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This study aims to investigate the correlation between oxidative stress and intra-abdominal fat (IAF) in obese young and middle-aged males.The present study included 136 male examinees in the Examination Center of the First Hospital of Qinhuangdao from October 10, 2015 to December 10, 2015. Then, clinical data, oxidative stress indices (8-iso-prostaglandin F2α [8-iso-PGF2α], malondialdehyde [MDA], and superoxide dismutase [SOD]), and IAF area were recorded. All subjects were assigned into 3 groups according to body mass index (BMI): obese group (BMI ≥ 28 kg/m, 43 subjects), overweight group (24 ≤ BMI < 28 kg/m, 46 subjects), and control group (BMI < 24 kg/m, 47 subjects). Then, statistical analysis was performed.There were significant differences in IAF area, leptin, adiponectin, 8-iso-PGF2α, MDA, SOD, fasting insulin (FINS), fasting blood glucose (FBG), and homeostasis model assessment-insulin resistance (HOMA-IR) among these 3 groups (P < .05). Male subjects in the obese group had higher leptin, 8-iso-PGF2α, MDA, FINS, and HOMA-IR levels, compared to subjects in the overweight and control groups. Furthermore, subjects in the overweight group had a larger IAF area and higher 8-iso-PGF2α, MDA, and FBG levels, when compared to controls. In addition, SOD was significantly lower in the obese and overweight groups than in the control group. However, there were no statistical differences in age, systolic and diastolic blood pressure, lipids, and islet β-cell secretion function (homeostasis model assessment-β) among these 3 groups (P ≥ .05). Moreover, the IAF area was positively correlated to 8-iso-PGF2α and MDA, and negatively correlated to SOD.Oxidative stress is significantly associated with the IAF area in obese males, and abdominal obesity could increase oxidative stress level and insulin resistance.

Objective: Lipid peroxidation induced by free-radical species plays a prominent role in myocardial injury following ischemia and reperfusion. However, there is a lack of data in different oxygen concentrations on myocardial lipid peroxidation during the early phase of reperfusion. In this study, we investigated whether ventilation with medium or normal concentration of oxygen would decrease the severity of myocardial lipid peroxidation and postresuscitation myocardial dysfunction., Design: Prospective, randomized, controlled experimental study., Setting: University-affiliated animal research institution., Subjects: Sixty-three healthy male Sprague-Dawley rats., Interventions: Animals were randomized into three groups: 1) 100% group, 2) 50% group, and 3) 21% group. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. Ventilation with 100%, 50%, or 21% oxygen was initiated in all groups during cardiopulmonary resuscitation and 1 hour following the return of spontaneous circulation. Normoxic ventilation was maintained thereafter., Measurements and Main Results: Myocardial function, including ejection fraction and myocardial performance index, were measured at baseline, 4, or 72 hours after resuscitation. Blood samples were drawn at baseline, 15 minutes, 1, 4, or 72 hours after resuscitation for the measurements of blood gas or biomarkers. Significantly better myocardial function and longer duration of survival were observed in the 50% group. Compared with the 21% and 100% groups, a mild hyperoxia and greater oxygen extraction with lower 8-iso-prostaglandin F2α were observed in the 50% group. Pearson correlation analysis confirmed that 8-iso-prostaglandin F2α was positively correlated with myocardial performance index at 4 hours postresuscitation., Conclusions: In a rat model of cardiac arrest and resuscitation, ventilation with 50% inspired oxygen during early postischemic reperfusion phase contributed to a decreased lipid peroxidation and a better myocardial function and duration of survival.

