thromboxane-b2 and Respiratory-Insufficiency

Bronchial hyperresponsiveness is a hallmark of asthma and many factors modulate bronchoconstriction episodes. A potential correlation of formaldehyde (FA) inhalation and asthma has been observed; however, the exact role of FA remains controversial. We investigated the effects of FA inhalation on Ovalbumin (OVA) sensitisation using a parameter of respiratory mechanics. The involvement of nitric oxide (NO) and cyclooxygenase-derived products were also evaluated. The rats were submitted, or not, to FA inhalation (1%, 90 min/day, 3 days) and were OVA-sensitised and challenged 14 days later. Our data showed that previous FA exposure in allergic rats reduced bronchial responsiveness, respiratory resistance (Rrs) and elastance (Ers) to methacholine. FA exposure in allergic rats also increased the iNOS gene expression and reduced COX-1. L-NAME treatment exacerbated the bronchial hyporesponsiveness and did not modify the Ers and Rrs, while Indomethacin partially reversed all of the parameters studied. The L-NAME and Indomethacin treatments reduced leukotriene B₄ levels while they increased thromboxane B₂ and prostaglandin E₂. In conclusion, FA exposure prior to OVA sensitisation reduces the respiratory mechanics and the interaction of NO and PGE₂ may be representing a compensatory mechanism in order to protect the lung from bronchoconstriction effects.

Topics: Administration, Inhalation; Airway Resistance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Cyclooxygenase 1; Dinoprostone; Disease Models, Animal; Eicosanoids; Formaldehyde; Gene Expression Regulation, Enzymologic; Leukotriene B4; Male; Membrane Proteins; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Rats, Wistar; Respiratory Insufficiency; Respiratory Mucosa; Thromboxane B2

An imbalance of vaso-constrictor and -dilator mediators has been implicated in the pathogenesis of the pulmonary hypertension accompanying neonatal hypoxemic respiratory failure (NHRF).. To characterize plasma PGE2, TXB2 and their ratio in normal newborns and in those with NHRF.. Twenty newborns with NHRF received inhaled PGE1 (IPGE1) by jet nebulizer in doses of 25, 50, 150 and 300 ng/kg/min followed by weaning. Blood for PGE2 and TXB2 assay using EIA was available in 8 neonates with NHRF prior to IPGE1. Umbilical cord arterial samples were also obtained at delivery from 10 normal newborns to serve as controls.. Compared to normal newborns, those with NHRF had significantly lower PGE2/TXB2 ratios after controlling for preterm gestation (< 37 weeks) and postnatal age (p < 0.05). Notably, all subjects except one in the NHRF group had a value of < 1.0 (range 0.1-1.2) compared to a value of > 1.0 in all subjects in the Control group (range 1.1-5.2).. Lower PGE2/TXB2 ratio in subjects with NHRF compared with controls reflects a predominance of vaso-constrictor activity in these patients as the basis of pulmonary hypertension. Plasma PGE2/TXB2 ratio may have important implications for the diagnosis and treatment of NHRF.

Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dinoprostone; Female; Humans; Hypoxia; Infant, Newborn; Male; Pilot Projects; Respiratory Insufficiency; Thromboxane B2

Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor. In the present study, the possible significance of hemolysin production was investigated in a model of septic lung failure through infusion of viable bacteria in isolated rabbit lungs; 10(4) to 10(7) E. coli/ml perfusate caused a dose- and time-dependent appearance of hemolysin, accompanied by release of potassium, thromboxane A2, and PGI2 into the perfusate. Concomitantly, marked pulmonary hypertension developed. Inhibitor studies suggested that the pressor response was predominantly mediated by pulmonary thromboxane generation. Administration of hemolysin-forming E. coli additionally caused a protracted, dose-dependent increase in the lung capillary filtration coefficient, followed by severe edema formation. The permeability increase was independent of lung prostanoid generation. An E. coli strain that releases an inactive form of hemolysin completely failed to provoke the described biophysical and biochemical responses. Preapplication of 2 x 10(8) human granulocytes was without effect in the present experimental model. We conclude that the hemolysin produced by low numbers of E. coli organisms can provoke thromboxane-mediated pulmonary hypertension and severe vascular leakage. E. coli hemolysin and, possibly, other related cytolysins may thus contribute directly to the pathogenesis of acute respiratory failure under conditions of sepsis or pneumonia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Blood Pressure; Capillary Permeability; Epoprostenol; Escherichia coli; Female; Hemolysin Proteins; Hypertension, Pulmonary; In Vitro Techniques; L-Lactate Dehydrogenase; Lung; Male; Neutrophils; Perfusion; Potassium; Pulmonary Artery; Rabbits; Receptors, Prostaglandin; Receptors, Thromboxane; Respiratory Insufficiency; Sulfonamides; Thromboxane B2; Thromboxanes

