dinoprost and Coronary-Disease

Long-term vascular complications still represent the main cause of morbidity and mortality in diabetic patients. Although randomized long-term clinical studies comparing the effects of conventional and intensive therapy have demonstrated a clear link between hyperglycemia and the development of complications of diabetes, they have not defined the mechanism through which excess glucose results in tissue damage. Evidence has accumulated indicating that oxidative stress may play a key role in the etiology of diabetic complications. Isoprostanes are emerging as a new class of biologically active products of arachidonic acid metabolism of potential relevance to human vascular disease. Their formation in vivo seems to reflect primarily, if not exclusively, a nonenzymatic process of lipid peroxidation. Enhanced urinary excretion of 8-iso-PGF(2alpha) has been described in association with both type 1 and type 2 diabetes mellitus, and correlates with impaired glycemic control. Besides providing a likely noninvasive index of lipid peroxidation in this setting, measurements of specific F(2) isoprostanes in urine may provide a sensitive biochemical end point for dose-finding studies of natural and synthetic inhibitors of lipid peroxidation. Although the biological effects of 8-iso-PGF(2alpha) in vitro suggest that it and other isoeicosanoids may modulate the functional consequences of lipid peroxidation in diabetes, evidence that this is likely in vivo remains inadequate at this time.

Topics: Animals; Antioxidants; Arachidonic Acids; Arteriosclerosis; Biomarkers; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Dietary Supplements; Dinoprost; F2-Isoprostanes; Humans; Hyperglycemia; Lipid Peroxidation; Oxidative Stress; Protein Isoforms; Vitamin E

Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans.. We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction.. Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables-including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine-6-8 hr after both exposures.. Particulate concentrations (mean +/- SE) in the exposure chamber (190+/-37 microg/m(3)) were higher than ambient levels (31+/-8 microg/m(3)) and levels in filtered air (0.5+/-0.4 microg/m(3); p<0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9+/-8.5 vs. 4.9+/-1.2 pg/mL, p<0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p<0.001 for all), CAPs exposure had no effect on vascular function in either group.. Despite achieving marked increases in particulate matter, exposure to CAPs--low in combustion-derived particles--did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans.

Topics: C-Reactive Protein; Cardiovascular System; Coronary Disease; Cross-Over Studies; Dinoprost; Double-Blind Method; Fibrinolysis; Humans; Inhalation Exposure; Male; Middle Aged; Particulate Matter; Tyrosine; Vasomotor System

We have reported that repeated sauna therapy improves impaired vascular endothelial function in a patient with coronary risk factors. We hypothesized that sauna therapy decreases urinary 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) levels as a marker of oxidative stress and conducted a randomized, controlled study. Twenty-eight patients with at least one coronary risk factor were divided into a sauna group (n = 14) and non-sauna group (n = 14). Sauna therapy was performed with a 60 degrees C far infrared-ray dry sauna for 15 minutes and then bed rest with a blanket for 30 minutes once a day for two weeks. Systolic blood pressure and increased urinary 8-epi-PGF(2alpha) levels in the sauna group were significantly lower than those in the non-sauna group at two weeks after admission (110 +/- 15 mmHg vs 122 +/- 13 mmHg, P < 0.05, 230 +/- 67 pg/mg x creatinine vs 380 +/- 101 pg/mg x creatinine, P < 0.0001, respectively). These results suggest that repeated sauna therapy may protect against oxidative stress, which leads to the prevention of atherosclerosis.

Topics: Adult; Body Mass Index; Coronary Disease; Diabetes Mellitus; Dinoprost; Endothelium, Vascular; Female; Heart Rate; Hematocrit; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Nitric Oxide Synthase; Oxidative Stress; Risk Factors; Steam Bath

