cardiovascular-agents and Hyperglycemia

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.

Topics: Anticoagulants; Antiviral Agents; Atherosclerosis; Cardiovascular Agents; COVID-19; COVID-19 Drug Treatment; Disseminated Intravascular Coagulation; Extracellular Traps; Hemorrhage; Humans; Hyperglycemia; Inflammation; Renin-Angiotensin System; SARS-CoV-2; Stroke; Thrombosis

The metabolic syndrome is a multiplex risk factor for atherosclerotic cardiovascular disease and type 2 diabetes. It is composed of atherogenic dyslipidemia, elevated blood pressure, insulin resistance and elevated glucose, a pro-thrombotic state, and a pro-inflammatory state. Excess energy intake and concomitant obesity are the major drivers of the syndrome. Lifestyle intervention can reverse metabolic risk factors, but at times, drug therapies or bariatric surgery may be required to control more overt risk factors.

Topics: Atherosclerosis; Bariatric Surgery; Cardiovascular Agents; Dyslipidemias; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Metabolic Syndrome; Obesity; Risk Factors; Risk Reduction Behavior; Treatment Outcome

Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF.

Topics: Acute Disease; Anemia, Iron-Deficiency; Cardio-Renal Syndrome; Cardiovascular Agents; Comorbidity; Diabetes Complications; Diuretics; Heart Failure; Humans; Hyperglycemia; Hypoglycemic Agents; Iron; Noninvasive Ventilation; Oxygen Inhalation Therapy; Prognosis; Pulmonary Disease, Chronic Obstructive

Diabetes mellitus (DM) and congestive heart failure (HF) commonly coexist in the same patient, and the presence of DM in HF patients is associated with increased adverse events compared with patients without DM. Recent guidelines regarding glycemic control stress individualization of glycemic therapy based on patient comorbid conditions and potential adverse effects of medical therapy. This balance in glycemic control may be particularly relevant in patients with DM and HF. In this review, we address data regarding the influence that certain HF medications may have on glycemic control. Despite potential modest changes in glycemic control, clinical benefits of proven pharmacologic HF therapies extend to patients with DM and HF. In addition, we review potential benefits and challenges associated with commonly used glycemic medications in HF patients. Finally, recent data and controversies on optimal glycemic targets in HF patients are discussed. Given the large number of patients with DM and HF and the health burden of these conditions, much needed future work is necessary to define the optimal glycemic treatment in HF patients with DM.

Topics: Cardiovascular Agents; Diabetes Complications; Heart Failure; Humans; Hyperglycemia; Hypoglycemic Agents; Treatment Outcome

Certain cardiovascular drugs have adverse effects on glucose homeostasis, which may lead to important long-term implications for increased risks of adverse outcomes. Thiazide diuretics, niacin, and beta-adrenergic blockers impair glucose homeostasis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have demonstrated beneficial metabolic effects. The newer vasodilating beta-blocking agents and calcium antagonists appear to be metabolically neutral. These considerations, in addition to meticulous attention to blood pressure control and lifestyle changes, have the potential to beneficially modify glycemia and long-term risks. These considerations have particular importance in younger patients who may also have pre-diabetes or the metabolic syndrome and who are likely to require therapy over the course of decades.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Cardiovascular Agents; Coronary Artery Disease; Glucose Intolerance; Homeostasis; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Metabolic Syndrome; Niacin; Risk Reduction Behavior; Sodium Chloride Symporter Inhibitors

Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.

