Prostanoids in neonates with persistent pulmonary hypertension

Hammerman, Cathy; Lass, Nancy; Strates, Elene; Komar, Karl; Bui, Kim-chi

doi:10.1016/s0022-3476(87)80520-6

Cited by 45 publications

(23 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hammerman et al ( 5 ) have reported elevated thromboxane levels in human infants with GBS sepsis and persistent pulmonary hypertension of the newborn, suggesting a pathogenic role for thromboxane in some of these cases. Therefore, it is possible that blood thromboxane levels may be elevated in human newborns with other forms of bacteremia.…”

Section: Discussionmentioning

confidence: 99%

Thromboxane-Associated Pulmonary Hypertension during Three Types of Gram-Positive Bacteremia in Piglets

1988

View full text Add to dashboard Cite

ABSTRACT. Thromboxane-associated pulmonary hypertension occurs in animals during intravenous infusion of group B streptococcus (GBS), a gram-positive neonatal pathogen. We postulated that other gram-positive neonatal pathogens, such as Streptococcus fecalis (ENT) and Staphylococcus epidermidis (S. epi) would also induce increased thromboxane synthesis and pulmonary hypertension when infused into piglets. We observed similar hemodynamic and gas exchange abnormalities during stepwise increases in the dose of GBS, Ent, and S. epi (n = 3,4, and 4 piglets receiving each bacteria, respectively). Pulmonary vascular resistance increased significantly in the absence of acidosis or reduced arterial or mixed venous pOz at a dose of 2.5 x 10' cfu/kg/h for Ent and S. epi. In 14 additional piglets, pulmonary vascular resistance increased markedly after 60 min of intravenous infusion of 4 f 1 x 10' cfu/kg/h for each organism (p < 0.05, GBS: 11.7 f 1.8 to 75.6 f 18.4 mm Hg/liter/min, Ent: 12.7 f 1.7 to 64.9 f 10.6 mm Hg/ liter/min, S. epi: 10.5 f 0.8 to 56.9 f 6.0 mm Hg/liter/ min), and blood thromboxane B2 levels increased (p < 0.05, GBS: 30 f 10 to 1830 f 330 pglml, Ent: 20 f 7 to 1110 f 300 pglml, S. epi: 31 f 9 to 1260 f 350 pg/ml).This dose of each bacteria caused a similar degree of mild arterial hypoxemia (57-66 mm Hg). The thromboxane synthetase inhibitor, dazmegrel, completely reversed pulmonary hypertension, reduced TxB2 levels to near baseline values, and partially reversed arterial hypoxemia despite ongoing bacterial infusion. We conclude that thromboxaneassociated pulmonary hypertension occurs in piglets during infusion of different gram-positive neonatal pathogens. (Pediatr Res 23: 553-556, 1988) Abbreviations cfu, colony forming units C.O., cardiac output DAZ, dazmegrel Ent, Streptococcus fecalis (enterococcus) P,,, proximal airway pressure P,,, systemic arterial pressure GBS, a common gram-positive neonatal pathogen, causes acute pulmonary hypertension, arterial hypoxemia, and decreased cardiac output when infused into both adult and neonatal animals (1-3). In animals with GBS bacteremia and in some human newborns with GBS sepsis, pulmonary hypertension is associated with elevated blood levels of TxB2, the stable metabolite of the potent vasoconstrictor thromboxane A2 (2, 4, 5). Inhibitors of thromboxane synthesis, such as DAZ (UK 38,485),can prevent or reverse pulmonary hypertension in animals with GBS bacteremia (4, 6).The fact that both gram-positive bacteria, e.g. GBS, and some gram-negative bacteria, e.g. E scherichia coli and Aeromonas hydrophilia (7,8), can cause thromboxane-associated pulmonary hypertension suggests a lack of bacterial specificity for this pulmonary vascular response. Gram-positive neonatal pathogens other than GBS, such as Ent and S. epi, can contribute to respiratory failure and morbidity in human newborns (9, 10).However, there are no reports on the pulmonary hemodynamic effects of these other gram-positive bacteria.We postulated that the intravenous infusion of gram-positive neona...

show abstract

Section: Discussionmentioning

confidence: 99%

Thromboxane-Associated Pulmonary Hypertension during Three Types of Gram-Positive Bacteremia in Piglets

1988

View full text Add to dashboard Cite

show abstract

“…Clinical diseases, such as group B streptococcal sepsis and some forms of persistent pulmonary hypertension of the newborn in the absence of sepsis, are associated with elevated levels of serum thromboxane B2 levels (10). Both entities are associated with right-to-left shunting of mixed venous blood through the patent ductus and/or the foramen ovale, producing profound hypoxemia unresponsive to assisted ventilation with 100% oxygen (6).…”

