Nephrol Dial Transplant (2003) 18: 1677-1678
© 2003 European Renal Association-European Dialysis and Transplant Association
Letters
Is coating of tubing required when endothelin-1 is infused intravenously?
Department of Nephrology and Hypertension University Medical Centre Utrecht The Netherlands Email: p.boer{at}azu.nl
Sir,
To prevent irreproducible results caused by adsorption losses, inert proteins are often added to buffers used in radioimmunological determinations of peptides in order to coat the walls of the assay tubes. Such adhesion preventing substances are not always used in preparing solutions of biologically active peptides for i.v. infusion. Both saline without additions [1,2] and saline with albumin [3] or modified polypeptide gelatins such as Polygeline [4] or Haemaccel [5–7] have been used as the vehicle. To investigate whether or not such additions are required, we compared changes in plasma endothelin-1 (ET-1) levels, blood pressure and kidney function in five healthy men during infusion of ET-1 dissolved in saline with or without the modified gelatin Gelofusine.
The study consisted of a 3 x 30 min baseline period, a 3 x 30 min vehicle period (Gelofusine or saline) and a 4 x 30 min ET-1 period (ET-1 dissolved in Gelofusine or saline, infused at a rate of 2.5 ng/min/kg body weight). The study was performed in a randomized two-way crossover design, separated by an interval of 3 days. Plasma ET-1 was measured by radioimmunoassay [7]. Systemic effects were monitored by measuring mean arterial pressure (MAP). Renal effects were assessed by measuring glomerular filtration rate (GFR, inulin clearance), effective renal plasma flow (ERPF, para-amino-hippurate clearance), filtration fraction (FF, from GFR and ERPF), renal blood flow (RBF, from ERPF and haematocrit), sodium excretion rate (NaE), and renal vascular resistance (RVR, from MAP and RBF) [7]. Statistical analysis was performed by two-way ANOVA for repeated measures and the studentized Newman–Keuls test for multiple comparisons on the means of the last two 30 min collections of the baseline, vehicle and ET-1 periods.
The results are shown in Table 1. During vehicle infusion (Gelofusine or saline), no significant changes occurred. During ET-1 infusion, plasma ET-1 levels increased significantly, but the increase was significantly larger when ET-1 was dissolved in Gelofusine. The ET-1 concentration in the infusion fluid did not differ from the expected value of 150 ng/ml (153 ± 6 ng/ml at the start, 152 ± 8 ng/ml at the end). When dissolved in saline, the ET-1 concentration at the start was significantly lower (83 ± 8 ng/ml) and dropped to still lower values at the end (38 ± 4 ng/ml). Taken together, the increases in plasma ET-1 were significantly correlated to the concentrations in the infusion fluid (Spearman rank correlation, r = 0.65, P = 0.04).
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MAP increased during ET-1 infusion, but the increase reached significance only when Gelofusine was used as the vehicle. Likewise, GFR decreased only significantly using Gelofusine. FF increased significantly and to the same extent both with saline and Gelofusine. RBF and NaE decreased significantly and RVR increased significantly both with saline and Gelofusine, but using Gelofusine the changes were significantly larger.
In sum, the directions of the systemic and renal effects of ET-1 dissolved in Gelosine or saline were as anticipated, but the effects were significantly stronger when ET-1 was dissolved in Gelofusine. We measured ET-1 concentrations both in infusion fluid and in plasma. Although the aim of using Gelofusine is to prevent adsorption of ET-1 to tubing and syringes, theoretically Gelofusine itself might also (unintentionally) bind ET-1, in which case the use of an additive would not be of great help. Apparently, this problem does not occur, as judged by the considerably higher ET-1 concentrations in Gelofusine containing infusion fluid and the concomitantly higher ET-1 plasma concentrations and stronger effects on MAP and renal function compared to those of saline. We conclude that the presence of an adhesion-preventing additive in the infusion solution is required when ET-1 is administered intravenously.
References
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[Abstract/Free Full Text]
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