prostaglandin-f1 and Ischemia

Despite increasing evidence supporting the involvement of neutrophils in ischemic and postischemic damages, the mechanisms underlying the early recruitment of these cells are not completely understood. In this report, the effects of conditioned media from hypoxic endothelial cells on neutrophil chemotaxis were investigated by biochemical and morphological studies. We showed that conditioned media collected from several endothelial cell origins submitted to hypoxia as well as ischemic rat liver perfusion liquids have a chemotactic activity for neutrophils. The role of various chemoattractant molecules like HETEs, platelet-activating factor, and cytokines such as interleukin-8 and interleukin-1 was examined in the same model. Chemotactic peptide contribution was ruled out as boiled conditioned media still trigger chemotaxis. However, cell treatment with cyclooxygenase inhibitors, neutralization of PGF(2alpha) biological activity with polyclonal antibodies, and the neutrophil preincubation with a specific PGF(2alpha) antagonist, all dramatically inhibited neutrophil chemotaxis. A strong chemoattractant effect of pure exogenous PGF(2alpha) or of a synthetic analog was also observed. The major effect of PGF(2alpha) on neutrophil chemotaxis was confirmed ex vivo in a rat liver perfusion ischemic model. These results suggest that PGF(2alpha), a prostanoid abundantly released by the endothelium of hypoxic or ischemic tissues, is a chemoattractant molecule that might be involved in the early recruitment of neutrophils in ischemic organs.

Topics: Animals; Cells, Cultured; Chemotactic Factors; Culture Media, Conditioned; Dinoprost; Endothelium, Vascular; Female; Humans; Hydroxyeicosatetraenoic Acids; Hypoxia; Interleukin-1; Interleukin-8; Ischemia; Liver Circulation; Neutrophil Infiltration; Prostaglandin Antagonists; Prostaglandins F; Rats; Rats, Wistar

ANP model in rats was used to determine the concentration of TXB2, PGF1 alpha in plasma and the ACE activity in serum in five groups. The concentration of TXB2, PGF1 alpha in all experimental groups was significantly different from that of control group (P < 0.05). The comparison of ACE activity was just the same as the above except that of 6 h. The factors leading to pancreatic ischemia functioned continously. We conclude that pancreatic ischemia is a continuous injury factor in ANP, and there is no reperfusion-injury in the course of the disease.

Topics: Animals; Female; Ischemia; Male; Pancreas; Pancreatitis, Acute Necrotizing; Peptidyl-Dipeptidase A; Prostaglandins F; Rats; Rats, Sprague-Dawley; Taurocholic Acid; Thromboxane B2

Six patients undergoing vascular reconstructive surgery were examined for evidence of oxygen-derived free radical (ORF) damage to the protein, immunoglobulin G (IgG). OFR damage was determined as an increase in the fluorescence (ex 360 nm em 454 nm) to ultraviolet absorption (280 nm) ratio of IgG, representing N-Formyl kynurenine and other as yet unidentified fluorophores. The IgG ratio was found to increase slightly during ischaemia and to undergo marked elevation upon reperfusion (275 +/- 405% baseline value at 40 min post-clamp; mean +/- sd). A high ratio was maintained post-reperfusion, even after 60 min reperfusion. Determination of thromboxane B2, (TXB2), leukotriene B4, (LTB4) and 6-keto prostaglandin F1 alpha, (PGF1a), revealed a decrease in their concentrations during ischaemia and a transient, marked increase on reperfusion. Only TXB2 concentrations were found to correlate with the IgG ratio (negative correlation, p < 0.05). No correlation was observed between von Willebrand antigen factor, a marker of endothelial cell damage and fluorescent IgG ratio. However, levels of the factor increased slightly during ischaemia and more sharply upon reperfusion. These preliminary results therefore suggest that a more likely source of the OFRs responsible for IgG damage is endothelial cell xanthine oxidase, rather than cyclo-oxygenase or lipoxygenase.

Topics: Aged; Free Radicals; Humans; Immunoglobulin G; Ischemia; Leg; Leukotriene B4; Middle Aged; Prostaglandins F; Reperfusion Injury; Thromboxane B2; Vascular Surgical Procedures; von Willebrand Factor

The circulating prostaglandins have been implicated as mediators of microcirculatory derangements in skin and skin-muscle flaps. The study described here investigated the roles of thromboxane A2 and prostacyclin, measured as thromboxane B2 (TxB2) and prostaglandin 6-keto-F1a (PGF1a), in ischemic skin flaps, and the effects of thromboxane synthetase inhibition on flap blood flow and survival. A canine ventral island flap model was used to measure the appearance of TxB2 and PGF1a in the central arterial and venous plasma, and in the tissue and venous effluent of acutely raised flaps; with and without pretreatment with the specific thromboxane A2 synthetase inhibitor UK38485. Prostaglandin levels change significantly during flap elevation, and can be modified beneficially by thromboxane A2 synthetase inhibition, causing dramatic increases in flap blood flow and survival, as predicted by intravital dye penetration. The results presented in this article suggest that the manipulation of these compounds may provide a method of producing a pharmacological delay phenomenon and perhaps even allow effective intervention in the failing flap.

Topics: Animals; Dogs; Epoprostenol; Female; Imidazoles; Ischemia; Platelet Aggregation; Prostaglandins F; Skin; Surgical Flaps; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

Topics: Acute Kidney Injury; Animals; Cyclosporins; Dinoprostone; Dogs; Glomerular Filtration Rate; Ischemia; Kidney; Phosphates; Prostaglandins E; Prostaglandins F; Regional Blood Flow; Thromboxane B2; Vascular Resistance