thromboxane-b2 and Heart-Diseases

To reveal changes in the thromboxane-prostacyclin balance and platelet aggregability in patients with various variants of minor cardiac abnormalities.. Six-five patients (mean age 23.0 +/- 0.7 years) with minor cardiac abnormalities and 10 apparently healthy individuals were examined. Platelet aggregation induced by adrenaline, adenosine diphosphate, collagen) and the plasma levels of thromboxane B2 (TxB) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) were determined.. Patients with abnormally located chordae (ALC) were found to have no deviations in the thromboxane-prostacyclin balance and platelet aggregability. Only decreased collagen aggregation was recorded in the groups of first-degree mitral prolapse (MP) and first-degree MP + ALC; in second-degree MP and second-degree MP + ALC, there was a reduction in platelet aggregation on all inductors and an increase in TxB2. Patients with myxomatous degeneration of the mitral valve exhibited reduced collagen-induced platelet aggregation and lower plasma 6-keto-PGF1alpha levels.. The most pronounced changes in the thromboxane-prostacyclin balance and platelet aggregability were found in patients with MP and second-degree regurgitation, three intracardiac micro-abnormalities, and myxomatous degeneration of the mitral valve.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Adolescent; Adult; Blood Platelets; Case-Control Studies; Collagen; Epinephrine; Female; Heart Diseases; Hemostasis; Humans; Male; Platelet Aggregation; Severity of Illness Index; Thromboxane B2; Ultrasonography; Young Adult

Treatment of HIV with AZT (zidovudine) may have toxic side effects as a result of multiple mechanisms. It is known that patients with AIDS may suffer from magnesium deficiency (MgD). We studied selected biochemical and histopathologic consequences of AZT administration (0.7 mg/mL in drinking water) with concurrent Mg-deficient (20% of normal) diet in male C57Bl/6N mice for 3 wk. Significant decreases in red blood cell glutathione (GSH) were evident in the Mg-deficient mice with or without AZT treatment, suggesting compromised antioxidant capacity in the blood. Although MgD alone led to a 1.9-fold increase in plasma thromboxane B(2) (TXB(2), derived from the highly vasoconstrictive TXA(2)), AZT + MgD increased the TXB(2) level 3.5-fold. AZT (+/-MgD) provoked prominent hepatic damage expressed by distortion of lobular architecture, nuclear and cellular swelling, and inflammatory lesions and loss of hepatocytes. AZT alone caused mild cardiac lesions, resulting in partial cardiac fibrosis, especially in the atrium. AZT + MgD caused only scattered small-size cardiac lesions consisting of microscopic foci of inflammatory infiltrates in the ventricles but led to more prominent lesions, fibrosis, and scars in the atrium. MgD or AZT alone caused varying degrees of skeletal muscle degeneration; in combination, more intense degeneration and regeneration of muscle cells were evident. In conclusion, it is suggested that both the decreased blood GSH and elevated plasma TXA(2) might contribute, at least in part, to the aggravated pathological damages observed in the atrium and skeletal muscle of the AZT-treated Mg-deficient mice.

Topics: Animals; Anti-HIV Agents; Glutathione; Heart Diseases; Liver; Magnesium Deficiency; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Myocardium; Thromboxane B2; Zidovudine

The experiment was conducted with SD male rats. After they had been each given an intravenous injection of high molecular weight dextran (0.8 ml/100 g body wt) once a day for 4 days, they were brought under the observation of ECG and mesentery microcirculation. Microthrombi were found in the venules and capillaries of each rat of the experimental group, while in the microcirculation of the control group rats, no microthrombi were found. No changes were found in the ECGs of the rats (n = 6) in the control group after the injections, while the rats in the subject group all suffered a rise in the S-T segment of ECG, an indication of myocardial injuries. The rise was significantly in positive correlation to the increase in microthrombi in number (r = 0.944, P < 0.01). The erythrocytes of the rats in the subject group clustered to become rouleau-like, and platelets aggregated by tens and hundreds to form microthrombi. Their blood also showed a significant decrease in number of platelets. The degree of platelet aggregation and the scores of the rise on ECG were significantly in positive correlation as shown by the results: y = 20 + 94x, r = 0.94, P < 0.01. The plasma TXB2 of the subject group increased obviously but the change of 6-K-PGF1 alpha in the blood was not significant. The content of plasma TXB2 and the scores that indicated the rise in the S-T segment of the ECG showed significantly a positive correlation by the analysis of linear regression equation: y = 109.997 +/- 116.25x, r = 0.889, P < 0.05. The activity of Na(+)-K(+)-ATPase on the myocardial cell membranes of the rats with microthrombi was significantly reduced as compared with that of the rats in the control group (P < 0.01). The activity of the Na(+)-K(+)-ATPase was significantly in negative correlation to the rise in the S-T segment of ECG (P < 0.05). This study demonstrates that the above changes are the causes of myocardial injuries in rats with circulatory thrombi.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dextrans; Electrocardiography; Erythrocyte Aggregation; Heart Diseases; Male; Microcirculation; Myocardium; Rats; Sodium-Potassium-Exchanging ATPase; Thrombosis; Thromboxane B2

