Specialized Proresolving Mediators in Symptomatic Women With Coronary Microvascular Dysfunction (from the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD [WARRIOR] Trial).

Resolvins and maresins, members of the specialized proresolving mediator (SPM) family, are omega-3 fatty acid-derived lipid mediators that attenuate inflammation. We hypothesized that they play a role in the pathophysiology of coronary microvascular dysfunction (CMD) in women with ischemia and no obstructive coronary disease. In a pilot study, we measured the D-series resolvins (D1, D2, D3, and D5), resolvin E1, maresin 1, docosahexaenoic acid, eicosapentaenoic acid (precursor of resolvin E1), and 18-hydroxyeicosapentaenoic acid by mass spectrometry in the peripheral blood of 31 women enrolled in the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial who had confirmed CMD assessed by coronary flow reserve. We compared SPM levels with 12 gender and age-matched reference subjects. Compared with the reference subject group, those with CMD had significantly lower plasma concentrations of resolvin D1 and maresin 1 and significantly higher levels of docosahexaenoic acid and 18-hydroxyeicosapentaenoic acid. In conclusion, insufficient or ineffective SPM production may play a role in the pathophysiology of CMD. If our results are validated in a larger cohort, omega-3 fatty acid supplementation could be tested as a novel treatment for these patients.

Protective effects of ginsenoside Rc against acute cold exposure-induced myocardial injury in rats.

Ginsenoside Rc is one of the cardinal bioactive components of Panax ginseng. The present study aimed to investigate whether ginsenoside Rc exerted protective effects against acute cold exposure-induced myocardial injury in rats. Forty rats were randomly assigned into four groups: Control, model, ginsenoside Rc 10 mg/kg, and 20 mg/kg groups. Rats were intragastrically administrated with ginsenoside Rc (10, 20 mg/kg) or vehicle daily for 7 days. On the seventh day, all rats except the control group were exposed to low temperature. Cardiac function, myocardial enzyme activities, hemorheology, and inflammatory response were detected. Histopathological examination and apoptosis of cardiac tissues were performed. The expressions of silent information regulator 1 (SIRT1), B-cell lymphoma (Bcl-2), Bcl-2-associated X (Bax), procaspase-3, and the mRNA (messenger RNA) level of SIRT1 were measured by western blot and real-time quantitative polymerase chain reaction (PCR) analysis. Ginsenoside Rc significantly improved cardiac function, diminished the activities of lactate dehydrogenase (LDH), aspartate aminotransferase, and creatine kinase isoenzyme (CK-MB), and regulated abnormal hemorheology in acute cold-exposed rats (p < 0.05 or p < 0.01). Furthermore, ginsenoside Rc could attenuate myocardial histological changes and structural abnormalities, decrease apoptotic cells and reduce the mRNA levels and activity of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 (p < 0.01). In addition, ginsenoside Rc upregulated the expressions of SIRT1, Bcl-2, and procaspase-3 and downregulated that of Bax (p < 0.01). The changes in both the mRNA and protein expression levels of SIRT1 were similar. The results of the current study suggested that ginsenoside Rc could alleviate acute cold exposure-induced myocardial injury in rats by inhibiting cardiomyocyte apoptosis via regulating SIRT1 expression and attenuating the inflammatory responses. PRACTICAL APPLICATION: The current study indicated that ginsenoside Rc could alleviate acute cold exposure-induced myocardial injury in rats. Ginsenoside Rc could be potentially used as a bioactive ingredient in processed functional food products or food supplements to prevent from acute cold exposure-induced myocardial injury.

Ischaemic heart and cerebrovascular disease mortality in uranium enrichment workers.

