thromboxane-b2 and Constriction--Pathologic

The authors investigated prostacyclin (PGI2) and thromboxane (TX) productions in peripheral venous blood after lower limb revascularization by percutaneous transluminal angioplasty (PTA) versus diagnostic angiography. The purpose of this study was to investigate PGI2/TX imbalance after PTA. This imbalance is of pathophysiologic importance and it is a potential sign of platelet function alteration.. Twenty-five patients requiring PTA were compared with 20 patients undergoing angiography alone from April 2004-December 2005 from a single vascular unit. Patient age range was 42-90 years, and the majority of patients were men. Prostaglandin F2-alpha (PGF2-alpha) and thromboxane B2 (TXB2) were measured sequentially (preprocedure, at 1 hour, and 24 hours after procedure). Differences between postprocedure and preprocedure level were compared statistically between angiography and PTA.. Baseline demographics were distributed equally between the two groups except presence of critical ischemia and ankle brachial pressure index, which were two significant confounders. TXB2 was significantly higher after PTA at 1 hour and 24 hours after PTA (P = .005 and P = .014 respectively), PGF2-alpha was significantly higher 24 hours after PTA only (P = .018) (Mann-Whitney U test).. PGI2/TX balance homeostasis is of significant pathophysiologic importance. The authors found that PTA results in significant PGI2/TX imbalance and shifts more toward increased TX production. This finding is partly suggestive of significant platelet activation. This imbalance in PGI2/TX level may have implications for future failure of PTA. Future research in reducing this platelet activation is recommended.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty; Ankle Brachial Index; Biomarkers; Blood Platelets; Constriction, Pathologic; Dinoprost; England; Epoprostenol; Female; Femoral Artery; Humans; Iliac Artery; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Activation; Prostaglandins I; Radiography, Interventional; Thromboxane A2; Thromboxane B2; Thromboxanes; Time Factors; Treatment Outcome

Plasma levels of 6-keto-prostaglandin F1 alpha (6kPGF1 alpha) and thromboxane (Tx) B2 have been assessed in sickle cell disease (SCD) with discrepant results. Inasmuch as direct measurement of plasma prostanoids is fraught with the problem of interfering substances, we assessed plasma 6kPGF1 alpha and TxB2 levels in patients with SCD by RIA after extraction of eicosanoids and separation by HPLC. We demonstrate that the 6kPGF1 alpha and TxB2 levels in children with SCD in steady state as well as in vaso-occlusive crisis (VOC) are significantly lower when compared with those from age-matched controls. The VOC plasma 6kPGF1 alpha and TxB2 levels were, however, significantly elevated when compared with those from children in steady state. Changes similar to those noted with unpaired plasma samples were also observed when paired steady state and VOC plasmas from the same patients were assessed. The ratio of TxB2 to 6kPGF1 alpha was, however, significantly elevated in patients with SCD in crisis when compared with eicosanoid ratios obtained during steady state. In an attempt to understand whether the abnormality in 6kPGF1 alpha was due to an impairment in endothelial cell prostacyclin-regenerating ability, we compared the ability of plasma from controls and children with SCD to activate arachidonic acid (AA) release and prostacyclin production by [14C]AA-prelabeled bovine aortic endothelial cells. Our results suggest that the decreased 6kPGF1 alpha levels in plasma from children with SCD was not due to an effect on substrate AA release but rather a modulatory effect of sickle plasma components on endothelial cell cyclooxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Anemia, Sickle Cell; Animals; Arachidonic Acid; Case-Control Studies; Cattle; Cells, Cultured; Child; Child, Preschool; Chromatography, High Pressure Liquid; Constriction, Pathologic; Endothelium, Vascular; Epoprostenol; Humans; Thromboxane B2; Vascular Diseases; Vasoconstrictor Agents; Vasodilator Agents

