Lung compartmentalization of inflammatory cells in sepsis.

Lung injury commonly occurs in the setting of systemic inflammatory response syndrome occurring during bacterial sepsis. There has been little work quantifying different leukocytes within the different compartments of the lung and their association with overt lung injury in sepsis. We examined the pathogenesis of lung injury after cecal ligation and puncture (CLP), a clinically relevant model of sepsis.

Time-dependent cardiovascular and inflammatory changes in acute endotoxemia.

The pathophysiology of experimental acute endotoxemia is a complex process involving both cardiovascular dysfunction and an inflammatory response. We have examined the correlation in hemodynamic changes and the pulmonary inflammatory response after lipopolysaccharide (LPS) administration with respect to time. Importantly, we have measured the lung and plasma levels of nitric oxide (NO) over time, as well as rapid generation of lung superoxide after LPS administration.

Effect of fluid resuscitation from endotoxin shock on lung transvascular fluid and protein exchange.

The hypothesis that volume expansion during septic shock produces a greater transvascular protein flux than volume expansion alone was tested in anesthetized sheep by giving a high dose of endotoxin (40 micrograms/kg) intravenously. After 0.5 h of systemic hypotension, Ringer lactate, equivalent to 8% body wt, was infused followed by an additional 4 h of lymph collection.

Zymosan-activated plasma causes prolonged decreases in PMN superoxide release in sheep.

It is well established that activation of neutrophils within the pulmonary circulation produces acute lung injury in which adherence of neutrophils to endothelial cells is an obligatory step in the mechanism of injury. The effects of in vivo activation of neutrophils on the in vitro responses of these cells to stimulation have not been determined, although such information may be important in understanding how different etiological factors may interact to produce infection or acute respiratory failure. By using an assay to sequentially measure superoxide anion (O2-) release from adherent neutrophils stimulated with phorbol myristate acetate (PMA), we measured the in vitro activation response of peripheral blood neutrophils isolated before and 24 h after infusion of zymosan-activated plasma (ZAP; or untreated plasma as a control), air bubbles, or PMA in awake, instrumented sheep.

Morphological analysis of the activation of adherent neutrophils in vitro.

One approach to study the inflammatory potential of neutrophils involves in vitro methods, using either adherent or suspended cells. In order to do structure-function studies, traditional methods require that experiments be done in parallel: one experiment for structure and another for function. In this report new morphological methods for coordinated structure-function studies on the same cells are described.

Biochemical analysis of the activation of adherent neutrophils in vitro.

The role played by neutrophil oxidative responses in host defense and injury is an area of active investigation. In order to study neutrophil responses in vitro, methods are required for cell purification, enumeration, and quantification of activation responses, which mimic the in vivo situation as closely as possible. In this communication (and its companion paper, Albertine et al.

Prostaglandin E1 prevents increased lung microvascular permeability during intravascular complement activation in sheep.

Prostaglandin E1 (PGE1) inhibits a variety of functions of activated neutrophils including respiratory burst, release of leukotriene B4, and adherence to endothelial cells. To determine if PGE, alters the pathophysiology of complement-induced lung vascular injury, experiments were conducted in anesthetized sheep with lung lymph fistulas given a 1-hour infusion of zymosan-activated plasma. PGE1 (30 ng/min/kg) or its saline vehicle was infused intravenously for 90 minutes beginning 30 minutes before the infusion of activated plasma.

Metabolic responses of women to exercise attributable to long term use of a manual wheelchair.

The purpose of this study was to determine the effects of long term use of a manual wheelchair by wheelchair-confined women (means = 14.6 years) on physiological responses to wheelchair ergometry. Six experimental subjects were compared to six able bodied women during maximal exercise as well as submaximal wheelchair ergometry at 50 and 80% of peak VO2.

The effects of cyclooxygenase inhibition on chemiluminescence and aggregation in sheep neutrophils.

Antiinflammatory actions of cyclooxygenase inhibitors may be related to inhibition of the synthesis and release of prostaglandins and thromboxane or to nonspecific actions of particular drugs. The role of cyclooxygenase products of arachidonic acid was studied in two leukocyte functions, free radical release and aggregation, after complement activation. Dose response curves were constructed after treatment with meclofenamate or ibuprofen.

Thromboxane as a mediator of pulmonary dysfunction during intravascular complement activation in sheep.

Intravascular complement activation results in thromboxane (TxA2) production, pulmonary hypertension, hypoxemia, and increased lung vascular permeability. The purpose of this study was to determine the role of TxA2 as a mediator of these responses. Experiments were made in anesthetized sheep subjected to intravenous injections of zymosan-activated plasma (ZAP) every 30 min for 4 h.