Sixteen sheep were surgically prepared for chronic study. Seven days later, Escherichia coli endotoxin (10 ng/kg/min, lipopolysaccharide (LPS) group, n = 10) or an equivalent amount of 0.9% NaCl (Control group n = 6) was administered. Between 1 and 8 h post-LPS, there was a hypodynamic state with low cardiac index (CI, LPS 5.0 +/- 0.2; sham 6.3 +/- 0.4 liters/min/m2 at 4 h). During this period, the left ventricular end-systolic pressure-diameter relationship (ESPDR), a sensitive index of myocardial contractility, was also lower (LPS 10.4 +/- 1.2; sham 17.2 +/- 0.8 mmHg/mm). Mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance index (PVRI) were remarkably increased 1 h after the administration of LPS (PAP:LPS 37.5 +/- 1.9; sham 21.8 +/- 0.9 mmHg, PVRI: LPS 600 +/- 58; sham 158 +/- 23 dynes x s x cm-5 x m2). The early changes in cardiopulmonary function occurred concomitantly with an elevation in tumor necrosis factor (LPS 1221 +/- 520; sham 0 +/- 0 pg/ml) and thromboxane B2 (LPS 1382 +/- 266; baseline 82 +/- 20 pg/ml) in arterial blood. Following this first phase, the sheep presented a persistent hyperdynamic state characterized by a significant increase in CI. The ESPDR continued to fall. By 24 h post-LPS the CI was 10.1 +/- 0.5 liters/min/m2 (sham, 6.3 +/- 0.3) but the ESPDR had fallen to 8.2 +/- 2.3 mmHg/mm (sham 16.0 +/- 3.0). The pulmonary hypertension was maintained for the duration of the LPS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Blood Pressure; Cardiac Output; Endotoxins; Female; Heart Diseases; Lung; Lung Injury; Myocardial Contraction; Neutrophils; Pulmonary Circulation; Sheep; Thromboxane B2; Tumor Necrosis Factor-alpha; Vascular Resistance; Ventricular Function, Left

We evaluated the effect of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) on pig cardiopulmonary function by intravenously infusing each cytokine individually or in combination (0.5 microgram/kg from 0 to 0.5 h + 5 ng.kg-1 x min-1 from 0.5 to 6 h for each cytokine). The role of eicosanoids in mediating the TNF-alpha + IL-1 alpha-induced cardiopulmonary dysfunction was also investigated by pretreating cytokine-infused pigs with CGS 8515 (5-lipoxygenase inhibitor) or indomethacin (cyclooxygenase inhibitor). Coinfusion of TNF-alpha with IL-1 alpha caused additive increases (P < 0.05) in total peripheral resistance and plasma concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha). The increases in mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), alveolar-arterial O2 gradient (AaDO2), alveolar dead space-to-tidal volume ratio (VD/VT), and plasma concentrations of thromboxane B2 were either additive or synergistic. CGS 8515 blocked the TNF-alpha + IL-1 alpha-induced increases (P < 0.05) in mean aortic pressure, total peripheral resistance (4-6 h), VD/VT (5-6 h), and, at 6 h, attenuated the increases in Ppa, PVR, and AaDO2. Indomethacin blocked or attenuated the cytokine-induced increases (P < 0.05) in Ppa, PVR, AaDO2, VD/VT, and plasma concentrations of thromboxane B2 and 6-keto-PGF1 alpha. The 1-to 2-h systemic hypotension, caused by TNF-alpha + IL-1 alpha, was not abrogated by either indomethacin or CGS 8515. The cytokines did not alter plasma concentrations of leukotriene B4 or 5-hydroxyeicosatetraenoic acid. We conclude that coinfusion of TNF-alpha with IL-1 alpha induces physiological responses that are additive or synergistic and that cyclooxygenase and 5-lipoxygenase products (other than leukotriene B4 and 5-hydroxyeicosatetraenoic acid) importantly mediate cardiopulmonary dysfunction in pigs infused with TNF-alpha + IL-1 alpha.

