adrenomedullin and Acidosis

To examine concentrations of three cardiovascular propeptides in umbilical cord plasma of neonates born to mothers with Type 1, Type 2 and gestational diabetes. Measurement of cardiovascular markers in umbilical cord plasma may potentially help identify neonates at risk of postnatal complications. Neonates born to mothers with diabetes have an increased risk of neonatal morbidity and mortality, and measurement of these new biomarkers may potentially help identify neonates at risk of these complications.. Copeptin, midregional proadrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) were measured in cord plasma of neonates (n = 63) born to mothers with the three types of diabetes. Associations with maternal glycemic control, mode of delivery and neonatal metabolic acidosis were examined.. Umbilical cord plasma copeptin concentrations were lowest in neonates after elective cesarean sections (6.1 pmol/l; interquartile range [IQR]: 4.5-9.1) compared with emergency cesarean sections (156 pmol/l; IQR: 9.6-311; p = 0.019) and vaginal delivery (831 pmol/l; IQR: 107-2407; p < 0.0001). MR-proADM was also affected by mode of delivery; however, this seemed more likely to be caused by an inverse association with the acid-base balance. In this population, only MR-proANP plasma concentrations were related to type of diabetes. Neonates born to mothers with Type 1 diabetes had higher concentrations (median 260 pmol/l; IQR: 222-318) compared with Type 2 diabetes (175 pmol/l; IQR: 169-200; p = 0.003) and gestational diabetes (200 pmol/l; IQR: 149-276; p = 0.009).. Umbilical cord plasma copeptin and MR-proADM concentrations primarily reflect perinatal stress associated with mode of delivery and the degree of fetal acidosis, whereas MR-proANP concentrations are higher in neonates born to mothers with Type 1 diabetes.

Topics: Acidosis; Adrenomedullin; Adult; Atrial Natriuretic Factor; Biomarkers; Delivery, Obstetric; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Blood; Glycopeptides; Humans; Infant, Newborn; Maternal-Fetal Relations; Pregnancy; Protein Precursors; Stress, Psychological

Management of trauma victims with uncontrolled hemorrhage remains a major problem in combat casualty care at the far-forward battlefield setting. The neuroendocrine response to hemorrhage is to maintain perfusion to the heart and brain, often at the expense of other organ systems. Decreased organ perfusion after hemorrhagic shock is associated with metabolic acidosis, in which the up-regulated endothelin-1 plays an important role. We have recently shown that vascular responsiveness to adrenomedullin (AM), a newly discovered vasodilator peptide, is depressed after hemorrhage and resuscitation. Down-regulation of AM binding protein (AMBP-1) appears to be responsible for this hyporesponsiveness. We therefore hypothesized that administration of AM/AMBP-1 would prevent metabolic acidosis after uncontrolled hemorrhage via down-regulation of endothelin-1.. Prospective, controlled, and randomized animal study.. A research institute laboratory.. Male Sprague-Dawley rats (275-325 g).. A rat model of uncontrolled hemorrhage with an extremely low volume of fluid resuscitation was used to mimic the combat situation.. Both lumbar veins of male adult rats were isolated and severed at the junction to the vena cava. The abdomen was kept open but covered with a saline wet gauze for 45 mins and then closed in layers. The animals received 1 mL of normal saline (vehicle) with or without AM (12 microg/kg of body weight) and AMBP-1 (40 microg/kg of body weight) over 45 mins. Various variables were measured at 4 hrs after resuscitation. The bleed-out volumes in the vehicle group and the AM/ AMBP-1 treatment group were 6.78 +/- 0.19 and 6.81 +/- 0.25 mL/rat, respectively. The results indicate that AM/AMBP-1 administration prevented metabolic acidosis, mitigated organ injury, down-regulated preproendothelin-1 gene expression, and decreased plasma levels of endothelin-1 after hemorrhage.. AM/AMBP-1 may provide a novel approach for the treatment of uncontrolled hemorrhage. The beneficial effect of AM/AMBP-1 is associated with down-regulation of endothelin-1.

Topics: Acidosis; Adrenomedullin; Animals; Blood Volume; Cardiac Output; Complement Factor H; Down-Regulation; Endothelin-1; Gene Expression; Hematocrit; Male; Oxygen; Rats; Rats, Sprague-Dawley; Renal Circulation; Resuscitation; RNA, Messenger; Shock, Hemorrhagic; Vasodilator Agents