Platelet-activating factor (PAF) is a cell membrane-derived ether lipid that plays an important role in acute lung vascular injury. We recently reported that PAF potentiates protamine-induced lung edema by enhancing pulmonary venoconstriction. As PAF is known to stimulate lung eicosanoid synthesis, we investigated the role of peptidoleukotrienes and other eicosanoids in this priming effect of PAF. Addition of PAF (1.6 nM), followed 10 min later by protamine (50 micrograms/ml), to perfusate of salt solution-perfused rat lungs resulted in marked arterial and venous constrictions and severe lung edema. Lung tissue thromboxane B2, 6-ketoprostaglandin F1 alpha and leukotriene C4 (LTC4) were markedly elevated 20 min after PAF/protamine. Pretreatment of the lungs with AA-861, a specific 5-lipoxygenase inhibitor, blocked PAF/protamine-induced leukotriene synthesis, arterial and venous constrictions, and lung edema. In addition, injection of LTC4 (1 microgram) markedly potentiated protamine-induced arterial and venous constrictions and caused lung edema similar to PAF/protamine. Indomethacin, a specific cyclooxygenase inhibitor, also reduced the vasoconstrictive and edemagenic responses to PAF/protamine. However, the pulmonary edema after LTC4/protamine was not blocked by indomethacin. In separate experiments, infusion of this "priming" dose of PAF into isolated perfused lungs induced LTC4 synthesis and augmented lung thromboxane A2 synthesis after arachidonic acid infusion. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism are involved in PAF-induced potentiation of protamine lung edema.

Topics: Animals; Arachidonic Acid; Benzoquinones; Constriction, Pathologic; Drug Synergism; Indomethacin; Leukotriene C4; Lipoxygenase Inhibitors; Male; Organ Size; Platelet Activating Factor; Premedication; Prostaglandins F; Protamines; Pulmonary Circulation; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Thromboxane B2; Vascular Resistance

The regional production of prostaglandin E2 and thromboxane B2 was investigated in the kidney with unilateral or bilateral ureteral obstruction for 24 hours in rats. The production of these eicosanoids was highest in the inner medulla both with or without ureteral obstruction, although the production rate by the tubules was relatively low in the obstructed kidney compared to the sham-operated control. A greater production of these vasoactive compounds was noted by glomeruli from the kidneys with unilateral or bilateral obstruction and the contralateral kidney with unilateral obstruction. Glomeruli obtained from the kidney with unilateral obstruction produced more thromboxane B2 than the kidney with bilateral obstruction, and the resultant TxB2/PGE2 ratio was higher in the unilaterally obstructed kidney. This difference in the glomerular thromboxane B2 production may be responsible for the haemodynamic changes between unilateral and bilateral ureteral obstructions. An increased prostaglandin E2 production by glomeruli from the contralateral kidney with unilateral obstruction may contribute to a compensatory response.

Topics: Animals; Constriction, Pathologic; Dinoprostone; Female; Kidney; Kidney Diseases; Rats; Rats, Sprague-Dawley; Thromboxane B2; Ureteral Obstruction

The effect of nedocromil sodium on PAF-acether- and antigen-induced bronchoconstriction (BC) and mediator release in lungs from actively sensitized guinea pigs and on the eosinophil content of bronchoalveolar lavage (BAL) was investigated. Guinea pigs were actively sensitized by two subcutaneous injections of 10 micrograms ovalbumin in 1 mg AI(OH)3 at 2-wk intervals. One week after the second (booster) injection, the lungs were removed, perfused in the absence or presence of indomethacin, and challenged at 10-min intervals with PAF-acether (1 and 100 ng) and with ovalbumin (1 micrograms). No inhibition of PAF-acether- and antigen-induced BC or mediator release from sensitized lungs was observed when nedocromil sodium (10 microM) was added directly to the buffer solution. By contrast, when guinea pigs were treated for 1 wk before the experiment with nedocromil sodium (30 mg/kg per day), BC and the release of leukotrienelike material (but not of thromboxane B2) to 1 ng PAF-acether were reduced by around 50% (p less than 0.05) and 62% (p less than 0.05), respectively. No inhibition was observed for 100 ng PAF-acether and 1 micrograms ovalbumin. Furthermore, nedocromil sodium markedly impaired histamine secretion induced by both PAF-acether and antigen administration. Nedocromil sodium did not affect the titers of circulating ovalbumin-specific immunoglobulin G, as detected by an enzyme-linked immunosorbent assay. The 1-wk treatment with nedocromil sodium also reduced markedly the proportion of eosinophils in the BAL of sensitized guinea pigs, whereas it was ineffective when injected once subcutaneously at the dose of 30 mg/kg 2 h before the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchi; Bronchoalveolar Lavage Fluid; Constriction, Pathologic; Eosinophils; Female; Guinea Pigs; In Vitro Techniques; Indomethacin; Leukotriene Antagonists; Leukotrienes; Male; Nedocromil; Ovalbumin; Platelet Activating Factor; Quinolones; Respiratory Hypersensitivity; Thromboxane B2

