Willinger C C, Schramek H, Pfaller K, Pfaller W, Deetjen P
Institute of Physiology, University of Innsbruck, Austria.
Clin Nephrol. 1995 Jul;44(1):32-43.
To test the oxyphoretic properties and potential nephrotoxic side-effects of polymerized hemoglobin solutions, isolated rat kidneys were perfused in a recirculating system for 180 min. Group I was perfused with a substrate enriched Ringer solution containing hydroxyethylstarch (HES) to produce isoncotic conditions. In group II HES was substituted in part by UPPBHb (34 g/l) with a high portion of low molecular weight molecules (= UPPBHb1). In group III 34 g/l of UPPBHb containing an increased fraction of high molecular weight polymers (= UPPBHb2) was used. Only UPPBHb2-perfused kidneys showed a reduced renal perfusate flow (RPF, 13.3 +/- 1.1 ml/min g kw), when compared to HES-perfused controls (15.5 +/- 0.8) and UPPBHb1 (15.1 +/- 1.2). Glomerular filtration rate (GFR) was significantly higher in UPPBHb1-perfused kidneys (902 +/- 107 vs 633 +/- 55 microliters/min g kw for HES). This difference became even more pronounced in the third hour of perfusion (474 +/- 125 vs. 103 +/- 33). In contrast, UPPBHb2 produced low initial GFR levels of 385 +/- 25, which had only a minor tendency to decline with time. Parallel to GFR, absolute reabsorption of sodium (TNa) andoxygen consumption (QO2) showed values of 110 +/- 16 and 5.46 +/- 0.33 mumol/min g kw in UPPBHb1-kidneys vs 83 +/- 6 and 5.09 +/- 0.27 in controls and vs 53 +/- 4 and 3.66 +/- 0.12 in UPPBHb2-kidneys. Fractional excretion of sodium (FENa), of potassium (FEK), and of water (FEH2O) in UPPBHb1 and UPPBHb2-perfused kidneys were not significantly different from HES-perfused controls at any time of perfusion. Urinary flow rate (UFR) was similar in UPPBHb1- and HES-kidneys. Nevertheless, control kidneys tended to render oliguric during the third hour of perfusion (UFR 19.9 +/- 4.1 microliters/min g kw), whereas UPPBHb1 preserved urinary flow in a better way (83.7 +/- 32.4). UFR of UPPBHb2-kidneys was significantly reduced initially (30.2 +/- 5.1 vs. 105 +/- 33 for HES), but increased steadily up to 67 +/- 23. In the UPPBHb1 and HES group, all functional parameters determined declined dramatically within the third hour of perfusion, whereas UPPBHb2 produced functional stability. The in vivo reaction pattern of renal autoregulation was better preserved in UPPBHb-perfused kidneys than in HES-perfused controls: 74 +/- 6 vs. 59 +/- 5 vs. 42 +/- 4% (of full autoregulatory response) for UPPBHb1, UPPBHb2, and HES kidneys, respectively. Light- and electron microscopic analysis revealed major alterations only for the outer medulla of HES-kidneys.(ABSTRACT TRUNCATED AT 400 WORDS)
为测试聚合血红蛋白溶液的携氧特性及潜在的肾毒性副作用，在循环系统中对分离的大鼠肾脏进行180分钟的灌注。第一组用含有羟乙基淀粉（HES）的底物富集林格溶液灌注以产生等渗状态。在第二组中，HES部分被UPPBHb（34克/升）替代，其中低分子量分子比例较高（=UPPBHb1）。在第三组中，使用含有高分子量聚合物比例增加的34克/升UPPBHb（=UPPBHb2）。与HES灌注的对照组（15.5±0.8）和UPPBHb1（15.1±1.2）相比，仅UPPBHb2灌注的肾脏肾灌注液流量（RPF，13.3±1.1毫升/分钟·克肾重）降低。UPPBHb1灌注的肾脏肾小球滤过率（GFR）显著更高（902±107对HES的633±55微升/分钟·克肾重）。这种差异在灌注的第三个小时变得更加明显（474±125对103±33）。相比之下，UPPBHb2产生的初始GFR水平较低，为385±25，且随时间仅有轻微下降趋势。与GFR平行，UPPBHb1肾脏中钠的绝对重吸收（TNa）和氧消耗（QO2）的值分别为110±16和5.46±0.33微摩尔/分钟·克肾重，而对照组分别为83±6和5.09±0.27，UPPBHb2肾脏分别为53±4和3.66±0.12。在灌注的任何时间，UPPBHb1和UPPBHb2灌注的肾脏中钠（FENa）、钾（FEK）和水（FEH2O）的分数排泄与HES灌注的对照组无显著差异。UPPBHb1和HES肾脏的尿流率（UFR）相似。然而，对照组肾脏在灌注的第三个小时倾向于少尿（UFR 19.9±4.1微升/分钟·克肾重），而UPPBHb1更好地维持了尿流（83.7±32.4）。UPPBHb2肾脏的UFR最初显著降低（30.2±5.1对HES的105±33），但稳步增加至67±23。在UPPBHb1和HES组中，所测定的所有功能参数在灌注的第三个小时内均显著下降，而UPPBHb2产生了功能稳定性。UPPBHb灌注的肾脏中肾自动调节的体内反应模式比HES灌注的对照组保存得更好：UPPBHb1、UPPBHb2和HES肾脏分别为74±6%、59±5%和42±4%（完全自动调节反应）。光镜和电镜分析显示仅HES肾脏的外髓质有主要改变。（摘要截断于400字）