OBJECTIVE: Linear and non-linear dose-response relationships between radiation absorbed dose to the lung from internally deposited uranium and external sources and circulatory system disease (CSD) mortality were examined in a cohort of 23 731 male and 5552 female US uranium enrichment workers. METHODS: Rate ratios (RRs) for categories of lung dose and linear excess relative rates (ERRs) per unit lung dose were estimated to evaluate the associations between lung absorbed dose and death from ischaemic heart disease (IHD) and cerebrovascular disease. RESULTS: There was a suggestion of modestly increased IHD risk in workers with internal uranium lung dose above 1 milligray (mGy) (RR=1.4, 95% CI 0.76 to 2.3) and a statistically significantly increased IHD risk with external dose exceeding 150 mGy (RR=1.3, 95% CI 1.1 to 1.6) compared with the lowest exposed groups. ERRs per milligray were positive for IHD and uranium internal dose and for both outcomes per gray external dose, although the CIs generally included the null. CONCLUSIONS: Non-linear dose-response models using restricted cubic splines revealed sublinear responses at lower internal doses, suggesting that linear models that are common in radioepidemiological cancer studies may poorly describe the association between uranium internal dose and CSD mortality.

Danlou tablet inhibits the inflammatory reaction of high-fat diet-induced atherosclerosis in ApoE knockout mice with myocardial ischemia via the NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Danlou tablet (DLT), a traditional herbal formula, has been used to treat chest discomfort (coronary atherosclerosis) in China. Although the anti-inflammatory activities of DLT have been proposed previously, the mechanisms of DLT in treating atherosclerosis with myocardial ischemia (AWMI) remain unknown. AIM OF THE STUDY: Atherosclerosis can result in heart disease caused by stenosis or occlusion of the lumen, resulting in myocardial ischemia, hypoxia, or necrosis. In recent years, changes in people's diets, increased stress, and secondary fatigue and obesity etc. have resulted in increases in the number of patients with atherosclerosis. In cases where the condition has further developed, patients may suffer from myocardial ischemia, hypoxia, or necrosis. Many traditional Chinese medicine compounds have been prescribed for the treatment of AWMI. DLT has been used to treat chest discomfort (coronary atherosclerosis) in China. Based on previous research, the aim of this study was to further investigate the effect of DLT on AWMI, and describe the underlying mechanisms. MATERIALS AND METHODS: To achieve this, an animal model of AWMI was established using apolipoprotein E (ApoE-/-) mice fed a high fat diet combined with isoprenaline (ISO) injection. For comparison, mouse models of only atherosclerosis and only myocardial ischemia were included. In the treatment groups, mice were treated daily with DLT at 700 mg/kg for four weeks. Echocardiographic evaluation, hematoxylin and eosin (H&E) staining, oil red O staining, ELISAs, Western blots, and immunohistochemical analyses were subsequently used to investigate the mechanism of DLT based on the NF-κB signaling pathway. RESULTS: The results indicate that the use of DLT is effective, to varying degrees, for the treatment of atherosclerosis, myocardial ischemia, and AWMI in mice. After DLT treatment, the left ventricular structure and morphology of the mice, the histopathology of cardiac tissue, and atherosclerotic plaques in the aortas all improved to varying degrees. DLT could play a therapeutic role by regulating the NF-κB signaling pathway related to inflammatory factors, including TNF-α, IL-6, IL-1ß, IL-8, MMP-1 and MMP-2, as well as protein expression of NF-κB p-50 and IκB-α, and positive cell expression of NF-κB p-50, IκB-α and phospho-NF-κB p-50 in the model mice. CONCLUSION: These preliminary results indicate that the therapeutic efficacy of DLT on high-fat diet-induced atherosclerosis in ApoE-/- mice with myocardial ischemia could be exerted at least in part by regulating the NF-κB signaling pathway.

Risk of Ischemic Heart Disease and Stroke in Prostate Cancer Survivors: A Nationwide Study in South Korea.

