Background Increased vascular permeability is an early sign of vascular damage and can be measured with the transcapillary escape rate of albumin (TERalb). Although TERalb has a multi-exponential kinetic model, most published TERalb data are based on mono-exponential kinetic models with variation in blood sampling schemes. Aim of this posthoc study was to evaluate the influence of variation in blood sampling schemes and the impact of mono- or bi-exponential analyses on the calculation of TERalb. Study participants were part of a cross-over intervention study protocol, investigating effects of sodium loading on blood pressure, endothelial surface layer and microcirculation. Multiple blood samples were drawn between 3 and 60 min after injection of radioactive iodide labeled human serum albumin (rHSA). Results In total 27 male participants with 54 measurements were included. For all participants the maximum serum radioactivity was reached within 20 min, while 85% of the participants had their maximum serum activity within 10 min. The TERalb calculated with the subsequently chosen T20–60 min reference scheme (6.19 ± 0.49%/h) was significantly lower compared to the TERalb of the T3–60 min, T5–60 min, and Tmax – 60 min schemes. There was no significant difference between the T20–60 min reference scheme and the T10–60 min and T15–60 min schemes. Bi-exponential kinetic modeling did not result in significant different observations compared to the mono-exponential kinetic analysis. Conclusions As there is variation in the timing of the maximum serum radioactivity of rHSA, blood sampling schemes starting before 10 min after administration of rHSA will result in a significant overestimation of TERalb. In addition, variation in kinetic modeling did not result in significant changes in TERalb. Therefore, we emphasize the need to standardize TERalb and for practical and logistical reasons advocate the use of a mono-exponential model with blood sampling starting 20 min after rHSA administration.

BackgroundIncreased vascular permeability is an early sign of vascular damage and can be measured with the transcapillary escape rate of albumin (TERalb). Although TERalb has a multi-exponential kinetic model, most published TERalb data are based on mono-exponential kinetic models with variation in blood sampling schemes. Aim of this study was to evaluate the influence of variation in blood sampling schemes and the impact of mono- or bi-exponential analyses on the calculation of TERalb. Study subjects were part of a cross-over intervention study protocol, investigating effects of sodium loading on blood pressure, endothelial surface layer and microcirculation. Multiple blood samples were drawn between 3 and 60 minutes after injection of radioactive iodide labeled human serum albumin (rHSA). ResultsIn total 27 male subjects were included. For all subjects the maximum serum radioactivity was reached within 20 minutes, while 86% of the subjects had their maximum serum activity within 10 min. The TERalb calculated with the subsequently chosen T20 – 60 min reference scheme (5.97 ± 0.39%/h) was significantly lower compared to the TERalb of the T3 – 60 min, T5 – 60 min, T10 – 60 min, and Tmax – 60 min schemes. There was no significant difference between the T20 – 60 min reference scheme and the T15 – 60 min scheme. Bi-exponential kinetic modeling did not result in significant different observations compared to the mono-exponential kinetic analysis.ConclusionsAs there is variation in the timing of the maximum serum radioactivity of rHSA, blood sampling schemes starting before 15-20 minutes after administration of rHSA will result in a significant overestimation of TERalb. In addition, variation in kinetic modeling did not result in significant changes in TERalb. Therefore, we emphasize the need to standardize TERalb and for practical and logistical reasons advocate the use of a mono-exponential model with blood sampling starting 20 minutes after rHSA administration.

Background Increased vascular permeability is an early sign of vascular damage and can be measured with the transcapillary escape rate of albumin (TERalb). Although TERalb has a multi-exponential kinetic model, most published TERalb data are based on mono-exponential kinetic models with variation in blood sampling schemes. Aim of this posthoc study was to evaluate the influence of variation in blood sampling schemes and the impact of mono- or bi-exponential analyses on the calculation of TERalb. Study participants were part of a cross-over intervention study protocol, investigating effects of sodium loading on blood pressure, endothelial surface layer and microcirculation. Multiple blood samples were drawn between 3 and 60 minutes after injection of radioactive iodide labeled human serum albumin (rHSA). Results In total 27 male participants with 54 measurements were included. For all participants the maximum serum radioactivity was reached within 20 minutes, while 85% of the participants had their maximum serum activity within 10 min. The TERalb calculated with the subsequently chosen T20 – 60 min reference scheme (6.19 ± 0.49%/h) was significantly lower compared to the TERalb of the T3 – 60 min, T5 – 60 min, and Tmax – 60 min schemes. There was no significant difference between the T20 – 60 min reference scheme and the T10 – 60 min and T15 – 60 min schemes. Bi-exponential kinetic modeling did not result in significant different observations compared to the mono-exponential kinetic analysis.Conclusions As there is variation in the timing of the maximum serum radioactivity of rHSA, blood sampling schemes starting before 10 minutes after administration of rHSA will result in a significant overestimation of TERalb. In addition, variation in kinetic modeling did not result in significant changes in TERalb. Therefore, we emphasize the need to standardize TERalb and for practical and logistical reasons advocate the use of a mono-exponential model with blood sampling starting 20 minutes after rHSA administration.