The Effects of Indomethacin on the Pulmonary Vascular Response to Hypoxia in the Premature and Mature Newborn Goat

Tyler, T.; Wallis, Rob; Leffler, Charles W.; Cassin, S.

doi:10.3181/00379727-150-39108

Cited by 49 publications

(36 citation statements)

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“…LeMer et al (4) reported that blocking prostaglandin synthesis with indomethacin markedly attenuated the decrease in pulmonary vascular resistance caused by ventilating the "in situ" perfused lung of the fetal goat. Using a similar preparation, Tyler et al (30) found that giving indomethacin shortly after the initiation of the ventilation raised pulmonary vascular resistance. Redding et al (3 1) reported that blocking prostaglandin synthesis with meclofenamate increased pulmonary vascular resistance in piglets in a manner inversely proportional to age during the 1st 12 days of life.…”

Section: Resultsmentioning

confidence: 99%

Indomethacin Does Not Diminish the Pulmonary Vascular Response of the Fetus to Increased Oxygen Tension

1988

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ABSTRACT. This study was performed to determineOxygen is one of the major stimuli decreasing pulmonary whether prostaglandins play a role in the increase in pul-vascular resistance at birth (1,(13)(14)(15). Assali et al., (16) and monary blood flow in the fetal lamb caused by an increase Heymann et al., (17) isolated the effect of a rise in oxygen tension in oxygen tension similar to that occurring at birth. To from the effect of ventilation of the lungs with a gas in acutely increase fetal oxygen tension without ventilating the lungs, instrumented fetal lambs by placing pregnant ewes in a hypernine pregnant ewes with chronically instrumented fetuses baric chamber at several atmospheres of pressure. Morin et al.were exposed to 100% oxygen at 3 atmospheres absolute (18) adapted this technique to study chronically instrumented pressure for 20 min in a hyperbaric chamber. This expo-fetal lambs and found that the entire increase in pulmonary sure increased pulmonary arterial oxygen tension in the blood flow that normally occurs at birth could be produced by nine fetuses from 20 f 1 to 54 f 9 torr. It increased an increase in oxygen tension alone. pulmonary blood flow from fetal to newborn values, 31 fThe current study was performed to determine whether the 3 to 295 2 20 ml/kg/min. It did not change pulmonary response of the fetal pulmonary circulation to oxygen is mediated arterial pressure, 52 f 2 torr during normoxia and 50 f 2 by prostaglandins. We measured the ability of prostaglandin torr during hyperoxia. Treating five of these fetuses with synthesis blockade by indomethacin to diminish the increase in 3.2 f 0.4 mg/kg of indomethacin during hyperbaric oxy-fetal pulmonary blood flow caused by an increase in oxygen genation did not alter these effects (Po2 = 51 f 8 torr, tension. pulmonary blood flow = 283 f 13 ml/kg/min, and pulmonary arterial pressure = 48 f 2 torr). We conclude that gestation were prepared for study. A catheter was passed from the maternal jugular vein into the right atrium for sampling of Abbreviations blood and for induction of anesthesia with 700 mg of sodium thiamylal. Surgery was then performed with the pregnant ewe PGD2, prostaglandin D2 under halothane anesthesia. The uterus was exposed through an PGE2, prostaglandin Ez abdominal incision, and the fetal head and neck were delivered 6-keto-PGE2, prostaglandin E2 through a uterine incision. An incision was made in the fetal ATA, atmosphere absolute pressure neck, and catheters were inserted into the carotid artery for measurement of systemic pressure and via the jugular vein into the superior vena cava for injection of radioactive microspheres. A left thoracotomy was performed, and a catheter was inserted into the main pulmonary artery, proximal to the branching of At birth there is a dramatic decrease in pulmonary vascular the right and left pulmonary arteries and the ductus arteriosus, resistance and increase in pulmonary blood flow (1, 2). The for measurement of pressure; sampling of blood gases and withincrease in pulmonary blood f...

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Section: Resultsmentioning

confidence: 99%

Indomethacin Does Not Diminish the Pulmonary Vascular Response of the Fetus to Increased Oxygen Tension

1988

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“…Potent prostanoid vasodilators, which contribute to the decrease in PVR after birth (3)(4)(5)(6), modulate the hypoxic pressor response in older animals of several species (1 7,33-35). Tyler et al (25) observed potentiation of HPV by indomethacin in isolated perfused left lower lobes of perinatal goats. This potentiation may have been greater in lungs of premature newborns than in lungs of mature newborns (25).…”

Section: Discussionmentioning

confidence: 98%

“…Tyler et al (25) observed potentiation of HPV by indomethacin in isolated perfused left lower lobes of perinatal goats. This potentiation may have been greater in lungs of premature newborns than in lungs of mature newborns (25). In contrast, Redding et al (24) did not observe an age-related difference in HPV in intact piglets either before or after meclofenamate.…”

