Absorption Of Albumin In The Subeschar Tissue Fluid And Its Pharmacokinetics Of The Burned Rabbits

Albumin can penetrate into the subeschar fluid (STF) and retent in it at the early stage after burn. These albumin would cause a decreasion of the plasma protein concentration, which resulting a sharp decline of the plasma colloid osmotic pressure (COP) and an increasion of the tissue fluid COP, and also enhancing the formation of edema after burn, that leading to further varieties of physiological and pathological changes of the body after burn. Vascular permeability would be increased after injury, the protein in the burn subeschar liquid are similar to serum levels, approximately 80% of plasma protein mainly albumin. Albumin infiltrated into and retented in subeschar fluid, that lowered the plasma protein concentration. But the albumin would keep in a stable state? Or it could be leaked out and absorpted as the small molecules? And the albumin returned could still play a relevant physiological function? All these need to be answered through the experiment.Our study tried to reveal the patterns of albumin distribution in the subeschar fluid. We establish the burned rabbit model, inject human albumin as tracer albumin into the subeschar of the burned rabbits, and then test the concentration of human albumin in blood to observe the dynamics parameters, analyze the pharmacokinetic changes, and finally we discovered some useful things on its distribution patterns. ObjectiveWe establish the burn model of rabbits and inject human albumin into their subscar. Test human albumin concentration of the blood to observe the dynamics of albumin, and then analyze the pharmacokinetic changes. All these are in order to reveal the distribution of macromolecules in the third space after burn.Methods1. Absorption of albumin in the subeschar tissue fluid and its pharmacokinetics of 8% TBSA third-degree burned rabbits Divide 34 New Zealand rabbits into experimental group and control group according to the random number table, each of 17. After feeding for 1 week, shear the back of the rabbits, and remove the hair by using sodium sulfide, induce anesthesia in the rabbits by using sodium pentobarbital, make the experimental group rabbits into a 8% TBSA third-degree burn(confirmed by the pathological section) model by useing the electricity burns instrument scald rabbits back for 15s in 100℃. Then inject human albumin into the subescar with a dose of 10ml (containing 1g human albumin) immediately after burn. Set rabbits free for drinking. Take 1.5ml blood samples at 2h, 4h, 8h, 16h, 24h, 48h, 72h after injury; Take the same treatment measures to the control group escept no burning. Put the blood samples aside for 2 hours, centrifugate them at 2100r/min for 15min, then use double-antibody (first anti-serum is the rabbit anti-human albumin antibody, second anti-serum is goat anti-rabbit IgG antibody) to detect the tracer albumin concentration, use biochemical analyzer to detect rabbit serum albumin. Calculate the pharmacokinetic parameters by 3P97 and analyze it by the statistical software SPSS13.0.2. Absorption of albumin in the subeschar tissue fluid and its pharmacokinetics of 40% TBSA third-degree burned rabbits Divide 40 New Zealand rabbits into experimental group and control group according to the random number table, each of 20. After feeding for 1 week, shear the back of the rabbits, and remove the hair by using sodium sulfide, induce anesthesia in the rabbits by using sodium pentobarbital, make the experimental group rabbits into a 40% TBSA third-degree burn(confirmed by the pathological section) model by useing the electricity burns instrument scald rabbits back for 15s in 100℃. Then inject human albumin into the subescar with a dose of 10ml (containing 1g human albumin) immediately after burn. Set rabbits free for drinking. Take 1.5ml blood samples at 2h, 4h, 8h, 16h, 24h, 48h, 72h, 96h, 120h after injury; Take the same treatment measures to the control group escept no burning. Put the blood samples aside for 2 hours, centrifugate them at 2100r/min for 15min, then use double-antibody (first anti-serum is the rabbit anti-human albumin antibody, second anti-serum is goat anti-rabbit IgG antibody) to detect the tracer albumin concentration, use biochemical analyzer to detect rabbit serum albumin. Calculate the pharmacokinetic parameters by 3P97 and analyze it by the statistical software SPSS13.0.Results1. There is a small absorption peak of tracer albumin at 8～48 hours after injection in control group: the control group of 8% TBSA come up to (180±12)μg/L, the control group of 40% TBSA come up to (209±9)μg/L. However, the all the tracer albumin absorpted (the area under the curve AUC) is about 10-3 times than the rabbit albumin.2. In the 8% TBSA third-degree burn, the tracer albumin concentration of experimental group reached the peak (421±10)μg/L at 8h; Pharmacokinetics analysis showed that it fitted two-compartment model best (W=1/C2). The distribution phase half-life (t1/2α) of tracer albumin experimental group is 4.0271h, significantly shorter than the control group t1/2α(12.0907h); The AUC of experimental group is 22336.38μg?h/ml, significantly more than the control group (5827.77μg?h/ml).3. In the 40% TBSA third-degree burn, the tracer albumin concentration of experimental group reached the peak (423±27)μg/L at 16h; Pharmacokinetics analysis showed that it fitted two-compartment model best (W=1/C2). The distribution phase half-life (t1/2α) of experimental group is 1.7326h, shorter than the control group t1/2α(8.8182h), and also shorter than 8% TBSA group t1/2α(4.0271h) ; The AUC of experimental group is 88814.84μg?h/ml, more than the control group (13738.47μg?h/ml), and also greater than 8% TBSA group (22336.38μg?h/ml).ConclusionThe results showed that:1. There is also the absorption phenomenon of the macromolecular substances such as albumin in the tissue under normal circumstances. its absorption rate and amount are both too smaller to influence the albumin concentration of plasma (the twe have 103 times in difference).2. The distribution phase half-life (t1/2α) of experimental group was significantly shorter than the control group, the area under the curve (AUC) of experimental group also increased significantly. All these indicate that the absorption of albumin would become earlier under the influence of burn, The absorption speed and volume will also be increased.3. With the aggravation of injury, the distribution phase half-life (t1/2α) of experimental group become shorter, the area under the curve (AUC) of experimental group increased. Tt shows that the time, speed and volume of the albumin absorption has something to do with the severity of burn.