Topics: Bone Marrow Transplantation; Capillary Permeability; Humans; Leukotriene E4; Pulmonary Edema; Respiratory Insufficiency; SRS-A; Syndrome; Thromboxane B2

Thromboxane B2 may be a mediator of neonatal persistent pulmonary hypertension. Elevated levels of plasma thromboxane and prostacyclin have been described previously in hypoxic newborn infants with neonatal pulmonary hypertension. We measured serial plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin) in 21 newborn infants with severe respiratory failure and pulmonary hypertension who required extracorporeal membrane oxygenation support. We sought to study (1) the evolution of plasma prostanoids in pulmonary hypertensive infants treated with extracorporeal membrane oxygenation and (2) whether different pulmonary hypertensive diagnostic subgroups have distinctive prostanoid profiles. Our data indicated that infants with meconium aspiration had significantly lower levels of plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha while receiving extracorporeal membrane oxygenation than did infants with persistent pulmonary hypertension but no meconium aspiration. Levels of all infants decreased progressively as extracorporeal membrane oxygenation support continued.

Topics: 6-Ketoprostaglandin F1 alpha; Carbon Dioxide; Epoprostenol; Extracorporeal Membrane Oxygenation; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Oxygen; Persistent Fetal Circulation Syndrome; Respiratory Insufficiency; Thromboxane B2

The role of prostanoids in respiratory failure during circulatory shock of intestinal origin was investigated in anesthetized, non-ventilated dogs by measuring PGF2 alpha thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) in arterial and mixed venous (right ventricle) blood samples during superior mesenteric artery occlusion-induced (SMAO) shock. Release of the SMAO caused a dramatic decrease in mean arterial blood pressure (MABP), arterial and mixed venous pO2, hyperventilation and a more than 2 fold increase in levels of prostanoid studied within 5 min. At the same time, arterial and mixed venous pCO2 and pH remained unchanged. Thereafter, 6-keto PGF1 alpha concentration decreased so that at 60 min post release it was not significantly different from that of control values. PGF2 alpha and TXB2 levels rose continuously during shock. Respiratory failure which occurred after declamping was characterized by low pO2 and oxygen saturation and hyperventilation throughout the experiment. Pulmonary metabolism of PGF2 alpha was significantly reduced in shock. Indomethacin significantly attenuated the magnitude of postocclusion hypotension and respiratory failure, furthermore reduced prostanoid production. The present results suggest that PGF2 alpha and thromboxane A2 released by intestinal tissues might play an important role in the development of respiratory failure in shock caused by intestinal ischemia.

Topics: Animals; Dogs; Indomethacin; Male; Mesenteric Vascular Occlusion; Prostaglandins; Respiratory Insufficiency; Shock; Thromboxane B2

