Effects Of Sodium Pyruvate- Hydroxyethyl Starch On Renal Function In Rats With 50% Total Body Surface Aera Burn Injury

Objective: Although hydroxyethyl starch(HES 130/0.4), as a colloidal solution in intravenous fluid therapy for hypovolemic shock, enables to increase plasma colloid osmotic pressure and effective circulating blood volume, there are injurious to the kidney and fibrinolytic system. To overcome these adverse effects of HES is indeed urgently required. Our previous studies showed that intravenous or oral administration of pyruvate could reduce multiple organ dysfunction caused by burn shock. Therefore, we hypothesize that pyruvate replaces acetate and excess chloride as a carrier soluion in HES, sodium pyruvate-containing HES, Na Pyr-HES, in fluid resuscitation can reduce renal damage in resuscitation of hypovolemic shock. This study focused on 1. the comparison of Na Pyr-HES with Na Ace-HES and Na Cl-HES on kidney function by determinations of renal blood flow on the kidney surface, renal function and histopathological alteratons in shock rats with 50% TBSAIII ° scald injury; 2. the discussion of protective effects of Na Pyr-HES on renal impairment and possible underlying mechanisms.Methods:1 Animal Model180 male SD rats weighing 220g-270 g, acclimated for one week after purchase, were fasted over night and freely drink before surgery. Sodium pentobarbital(50mg/kg) by intraperitoneal injection was used for anesthesia. After cutting off the hair on the back and abdomen and inserting aspetically the jugular vein catheter, the rats were placed in a rectangular prefabricated form, the bare skin with protection of the remaining part was immersed in boiling water(100℃ water bath) for 15 seconds in back and 8 seconds in abdomen, caused 50% Total Body Surface Aera III°burn. Rats were dried after scald immediately. The rats in the sham control group were immersed into warm water(37℃, the back for 15 s and the abdomen for 8s). By using a specific vest fixed the rats with the connection of intravenous catheter and blood auxiliary devices and the infusion pump, placed rats back in the cage. The universal shaft device ensured continuous fluid infusion while rats were moving freely in the cage.2 Grouping and treatmentRats were divided into three experimental groups: burn with infusion of colloids of sodium pyruvate- hydroxyethyl starch(Na Pyr-HES) group(Group SP, N=40), sodium acetate- hydroxyethyl starch(Na Ace-HES, N=40) group(Group SA, N=40) and sodium chloride- hydroxyethyl starch(Na Cl-HES) group(Group SN, N=40), resectively. Another control groups were the sham burn group(Group S, N=40) and the burn with no fluid infusion group(Group N, N=20). According to different observation time, each scald group was divided into four subgroups: 4h,8h, 12 h and 24 h after scald(n=10) for research and compare changes in renal function in each group.3 Method and dosage of fluid resuscitation:Fluid infusion was taken via the jugular vein catheter. The total amount of intravenous fluids were 0.75ml/kg × 1% TBSA(1/2 colloidal rehydration formula) of various HES and the equal volume of Acetated Ringer’s solution(AR) with the colloid to crystalloid ratio of 1: 1 witnin 12 h resuscitation: infusion with AR for the first 4h followed by various HES for 8h. Micro-infusion pumps were used in strict accordance with the calculated infusion rate.4 Indicators detection and MethodsAt 4h, 8h, 12 h and 24 h after burns, the followings were conducted in each rat: vis laparotomy, renal blood flow(RBF) on the kidney surface measured by laser Doppler; renal vascular permeability in kidney tissues detected with the FITC assay; kidneys were harvested and kidney tissue water contents determined by the proportion of dry over wet method and the HE staining of renal tissues was examined for morphological alterations; Then, determinations of renal tissue homogenates were carried out for xanthine oxidase(XOD), hydrogen peroxide(H2O2), malondialdehyde(MDA) level changes. Finally, blood samples drawn from the abdominal aorta for plasma renal-specific indicators: neutrophils enzyme related lipid carrier protein gelatin(NGAL), alpha 1 microglobulin(α 1-MG) and cystatin C(Cyst-C) contents and Cr, BUN and the bladder puncture taken for urine texts of NGAL and α1-MG contents.Results:1 Renal blood flow(RBF): RBF in groups with burns and various fluid resuscitation after scald was significantly lower than that in group S, but higher than in