In this study using national health insurance data, we investigated the risk of ischemic heart disease (IHD) and stroke among prostate cancer (PC) survivors compared with the general population, as well as the risk of cardiovascular disease (CVD) according to primary treatment. A total of 48,298 PC patients diagnosed from 2007 to 2013 were included and matched to non-cancer controls. Compared to the general population, PC survivors had a slightly lower risk of IHD (adjusted hazard ratio [aHR] = 0.89, 95% confidence interval [CI] 0.83-0.96) or stroke (aHR 0.90, 95% CI 0.87-0.95). Especially, survivors who underwent surgery had lower risks of IHD (aHR 0.70, 95% CI 0.61-0.80) or stroke (aHR 0.73, 95% CI 0.67-0.81). Compared to survivors in the active surveillance/watchful waiting group, the androgen deprivation therapy (ADT) group had a significantly greater risk of stroke (aHR 1.16, 95% CI 1.02-1.32), but the IHD risk was not significantly elevated (aHR 1.06, 95% CI 0.88-1.29). In conclusion, PC survivors had a slightly lower risk of CVD compared to the general population, which was attributable to self-selection for PSA screening, specifically in the surgery-only group. CVD risk was dependent on treatment received, and attention should be given to patients who receive ADT.

Reduction of Cold Ischemic Injury with the Addition of Compound Glycyrrhizin in HTK Solution in a Mouse Heart Transplantation Model.

Cold ischemic injury in heart storage is an important issue pertaining to heart transplantation. This study aims to evaluate the addition of compound glycyrrhizin (CG) in histidine-tryptophan-ketoglutarate (HTK) solution on chronic isograft injury in comparison to traditional HTK solution.Hearts of mouse were stored for 8 h in 4°C cold preservation solution and then transplanted heterotopically into mouse. Five groups were evaluated: HTK, low dose of CG solution (LCG), medium dose of CG solution (MCG), high dose of CG solution (HCG), and hearts without cold ischemia (sham). Survival was assessed. Time to restoration of heartbeat and strength of the heartbeat was measured. Lactate dehydrogenase (LDH) and creatine kinase (CK) levels in the preservation solution were determined. The myocardial damage and interstitial fibrosis of transplanted hearts were evaluated. TGF-ß1 expression in the transplanted hearts was assessed.Addition of CG to HTK solution significantly attenuated cold ischemic injury during cold storage, as evidenced by the lower time to restoration of heartbeat, higher strength of the heartbeat, lower LDH, and CK leakage. After transplantation, hearts stored in HTK solution containing CG had decreased the myocardial damage and interstitial fibrosis, compared with those stored without CG. The percentage of TGF-ß1-positive cells and TGF-ß1 level in the transplanted hearts were also decreased when stored in CG-containing HTK solution.The addition of CG to HTK solution attenuates cold ischemic injury during cold storage.

Cardioprotective effect of acupuncture for percutaneous coronary intervention-related myocardial injury in patients with coronary artery disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Although patients with coronary artery disease (CAD) rely increasingly upon percutaneous coronary intervention (PCI), this therapy causes subsequent the complications of myocardial injury. Acupuncture safely protects the heart from ischemic injury; however, the efficacy of acupuncture for periprocedural myocardial injury after PCI remains unclear. METHODS: Seven databases in English and Chinese including PubMed, Web of Science, Cochrane Library, Embase, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Wanfang Database will be searched. Randomized controlled trials (RCTs) that use acupuncture to treat PCI-related myocardial injury in patients with CAD, regardless of blinding. The crossover randomized trials will be included, but only the pre-crossover data will be analyzed to avoid carryover effects. We will exclude non-RCTs, qualitative studies, uncontrolled clinical trials, and laboratory studies. The measurement of concentration of cardiac troponin (T or I) and MB isoenzyme of creatine kinase will be used as primary outcome. Postprocedural cardiac function and the major adverse cardiac/cerebrovascular event rate will be assessed as secondary outcome. Relevant data were collected independently by 2 reviewers and the third reviewer was responsible for resolving discrepancies through discussion. The Review Manager V.5.3.3 s will be used to perform the data synthesis and subgroup analysis. DISCUSSION: This systematic review and meta-analysis would provide convincing evidence of various types of acupuncture that specifically focuses on cardioprotective effect of acupuncture on PCI-related myocardial injury. REGISTRATION: Open Science Framework (OSF) registries (osf.io/n2e6t) with the registration DOI: 10.17605/OSF.IO/79H2E.