The clinical use of interleukin-2 (IL-2) is limited by severe cardiopulmonary dysfunction. This study examines the mechanism of respiratory failure related to IL-2, using sheep with chronic lung lymph fistulae. Awake animals were infused with an intravenous (I.V.) bolus of IL-2 10(5) U/kg (n = 5) or its excipient (EXC) control (n = 3), every 8 hours for 4 to 5 days. Cardiopulmonary function was monitored daily for at least one 8-hour period. Within 2 hours after each IL-2 administration, mean pulmonary arterial pressure (MPAP) rose. On Day 1, the mean rise was from 13 to 26 mmHg (p less than 0.05), and on Day 5, to 29 mmHg (p less than 0.05). MPAP returned to baseline levels after 2-3 hours. Pulmonary arterial wedge pressure was unchanged from 4 mmHg. There were transient falls in arterial oxygen tension, from 88 to 77 mmHg on Day 1 and to 73 mmHg (p less than 0.05) on Day 5. Lung lymph flow (QL) rose from 2.4 to 6.8 ml/30 minutes (p less than 0.05) on Day 1, and from 4.7 to 10.2 ml/30 minutes (p less than 0.05) on Day 5, whereas the lymph/plasma protein ratio increased on Day 1 from 0.69 to 0.83 (p less than 0.05) and from 0.63 to 0.71 (p less than 0.05) on Day 5. This documents an increase in pulmonary microvascular permeability. Thromboxane (Tx)B2 levels increased transiently after each IL-2 injection in plasma from 195 to 340 pg/ml (p less than 0.05) and in lung lymph from 222 to 772 pg/ml (p less than 0.05) on Day 1, and to similar levels on Day 5. There was a progressive rise in cardiac output from 5.7 to 8.6 1/minute (p less than 0.05) during the 5 days of infusion. Systemic blood pressure did not change. Temperature rose from 39.1 to 41.2 C (p less than 0.05), and shaking chills were common. There was a progressive fall in leukocyte count, from 8.4 to 3.2 X 10(3)/mm3 (p less than 0.05) by Day 5, reflecting a 77% fall in lymphocytes. Lung lymph lymphocyte counts rose, and lymphocyte clearance increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Capillary Permeability; Disease Models, Animal; Female; Fistula; Hemodynamics; Interleukin-2; Leukocyte Count; Lung; Lymph; Lymph Node Excision; Lymphocytes; Proteins; Recombinant Proteins; Respiratory Insufficiency; Sheep; Thromboxane B2; Time Factors

The major complication of extracorporeal membrane oxygenation (ECMO) for the treatment of neonatal respiratory failure is bleeding related to heparinization. Systolic hypertension has emerged as another serious side effect in our experience. Thirty-eight of the first 41 newborns we treated with ECMO developed a systolic blood pressure greater than 90 mm Hg. The mean hypertension index (HI blood = hours greater than 90/hr on ECMO) was 0.17 +/- 0.16. Possible biochemical mediators were assayed in 17 patients. Plasma renin activity (PRA), aldosterone, epinephrine, norepinephrine, prostaglandin E2, thromboxane, and antidiuretic hormone were elevated. Angiotensin-converting enzyme (ACE) and prostacyclin were not elevated. Eighteen patients (44%) had intracranial hemorrhage (ICH), and 11 patients (27%) had clinically significant ICH. The HI was significantly (p less than 0.005) lower in those patients without ICH (0.11 +/- 0.01) than in those patients with ICH (0.25 +/- 0.04). PRA at hour 12, day 2, and day 3 was significantly higher (p less than 0.05) in patients experiencing ICH (62 +/- 42; 93 +/- 15; 73 +/- 30 ng/ml/hr) than in those without ICH (27 +/- 25; 14 +/- 8; 12 +/- 4 ng/ml/hr). An aggressive approach to medical management evolved that included hydralazine, nitroglycerine, and captopril, which protected against ICH. Two of 23 patients (9%) treated with the protocol sufferred clinically significant ICH, whereas nine of 18 patients (50%) treated before implementation of the protocol experienced ICH. The ACE inhibitor captopril was most effective in the control of hypertension. We conclude that systolic hypertension is common during neonatal ECMO, is associated with ICH, and is related to a high PRA. Aggressive management of hypertension during ECMO can reduce the incidence of ICH, and captopril is an important component of this aggressive medical management.

Topics: Aldosterone; Cardiac Output; Catecholamines; Humans; Hypertension; Infant, Newborn; Oxygenators, Membrane; Peptidyl-Dipeptidase A; Prostaglandins; Renin; Respiratory Insufficiency; Thromboxane B2; Vasopressins

