indium-oxine and Shock--Septic

In an intensive care setting we studied the effects of pentoxifylline on hemodynamics, gas-exchange and platelet sequestration in multiple organs in three groups of sheep exposed to endotoxin shock (n = 7 in each). Group P-E was given pentoxifylline before and group E-P after E. coli endotoxin infusion, while group E received normal saline (controls). The endotoxin infusion caused a three-fold increase in pulmonary artery pressure (PAP) and a significant decrease in mean arterial pressure (25-30%; MAP), respiratory compliance (CT; 60%) and arterial oxygen tension (65-70%; Pao2) in all groups after 30 min. After 4 h MAP had improved significantly in the pretreated animals (group P-E) and arterial pH, Pao2 and CT improved in both pentoxifylline-treated groups compared with the controls. On the other hand, the effects of endotoxin on PAP and cardiac index were not significantly influenced by pentoxifylline treatment. In addition, there was a pronounced platelet sequestration in the lungs and in the liver in groups E and E-P during the 4 h study, but in the pretreated group (group P-E) the changes were significantly less marked (P < 0.01). The wet-to-dry weight ratios of the lungs were significantly lower in both pentoxifylline-treated groups compared with the controls (P < 0.01). It was concluded that pentoxifylline modified the effects of endotoxin on hemodynamics, gas exchange and platelet sequestration in the lungs and liver in sheep when it was given prior to endotoxin. However, when it was given after hemodynamic and respiratory signs of shock had appeared, the effects were more moderate.

Topics: Animals; Blood Circulation; Blood Platelets; Blood Pressure; Cardiac Output; Endotoxins; Escherichia coli; Hemodynamics; Indium Radioisotopes; Liver; Lung; Lung Compliance; Organ Size; Organometallic Compounds; Oxygen; Oxyquinoline; Pentoxifylline; Pulmonary Artery; Pulmonary Gas Exchange; Radionuclide Imaging; Sheep; Shock, Septic

Leucocyte sequestration in various organs during endotoxin-induced shock in sheep was studied using leucocytes labelled with indium 111 oxine. A moderate dose of Escherichia coli endotoxin (10 micrograms/kg body weight) was slowly infused intravenously in 16 sheep, 9 of which subsequently received a continuous i.v. infusion of low-molecular-weight dextran (LMWD) given at an infusion rate of 15 ml/h over 4 h, starting 30 min after administration of the endotoxin. By that time, signs of acute lung injury had developed, thus mimicking a clinical situation. The remaining animals were untreated and served as controls. A marked increase in lung, liver and kidney leucocyte sequestration, together with a sharp, corresponding drop in splenic activity and leucocyte count in peripheral blood, occurred shortly after the endotoxin infusion in both groups. However, after 90 min there was a significantly lower leucocyte activity in the lungs, liver and kidneys of LMWD-treated animals as compared with controls. Less marked hemodynamic and respiratory alterations were also observed in animals treated with LMWD. The present study confirms previous reports that significant leucocyte sequestration in the lungs occurs early during endotoxemia. Furthermore, we found that leucocyte sequestration also occurs in the liver and kidneys, which could explain the development of multi-organ failure, frequently described in clinical sepsis. Even after injury to organs, LMWD infusion seems to be beneficial by significantly lowering leucocyte sequestration and could therefore be justified as an addition to the arsenal of interventions used in the treatment of endotoxemia.

Topics: Animals; Dextrans; Endotoxins; Escherichia coli; Escherichia coli Infections; Indium Radioisotopes; Leukocytes; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Sheep; Shock, Septic

