Role Of Glutamate On The Ventilatory Response To Hypoxia During Lactic Acid Infusion In Newborn Piglets. ♦ 1638

Davila, Gianina; Ovalle, Oscar Garza; Hehre, Dorothy; Devia, Carlos; Huang, Jian; Bancalari, Eduardo; Suguihara, Cleide

doi:10.1203/00006450-199804001-01660

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“…A depression in the ventilatory response to hypoxia was noted in awake newborn piglets with induced lactic acidosis when the BE was Ͼ Ϫ12 mM (40). In the present study, the basal BE decreased after E. coli endotoxin administration, but remained within the normal range.…”

Section: Discussionmentioning

confidence: 52%

The Effect of Escherichia coli Endotoxin Infusion on the Ventilatory Response to Hypoxia in Unanesthetized Newborn Piglets

et al. 2003

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To determine the effects of endotoxemia on the neonatal ventilatory response to hypoxia, 17 chronically instrumented and unanesthetized newborn piglets (Յ7 d) were studied before and 30 min after the administration of Escherichia coli O55:B5 endotoxin (n ϭ 8) or normal saline (n ϭ 9). Minute ventilation, oxygen consumption, heart rate, arterial blood pressure, and blood gases were measured during normoxia and 10 min of hypoxia (fraction of inspired oxygen, 0.10). Basal ventilation was not modified by E. coli endotoxin infusion (mean Ϯ SE, 516 Ϯ 49 versus 539 Ϯ 56 mL/min/kg), but the ventilatory response to hypoxia was markedly attenuated at 1 min (955 Ϯ 57 versus 718 Ϯ 97 mL/min/kg, p Ͻ 0.002, saline versus endotoxin) and at 10 min (788 Ϯ 51 versus 624 Ϯ 66 mL/min/kg, p Ͻ 0.002). A larger decrease in oxygen consumption was observed during hypoxia and endotoxemia (6.3 Ϯ 2.8 versus 18.3 Ϯ 2.7%, p Ͻ 0.03, pre-versus post-endotoxin). A significant correlation was demonstrated between the changes in minute ventilation and oxygen consumption with hypoxia during endotoxemia (r ϭ 0.9, p Ͻ 0.002). The ventilatory response to hypoxia was not modified by the saline infusion. These data show a significant attenuation in the ventilatory response to hypoxia during E. coli endotoxemia. This decrease in ventilation was associated with a significant decrease in the metabolic rate during hypoxia and endotoxemia. Changes in the breathing pattern and apnea episodes are frequently associated with neonatal sepsis, especially in the preterm infant (1). It has also been observed that the administration of Escherichia coli endotoxin to anesthetized adult cats produced an abrupt apnea followed by transient rapid and shallow breathing (2). However, the mechanisms explaining these changes in breathing pattern are not clearly understood. Respiratory muscle fatigue, a decrease in lung compliance, and an increase in pulmonary resistance have been cited as possible mechanisms for the ventilatory changes observed during Gram-positive and -negative septicemia (3-6).It is well known that a variety of inflammatory mediators such as cytokines, prostaglandins, leukotrienes, and NO are released during sepsis or endotoxemia (3, 6, 7). Furthermore, the changes in the breathing pattern observed during E. coli infusion to adult cats were eliminated in the animals pretreated with indomethacin or thromboxane A 2 receptor antagonist (2). On the other hand, it has been demonstrated that prostaglandins and NO may mediate the ventilatory depression observed during hypoxia in newborn animals (8, 9). Therefore, the increased release of these inflammatory mediators may further depress the ventilatory response to hypoxia during E. coli endotoxemia.The increased circulating cytokines during sepsis or endotoxemia can induce a systemic inflammatory response involving the microvascular system and trigger hemodynamic changes (7, 10, 11). These changes result in maldistribution of blood flow to different organs, which may be accompanied by January 31, 2002; accepted Dec...

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Section: Discussionmentioning

confidence: 52%