Topics: Adult; Assisted Circulation; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Chloride; Cardiovascular Agents; Cardiovascular Diseases; Charcoal; Child, Preschool; Combined Modality Therapy; Drug Overdose; Enema; Extracorporeal Circulation; Fat Emulsions, Intravenous; Fluid Therapy; Glucagon; Heart; Humans; Hyperglycemia; Infant; Muscle, Smooth, Vascular; Plasmapheresis; Poisoning; Practice Guidelines as Topic

Diabetes mellitus (DM) is a worldwide epidemic. Its prevalence is rapidly increasing in both developing and developed countries. Coronary heart disease (CHD) is highly prevalent and is the major cause of morbidity and mortality in diabetic patients. The purpose of this review is to assess the clinical impact of recent advances in the epidemiology, prevention, and management of CHD in diabetic patients. A systematic review of publications in this area, referenced in MEDLINE in the past 5 years (2000 to 2005), was undertaken. Patients with CHD and prediabetic states should undergo lifestyle modifications aimed at preventing DM. Pharmacological prevention of DM is also promising but requires further study. In patients with CHD and DM, routine use of aspirin and an angiotensin-converting enzyme inhibitor (ACE-I)--unless contraindicated or not tolerated-and strict glycemic, blood pressure, and lipid control are strongly recommended. The targets for secondary prevention in these patients are relatively well defined, but the strategies to achieve them vary and must be individualized. Intense insulin therapy might be needed for glycemic control, and high-dose statin therapy might be needed for lipid control. For blood pressure control, ACE-Is and angiotensin receptor blockers are considered as first-line therapy. Noncompliance, particularly with lifestyle measures, and underprescription of evidence-based therapies remain important unsolved problems.

Topics: Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Coronary Disease; Diabetes Mellitus, Type 2; Dyslipidemias; Health Behavior; Humans; Hyperglycemia; Hypertension; Insulin Resistance; Life Style; Metabolic Syndrome; Treatment Refusal

Coronary artery bypass graft (CABG) procedures are among the most frequently performed surgical procedures in the United States. People with cardiovascular disease who also have diabetes have a greater risk of poor outcomes after CABG procedures than patients who do not have diabetes. This literature review examines current information regarding perioperative blood glucose (BG) control. It emphasizes BG control in adults during the hypothermic period of cardiopulmonary bypass. Hyperglycemia, not the diagnosis of diabetes, significantly increases the risk of adverse clinical outcomes, longer hospitalizations, and increased health care costs.

Topics: Adult; Blood Glucose; Cardiovascular Agents; Coronary Artery Bypass; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Humans; Hyperglycemia; Hypothermia, Induced; Insulin; Perioperative Nursing; Risk Factors

Topics: Anticholesteremic Agents; Arteriosclerosis; Cardiovascular Agents; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Treatment Outcome

Topics: Analgesics; Animals; Anticholesteremic Agents; Bacteria; Cardiovascular Agents; Drug Evaluation, Preclinical; Humans; Hyperglycemia; Neoplasms; Protease Inhibitors

Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes.. To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation.. Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021.. Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses.. The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2).. Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively.. Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival.. ClinicalTrials.gov Identifier: NCT03640949.

Topics: Aged; Cardiovascular Agents; Confidence Intervals; Denmark; Double-Blind Method; Epinephrine; Female; Glucocorticoids; Heart Arrest; Humans; Hyperglycemia; Hyponatremia; Male; Methylprednisolone; Neurologic Examination; Placebos; Return of Spontaneous Circulation; Treatment Outcome; Uncertainty; Vasoconstrictor Agents; Vasopressins

