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Biomedical subjects

R I Clyman

Publications and source records attributed to R I Clyman.

At least 73 records · Page 4Linked to original sources
PubMed1987

Lung vascular effects of lipid infusion in awake lambs.

Numerous reports have shown that intravascular lipid infusion may cause pulmonary dysfunction in a variety of species, including humans. To determine the effects of parenteral lipid on neonatal pulmonary hemodynamics, lung fluid filtration, and respiratory gas exchange, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, lymph and plasma protein concentrations, and partial pressures of oxygen and carbon dioxide in arterial blood of 11 awake chronically catheterized lambs that received a 2-3 h control infusion of glucose-saline solution followed by Intralipid at a dose of 67.5, 125, or 250 (mg/h)/kg body weight for 6 h. Intralipid caused an acute dose-dependent increase in pulmonary arterial pressure, with no significant change in cardiac output or left atrial pressure. The pulmonary hypertension, which lasted for at least 2 h, was accompanied by a greater than 50% increase in lung lymph flow and a significant decrease in lymph protein concentration relative to plasma protein concentration. Pulmonary artery pressure gradually decreased to control values during the final 2 h of lipid infusion, but lymph flow remained 35% above control and lymph protein concentration remained low. Lipid infusion also was associated with a modest decrease in PaO2. Both arterial and venous administration of lipid gave similar results. In separate studies, lipid infusion caused a significant increase in plasma concentrations of thromboxane B2, the stable metabolite of thromboxane A2, without affecting plasma concentrations of 6-keto prostaglandin F1 alpha, the stable metabolite of prostacyclin. Pretreatment with imidazole, which attenuated the lipid-induced increase in thromboxane B2 concentration, completely blocked the pulmonary hemodynamic response to lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Theophylline treatment in the extubation of infants weighing less than 1,250 grams: a controlled trial.

The role of theophylline in weaning infants weighing less than 1,250 g at birth from mechanical ventilation was evaluated. Infants were randomized into control or theophylline treatment groups when they required minimal ventilatory support (peak inspiratory pressure 12 cm H2O, positive end-expiratory pressure 2 cm H2O, rate 12 breaths per minute, and FiO2 less than 0.3), and they were extubated 24 hours later. Infants required reintubation if they had (1) PaCO2 greater than 55 mm Hg and pH less than 7.20, (2) FiO2 greater than 0.5, or (3) apnea associated with a heart rate less than 100 beats per minute that required frequent stimulation (more than 20 episodes during a 16-hour period). Among 32 infants (birth weight less than 1,000 g) who reached minimal ventilatory support before seven days after delivery, 13 of 18 (72%) control infants required reintubation, whereas only four of 14 (28%) theophylline-treated infants required reintubation. On the other hand, among infants (birth weight less than 1,000 g) who reached minimal ventilatory support after seven days following delivery, only one of six (17%) of the control group required reintubation and no improvement could be seen with theophylline treatment. Similarly, among control infants (birth weight 1,001 to 1,250 g), only ten of 45 (23%) required reintubation after reaching low intermittent manditory ventilation settings. In summary, most infants recovering from respiratory distress syndrome who had birth weights (1) greater than 1,000 g or (2) less than 1,000 g and who were older than seven days could be successfully extubated from minimal ventilatory support without theophylline treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea↗
PubMed1986

Regulation of breathing movements in fetal sheep by prostaglandin E2.

In fetal sheep, plasma prostaglandin (PG) E2 concentrations are high, and fetal breathing movements (FBM) occur intermittently, primarily during low-voltage fast electrocortical activity (LVFA). There is evidence suggesting that prostaglandins, specifically PGE2, may regulate FBM. To define the physiological role of PGE2 in regulation of FBM, we infused meclofenamate (0.9 mg X kg-1 X h-1), a prostaglandin synthetase inhibitor, into six fetal sheep to suppress endogenous prostaglandin production. Afterward, PGE2 was added in mean doses of 9, 18, 36, and 90 ng X kg-1 X min-1. Meclofenamate decreased PGE2 concentrations and increased FBM, especially during high-voltage slow electrocortical activity (HVSA). Addition of PGE2 reversed the effects of meclofenamate, increasing PGE2 concentrations and decreasing FBM, especially during HVSA. The response to PGE2 was dose dependent; the overall incidence of FBM and incidences of FBM during HVSA and LVFA were inversely correlated with both the infused PGE2 dose and the mean PGE2 concentration. At higher doses of PGE2, FBM occurred intermittently and only during LVFA; thus PGE2 infusion restored the physiological pattern of FBM. These results indicate that PGE2 regulates FBM by inhibiting FBM during HVSA.

Animals↗
PubMed1985

Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs.

We have created a totally synthetic, protein-free surfactant (Exosurf) composed of dipalmitoylphosphatidylcholine, hexadecanol, and tyloxapol. We studied the effects of endotracheal instillation of Exosurf on survival and pulmonary function of preterm lambs delivered at 131 to 133 days gestation (term 148 days). Exosurf treatment was compared with instillation of surface-active material prepared from lung lavages of adult sheep and with no instillation. Lambs were delivered by cesarean section, paralyzed, and mechanically ventilated. The Exosurf group survived longer (80% alive at 11 hours) than did the no instillation group (30% alive at 11 hours) (P less than 0.05). There were no statistically significant differences between the Exosurf and sheep surfactant groups. We conclude that Exosurf, a synthetic surfactant, produces significant improvement in survival and pulmonary function in preterm lambs.