Our objective was to evaluate whether isocaloric replacement of refined rice with whole grains and other plant products as a form of powder reduces coronary artery disease (CAD) risk factors, such as insulin demand and lipid peroxidation in CAD patients. Seventy-six male patients with CAD were randomly assigned to either a group ingesting a whole-grain meal daily or a control group for 16 weeks. In the whole-grain group, serum concentrations of glucose and insulin decreased by 24% and 14%, respectively, without altering body weight and energy intake, whereas daily intakes of fiber and vitamin E increased by 25% and 41%, respectively. Consumption of whole grains and legume powder in CAD patients without diabetes decreased fasting levels of glucose and insulin. The areas under the curve for insulin and glucose during the oral glucose tolerance test were also decreased. CAD patients with diabetes in the whole-grain group also showed reductions in fasting glucose and in the area under the curve for glucose. In the whole-grain group, plasma malondialdehyde and homocysteine and urinary 8-epi-prostaglandin F(2alpha) concentrations decreased by approximately 28%. Also, lipid-corrected concentrations of alpha-carotene, retinol, tocopherols, and lycopene increased by 11% to 40%, and the percentage composition of n-6 fatty acids of serum phospholipid increased by 14% in the whole-grain group. The replacement of refined rice with whole grain and legume powder as a source of carbohydrate in a meal showed significant beneficial effects on glucose, insulin, and homocysteine concentrations and lipid peroxidation in CAD patients. These effects are likely to substantially reduce the risk factors for CAD and diabetes.

Topics: Area Under Curve; Blood Glucose; Carotenoids; Cholesterol, HDL; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Dinoprost; Edible Grain; F2-Isoprostanes; Fabaceae; Glucose Tolerance Test; Homocysteine; Humans; Insulin; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Powders; Risk Factors

Low high-density lipoprotein (HDL) levels are major predictors of cardiovascular (CV) events, even in patients on statin treatment with low-density lipoprotein (LDL) at target. In animal models HDLs protect LDL from oxidation and blunt platelet activation. Our study aimed to examine whether HDL levels are related to in vivo oxidative stress and platelet activation, as determinants of atherothrombosis.. Urinary 8-iso-PGF2α and 11-dehydro-TXB2, in vivo markers of oxidative stress and platelet activation, respectively, were measured in 65 coronary heart disease (CHD) normocholesterolemic patients with HDL ≤35 mg/dL, and in 47 CHD patients with HDL >35 mg/dL. The 2 eicosanoids were also measured before and after an intensive exercise program in sedentary people (n=18) and before and after fenofibrate treatment in otherwise healthy subjects with low HDL (n=10). Patients with HDL ≤35 mg/dL showed significantly higher urinary 8-iso-PGF2α (median [25th to 75th percentiles]: 289 [189 to 380] versus 216 [171 to 321] pg/mg creatinine, P=0.019) and 11-dehydro-TXB2 (563 [421 to 767] versus 372 [249 to 465] pg/mg creatinine, P=0.0001) than patients with higher HDL. A direct correlation was found between urinary 8-iso-PGF2α and 11-dehydro-TXB2 in the entire group of patients (ρ=0.77, P<0.0001). HDL levels were inversely related to both 8-iso-PGF2α (ρ=-0.32, P=0.001) and 11-dehydro-TXB2 (ρ=-0.52, P<0.0001). On multiple regression, only 8-iso-PGF2α (β=0.68, P<0.0001) and HDL level (β=-0.29, P<0.0001) were associated with urinary 11-dehydro-TXB2 excretion, independent of sex, age, smoking, hypertension, diabetes, previous myocardial infarction, total cholesterol, LDL, and triglycerides. Both intensive exercise and fenofibrate treatment significantly reduced the 2 eicosanoids in healthy subjects, in parallel with an HDL increase.. A low HDL phenotype, both in CHD patients and in healthy subjects, is associated with increased lipid peroxidation and platelet activation. These data provide novel insight into the mechanisms linking low HDL with increased CV risk.

Topics: Aged; Arachidonic Acids; Case-Control Studies; Cholesterol, HDL; Coronary Disease; Cross-Sectional Studies; Dinoprost; Exercise; Exercise Therapy; Female; Fenofibrate; Humans; Hypoalphalipoproteinemias; Hypolipidemic Agents; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Phenotype; Platelet Activation; Risk Factors; Sedentary Behavior; Thromboxane B2

Endothelial dysfunction, which is more often observed in conduit arteries such as the aorta, carotid, femoral, and brachial arteries, is largely due to alterations in cellular signal transduction initiated by an escalating cycle of damage triggered by oxidative stress. This phenomenon is exacerbated in the elderly, where a progressive loss of vascular endothelial function and concurrent loss of vasomotor control is frequent. In a previous study, we demonstrated that the wild artichoke (Cynara cardunculus) is able to increase the production of the vasorelaxant factor nitric oxide by cultured aortic endothelial cells. We now extended that study to verify (1) the vasorelaxant potential of C. cardunculus on isolated rat aortic rings and (2) whether the vasomodulating properties of C. cardunculus are maintained in vivo, after administration to aged rats. The results demonstrate that the wild artichoke and its main components, namely, luteolin and apigenin, improve aortic relaxation when added to the incubation bath. Moreover, the feeding of wild artichoke [10 mg (kg of polyphenols)(-1) day(-1)] to aged rats significantly restores proper vasomotion, to a degree similar to that observed in young animals. This study provides further justification to the advice to consume wild greens as part of a balanced diet and suggests that close attention should be paid to the diet of the elderly, because it can effectively modulate important parameters of cardiovascular risk.