Background: Endothelial cell (EC) dysfunction represents the first manifestation of atherosclerotic disease. Restoration of endothelium via seeding or transfection is hampered by local alterations in flow, inflammation, and metabolic activation. Perivascular EC matrix implants are shielded from these forces and still control vascular repair. The host immune response to such implants, however, remains largely unknown. We investigated the effect of embedding of ECs within 3-dimensional matrices on host immune responses in vitro and in vivo., Methods and Results: We compared expression of major histocompatibility complex (MHC), costimulatory, and adhesion molecules by free aortic ECs or ECs embedded in Gelfoam matrices by flow-cytometry. T-cell proliferation was assessed by [3H] thymidine incorporation. Humoral immune response (ELISA and FACS analysis) and cellular (histopathology) infiltration were investigated after subcutaneous injection of free porcine aortic ECs (PAEs) or of a Gelfoam/EC block, or after concomitant injection of PAEs adjacent to Gelfoam in rats. Aortic ECs embedded in Gelfoam expressed lower levels of MHC class II, costimulatory, and adhesion molecules compared with free ECs (P<0.001), and induced 3-fold less proliferation of human CD4+ T-cells (P<0.0005). Implantation of a Gelfoam/EC block in rats nearly abrogated the immune response with 1.75- to 9.0-fold downregulation in tumor necrosis factor-alpha, interleukin-6, monocyte chemotactic protein-1, and PAE-specific immunoglobulin G (P<0.005) and 3.3- to 4.5-fold reduction in leukocytic tissue infiltration. Injecting PAEs adjacent to Gelfoam induced a significant response comparable to that of free implanted PAEs., Conclusions: Embedding ECs within 3-dimensional matrices alters the host immune response by inhibiting expression of MHC class II, costimulatory, and adhesion molecules, offering the rationale to develop novel therapies for vascular diseases.

Vascular serotonin 5-HT1 receptors have quiescent constrictor activity that is activated by other vasoactive agents such as histamine. Previously, we observed that the 5-HT1-selective agonist 5-carboxamidotryptamine (5-CT) potentiated histamine-stimulated arachidonic acid (AA) mobilization and prostaglandin production in human aortic endothelial cells (HAEC). In the present study, 5-CT was found to potentiate histamine-stimulated calcium mobilization but had no effect on intracellular calcium when added alone. Treatment of HAEC with human low-density lipoprotein (LDL) for 20 hours inhibited the histamine- plus 5-CT-stimulated production of prostaglandin F2alpha (PGF2alpha) and the prostacyclin metabolite 6-keto-PGF1alpha. However, the effects of histamine and histamine potentiation by 5-CT on intracellular Ca mobilization and AA release were resistant to LDL treatment. Conversely, the subsequent receptor-independent conversion of AA to prostaglandins was inhibited by LDL. These results demonstrate that histamine and serotonin receptor activity, measured as the stimulation of Ca and AA mobilization, is resistant to LDL exposure under mild oxidizing conditions, whereas the receptor-independent synthesis of prostaglandins is inhibited by LDL. The results also suggest that the LDL-stimulated mobilization of cellular AA is responsible for the LDL-mediated inhibition of prostaglandin synthesis. These findings suggest a mechanism by which LDL and/or atherosclerosis could promote the vascular liberation of AA that is not converted to endothelium-derived prostaglandins and is therefore available as substrate for the production of other eicosanoids.

Angiotensin II (Ang II) type 1 receptor (AT(1)) antagonists such as losartan (LOS) are widely used for the treatment of hypertension and elicit antiinflammatory and antiaggregatory in vitro and in patients, although the underlying mechanism are unclear. Following computer-based molecule similarity, we proposed that on cytochrome-P450 degradation, the LOS metabolite EXP3179 is generated, which shows molecule homology to indomethacin, a cyclooxygenase inhibitor with antiinflammatory and antiaggregatory properties. Subsequently, serum-levels of EXP3179 were determined for 8 hours in patients receiving a single oral dose of 100 mg LOS. High-performance liquid chromatography followed by liquid chromatography-mass spectrometry (GC-MS) [corrected] from serum samples revealed a maximum of 10(-7) mol/L for EXP3179 peaking between 3 to 4 hours. The increase in serum-EXP3179 levels was associated with a significant reduction in platelet aggregation in vivo (-35+/-4%, P<0.001 versus control). EXP3179 generation was investigated in a chemical reaction mimicking the liver cytochrome-P450-dependent LOS-degradation and human endothelial cells were exposed to Ang II or lipopolysaccharides (LPS) in the presence of EXP3179 (10(-7) mol/L). LPS- and Ang II-induced COX-2 transcription was abolished by EXP3179. Moreover, EXP3179 significantly reduced Ang II- and LPS-induced formation of prostaglandin F2alpha as determined by GC-MS [corrected]. Thus, antiinflammatory properties of LOS are mediated via its EXP3179 metabolite by abolishing COX-2 mRNA upregulation and COX-dependent TXA2 and PGF2alpha generation. Serum levels of EXP3179 are detectable in patients in concentrations that exhibit antiinflammatory and antiaggregatory properties in vitro.