To assess the role of platelets in thrombohemorrhagic complications of acute respiratory failure (ARF), we studied platelet function in 13 ARF patients admitted for intensive care, in six acutely ill intensive care patients without evidence of acute lung injury (non-ARF), and in 10 normal subjects. Platelet counts in ARF and non-ARF patients were similar to the normal range. The bleeding time of the ARF patients (8.5 +/- 0.9 min) was significantly longer (p less than 0.01) than the normal (4.8 +/- 0.2 min) but similar to non-ARF patients (5.4 +/- 0.8 min). The bleeding time prolongations in ARF patients were unrelated to platelet concentration. Platelet aggregation induced by ADP and thrombin was normal in both ARF and non-ARF patient groups. The epinephrine response was impaired in one non-ARF patient and in three ARF patients; collagen-induced aggregation was absent in two ARF patients, with a prolonged bleeding time. Levels of VIII:C and vWF in both groups of patients were similar to the normal level, but VIIIR:Ag levels in ARF patients (407 +/- 45% of normal) were higher (p less than 0.01) than in both non-ARF patients (210% +/- 10%) and normal subjects (106% +/- 4). The electrophoretic mobility of VIIIR:Ag was abnormal in ARF patients. The prolonged bleeding time in ARF patients appears to result from the qualitative and quantitative VIIIR:Ag defect. beta-Thromboglobulin levels were greater (p less than 0.01) in ARF patients (87.6 +/- 6.9 ng/ml; p less than 0.001) than in non-ARF patients (46.2 +/- 3.1 ng/ml) or in normal subjects (25.3 +/- 2.5 ng/ml p less than 0.0001). However, platelet factor 4 plasma levels in ARF patients (18 +/- 1.6 ng/ml) did not differ from those in non-ARF patients (15.0 +/- 3.0 ng/ml), but both were significantly different from normal (6.1 +/- 0.8 ng/ml). Plasma thromboxane B2 (T X B2) levels were not different from normal values in either ARF or non-ARF patients, but 6-keto-PGF1 alpha levels were significantly reduced (p less than 0.01) in ARF patients (215 +/- 43 pg/ml) compared to normal values (381 +/- 34 pg/ml). Non-ARF patients had 6-keto-PGF1 alpha levels (285 +/- 111 pg/ml) midway between the normal values and those of ARF patients. Our results suggest that in vivo platelet activation occurs in ARF. ARF patients have quantitative and qualitative platelet defects that may contribute to thrombotic and hemorrhagic complications.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antigens; beta-Thromboglobulin; Bleeding Time; Blood Platelets; Factor VIII; Female; Humans; Lung; Male; Middle Aged; Platelet Aggregation; Platelet Count; Platelet Factor 4; Respiratory Insufficiency; Thromboxane B2; von Willebrand Factor

Arterial plasma concentrations of thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) were measured during endotoxin-induced acute respiratory failure (ARF) in anesthetized 10-12 wk old pigs. A 4.5 hour (hr) infusion of endotoxin resulted in a biphasic pattern of ARF. Phase 1 (0-2 hr) was characterized by increased pulmonary artery pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient (delta A-aO2), and decreased cardiac index (CI) and lung dynamic compliance (LDC). Following a return of PVR and CI values towards baseline, a second phase (2-4.5 hr) of deteriorating function occurred and was characterized by additional increases in PVR and delta A-aO2 and decreases in CI and LDC. Baseline (i.e., 0 hr) plasma TxB2 concentrations were 241 +/- 24 pg/ml; these values peaked at 0.5 hr (3228 +/- 712 pg/ml) and declined to 1635 +/- 453 pg/ml at 4.5 hr. Plasma concentrations of PGF2 alpha slowly increased from a baseline value of 154 +/- 32 pg/ml to 2355 +/- 738 pg/ml at 4.5 hr, while PGF1 alpha values increased from 54 +/- 2 pg/ml at 0 hr to 503 +/- 172 pg/ml at 4.5 hr. Time-matched control pigs showed no changes in pulmonary hemodynamics or in plasma TxB2, PGF2 alpha or PGF1 alpha levels. These results indicate that cyclooxygenase products are increased during both phases of endotoxin-induced ARF in pigs.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Arteries; Dinoprost; Endotoxins; Escherichia coli; Hemodynamics; Lung; Prostaglandins F; Respiratory Insufficiency; Swine; Thromboxane B2