Smoking Water-Pipe, Opium Use and Prevalence of Heart Disease: A Cross-sectional Analysis of Baseline Data from the Pars Cohort Study, Southern Iran.

BACKGROUND: Associations between hookah and opium use and an increased risk of ischemic heart disease (IHD) have been suggested in a few studies, but more research is needed on the nature of these associations. We aimed to investigate the association between hookah and opium use and the prevalence of IHD in a population with relatively high prevalence of these exposures in Iran. METHODS: Using baseline data from the Pars Cohort Study (PCS), a prospective study of individuals aged 40-75 years in Fars province, southern Iran, we calculated adjusted and crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the independent association of hookah and opium use with prevalence of IHD. RESULTS: Of 9248 participants, 10.2% (95% CI: 9.5, 10.9) had self-reported IHD. Prevalence of ever use of hookah and opium was 48.9% (95% CI: 44.6, 53.6) and 10.2% (95% CI: 8.3, 12.5) among those with IHD, and 37.0% (95% CI: 35.7, 38.3) and 8.1% (95% CI: 7.5, 8.7) among those without IHD, respectively. Adjusted OR for the association with prevalence of IHD was 1.26 (95% CI: 1.08, 1.46) for hookah use and 1.71 (95% CI: 1.30, 2.24) for opium abuse. No dose-response association was found between hookah and prevalence of IHD. CONCLUSION: Hookah and opium abuse were associated with prevalent IHD in this study. Although more research is needed on these associations, particularly in prospective settings, reducing hookah and opium use could potentially reduce IHD risk.

PRE-WORKOUT SUPPLEMENT INDUCED CARDIAC ISCHAEMIA IN A YOUNG FEMALE.

The popularity of pre-workout supplements is rising amongst professional athletes and fitness enthusiasts. Despite increased usage, the safety profile of pre-workout supplements is likely to be not well understood. Additionally, many different brands use various undisclosed proprietary blends of active ingredients creating safety regulation difficulties. This lack of oversight could prove unsafe for certain patients. This patient MK is a 33-year-old healthy housewife who presented with central chest tightness, pre-syncope and mild dyspnoea to the emergency department via ambulance. The presentation was in the context of recent strenuous exercise and ingestion of a pre-workout supplement (Alpha Lean-7). Most striking in her presentation was a troponin rise of 50 ng/L, while not very high it is unusual given her lack of cardiac risk factors. She had a 3-day uneventful admission with a downtrending troponin prior to discharge. This case highlights the possible dangers of pharmacologically active ingredients in pre-workout supplements.

[Iron and stable ischemic heart disease - lessons from heart failure]. / Ferro e cardiopatia ischemica stabile ­ lezioni dallo scompenso cardiaco.

Iron is an essential element for cardiomyocyte viability and contractility. Systemic iron deficiency, even without anemia, is reflected by iron deficiency in cardiomyocytes. As in other cells, there is here a complex, local and autonomous regulation of iron metabolism, based on two molecular systems: the hepcidin/ferroportin/transferrin receptor-1 axis; and the iron regulatory proteins-1,2 system. These molecular pathways allow cardiomyocytes to react to changes in serum iron availability. In mice, dietary manipulations of serum iron availability or cardio-specific deletions and mutations of regulatory genes for intracellular iron metabolism have clarified some aspects of the causal relationship between cardiomyocyte iron deficiency and the development of severe heart failure, prevented by intravenous iron treatment even without the occurrence of iron deficiency (sideropenic) anemia. The deleterious effects of iron deficiency and hypoxia on gene expression of the main regulators of intracellular iron and oxygen metabolism and on cardiac function are very similar in heart failure and in chronic stable ischemic heart disease, and conjure towards cardiomyocyte injury. We here hypothesize that in non-anemic patients with stable ischemic heart disease a chronic or acute serum iron deficiency can amplify the chronic activation of the cardiomyocyte hypoxia-inducible factor-1α. As a consequence, cardiac adaptative responses to chronic hypoxia/ischemia are significantly impaired, and cardiac dysfunction exacerbated. We hypothesize that, in such patients, iron replacement through forced iron supplementation may replete cardiomyocyte iron deficiency and improve ischemic heart disease. This hypothesis requires further experimental studies, but also, and already now, specific clinical trials.

