dinoprost and Myocardial-Infarction

The Intrinsic Sympathetic Activity (ISA) of the beta-1-adrenoceptor blocker celiprolol was tested in a series of pharmacological and clinical investigations. Celiprolol shows much more pronounced positive chronotropic effects in spontaneously beating atria of cats than in those of guinea-pigs and rats. Positive inotropic effects of celiprolol are much pronounced in the left kitten atrium, but scarcely demonstrable in the kitten papillary muscle. Celiprolol has no influence on the adenylyl cyclase activity of the dog heart. In reserpinized rats and reserpinized, adrenalectomized, vagotomized cats celiprolol increases the heart rate to the same extent as the beta-blocker pindolol. In ganglion-blocked dogs celiprolol distinctly increases heart rate and left ventricular contraction force. Celiprolol relaxes isolated human arterial and venous strips and induces a transient increase of the femoral arterial blood flow in anaesthetized dogs. Celiprolol relaxes isolated bovine tracheal muscle preparations and reduces the airway resistance in anaesthetized cats infused with serotonin. The intrinsic chronotropic effects of celiprolol in cat atria in vitro and in reserpinized rats in vivo and the relaxing effects of celiprolol in isolated bovine tracheal muscles are antagonized by propranolol, and therefore these actions may be explained by the ISA of celiprolol. However the vascular relaxing effects of celiprolol in vitro and in vivo and the bronchodilating effects in the serotonin-infused cat are not blocked by propranolol. In order to obtain a more precise characterization of these surprising effects, further pharmacological investigations were done. In the isolated femoral artery of the dog the concentration-response curve of calcium chloride is not influenced by celiprolol while it is antagonized by verapamil. A serotonin antagonistic effect cannot be demonstrated for celiprolol either in receptor binding studies or on the blood pressure of anaesthetized dogs. Celiprolol inhibits the methacholine bronchospasm in rats and the prostaglandin F2 alpha-induced bronchoconstriction in cats. The histamine-induced bronchoconstriction in dogs is scarcely affected by celiprolol while it is enhanced by propranolol. In radioligand studies celiprolol shows a tenfold higher affinity for alpha-2 in comparison to alpha-1 receptors. Celiprolol enhances the inhibitory effect of clonidine in the electrically stimulated vas deferens of the rat in vitro.(ABSTRACT TRUNCATED AT 400 WOR

Topics: Adrenergic beta-Antagonists; Animals; Asthma; Blood Coagulation; Bronchi; Bronchial Spasm; Calcium Channel Blockers; Celiprolol; Dinoprost; Heart; Hemodynamics; Histamine; Humans; Myocardial Infarction; Propanolamines; Prostaglandins F; Receptors, Adrenergic, alpha; Respiration; Serotonin Antagonists; Sympathomimetics

Recent studies have shown, that chronic flavonoids treatment improves vascular function and cardiovascular remodeling by decreasing superoxide anion production as well as by increasing NO realize from endothelial cells. A progressive decrease in systolic blood pressure and reduction of low-density lipoprotein oxidation (Ox-LDL) has also been reported. However, none of these studies were done in patient with coronary artery disease treated with statins. This was a double-blind, placebo-controlled, parallel trial. Forty-four patients (11 women and 33 men, mean age 66 years) who survived myocardial infraction and have received statin therapy for at least 6 months (80% dose of 40 mg/day simvastatin) were included in the study. The subjects were randomised to receive either 3 x 85 mg/day of chokeberry flavonoid extract (Aronia melanocarpa E) or placebo for a period of 6 weeks. The study extract was a commercially-available (OTC) product of the following declared composition: anthocyans (about 25%), polymeric procyanidines (about 50%) and phenolic acids (about 9%). Compared to placebo (ANOVA and Tukey's test), flavonoids significantly reduced serum 8-isoprostans (p<0.000) and Ox-LDL levels (p<0.000) (by 38 and 29%, respectively), as well as hsCRP (p<0.007) and MCP-1 (p<0.001) levels (by 23 and 29%, respectively). In addition, significant increase in adiponectin (p<0.03) levels and reduction in systolic and diastolic blood pressure by a mean average of 11 and 7.2 mmHg, respectively were found.. In view of the fact that chokeberry flavonoids reduce the severity of inflammation, regardless of statins, they can be used clinically for secondary prevention of ischaemic heart disease.

Topics: Adiponectin; Aged; Blood Pressure; C-Reactive Protein; Dinoprost; Double-Blind Method; Drug Therapy, Combination; Endopeptidases; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Lipoproteins, LDL; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Photinia; Phytotherapy; Plant Extracts

Previous studies support a role of oxygen-free radicals in the development of congestive heart failure (CHF). The aim of this study was to investigate whether lipid peroxidation is increased in CHF patients on modern pharmacological therapy and whether there is a positive correlation between plasma levels of markers of lipid peroxidation and severity of heart failure (HF). Plasma malondialdehyde (MDA) and isoprostanes are often used as markers of lipid peroxidation and oxidative stress. We also studied whether long-term treatment with isosorbide-5-mononitrate (IS-5-MN) in combination with standard HF therapy affects P-MDA levels in patients with evidence of left ventricular (LV) dysfunction following acute myocardial infarction (AMI).. Ninety-two patients with clinical or echocardiographic evidence of LV-dysfunction following AMI were randomized to treatment with either IS-5-MN or placebo. In a subgroup of 83 patients with available plasma MDA, echocardiography, right-heart catherization, and plasma natriuretic peptides were evaluated. Control subjects were 80 healthy blood donors. A second study group consisted of 56 patients with CHF, evaluated with respect to LV function, brain natriuretic peptide and markers of oxidative stress (P-MDA and 8-isoprostane). The second control group comprised 50 healthy subjects.. Lipid peroxidation measured by P-MDA and 8-isoprostane was not increased in patients with LV dysfunction treated with standard HF therapy. No positive correlation was found to the severity of HF. Long-term IS-5-MN therapy did not influence P-MDA concentrations.. Although results from many experimental and clinical studies suggest that oxidative stress is increased in HF, this may not be true for patients treated with beta blockers and inhibitors of the renin-angiotensin system.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Captopril; Comorbidity; Delayed-Action Preparations; Dinoprost; Female; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Lipid Peroxidation; Losartan; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nitric Oxide Donors; Oxidative Stress; Ramipril; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left

In acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), myocardial injury results from complex processes during both ischemia and reperfusion. Release of reactive oxygen species (ROS) may contribute to the accumulated myocardial damage.. To examine by frequent sampling of peripheral blood oxidative stress and early inflammation in patients undergoing primary PCI for AMI. Secondly, to assess whether a correlation exists between these parameters and the extent of myocardial damage.. Sixteen patients undergoing primary PCI within 6 h of AMI onset were included. Peripheral blood was sampled at start of procedure (t0) and repeatedly over 24 h following reperfusion. Main plasma analyses were: 8-iso-PGF2alpha (oxidative stress), 15-keto-dihydro-PGF2alpha (cyclooxygenase-mediated inflammation); and troponin-T (myocardial injury). Additional analyses included: total antioxidant status (TAS); vitamins; hsCRP and lipids.. 8-Iso-PGF2alpha increased following restoration of blood flow, returned to t0 values after 3 h and was reduced below t0 the following day. TAS decreased significantly from t0 to the next day. There was no significant correlation between 8-iso-PGF2alpha and troponin T values. 15-Keto-dihydro-PGF2alpha was elevated during the first hour. There was a major rise in hsCRP after 24 h.. Following reperfusion by primary PCI in AMI, oxidative stress and an inflammatory response are induced immediately. A rise in 8-iso-PGF2a during ischemia indicate that ROS generation may also take place during severely reduced coronary blood flow and hypoxia. No direct relationship between 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha and troponin T was evident. The present study adds to the increasingly complex pathophysiological roles of ROS acting both as signal molecules and as mediators of tissue injury.