Ranolazine is a novel antianginal shown in an exploratory analysis in patients with diabetes mellitus and chronic angina to be associated with a decline in hemoglobin A(1c) (HbA(1c)). We designed a prospective evaluation of the effect of ranolazine on hyperglycemia as part of a randomized, double-blind, placebo-controlled outcomes trial.. We compared HbA(1c) (percentage) and the time to onset of a > or =1% increase in HbA(1c) among 4918 patients with acute coronary syndrome randomized to ranolazine or placebo in the MERLIN-TIMI 36 trial. Ranolazine significantly reduced HbA(1c) at 4 months compared with placebo (5.9% versus 6.2%; change from baseline, -0.30 versus -0.04; P<0.001). In patients with diabetes mellitus treated with ranolazine, HbA(1c) declined from 7.5 to 6.9 (change from baseline, -0.64; P<0.001). Diabetic patients were more likely to achieve an HbA(1c) <7% at 4 months with ranolazine compared with placebo (59% versus 49%; P<0.001) and were less likely to have a > or =1% increase in HbA(1c) (14.2% versus 20.6% at 1 year; hazard ratio, 0.63; 95% confidence interval, 0.51 to 0.77; P<0.001). Moreover, ranolazine reduced recurrent ischemia in diabetic patients (hazard ratio, 0.75; 95% confidence interval, 0.61 to 0.93; P=0.008). Notably, in patients without diabetes mellitus at baseline, the incidence of new fasting glucose >110 mg/dL or HbA(1c) > or =6% was reduced by ranolazine (31.8% versus 41.2%; hazard ratio, 0.68; 95% confidence interval, 0.53 to 0.88; P=0.003). Reported hypoglycemia did not increase with ranolazine (P=NS).. Ranolazine significantly improved HbA(1c) and recurrent ischemia in patients with diabetes mellitus and reduced the incidence of increased HbA(1c) in those without evidence of previous hyperglycemia. The mechanism of this effect is under investigation.

Topics: Acetanilides; Acute Coronary Syndrome; Aged; Blood Glucose; Cardiovascular Agents; Diabetes Complications; Diabetes Mellitus; Double-Blind Method; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Male; Metabolic Syndrome; Middle Aged; Piperazines; Prospective Studies; Ranolazine; Recurrence

People with non-diabetic hyperglycaemia might be at risk of lacking adequate control for cardiovascular risk factors. Our aim was to determine the extent of health care utilization and provision in primary care and to evaluate the risk of cardiovascular disease in persons with an elevated risk score in a stepwise diabetes screening programme.. A total of 56,978 non-diabetic patients, aged 50-70 years, from 79 practices in the Netherlands were invited to participate in a screening programme starting with a questionnaire. Those with an elevated score, underwent further glucose testing. Screened participants with type 2 diabetes (n = 64), impaired glucose tolerance (IGT) (n = 62), impaired fasting glucose (IFG) (n = 86), and normal glucose tolerance (NGT) (n = 142) were compared after three years regarding use of medication, care provider encounters and occurrence of CVD.. In all glucose regulation categories cardiovascular medication was prescribed more frequently during follow-up with the strongest increase in diabetic patients. Number of practice visits was higher in diabetic patients compared to those in the other categories. Glucose, lipids, and blood pressure were measured most frequently in diabetic patients. Numbers of cardiovascular events in participants with NGT, IFG, IGT and diabetes were 16.7, 32.6, 17.3 and 15.7 per 1,000 person-years (non significant), respectively.. After three years of follow-up, screened non-diabetic participants with an elevated risk score had cardiovascular event rates comparable with diabetic patients. Screened non-diabetic persons are at risk of lacking optimal control for cardiovascular risk factors while screen-detected diabetic patients were controlled adequately.

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Drug Utilization; Female; Follow-Up Studies; Humans; Hyperglycemia; Hypolipidemic Agents; Incidence; Male; Mass Screening; Middle Aged; Netherlands; Practice Patterns, Physicians'; Risk Assessment; Treatment Outcome

