at T1 may indicate myocardial injury, but this impact was not different between groups. The qualitative model of troponin I was not significant to indicate myocardial injury.