Background: The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on the endogenous formation of F2-isoprostanes and 8-epi-prostaglandin (PG) F2alpha as possible markers of lipid peroxidation in preterm infants during their first weeks of life., Methods: In a prospective, randomized, double-blind study, infants received either formula enriched with LCP (n = 8), standard preterm formula (n = 7), or (expressed) breast milk (n = 8). Urine was sampled at study entry and after the study period of 3 weeks. The formation of F2-isoprostanes and 8-epi-PGF2alpha was evaluated by measuring the urinary excretion by gas chromatography-mass spectrometry., Results: No differences in the urinary excretion of F2-isoprostanes and 8-epi-PGF2alpha were observed at the end of the study period., Conclusions: This result suggests that supplementation of a preterm formula with LCP for a period of 3 weeks does not stimulate lipid peroxidation in preterm infants.

In a previous work, we postulated that endothelial cells possess only the following 2 enzymes involved in prostanoid synthesis: cyclooxygenase and prostacyclin synthase. The present work focused on investigating the expression of prostaglandin (PG) E synthase (PGES) in vascular cells. After incubation of vascular smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) with [(14)C]arachidonic acid, the profile of prostanoid synthesis was assessed by HPLC. Untransformed PGH(2) released by the cells was evaluated as the difference in the formation of PGF(2alpha) in the incubations performed in the presence and in the absence of SnCl(2). Resting SMCs and SMCs stimulated with phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha formed PGE(2) and PGI(2) (evaluated as 6-oxo-PGF(1alpha)), and in the presence of SnCl(2) only a small amount of PGE(2) was deviated toward PGF(2alpha). In contrast, resting and stimulated HUVECs produced PGI(2), PGE(2), PGF(2alpha), and PGD(2), and SnCl(2) completely diverted PGE(2) and PGD(2) toward PGF(2alpha). Reverse transcriptase-polymerase chain reaction analysis shows that mRNA encoding for PGES was not present in HUVECs and in endothelial cells from saphenous vein. Nevertheless, PGES was expressed in SMCs and induced by IL-1beta and TNF-alpha, and by PMA and LPS, although to a lesser extent. Whereas SMC stimulation led to an increase in the synthesis of PGE(2) and PGI(2) but not of untransformed PGH(2), stimulation of endothelial cells resulted in an enhanced release of the vasoconstricting prostanoid PGH(2).

Background: Unstable angina is associated with enhanced lipid peroxidation and reduced antioxidant defenses. We have previously reported aspirin failure in the suppression of enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation in this setting. We tested the hypothesis that the in vivo formation of the F(2)-isoprostane 8-iso-prostaglandin (PG)F(2alpha), a bioactive product of arachidonic acid peroxidation, is enhanced in unstable angina and contributes to aspirin-insensitive TX biosynthesis., Methods and Results: Urine samples were obtained from patients with unstable angina (n=32), stable angina (n=32), or variant angina (n=4) and from 40 healthy subjects for the measurement of immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2). 8-Iso-PGF(2alpha) excretion was significantly higher in patients with unstable angina (339+/-122 pg/mg creatinine) than in matched patients with stable angina (236+/-83 pg/mg creatinine, P:=0.001) and control subjects (192+/-71 pg/mg creatinine, P:<0.0001). In patients with unstable angina, 8-iso-PGF(2alpha) was linearly correlated with 11-dehydro-TXB(2) excretion (rho=0.721, P:<0.0001) and inversely correlated with plasma vitamin E (rho=-0.710, P:=0. 004). Spontaneous myocardial ischemia in patients with variant angina or ischemia elicited by a stress test in patients with stable angina was not accompanied by any change in 8-iso-PGF(2alpha) excretion, thus excluding a role of ischemia per se in the induction of increased F(2)-isoprostane production., Conclusions: These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.