Topics: Acute Disease; Adult; Aged; Coronary Vessels; Dinoprost; Female; Humans; Hydroxylation; Inflammation; Lipid Metabolism; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Serum Albumin; Troponin T

Early reperfusion therapy improves the clinical outcomes of patients with acute myocardial infarction (AMI), but benefits are limited by reperfusion injury in some patients. We examined the effect of nicorandil, a hybrid of K(ATP) channel opener and nicotinamide nitrate, on reactive oxygen species (ROS) formation and clinical outcomes after primary percutaneous coronary intervention (PCI) for AMI.. Fifty-eight patients with AMI were randomized into control (n = 25) and nicorandil pretreatment groups (n = 33). In the nicorandil group, nicorandil (4 mg as a bolus injection followed by constant infusion at 8 mg/hour for 24 hours) was administered just after admission. ROS formation was assessed by measuring urinary excretion of 8-epi-prostaglandin F2alpha (PGF2alpha) and compared between the 2 groups. Cardiac function and the incidence of reperfusion injury and cardiac events were also compared.. Urinary 8-epi-PGF2alpha excretion was increased 2-fold at 60 to 90 minutes after PCI in the control group, whereas it was unchanged after PCI in the nicorandil group (P <.0001 between the 2 groups). The incidence of no-reflow phenomenon was lower in the nicorandil group than in the control group. Left ventricular ejection fraction and cardiac index at 6 months were greater in the nicorandil group than in controls. Plasma brain natriuretic peptide level at 6 months was lower in the nicorandil group. Incidences of inhospital cardiac events and rehospitalization were lower in the nicorandil group than in controls.. Nicorandil improves cardiac function and clinical outcomes in patients with AMI. Suppression of ROS formation may be involved in the mechanism.

Topics: Aged; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Infarction; Nicorandil; Premedication; Pulmonary Wedge Pressure; Reactive Oxygen Species; Stroke Volume; Treatment Outcome; Vasodilator Agents; Ventricular Function, Left

Allopurinol, an inhibitor of xanthine oxidase, was shown to improve the regional ventricular function after coronary artery occlusion and reperfusion in animal models. The effects of oral administration of allopurinol on a transient increase in free radical generation after primary percutaneous transluminal coronary angioplasty (PTCA) in patients with acute myocardial infarction (AMI) and on their clinical outcomes were examined. Thirty-eight AMI patients undergoing primary PTCA were randomly assigned to control (group 1, n = 20) and allopurinol treatment groups (group 2, n = 18). Allopurinol (400 mg) was administered orally just after the admission (approximately 60 min before reperfusion). Free radical production was assessed by successive measurement of urinary excretion of 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) after PTCA. Urinary 8-epi-PGF(2alpha) excretion was increased by twofold at 60-90 min after PTCA compared with the baseline value in group 1. This increase was completely inhibited in group 2. Plasma allopurinol concentration was 1,146 +/- 55 ng/ml in group 2 when reperfusion was achieved. Slow flow in the recanalized coronary artery after PTCA occurred less frequently in group 2 than in group 1. Cardiac index determined just after reperfusion and left ventricular ejection fraction at 6 months after PTCA were both significantly greater in group 2 than in group 1 although pulmonary capillary wedge pressure was similar in the two groups. In conclusion, allopurinol pretreatment is effective in inhibiting generation of oxygen-derived radicals during reperfusion therapy and the recovery of left ventricular function in humans.

Topics: Administration, Oral; Aged; Allopurinol; Angioplasty, Balloon, Coronary; Dinoprost; Electrocardiography; F2-Isoprostanes; Female; Free Radical Scavengers; Free Radicals; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion Injury; Oxypurinol; Ventricular Function, Left

Reactive oxygen species are thought to mediate reperfusion injury after rapid revascularization for acute myocardial infarction (AMI) and 8-epi prostaglandin (PG) F2alpha, a free-radical catalyzed product of arachidonic acid, has been proposed as an indicator of oxidative stress in vivo during myocardial reperfusion. The time course of urinary 8-epi PGF2alpha excretion after primary coronary angioplasty (PTCA) for AMI was investigated, as well as the effect of prior administration of vitamin C. Urine samples, 1 before and 5 after primary PTCA (0-30, 30-60, 60-90, 90-120 and 120-150 min), were collected in 11 patients with AMI undergoing primary PTCA (Group 1), 10 patients with AMI treated with water-soluble vitamin C at an initial dose of 2.0 g followed by a constant infusion at 20mg/min prior to primary PTCA (Group 2), and 6 patients with stable effort angina undergoing elective PTCA (Group 3). 8-epi PGF2alpha was measured by enzyme immunoassay. There were no significant differences in urinary 8-epi PGF2alpha excretion at baseline among the 3 groups. In Group 1, urinary 8-epi PGF2alpha excretion (ng/mmol creatinine) significantly increased from 60+/-8 at baseline to 122+/-16 at 60-90 min (p<0.001), and declined to the baseline level at 120-150 min after primary PTCA. In Group 2, it also increased from 72+/-12 to 123+/-15 at 60-90 min (p<0.01), and the percent increase did not differ from that in Group 1. In Group 3, it remained unchanged during the study period. The free radical production is rapidly and transiently enhanced after primary PTCA for AMI, and vitamin C fails to suppress it.

Topics: Aged; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Dinoprost; F2-Isoprostanes; Female; Free Radicals; Humans; Male; Middle Aged; Myocardial Infarction

All 701 heart infarction patients admitted to 15 hospitals in the district of Cottbus between 1981 and 1983 were randomly administered 30, 60 or 1000 mg aspirin daily according to the territorial affiliation of their local hospitals. The physical and drug therapy during the 2 years follow-up was highly standardized; deviations--as far as they occurred--were documented. Lower all-cause mortality was statistically demonstrated in patients over 60 and a lower fatal reinfarction rate in patients over 50 as well as in men. Deaths and fatal reinfarctions were significantly lower among patients with a history of angina pectoris, marked ST-depression, with an infarction location except for the posterior wall and among hypercholesterolemic patients. The preventive effect of 60 mg aspirin daily was less than that of 30 mg in comparison to the 1000 mg group. Side effects were seen in 4 and 8% (first and second year), respectively, of the patients administered 30 mg aspirin as opposed to 22 and 17% in patients allocated 1000 mg. We conclude that the optimum dose of aspirin for preventing reinfarctions could be as low as 30 mg daily.

Topics: Aged; Aspirin; Dinoprost; Follow-Up Studies; Gastrointestinal Diseases; Germany; Hospitals, District; Humans; Middle Aged; Myocardial Infarction; Random Allocation; Recurrence; Survival Rate; Thromboxane B2

In a secondary prevention study 867 male and female patients with myocardial infarction (MI) were divided 3 weeks after onset of MI into 4 treatment groups: I - 273 patients received additionally to their common medication 1000 mg ASA/d; II - 313 patients got 60 mg ASA/d; III - 208 patients 30 mg ASA/d resp.; IV - 73 patients received no ASA administration due to ASA contraindications. One year after onset of MI the following parameters were checked: mortality, malignant arrhythmia, exercise tolerance, gastrointestinal symptoms and hemorrhage as typical side effects of ASA, formation of thromboxane B2 and PGF2 alpha in clotting whole blood. The low dose of 30 mg ASA/d reśultes in a clear reduction of ASA side effects (6,4% of patients with symptoms) in comparison to group I (15,9% of patients with symptoms), in a tendency to decreased mortality, and in unchanged frequency of malignant arrhythmias resp. Concerning the maximum exercise tolerance no significant difference could be observed in all 4 groups investigated. Estimations of serum thromboxane B2 by radioimmunoassay and gas chromatography revealed strong inhibitions of the thromboxane formation in all patients with ASA administrations; even the low dose of 30 mg ASA/d decreased thromboxane B2 by more than 95%.

Topics: Adult; Aged; Aspirin; Clinical Trials as Topic; Dinoprost; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Prostaglandins F; Thromboxane B2; Thromboxanes

Cardioprotective actions of ischemic postconditioning (IPostC) against ischemia/reperfusion (I/R) injury are abolished in diabetic hearts. This study has investigated the combined effects of IPostC and vildagliptin (Vilda) on myocardial function and infarct size (IS) against I/R injury in diabetic myocardium.. Diabetes was induced by a high-fat diet/low dose of streptozotocin (35 mg/kg; intraperitoneally) in Wistar rats (200-250 g) and lasted for 12 weeks. Vilda (6 mg/kg/d) was orally administered for 5 weeks in diabetic groups after seventh week of diabetes. At the end of the 12-week period, the hearts of rats were removed and subjected to 35-minute regional ischemia (through left anterior descending ligation) followed by 60-minute reperfusion, on Langendorff apparatus. Ischemic postconditioning was induced by 6 repetitive cycles of 10-second ischemia and 10-second reperfusion, immediately at the onset of the reperfusion. Myocardial hemodynamic was measured throughout the experiment. The IS was assessed by triphenyltetrazolium chloride staining method. The myocardial contents of troponin-I (cTnI), interleukin-6 (IL-6), and 8-isoprostane were measured in the homogenate from ischemic zone of left ventricles by enzyme-linked immunosorbent assay kit.. Pretreatment of the diabetic rats with Vilda significantly recovered the diabetes-induced reduction in left ventricular developed pressures and contractility at the baseline ( P < .05 to P < .01). After I/R injury, IPostC could not significantly improve the myocardial function, cTnI content, and IS of the diabetic hearts. However, in Vilda-treated hearts, concomitant application of IPostC significantly recovered the heart functions, returned cTnI content as well as myocardial IL-6 and 8-isoprostane levels back to the control values ( P < .01 to P < .001), and reduced IS more effectively (by 45%) in comparison to the diabetic group ( P < .001).. Besides its glycemic and lipid profile controlling effects, Vilda has a protective effect on heart function and tends to restore cardioprotective effects of IPostC on diabetic hearts.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Dinoprost; Dipeptidyl-Peptidase IV Inhibitors; Insulin; Interleukin-6; Ischemic Postconditioning; Isolated Heart Preparation; Lipids; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Rats, Wistar; Troponin I; Ventricular Function, Left; Ventricular Pressure; Vildagliptin

