Assay interference as a cause of false positive troponin T elevation in emergency department patients.

BACKGROUND: Troponin assays are used in the diagnosis of myocardial injury and may show elevated results for a variety of reasons. However it is increasingly recognised that cardiac troponin elevation may in some cases be due to assay interference. This is of significant importance as a misdiagnosis of myocardial injury may lead to unnecessary and potentially harmful investigation and treatment for patients. We sought to confirm the accuracy of cardiac high sensitivity troponin T (chsTnT) elevation in an unselected group of patients presenting to the emergency department, by using a second confirmatory cardiac high sensitivity troponin I (chsTnI) assay. METHODS: We identified patients presenting to two local emergency departments over a five-day period who had chsTnT levels measured as part of routine clinical care. All samples with elevated chsTnT levels (above the 99% centile URL) were retested for chsTnI in order to confirm true myocardial injury. RESULTS: A total of 74 samples from 54 patients were analysed for chsTnT and chsTnI. 7 samples (9.5%) had chsTnI levels < 5 ng/L suggesting assay interference as the cause of chsTnT elevation. CONCLUSIONS: Assay interference leading to false positive troponin elevation may be more common than many physicians appreciate and can potentially lead to harmful investigation and treatment for patients. In cases where the diagnosis of myocardial injury is uncertain, a second alternative troponin assay should be performed to confirm true myocardial injury.

Vasoactive and permeability effects of vascular endothelial growth factor-165 in the term in vitro dually perfused human placental lobule.

Vascular endothelial growth factor (VEGF) is an important vasodilator and effector of permeability in systemic blood vessels. Molecular and tissue culture techniques have provided evidence for its placental synthesis and release. Using an in vitro dual-perfusion model of the term placental lobule from normal pregnancy, we report here the relative secretion of total VEGF, soluble VEGF receptor (VEGFR)-1, and free VEGF into the maternal and fetoplacental circulations of the placenta. We tested the hypothesis that VEGF has vasomotor and permeability effects in the fetoplacental circulation of the human placenta, and we examined the broad intracellular pathways involved in the vasodilatory effect that we found. We show that total VEGF is released into the fetal and maternal circulations in a bipolar fashion, with a bias toward maternal side output. Soluble VEGFR-1 was also secreted into both circulations with bias toward the maternal side. Consequently, free VEGF (12.8 +/- 2.4 pg/ml, mean +/- se) was found only in the fetoplacental circulation. VEGF-165 was found to be a potent vasodilator of the fetoplacental circulation (maximum response: 77% of previous steady-state fetal-side inflow hydrostatic pressure after preconstriction with U46619; EC(50) = 71 pm). This vasodilatory effect was mediated by the VEGFR-2 receptor and nitric oxide in a manner-independent of the involvement of prostacyclin and the src-family tyrosine kinases. However, nitric oxide could explain only 50% of the vasodilatory effect. Finally, we measured the permeability of the perfused placenta to inert hydrophilic tracers and found no difference in the presence and absence of VEGF.