Topics: 6-Ketoprostaglandin F1 alpha; Albumins; Animals; Arachidonic Acids; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Cytokines; Dinoprost; Drug Synergism; Eicosanoids; Heart; Heart Diseases; Hydroxyeicosatetraenoic Acids; Indomethacin; Injections, Intravenous; Interleukin-1; Leukotriene B4; Lipoxygenase Inhibitors; Lung; Lung Diseases; Naphthoquinones; ortho-Aminobenzoates; Swine; Thromboxane B2; Tumor Necrosis Factor-alpha; Vascular Resistance

Administration of exogenous adenosine triphosphate (ATP) as a vasodilator during cardiopulmonary bypass was assessed in consecutive adult patients (n = 24) who demonstrated a high arterial perfusion pressure (mean, > 90 mm Hg). The action of ATP was characterized by rapid induction and stabilization of the blood pressure level. The dose of ATP ranged from 0.68 to 2.68 mg/min. Within 1 minute after the administration, there was a significant reduction in the perfusion pressure from 102 +/- 18 mm Hg (mean +/- standard deviation) to 72 +/- 19 mm Hg. The ATP was then able to maintain the desired pressure of 69 +/- 12 mm Hg at 5 minutes, 67 +/- 12 mm Hg at 10 minutes, and consistent values thereafter. After the ATP administration was discontinued, there was a prompt recovery of pressure without bradyarrhythmia. The frequency and amount of inotropes used were consistent with the control group (n = 26). Although the administration of ATP reduced the increase in serum catecholamine concentration, there were no significant changes in other vasoactive mediators (eicosanoid, angiotensin II, endothelin) between the two groups during cardiopulmonary bypass. There was neither an accumulation of metabolic products (uric acid, phosphate) nor a decrease in the level of divalent cation (Ca2+), which is observed when the cations combine with phosphates or adenosine nucleotides. This study confirmed the efficacy and safety of ATP infusion during cardiopulmonary bypass.

Topics: Adenosine Triphosphate; Adult; Aged; Angiotensin II; Blood Pressure; Cardiopulmonary Bypass; Coronary Artery Bypass; Endothelins; Epinephrine; Female; Heart Defects, Congenital; Heart Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Norepinephrine; Prostaglandins F; Thromboxane B2; Vascular Resistance; Vasodilator Agents

The exposure of cardiac cells to OFR generated artificially, showed a marked decrease (p less than 0.01) in cellular utilization of glucose along with a significant decrease in calcium uptake (p less than 0.05). We have also provided evidence for a direct relationship of neutrophil OFR production with the extent of myocardial ischemia in patients of myocardial infarction. Our data provides evidence for implication of OFR in myocardial injury and the pivotal role played by modulators like calcium, ECGF and prostaglandins in potentiating damage to the myocardium.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Animals; Calcium; Coronary Artery Disease; Endothelial Growth Factors; Female; Free Radicals; Glucose; Heart Diseases; Humans; In Vitro Techniques; Indomethacin; Macaca mulatta; Male; Mice; Middle Aged; Myocardium; Oxidation-Reduction; Oxygen; Thromboxane B2

Many organs have the capacity to form prostanoids. Under pathophysiological conditions the biosynthesis of TXB2 and 6-oxo-PGF1 alpha is markedly increased in the myocardium and the gastric mucosa. Tumor growth is linked with an enhanced prostanoid formation. Furthermore a rise of the PG content could be found in the liquor, aqueous humor and urine under diseases of the related organs. These results could be of some significance for diagnosis and therapy control.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aqueous Humor; Brain Diseases; Child; Gastric Mucosa; Gastritis; Guinea Pigs; Heart Diseases; Humans; Hypertension, Portal; In Vitro Techniques; Indomethacin; Kidney Transplantation; Myocardium; Skin Neoplasms; Thromboxane B2

This study was performed to determine the relationship between plasma concentration of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a and atrial thrombosis in patients with mitral stenosis (MS). By radioimmunoassay and pathological examination, peripheral plasma TXB2 level was remarkably higher in patients with MS and persistent atrial fibrillation (AF) than in patients with MS but without AF (P less than 0.01). Plasma TXB2 level was significantly higher in patients with than in those without atrial thrombosis (P less than 0.05). There was no significant difference in plasma 6-keto-PGF1 alpha, plasma prostanoids level in peripheral venous blood correlated closely with that in left atrial blood. Patients with high plasma TXB2 level had a greater incidence of microthrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Atrial Fibrillation; Female; Heart Diseases; Humans; Male; Middle Aged; Mitral Valve Stenosis; Rheumatic Heart Disease; Thrombosis; Thromboxane B2