There are limited prospective data evaluating the role of urinary F2-IsoP and NOX2 as predictive markers in atrial fibrillation (AF). The aim of this study was to analyse the role of urinary prostaglandin PGF2alpha (8-iso-PGF2α) and NOX2, markers of systemic oxidative stress, in predicting cardiovascular (CV) events and mortality in anticoagulated non-valvular AF patients. This was a prospective study including 1,002 anticoagulated AF patients, followed for a median time of 25.7 months (interquartile range: 14.8-50.9). All major CV events, CV deaths and all-cause deaths were considered as primary outcomes of the study. CV events included fatal/nonfatal ischaemic stroke, fatal/nonfatal myocardial infarction (MI), cardiac revascularisation and transient ischaemic attack (TIA). Oxidative stress biomarkers, such as urinary 8-iso-PGF2α and serum sNOX2-dp, a marker of NOX2 activation, were measured. A CV event occurred in 125 patients (12.5 %); 78 CV deaths and 31 non-CV deaths were registered. 8-iso-PGF2α and sNOX2-dp were correlated (Rs=0.765 p< 0.001). A significant increased cumulative incidence of CV events and CV deaths was observed across tertiles for 8-iso-PGF2α and sNOX2-dp. An increased rate of all-cause death was observed across tertiles of urinary 8-iso-PGF2α. In Cox or Fine and Gray models, 8-iso-PGF2α predicted CV events and CV and non-CV deaths. The addition of tertiles of 8-iso-PGF2α to CHA2DS2-VASc score improved ROC curves for each outcome and NRI for CV events (0.24 [0.06-0.53] p=0.0067). The study shows that in AF patients 8-iso-PGF2α and NOX2 levels are predictive of CV events and total mortality. F2-IsoP may complement conventional risk factors in prediction of CV events.

Topics: Aged; Aged, 80 and over; Area Under Curve; Atrial Fibrillation; Biomarkers; Brain Ischemia; Cause of Death; Cerebrovascular Disorders; Dinoprost; Female; Humans; Incidence; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Membrane Glycoproteins; Middle Aged; Myocardial Infarction; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Factors; ROC Curve; Rome; Stroke; Time Factors

Activation of PKCβ (protein kinase Cβ) plays a critical role in myocardial I/R (ischaemia/reperfusion) injury in non-diabetic rodents. In the myocardium of diabetes, PKCβ2 overexpression is associated with increased vulnerability to post-ischaemic I/R injury with concomitantly impaired cardiomyocyte Cav (caveolin)-3 and Akt signalling compared with non-diabetic rats. We hypothesized that myocardial PKCβ overexpression in diabetes exacerbates myocardial I/R injury through impairing Cav-3/Akt signalling. Streptozotocin-induced diabetic rats were treated with the selective PKCβ inhibitor ruboxistaurin (RBX, 1 mg/kg per day) for 4 weeks, starting from 1 week after diabetes induction, before inducing myocardial I/R achieved by occluding the left descending coronary artery followed by reperfusion. Cardiac function was measured using a pressure-volume conductance system. In an in vitro study, cardiac H9C2 cells were exposed to high glucose (30 mmol/l) and subjected to hypoxia followed by reoxygenation (H/R) in the presence or absence of the selective PKCβ2 inhibitor CGP53353 (1 μmol/l), siRNAs of PKCβ2 or Cav-3 or Akt. Cell apoptosis and mitochondrial membrane potential were assessed by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) and JC-1 staining respectively. RBX significantly decreased post-ischaemic myocardial infarct size (35±5% compared with 49±3% in control, P<0.05) and attenuated cardiac dysfunction, and prevented the reduction in cardiac Cav-3 and enhanced phosphorylated/activated Akt (p-Akt) in diabetic rats (P<0.05). H/R increased cardiomyocyte injury under high glucose conditions as was evident by increased TUNEL-positive and increased JC-1 monomeric cells (P<0.05 compared with control), accompanied with increased PKCβ2 phosphorylation/activation and decreased Cav-3 expression. Either CGP53353 or PKCβ2 siRNA significantly attenuated all of these changes and enhanced p-Akt. Cav-3 gene knockdown significantly reduced p-Akt and increased post-hypoxic cellular and mitochondrial injury despite a concomitant reduction in PKCβ2 phosphorylation. PKCβ2 inhibition with RBX protects diabetic hearts from myocardial I/R injury through Cav-3-dependent activation of Akt.

Topics: Animals; Apoptosis; Caveolin 3; Cell Line; Diabetes Mellitus, Experimental; Dinoprost; Enzyme Activation; Indoles; Isoprostanes; Male; Maleimides; Membrane Potential, Mitochondrial; Mitochondria, Heart; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Phosphorylation; Phthalimides; Protein Kinase C beta; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; RNA Interference; Signal Transduction; Time Factors; Transfection; Ventricular Function, Left

In the present study, we tested the hypothesis that oxidative stress could be implicated in myocardial damage during the acute phase of pneumonia. NOX2 activation, the catalytic subunit of NADPH oxidase, and high-sensitivity cardiac troponin T (hs-cTnT) elevation have been analyzed in two hundred forty-eight consecutive patients hospitalized for community-acquired pneumonia. Serum NOX2-derived peptide (sNOX2-dp), a marker of NOX2 activation, and 8-isoprostaglandin F2α (8-iso-PGF2α), a marker of oxidative stress, were measured upon admission; serum hs-cTnT and ECG were measured every 12 and 24 h, respectively. One hundred thirty-five patients (54%) showed elevated serum levels of hs-cTnT (>0.014 μg/L). A logistic regression analysis showed sNOX2-dp (p<0.001), Pneumonia Severity Index score (p<0.001), renal failure (p=0.024), and ejection fraction (p<0.001) as independent predictors of elevated serum levels of hs-cTnT. Serum sNOX2-dp was linearly correlated with hs-cTnT (Rs=0.538; p<0.001) and 8-iso-PGF2α (Rs=0.354; p<0.001). The study provides the first evidence of a significant association between serum cardiac Troponin T elevation and NOX2 upregulation in patients with pneumonia. This finding raises the hypothesis that NOX2-derived oxidative stress may be implicated in myocardial injury and that its inhibition could be a novel therapeutic strategy to limit it.

Topics: Aged; Aged, 80 and over; Biomarkers; Cohort Studies; Community-Acquired Infections; Dinoprost; Female; Humans; Logistic Models; Male; Membrane Glycoproteins; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardium; NADPH Oxidase 2; NADPH Oxidases; Odds Ratio; Oxidative Stress; Pneumonia; Reactive Oxygen Species; Severity of Illness Index; Troponin T; Up-Regulation

Elevated asymmetric dimethylarginine (ADMA) is associated with an increased risk of coronary artery disease. A prognostic value of ADMA following coronary artery bypass grafting (CABG) is unknown. The aim of the current study was to assess the effect of CABG on ADMA and oxidative stress and determine their associations with postoperative complications.. In 158 consecutive patients (35 women, 123 men, aged 65.2 ± standard deviation 8.2 years) undergoing isolated, elective CABG procedure, we measured plasma ADMA and 8-iso-prostaglandin F2α (8-iso-PGF2α) preoperatively and twice postoperatively: 18-36 h and 5-7 days after surgery. The primary end points were postoperative myocardial infarction (PMI) and in-hospital cardiovascular death.. ADMA increased from 0.56 ± 0.06 μmol/l at baseline by 68% to 0.94 ± 0.11 μmol/l at 18-36 h after CABG, and then decreased by 20% to 0.75 ± 0.12 μmol/l on 5-7 days postoperatively (P = 0.0001 for all comparisons). A similar pattern of changes was observed for 8-iso-PGF2α. Thirteen (8.2%) patients developed PMI, and 6 patients (3.8%) died during the early postoperative period because of extensive PMI. PMI and early perioperative mortality were positively associated with ADMA and 8-iso-PGF2α.. A marked increase of ADMA and oxidative stress is observed within the first days following CABG, and is associated with unfavourable early post-CABG outcomes, including PMI and in-hospital cardiovascular death.

