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D D Bensard

Publications and source records attributed to D D Bensard.

42 records · Page 3Linked to original sources
PubMed1991

Marginating neutrophils are reversibly adherent to normal lung endothelium.

Neutrophils have been implicated in the pathogenesis of several inflammatory lung disorders including asthma, emphysema, and adult respiratory distress syndrome. The precursors of these destructive cells are thought to be marginating neutrophils that, although intravascular, remain intimately associated with endothelium, resisting the shearing forces of flowing blood. The purposes of this study were (1) to examine a method for quantitating marginating lung neutrophils, (2) to assess the adherence of marginating neutrophils to normal lung endothelium, and (3) to determine the reversibility of neutrophil-endothelial cell adherence. Rats were anesthetized and ventilated, and their lungs were exposed through a median sternotomy. The left lung was tied off with blood in situ and the right lung was perfused intraarterially with colloid for 2 minutes. In separate experiments, both left and right lungs were perfused intraarterially with colloid for 25 minutes. Myeloperoxidase, a neutrophil granule enzyme, was related to lung neutrophils. Dithionite-sensitive optical density (DSOD) was related to lung hemoglobin. Marginating lung neutrophils were quantitated by measuring the peroxidase activity of normal blood-perfused lung (myeloperoxidase assay) and subtracting from it the fraction of activity corresponding to the lung blood content (DSOD). The marginating neutrophil pool was identified by 2.1 units myeloperoxidase (5 x 10(6) neutrophils) per gm wet lung. Although the marginating pool was depleted by 54% during 2 minutes of lung colloid perfusion, lung erythrocytes (DSOD) were decreased by a significantly greater 93% (p less than 0.05). Lungs perfused with colloid for 25 minutes had negligible remaining myeloperoxidase activity. We conclude that (1) marginating lung neutrophils can be quantitated with the myeloperoxidase and DSOD assays, (2) marginating neutrophils are relatively adherent to normal lung endothelium compared with intravascular erythrocytes, and (3) the adherence of marginating neutrophils is fully reversible.

Animals↗
PubMed1991

The role of platelet activating factor and its antagonists in shock, sepsis and multiple organ failure.

PAF has been implicated as a mediator of shock, sepsis and MOF. The results of experimental data demonstrate that PAF induces changes characteristic of endotoxemia and sepsis, including systemic hypotension and diffuse microvascular leakage. These effects are prevented by PAF antagonists. PAF induces many of the characteristic changes of MOF, including functional impairment in the lung, kidney, gastrointestinal tract and heart. PAF antagonists will inhibit these adverse effects. PAF antagonists are now being manufactured by a number of pharmaceutical companies studying the beneficial effects of PAF antagonists in human disease. Data from these studies promise valuable information with significant clinical relevance to the practicing surgeon.

Animals↗
PubMed1991

Pretreatment with a nontoxic derivative of endotoxin induces functional protection against cardiac ischemia/reperfusion injury.

We hypothesized that low-dose pretreatment of an intact animal with a nontoxic derivative of endotoxin, monophosphoryl lipid A (MPL), would induce protection against cardiac ischemia/reperfusion (I/R) injury. The purposes of this study were to investigate whether MPL pretreatment would induce functional protection against cardiac I/R injury, to delineate the temporal induction of protection, and to examine antioxidant enzyme induction as a mechanism of protection. Rats were administered a 5 mg/kg dose of MPL at 2 hours and 24 hours before a 25-minute, global, 37 degrees C ischemic insult followed by reperfusion (modified Langendorff). At 40 minutes of reperfusion, ventricular function was assessed (ventricular balloon; developed pressure, rate of contraction, rate of relaxation). Hearts from rats pretreated with MPL 24 hours before isolation exhibited preservation of ventricular function (p less than 0.05). After I/R, hearts from rats pretreated with MPL 24 hours before isolation had increased (p less than 0.05) catalase activity compared to saline pretreated controls and rats pretreated with MPL 2 hours before isolation. We conclude that (1) pretreatment with MPL induces functional protection against cardiac I/R injury, (2) protection (not evident at 2 hours) is maximal at 24 hours, suggesting enzyme induction, and (3) increased catalase activity correlates with the functional protection.