Topics: Aging; Animals; Aorta, Thoracic; Biomarkers; Chromatography, High Pressure Liquid; Coronary Disease; Cynara; Dinoprost; Endothelin-1; Flavonoids; In Vitro Techniques; Male; Muscle Relaxation; Muscle, Smooth, Vascular; Oxidative Stress; Phenols; Plant Extracts; Polyphenols; Rats; Rats, Inbred BN; Rats, Inbred F344; Rats, Sprague-Dawley

Oxidative stress is involved in the pathophysiology of atherosclerosis, diabetes mellitus, hypertension, obesity, and cigarette smoking, all of these being risk factors for coronary heart disease (CHD). We tested the hypothesis that risk factors of CHD are associated with abundant systemic oxidative stress.. We conducted a case-control study with 93 CHD patients and 93 control subjects frequency-matched by age and sex. Urinary excretion of the F2-isoprostane 8-iso-prostaglandin (PG) F2alpha and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha, were measured by gas chromatography-tandem mass spectrometry. Body mass index, systolic blood pressure, and C-reactive protein were elevated in CHD patients (P<0.01). Urinary 8-iso-PGF2alpha and 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha also differed, from 77 (interquartile range, 61-101) to 139 (93-231) pmol/mmol creatinine and from 120 (91-151) to 193 (140-275) pmol/mmol in control subjects and case subjects, respectively (P<0.001). 8-iso-PGF2alpha and its metabolite were highly correlated (Spearman's rho=0.664, P<0.001). HDL cholesterol was diminished in CHD patients (P<0.001). All of these characteristics predicted CHD in univariate analysis. In a multivariate model, the odds ratios were increased only for 8-iso-PGF2alpha (> or =131 pmol/mmol, P<0.001) and C-reactive protein (>3 mg/L, P<0.01), ie, by 30.8 (95% CI, 7.7-124) and 7.2 (1.9-27.6), respectively. 8-iso-PGF2alpha was found to be a novel marker in addition to known risk factors of CHD, ie, diabetes mellitus, hypercholesterolemia, hypertension, and smoking. Urinary excretion of 8-iso-PGF2alpha correlated with the number of risk factors for all subjects (P<0.001 for trend).. 8-iso-PGF2alpha is a sensitive and independent risk marker of CHD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Case-Control Studies; Comorbidity; Coronary Disease; Diabetes Mellitus; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Germany; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Obesity; Oxidative Stress; Risk Factors; Sensitivity and Specificity; Smoking

Topics: Biomarkers; Coronary Angiography; Coronary Disease; Dinoprost; Gas Chromatography-Mass Spectrometry; Humans; Immunoenzyme Techniques; Risk Factors

The aim of the present study was to investigate whether the isoprostane 8-epi-PGF2 alpha differently accumulates in semilunar valves of patients suffering from coronary heart disease (CHD, n = 19) as compared to valves from healthy heart donors (controls, n = 6). Sections from isolated aortic and pulmonary valves were analyzed by semiquantitative immunohistochemistry. The 8-epi-PGF2 alpha-content was determined by using a specific radioimmunoassay. The accumulation of 8-epi-PGF2 alpha in both valves was higher in CHD-patients in comparison to controls (Aortic valves: 36.49 +/- 11.26% vs. 15.78 +/- 3.04%; pulmonary valves: 46.79 +/- 9.80% vs. 14.99 +/- 3.57%). The results from the radioimmunoassay revealed comparable findings in both groups (CHD vs. controls: 395.95 +/- 86.09 vs. 139.50 +/- 47.46 pg/mg protein in the aortic valves and 430.47 +/- 76.30 vs. 147.33 +/- 53.84 pg/mg protein in pulmonary valves). Pulmonary valves seem to be more susceptible to oxidative stress than aortic valves as evidenced by a higher accumulation of 8-epi-PGF2 alpha in CHD patients. Considering the data presented in this study, we suggest that 8-epi-PGF2 alpha is a valuable indicator of oxidative injury in human semilunar valves.

