The saline infusion test for primary aldosteronism: implications of immunoassay inaccuracy

Context Diagnosis of primary aldosteronism (PA) for many patients depends on positive results for the saline infusion test (SIT). Plasma aldosterone is often measured by immunoassays, which can return inaccurate results. Objective Establish whether differences in aldosterone measurements by immunoassay versus mass spectrometry (MS) might impact confirmatory testing for PA. Methods This study, involving 240 patients tested using the SIT at five tertiary-care centers, assessed discordance between immunoassay and MS-based measurements of plasma aldosterone. Results Plasma aldosterone measured by Liaison and iSYS immunoassays were respectively 86% and 58% higher than by MS. With an immunoassay-based SIT cut-off for aldosterone of 170 pmol/L, 78 and 162 patients had respective negative and positive results. All former patients had MS-based measurements of aldosterone <117 pmol/L, below MS-based cutoffs of 162 pmol/L. Among the 162 patients with pathogenic SIT results, MS returned non-pathologic results in 62, including 32 under 117 pmol/L. Repeat measurements by an independent MS method confirmed non-pathogenic results in 53 patients with discordant results. Patients with discordant results showed a higher (P<0.0001) prevalence of non-lateralized than lateralized adrenal aldosterone production than patients with concordant results (83%vs28%). Among patients with non-lateralized aldosterone production, 66% had discordant results. Discordance was more prevalent for the Liaison than iSYS immunoassay (32%vs16% P=0.0065) and was eliminated by plasma purification to remove interferents. Conclusions These findings raise concerns about the validity of immunoassay-based diagnosis of PA in over 60% of patients with presumed bilateral disease. We provide a simple solution to minimize immunoassay inaccuracy-associated misdiagnosis of PA.

Roasted Tartary Buckwheat Bran as a Material for Producing Rutin-Rich Tea Beverages

Tartary buckwheat bran, a byproduct of buckwheat milling, is commonly treated as waste. The present study examined the rutin content during successive infusions of roasted Tartary buckwheat bran and grain to develop a functional Tartary buckwheat tea. Samples (6 g) of roasted Tartary buckwheat bran and grain were rinsed with 300 mL of hot water (>95 °C) for 0.5 min. For the first infusion test, the tea infusion sample of roasted Tartary buckwheat bran contained a distinctly higher amount of rutin (389 mg/L) than that of the roasted Tartary buckwheat grain (68 mg/L). Overall, rutin was more effectively extracted from roasted Tartary buckwheat bran, as compared to roasted Tartary buckwheat grain.

Analysis of relative changes in pulse shapes of intracranial pressure and cerebral blood flow velocity during infusion test

Objective: Analysis of relative changes in the shapes of pulse waveform of intracranial pressure (ICP) and transcranial Doppler cerebral blood flow velocity (CBFV) may provide information on intracranial compliance. We tested this hypothesis, introducing an index named the Ratio of Pulse Slopes (RPS) that is based on inclinations of the ascending parts of ICP and CBFV pulse waveforms. It has hypothetically a simple interpretation: 1 – good compliance, the less than 1, reduced compliance. Here, we investigated the usefulness of RPS for intracranial compliance assessment. Approach: ICP and CBFV signals recorded simultaneously in 30 normal pressure hydrocephalus patients during infusion test were retrospectively analysed. CBFV was measured in the middle cerebral artery. Changes in RPS during the test were compared to changes in the height ratio of the first and second peak of ICP pulse (P1/P2) and the shape of ICP pulse classified from normal (1) to pathological (4). Values are medians (lower, upper quartiles). Main results: There was a significant correlation between baseline RPS and brain elasticity (R = -0.55, p=0.0018). During infusion test, both RPS and P1/P2 decreased with rising ICP (RPS: 0.80 (0.56, 0.92) vs. 0.63 (0.44, 0.80), p = 0.00015; P1/P2: 0.58 (0.50, 0.91) vs. 0.52 (0.36, 071), p=0.00009) while the ICP pulses became more pathological in shape (class: 3 (2, 3) vs. 3 (3, 4), p=0.04). The magnitude of decrease in RPS during infusion was inversely correlated with baseline P1/P2 (R= -0.40, p<0.03). Significance: During infusion, the slopes of ascending parts of ICP and CBFV pulses become increasingly divergent with a shift in opposite directions. RPS seems a promising methodological tool to monitor brain compliance with no additional volumetric manipulation required.

Total Effective Vascular Compliance of a Global Mathematical Model for the Cardiovascular System

In this work, we determined the total effective vascular compliance of a global closed-loop model for the cardiovascular system by performing an infusion test of 500 mL of blood in four minutes. Our mathematical model includes a network of arteries and veins where blood flow is described by means of a one-dimensional nonlinear hyperbolic PDE system and zero-dimensional models for other cardiovascular compartments. Some mathematical modifications were introduced to better capture the physiology of the infusion test: (1) a physiological distribution of vascular compliance and total blood volume was implemented, (2) a nonlinear representation of venous resistances and compliances was introduced, and (3) main regulatory mechanisms triggered by the infusion test where incorporated into the model. By means of presented in silico experiment, we show that effective total vascular compliance is the result of the interaction between the assigned constant physical vascular compliance and the capacity of the cardiovascular system to adapt to new situations via regulatory mechanisms.