Spinosin and 6'''­Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats.

Investigating active compounds from Chinese herbal medicine that can rescue myocardial cells is a good approach to preserve cardiac function. Several herbal formulae that containing Semen Ziziphi Spinosae (SZS), also called Suanzaoren in Chinese, are clinically effective in the treatment of patients with acute myocardial infarction (AMI). The present study aimed to investigate the cardioprotective effects of spinosin and 6'''­feruloylspinosin, two flavonoid glycosides from SZS, in a rat model of myocardial ischemia and reperfusion. The left anterior descending artery (LAD) was occluded to induce myocardial ischemia. Spinosin or 6'''­feruloylspinosin (5 mg/kg) was intraperitoneally injected into rats 30 min before LAD ligation. The protein levels of myocardial enzymes in the serum, the extent of tissue injury and the rate of apoptosis were examined after AMI in rats with or without pretreatment with spinosin or 6'''­feruloylspinosin. Western blotting was performed to investigate the potential mechanisms underlying the function of these two flavonoid glycosides. The present results suggested that pretreatment with spinosin or 6'''­feruloylspinosin significantly attenuated myocardial tissue injury, and reduced myocardial enzyme release and cell apoptosis in AMI rats. In addition, spinosin treatment increased light chain 3B­II and 6'''­feruloylspinosin, and reduced p62, indicating that autophagy was promoted after drug treatments. Treatments of spinosin and 6'''­feruloylspinosin led to the reduction of glycogen synthase kinase­3ß (GSK3ß) phosphorylation at Tyr216, and the increase of peroxisome proliferator­activated receptor γ coactivator (PGC)­1α and its downstream signaling proteins, including nuclear factor (erythroid­derived 2)­like 2 (Nrf2) and hemeoxygenase1 (HO­1). The present data suggested that SZS flavonoids could protect myocardial cells against acute heart ischemia­reperfusion, probably via the inhibition of GSK3ß, which increased autophagy and the activity of the PGC­1α/Nrf2/HO­1 pathway.

Exploratory analysis of traditional risk factors of ischemic heart disease (IHD) among predominantly Malay Malaysian women.

BACKGROUND: The risk factors of ischemic heart disease (IHD) specific for women are less well studied. However, knowing the risk factors of IHD for women will empower women themselves to be better informed and thus can help them in decision making concerning their health condition. The objective of this study is to explore the commonly studied risk factors of ischemic heart disease (IHD) among a group of Malaysian women. METHODS: A case control study was conducted among 142 newly diagnosed IHD women patients registered in government hospitals in Terengganu, Malaysia and their 1:1 frequency matched population controls. Data on sociodemographic and socioeconomic profile, co-morbidities, lifestyle factors related to physical activities, dietary fat intake, stress, passive smoking history, anthropometric measurements and biochemical markers were obtained. RESULTS: Middle aged women were recruited with women diagnosed with diabetes (aOR = 1.92, 95% CI: 1.11-3.31), having low HDL-C (aOR = 3.30, 95% CI: 1.28-8.27), those with positive family history of IHD (aOR = 1.92, 95% CI:1.13-3.26) and passive smokers (aOR = 2.99, 95% CI:1.81-4.94) were at higher odds of IHD. CONCLUSIONS: The findings are useful for public health interventions and policy making focusing on specific women population.