Background: Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation., Methods and Results: Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion., Conclusions: We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

The tissue-fixed macrophage (Mphi) plays a key role in coordinating the excessive inflammatory response following shock or sepsis. Reactive oxygen intermediates have been recently described as second messengers involved in signal transduction in these cells, including the activation of the transcription factors NF-kappaB and AP-1. The dithiocarbamates are potent antioxidants that inhibit NF-kappaB activation. We postulated that dithiocarbamates would inhibit Mphi activation via inhibition of NF-kappaB. Rabbit alveolar Mphi were obtained by bronchoalveolar lavage and exposed to either pyrrolidine dithiocarbamate (PDTC) or diethyl dithiocarbamate (DDTC) followed by stimulation with LPS (10 ng/mL). Supernatants were analyzed for TNF and prostaglandin E2, (PGE2) and F2-isoprostane (ISP), a marker of membrane lipid peroxidation, production at 18 h. PDTC and DDTC significantly enhanced production of TNF while inhibiting PGE2 and ISP production compared with LPS alone (p < .05). Northern blots revealed increased mRNA for TNF after pretreatment with PDTC, compared with LPS alone. Western blots and oligonucleotide gel shifts of nuclear proteins revealed inhibition of NF-kappaB activation by both PDTC and DDTC. AP-1 activity was shifted to earlier time points by PDTC pretreatment. These results demonstrate transcriptional and functional enhancement of TNF production despite inhibition of NF-kappaB activation. This may be due in part to a loss of autocrine feedback inhibition by PGE2 and enhancement of AP-1 activity. On the basis of these results, we conclude NF-kappaB may be necessary but, in contrast to prior analyzes, is not sufficient for optimal response of the alveolar Mphi to endotoxin.

Oxygen exposure for a sufficient duration at high partial pressure results in pulmonary edema in humans and animals. Although the specific mediators of oxygen toxicity are unknown, evidence suggests that oxygen-based radicals such as superoxide anion (O2.) are increased in the lungs in the presence of hyperoxia and contribute to this injury. A series of isomeric prostanoid compounds, the isoprostanes, are formed by the free radical-initiated lipid peroxidation of arachidonic acid (AA). One of these isomers, 8-iso-PGF2alpha, is elevated in the bronchial alveolar lavage fluid of rats exposed to 90% oxygen for 48 h and is associated with a significant increase in protein accumulation in the pulmonary extravascular space. Alveolar macrophages (AMs) are capable of producing large quantities of (O2.), suggesting a role in pulmonary oxygen toxicity. We hypothesized that isolated rat AMs exposed to hyperoxia generate increased amount of 8-iso-PGF2alpha. AMs were exposed to air or 90% oxygen for 6, 12, 24, 48, 72, 96, and 120 h in the absence and presence of AA and/or calcium ionophore (A23187) and 8-iso-PGF2alpha was measured in the culture media. Exposure of primary cultures of AMs to 90% oxygen resulted in a significant increase in 8-iso-PGF2alpha in the media (25 +/- 2 pg/mL) compared with air-exposed controls (14 +/- 1 pg/mL). The addition of 10 microM AA and 2 microM A23187 to the culture media resulted in a marked increase in 8-iso-PGF2alpha production by AMs exposed to air and 90% oxygen. However, treatment of AMs with the combination of AA and A23187, followed by exposure to 90% oxygen for 72 h, resulted in a 27-fold increase in 8-iso-PGF2alpha compared with media alone and 90% oxygen. AMs metabolized free and phospholipid-bound AA to 8-iso-PGF2alpha, an activity enhanced in the 90% oxygen environment. Finally, acetylsalicylic acid, a cyclooxygenase inhibitor and free radical scavenger, reduced but did not abolish production of 8-iso-PGF2alpha. This study provides evidence that AMs produce a free radical-mediated isomeric prostaglandin compound that may be involved in pulmonary oxygen toxicity.