Topics: Aged; Aortic Valve; Coloring Agents; Coronary Disease; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Isoprostanes; Male; Middle Aged; Myocardium; Pulmonary Valve; Radioimmunoassay

Oxidatively modified phospholipids with fragmented acyl chains have attracted much interest because of their proinflammatory activity and their potential involvement in atherosclerosis. They can be formed in vitro by free radical treatment of unsaturated phospholipids but it is not known under which conditions they accumulate in vivo. We assayed one species of fragmented phosphatidylcholine (PC) in human blood plasma by high performance liquid chromatography after precolumn derivatization with chloromethylanthracene. Structural analysis suggested that fragmented PC was a diacyl species with a palmitoyl group and a short oxidized residue, which most likely had four carbons. The concentration of fragmented PC was higher in elderly individuals with coronary heart disease than in young healthy controls. Smoking one cigarette acutely increased the concentration of fragmented PC in healthy adults. Fragmented PC also increased in the reperfusion period after treatment with cardiopulmonary bypass. The increase coincided with a surge of circulating neutrophils. In rats, the plasma concentration of fragmented PC was elevated by vitamin E deficiency and exposure to high oxygen. The data demonstrate that fragmented PC increases in blood plasma in response to various forms of oxidative stress.

Topics: Adult; Age Factors; Aged; Animals; Cardiopulmonary Bypass; Coronary Disease; Dinoprost; Female; Free Radicals; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Phosphatidylcholines; Platelet Activation; Rats; Rats, Wistar; Reperfusion; Smoking; Vitamin E

We have previously shown that superoxide anion (O2-) stimulates the release of vasoconstrictor prostanoids and induces a prolonged rise in coronary perfusion pressure (CPP) that persists even after removal of O2-. In this study, we tested the hypothesis that the increased CPP is mediated by activation of TxA2/ PGH2 (TP) receptors and protein kinase C (PKC)-dependent mechanisms. In Langendorff perfused rat hearts, O2- was applied for 15 min and then washed out over a period of 20 min. Application of O2- increased the release of vasoconstrictive (TxA2 and PGF2alpha) and decreased vasodilating (PGI2 and PGE2) prostanoids. Although indomethacin (10 microM), a cyclooxygenase inhibitor, attenuated the rise in CPP during O2- perfusion, the increase was not completely blocked. OKY 046Na (10 microM), a thromboxane synthase inhibitor, had no effect on O2--induced increases in CPP, whereas ONO 3708 (10 microM), a TP receptor antagonist, suppressed this effect. PKC activity was also elevated by more than 50% by O2- perfusion. CPP typically increased throughout the O2- wash-out. This post-O2- vasoconstriction was not inhibited by indomethacin, nitroglycerin or nitrendipine. In contrast, ONO 3708 (10 microM) and two PKC inhibitors, staurosporine (10 nM) and calphostin C (100 nM), completely blocked the rise in CPP, and even elicited vasodilation. PDBu enhanced the post-O2- vasoconstriction. We conclude that O2--induced coronary vasoconstriction is initially mediated by TP receptors, but activation of PKC sustains the response.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Calcium Channel Blockers; Cardiovascular Agents; Coronary Disease; Dinoprost; Enzyme Inhibitors; In Vitro Techniques; Indomethacin; Male; Methacrylates; Naphthalenes; Perfusion; Prostaglandins; Protein Kinase C; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin; Receptors, Thromboxane; Receptors, Thromboxane A2, Prostaglandin H2; Staurosporine; Superoxides; Thromboxane A2; Thromboxane-A Synthase; Vasoconstrictor Agents