Ischemia stimulates thromboxane (Tx) synthesis. This study tests the hypothesis that the cardiopulmonary dysfunction that may follow aortic declamping is related to Tx. Anesthetized dogs (N = 15) were subjected to 4 hours of infrarenal aortic cross-clamping. In untreated control animals (N = 7), plasma levels of TxB2 rose from 654 +/- 74 pg/mL to 1238 +/- 585 pg/mL at 5 min (p less than 0.05), and to 3174 +/- 912 pg/mL 3 hours after declamping (p less than 0.05). Mean pulmonary artery pressure (MPAP) rose 5 min after declamping from 13 +/- 2 mmHg to 21 +/- 2 mmHg (p less than 0.05). Cardiac Index (CI) declined during ischemia from 181 +/- 30 mL/kg.min to 128 +/- 16 mL/min.kg (p less than 0.05), and to 80 +/- 8 mL/min.kg after 4 hours of reperfusion (p less than 0.05). Platelet counts declined but platelets labeled with In 111 did not accumulate in the lungs, whereas quantitative counts of polymorphonuclear leukocytes (PMN) in the lungs 4 hours after declamping yielded 213 +/- 33 PMN/25 high power fields (HPF) in dependent areas of the lung and 153 +/- 26 PMN/25 HPF in nondependent areas. The wet/dry weight ratio of the lungs was not elevated, although foci of proteinaceous exudate and PMNs in alveoli were noted. Another group of dogs (N = 8) were pretreated by random choice with the Tx synthase inhibitor OKY-046 2 mg/kg IV every 2 hours, which led to: lower TxB2 levels at baseline 95 +/- 35 pg/mL (p less than 0.05), 5 min after ischemia 140 +/- 93 pg/mL and after 3 hours of reperfusion 122 +/- 36 (p less than 0.05); lower MPAP, 16 +/- 2 mmHg (p less than 0.05); higher CI throughout (p less than 0.05); normal histology and reduced pulmonary PMN sequestration both in dependent 127 +/- 15 PMN/25 HPF and nondependent areas of the lungs 95 +/- 11 PMN/25 HPF (p less than 0.05). In animals undergoing sham ischemia (N = 3), levels of TxB2 and cardiopulmonary function remained unchanged from baseline. There were 150 PMN/25 HPF in dependent and 85 PMN/25 HPF in nondependent lung areas. The results indicate that ischemia-generated Tx mediates a rise in MPAP, a fall in CI, and PMN entrapment in the lungs.

Topics: Animals; Blood Pressure; Cardiac Output; Dogs; Female; Hypertension, Pulmonary; Ischemia; Leg; Leukocyte Count; Lung; Methacrylates; Neutrophils; Platelet Count; Respiratory Insufficiency; Thromboxane A2; Thromboxane B2; Time Factors

Plasma levels of thromboxane A2 and prostacyclin have been elevated during experimental acute respiratory failure (ARDS). The present study evaluates the relationship of plasma levels of thromboxane A2 and prostacyclin, measured by radioimmunoassay as the stable metabolites thromboxane B2 (TxB) and prostaglandin 6-K-F1 alpha (PGI) to the incidence of clinical ARDS. Sixty-seven consecutive patients at risk for ARDS were studied prospectively. TxB, PGI, platelet, and leukocyte counts were measured daily for up to 5 days. Of 55 patients without cerebral injury, 25 (45%) developed ARDS, and 30 did not. Of 12 patients with cerebral injury, none developed ARDS. This difference was highly significant (P less than 0.01). TxB was increased and age lower with head injury (P less than 0.05). PGI was significantly lower in ARDS (110 +/- 32 vs 227 +/- 211 pg/ml, P less than 0.05), and mean TxB was unchanged. TxB was increased in age greater than 60 and decreased with prostaglandin inhibitors. ARDS was significantly associated with TxB greater than 70 pg/ml, PGI below the detectable level of 103 pg/ml, TxB/PGI ratio greater than 0.7, and age greater than 60 years. Peak TxB occurred before or simultaneously with onset of ARDS in 68%. Leukocytes were decreased in ARDS (8.6 +/- 4 vs 11.1 +/- 4.4 X 10(3)/mm3) and platelets were unchanged. ARDS was decreased with steroid therapy. Elevated TxB is related to a high incidence of ARDS. Elevated PGI may protect against ARDS. Cerebral injury patients in this study were resistant to ARDS in spite of increased TxB.