Background: The role of oxidant stress in cardiac ischemia/reperfusion injury in humans remains controversial. This is due, in part, to the limitations of available indices of oxidant stress in vivo. Isoprostanes are stable, free radical-catalyzed products of arachidonic acid. We assessed their formation in patients undergoing coronary reperfusion via percutaneous transluminal coronary angioplasty (PTCA)., Methods and Results: We developed specific, mass spectrometry assays for two structurally distinct F2 isoprostanes, 8-epi-PGF2alpha and IPF2alpha-I. Urine samples for isoprostane determination were collected in patients undergoing coronary arteriography (n=11), elective PTCA (n=15), and angiography after thrombolysis for acute myocardial infarction (MI) (n=10). Urinary levels (pmol/mmol creatinine) of both isoprostanes were markedly increased from baseline in the first 6 hours after PTCA for acute MI (105+/-17.8 versus 230+/-66 for 8-epi-PGF2alpha [P=.009] and 466+/-91 versus 833+/-153 for IPF2alpha-I [P=.001]) and returned toward preprocedural values by 24 hours (122+/-18 for 8-epi-PGF2alpha and 457+/-102 for IPF2alpha-I). There was a slight increase in urinary 8-epi-PGF2alpha levels (64.7+/-9.5 versus 84.9+/-10.6; P=.02) after diagnostic coronary arteriography and elective PTCA (88.7+/-7.5 versus 114.3+/-16.1; P=.01). A striking correlation was observed (r=.68, P<.0001; n=33) between urinary 8-epi-PGF2alpha and IPF2alpha-I levels in patients receiving thrombolytic agents for acute MI., Conclusions: Urinary F2 isoprostane levels are elevated in patients after treatments resulting in reperfusion for acute MI. These findings provide evidence consistent with increased oxidant stress in vivo in this setting. Measurement of urinary isoprostanes may offer a noninvasive approach to the assessment of oxidant stress and the efficacy of antioxidant therapies in these syndromes.

F2-isoprostanes are bioactive prostaglandin (PG)-like compounds that are produced from arachidonic acid through a nonenzymatic process of lipid peroxidation catalyzed by oxygen free-radicals. 8-Epi-PGF2 alpha may amplify the platelet response to agonists, circulates in plasma, and is excreted in urine. We examined the hypothesis that the formation of 8-epi-PGF2 alpha is altered in patients with hypercholesterolemia and contributes to platelet activation in this setting. Urine samples were obtained from 40 hypercholesterolemic patients and 40 age- and sex-matched control subjects for measurement of immunoreactive 8-epi-PGF2 alpha. Urinary excretion of 11-dehydro-thromboxane (TX) B2, a major metabolite of TXA2, was measured as an in vivo index of platelet activation. Low-dose aspirin, indobufen, and vitamin E were used to investigate the mechanism of formation and effects of 8-epi-PGF2 alpha on platelet activation. Urinary 8-epi-PGF2 alpha was significantly (P = .0001) higher in hypercholesterolemic patients than in control subjects: 473 +/- 305 versus 205 +/- 95 pg/mg creatinine. Its rate of excretion was inversely related to the vitamin E content of LDL and showed a positive correlation with urinary 11-dehydro-TXB2. Urinary 8-epi-PGF2 alpha was unchanged after 2-week dosing with aspirin and indobufen despite complete suppression of TX metabolite excretion. Vitamin E supplementation was associated with dose-dependent reductions in both urinary 8-epi-PGF2 alpha and 11-dehydro-TXB2 by 34% to 36% and 47% to 58% at 100 and 600 mg daily, respectively. We conclude that the in vivo formation of the F2-isoprostane 8-epi-PGF2 alpha is enhanced in the vast majority of patients with hypercholesterolemia. This provides an aspirin-insensitive mechanism possibly linking lipid peroxidation to amplification of platelet activation in the setting of hypercholesterolemia. Dose-dependent suppression of enhanced 8-epi-PGF2 alpha formation by vitamin E supplementation may contribute to the beneficial effects of antioxidant treatment.