Topics: Aged; Arginine; Coronary Artery Bypass; Dinoprost; Female; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Postoperative Complications

Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI).. Consecutive patients with STEMI (n = 116) were enrolled <24-h of symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFα), 8-isoprostane, nitric oxide (NOx) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography.. Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFα, 8-isoprostane levels or CTB. The rise in NOx from D1 to D5 was inferior [3.5(-1; 10) vs. 5.5(-1; 12); p < 0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p = 0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thiobarbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r = 0.72; p = 0.014) and FMD (r = -0.61; p = 0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25-132; p = 0.032) and 180 days (OR 3.3; 95% CI 1.03-10.7; p = 0.044).. An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome.

Topics: Aged; Angiography; C-Reactive Protein; Cholesterol Ester Transfer Proteins; Dinoprost; Endothelium, Vascular; Female; Humans; Interleukin-2; Lipoproteins, HDL; Male; Middle Aged; Myocardial Infarction; Nitric Oxide; Oxygen; Prospective Studies; Registries; Thiobarbituric Acid Reactive Substances; Treatment Outcome; Tumor Necrosis Factor-alpha; Vascular Diseases

Large body of evidences accumulated in clinical and epidemiological studies indicate that hearts of diabetic subjects are more sensitive to ischemia reperfusion injury (IRI), which results in a higher rate of mortality at post-operation than that of non-diabetes. However, experimental results are equivocal and point to either increased or decreased susceptibility of the diabetic hearts to IRI, especially at the early stage of the disease. The present study was designed to test the hypothesis that the duration/severity of the indexed ischemia is a major determinant of the vulnerability to myocardial IRI at early stage of diabetes.. Four weeks streptozotocin (STZ)-induced diabetic (D) and non-diabetic (C) Sprague-Dawley rats were randomly assigned to receive 30 or 45 min of left anterior descending artery ligation followed by 2 or 3 hours of reperfusion, respectively. Cardiac function was recorded by using Pressure-Volume (PV) conduction system. Myocardial infarct size was determined with triphenyltetrazolium chloride staining. Plasma Creatine kinase-MB (CK-MB), Lactate dehydrogenase (LDH) release, myocardial nitric oxide(NO) content and nitrotyrosine formation, 15-F(2t)-Isoprostane and plasma superoxide dismutase (SOD) were measured with colorimetric assays. Cardiomyocyte apoptosis was assessed by TUNEL staining. Myocardial TNFα, Caspase-3, STAT3, Akt, and GSK-3β were determined by Western blotting.. Prolongation of ischemia but not reperfusion from 30 min to 45 min significantly increased infarct size in D compared to C rats (P < 0.05), accompanied with significantly increased plasma CK-MB (P < 0.05). Prolongation of the duration of either ischemia or reperfusion significantly increased plasma LDH release and myocardial 15-F(2t)-Isoprostane and reduced plasma SOD activity, with concomitant reduction of myocardial NO and increase of nitrotyrosine formation in D relative to C (P < 0.05). Prolongation of ischemia and reperfusion significantly reduced left ventricular ejection fraction and increased the peak rate of pressure, accompanied with increased end systolic pressure in D relative to C rats (P < 0.05) but reduced phosphorylations of myocardial STAT3 at site Ser727 and Akt at site Ser473 as well as GSK-3β at Ser 9 (P < 0.05).. Diabetic hearts, even at early stage of the disease are more sensitive to IRI, and this increased severity of post-ischemic myocardial injury depends more on the duration of ischemia than that of reperfusion.

Topics: Animals; Biomarkers; Caspase 3; Creatine Kinase, BB Form; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dinoprost; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; L-Lactate Dehydrogenase; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Nitric Oxide; Oxidative Stress; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Severity of Illness Index; STAT3 Transcription Factor; Stroke Volume; Superoxide Dismutase; Time Factors; Tumor Necrosis Factor-alpha; Tyrosine; Ventricular Function, Left; Ventricular Pressure

The decoction of American Ginseng and Corydalis Tuber has been widely used for treatment of cardiovascular diseases due to their anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate the anti-apoptotic effect of Shenyuan, which is composed of the bioactive components extracted from the mixture of American Ginseng and Corydalis Tuber, and to explore potential mechanisms involved in the regulation of apoptosis.. A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Thirty-eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kg·d, n=6); Group M, AMI+moderate-dose Shenyuan (320 mg/kg·d, n=6); Group H, AMI+high-dose Shenyuan (400 mg/kg·d, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kg·d, n=6). The treatment of Shenyuan or Metoprolol started one week before AMI and continued for another two weeks after AMI.. Treatment with all doses of Shenyuan as well as Metoprolol produced a significant decrease of apoptotic index (P < 0.05), which was confirmed by TUNEL staining method. This anti-apoptotic effect was accompanied by less release of cardiac enzymes and limit of infarct size. In Group H, levels of MDA, 8-iso-prostaglandin F2α, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly increased (P < 0.05). In groups M and L, some results did not show statistical difference. There was no statistical difference in cardiac function between treatment groups and Group C.. Shenyuan treatment significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs with a large anterior wall AMI. This was accompanied by less release of cardiac enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may have a therapeutic role in improving the natural process of AMI.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Corydalis; Creatine Kinase, MB Form; Dinoprost; Drugs, Chinese Herbal; Endoplasmic Reticulum Stress; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Oxidative Stress; Panax; Plant Tubers; Proto-Oncogene Proteins c-bcl-2; Swine; Troponin I

Enhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event.. Consecutive patients (n=372) admitted within the first 24 h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2 g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type α (TNF-α), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up.. The decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-α and CRP less intense during the first 5 days in LS than in HS patients (p<0.05). Sodium intake correlated with change in plasma BNP between admission and fifth day (r=0.46; p<0.0001). End-diastolic volumes of left atrium and left ventricle were greater in HS than in LS patients (p<0.05). In the first 30 days after MI and up to 4 years afterwards, total mortality was higher in HS than in LS patients (p<0.05).. Excessive sodium intake increases oxidative stress, inflammatory response, myocardial stretching and dilatation, and short and long-term mortality after STEMI.

Topics: Adult; C-Reactive Protein; Creatine Kinase, MB Form; Dinoprost; Female; Follow-Up Studies; Humans; Interleukin-2; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Oxidative Stress; Sodium; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7×) and endothelin-1 protein (1.2×) and mRNA (1.4×) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.

Topics: Allopurinol; Analysis of Variance; Animals; Antioxidants; Atrasentan; Biomarkers; Cyclic N-Oxides; Dinoprost; Disease Models, Animal; Endothelin A Receptor Antagonists; Endothelin-1; Fibrosis; Gout Suppressants; Hypertrophy, Left Ventricular; Hyperuricemia; Isoprostanes; Male; Myocardial Infarction; Myocardium; Oxidative Stress; Pyrrolidines; Rats; Rats, Wistar; Receptor, Endothelin A; RNA, Messenger; Spin Labels; Superoxides; Time Factors; Up-Regulation; Uric Acid; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Xanthine Oxidase

Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin (APN), an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine (NAC) and/or allopurinol (ALP) can attenuate APN deficiency and myocardial ischemia reperfusion (MI/R) injury in the early stage of diabetes.. Control or streptozotocin (STZ)-induced diabetic rats were either untreated (C, D) or treated with NAC (1.5 g/kg/day) or ALP (100 mg/kg/day) or their combination for four weeks starting one week after STZ injection. Plasma and cardiac biochemical parameters were measured after the completion of treatment, and the rats were subjected to MI/R by occluding the left anterior descending artery for 30 min followed by 2 h reperfusion. Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2), reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3) and endothelial nitric oxide synthase (eNOS) but increased IL-6 and TNF-α (all P<0.05 vs. C). NAC but not ALP increased cardiac APN concentrations and AdipoR2 expression in diabetic rats. ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats. Further, NAC and ALP, respectively, decreased postischemic myocardial infarct size and creatinine kinase-MB (CK-MB) release in diabetic rats, while their combination conferred synergistic protective effects. In addition, exposure of cultured rat cardiomyocytes to high glucose resulted in significant reduction of cardiomyocyte APN concentration and AdipoR2 protein expression. APN supplementation restored high glucose induced AdipoR2 reduction in cardiomyocytes.. NAC and ALP synergistically restore myocardial APN and AdipoR2 mediated eNOS activation. This may represent the mechanism through which NAC and ALP combination greatly reduces MI/R injury in early diabetic rats.

