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Biomedical subjects

D Kong

Publications and source records attributed to D Kong.

65 records · Page 4Linked to original sources
PubMed1987

Absence of prostaglandin changes associated with protamine administration in patients with pulmonary hypertension.

In patients with pre-existing pulmonary hypertension, severe pulmonary vasoconstriction has been observed following protamine administration. Thromboxane A2, a potent vasoconstrictor, is capable of producing increases in pulmonary vascular resistance, and animal studies suggest that heparin-protamine complexes stimulate thromboxane A2 synthesis. This study assessed the effect of protamine administration on hemodynamics and on plasma thromboxane A2 and its biologic antagonist, prostacyclin, by serial measurement of the stable metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha, respectively. Ten adults with pulmonary artery hypertension undergoing elective mitral valve replacement were studied. After termination of cardiopulmonary bypass, baseline hemodynamic measurements were obtained and arterial blood for prostanoid analysis was sampled. Hemodynamic and prostanoid measurements were obtained 5, 10, 15, and 30 minutes after the protamine infusion began. Prostanoid levels were performed by double antibody radio-immunoassay. No significant hemodynamic changes occurred and no significant changes in prostanoid levels were observed. It is concluded that in patients with pulmonary hypertension, heparin-protamine complexes do not consistently raise circulating thromboxane levels, and the relationships among prostanoids, pulmonary hypertension, and systemic hypotension are still not clear.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Methylprednisolone on circulating eicosanoids and vasomotor tone after endotoxin.

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin. The stable metabolites of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay. Methylprednisolone by itself did not alter circulating eicosanoids but when given 2.5 h before endotoxin not only failed to inhibit endotoxin-induced eicosanoid production but actually resulted in higher circulating levels of 6-keto-PGF1 alpha (P less than 0.05) compared with animals receiving endotoxin alone. Indomethacin prevented the steroid-enhanced concentrations of 6-keto-PGF1 alpha after endotoxin and prevented the greater fall (P less than 0.05) in systemic blood pressure and systemic vascular resistance with steroid plus endotoxin than occurred with endotoxin alone. Administration of methylprednisolone immediately before endotoxin resulted in enhanced levels (P less than 0.05) of both TxB2 and 6-keto-PGF1 alpha but with a fall in systemic blood pressure and vascular resistance similar to the animals pretreated by 2.5 h. In contrast to the early steroid group in which all of the hypotensive effect was due to eicosanoids, in the latter group steroids had an additional nonspecific effect. Thus, in vivo, high-dose steroids did not prevent endotoxin-induced increases in eicosanoids but actually increased circulating levels of TxB2 and 6-keto-PGF1 alpha with a physiological effect favoring vasodilation.

Animals↗
PubMed1985

The antioxidant activity of alpha-tocopherol-bovine serum albumin complex in micellar and liposome autoxidations.

A comparison is made of the antioxidant activity of a water-soluble form of alpha-tocopherol complexed with bovine serum albumin (alpha-T X BSA) with that of micellar alpha-tocopherol and aqueous 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (Trolox) to inhibit autoxidation of linoleic acid in sodium dodecyl sulfate micelles. The peroxyl radical trapping ability of alpha-T X BSA compares favorably with that of alpha-tocopherol and Trolox, and all three can be used in quantitative measurements of the susceptibility of the micellar substrate to undergo autoxidation: the oxidizability, for reactions initiated in the micellar phase by di-tertbutylhyponitrite (DBHN) or in the aqueous phase by azobisamidinopropane hydrochloride (ABAP). alpha-Tocopherol and Trolox are also effective antioxidants to inhibit DBHN- or ABAP-initiated autoxidations of dilinoleoylphosphatidylcholine (DLPC) liposomes prepared as multilamellar or unilamellar bilayers characterized by 31P NMR spectra. The oxidizability of DLPC liposomes is determined by various combinations of water-soluble and lipid-soluble initiators and the antioxidants, alpha-tocopherol and Trolox. In contrast, alpha-T X BSA does not effectively trap peroxyl radicals when it is added after initiation of autoxidation in the lipid phase (DBHN) or in the aqueous phase (ABAP). The radical trapping ability of alpha-T X BSA becomes evident if it is mixed with the DLPC for some hours before initiation. This result is interpreted in terms of diffusion of alpha-tocopherol from the bound alpha-T X BSA form to the liposome before it exhibits antioxidant activity.

