cyclic-gmp and Respiratory-Distress-Syndrome--Newborn

Infant respiratory distress syndrome (RDS) involves inflammatory processes, causing an increased expression of inducible heme oxygenase with subsequent production of carbon monoxide (CO). We hypothesized that increased production of CO during RDS might be responsible for increased plasma levels of vasodilatory cGMP and, consequently, low blood pressure observed in infants with RDS. Fifty-two infants (no-RDS, n = 21; RDS, n = 31), consecutively admitted to the neonatal intensive care unit (NICU) between January and October 2003 were included. Hemoglobin-bound carbon monoxide (COHb), plasma cGMP, plasma nitric oxide (NOx), and bilirubin were determined at 0-12, 48-72, and at 168 h postnatally, with simultaneous registration of arterial blood pressure. Infants with RDS had higher levels of cGMP and COHb compared with no-RDS infants (RDS vs. no-RDS: cGMP ranging from 76 to 101 vs. 58 to 82 nmol/l; COHb ranging from 1.2 to 1.4 vs. 0.9 to 1.0%). Highest values were reached at 48-72 h [RDS vs. no-RDS mean (SD): cGMP 100 (39) vs. 82 (25) nmol/l (P < 0.001); COHb 1.38 (0.46) vs. 0.91 (0.26)% (P < 0.0001)]. Arterial blood pressure was lower and more blood pressure support was needed in RDS infants at that point of time [RDS vs. no-RDS mean (SD): mean arterial blood pressure 33 (6) vs. 42 (5) mmHg (P < 0.05)]. NOx was not different between groups and did not vary with time. Multiple linear regression analysis showed a significant correlation between cGMP and COHb, suggesting a causal relationship. Mean arterial blood pressure appeared to be primarily correlated to cGMP levels (P < 0.001). We conclude that a CO-mediated increase in cGMP causes systemic vasodilation with a consequent lower blood pressure and increased need for blood pressure support in preterm infants with RDS.

Topics: Biomarkers; Blood Pressure; Carbon Monoxide; Cyclic GMP; Humans; Hypotension; Infant, Newborn; Respiratory Distress Syndrome, Newborn; Statistics as Topic

A low blood pressure is common in preterm infants with respiratory distress syndrome (RDS). A diminished vascular resistance appears to be an important cause. The endogenous production of nitric oxide (NO), a mediator of vascular smooth muscle relaxation, has been shown to be higher in infants with RDS than in those without. Infants with persistent pulmonary hypertension showed decreased endogenous NO levels as compared with controls. Severe RDS in preterm infants may be accompanied by persistent pulmonary hypertension. To elucidate the role of NO in RDS and low blood pressure, we determined the endogenous NO production in infants with and without RDS by measuring urinary nitrite and nitrate excretions and plasma cGMP levels. In consecutively admitted preterm infants (gestational age <32 weeks), urine samples for measurement of NO(2) and NO(3) and plasma samples for the determination of the cGMP concentrations were serially collected during the 1st week of life. Arterial blood pressure, therapy to support blood pressure, and additional relevant clinical data were registered simultaneously. 27 infants with and 39 without RDS were included. The urinary NO(x) levels increased in all patients and were not different between both groups. The plasma cGMP concentrations were higher in the RDS group on days 2, 3, 4, and 7 (p < 0.05). The severity of RDS was positively correlated with plasma cGMP (r = 0.50, p = 0.0001). Although the arterial blood pressure did not differ between the groups, more blood pressure support was needed in the RDS infants during the first 4 days (p < 0.05). A positive correlation was found between blood pressure support and plasma cGMP (r = 0.34, p < 0.0001). The endogenous NO production was not different in infants with and without RDS. Increased plasma cGMP levels in the RDS infants were associated with the severity of RDS and the intensity of antihypotensive treatment. The origin of cGMP in infants with RDS requires further research.

Topics: Blood Pressure; Cyclic GMP; Gestational Age; Humans; Hypotension; Infant, Newborn; Infant, Premature; Nitrates; Nitric Oxide; Nitrites; Respiration, Artificial; Respiratory Distress Syndrome, Newborn

The role of atrial natriuretic peptide (ANP), in the perinatal period, is at present unclear. In adults urinary cyclic guanosine monophosphate (cGMP) is considered an index of the biological activity of plasma ANP. The aim of this study was to determine the relationship between plasma ANP, cGMP excretion (cGMPex) and sodium excretion (Naex) in preterm infants in the first days after birth. Sequential, 4 hourly, measurements of plasma ANP, cGMPex and Naex were made in 12 male neonates of median gestational age 27 weeks (range 25-33) and median birth weight 0.981 kg (range 0.635-2.029) over a median period of 5.2 days (range 2.3-10). The ratios of cGMPex to ANP and of Naex to cGMPex were each plotted against postnatal age. The ratio of cGMPex to ANP increased ten fold in the first 3-4 days after birth but then remained relatively constant; the ratio of Naex to cGMPex showed a steady increase from birth. We conclude that, in extremely immature infants, renal sodium loss in response to cGMP increases rapidly during the first 10 days after birth. In addition, after 3-4 days from birth, plasma ANP ia associated with a constant proportionate rate of cGMP excretion though, as the plateau ratio of cGMPex to ANP varied widely between babies, cGMPex cannot be used to predict plasma ANP in cross sectional studies. These changes may reflect postnatal adaptation and/or maturation of both ANP receptors and cGMP mediated cascades. In the immediate postnatal period, plasma ANP may also have a non-renal role.

Topics: Age Factors; Atrial Natriuretic Factor; Cyclic GMP; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Respiratory Distress Syndrome, Newborn; Sodium

Topics: Cyclic AMP; Cyclic GMP; Humans; Infant, Newborn; Respiratory Distress Syndrome, Newborn