Background: Halothane can be reductively metabolized to free radical intermediates that may initiate lipid peroxidation. Hypoxia and phenobarbital pretreatment in Sprague-Dawley rats increases reductive metabolism of halothane. F(2)-isoprostanes, a novel measure of lipid peroxidation in vivo, were used to quantify halothane-induced lipid peroxidation in rats., Methods: Rats were exposed to 1% halothane or 14% O(2) for 2 h. Pretreatments included phenobarbital, isoniazid, or vehicle. Rats also were exposed to halothane, enflurane, and desflurane at 21% O(2). Lipid peroxidation was assessed by mass spectrometric quantification of F(2)-isoprostanes., Results: Exposure of phenobarbital-pretreated rats to 1% halothane at 21% O(2) for 2 h caused liver and plasma F(2)-isoprostane concentrations to increase fivefold compared to nonhalothane control rats. This halothane-induced increase was enhanced by 14% O(2), but hypoxia alone had no significant effect. Alanine aminotransferase activity at 24 h was significantly increased only in the 1% halothane/14% O(2) group. The effect of cytochrome P450 enzyme induction on halothane-induced F(2)-isoprostane production and liver injury was determined by comparing the effects of isoniazid and phenobarbital pretreatment with no pretreatment under hypoxic conditions. Halothane caused 4- and 11-fold increases in plasma and liver F(2)-isoprostanes, respectively, in non-pretreated rats, whereas isoniazid pretreatment had no effect. Phenobarbital pretreatment potentiated halothane-induced lipid peroxidation with 9- and 20-fold increases in plasma and liver F(2)-isoprostanes, respectively. Alanine aminotransferase activity was increased only in this group. At ambient oxygen concentrations, halothane but not enflurane or desflurane, caused F(2)-isoprostanes to increase., Conclusions: Specific halothane-induced lipid peroxidation was demonstrated in Sprague-Dawley rats using quantification of F(2)-isoprostanes and was increased by hypoxia and phenobarbital pretreatment, but not isoniazid pretreatment.

Changes in endogenous pancreas production of prostaglandins D2, F2 alpha, E2, and E1 in early stages of acute necrotizing pancreatitis induced by intraductal administration of 3.5% sodium taurocholate have been determined by radioimmunoassay of chromatographically purified tissue extracts. For this purpose 18 male Wistar rats were randomized in three groups: control, pancreatitis, and pancreatitis plus indomethacin. Pancreas tissue samples were obtained 5 min after pancreatitis induction. In the pancreatitis-induced group, prostaglandins D2, F2 alpha, and E2 show significantly increased tissue levels relative to the controls whereas prostaglandin E1 remains unmodified. These results suggest a role for series 2 prostaglandins in the earlier stages of pancreatitis.

Objective: To determine whether ritodrine-stimulated production of prostaglandin (PG) F2 alpha by pregnant uterine tissues can be blocked by the concurrent administration of ketorolac, a PG synthesis inhibitor., Methods: We infused saline, ritodrine, ketorolac, or a combination of ritodrine and ketorolac into chronically catheterized pregnant sheep. Concentrations of PGF2 alpha in uterine venous plasma were measured by radioimmunoassay at 0, 1, 2, 3, 4, and 24 hours during the infusions., Results: Ritodrine significantly increased uterine venous PGF2 alpha; mean percent increases at 4 hours were 330% and 380%, and at 24 hours 370%, compared with controls. During concurrent ritodrine and ketorolac infusion, there was no increase in uterine venous PGF2 alpha at any time., Conclusions: Ketorolac completely blocks ritodrine-stimulated production of PGF2 alpha in pregnant uterine tissues. We conclude that ritodrine stimulates PG production through mobilization of arachidonic acid, and this can be effectively blocked with a PG synthesis inhibitor. This finding may have important clinical applications in the treatment of preterm labor.

The effect of reperfusion following hemorrhagic shock on splanchnic prostanoid release was studied. Anesthetized male rats were bled to a mean arterial blood pressure of 30 mmHg for 30 minutes and either killed or treated with shed blood for 60 minutes and then killed. The superior mesenteric arterial bed was cannulated and perfused in vitro with oxygenated Krebs. Collected venous effluent (up to 180 minutes) was analyzed for 6-keto-PGF1 alpha (PGI2 metabolite), PGE2, PGF2 alpha, and thromboxane B2 by radioimmunoassay in shock, shock plus reperfusion, and sham groups. The major prostanoid released was 6-keto-PGF1 alpha and was three times higher in the shock group compared to the sham group (p less than 0.05). Reperfusion of shed blood abolished the increase in 6-keto-PGF1 alpha found in the shock group (p less than 0.05). These data show that the attempt of the rat splanchnic bed to compensate for hemorrhagic shock by increasing release of PGI2 (potent vasodilator) was abolished during reperfusion of blood.