Linoleic Acid↗
PubMed1984

Regional blood flow and pulmonary thromboxane release after sublethal endotoxin infusion in sheep.

Fifteen minutes after intravenous Escherichia coli endotoxin (EN) infusion the sheep lung transiently releases into the systemic circulation up to 12 micrograms of thromboxane A2 (TxA2)/min measured by radioimmunoassay as its metabolite thromboxane B2 (TxB2). To determine whether lung thromboxane release alters regional blood flow (RBF) we injected microspheres before and 20, 30, and 100 minutes after EN infusion in 13 awake sheep. In seven untreated control sheep (group 1) pulmonary vascular resistance (PVR) increased threefold at 20 and 30 minutes after EN infusion, coinciding with a large transpulmonary blood concentration gradient of TxB2. There was no measured RBF change to any systemic tissue or organ except the right ventricle at 20 minutes after EN infusion, when blood flow per gram of tissue doubled. In six sheep (group 2) treated with intravenous ibuprofen before EN infusion there was no increase in PVR, plasma TxB2, or blood flow to the right ventricle, and no difference of RBF to any other organ or tissue when compared to group 1. TxA2 is a potent local pulmonary vasoconstrictor but it rapidly hydrolyzes. Its short half-life and the circulatory delay in systemic arterial delivery prevent TxA2 from acting as a circulating vasoconstrictor.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Thromboxane and prostacyclin (epoprostenol) during exercise in diffuse pulmonary fibrosis.

Plasma thromboxane A2, a vasoconstrictor, and plasma prostacyclin (epoprostenol), a vasodilator, were assessed by double-antibody radioimmunological assay of their respective stable circulating metabolites, thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha, in 9 patients with severe diffuse pulmonary fibrosis (DPF), who were known to become hypo-oxaemic during exercise, and in 9 healthy volunteers. In the 7 patients with the most severe DPF, mean arterial PO2 fell from 68 mm Hg at rest to 51 mm Hg at peak aerobic exercise, and mean TxB2 increased to twice the value at rest. The 9 controls remained oxygen saturated throughout exercise; their mean TxB2 did not change during aerobic exercise, but during anaerobic exercise increased to twice the value at rest, and increased further during recovery. There were no significant changes in 6-keto-prostaglandin F1 alpha in either group. The selective release of TxB2 during aerobic exercise in hypo-oxaemic patients suggests that thromboxane mediates hypoxic pulmonary vasoconstriction. Its release in normal man during anaerobic exercise may reflect a more general response to the metabolic changes of tissue hypoxia.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Thromboxane and pulmonary hypertension following E. coli endotoxin infusion in sheep: effect of an imidazole derivative.

We assessed the effect of a specific thromboxane synthetase inhibitor (an imidazole derivative) on pulmonary hemodynamics and the concentrations of TxB2 (TxA2), 6-keto-PGF1 alpha (PGI2), and PGF2 in pulmonary lymph and transpulmonary blood samples following intravenous administration of E. coli endotoxin (1 microgram/kg) in sheep. In control animals the rise in pulmonary artery pressure correlated with increases in plasma and lymph TxB2 concentrations and large transpulmonary concentration gradients of this metabolite were measured. In imidazole treated animals both pulmonary hypertension as well as increases in plasma and lymph TxB2 concentrations were substantially reduced. In contrast, peak concentrations of 6-keto-PGF1 alpha (PGI2) and PGF2 alpha were severalfold higher than those measured in control animals. This suggests a shunting of endoperoxide metabolism towards prostacyclin and primary prostaglandins and documents the specificity of the thromboxane synthetase inhibitor. Our study provides evidence that endotoxin-induced pulmonary hypertension is mediated by pulmonary synthesis of TxA2.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Role of thromboxane and prostacyclin in pulmonary vasomotor changes after endotoxin in dogs.