Animals↗
PubMed1985

Persistent responsiveness of the neonatal ductus arteriosus in immature lambs: a possible cause for reopening of patent ductus arteriosus after indomethacin-induced closure.

Reopening of the ductus arteriosus after successful indomethacin-induced closure has become a major problem with indomethacin treatment. In full-term human newborns and lambs, the ductus behaves like ischemic tissue after its initial constriction. Its ability to continue to relax or contract depends on the amount of left-to-right shunt through the ductus lumen. To see if ductus constriction in preterm lambs would produce the same loss of ductus responsiveness, we delivered 42 lambs by cesarean section and ventilated them for 6.6 +/- 0.5 (+/- SE) hr. We measured ductus arteriosus resistance and left-to-right shunt with the use of radionuclide-labeled microspheres. After the hemodynamic measurements were obtained, the ductus was studied in vitro. Immature lambs were more likely to have reactive ductus (after their initial ductus constriction) than were more mature lambs. This was due to a diminished degree of ductus constriction as well as persistence of ductus responsiveness in immature lambs when compared with more mature lambs. This persistence of ductus responsiveness in immature lambs after ductus constriction may account for the high reopening rate in preterm infants after successful indomethacin-induced closure.

Animals↗
PubMed1985

Thromboxane is not responsible for the high pulmonary vascular resistance in fetal lambs.

The factors responsible for the high pulmonary vascular resistance in the fetus are not well known. Thromboxane (TX) A2 is a potent pulmonary vasoconstrictor. To determine whether TXA2 may play a role in fetal pulmonary vasoconstriction, we infused the specific TX synthetase inhibitor U63,557A into eight chronically instrumented fetal lambs (134-137 days gestational age, full term 145 days) and measured pulmonary blood flow, pulmonary and systemic arterial pressure, and heart rate. U63,557A (3 mg/kg as a bolus then 3 micrograms/kg/min for 120 min infused in the main pulmonary artery) did not change pulmonary blood flow, pulmonary mean arterial pressure, and pulmonary vascular resistance during the infusion and during 2 h following the end of the infusion. During the infusion, TXB2 arterial plasma concentrations decreased from 106.1 +/- 17.5 to 8.7 +/- 2.9 pg/ml. In three of the fetal lambs, immediately after the 2-h infusion of U63,557A, we infused the leukotriene end-organ antagonist FPL 57231 into the main pulmonary artery (1 mg/kg/min for 60 min). TXA2 synthesis inhibition did not prevent the pulmonary vasodilation induced by FPL 57231. Pulmonary blood flow increased from 64.8 +/- 24.4 to 669.5 +/- 65.6 ml/min/100 g lung tissue during the FPL 57231 infusion. We conclude that TXA2 does not play a role in the maintenance of elevated fetal pulmonary vascular tone, either directly or as a mediator of leukotriene action.

Animals↗
PubMed1985

Does indomethacin cause extension of intracranial hemorrhages: a preliminary study.

Thirty-six infants who had an intracranial hemorrhage (diagnosed by cranial ultrasound) within four days after delivery (mean age 2.4 +/- 0.9 (SD) days), were reexamined at three- to seven-day intervals for extension of their intracranial hemorrhage. Seventeen infants had a patent ductus arteriosus and were treated with indomethacin after the initial intracranial hemorrhage was diagnosed. The age for starting indomethacin was 3.8 +/- 1.1 days. Nineteen infants did not have a patent ductus arteriosus and did not receive indomethacin. Both the indomethacin-treated and nontreated groups were similar in birth weight, gestational age, Apgar scores, gender, incidence of respiratory distress, as well as the location and the degree of hemorrhage in the initial scans. Only one of 17 (6%) infants who received indomethacin v tow of 19 (11%) infants who did not receive it, had extension of their initial intracranial hemorrhage. Although indomethacin may alter platelet function, it does not appear to cause extension of a preexisting intracranial hemorrhage.

Cerebral Hemorrhage↗
PubMed1984

Meclofenamate and prostaglandin E2 affect breathing movements independently of glucose concentrations in fetal sheep.

Fetal breathing movements in sheep are stimulated by infusions of a prostaglandin synthetase inhibitor, meclofenamate; they are inhibited by prostaglandin E2. Recent studies suggest that these effects are mediated through changes in fetal plasma glucose concentrations. We infused into chronic fetal sheep preparations (1) glucose, (2) meclofenamate, and (3) prostaglandin E2, followed by prostaglandin E2 and glucose together. Infusions of glucose alone did not affect fetal breathing movements despite a significant twofold increase in glucose concentrations. During meclofenamate infusions, fetal breathing movements increased from 34.9% to 80.6% (p less than 0.005); glucose concentrations did not change. During prostaglandin E2 infusions, fetal breathing movements decreased from 36.5% to 4.1% (p less than 0.005) without any change in glucose concentrations; the addition of glucose did not alter the effects of prostaglandin E2 on fetal breathing movements. We conclude that fetal infusions of glucose in sheep do not affect fetal breathing movements and the effects on these breathing movements produced by meclofenamate and prostaglandin E2 are independent of the changes in plasma glucose concentrations.