Dialysis-induced hypoxemia: membrane dependent and membrane independent causes.

Hypoxemia during hemodialysis may result from several differing processes. We initially studied patients undergoing standard acetate hemodialysis. At 15 minutes of dialysis, leukopenia (primarily neutropenia), a decline of platelet count, and hypoxemia occurred, but without a significant change in mean minute ventilation.

Arachidonate cyclooxygenase metabolites as mediators of complement-initiated lung injury.

The pulmonary effects of intravascular complement activation can be divided into those that are initial events of activation and those that depend on the duration of intravascular activation. Pulmonary leukostasis is both an initial event and one that persists as long as intravascular complement activation is ongoing. This event is independent of synthesis and release of cyclooxygenase products of arachidonic acid.

Aggregation and thromboxane synthesis and release in isolated sheep neutrophils and lymphocytes in response to complement stimulation.

In an attempt to determine possible cellular sources of thromboxane synthesis and release during intravascular complement activation, we prepared pure, viable fractions of neutrophils and lymphocytes from sheep blood. Lymphocytes were also isolated from thoracic duct lymph. Blood neutrophils and lymphocytes release thromboxane and the cells aggregate when challenged with zymosan-activated plasma.

Thrombin-induced lung vascular injury. Roles of fibrinogen and fibrinolysis.

We examined the contributions of fibrin and the fibrinolytic mechanism in mediating the thrombin-induced lung vascular injury. Studies were made in sheep in which alterations in lung transvascular fluid and protein exchange were assessed using the lung lymph fistula preparation. Group I(n = 10) control sheep in which left atrial pressure was raised to increase pulmonary lymph flow (Qlym); Group II(n = 8) control sheep in which thrombin was infused intravenously (58.

Granulocytes mediate the increase in pulmonary vascular permeability after thrombin embolism.

We examined the effect of pulmonary embolization with microthrombi on the lung vascular permeability to proteins and the role of platelets and granulocytes as putative cellular factors in mediating the alterations in permeability. Anesthetized artificially ventilated sheep were prepared with lung lymph fistulas. Pulmonary embolization was induced using thrombin.

Prevention of increased pulmonary vascular permeability after pancreatitis by granulocyte depletion in sheep.

We examined the role of granulocytes in the development of increased pulmonary vascular permeability during acute pancreatitis in acute sheep lung lymph preparation. One group of animals was depleted of 95% of circulating granulocytes by injection of hydroxyurea. In this group and in a second group of control animals, acute hemorrhagic pancreatitis was produced by injection of trypsin and sodium taurocholate acid into the pancreas.

Increased lung vascular permeability after pancreatitis and trypsin infusion.

We examined the role of proteases in mediating lung vascular injury after acute hemorrhagic pancreatitis. Studies were made in sheep in which pulmonary lymph was collected for assessment of the changes in transvascular fluid and protein exchange. The induction of pancreatitis by injection of trypsin and sodium taurocholate into the pancreas resulted in increases in pulmonary lymph flow and transvascular protein clearance (lymph flow x lymph-to-plasma protein concentration ratio).

Lung fluid balance after pulmonary embolization: effects of thrombin vs. fibrin aggregates.

We examined the relationship between the activation of fibrinolysis and the increase in lung vascular permeability after pulmonary microembolization (PM). Sheep were prepared with lung lymph fistulas to assess pulmonary transvascular fluid and protein dynamics. Studies were made in three groups: group I (n = 8) in which PM was induced by an iv infusion of thrombin (60 +/- 13 NIH U/kg); group II (n = 7) in which PM was induced by an iv infusion of 50-micrometers-diameter fibrin microaggregates (0.

Mechanisms of lung vascular injury after intravascular coagulation.

Pulmonary intravascular coagulation and the resultant microembolization increase lung vascular permeability to proteins. The increase in permeability is mediated by the activation of cellular and humoral factors after intravascular coagulation. In particular, intravascular coagulation results in sequestration and activation of leukocytes, which appears to be of primary importance in mediating the lung vascular injury.

Physiological and performance characteristics of United States championship class orienteers.

The purpose of this investigation was to study the anaerobic and aerobic power of female and male United States championship orienteers and relate these data to competitive performance. In addition, it was considered valuable to obtain a general physical description of the athletes. Anthropometrically, neither the females (n=5) nor the males (n=13) conformed to a somatotype classification typical of endurance athletes.