title: Is carbon monoxide-mediated cyclic guanosine monophosphate production responsible for low blood pressure in neonatal respiratory distress syndrome?
abstract: 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.
authors.affiliation: Department of Neonatology, Rm. KE.04.123.1, Wilhelmina Children's Hospital, University Medical Center, PO Box 85090, 3508 AB Utrecht, The Netherlands. f.vanbel@wkz.azu.nl
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Vincent
authors.initials: V
authors.lastname: Latour
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Vreman
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Johannes
authors.initials: J
authors.lastname: Egberts
authors.forename: Tannette G
authors.initials: TG
authors.lastname: Krediet
mesh_terms: D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002248:Carbon Monoxide / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D006801:Humans; D007022:Hypotension / Q000097:blood* / Q000209:etiology; D007231:Infant, Newborn; D012127:Respiratory Distress Syndrome, Newborn / Q000097:blood* / Q000150:complications; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; D002248:Carbon Monoxide; D006152:Cyclic GMP