The dynamic behavior of indium-111 oxine-labeled leukocytes was simultaneously recorded in multiple organs during endotoxin shock in sheep. Also, the effects of the beta-2 receptor agonist terbutaline were studied. An experimental protocol was designed to mimic a clinical condition in an intensive care setting as far as possible. The animals were ventilated with 50% oxygen to avoid hypoxemia and were given large amounts of intravenous fluids to reduce adverse effects of hypovolemia. A moderate dose of E. coli endotoxin (10 micrograms/kg bwt) was given by intravenous infusion to 14 adult sheep, seven of them receiving continuous intravenous infusion of terbutaline (20 micrograms/kg/hr) during 4 hr, starting 30 min after endotoxin, when signs of lung injury had developed. The other seven acted as controls. A marked pulmonary and hepatic leukocyte sequestration together with a sharp drop in leukocyte counts in peripheral blood occurred within minutes after start of the endotoxin infusion in both groups. However, no changes were observed in the kidneys or the gut. After 60 min and until the end of the experiment, there was a significantly lower activity in the lungs and in the liver of the animals treated with terbutaline than in the controls (P less than .01). Furthermore, less marked hemodynamic and respiratory alterations occurred in the terbutaline group compared with the controls. This study confirms the results of other investigators showing that significant leukocyte sequestration occurs in the lungs during endotoxemia, but it also demonstrates that leukocytes sequestrate in the liver, although slightly less than in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Agonists; Animals; Endotoxins; Escherichia coli; Hydroxyquinolines; Indium Radioisotopes; Leukocytes; Liver; Lung; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Sheep; Shock, Septic; Terbutaline

Using a sheep model, platelet sequestration in lungs, liver, kidney, spleen, and brain was studied after the injection of Indium-111-oxine-labeled platelets and E. coli lipopolysaccharide. Immediately following endotoxin-induced shock, platelet sequestration was observed in lungs, liver, and kidney with corresponding decrease in measured Indium-111-oxine platelets in spleen and circulating blood. There was also a decrease in platelet counts as measured in a phase contrast microscope. The early platelet sequestration in lung, liver, and kidney was followed by platelet disaggregation and another phase of platelet sequestration which continued until the death of the animal. No platelet sequestration was observed in the brain.

Topics: Animals; Blood Pressure; Indium Radioisotopes; Kidney; Liver; Lung; Organometallic Compounds; Oxyquinoline; Platelet Aggregation; Radionuclide Imaging; Sheep; Shock, Septic

This study describes the effects of the beta 2 receptor agonist terbutaline on platelet sequestration in sheep exposed to endotoxin shock. The in vivo behavior of Indium-111-labeled platelets was followed simultaneously in the lungs, liver, spleen, and kidneys. The effects on the respiratory function and the central hemodynamics were also followed. Twelve adult sheep were given endotoxin (10 micrograms/kg bw), and six of those received a continuous intravenous infusion of terbutaline (20 micrograms/kg/hr) during 4 hr, starting 30 min after injection of endotoxin. The other six acted as controls. It was found that a marked pulmonary and hepatic platelet sequestration occurred during and just after the endotoxin infusion and was followed by a marked platelet disaggregation within 30 min in both groups. Three hours after the endotoxin a second wave of platelet trapping occurred in the control animals in both the lungs and the liver, while no such increase was seen in the terbutaline-treated animals. In the spleen, however, there was a decrease in platelet sequestration after endotoxin in both groups, and in the kidneys only minor changes occurred. Furthermore, less marked hemodynamic and respiratory alterations occurred in the terbutaline group compared with the controls. It was concluded that terbutaline decreased sequestration of platelets in the lungs and in the liver of sheep in endotoxin shock, which may be of importance in the development of multiple organ failure.

Topics: Animals; Blood Platelets; Hydroxyquinolines; Indium Radioisotopes; Liver; Lung; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging; Sheep; Shock, Septic; Terbutaline

It has been reported in earlier in vitro studies that soft tissue trauma and endotoxin-induced shock causes pulmonary platelet trapping (PPT). This paper describes a noninvasive in vivo technique for dynamic studies of PPT in rabbits. Autologous platelets were labeled with 111In and reinfused into the animals. The following day, the rabbits were anesthetized and placed in a supine position under a scintillation camera. Continuous measurement of the activity distribution in the animal was performed for 35 min. The first 5 min represented a preshock measurement, whereafter endotoxin E. coli was injected IV. The following 2-3 min showed a sudden increase of radioactivity in the lungs indicating PPT, and thereafter a slow decrease to almost the preshock level. A simultaneous decrease in the number of platelets and the radioactivity in peripheral blood also indicated the induction of PPT. This study clearly shows that PPT can be detected in vivo with an easy, noninvasive scintillation camera method.

Topics: Animals; Blood Platelets; Endotoxins; Escherichia coli Infections; Indium; Lung; Organometallic Compounds; Oxyquinoline; Platelet Count; Rabbits; Radioisotopes; Radionuclide Imaging; Scintillation Counting; Shock, Septic