Catalpol Ameliorates Neointimal Hyperplasia in Diabetic Rats.

Catalpol, an iridoid glycoside, is an isolated natural product of Rehmannia glutinosa, which has been reported to have antidiabetic properties. This study investigated the vascular protective effects of catalpol in hyperglycemic rats with balloon-injured carotid arteries. Balloon injury stress led to the upregulation of monocyte chemoattractant protein-1 expression in rats with streptozotocin-induced diabetes. Western blotting and real-time PCR were performed. In situ hybridization, immunohistochemistry, and confocal analyses were employed. Monocyte chemoattractant protein-1 levels were increased through streptozotocin induction or balloon injury. After treatment with catalpol, the neointimal hyperplasia area was reduced 2 weeks after balloon injury in hyperglycemic rats. Real-time PCR and immunohistochemical analysis demonstrated reduced levels of monocyte chemoattractant protein-1 2 weeks after the balloon injury. Monocyte chemoattractant protein-1 expression was significantly increased in balloon-injured rats compared with the control groups. Thus, treatment with catalpol affected monocyte chemoattractant protein-1 expression. This study demonstrated that catalpol downregulated monocyte chemoattractant protein-1 expression in carotid arteries and ameliorated neointimal hyperplasia in hyperglycemic rats. The suppressive effect of monocyte chemoattractant protein-1 suggests that it plays a key role in neointimal hyperplasia. The results imply that catalpol is potentially effective for preventing hyperglycemia-related ischemic cardiac diseases.

Bundle branch reentrant ventricular tachycardia: review and case presentation.

Bundle branch reentrant ventricular tachycardia (BBRVT) is characterized by a unique, fast (200-300 beats/min), monomorphic wide complex tachycardia (WCT) associated with syncope, hemodynamic compromise, and cardiac arrest. It is challenging to diagnose, requiring a His bundle recording and specific pacing maneuvers. The overall incidence has been reported to be up to 20% among patients with non-ischemic cardiomyopathy (NICM) undergoing electrophysiologic studies. We report a case of BBRVT in a patient with ischemic cardiomyopathy (ICM) presenting as a WCT with recurrent implantable-cardioverter-defibrillator (ICD) shocks. We describe all the characteristic features of BBRVT and discuss its differential. We also discuss the role of ablation for this condition.

The Effects of Long-Term, Low- and High-Dose Beta-Carotene Treatment in Zucker Diabetic Fatty Rats: The Role of HO-1.

Nowadays, there is a growing interest in compounds derived from plants as potential raw materials for drug development. One of the most studied compounds is beta-carotene (BC). Several clinical studies can be found investigating the cardiovascular effects of BC, however, all these results are controversial. There is an increasing body of evidence showing that besides the well-known antioxidant properties, under strong oxidative circumstances, BC could become prooxidant as well. In this study, we investigated the effects of long-term, low- and high-dose BC treatment in ischemic/reperfused (ISA/REP) hearts isolated from Zucker diabetic fatty (ZDF) rats. The animals were treated with various daily doses of BC for 4 weeks and then hearts were isolated and subjected to 30 min of global ischemia (ISA) followed by 120 min of reperfusion (REP). Blood glucose levels were measured before, after two weeks, and at the end of the treatment. In isolated hearts, the myocardial function was registered. At the end of the reperfusion period, the infarct size (IS) and heme oxygenase-1 (HO-1) expression were measured. The results showed that a low dose of BC treatment significantly improved postischemic recovery, which was reflected in a decreased IS. Interestingly, when BC was applied at high concentrations, the observed protective effects were lost. Although BC treatment increased HO-1 expression, we did not observe a better heart function and/or decreased IS in the high-dose-treated group. Glucose tolerance tests showed a concentration-independent decrease in blood glucose levels. Our results suggest that long-term, low-dose BC treatment could be effective in the treatment of type-2-diabetes and related cardiovascular diseases.

