Anti-inflammatory properties of enamel matrix derivative in human blood.

Background And Objective: Enamel matrix derivative (EMD), extracted from porcine tooth buds, has been shown to promote periodontal healing in patients with severe periodontitis. This involves modulation of the inflammatory response followed by the onset of periodontal regeneration. Based on these observations, we examined the ability of EMD to modulate the release of a pro-inflammatory cytokine [tumor necrosis factor (TNF)-alpha], an anti-inflammatory cytokine (interleukin-10) and a chemokine (interleukin- 8) in whole human blood challenged by bacterial cell wall components.

Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain.

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this.

The role of Kupffer cell inhibition in porcine endotoxemia.

The selective Kupffer cell inhibitor gadolinium chloride (GdCl3) has been demonstrated to protect animals from lethality in experimental endotoxemia and sepsis in rodent models. This study was designed to investigate the effect of Kupffer cell blockade on the early response to endotoxin in a large animal model. Using a porcine endotoxemia model, animals were randomized to receive either GdCl3 (10 mg/kg or 30 mg/kg; n = 8 in each group) or vehicle saline (n = 8) 24 h before exposure to endotoxin.

Selective inhibition of inducible nitric oxide synthase maintains haemodynamic stability without untoward consequences for hepatic function or morphology.

Objective: To examine the effects of the inducible nitric oxide synthase inhibitor aminoethyl-isothiourea (AE-ITU) on haemodynamic measurements, and correlate these with hepatic morphology and function in a porcine model of endotoxaemia.

Design: Experimental study.

Animals: 15 juvenile pigs.

The nitric oxide donor sodium nitroprusside protects against hepatic microcirculatory dysfunction in early endotoxaemia.

Objective: Endotoxin rapidly inhibits the activity of the constitutive endothelial nitric oxide synthase (ecNOS); this precedes the production of NO from inducible NOS (iNOS). This leaves a period in early endotoxaemia with a supposed scarcity of NO. The present study was conducted to examine the effects of external supplementation of NO on liver microcirculation and function.

Hepatic oxygen metabolism in porcine endotoxemia: the effect of nitric oxide synthase inhibition.

The role of endotoxin (lipopolysaccharide, LPS) and nitric oxide in hepatic oxygen metabolism was investigated in 36 pigs receiving 1) LPS (1.7 microgram. kg-1.

Effects of the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl ester and aminoethyl-isothiourea on the liver microcirculation in rat endotoxemia.

Background/methods: The question whether nitric oxide protects or impairs organ perfusion during early endotoxemia has not been completely answered. To evaluate the regulative function of nitric oxide on organ microvascular perfusion and leukocyte accumulation during endotoxemia, we studied the influence of a non-selective nitric oxide inhibitor and a preferential inducible nitric oxide synthase inhibitor (respectively, N(G)-nitro-L-arginine methyl ester and aminoethyl-isothiourea) on liver microcirculation (intravital fluorescence microscopy) in a rat model.

Results: Two hours after intraportal injection of lipopolysaccharide (5 mg/kg in 10 min) the rats were randomly treated and received a bolus dose of N(G)-nitro-L-arginine methyl ester (10 mg/kg, n = 7), aminoethyl-isothiourea (10 mg/kg, n = 6) or normal saline, (n = 7).

Aminoethyl-isothiourea, a selective inhibitor of inducible nitric oxide synthase activity, improves liver circulation and oxygen metabolism in a porcine model of endotoxemia.

The role of nitric oxide (NO) in hepatic oxygen transport is unclear. We investigated the effects of aminoethyl-isothiourea (AE-ITU), a selective inhibitor of iNOS activity, on liver blood flow and oxygen consumption (VO2H) in the pig. Endotoxin (lipopolysaccharide, LPS) was given intraportally (1.

Use of selective and nonselective nitric oxide synthase inhibitors in rat endotoxemia: effects on hepatic morphology and function.

Endotoxin has profound effects on nitric oxide (NO) production, and considerable controversies exist as to whether these alterations are beneficial or deleterious. Increased mortality has been reported from nonselective inhibition of NO synthase. Results from selective inhibition of the inducible isoform (iNOS) appear largely positive.

Modulators of nitric oxide in porcine endotoxemia: effects on hepatic oxygen delivery and consumption.

In a porcine model of endotoxemia we have studied the effects of nitric oxide (NO) on hepatic oxygen delivery and consumption. After 3 h of endotoxemia, NO biosynthesis was modulated by a bolus dose of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Fifteen minutes thereafter a continuous infusion of the NO donor sodium nitroprusside (SNP) was started.

The NO donor sodium nitroprusside reverses the negative effects on hepatic arterial flow induced by endotoxin and the NO synthase inhibitor L-NAME.