Analysis of Variance↗
PubMed1990

Induction of endogenous tissue antioxidant enzyme activity attenuates myocardial reperfusion injury.

Efforts to reduce reperfusion injury have focused on exogenous therapies; however, endogenous attenuation of reperfusion injury can be induced by a single sublethal dose of endotoxin (ETX) prior to ischemia. The purposes of this study were to investigate (i) the early neutrophil-endothelial (PMN-EC) adherence, (ii) the associated myocardial oxidant stress, (iii) the relationship of oxidant stress to antioxidant enzyme activity, and (iv) the correlation of increased antioxidant enzyme activity to myocardial recovery following ischemia/reperfusion (I-R) injury at 36 hr. Rats were administered a sublethal dose (2% of LD50) of endotoxin (500 micrograms/kg, ip, Salmonella typhimurium). At 6 hr, myocardial neutrophil accumulation (histology), hydrogen peroxide (H2O2) levels, and myocardial tissue glutathione (glutathione and oxidized glutathione) levels were determined. At 24 hr myocardial tissue glutathione levels and catalase (CAT) activity were assayed. At 36 hr, myocardial tissue superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and glucose-6-phosphate dehydrogenase (G-6-PD) were assayed. At 36 hr, hearts were subjected to a standard (20 min, global, 37 degrees C) ischemic insult followed by reperfusion. At 40 min of reperfusion, ventricular function was assessed (ventricular balloon; ventricular developed pressure +dP/dt, and -dP/dt).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Reversible lung neutrophil accumulation can cause lung injury by elastase-mediated mechanisms.

Neutrophils have been implicated in multiple models of end-organ injury. The purposes of this study were to determine whether (1) a sublethal septic insult promotes lung neutrophil accumulation, (2) this pulmonary neutrophil accumulation is reversible, (3) these accumulated neutrophils can be activated to injure lung, and (4) this pulmonary neutrophil accumulation obligates lung injury. Rats were administered low-dose endotoxin, 500 micrograms/kg, intraperitoneally, and at 6 or 12 hours, lungs were harvested and assayed for myeloperoxidase, a marker of neutrophil accumulation, and iodine 125-labeled albumin uptake, a marker of lung injury. A second set of rats were administered low-dose endotoxin and at 6 or 12 hours were given a neutrophil activator formyl-norleucyl-leucyl-phenylalanine (FNLP) 250 micrograms/kg, intravenously. At 8 or 14 hours, lungs were harvested and assayed for 125I-labeled albumin uptake. A third set of rats were administered low-dose endotoxin, and at 5 1/2 hours 30 minutes before FNLP administration, they were given a neutrophil elastase inhibitor, methyoxysuccinyl-L-alanine-L-alanine-L-proline-L-valine-chlorometh yl ketone, 2.5 mg/kg, intraperitoneally. At 6 hours rats were given FNLP, and at 8 hours lungs were harvested and assayed for 125I-labeled albumin uptake. The following results were obtained: (1) low-dose endotoxin caused a transient increase (p less than 0.05) in lung neutrophil accumulation at 6 hours, which was resolved by 12 hours; (2) lung 125I-labeled albumin uptake was unchanged both 6 and 12 hours after isolated low-dose endotoxin administration; (3) neutrophil activation increased (p less than 0.05) lung 125I-labeled albumin uptake when imposed 6 but not 12 hours after low-dose endotoxin administration; and (4) elastase inhibition decreased (p less than 0.05) the lung 125I-labeled albumin uptake promoted by endotoxin and FNLP. We conclude that sublethal endotoxemia causes a reversible lung neutrophil accumulation and that this lung neutrophil accumulation does not obligate lung injury; but activation of these accumulated neutrophils can promote lung injury, and this neutrophil-associated lung injury is mediated in part by neutrophil elastase.

Amino Acid Chloromethyl Ketones↗