Roles of Autophagy in Ischemic Heart Diseases and the Modulatory Effects of Chinese Herbal Medicine.

Autophagy is an evolutionarily conserved degradation process which eliminates dysfunctional proteins and cytoplasmic components to maintain homeostasis for cell survival. Increasing evidence has demonstrated the modulatory role of autophagy in ischemic heart diseases (IHDs). Traditionally, this process has been recognized as having protective functions, such as inhibiting atherosclerosis progression and reducing cell death during the ischemic phase. However, recent studies have suggested its dual roles in myocardial ischemia/reperfusion (MIR) injury. Excessive autophagy may play a deleterious role in cardiac function, due to overwhelming clearance of cellular constituents and proteins. Hence modulation of autophagy to increase cardiomyocyte survival and improve cardiac function is meaningful for the treatment of IHD. Chinese herbal medicine, including extractive compounds and patented drugs, has shown its potential role in treating IHD by addressing autophagy-related mechanisms. This review summarizes the updated knowledge on the molecular basis and modulatory role of autophagy in IHD and the recent progress of Chinese herbal medicine in its treatment.

Kudiezi injection mitigates myocardial injury induced by acute cerebral ischemia in rats.

BACKGROUND: Kudiezi (KDZ) injection is commonly used in traditional Chinese medicine as treatment for cerebral infarction and angina pectoris. The present study investigated the therapeutic effects of KDZ injection on myocardial injury induced by acute cerebral ischemia and the possibly protective mechanisms. METHODS: Rats were divided into three groups: sham, 6h-ischemia, and KDZ treatment (KDZ). The neurological deficits were determined by the Garcia score. The cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content was also evaluated. Serum creatinine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) activity, myocardial tissue malondialdehyde (MDA) levels, L-Glutathione (GSH) levels, and superoxide dismutase (SOD) activity as well as mitochondrial cytochrome c oxidase (COX) activity were determined. Mitochondrial COX I and COX III mRNA expressions of myocardial tissues were measured by RT-PCR. RESULTS: Impaired neurological function and brain edema were observed in the 6h-ischemia group. TTC staining showed that the 6h-ischemia group had larger infarct zones than the sham group. Myocardial ischemic changes (widened myocardial cell gap, cracks, and obvious edema) were detected in the 6h-ischemia group compared with the sham group, with elevated serum CK-MB activity and CK and LDH levels. Electrocardiography showed lower medium frequency (MF) and high frequency (HF) in the 6h-ischemia group compared with the sham group. In myocardial tissue, COX activity was elevated in the 6h-ischemia compared with the sham group, while SOD, GSH, and MDA levels, and COX I and COX III mRNA expressions remained unchanged. KDZ injection decreased neurological impairment, brain edema, gaps between cells, and infarct size. Compared with the 6h-ischemia group, it reduced serum CK-MB activity and CK and LDH levels, and MDA levels in myocardial tissue. KDZ significantly increased GSH levels, SOD activity, and mitochondria COX activity and the expression of COX I and COX III mRNA in myocardial tissue compared with the sham group. CONCLUSION: KDZ injection had a protective effect against cerebral ischemia in rats. KDZ injection could also alleviate myocardial injury after acute cerebral ischemia in rats. The possible mechanisms involve the regulation of the oxidative stress/antioxidant capacity after cerebral ischemia.

Calpain inhibition modulates glycogen synthase kinase 3ß pathways in ischemic myocardium: A proteomic and mechanistic analysis.