Ischemia and reperfusion alter the reactivity of large coronary arteries, but the effect of ischemia and reperfusion on the coronary microcirculation has been less well defined. Elevated circulating levels of vasopressin are associated with cardiopulmonary bypass and numerous other clinical states in which vascular ischemia and reperfusion may occur. We examined the effects of ischemia with and without reperfusion on the responses to vasopressin of both large coronary arteries and coronary arterial microvessels. Studies were performed on vessels from control dogs (n = 8), dogs undergoing 1 hour of ischemia only (n = 8), and dogs undergoing 1 hour of ischemia followed with 1 hour of reperfusion (n = 9). Rings of proximal obtuse marginal coronary arteries distal to the site of circumflex coronary artery occlusion were studied in isolated organ chambers. Coronary microvessels (110 to 220 microns in diameter) were studied in a pressurized (20 mm Hg), no-flow state with a microvessel imaging apparatus and electronic dimension analyzer. Microvessels were preconstricted with the thromboxane A2 analog U46619. Responses of large vessel rings were studied in the nonpreconstricted state and after preconstriction with prostaglandin F2 alpha. Large vessel response to vasopressin was minimal and not altered by ischemia with or without reperfusion. In contrast, ischemia markedly affected the coronary microvascular response to vasopressin (10 to 1000 microU/ml). Control coronary microvessels constricted minimally to vasopressin (4% +/- 2% of the baseline diameter), while microvessels after either ischemia alone or ischemia followed by reperfusion constricted 22% +/- 5% and 21% +/- 3%, respectively (p less than 0.05 versus control for both). Hemoglobin, which inactivates the endothelium-derived relaxing factor, augmented microvascular constrictions to vasopressin in all groups to a similar extent. Relaxations to the endothelium-independent agent nitroglycerin were not altered by ischemia. Constrictions of the coronary microcirculation to vasopressin in conditions such as cardiopulmonary bypass or myocardial ischemia, in which circulating levels of vasopressin are increased, may predispose to persistent myocardial ischemia in the perioperative setting.

Topics: Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Dinoprost; Dogs; Microcirculation; Myocardial Reperfusion; Myocardial Reperfusion Injury; Nitroglycerin; Prostaglandin Endoperoxides, Synthetic; Vasoconstriction; Vasopressins

Myocardial ischemia inhibits endothelium-dependent relaxation stimulated by the coagulant peptide, thrombin. To investigate whether activation of endogenous thrombin contributed to this reduction in relaxant sensitivity, the effects of pretreatment of dogs with the coumarin anticoagulant, brodifacoum, were studied. Experiments were performed in both normal coronary vasculature and coronary vasculature exposed to 90 min of myocardial ischemia, with or without 60 min of subsequent reperfusion. Ischemia was induced in the left anterior descending artery (LAD); nonischemic vessels from the left circumflex (LCX) artery of the same animals were used as control. Thrombin caused dose-dependent relaxation in isolated LCX preconstricted with prostaglandin F2 alpha (Emax of 89.1 +/- 2.33%). Relaxation was reduced by 90 min of ischemia (Emax of 27.5 +/- 8.0%; p less than 0.05), and further reduced after subsequent reperfusion (Emax of 8.7 +/- 8.7%). However, maximum relaxations to acetylcholine, calcimycin, and isoproterenol were unchanged after ischemia (Emax greater than 90% in all groups). Brodifacoum had no effect on thrombin-induced relaxation in control vessels (Emax of 83.0 +/- 3.5%), or on relaxation in response to acetylcholine, calcimycin, or isoproterenol (Emax greater than 90%). In contrast, brodifacoum markedly reduced thrombin-induced relaxation after ischemia (Emax of 3.3 +/- 3.3%; p less than 0.05) yet significantly preserved the relaxant response to thrombin after ischemia and reperfusion (Emax of 36.6 +/- 4.3%). Infusion of the thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), during ischemia and reperfusion also preserved in part the relaxant response induced by thrombin (Emax of 30.0 +/- 5.1%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 4-Hydroxycoumarins; Acetylcholine; Amino Acid Chloromethyl Ketones; Animals; Blood Coagulation; Calcimycin; Coronary Disease; Dinoprost; Dogs; Endothelium, Vascular; In Vitro Techniques; Isoproterenol; Male; Muscle Relaxation; Nitric Oxide; Thrombin

In continuation of investigations on primary hyperlipidaemias, we determined serum thromboxane (TX) B2 and prostaglandin (PG) F2 alpha after standardized blood clotting in patients without hyperlipidaemia and without (group 1, n = 11) or with coronary heart disease (CHD; group 2, n = 5), in patients with familial combined hyperlipoproteinaemia and without (group 3, n = 4) or with CHD (group 4, n = 5), as well as in patients with familial hypercholesterolaemia and CHD (group 5, n = 5). TXB2 was detected by gas chromatography and PGF2 alpha by means of radioimmunoassay. The TXB2 level did not differ significantly between the groups, but there was a tendency to higher values in hyperlipidaemia, while in group 5 the level tended to decrease with rising serum LDL-cholesterol and in group 3 it tended to increase with rising serum apolipoprotein B. The PGF2 alpha level was significantly lower in group 4 than in groups 1 and 3. It showed in group 5 a negative correlation with serum LDL-cholesterol and in group 3 a positive correlation with serum triglycerides.