Section: Discussionmentioning

confidence: 99%

“…This experience has prompted a search for endogenous vasoactive substances which increase PVR in the absence of alveolar hypoxia, any of which may play a pathogenic role in some infants with PPHN. Hammerman, et al (10) have reported increased serum levels of thromboxane B2, the stable metabolite of the pulmonary vasoconstrictor thromboxane A2, in some infants with PPHN. Stenmark et al (1 1) have measured elevated levels of vasoconstrictor leukotrienes C4 and D4 in the bronchial washings of infants with PPHN.…”

mentioning

confidence: 99%

Effects of Respiratory Alkalosis on Thromboxane-Induced Pulmonary Hypertension in Piglets

et al. 1988

View full text Add to dashboard Cite

ABSTRACT. Acute hypoxic pulmonary vasoconstriction PVR, pulmonary vascular resistance is attenuated by respiratory alkalosis. It is unknown if SVR, systemic vascular resistance alkalosis similarly reduces pulmonary vasoconstriction HR, heart rate produced by thromboxane A2. Respiratory alkalosis does Paw, peak proximal airway pressure not always attenuate persistent pulmonary hypertension in Pvoz, mixed venous oxygen tension newborns, some of whom have elevated serum thromboxane B2 levels. We hypothesized that alkalosis attenuates thromboxane-induced ~ulmonary vasoconstriction less than it does hypoxic vasoconstriction in infants. Hemodynamic responses to respiratory alkalosis during pulmonary vasoconstriction produced in random order by breathing 12% inspired oxygen and by infusing 0.1 j.~g/kg/ min of the thromboxane-mimetic U46,619 were compared in eight 2-wk-old piglets. Hypoxia increased mean pulmonary artery pressure from 12 f 3 to 29 f 2 mm Hg and pulmonary vascular resistance (PVR) from 11 f 4 to 25 f 8 mmHg/L/min; U46,619 increased pulmonary artery pressure from 16 +. 5 to 37 f 6 mm Hg and PVR from 14 f 5 to 51 f 17 mm Hg/liter/min. U46,619 also decreased cardiac output accounting in part for the greater increase in PVR compared to hypoxia-induced vasoconstriction. Respiratory alkalosis decreased PVR to 14 f 6 mm Hg/ literlmin during exposure to hypoxia and to 28 f 9 mm Hg/liter/min during infusion of U46,619. In six additional piglets with U46,619-induced pulmonary vasoconstriction, the effects of lung stretch and hypocapnic alkalosis were separated by doubling tidal volume and then adding inspired COz to return PaC02 to prehyperventilation levels. Respiratory alkalosis decreased PVR from 52 f 36 to 35 2 21 mm Hg/liter/min. Despite the increased tidal volume, PVR increased to 53 f 35 Hg/liter/min when PaCOz returned to 44 f 5 mm Hg. Respiratory alkalosis rather than lung stretch reduces thromboxane-induced and hypoxia-induced pulmonary vasoconstriction by equal proportions. (Pediatr Res 24: 558-562, 1988) Abbreviations CO, cardiac output HPV, hypoxic pulmonary vasoconstriction Acute HPV in both adult and young animals is attenuated by respiratory and metabolic alkalosis (1-4). Although alveolar hypoxia is not necessarily the cause of idiopathic PPHN, clinicians hyperventilate infants with PPHN to produce respiratory alkalosis in an attempt to selectively reduce PVR, increase pulmonary blood flow, and improve arterial oxygenation by reducing rightto-left shunting of venous blood through the ductus arteriosus and foramen ovale (5, 6). Despite ventilation with 1.0 F I O~ and hyperventilation, pulmonary hypertension does not fall below systemic levels in some of these infants, leading to a mortality of 17% or more (7)(8)(9). This experience has prompted a search for endogenous vasoactive substances which increase PVR in the absence of alveolar hypoxia, any of which may play a pathogenic role in some infants with PPHN. Hammerman, et al. (10) have reported increased serum levels of thromboxane B2, the stab...

show abstract

“…GBS sepsis in human neonates is associated with hypoxemia, pulmonary hypertension, shock, and high mortality (1)(2)(3). Neonatal animal models of i.v.…”

mentioning

confidence: 99%

Group B Streptococcal Sepsis in Piglets: Effect of Combined Pentoxifylline and Indomethacin Pretreatment

et al. 1992

View full text Add to dashboard Cite

show abstract

Prostanoids in neonates with persistent pulmonary hypertension

Cited by 45 publications

References 9 publications

Thromboxane-Associated Pulmonary Hypertension during Three Types of Gram-Positive Bacteremia in Piglets

Thromboxane-Associated Pulmonary Hypertension during Three Types of Gram-Positive Bacteremia in Piglets

Effects of Respiratory Alkalosis on Thromboxane-Induced Pulmonary Hypertension in Piglets

Group B Streptococcal Sepsis in Piglets: Effect of Combined Pentoxifylline and Indomethacin Pretreatment

Contact Info

Product

Resources

About