group N(P<0.05); at 8h, 12 h and 24 h after injury, the RBF in the SP group was significantly higher than that in SA and SN groups(P<0.05), and ir was higher in group SA than in group SN(P<0.05).2 Renal vascular permeability: Renal vascular permeability was significantly higher in groups with burn and fluid infusion than in group S, but less than group(P<0.05), At 8h, 12 h and 24 h after injury, it was significantly lower in group SP and SN than in group SN(P<0.05), the group SP is lower than SA group only at 8h(P<0.05).3 Kidney tissue water content: The tissue moisture was increased in each group after injury, compared to the S group, but less than in the N group(P<0.05). The renal tissue water content was lower in the SP group than in SA and SN groups at 8h and 12 h time points, and it was lower in the SA group than in the SN group at 8h and 24h(P<0.05).4 Kidney tissue Pathology: Renal tissue pathological exams showed obvious alterations after injury in each rehydration group and damage was also various at each time point. Kidney damage was significantly lighter in the SP group than in the SN group at each time point, the pathological alteration was attenuated in the SA group, compared to the SN group at 8h and12 h, but it appeared no significant different at 24 h among resuscitation groups.5 The content of renal tissue XOD activity and H2O2, MDA: H2O2, MDA and XOD levels of renal tissues were significantly higher in each group after injury than in the S group, but less than in the N group(P<0.05); at 8h, 12 h and 24 h after injury, H2O2 and MDA contents were significantly lower in SP and SA groups than in the SN group, the XOD activity at 8h and 12 h was significantly lower in the SP than in the SA group(P<0.05), but only at 8h were H2O2 and MDA contents of the SP group significantly lower relative to the SA group(P<0.05), there were no significant differences among the two infusion groups at 24 h.6 Blood NGAL, Cyst-C and α-MG contents: Blood NGAL, Cyst-C and α1-MG levels were higher in various fluid resuscitation groups than in the S group, but less than in the N group at each time point(P<0.05), they were significantly lower in the SP and SA groups, compared to the SN group at 8h, 12 h and 24 h after injury(P<0.05); NGAL and α1-MG contents were lower in group SP than in group SA(P<0.05) at the times of 8h and 12 h after burn injury; the Cyst-C content of the SP group was significantly lower compared to the SA group at(the time of) 8h only(P<0.05).7 Urine NGAL and α1-MG contents: Urine NGAL and α-MG levels were significantly higher in various fluid resuscitation groups than in the S group, but less than in the N group at each time point(P<0.05), while the urine NGAL content was significantly lower in the SP and SA groups than in the SN group at(all) the two time points after 8h(P<0.05); it was significantly lower in group SP relative to group SA at 8h(P<0.05); urinary α1-MG between SP and SA group at each time point was not significant different.8 Plasms creatinine(Cr) and blood urea nitrogen(BUN) levels: Cr levels showed no significant differences among each group expect group N, but were lower, compared to group N at 4h, 8h and 12h(P<0.05). The levles were hghter in all injuried groups than in the S group at all time points(P<0.05). The creatinine began gradually to rise since 12 h in the three groups with fluid infusion,and the level was profoundly increased in the groups, but was lower in the SP group than in SA and SN groups and also lower in group SA relative to group SN at 24h(P <0.05). BUN levels showed no significant differences among each group expect group N, but were lower, compared to group N at 4h, 8h and 12h(P<0.05),The levels were significantly lower in group SP than in groups SA and SN(P<0.05) and also markedly lower in the SA group than in the SN group at 24 h(P<0.05).Conclusion:1 Present data for the first time indicated that compared with Na Cl-HES and Na Ace-HES, Na Pyr-HES(130/0.4) increased renal blood flow, reduced renal vascular permeability and edema in renal tissues and improved renal function and histopathological damage in rats subjected to burn injury. Na Pyr-HES was superior to Na Ace-HES and Na Cl-HES in the renal protection in burns, which may be of a potential clinical value.2 Na Pyr-HES could significantly improve kidney ischemia, reduce renal oxidative and specific kidney indicators level, this might be one of the mechanism that Na Pyr-HES protecting kidney.