Section: Discussionmentioning

confidence: 98%

“…If the pulmonary vasculature of sheep undergoes the same involution seen in other species, then some mechanism other than muscularization is required to explain why HPV was depressed in the isolated lungs of our younger lambs. Many studies suggest that dilator PG may contribute to the normally low PVR occurring during normoxia and may modulate HPV (6,16,17,24,25,(33)(34)(35). Potent prostanoid vasodilators, which contribute to the decrease in PVR after birth (3)(4)(5)(6), modulate the hypoxic pressor response in older animals of several species (1 7,33-35).…”

Section: Discussionmentioning

confidence: 99%

“…In goats, indomethdecreased with age. (Pediatr Res 23: 580-584, 1988) acin-enhanced normoxic PVR in perfused left lower lobes of both premature and mature newborns; however, in this species Abbreviations HPV was potentiated in both age groups (25). In isolated perfused lungs from 2-to 3-month-old lambs, however, there was no effect 6-keto-PGF,,, 6-keto-prostaglandin F,, of indomethacin on steady-state pulmonary pressures during PVR, pulmonary vascular resistance graded hypoxia (26,27).…”

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confidence: 84%

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Age-Dependent Effects of Indomethacin on Hypoxic Vasoconstriction in Neonatal Lamb Lungs

Tod

et al. 1988

Pediatr Res

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ABSTRACT. Although smooth muscle is abundant in the PVR decreases dramatically when ventilation is initiated at pulmonary vessels of young animals at birth, it is not clear birth (1)(2)(3)(4)(5)(6)(7). This is likely a consequence of mechanical distention if these vessels respond more vigorously to hypoxia than of the lung (1, 2), increased oxygen tension (1, 2), and release of the less muscular vessels of older neonates. To determine dilator PG (2-6). Subsequent decreases in normoxic PVR have the effect of age on the pulmonary vascular response to been well documented in the growing piglet (7) and in other hypoxia during the neonatal period in a single species, we species (2,8,9). In contrast, age-related changes in HPV are less measured the steady-state stimulus-response relationship clear. It has been suggested that the extent of arteriolar muscubetween inspired oxygen tension (200, 50, 30 and 0 mm larization determines the vigor of HPV (10-12). In this case, the Hg) and pulmonary artery pressure-flow curves in isolated newborn animal with its highly muscularized vessels (2, 7, 9, 10) blood perfused lungs from 2-to 4-and 12-to 14-day-old should have a more vigorous hypoxic response than the older lambs. Hypoxic vasoconstriction was attenuated in the animal. Although some studies show an age-dependent decrease younger newborns at an inspired oxygen tension of 50 mm in HPV (8, 13), others report an increase with age (10, 14, 15). Hg, but not at the other oxygen tensions. To determine ifOne possible explanation for these apparently conflicting rethis age-related difference was due to differences in mod-sults is that the vigor of HPV may be influenced by factors other ulation of hypoxic vasoconstriction by cyclooxygenase than vascular muscularization. For instance, there could be ageproducts, we assayed the metabolite of prostacyclin, 6-dependent differences in the modulation of HPV by pulmonary keto-prostaglandin El, in the perfusate and determined the vasodilators. Although vasodilators such as PGI, are released effects of indomethacin (40 pglml) on the hypoxic stimulus-during HPV in both young neonates and mature animals (1 6, response relationship. There was no age-related difference 17), the action and metabolism of various PG may vary with age in perfusate concentration of 6-keto-prostaglandin El, at (18, 19). For example, the vasodilator PGE2 (20) is more slowly any oxygen tension. However, indomethacin reversed the metabolized in the neonate (18). PGD2 is a pulmonary vasodiage-dependent attenuation of hypoxic vasoconstriction at lator in neonatal lambs, but a vasoconstrictor in older animals inspired oxygen tension = 50 mm Hg such that in indo-(21-23). Such differences may be partially responsible for the methacin-treated lungs pulmonary vasomotor tone was variable effects of cyclooxygenase inhibition on the developing higher in 2-to 4-day-old lungs than in 12-to 14-day-old pulmonary vasculature. In the intact pig, meclofenamate inlungs. This marked enhancement of hypoxic reactivity by creased normoxic PV...

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Hypoxic vs Septic Pulmonary Hypertension

Hammerman

Komar²,

Abu-Khudair³

1988

Am J Dis Child

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The Effects of Indomethacin on the Pulmonary Vascular Response to Hypoxia in the Premature and Mature Newborn Goat

Cited by 49 publications

References 0 publications

Indomethacin Does Not Diminish the Pulmonary Vascular Response of the Fetus to Increased Oxygen Tension

Indomethacin Does Not Diminish the Pulmonary Vascular Response of the Fetus to Increased Oxygen Tension

Age-Dependent Effects of Indomethacin on Hypoxic Vasoconstriction in Neonatal Lamb Lungs

Hypoxic vs Septic Pulmonary Hypertension

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