Topics: Acetylcysteine; Adiponectin; Allopurinol; Animals; Antioxidants; Biomarkers; Blood Glucose; Creatine Kinase, MB Form; Diabetes Complications; Dinoprost; Drug Synergism; Gene Expression Regulation; Hemodynamics; Interleukin-6; Isoprostanes; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Adiponectin; Signal Transduction; Tumor Necrosis Factor-alpha

Oxidative stress may play a causative role in myocardial ischemia-reperfusion injury. However, it is a relatively understudied aspect regarding an optimal timing of antioxidant intervention during ischemia-reperfusion. The present study investigates the effect of different treatment regimens of Salvia miltiorrhiza (SM) herb extracts containing phenolic compounds that possess potent antioxidant properties on postischemic myocardial functional recovery in the setting of global myocardial ischemia and reperfusion. Langendorff-perfused rat hearts were subjected to 40 min of global ischemia at 37 degrees C followed by 60 min of reperfusion, and were randomly assigned into the untreated control and 2 SM-treated groups (n = 7 per group). In treatment 1 (SM1), 3 mg/mL of water soluble extract of SM was given for 10 min before ischemia and continued during ischemia through the aorta at a reduced flow rate of 60 microL/min, but not during reperfusion. In treatment 2 (SM2), SM (3 mg/mL) was given during the first 15 min of reperfusion. During ischemia, hearts in the control and SM2 groups were given physiological saline at 60 microL/min. The SM1 treatment reduced the production of 15-F2t-isoprostane, a specific index of oxidative stress-induced lipid peroxidation, during ischemia (94 +/- 20, 43 +/- 6, and 95 +/- 15 pg/mL in the coronary effluent in control, SM1, and SM2 groups, respectively; p < 0.05, SM1 vs. control or SM2) and postponed the onset of ischemic contracture. However, SM2, but not the SM1 regimen, significantly reduced 15-F2t-isoprostane production during early reperfusion and led to optimal postischemic myocardial functional recovery (left ventricular developed pressure 51 +/- 4, 46 +/- 4, and 60 +/- 6 mmHg in the control, SM1, and SM2 groups, respectively, at 60 min of reperfusion; p < 0.05, SM2 vs. control or SM1) and reduced myocardial infarct size as measured by triphenyltetrazolium chloride staining (26% +/- 2%, 22% +/- 2%, and 20% +/- 2% of the total area in the control, SM1, and SM2 groups, respectively, p < 0.05, SM2 vs. control). It is concluded that S. miltiorrhiza could be beneficial in the treatment of myocardial ischemic injury and the timing of administration seems important.

Topics: Animals; Antioxidants; Dinoprost; Drugs, Chinese Herbal; Endothelin-1; In Vitro Techniques; Male; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Organ Size; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Salvia miltiorrhiza; Time Factors; Ventricular Function, Left

Oxidative stress has been implicated in the pathogenesis of atherogenesis. The aim of our study is to examine whether the plasma 8-iso-prostaglandin F(2alpha) level, a marker of oxidative stress, is elevated in patients with acute myocardial infarction.. Three groups of patients were enrolled: (1) patients with no or minimal coronary artery disease (CAD) (n = 15); (2) patients with stable CAD (n = 31); (3) patients with acute myocardial infarction (n = 13).. Plasma 8-iso-prostaglandin F(2alpha) levels were significantly elevated (p < 0.001) in patients with acute myocardial infarction (290.7 +/- 73.9 pg/ml) as compared to patients with stable CAD (182.0+75.7 pg/ml) and patients with no significant CAD (118.9 +/- 85.5 pg/ml). This remained significant after correcting for coronary atherosclerosis risk factors, age, extent of atherosclerosis, and C-reactive protein (CRP) level.. Plasma 8-iso-prostaglandin F(2alpha) levels are elevated in patients with acute myocardial infarction. Endogenous oxidative stress may contribute to the pathogenesis of atherosclerosis and its complications, namely myocardial infarction.

Topics: Acute Disease; Biomarkers; Coronary Artery Disease; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Risk Factors

Hyperoxic pretreatment (>95% O(2)) can evoke myocardial adaptation to ischemia, a method which is potentially clinically usable. We wanted to investigate the role of tumor necrosis factor alpha (TNFalpha) and its p55 receptor (receptor I) in signaling of hyperoxic adaptation to ischemia. Mice deficient for TNFalpha (TNFalpha -/-) or the TNF receptor I (TNFRI -/-) gene and their wild types were subjected to 60 minutes of hyperoxia or sham treatment. Their lungs were then collected for immunoblotting, their hearts isolated and subjected to global ischemia and reperfusion in a Langendorff system, and aortic rings mounted in organ baths for reactivity studies. Hyperoxia increased expression of TNFalpha and TNFalpha converting enzyme in pulmonary proteins from wild type mice, in which hyperoxia increased myocardial tolerance to ischemia. Post-ischemic heart function was improved and infarct size reduced in wild type mice, but not in TNFalpha -/- or TNFRI -/-. The contractile response to TNFalpha on aortic rings was attenuated by hyperoxic pretreatment and by TNFRI -/-. Thus we conclude that TNFalpha, acting through TNFRI, appears important for the protective effects of hyperoxia.

Topics: Acetylcholine; ADAM Proteins; ADAM17 Protein; Animals; Aorta; Dinoprost; Enzyme-Linked Immunosorbent Assay; Hyperoxia; Ischemic Preconditioning, Myocardial; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardial Ischemia; Nitroprusside; Phenylephrine; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha; Vasoconstrictor Agents; Vasodilator Agents; Ventricular Pressure

Reactive oxygen species induce formation of 15-F(2t)-isoprostane (15-F(2t)-IsoP), a specific marker of in vivo lipid peroxidation, which is increased after myocardial ischemia and during the subsequent reperfusion. 15-F(2t)-IsoP possesses potent bioactivity under pathophysiological conditions. However, it remains unknown whether 15-F(2t)-IsoP, by itself, can influence myocardial ischemia-reperfusion injury (IRI). Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit (KH) solution at a constant flow rate of 10 ml/min. 15-F(2t)-IsoP (100 nM), SQ-29548 (1 microM, SQ), a thromboxane receptor antagonist that can abolish the vasoconstrictor effect of 15-F(2t)-IsoP, 15-F(2t)-IsoP + SQ in KH, or KH alone (vehicle control) was applied for 10 min before induction of 40 min of global ischemia followed by 60 min of reperfusion. During ischemia, saline (control), 15-F(2t)-IsoP, 15-F(2t)-IsoP + SQ, or SQ in saline was perfused through the aorta at 60 microl/min. 15-F(2t)-IsoP, 15-F(2t)-IsoP + SQ, or SQ in KH was infused during the first 15 min of reperfusion. Coronary effluent endothelin-1 concentrations were significantly higher in the group treated with 15-F(2t)-IsoP than in the control group during ischemia and also in the later phase of reperfusion (P < 0.05). Infusion of 15-F(2t)-IsoP increased release of cardiac-specific creatine kinase, reduced cardiac contractility during reperfusion, and increased myocardial infarct size relative to the control group. SQ abolished the deleterious effects of 15-F(2t)-IsoP. 15-F(2t)-IsoP exacerbates myocardial IRI and may, therefore, act as a mediator of IRI. 15-F(2t)-IsoP-induced endothelin-1 production during cardiac reperfusion may represent a mechanism underlying the deleterious actions of 15-F(2t)-IsoP.

Topics: Animals; Blood Pressure; Creatine Kinase; Creatine Kinase, MB Form; Dinoprost; Endothelin-1; Heart; In Vitro Techniques; Isoenzymes; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents

Diabetic patients manifest an increased incidence of heart failure (HF) after myocardial infarction (MI), which presages an increase in morbidity and mortality. Although oxidative stress has been implicated in diabetic complications, oxidative stress status associated with comorbid conditions that frequently accompany diabetes remains unknown. Therefore, we examined antioxidants and oxidative stress in the surviving myocardium in relation to ventricular function during diabetic HF following MI. MI was produced in diabetic and nondiabetic rats by ligation of the left coronary artery. At 4 weeks post-MI, LV systolic pressure (LVSP), rate of pressure rise (+dP/dt), and rate of pressure decay (-dP/dt) were depressed to a significantly greater extent in diabetic compared to nondiabetic MI animals. Higher levels of myocardial 8-isoprostane (8-iso PGF(2alpha)), oxidized glutathione (GSSG), as well as greater upregulation of superoxide dismutase (SOD) and catalase (CAT) protein expression paralleled by increases in enzymatic activity was observed in the diabetic MI animals, indicating higher oxidative stress. These data demonstrate a greater derangement of oxidative stress in the surviving tissues of diabetic post-MI rat hearts concomitant with an increased functional severity of HF, and suggest that chronic antioxidant therapy may be useful for the prophylaxis of subsequent HF after MI associated with diabetes.