Interleukin-2 (IL-2) produces toxicity characterized by generalized edema within 24 hours. This study tests whether the rate of IL-2 administration modulates the onset of edema and examines thromboxane (Tx) and neutrophils as possible mediators of this event. Recombinant human IL-2, 10(5) U (n = 7), 10(6) U (n = 9), or vehicle (n = 8) were given to anesthetized rats intravenously during a period of 1 hour. At 6 hours edema, as measured by increase in wet to dry weight (w/d) ratio, was present in the heart, liver, and kidney, with 10(5) U IL-2 and in the lung, heart, liver and kidney, with 10(6) U IL-2, relative to values with vehicle-infused controls (all p less than 0.05). With a 1-hour infusion of 10(6) U IL-2, there was an increase in plasma thromboxane (Tx)B2 level to 1290 +/- 245 pg/mL, higher than 481 +/- 93 pg/mL in control rats (p less than 0.05); lung polymorphonuclear leukocyte (PMN) sequestration of 53 +/- 7 PMN/10 higher-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05); and increased bronchoalveolar lavage (BAL) fluid protein concentration of 1970 +/- 210 micrograms/mL relative to 460 micrograms/mL in controls (p less than 0.05). When 10(6) U IL-2 was given as a 1-minute intravenous bolus (n = 9), edema was not demonstrated, plasma TxB2 levels were similar to controls, there was no leukosequestration, and BAL protein levels were normal. These data indicate that a constant infusion but not the rapid bolus administration of IL-2 produces in rats multiple-system organ edema, increased plasma TxB2, sequestration of PMNs, and microvascular permeability. These findings may explain the early toxicity seen in patients given high-dose IL-2 in cancer treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchoalveolar Lavage Fluid; Edema; Heart Diseases; Infusions, Intravenous; Injections, Intravenous; Interleukin-2; Kidney Diseases; Liver Diseases; Male; Neutrophils; Pulmonary Edema; Rats; Rats, Inbred Strains; Recombinant Proteins; Thromboxane A2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Dinoprostone; Female; Heart Diseases; Humans; Male; Middle Aged; Radioimmunoassay; SRS-A; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Alprostadil; Arachidonic Acids; Extracorporeal Circulation; Female; Heart Diseases; Humans; Male; Middle Aged; Prostaglandins; Thromboxane B2

Plasma thromboxane B2 (TxB2) level were measured in patients with various disease, and its changes were investigated in patients who underwent various operations. The following results were obtained. Plasma TxB2 values in patients with TAO, heart disease, and malignant disease were significantly elevated compared with healthy control. Plasma TxB2 values during operation and immediate period after operation were significantly elevated compared with preoperative values. Plasma TxB2 level was markedly elevated in bypass operation when synthetic prosthesis were used. In patients with malignant disease, plasma TxB2 values significantly decreased after removal of tumor compared with preoperative values. In cardiopulmonary bypass, TxB2 level were markedly elevated ten minutes after beginning, and then decreased gradually until the end of cardiopulmonary bypass. The factors which are considered to be related to elevation of plasma TxB2 level during the operation and the postoperative period are as follows: a) surgical intervention, b) anesthesia, c) thromboembolic complication, d) grafting of synthetic prosthesis. e) valve replacement and f) cardiopulmonary bypass. The positive correlation between beta-TG and TxB2 level was found. TxB2 measurement is complex and too expensive, while measurement of beta-TG is very easy and cheap. Because of their good correlation, beta-TG is used as substitute for TxB2 in daily practice.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Vessel Prosthesis; Cardiopulmonary Bypass; Female; Heart Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Monitoring, Physiologic; Neoplasms; Surgical Procedures, Operative; Thromboxane B2

Topics: Adolescent; Adult; Aged; Blood Coagulation; Cardiopulmonary Bypass; Child; Epoprostenol; Female; Fibrinolysis; Heart Diseases; Humans; Male; Middle Aged; Thromboxane B2; Thromboxanes

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Child; Extracorporeal Circulation; Female; Heart Diseases; Hemoglobins; Humans; Male; Middle Aged; Platelet Count; Thromboxane B2