Topics: 6-Ketoprostaglandin F1 alpha; Adrenal Cortex Hormones; Age Factors; Craniocerebral Trauma; Epoprostenol; Female; Humans; Male; Platelet Count; Prostaglandin Antagonists; Respiratory Insufficiency; Thromboxane B2; Thromboxanes

An early event in the evolution of acute respiratory failure (ARF) is thought to be the activation of platelets, their pulmonary entrapment and subsequent release of the smooth muscle constrictor serotonin (5HT). This study tests the thesis that inhibition of 5HT will improve lung function. The etiology of ARF in the 18 study patients was sepsis (N = 10), aspiration (N = 3), pancreatitis (N = 1), embolism (N = 2), and abdominal aortic aneurysm surgery (N = 2). Patients were divided into two groups determined by whether their period of endotracheal intubation was less than or equal to 4 days (early ARF, N = 12) or greater than 4 days (late ARF, N = 6). Transpulmonary platelet counts in the early group showed entrapment of 26,300 +/- 5900 platelets/mm3 in contrast to the late group where there was no entrapment (p less than 0.05). The platelet 5HT levels in the early group were 55 +/- 5 ng/10(9) platelets, values lower than 95 +/- 15 ng/10(9) platelets in the late ARF group (p less than 0.05), and 290 +/- 70 ng/10(9) platelets in normals. The selective 5HT receptor antagonist, ketanserin was given as an intravenous bolus over 3 minutes in a dose of 0.1 mg/kg, followed by a 30-minute infusion of 0.08 mg/kg. During this period mean arterial pressure (MAP) fell from 87 +/- 5 to 74 +/- 6 mmHg (mean +/- SEM) (p less than 0.05). One and one-half hours following the start of therapy, MAP returned to baseline. At this time, patients with early ARF showed decreases in: physiologic shunt (Qs/QT) from 26 +/- 3 to 19 +/- 3 (p less than 0.05); peak inspiratory pressure from 35 +/- 2 to 32 +/- 2 cmH2O (p less than 0.05) and in mean pulmonary arterial pressure from 32 +/- 2 to 29 +/- 1 mmHg (p less than 0.05). At 4 hours all changes returned to baseline levels. In early ARF ketanserin did not alter pretreatment values of: pulmonary arterial wedge pressure, 17 +/- 3 mmHg; cardiac index, 2.8 +/- 0.3 L/min X m2; platelet count, 219,000 +/- 45,000/mm3; platelet 5HT, 55 +/- 5 ng/10(9) platelets; plasma 5HT, 142 +/- 21 ng/ml; plasma thromboxane B2, 190 +/- 30 pg/ml; or plasma 6-keto-PGF1 alpha, 40 +/- 10 pg/ml. Ketanserin infusion in patients with late ARF yielded no benefit. In both ARF groups the decreases in QS/QT were inversely related to the duration of intubation (r = 0.70; p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Aged; Blood Platelets; Blood Pressure; Cardiac Output; Female; Humans; Intubation, Intratracheal; Ketanserin; Male; Middle Aged; Piperidines; Platelet Count; Pulmonary Wedge Pressure; Respiratory Function Tests; Respiratory Insufficiency; Serotonin; Serotonin Antagonists; Thromboxane B2

Blockade of the arachidonic acid cascade has been shown to improve survival and hemodynamic alterations in animal models of sepsis and acute respiratory failure (ARF). The effects of intravenous ibuprofen, a cyclooxygenase inhibitor, were observed in 20-30 kg pigs with ARF induced by a continuous LD100 infusion of live Pseudomonas aeruginosa (2 X 10(8)/20 kg/min). Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250-ml tidal volume and 0.5 FiO2. Pigs were randomly assigned to three groups: Group I received 2 bolus infusions of ibuprofen (12.5 mg/kg) at 20 and 210 min after baseline; Group II had Ps. aeruginosa (2 X 10(8) CFU/20 kg/min) only; Group III received Ps. aeruginosa and 12.5 mg/kg of ibuprofen at 20 and 210 min of ARF. Ibuprofen alone caused no significant changes in cardiorespiratory parameters. With Ps. aeruginosa infusion, significant pulmonary hypertension, hypoxemia, increased intrapulmonary shunt fraction, and systemic hypotension occurred. In the septic animals treated with ibuprofen, oxygenation was improved by a significant decrease in shunt, pulmonary edema, and pulmonary hypertension.

Topics: Acute Disease; Animals; Disease Models, Animal; Hemodynamics; Ibuprofen; Lung; Male; Pseudomonas Infections; Respiratory Insufficiency; Swine; Thromboxane B2

Topics: Animals; Arachidonic Acids; Blood Platelets; Female; Indomethacin; Infusions, Parenteral; Platelet Aggregation; Prostaglandins; Prostaglandins D; Rabbits; Respiratory Insufficiency; Sulfinpyrazone; Thromboxane B2; Thromboxanes