Plasma norepinephrine (NE) and brain natriuretic peptide (BNP, termed BNP-45 in rats) are considered as essential neurohormones indicating heart failure progression. The purposes of this study were to examine the effects of ivabradine (IBD) on cardiac function and plasma NE and BNP-45 after chronic ischemic heart failure (CHF) in non-diabetic rats and diabetic rats. We further determined if sympathetic NE uptake-1 (a major pathway to metabolize NE) mechanism is responsible for the role played by IBD.. We ligated rat's coronary artery to induce CHF; and injected streptozotocin (STZ) to induce diabetic hyperglycemia. Echocardiography was employed to determine cardiac function. We used ELISA to examine plasma NE and BNP-45; and Western Blot analysis to examine the protein levels of NE uptake-1 in sympathetic nerves.. CHF increased the levels of NE and BNP-45 in non-STZ rats and STZ rats. Systemic injection of IBD significantly attenuated the augmented NE and BNP-45 and impaired left ventricular function induced by CHF in those rats. This effect appeared to be less in STZ rats. A liner relation was observed between the NE/BNP-45 levels and left ventricular function after administration of IBD. Also, IBD was observed to have a recovery effect on the downregulated NE uptake-1 evoked by CHF, but to a smaller degree in STZ rats.. Our data revealed specific signaling mechanisms by which IBD improves the cardiac function as IBD alleviates impaired NE uptake-1and thereby decreases heightened NE and BNP-45 induced by CHF. Our data also demonstrated that the effects of IBD are weakened after diabetic hyperglycemia likely due to worsen NE uptake-1 pathway. Thus, targeting sympathetic NE uptake-1 signaling molecules has clinical implications for treatment and management of CHF in diabetes. Our data were also to shed light on strategies for application of this drug because NE and BNP play an important role in regulation of progression and prognosis of CHF, and in particular, because IBD affects NE uptake-1 pathway in hyperglycemic animals to a less degree.

Topics: Animals; Benzazepines; Cardiovascular Agents; Coronary Vessels; Diabetes Mellitus, Experimental; Disease Models, Animal; Echocardiography; Heart Failure; Heart Function Tests; Hyperglycemia; Ivabradine; Ligation; Male; Myocardial Infarction; Nerve Tissue Proteins; Norepinephrine; Rats; Rats, Sprague-Dawley; Signal Transduction; Streptozocin

This registry study aimed to evaluate the effects of supplementation with pycnogenol on altered endothelial function (EF) in borderline hypertensive, hyperlipidemic and hyperglycemic subjects without atherosclerotic changes in their main arteries and no coronary artery disease.. Flow mediated dilatation (FMD) and endothelium-independent (EID) dilatation were measured with brachial ultrasound after occlusion. Also, after occlusion, laser Doppler (LDF) flux and distal straingauge flow were measured. Oxidative stress (oxstress) was evaluated at 8 and 12 weeks. 93 subjects with borderline symptoms were enrolled into the study: 32 hypertensives, 31 hyperlipidemics, 30 hyperglycemics. All participants were instructed to follow the best available management to control their symptoms. In addition to best management, half of the subjects in each group used 150 mg/day Pycnogenol(®). 31 normal subjects were included as control.. After 12 weeks metabolic values and blood pressure were back to normal in all subjects. Values were slightly better under Pycnogenol(®). FMD increased after 8 weeks from an average 5.3;3.4% to 8.2;2.2% with a further increase to 8.8;3.1% (P<0.05) at 12 weeks. No effects were found in controls and normal subjects. EID of normal subjects was consistently higher with 26%. LDF skin flux increased with Pycnogenol(®) at 8 weeks and 12 weeks. The final flux increase was not different from normal values. In controls flux after occlusion was not improved at 8 weeks; there was a significant but minor increase at 12 weeks. Flux increases were superior in all Pycnogenol(®) subjects. In Pycnogenol(®) subjects, limb flow after occlusion increased at 8 weeks with a further increase at 12 weeks. In controls inclusion flow after occlusion was comparable at 8 and 12 weeks. Oxidative stress was significantly decreased in Pycnogenol(®) subjects at 8 and 12 weeks. Minor differences were observed in controls.. This open registry study indicates that Pycnogenol(®) improves EF in preclinical, borderline subjects in a macro-microcirculatory model. This observation may suggest an important preventive possibility for borderline hypertensive, hyperglycemic and hyperlipidemic subjects.