Cyclooxygenase inhibitors prevent the pulmonary vasomotor changes in response to low-dose endotoxin. We, therefore, explored the role of two highly vasoactive prostanoids, thromboxane A(2), a vasoconstrictor, and prostacyclin, a vasodilator, in the transient pulmonary vasoconstriction and subsequent loss of alveolar hypoxis vasoconstriction (AHPV) that follows endotoxin. AHPV was tested in the dog with a double-lumened endotracheal tube allowing ventilation of one lung with nitrogen as a hypoxic challenge while the other lung was ventilated with oxygen to maintain systemic oxygenation. Relative distribution of perfusion to the two lungs was assessed with intravenous (133)Xe and external scintillation detectors. The stable metabolites of thromboxane and prostacyclin, i.e., thromboxane B(2) and 6-keto-prostaglandin F(1alpha) were measured in plasma with radioimmunoassay. 15 mug/kg i.v. of endotoxin induced no rise in pulmonary vascular resistance (PVR), but prevented AHPV so that the initial 33% (+/-2 SEM) decrease in perfusion to the hypoxic lung became only a 2% (+/-1) decrease. Circulating levels of thromboxane and prostacyclin concurrently rose (P < 0.01) from nondetectable levels to 380 pg/ml (+/-40) and 360 pg/ml (+/-130). 150 mug/kg of endotoxin induced a transient rise in PVR from 4.09 to 9.00 mm Hg/liter per min in association (r = 0.89, P < 0.01) with a sharp rise in thromboxane levels to 4,460 pg/ml (+/-1,350) whereas prostacyclin levels were elevated less markedly to 550 pg/ml (+/-400). Prostaglandin F(2alpha), another vasoconstrictor, was not elevated. 30 min after endotoxin when PVR was again base line and AHPV lost, thromboxane fell significantly (P < 0.01) to 2,200 pg/ml (+/-1,100) whereas prostacyclin remained elevated at 360 pg/ml (+/-135), a level similar to that seen when 15 mug/kg of endotoxin induced loss of AHPV. Indomethacin prevented the rise in thromboxane and prostacyclin after endotoxin as well as the changes in pulmonary vasomotor tone. Thus, a complex interaction between thromboxane and prostacyclin is involved in the pulmonary vasomotor response to low-dose endotoxin.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Inhibition of thromboxane A2 production does not improve post-ischemic brain hypoperfusion in the dog.

In a canine model of global brain ischemia, six dogs received a selective thromboxane A2 synthetase inhibitor, UK 38,485 (dazmagrel) before the ischemic event; six received a saline placebo. Cerebral blood flow (CBF), systolic and diastolic arterial pressure, cardiac output, pH, PaCO2, PaO2, and arterial and jugular-vein thromboxane B2 (a stable metabolite of thromboxane A2) and 6-keto PGF1 alpha (a stable metabolite of prostacyclin) were measured at baseline, after release of aortic and venae caval occlusion and at intervals up to 120 min thereafter. Treated animals showed nearly complete post-ischemic inhibition of thromboxane B2 production; control animals showed increases in jugular venous thromboxane B2. Arterial and jugular venous levels of 6-keto PGF1 alpha were significantly higher in treated animals at most post-ischemic intervals. CBF in both groups was similar to baseline values at time 0, then declined similarly in both groups by 30 min to approximately equal to 35% of baseline values where it remained thereafter. There were no significant differences in other variables at any interval. We conclude that inhibition of thromboxane A2 production does not alter post-ischemic brain hypoperfusion.

Animals↗