BACKGROUND: Calpain inhibition has an enhancing effect on myocardial perfusion and improves myocardial density by inhibiting glycogen synthase kinase 3ß (GSK-3ß) and up-regulating downstream signaling pathways, including the insulin/PI3K and WNT/ß-catenin pathways, in a pig model of chronic myocardial ischemia in the setting of metabolic syndrome. METHODS: Pigs were fed a high-fat diet for 4 weeks, then underwent placement of an ameroid constrictor to the left circumflex artery. Three weeks later, the animals received no drug (high-cholesterol controls [HCC]), a high-dose calpain inhibitor (HCI), a low-dose calpain inhibitor (LCI), or a GSK-3ß inhibitor (GSK-3ßI). The diets and drug regimens were continued for 5 weeks and the myocardial tissue was harvested. RESULTS: Calpain and GSK-3ß inhibition caused an increase in myocardial perfusion ratios at rest and during pacing compared with controls. Pigs in the LCI and HCI groups had increased vessel density in the ischemic myocardium, and pigs in the GSK-3ßI group had increased vessel density in the ischemic and nonischemic myocardium compared with the HCC group. Calpain inhibition modulates proteins involved in the insulin/PI3K and WNT/ß-catenin pathways. Quantitative proteomics revealed that calpain and GSK-3ß inhibition significantly modulated the expression of proteins enriched in cytoskeletal regulation, metabolism, respiration, and calcium-binding pathways. CONCLUSIONS: In the setting of metabolic syndrome, calpain or GSK-3ß inhibition increases vessel density in both ischemic and nonischemic myocardial tissue. Calpain inhibition may exert these effects through the inhibition of GSK-3ß and up-regulation of downstream signaling pathways, including the insulin/PI3K and WNT/ß-catenin pathways.

Habitual coffee consumption and risk of type 2 diabetes, ischemic heart disease, depression and Alzheimer's disease: a Mendelian randomization study.

Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer's disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer's disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies. Childhood cognition was used as a negative control outcome. Genetically predicted coffee consumption was not associated with T2DM (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.76 to 1.36), depression (0.89, 95% CI 0.66 to 1.21), Alzheimer's disease (1.17, 95% CI 0.96 to 1.43), IHD (0.96, 95% CI 0.80 to 1.14), lipids, glycemic traits, adiposity or adiponectin. Coffee was unrelated to childhood cognition. Consistent with observational studies, coffee was unrelated to IHD, and, as expected, childhood cognition. However, contrary to observational findings, coffee may not have beneficial effects on T2DM, depression or Alzheimer's disease. These findings clarify the role of coffee with relevance to dietary guidelines and suggest interventions to prevent these complex chronic diseases should be sought elsewhere.

Association between serum long-chain omega-3 polyunsaturated fatty acids and cognitive performance in elderly men and women: The Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND/OBJECTIVES: Fish intake and the long-chain omega-3 polyunsaturated fatty acids (PUFAs) in fish have been suggested to lower the risk of cognitive decline. We assessed whether serum long-chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are associated with performance on neuropsychological tests in an older population and whether exposure to methylmercury, mainly from fish, or apolipoprotein-E4 (Apo-E4) phenotype can modify the associations. SUBJECTS/METHODS: A total of 768 participants from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were included. Cognitive function was measured using five neuropsychological tests: the Trail Making Test, the Verbal Fluency Test, the Selective Reminding Test, the Visual Reproduction Test and the Mini Mental State Exam. Multivariate-adjusted analysis of covariance and linear regression were used to analyze the cross-sectional associations. RESULTS: We found statistically significant associations between serum EPA+DPA+DHA and better performance in the Trail Making Test and the Verbal Fluency Test. The individual associations with EPA and DHA were similar with the findings with EPA+DPA+DHA, although the associations with DHA were stronger. No associations were observed with serum DPA. Pubic hair mercury content was associated only with a worse performance in the Trail Making Test, and mercury had only little impact on the associations between the serum PUFAs and cognitive performance. Apo-E4 phenotype did not modify the associations with PUFAs or mercury. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentrations were associated with better performance on neuropsychological tests of frontal lobe functioning in older men and women. Mercury exposure or Apo-E4 phenotype had little impact on cognitive performance.