Topics: Adult; Antioxidants; Biomarkers; Blood Flow Velocity; Blood Glucose; Blood Pressure; Brachial Artery; Cardiovascular Agents; Case-Control Studies; Endothelium, Vascular; Female; Flavonoids; Humans; Hyperglycemia; Hyperlipidemias; Hypertension; Laser-Doppler Flowmetry; Lipids; Male; Middle Aged; Oxidative Stress; Plant Extracts; Plethysmography; Predictive Value of Tests; Registries; Time Factors; Treatment Outcome; Ultrasonography; Vasodilation

Postoperative atrial fibrillation (AF) is a common complication following coronary artery bypass grafting (CABG). We investigated the risk factors for postoperative AF and analyzed the relationship between blood sugar concentration (BS) and AF after CABG.. A total of 199 consecutive patients who underwent isolated CABG were retrospectively examined and classified according to the presence (n=95) or absence (n=104) of postoperative AF. On univariate analysis mean postoperative BS (P<0.001), postoperative drainage volume (P<0.001), age (P=0.034), presence of diabetes mellitus (DM; P=0.004), and postoperative estimated glomerular filtration rate (P=0.032) were significant risk factors for postoperative AF. On multivariate analysis mean postoperative BS (OR, 1.041; 95% CI: 1.008-1.079; P<0.001), postoperative drainage volume (OR, 1.003; 95% CI: 1.001-1.006; P=0.001), and age (OR, 1.040; 95% CI: 1.002-1.083; P=0.041) were significant risk factors for postoperative AF. Postoperative AF often occurred in patients with high postoperative BS, irrespective of DM. The BS cut-off that predicted postoperative AF occurrence was 180 mg/dl. A strong positive correlation existed between the time of the maximum postoperative BS and AF onset time (ρ=0.746).. Mean postoperative BS and postoperative drainage volume are risk factors for AF after CABG. AF was strongly associated with maximum postoperative BS. Intensive glycemic control could reduce AF occurrence after CABG.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Blood Glucose; Cardiovascular Agents; Case-Control Studies; Cerebral Infarction; Comorbidity; Coronary Artery Bypass; Diabetes Mellitus; Female; Humans; Hyperglycemia; Male; Odds Ratio; Postoperative Complications; Retrospective Studies; Risk Factors

This report contains authors own data about hyperglycemia impact on main functional properties of endothelial cells, mesenchymal stem cells and circulating progenitor cells, which define their participation in angiogenesis. Obtained data shows that cultivation of endothelial cells in hyperglycemic conditions leads to decrease of their ability for targeted migration and vascular-like structures formation on matrigel, and to suppression of VEGF receptors expression in these cells. Mesenchymal stem cells cultivated in hyperglycemic conditions have altered expression profile, decreased ability to stimulate angiogenesis via paracrine activity. Hyperglycemia in CHD patients with concomitant diabetes mellitus type II most probably lead to circulating bone marrow progenitor cells mobilisation distortion in response to tissue ischemia and damage to the endothelium, that can infringe upon their participation in endothelium reparation and angio- and vasculogenesis in the ischemic conditions. Found distortions can be used as targets for the treatment aimed at cardiovascular complications prevention in diabetic patients.

Topics: Bone Marrow Cells; Cardiovascular Agents; Cell Movement; Diabetes Mellitus; Drug Discovery; Endothelial Cells; Endothelium, Vascular; Humans; Hyperglycemia; Myocardial Ischemia; Neovascularization, Physiologic; Receptors, Vascular Endothelial Growth Factor; Secondary Prevention; Stem Cells

