Indomethacin Does Not Alter the Circulating Catecholamine Response to Asphyxia in the Neonatal Piglet

Abstract

ABSTRACT. The response of circulating catecholamines to asphyxia in unanesthetized, spontaneously breathing neonatal piglets was measured before and after treatment with indomethacin. Prior to treatment with indomethacin, baseline levels [geometric mean, pg/ml (95% confidence limits)] of D, E, and N were 162 (99-266), 174 (52-579), and 380 (286-506), respectively. Inhalation of 10% 02/9% CO? for 20 min caused significant increases in arterial levels of all three catecholamines to 389 (230-659, 1514 (993-2306), and 3802 (2731-5293), respectively. Treatment with indomethacin (5 mg/kg, intravenous) did not significantly alter either baseline levels of the catecholamines or the levels after 20 min of the asphyxiating gas. In time control piglets, baseline levels and the response to asphyxia were similar before and after placebo. These results suggest that the circulating catecholamine response to asphyxia of the neonatal piglet is independent of the prostaglandin system. (Pediatr Res 21: 534-537,1987) Abbreviations PGE2, prostaglandin E2 IND, indomethacin E, epinephrine PGI?, prostaglandin I? D, dopamine N, norepinephrine Prostanoids (1) and catecholamines (2) are potential modulators of neonatal circulatory and metabolic function under normal conditions and in response to stress. There is evidence suggesting an interdependence of the control of prostanoid and catecholamine release in various organs. For example, in several organ systems in the adult the release of N from adrenergic nerve endings in response to nerve stimulation is augmented by IND (3). This augmentation is believed to be due to inhibition of a putative prostaglandin-mediated negative feedback loop which modulates sympathetic neurotransmission in vascular smooth muscle. Furthermore, adrenal release of catecholamines also may be augmented by IND (4).Increased circulating levels of catecholamines are important Received March 19, 1986; accepted December 24, 1986. Reprint requests Robert S. Green, M.D., Newborn Center, 853 Jefferson Avenue, Room 201, Memphis, TN 38 163.Supported in part by grants in aid from the National Institutes of Health, the American Heart Association, the Tennessee Heart Association, and a Program Project Grant from the National Institutes of Health. C.W.L. is an Established Investigator of the American Heart Association.in the newborn's adaptation to a variety of stimuli such as asphyxia, including the events of normal labor and delivery (5). Circulating prostaglandin levels are increased in the newborn compared to the older child and adult (6), and activation of the prostaglandin system in several organs is an important part of the neonatal response to asphyxia (7-9). Thus, interaction of the catecholamine and prostanoid systems in the neonatal period would be significant both because it could be important in the circulatory and metabolic adjustments to asphyxia and because agonists and antagonists of both of these systems are in common use clinically (1 0-12).In the present study we test the hypothesis that inhibition of pr...

Indomethacin‐induced impairment of regional cerebrovascular reactivity: implications for respiratory control

“…; Green et al . ). Furthermore, any possible affect of INDO on the peripheral chemoreceptors is unlikely.…”

Influence of indomethacin on the ventilatory and cerebrovascular responsiveness to hypoxia

“…Indomethacin was used in this study as a pharmacological means to reduce cerebrovascular CO 2 reactivity in healthy resting humans without concomitant changes in cerebral metabolic rate (Hohimer et al 1985;Kraaier et al 1992) or plasma catecholamine concentrations (Green et al 1987;Staessen et al 1984;Wennmalm et al 1984). Studies have shown that the peak effect of INDO (100 mg) on reducing MCAv occurs at *90 min and persists for [4 h following ingestion (Markus et al 1994;Xie et al 2006).…”

“…Accordingly, the authors concluded that INDO lowers CBF and cerebrovascular CO 2 reactivity by selective inhibition of prostaglandin H synthase and prostacyclin receptor-mediated responses (Parfenova et al 1995b). Moreover, numerous studies have found that INDO lowers CBF and attenuates the cerebrovascular reactivity to CO 2 (Bruhn et al 2001;Eriksson et al 1983;Ivancev et al 2009;Kastrup et al 1999;Markus et al 1994;St Lawrence et al 2002;Wennmalm et al 1983) without concomitant changes in cerebral metabolic rate (Hohimer et al 1985;Kraaier et al 1992) or plasma catecholamines (Green et al 1987;Staessen et al 1984;Wennmalm et al 1984).…”

Influence of indomethacin on ventilatory and cerebrovascular responsiveness to CO2and breathing stability: the influence of Pco2gradients

“…Indomethacin (INDO) is a potent reversible cyclooxygenase inhibitor that blocks prostaglandin production in the cerebrovasculature, thereby decreasing CBF and attenuating the cerebrovascular CO 2 reactivity (6,17,36,53) without concomitant changes in metabolic rate (26,35) or plasma catecholamines (25,54,58). This unique feature makes INDO an ideal tool for investigating the role of cerebrovascular CO 2 reactivity in the control of breathing in humans.…”