In previous studies we have observed that the nitric oxide synthase inhibitor L-NAME induces a profound deterioration of liver circulation in experimental endotoxemia. Using the same porcine model we now have evaluated the possibility of modulating these effects with the nitric oxide donor sodium nitroprusside. Infusion of endotoxin led to a gradual deterioration of hemodynamic parameters, including liver blood flow.

Complement activation during cardiopulmonary bypass: comparison between the use of large volumes of plasma and dextran 70.

Cardiopulmonary bypass surgery may be complicated by a systemic inflammatory reaction, which has been ascribed to the activation of complement. For such activation, the choice of priming solution for the heart-lung machine may be of importance. The peripheral blood of two groups of 10 patients, either exposed to dextran 70 or to plasma as priming solutions, was therefore studied pre-, per-, and postoperatively.

Hemostasis after open-heart surgery with extreme or moderate hemodilution.

Patients who received aortic disc valves during cardiopulmonary bypass (CPB) with extreme hemodilution, obtained with preoperative blood withdrawal, infusion of acetate solution and use of blood-free priming fluid, bled less than patients operated with moderate dilution. One hour after CPB with extreme dilution when the autologous blood had been reinfused, platelet adhesiveness was twice as high as in the moderate dilution group. Other parameters of platelet function, coagulation and fibrinolysis did not differ between the groups.

The effect of ethanol intake on propoxyphene absorption and biotransformation in dogs.

The effect of ethanol (0.5 and 1.0 g/kg) on gastrointestinal absorption and presystemic biotransformation of propoxyphene (4 mg/kg) was studied in dogs in a crossover design.

Ionized calcium in plasma during cardiopulmonary bypass.

The composition of the priming fluid in the heart-lung machine is of importance for the homeostasis of the patient during and after cardiopulmonary bypass. We have studied the effect of 5 different priming solutions on the degree of ionization of calcium. The primingsolutions all contained 1700 ml of a basic solution and 800 ml of one of the following solutions: CPD-plasma CPD-plasma added heparine and CaCl2 heparinized plasma 5% albumin in saline 6% dextran 70 in saline.

Neuromuscular blocking effects of atracurium, vecuronium and pancuronium during bolus and infusion administration.

The potencies of atracurium, vecuronium and pancuronium were compared using bolus injections and continuous infusions. The sizes of the bolus injections were based on previously determined cumulative dose-response relationships. Dose requirements for 90% and 50% sustained blockade were estimated by use of continuous infusion, and the corresponding plasma concentrations were measured for vecuronium and pancuronium.

Dextran 70 versus donor plasma as colloid in open-heart surgery under extreme haemodilution.

Dextran 70 and donor plasma were compared as colloid in the priming solution during heart-lung perfusion in open-heart surgery. The patients underwent surgery for coronary artery or aortic valve disease. One group of nine patients had plasma in the priming solution, while ten patients received dextran 70.

Early postoperative changes with different priming solutions in open-heart surgery.

The consequences of substituting dextran 70 (Macrodex) for human plasma in the priming solution were studied during the first 48 hours after open-heart surgery. Twenty patients undergoing elective surgery for coronary artery disease were selected for the study. Clinical, haemodynamic, metabolic and roentgenologic parameters were monitored.

Pulsatile vs. non-pulsatile flow during cardiopulmonary bypass. A comparison of early postoperative changes.

The aim of the study was to evaluate possible haemodynamic and metabolic effects of pulsatile flow in cardiopulmonary bypass. The subjects were 20 patients undergoing coronary artery bypass grafting. They had no complicating diseases.

The influence of open-heart surgery during extreme hemodilution on the hemostatic mechanism in the dog.

12 Labrador retriever dogs had mitral disc valves implanted during cardiopulmonary bypass (CPB) with extreme hemodilution, obtained with preoperative blood withdrawal, the use of blood-free priming fluid during perfusion, and retransfusion of autologous blood. Before operation, platelet adhesiveness as well as the reactivity of the intrinsic and extrinsic coagulation systems were markedly higher than in man. During CPB, the number of functioning platelets was very low, but increased after retransfusion, and were after 4 h twice as high as in 7 human patients who received aortic disc valves during CPB with extreme dilution.

Mitral disc valve implantation in the dog: early and late valve thrombosis and its prevention.

Valve thrombosis and its prevention was studied in 33 Labrador retriever dogs who received Hall-Haster mitral disc valves during extracorporeal circulation with extreme hemodilution. Three antithrombotic regimes were used. (1) 12 dogs received 1 g heparin preoperatively, and Warfarin tablets from the first postoperative day.

Monitoring of intracranial pressure after open-heart surgery.

Brain damage following open-heart surgery is receiving increasing attention. Efforts are being made to improve the setting for cardiac surgery so as to avoid such complications. When they occur, their recognition is retrospective, when the cerebral lesion is inevitable.