Topics: Adult; Aged; Apolipoproteins A; Apolipoproteins B; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Dinoprost; Female; Humans; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Lipids; Male; Middle Aged; Thromboxane B2; Triglycerides

The important role played by prostaglandins in the pathogenesis of coronary disease and essential hypertension is well known. The authors have attempted to reveal a relationship between blood levels of natural autoantibodies to PGF2 alpha and PGE2 and specific features of coronary disease and essential hypertension course and complications. A total of 87 subjects were examined, 23 of these--normal controls, 25 patients with myocardial infarction, 22 with angina pectoris, and 17 with essential hypertension. Solid-phase enzyme immunoassay was employed to detect anti-PGF2 alpha and anti-PGE2 antibodies. These antibodies were found in normal subjects, coronary patients and hypertensives. Blood levels of these antibodies correlated with some complications of coronary disease and essential hypertension. These results permit a hypothesis that the pathogenetic physiologic role of the detected natural antibodies to prostaglandins consists in their defense homeostatic function.

Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases; Coronary Disease; Dinoprost; Dinoprostone; Humans; Hypertension; Middle Aged

Topics: Arrhythmias, Cardiac; Blood Viscosity; Coronary Disease; Dinoprost; Heart Conduction System; Humans; Nucleotides, Cyclic; Platelet Aggregation; Prognosis; Thrombosis; Thromboxane B2

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

This study was carried out to investigate the possible contribution of endogenous prostaglandin (PG) production to failure of contractile recovery following reperfusion of hypoperfused isolated rat hearts. A 90% reduction in coronary flow rate for 60 min resulted in a time-dependent depression of contractile force and an elevation in resting tension. Reperfusion produced a slight (approximately 11%) recovery of contractile force, whereas resting tension remained elevated. Reperfusion was a potent stimulus for PG (as assessed by 6 keto-PGF1 alpha) release and resulted in levels that were significantly higher than those observed prior to ischemia. When PG synthesis was inhibited by the nonsteroidal anti-inflammatory drugs ibuprofen, indomethacin, or acetylsalicylic acid (ASA), recovery of ventricular contractility on reperfusion was significantly higher than that seen in the absence of drugs. Ibuprofen was the most effective, producing an average recovery of 70% (P less than 0.05 from control). Indomethacin and ASA produced approximately a 40% (P less than 0.05) and 35% (P less than 0.05) recovery of contractile force, respectively. The improved recovery in contractility was significantly depressed by the addition of low concentrations of prostacyclin (PGI2) and PGF2 alpha, whereas PGE2 and 6 keto-PGF1 alpha, the hydrolysis product of PGI2, were ineffective. The effects on resting tension were inconsistent. PG release during reperfusion was unrelated either to the length of the initial period of reduced coronary flow or the degree of contractile recovery; it was attenuated either by a reduction in or by an elevation of Ca concentration. These results indicate that endogenous PGs mediate, at least in part, reperfusion-associated failure of ventricular function.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Coronary Circulation; Coronary Disease; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Epoprostenol; Ibuprofen; Indomethacin; Male; Myocardial Contraction; Myocardium; Perfusion; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains

Blood endogenous prostaglandins, E, F2 alpha, prostacyclin and thromboxane levels were measured in the ascending aorta and the coronary sinus of 32 patients (29 males and 3 females) with paroxysmal supraventricular arrhythmias (atrial fibrillation and supraventricular tachycardia) during the sinus rhythm and an arrhythmic paroxysm. Group 1 was made up by 22 patients with idiopathic cardiac rhythm disorders, and group 2 comprised 10 coronary patients with arrhythmias. A relationship was demonstrated between cardiac endogenous prostanoids balance and the clinical pattern of cardiac rhythm abnormality (duration and frequency of paroxysms) as well as changes in cardiac prostanoid rations associated with tachyarrhythmic paroxysms.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Chronic Disease; Coronary Disease; Dinoprost; Female; Humans; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Tachycardia, Paroxysmal; Tachycardia, Supraventricular; Thromboxane B2