There is a relationship between severity of bacterial bronchial asthma clinical symptoms and plasma 6-keto-PGF1 alpha, TxB2: in moderate disease against grave one as well as in clinical versus subclinical forms (remission) relevant indices are reduced. On the one hand elevated content of blood 6-keto-PGF1 alpha seems compensatory rising in response to TxB2 bronchoconstriction. On the other hand, it impairs microcirculation and enhances mediators of inflammation, promotes exudation and edema of bronchoalveolar mucosa, thus contributing to obstruction.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Asthma; Bronchi; Constriction, Pathologic; Female; Humans; Male; Microcirculation; Middle Aged; Thromboxane B2

The left anterior descending coronary artery (LAD) of five dogs was ligated, and blood was withdrawn from the great cardiac vein, left marginal cardiac vein, femoral vein, and aorta. After ligation, immunoreactive 6-ketoprostaglandin (PG) F1 alpha rose from less than 0.1 to a mean value of 1.2 pmol/ml plasma in the great cardiac vein (GCV) and 0.88 pmol/ml in the left marginal vein, with no change in peripheral circulation. Immunoreactive thromboxane (TX) B2 remained below 0.075 pmol/ml throughout the experiments. LAD of 11 dogs was stenosed 60-80% with consequent cyclical reductions in blood flow. 6-Keto-PGF1 alpha in GCV rose in seven dogs (range 0.5-2.2 pmol/ml) and remained unchanged in four. No change was observed in peripheral plasma levels of 6-keto-PGF1 alpha. In these experimental conditions TXB2 remained below 0.075 pmol/ml. Lactate concentrations rose in both experimental conditions in GCV but not in peripheral circulation or in the left marginal vein. This study confirms a link between cardiac ischemia and increased coronary prostacyclin release, but we were unable to detect a similar correlation with TXB2 in plasma.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arteries; Constriction, Pathologic; Coronary Circulation; Coronary Disease; Dogs; Ligation; Male; Thromboxane B2; Thromboxanes

The hemodynamic effects of intracoronary leukotriene C4 (0.3 to 10.0 micrograms) in seven anesthetized dogs with normal and severely narrowed coronary arteries were examined. Intracoronary leukotriene C4 caused a significant dose-related reduction in coronary blood flow in both normal and narrowed coronary arteries with no effect on heart rate or mean arterial pressure. However, left ventricular end-diastolic pressure increased at the 10.0 micrograms dose. The reduction of blood flow in normal and narrowed coronary arteries in response to leukotriene C4 was similar. At the peak effects of leukotriene C4, there was evidence of intracoronary thromboxane A2 release. To examine the contribution of thromboxane A2 release to the coronary vasoconstrictor effects of leukotriene C4, dogs were administered leukotriene C4 after indomethacin pretreatment. The decrease in coronary blood flow was not significantly affected by pretreatment of the animals with indomethacin. However, indomethacin lowered baseline levels of thromboxane B2 and blocked the release of thromboxane A2 after leukotriene C4 administration. Thus, intracoronary leukotriene C4 causes direct dose-dependent decrease in coronary blood flow of similar magnitude in both normal and narrowed coronary arteries. These coronary hemodynamic effects of leukotriene C4 in dogs are not mediated by release of thromboxane A2. Leukotriene C4 released from activated leukocyte in the intracoronary thrombus or in the injured myocardium may reduce coronary blood flow and adversely influence the fate of the affected myocardial tissue.

Topics: Animals; Blood Pressure; Constriction, Pathologic; Coronary Circulation; Coronary Disease; Dogs; Dose-Response Relationship, Drug; Female; Hemodynamics; Indomethacin; Leukocytes; Male; SRS-A; Thromboxane A2; Thromboxane B2

Topics: Angina Pectoris; Arachidonic Acids; Aspirin; Constriction, Pathologic; Coronary Disease; Dietary Fats; Epoprostenol; Fatty Acids, Unsaturated; Fish Oils; Humans; Platelet Aggregation; Risk; Thromboxane B2