Topics: Animals; Antioxidants; Cardiac Output, Low; Catalase; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Dinoprost; Glutathione Disulfide; Male; Myocardial Infarction; Myocardium; Oxidative Stress; Proteins; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Adrenomedullin (AM) is expressed in cardiac tissue, and plasma AM levels increase in patients with acute myocardial infarction (MI). This study was performed to determine whether AM administration immediately after acute MI inhibits progression of heart failure in rats.. Rats were infused with 1.0 microg/h IP AM or saline over 7 days immediately after MI inducted by left coronary ligation and were examined 9 weeks after MI. Compared with the saline infusion, AM infusion significantly improved survival (59% versus 81%; P<0.05) and body weight gain (32%; P<0.01) and reduced heart weight (-28%; P<0.01), lung weight (-26%; P<0.01), left ventricular (LV) end-diastolic pressure (11.4+/-2.0 versus 4.0+/-0.6 mm Hg, mean+/- SEM; P<0.01), collagen volume fraction of noninfarcted LV (-39%; P<0.05), and plasma levels of endogenous rat AM (-38%; P<0.05) without affecting infarct size. To investigate the mechanism of AM actions, another series of MI rats infused with AM were killed on day 7. AM infusion had no effect on organ weights and hemodynamic parameters on day 7 of MI but significantly reduced urinary excretion of isoprostane (-61%; P<0.01) and noninfarcted LV mRNA levels of ACE (-31%; P<0.05) and p22-phox (-30%; P<0.05).. AM administration during the early period of MI improved the survival and ameliorated progression of LV remodeling and heart failure. This beneficial effect was accompanied by reductions in oxidative stress and ACE mRNA expression in noninfarcted LV in the AM infusion period.

Topics: Adrenomedullin; Aldosterone; Animals; Body Weight; Dinoprost; Disease Progression; Drug Evaluation, Preclinical; Heart Failure; Hemodynamics; Ligation; Lung; Male; Membrane Transport Proteins; Models, Animal; Myocardial Infarction; Myocardium; NADPH Dehydrogenase; NADPH Oxidases; Organ Size; Peptides; Peptidyl-Dipeptidase A; Phosphoproteins; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; RNA, Messenger; Ventricular Remodeling

The role of oxidative stress in clinical cardiology is still controversial. The aims of the present study were to examine if minor ischaemic episodes as may occur during elective percutaneous coronary intervention (PCI) induce oxidative stress and, eventually, if oxygen stress correlates with myocardial injury. Thirty eight and nine patients underwent PCI and diagnostic coronary angiography, respectively. Peripheral blood was sampled at different time points for plasma analyses of: 8-iso-PGF2alpha (free radical-mediated oxidative stress); 15-keto-dihydro-PGF2alpha (cyclooxygenase-mediated inflammation); troponin-T (myocardial injury); hsCRP, vitamin A and vitamin E; and, total antioxidants status (TAS). In both groups 8-iso-PGF2alpha increased transiently by approximately 80% (p < 0.001) during the procedure. There was a minor troponin-T release (p < 0.001) after PCI, but no correlation with 8-iso-PGF2alpha. Troponin-T did not increase after angiography. 15-keto-dihydro-PGF2alpha decreased by 50% after ended procedure, but increased by 100% after 24 h compared to baseline. hsCRP increased significantly (p < 0.001) from baseline to the next day in the PCI-group, but not in the angiography group. Vitamins and TAS decreased slightly after the procedures. It is concluded that a moderate oxidative stress was induced by both elective PCI and coronary angiography but that no correlation was found between oxidative stress and myocardial injury in this setting. This indicates that other mechanisms than ischaemia-reperfusion episodes caused an elevation in plasma isoprostane such like the injury at a vascular site mutual for both procedures. A secondary finding from the study was elevated markers of early inflammatory response, not only after PCI, but also after angiography.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Angioplasty, Balloon, Laser-Assisted; Antioxidants; Biomarkers; C-Reactive Protein; Coronary Angiography; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Troponin T; Vitamin A; Vitamin E

To examine the correlation between 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) levels in the plasma and myocardial tissue of rats with myocardial ischemia and observe the intervention effect of N-acetylcysteine (NAC), for the purpose of assessing the value of 8-iso-PGF2alpha in estimating the extent of free radical damage and implementing possible interventions.. Forty-five Wistar rats were divided into ischemia, ischemia+NAC and control groups, and in the former 2 groups, acute myocardial ischemia models were produced by pituitrin. Elevated ST segment in ECG served as the indicator for myocardial ischemia. Rats in ischemia+NAC group were pre-treated with NAC (0.1 g/kg x d) for three weeks before the ischemia 8-iso-PGF2alpha levels in the plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA).. In ischemia group, the 8-iso-PGF2alpha levels in the plasma and myocardial tissue were 187.4+/-45.8 pg/ml and 259.3+/-47.5 pg/g, respectively, higher than those in the control group (60.4+/-13.7 pg/ml and 88.6+/-16.9 pg/g, respectively, P<0.01) and those in ischemia+NAC group (88.2+/-16.4 pg/ml and 109.4+/-24.7 pg/g, respectively, P<0.01). A positive correlation was noted between the 8-iso-PGF2alpha levels in the plasma and myocardial tissue (r=0.865, P<0.01). In comparison with the control group, elevation of the ST segment of ECG in rats with myocardial ischemia was obvious, and the peak elevation occurred 45 min after ischemia (0.34+/-0.05 mV, P<0.01). Pre-treatment with NAC proved to help alleviate the subsequent ischemia, with ST segment elevation of only 0.18+/-0.05 mV.. In condition of acute myocardial ischemia in rats, 8-iso-PGF2alpha levels tend to increase, which can be indicative of the degree of myocardial ischemia. NAC pre-treatment can alleviate the ischemic condition by offsetting the damage caused by the free radicals.

Topics: Acetylcysteine; Animals; Dinoprost; Electrocardiography; F2-Isoprostanes; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar

Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia-reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose-response to phenylephrine (PHE), prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 +/- 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 +/- 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Coronary Circulation; Dinoprost; Endothelin-1; Heart Rate; Hyperoxia; Male; Myocardial Infarction; Nitroprusside; Phenylephrine; Rats; Rats, Sprague-Dawley; Rats, Wistar; Vasoconstriction; Vasodilation; Vasodilator Agents; Ventricular Function

8-iso-prostaglandin F(2 alpha)(8-iso-PGF(2 alpha)), a representative isoprostane, has been reported to be a reliable marker for oxidant stress in vivo. To examine if 8-iso-PGF(2 alpha)is generated in patients with acute myocardial infarction (AMI), we measured the level of immunoreactive 8-iso PGF(2 alpha)in the great cardiac vein as well as classical eicosanoids, 6-keto-prostaglandin F(1 alpha)(6-keto-PGF(1 alpha)) and thromboxane B(2)(TXB(2)) in the process of urgent coronary balloon angioplasty. Fourteen patients with anterior AMI were divided into two groups: the totally occluded (n=7) and the already perfused groups (n=7). In the former, transient elevation of 8-iso-PGF(2 alpha)was observed immediately after the angioplasty, i.e. the ratio of post-angioplasty level to pre-level was approximately 2.4 for 8-iso-PGF(2 alpha), 14 for 6-keto-PGF(1 alpha), and 5 for TXB(2). In the already perfused group, the levels of these eicosanoids were unchanged. In the totally occluded group, peak creatine phosphokinase in a peripheral vein was correlated with the level of 8-iso-PGF(2 alpha)(r(2)=0.841, P<0.01), but not with those of the other two eicosanoids. In conclusion, transcardiac 8-iso-PGF(2 alpha)generation is a reliable marker for the size of myocardium exposed to oxidant stress.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angioplasty, Balloon, Coronary; Creatine Kinase; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardium; Oxidative Stress; Oxygen; Reperfusion; Thromboxane B2; Time Factors