Arrhythmias were produced by ouabain (2.7 X 10(-7) M) in isolated perfused guinea pig hearts. In control hearts the average time to onset of arrhythmias following exposure to ouabain was approximately 35 min. Ligation of the left anterior descending coronary artery significantly shortened the time to arrhythmias to about 15 min. This effect of ligation was attenuated significantly by pretreating the hearts with acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs. In contrast, the protective influence of ASA was reversed by either prostaglandin (PG) E2, PGF2 alpha, or PGI2 (2.8 X 10(-9) M). When PGE2 or PGI2 were present in the absence of ASA, the time to arrhythmias following ouabain administration was significantly shortened. PGF2 alpha had no effect in these experiments. The sensitivity was enhanced significantly by treatment with arachidonic acid. This effect was reduced by treatment with ASA or indomethacin. Prostaglandin production during the experiments was estimated by monitoring release of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin. Abbreviation of time to arrhythmias by ligation was greatest in hearts that released large amounts of 6-keto-PGF1 alpha and least in those that released low amounts. These results suggest that coronary ligation potentiates the arrhythmogenic effects of ouabain by a mechanism probably mediated by prostaglandin(s).

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Arrhythmias, Cardiac; Aspirin; Coronary Circulation; Coronary Disease; Coronary Vessels; Dinoprost; Dinoprostone; Epoprostenol; Guinea Pigs; Ibuprofen; Indomethacin; Ligation; Male; Ouabain; Perfusion; Prostaglandins; Prostaglandins E; Prostaglandins F; Time Factors

We have briefly summarized only the data obtained in our own laboratory without including an extensive literature review. We have evaluated the changes in platelet membrane phospholipids and prostanoid formation in platelets. In atherosclerosis platelets show an activated prostanoid formation, whereas the plasma PGI2 levels are decreased.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Arachidonic Acids; Arteriosclerosis; Blood Platelets; Coronary Disease; Dinoprost; Humans; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Reference Values; Serum Albumin, Bovine

We investigated thromboxane B2 (TxB2), 6-keto-PGF1 alpha (6KPGF1 alpha reflecting prostacyclin), PGE2 and PGF2 alpha plasma levels; TxB2, PGE2 and PGF2 alpha platelet production and platelet aggregation response in ascending aorta (reflecting trans-pulmonary difference) and in venous coronary sinus (reflecting transcardiac difference) simultaneously in patients with ischemic heart disease, before and after right-atrial administration of 3 mg ISDN bolus. Transcardiac differences were scarce before as well as after ISDN administration. In aortic blood, ISDN administration into the right atria resulted in a significant increase in prostacyclin and PGF2 alpha plasma levels (472% and 242%, respectively), a decrease of both PGE2 plasma level (-173%) and PGE2 platelet production (-485%) and a marked lowering of platelet aggregation response to ADP, concomittantly. In contrast, TxB2-related features were poorly affected by ISDN. In coronary sinus blood, the aortic increase in 6KPGF1 alpha and PGF2 alpha plasma levels was detected to a lower extent whereas the characteristics of platelet aggregation had returned to control levels. By contrast, PGE2 plasma level (-191%) and PGE2 platelet production (-133%) were lower than prior ISDN administration. The results we report here, strongly support the view that ISDN promotes release of prostacyclin and PGF2 alpha from the lung and inhibit PGE2 production. These prostanoids may be responsible for the concomittant platelet reactivity lowering, thus providing a basis for understanding how ISDN might relieve myocardial ischemia favoring prostanoid mediated vasodilation and inhibition of platelet reactivity.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Aged; Coronary Disease; Dinoprost; Dinoprostone; Eicosanoic Acids; Epoprostenol; Humans; Isosorbide Dinitrate; Lung; Male; Middle Aged; Platelet Aggregation; Prostaglandins E; Prostaglandins F; Thromboxane B2

Topics: Alprostadil; Coronary Disease; Dinoprost; Heart Failure; Humans; Prostaglandins A; Prostaglandins E; Prostaglandins F

Topics: Adaptation, Physiological; Adult; Aged; Alprostadil; Chronic Disease; Coronary Disease; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Contraction; Prostaglandins A; Prostaglandins E; Prostaglandins F

Prostaglandins (PGA1, PGE1 and PGF2 alpha) were assayed in 15 patients with chronic coronary disease during an anginal attack induced through frequent atrial stimulation. Measurements from eleven patients with intact coronary arteries served as control. Lactate extraction coefficient was used as a biochemical indicator of myocardial ischemia; the latter was associated with increased production of coronary sinus PGF2 alpha and arterial PGA1. No correlation could be established between PG levels in the studied series, the extent of ST depression on electrocardiograms, lactate extraction level and hemodynamic manifestations.

