The purpose of this study was to determine both the short-term effects on cardiac development and embryo growth and the long-term effects on cardiac function and body composition of in utero caffeine exposure. Pregnant mice (C57BL/6) were exposed to hypoxia (10% O(2)) or room air from embryonic days (E) 8.5-10.5, and treated with caffeine (20 mg/kg, i.p.) or vehicle (normal saline, 0.9% NaCl). This caffeine dose results in a circulating level that is equivalent to 2 cups of coffee in humans. Hypoxic exposure acutely reduced embryonic growth by 30%. Exposure to a single dose of caffeine inhibited cardiac ventricular development by 53% in hypoxia and 37% in room air. Caffeine exposure resulted in inhibition of hypoxia-induced HIF1alpha protein expression in embryos by 40%. When offspring from dams treated with a single dose of caffeine were studied in adulthood, we observed that caffeine treatment alone resulted in a decrease in cardiac function of 38%, as assessed by echocardiography. We also observed a 20% increase in body fat with male mice exposed to caffeine. Caffeine was dissolved in normal saline, so it was used as a control. Room air controls were used to compare to the hypoxic mice. Exposure to a single dose of caffeine during embryogenesis results in both short-term effects on cardiac development and long-term effects on cardiac function.
Heart failure is a common problem in the ever growing population of patients with palliated congenital heart disease. It is frequently complicated by hyponatremia that has been associated with increased morbidity and mortality. Tolvaptan is a vasopressin receptor antagonist that has been effective in improving hyponatremia and congestive symptoms in adults with chronic heart failure. We describe the short-term use of tolvaptan to treat hyponatremic hypervolemia in an adolescent patient with chronic heart failure in the setting of palliated congenital heart disease prior to definitive surgical intervention. In this case, the patient had improvement in hyponatremia and a decrease in body weight, without any adverse effects.
Introduction: Acute kidney injury (AKI) is a common and serious complication in patients undergoing cardiac surgery and is associated with adverse outcomes. TIMP-2 and IGFBP-7 are cell cycle arrest proteins that are detected in urine during periods of kidney stress or injury. The NephroCheck™ system measures urine concentrations of these two biomarkers and calculates a score which has been validated in adults as a predictor of AKI. The utility of these markers in identifying AKI in neonates after congenital heart surgery (CHS) has not been determined. Hypothesis: Concentrations of TIMP-2 and IGFBP-7 as measured by the NephroCheck™ system will be elevated in neonates with AKI following CHS requiring cardiopulmonary bypass (CPB). Methods: We conducted a single center, prospective, observational study in neonates less than 31 days old undergoing CHS requiring CPB between 9/2017 and 5/2019. Urine samples were collected and analyzed using the NephroCheck™ system prior to surgery and at 6, 12, 24 and 96 hours (h) post CPB. All patients were evaluated for staging of AKI using the Acute Kidney Injury Network criteria (AKIN). Wilcoxon Rank Sum tests were used to compare the medians of the NephroCheck™ values in the AKIN negative and positive groups for each of the time points. ROC curves and AUCs with 95% CIs were used to measure how well the NephroCheck™ values predict the AKIN negative and positive status of the patients. Results: Thirty-six patients were included, 56% were male. Median age and weight were 7 days and 3.14 kg. Pre-surgically, no patients met AKI definition by AKIN criteria or by NephroCheck™ values. Post surgically, 52% of patients had AKI by AKIN criteria. All patients with AKI had elevated biomarkers. The presence of elevated biomarkers as determined by NephroCheck™ had a statistically significant association for the presence of AKI at the 6 h (p = 0.036) and 24 h (p = 0.00037) time points. Of all time points analyzed, samples obtained at 24h were best at predicting the development of AKI in the post-surgical period (AUC: 0.848). Conclusions: Elevation in urine concentration of TIMP-2 and IGFBP-7 is associated with AKI in neonates after CHS requiring CPB. Urinary biomarkers levels 24 h after CPB are good predictors of AKI in this population.
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