We examined the role of cyclooxygenase-2 (COX-2) in the late phase of ischemic preconditioning (PC). A total of 176 conscious rabbits were used. Ischemic PC (six cycles of 4-min coronary occlusions/4-min reperfusions) resulted in a rapid increase in myocardial COX-2 mRNA levels (+231 +/- 64% at 1 h; RNase protection assay) followed 24 h later by an increase in COX-2 protein expression (+216 +/- 79%; Western blotting) and in the myocardial content of prostaglandin (PG)E(2) and 6-keto-PGF(1alpha) (+250 +/- 85% and +259 +/- 107%, respectively; enzyme immunoassay). Administration of two unrelated COX-2 selective inhibitors (NS-398 and celecoxib) 24 h after ischemic PC abolished the ischemic PC-induced increase in tissue levels of PGE(2) and 6-keto-PGF(1alpha). The same doses of NS-398 and celecoxib, given 24 h after ischemic PC, completely blocked the cardioprotective effects of late PC against both myocardial stunning and myocardial infarction, indicating that COX-2 activity is necessary for this phenomenon to occur. Neither NS-398 nor celecoxib lowered PGE(2) or 6-keto-PGF(1alpha) levels in the nonischemic region of preconditioned rabbits, indicating that constitutive COX-1 activity was unaffected. Taken together, these results demonstrate that, in conscious rabbits, up-regulation of COX-2 plays an essential role in the cardioprotection afforded by the late phase of ischemic PC. Therefore, this study identifies COX-2 as a cardioprotective protein. The analysis of arachidonic acid metabolites strongly points to PGE(2) and/or PGI(2) as the likely effectors of COX-2-dependent protection. The recognition that COX-2 mediates the antistunning and antiinfarct effects of late PC impels a reassessment of current views regarding this enzyme, which is generally regarded as detrimental.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Gene Expression Regulation, Enzymologic; Ischemic Preconditioning; Isoenzymes; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Stunning; Myocardium; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Pyrazoles; Rabbits; Sulfonamides; Transcription, Genetic

Abnormalities of vasomotor tone are characteristic of heart failure. This study was designed to assess the effects of chronic heart failure on endothelium-dependent relaxation in both large conduit arteries and small resistance vessels and to determine whether or not impaired nitric oxide (NO) production is involved. Segments of pulmonary artery (PA), abdominal aorta (AA), and small mesenteric artery (MA) were harvested from rats with heart failure resulting from coronary artery ligation and from sham-operated controls. Organ-bath experiments done in the presence of indomethacin to avoid the influence of vasodilatory prostanoids demonstrated that relaxation to acetylcholine (ACh) was impaired in the PA but not the AA or MA of the group with heart failure. Endothelium-independent relaxation to nitroglycerin was not significantly affected by the development of heart failure. Constriction to prostaglandin (PG) F(2alpha) was enhanced in PA but not in AA or MA segments. Preincubation with N(omega)-nitro-L-arginine (NNA) to inhibit the production of NO increased baseline force in vessels from all three beds, but the effect was greatest in the PA. Although relaxation to ACh was significantly diminished by NNA in the PA, it was not completely abolished. Furthermore, ACh-mediated relaxation in the presence of NAA was still impaired in the group with heart failure compared with the sham-operated control group. NNA had only mild effects on ACh-mediated relaxation in MA. These results demonstrate that (a) the mediators of endothelium-dependent relaxation may vary throughout the arterial circulation, (b) the contribution of NO to endothelium-dependent relaxation is substantial in PA and minimal in mesenteric resistance vessels, (c) endothelium-dependent relaxation is not uniformly impaired throughout the arterial bed by the development of heart failure, and (d) although a defect in NO production may account for enchanced vasoconstriction seen in response to PGF(2alpha), it does not account for the diminished vasodilatory response to ACh in this experimental model of heart failure.

Topics: Acetylcholine; Animals; Aorta, Abdominal; Dinoprost; Endothelium, Vascular; Heart Failure; Hemodynamics; In Vitro Techniques; Male; Mesenteric Arteries; Muscle Relaxation; Muscle, Smooth, Vascular; Myocardial Infarction; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Nitroglycerin; Pulmonary Artery; Rats

Myocardial reperfusion is believed to be associated with free radical injury. However, indexes of oxidative stress in vivo have been limited by their poor specificity and sensitivity. Isoprostanes are stable products of arachidonic acid formed in a nonenzymatic, free radical-catalyzed manner. We have developed a sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG) F2 alpha.. To address its utility as an index of oxidative stress during coronary reperfusion, we measured urinary levels by gas chromatography/mass spectrometry in a canine model of coronary thrombolysis, in patients with acute myocardial infarction treated with thrombolytic therapy, and in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2 alpha was unchanged after circumflex artery occlusion in a canine model of coronary thrombolysis (n = 13; 437.2 +/- 56.4 versus 432.7 +/- 55.2 pmol/mmol creatinine) but increased significantly (P < .05) immediately after reperfusion (553.8 +/- 64.7 pmol/mmol). Urinary levels were increased (P < .001) in patients (n = 12) with acute myocardial infarction given lytic therapy (265.8 +/- 40.8 pmol/mmol) compared with age-matched control subjects (n = 20; 91.5 +/- 11.8 pmol/mmol) and patients with stable coronary disease (n = 20; 95.7 +/- 6.3 pmol/mmol). Preoperative levels rose from 113.2 +/- 11.8 to 248.2 +/- 86.3 pmol/mmol at 30 minutes into revascularization to 332.2 +/- 82.6 pmol/mmol by 15 minutes after global myocardial reperfusion (P < .05) and dropped to 181.2 +/- 50.4 pmol/mmol at 30 minutes and 120.2 +/- 9.9 pmol/mmol at 24 hours after bypass surgery (n = 5). Corresponding changes in spin adduct formation, found with electron paramagnetic resonance, were noted in 2 patients.. These data support the hypothesis that free radical generation occurs during myocardial reperfusion. Measurement of isoprostane production may serve as a noninvasive index of oxidative stress.

Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Coronary Artery Bypass; Dinoprost; Dogs; Electron Spin Resonance Spectroscopy; Female; Gas Chromatography-Mass Spectrometry; Humans; Lipoproteins, LDL; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Oxidative Stress; Sensitivity and Specificity; Thrombolytic Therapy

The role of oxidant stress in cardiac ischemia/reperfusion injury in humans remains controversial. This is due, in part, to the limitations of available indices of oxidant stress in vivo. Isoprostanes are stable, free radical-catalyzed products of arachidonic acid. We assessed their formation in patients undergoing coronary reperfusion via percutaneous transluminal coronary angioplasty (PTCA).. We developed specific, mass spectrometry assays for two structurally distinct F2 isoprostanes, 8-epi-PGF2alpha and IPF2alpha-I. Urine samples for isoprostane determination were collected in patients undergoing coronary arteriography (n=11), elective PTCA (n=15), and angiography after thrombolysis for acute myocardial infarction (MI) (n=10). Urinary levels (pmol/mmol creatinine) of both isoprostanes were markedly increased from baseline in the first 6 hours after PTCA for acute MI (105+/-17.8 versus 230+/-66 for 8-epi-PGF2alpha [P=.009] and 466+/-91 versus 833+/-153 for IPF2alpha-I [P=.001]) and returned toward preprocedural values by 24 hours (122+/-18 for 8-epi-PGF2alpha and 457+/-102 for IPF2alpha-I). There was a slight increase in urinary 8-epi-PGF2alpha levels (64.7+/-9.5 versus 84.9+/-10.6; P=.02) after diagnostic coronary arteriography and elective PTCA (88.7+/-7.5 versus 114.3+/-16.1; P=.01). A striking correlation was observed (r=.68, P<.0001; n=33) between urinary 8-epi-PGF2alpha and IPF2alpha-I levels in patients receiving thrombolytic agents for acute MI.. Urinary F2 isoprostane levels are elevated in patients after treatments resulting in reperfusion for acute MI. These findings provide evidence consistent with increased oxidant stress in vivo in this setting. Measurement of urinary isoprostanes may offer a noninvasive approach to the assessment of oxidant stress and the efficacy of antioxidant therapies in these syndromes.