Topics: Alprostadil; Arteries; Coronary Disease; Coronary Vessels; Dinoprost; Electric Stimulation; Hemodynamics; Humans; Lactates; Middle Aged; Prostaglandins A; Prostaglandins E; Prostaglandins F; Veins

We investigated the mechanism of the reperfusion-accelerated mitochondrial dysfunction. To clarify this mechanism, we performed the following experiments using 40 mongrel dogs. Experiment I: Prostaglandin (PG) E and F2 alpha levels in the great cardiac vein (GCV) were examined before, during occlusion and after reperfusion of the left anterior descending coronary artery (LAD). Experiment II: Heart mitochondria were prepared from the normal area and the occluded or the reperfused area after 15 min of the LAD occlusion, or after 5 min of reperfusion following the occlusion with or without premedication of indomethacin. The PGE level in the GCV did not change significantly during occlusion, but increased significantly soon after reperfusion. Mitochondrial dysfunction was caused by occlusion and further accelerated by reperfusion. The PG E level in mitochondria isolated from the reperfused area increased significantly. Indomethacin significantly prevented both the increase in PG E and the acceleration of mitochondrial dysfunction by reperfusion. These results suggest that the increase in PG E level is closely related to the reperfusion-accelerated mitochondrial dysfunction, and that premedication with indomethacin significantly prevented the extension of mitochondrial dysfunction induced by coronary reperfusion.

Topics: Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Dinoprost; Dogs; Female; Indomethacin; Male; Mitochondria, Heart; Perfusion; Prostaglandins E; Prostaglandins F

This study was designed to clarify the mechanism of reperfusion arrhythmia. In the mongrel dogs, the left anterior descending coronary artery was occluded for 15 min and then the ligation was released. The dogs were divided into two groups: one was the control group, and the other the indomethacin group in which indomethacin, an inhibitor of prostaglandin (PG) biosynthesis, was premedicated at 30 min before ligation. The ventricular multiple response threshold (VMRT), and plasma levels of K+, PG E and PG F2 alpha were measured in the great cardiac vein before and during occlusion, and after reperfusion. In the control group, during occlusion, VMRT decreased and did not return to normal soon after reperfusion. The levels of PG E and PG F2 alpha in the great cardiac vein did not change significantly during occlusion; however, PG E became significantly elevated after reperfusion. In the indomethacin group, the time course of VMRT was essentially similar to that of the control group during occlusion; however, lowering of VMRT after reperfusion was prevented significantly. The PG F2 alpha level in the great cardiac vein did not elevate after reperfusion or during occlusion. In both groups, the level of K+ in the great cardiac vein was elevated during occlusion, but rapidly decreased to normal after reperfusion. These results suggest that PG E, as a washout metabolite, is a key factor in evoking reperfusion arrhythmia.

Topics: Animals; Arrhythmias, Cardiac; Coronary Circulation; Coronary Disease; Dinoprost; Dogs; Female; Indomethacin; Male; Potassium; Prostaglandins E; Prostaglandins F

In our ongoing studies of the interrelationship between platelets and the vascular wall we found that an accurate estimate could be made of the clinical condition and more effective therapy prescribed when we monitored alterations in the plasma levels of TXB2. For this purpose we devised a radioimmunoassay with I125-TXB2-Tyramide. Patients with ischemic heart disorders, cerebral apoplexy, diabetes mellitus, Buerger's disease, Takayasu disease etc., all had statistically high levels of TXB2 as compared with healthy controls. In particular, patients with myocardial infarction, cerebral thrombosis and/or hemorrhage all revealed increases in levels of TXB2 and these levels increased in parallel with a worsening of the clinical condition, and there was always a re-increase in TXB2 level before a recurrence of an attack. As plasma TXB2 levels clearly reflect thrombogenic disorders, the assessment of these levels on a routine basis, enables a more accurate diagnosis, an indication of possible recurrences, and more effective chemotherapy and rehabilitation.

Topics: Adolescent; Adult; Arteriosclerosis; Arteriosclerosis Obliterans; Child; Chromatography, Gel; Circadian Rhythm; Coronary Disease; Diabetes Mellitus; Dinoprost; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Prostaglandins F; Takayasu Arteritis; Thromboangiitis Obliterans; Thromboxane B2; Thromboxanes