We investigated the expression of the proinflammatory cytokine interleukin (IL)-17 in cardiac fibroblasts and its induction by high glucose (HG). Our results show that primary mouse cardiac fibroblasts (mCFs) secrete low basal levels of IL-17 and that HG (25 mM D-glucose) as opposed to low glucose (5 mM D-glucose + 20 mM mannitol) significantly enhances its secretion. HG induces IL-17 mRNA expression by both transcriptional and posttranscriptional mechanisms. HG induces phosphoinositide 3- kinase [PI3K; inhibited by adenoviral (Ad).dominant negative (dn)PI3Kp85], Akt (inhibited by Ad.dnAkt1), and ERK (inhibited by PD-98059) activation and induces IL-17 expression via PI3K-->Akt-->ERK-dependent signaling. Moreover, mCFs express both IL-17 receptors A and C, and although IL-17RA is upregulated, HG fails to modulate IL-17RC expression. Furthermore, IL-17 stimulates net collagen production by mCFs. Pretreatment with the phytoalexin resveratrol blocks HG-induced PI3K-, Akt-, and ERK-dependent IL-17 expression. These results demonstrate that 1) cardiac fibroblasts express IL-17 and its receptors; 2) HG upregulates IL-17 and IL-17RA, suggesting a positive amplification loop in IL-17 signaling in hyperglycemia; 3) IL-17 enhances net collagen production; and 4) resveratrol can inhibit these HG-induced changes. Thus, in hyperglycemic conditions, IL-17 may potentiate myocardial inflammation, injury, and remodeling through autocrine and paracrine mechanisms, and resveratrol has therapeutic potential in ameliorating this effect.

Topics: Animals; Cardiovascular Agents; Cell Culture Techniques; Cells, Cultured; Collagen; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Flavonoids; Glucose; Hyperglycemia; Interleukin-17; Male; Mice; Mice, Inbred C57BL; Myocardium; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Receptors, Interleukin; Receptors, Interleukin-17; Resveratrol; RNA, Messenger; Signal Transduction; Stilbenes; Time Factors; Up-Regulation

To determine the effect of insulin for the management of hyperglycaemia in non-diabetic patients presenting with acute coronary syndrome.. An observational study from the MINAP (National Audit of Myocardial Infarction Project) database during 2003-5 in 201 hospitals in England and Wales. Patients were those with a final diagnosis of troponin-positive acute coronary syndrome who were not previously known to have diabetes mellitus and whose blood glucose on admission was > or = 11 mmol/l. The main outcome measure was death at 7 and 30 days.. Of 38,864 patients who were not previously known to be diabetic, 3835 (9.9%) had an admission glucose > or = 11 mmol/l. Of patients having a clear treatment strategy, 36% received diabetic treatment (31% with insulin). Mortality at 7 and 30 days was 11.6% and 15.8%, respectively, for those receiving insulin, and 16.5% and 22.1%, respectively, for those who did not. Compared with those who received insulin, after adjustment for age, gender, co-morbidities and admission blood glucose concentration, patients who were not treated with insulin had a relative increased risk of death of 56% at 7 days and 51% at 30 days (HR 1.56, 95% CI 1.22 to 2.0, p<0.001 at 7 days; HR 1.51, 95% CI 1.22 to 1.86, p<0.001 at 30 days).. In non-diabetic patients with acute coronary syndrome and hyperglycaemia, treatment with insulin was associated with a reduction in the relative risk of death, evident within 7 days of admission, which persists at 30 days.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Blood Glucose; Cardiovascular Agents; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Myocardial Reperfusion; Treatment Outcome

Topics: Acute Disease; Brain Edema; Brain Ischemia; Cardiovascular Agents; Case Management; Combined Modality Therapy; Decompression, Surgical; Fever; Humans; Hyperglycemia; Hypertension; Hypoxia; Intracranial Hypertension; Pneumonia; Thrombolytic Therapy; Urinary Tract Infections; Water-Electrolyte Imbalance

Topics: Adrenalectomy; Adrenergic Agents; Animals; Autonomic Nerve Block; Body Temperature; Cardiovascular Agents; Dogs; Ergoloid Mesylates; Ergot Alkaloids; Hyperglycemia; Hypothermia; Oxytocics

Topics: Cardiovascular Agents; Dihydroergotoxine; Epinephrine; Ergot Alkaloids; Hyperglycemia; Oxytocics