Topics: Aged; Angioplasty, Balloon, Coronary; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Postoperative Period; Thrombolytic Therapy

Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes. Myocyte hypertrophy was induced specifically by PGF2 alpha. Myocytes exposed to this prostanoid in culture increased in size and protein content. The contractile fibrils within the cells became organized into parallel arrays, and the cells tended to cluster and beat spontaneously. PGF2 alpha also induced the expression of c-fos, atrial natriuretic factor (ANF), and alpha-skeletal actin in these cells. The effects of PGF2 alpha were compared with several known cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor, cardiotrophin-1, and angiotensin II). PGF2 alpha was found to be intermediate in potency among the factors but induced a level of ANF production that was approximately 10-fold higher than any of the other effectors. Responsiveness to PGF2 alpha was not limited to neonatal cardiocytes. Ventricular myocytes isolated from adult rats also responded specifically to PGF2 alpha with a morphological change similar to that observed with phenylephrine and by producing ANF. In rats, chronic administration of fluprostenol, a potent agonist analogue of PGF2 alpha, resulted in a dose-dependent increase in heart weight- and ventricular weight-to-body weight ratios. The amount of PGF2 alpha extractable from the hearts of rats with cardiac hypertrophy induced by myocardial infarction was also found to be greater than that in sham-operated control rats. These results indicate that PGF2 alpha may play an important role in inducing cardiac hypertrophy.

Topics: Aging; Animals; Animals, Newborn; Atrial Natriuretic Factor; Cardiomegaly; Cells, Cultured; Dinoprost; Heart; Male; Myocardial Infarction; Myocardium; Phenylephrine; Prostaglandins; Prostaglandins F, Synthetic; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors

In 47 patients with acute myocardial infarction and in 17 healthy volunteers blood concentration and urinary excretion of PGE2, PGF2 alpha, 6-keto-PGF1 alpha--hydrolysis product of prostacyclin--and TXB2 were determined using RIA. Myocardial infarction patients were found to have significantly higher blood level and urinary excretion of 6-keto-PGF1 alpha, higher blood level of PGF2 and higher urinary excretion of TXB2 than controls, PGE2 urinary excretion was significantly lower. Increased excretion of 6-keto-PGF1 alpha was observed in patients with ventricular arrhythmias. Excretion of all determined prostaglandins was increased in patients with myocardial infarction complicated by atrioventricular block as compared to the other patients. The results suggest, that increase of prostacyclin synthesis in the acute phase of myocardial infarction may provide protection mechanism against heart muscle damage and improve coronary blood flow.

Topics: Adult; Aged; Arrhythmias, Cardiac; Dinoprost; Dinoprostone; Epoprostenol; Fatty Acids, Unsaturated; Female; Humans; Male; Middle Aged; Myocardial Infarction; Reference Values; Thromboxanes

Concentration of PGF2 alpha were correlated to those of antiprostaglandin antibodies IgM and IgG to this mediator in donors and myocardial infarction patients. In donors correlation between PGF2 alpha concentration and IgG antibody levels is positive. In uneventful myocardial infarction relevant correlation partially recovered at the expense of IgM antibodies. This is not true for complicated myocardial infarction.

Topics: Adult; Antibodies; Dinoprost; Humans; Immunity, Innate; Immunoenzyme Techniques; Immunoglobulins; Middle Aged; Myocardial Infarction

We experienced a case of myocardial infarction associated with pulmonary edema in a patient with hydatidiform mole probably due to methylergometrin and prostaglandin F2 alpha (PGF2 alpha) administered during the operation. A 26-year-old woman was scheduled to have curettage for hydatidiform mole under general anesthesia. She had no previous history of cardiopulmonary disease. During the operation, 0.4 mg of methylergometrin was administered intravenously to induce uterine contraction. Because the contraction was not sufficient, 2 mg of PGF2 alpha was given into the uterine muscle. A few minutes later blood pressure and heart rate increased abruptly and arterial blood gas analysis showed hypoxia and respiratory acidosis. Pulmonary edema was confirmed by chest X-P. After ordinary treatment for pulmonary edema, she was transferred to ICU. Postoperative examinations of ECG, serum enzymes and echocardiography revealed anterior subendocardial infarction. About one month later, methylergometrin test was performed during coronary angiography and this induced coronary vasospasm. PGF2 alpha is also known to cause peripheral as well as pulmonary vasoconstriction. Acute myocardial infarction induced by methylergometrin and PGF2 alpha may be a possible cause of this episode.

Topics: Adult; Curettage; Dinoprost; Female; Humans; Hydatidiform Mole; Methylergonovine; Myocardial Infarction; Pregnancy; Pulmonary Edema

The effect of PGF2 alpha on glucose synthesis de novo in a healthy rat organism and those with coronary occlusion-myocardial infarction was studied. There was observed prostaglandin's metabolic action simultaneously at one direction: there was increased the concentration of non-nitric precursors of gluconeogenesis in blood of animals of both groups, final disintegration product of tissue proteins, the gluconeogenic activity of key enzymes and therefore the concentration of newly formed glucose went up as so as glycogen in liver, cardiac and skeletal muscle. Seemingly, PGF2 alpha stimulates the intensity not only of gluco-, but glyconeogenesis having cardioprotective action. At the same time metabolic effect of PGF2 alpha is strongly marked in coronary occlusion rat with myocardial infarction.

Topics: Animals; Blood Glucose; Dinoprost; Dose-Response Relationship, Drug; Gluconeogenesis; Kidney Cortex; Liver; Male; Muscles; Myocardial Infarction; Myocardium; Rats; Time Factors

Topics: Angina Pectoris; Coal Mining; Coronary Disease; Dinoprost; Humans; Lipid Peroxidation; Malondialdehyde; Myocardial Infarction; Nucleotides, Cyclic; Occupational Diseases; Physical Exertion; Prostaglandins E; Ukraine

The ELISA test was performed on sera of normal donors and patients with myocardial infarction (MI) and essential hypertension (EH) to detect autoantibodies against prostaglandin F2 alpha (a-PGF2 alpha). The a-PGF2 alpha level was much higher after immune complexes dissociation. Baseline a-PGF2 alpha was elevated in EH patients with a sudden rise in blood pressure, and in MI patients without hypertension and unstable angina. MI patients with bradyarrhythmias also had elevated a-PGF2 alpha levels. Baseline a-PGF2 alpha was rather low in the sera of donors, chronic EH patients with hypertension and unstable angina, suggesting that a-PGF2 alpha has a physiological role to play.

Topics: Adult; Aged; Autoantibodies; Dinoprost; Enzyme-Linked Immunosorbent Assay; Humans; Hypertension; Middle Aged; Myocardial Infarction; Prostaglandins F; Reference Values

Topics: Adult; Aged; Alprostadil; Arrhythmias, Cardiac; Dinoprost; Humans; Male; Middle Aged; Myocardial Infarction; Prostaglandins F; Shock, Cardiogenic

Topics: Adult; Aged; Alprostadil; Dinoprost; Humans; Male; Middle Aged; Myocardial Infarction; Prostaglandins F; Time Factors

Topics: Adult; Aged; Dinoprost; Dipyridamole; Humans; Hydrocortisone; Middle Aged; Myocardial Infarction; Prostaglandins E; Prostaglandins F

In order to diagnose patients in thrombotic state, it is quite important to detect increased concentration of plasma thromboxane B2 (TXB2), a stable catabolite of TXA2. To determine plasma TXB2 levels with high sensitivity and selectivity, we employed gas chromatography-mass spectrometry (GC/MS). The trimethylsilyl (TMS) ether derivatives conventionally employed in GC/MS analysis of prostanoids are not suitable for quantitation of plasma prostanoids, because the mass spectra are deficient in ions with high intensity in the high mass range and TMS ether derivatives are sensitive to moisture. To solve these problems we employed tert-butyldimethylsilyl (t-BDMS) ether derivatives, based on the observation that t-BDMS ether derivatives afforded abundant ions at [M-57]+ and showed good hydrolytic stability. The reaction conditions of tert-butyldimethylsilylation were also examined to optimize the selected ion monitoring response. The t-BDMS ether derivatives of prostanoids were successfully analyzed with a short capillary column with a relatively large diameter, with maintaining good separation. In conjunction with the use of reversed-phase high performance liquid chromatography as purification procedure, a sensitive and reproducible stable isotope dilution assay of plasma TXB2 was developed. The values obtained by this method correlated well with those obtained by the radioimmunoassay we have developed.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angina Pectoris; Coronary Vasospasm; Dinoprost; Dinoprostone; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Myocardial Infarction; Organosilicon Compounds; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Silicon; Thromboxane B2; Thromboxanes

Topics: Adult; Aspirin; Child; Dinoprost; Female; Humans; Indomethacin; Male; Myocardial Infarction; Physical Exertion; Prostaglandins F; Renin-Angiotensin System; Sulfinpyrazone

Topics: Animals; Blood Glucose; Coronary Circulation; Coronary Vessels; Dinoprost; Dogs; Indomethacin; Lactates; Lactic Acid; Ligation; Myocardial Infarction; Prostaglandins F