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Biomedical subjects

J R Fletcher

Publications and source records attributed to J R Fletcher.

At least 91 records · Page 5Linked to original sources
PubMed1980

The distribution of lipopolysaccharide in normocomplementemic and C3-depleted rabbits and rhesus monkeys.

To examine the role of complement (C3) in determining the fate of lipopolysaccharide (LPS) in vivo, the distribution of LPS was studied in normocomplementemic (NC) and C3-depleted animals (pretreated with cobra venom factor [CoF]) after intravenous injection of highly purified, radioiodinated Salmonella minnesota R595 LPS. After injection of a lethal (250 micrograms) or nonlethal (5 micrograms) dose of LPS in NC and CoF rabbits and a lethal (5 mg/kg) dose of LPS in rhesus monkeys, the LPS disappeared from blood in a biphasic manner. In all cases, a substantial portion of the dose was removed from blood in an initial disappearance phase (t1/2 < 15 minutes), which, in some cases, was accelerated in CoF-treated animals. LPS remaining in blood beyond 30 minutes persisted with a much increased half-life (> 5 hours). Liver contained the major portion (40%) of tissue-bound LPS (determined by use of 131I-BSA blood marker) in animals killed 3--5 hours after injection. The distribution of LPS in rabbits was found to be dose-indpendent and only minimally changed by prior depletion of C3. In addition, the tissue distribution and cellular localization of LPS in monkeys was similar to that we have reported previously for R595 LPS in NC rabbits and was not substantially changed by prior CoF treatment. These results indicate that binding of C3 to intravenously injected LPS is not required for the initial rapid disappearance from blood. Further, the uptake of LPS by cellular targets, notably the hepatic macrophages (Kupffer cells), is not altered by in vivo decomplementation.

Animals↗
PubMed1979

Lidocaine treatment following baboon endotoxin shock improves survival.

Baboons treated with lidocaine (2 mg/kg/hr) after shock from endotoxin were compared to untreated controls in an LD70 E coli endotoxin (4 mg/kg) model. Survival, systemic and pulmonary arterial pressures, cardiac output, white blood cell and platelet counts, blood gases and arterial and mixed venous PGE and PGF 2 alpha levels were determined. Baboons receiving lidocaine had a better (P less than 0.05) survival at 72 hours than the controls. Circulatory function was improved with lidocaine; however, white blood cell and platelet counts, blood gases, and the prostaglandin release were similar in both groups. The mechanism by which lidocaine improves survival in baboon endotoxin shock appears to be unrelated to its effects on white blood cells, platelets, or the prostaglandin release.

Animals↗
PubMed1978

E. coli endotoxin shock in the dog; treatment with lidocaine or indomethacin.

1 Dogs treated with lidocaine (1 mg kg-1 h-1) or indomethacin (1.5 mg/kg) before and after an LD60 dose (1 mg/kg) of E. coli endotoxin survived for at least 72 h. 2 Although all dogs in both treated groups survived, only those treated with indomethacin were significantly protected against the fall in the arterial blood pressure 1 to 2 min following endotoxin administration. 3 Endotoxin increased the plasma prostaglandin F2alpha (PGF2alpha) concentration in the control and lidocaine-treated groups, however, no increase was observed with indomethacin treatment. 4 Neither lidocaine nor indomethacin alone had any significant effect on the parameters measured in this model. 5 Following the administration of endotoxin, lidocaine-treated animals had significantly decreased plasma fibrinogen concentrations when compared to the other groups. 6 This study suggests that lidocaine, a local anaesthetic and a drug widely used for cardiac arrhythmias, might offer protection in endotoxin shock.

Animals↗
PubMed1978

Platelet aggregation in rabbits made tolerant to endotoxin.

Endotoxin may cause abnormal deposition of platelet-endotoxin aggregates, and this event could have damaging effects. We compared the aggregation characteristics of platelets from rabbits made tolerant to the lethal effects of endotoxin with those of platelets from normal rabbits. Platelets from tolerant rabbits aggregated more rapidly (greater than 90 s faster) in the presence of endotoxin than did platelets from nontolerant animals. Furthermore, platelets from tolerant animals aggregated reversibly. These characteristics of platelets from tolerant animals are due to humoral factors in the plasma, because 1:1 dilution of normal platelet-rich plasma with plasma from tolerant rabbits caused the normal platelets to behave like those from tolerant animals. Survival after challenge with lethal quantities of endotoxin was enhanced in tolerant rabbits; this may be due to promotion of more efficient removal of endotoxin-platelet complexes from the blood by the reticuloendothelial system.

Animals↗
PubMed1978

Baboon veno-arterial cardiopulmonary bypass without anticoagulants.

Four hr veno-arterial cardiopulmonary bypass via a median sternotomy utilizing a membrane oxygenator was done in 15 baboons. A comparison of perfusion with and without anticoagulants was made. From this study systemic heparin had no advantage over no anticoagulants. These findings, in a clinically-relevant primate model, suggest that the scientific basis for the use of systemic heparin in membrane oxygenation is unclear.

Animals↗
PubMed1978

The effect of complement depletion on bacterial lipopolysaccharide (LPS)-induced hemodynamic and hematologic changes in the Rhesus monkey.

Lipopolysaccharide (LPS) isolated from Salmonella minnesota R595 or from Escherichia coli 0111:B4 induces hypotension in rhesus monkeys with normal complement levels. This hypotension is accompanied by decreased total peripheral resistance. The depletion of C3 and terminal complement components by prior intraperitoneal administration of the anticomplementary protein cobra factor did not alter the hemodynamic changes which occur following the rapid injection of 5 mg/kg of R595 LPS, the infusion of 500 microgram/kg of R595 LPS, or the injection of 500 microgram/kg of 0111:B4 LPS. We conclude that the LPS-induced hemodynamic changes in the subhuman primate are medicated by pathways which do not require the participation of C3. The kinetics and extent of the neutropenia and thrombocytopenia resulting from the injection of 0111:B4 or R595 LPS were not latered by prior depletion of greater than 95% of the plasma C3.

Animals↗
PubMed1977

Modification, by aspirin and indomethacin, of the haemodynamic and prostaglandin releasing effects of E. coli endotoxin in the dog.

1 Dogs treated with aspirin (10 mg/kg) or indomethacin (1.5 mg/kg) 45 min before, and 3 h after, an LD50 dose (1 mg/kg) of E. coli endotoxin were alive 72 h later. 2 Although all dogs in both treated groups survived, only those treated with indomethacin were protected against the fall in blood pressure 1-2 min following endotoxin. 3 Endotoxin increased the level of prostaglandin F2alpha in both the mixed venous and arterial blood. No increase was observed in the aspirin and indomethacin-treated groups. 4 Aspirin and indomethacin treatment did not modify thrombocytopaenia or blood coagulation parameters following endotoxin.

Animals↗