Animals↗
PubMed1984

Decreased contractility of the ductus arteriosus in experimental pulmonic stenosis.

Delayed closure of the ductus arteriosus after birth has been observed in newborn infants with critical pulmonic stenosis and in newborn lambs with experimental pulmonic stenosis. This delayed ductal closure may be caused by a decreased ability of the muscle to contract when exposed to oxygen or to an increased production of or sensitivity to prostaglandin (PG) E2, the endogenous ductus arteriosus vasodilator. To determine whether the abnormal hemodynamic pattern during fetal life associated with pulmonic stenosis alters the responsiveness of the ductus arteriosus, we operated on 10 fetal lambs of gestational ages 70 to 77 days (term is 148 days) and placed a band around the pulmonary artery. Catheterization at 137 to 142 days showed severe pulmonic stenosis. We then studied isolated rings of ductus arteriosus from these lambs. The oxygen-induced increase in tension in rings of ductus arteriosus from lambs with pulmonic stenosis was significantly decreased (2.55 +/- 0.38; n = 10) compared with rings from control lambs (4.03 +/- 0.51; n = 6, p less than .03). There was no difference between the two groups in either the amount of PGE2 released by the rings or in the sensitivity (expressed as median effective dose) of the rings to PGE2. There was also no difference in the increase in tension when endogenous PGE2 was inhibited by indomethacin. We conclude that delayed closure of the ductus arteriosus in lambs with experimental pulmonic stenosis is not caused by increased sensitivity to or production of PGE2 in the ductus arteriosus (as it is in premature lambs) but rather is the result of a diminished ability of the ductus arteriosus to contract when exposed to oxygen.

Animals↗
PubMed1983

Effect of gestational age on ductus arteriosus response to circulating prostaglandin E2.

Premature newborn lambs with a patent ductus arteriosus have higher plasma prostaglandin E2 concentrations than near-term newborn lambs with a contricted ductus arteriosus. To see whether these concentrations of PGE2 could produce patency of the ductus arteriosus, we studied eight near-term lambs (with constricted ductuses) delivered by cesarean section, paralyzed, and mechanically ventilated. After ductus arteriosus resistance and plasma PGE2 concentrations had stabilized, a continuous PGE2 infusion into the superior vena cava was started to determine threshold concentrations needed to dilate the ductus in vivo. By two hours after birth, circulating PGE2 concentrations in near-term lambs were considerably less then the threshold concentration, and the ductuses were constricted. In five premature newborn lambs, significantly lower concentrations of PGE2 were required to dilate the ductus: threshold and ED50 concentrations were one sixth and one third, respectively. In these premature lambs during the first two hours after birth, circulating PGE2 concentrations were twice as high as the calculated in vivo threshold level. Therefore, circulating PGE2 concentrations probably played a significant role in the patency of the ductus arteriosus in these premature lambs.

Animals↗
PubMed1983

Videophone use improves maternal interest in transported infants.

A telephone video transmission unit was utilized to assist in the attachment of mothers to their transported sick infants. To evaluate its effectiveness, the number of telephone calls to the ICN made by the mothers using the unit was used as a variable to "quantify" interest in their newborns; this was compared with the number of calls made by a matched group of mothers who did not utilize the videophone. There was a significantly larger number of calls made by the study mothers both while hospitalized and after discharge when they no longer had use of the videophone. Use of the unit appeared to alleviate some maternal anxieties and encouraged early endearment by the study mothers. How this affects the long-term relationship between infant and mother will require further follow-up investigation.

Anxiety↗
PubMed1983

Factors determining the loss of ductus arteriosus responsiveness to prostaglandin E.

The ductus arteriosus of the newborn infant varies in its ability to dilate when doses of prostaglandin E (PGE) are administered. We infused PGE2 into 15 late-gestation newborn lambs to determine which factors regulate the ability of the ductus arteriosus to respond to PGE. PGE2 dilated the ductus in 10 lambs (responders); in five other lambs, despite similar PGE2 concentrations, there was no effect (nonresponders). The measured ductus resistance after the PGE2 infusion was directly related to the ductus resistance before the infusion. Responders had a larger left-to-right shunt through the ductus before the PGE infusion than nonresponders. Ductus that were isolated and studied in vitro from lambs that were nonresponsive to PGE2 (in vivo) were limited in their ability to relax with PGE2 as well as to actively contract with oxygen and indomethacin. This generalized loss of ductus responsiveness was directly related to the amount of the left-to-right shunt through the lumen of the ductus. These observations are consistent with the hypothesis that the constriction of the ductus arteriosus after birth limits the ability of the ductus to respond to PGE therapy.

Animals↗
PubMed1982

Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants.

We performed a double-blind, controlled study of prophylactic indomethacin therapy in 47 premature infants (less than 1700 g) who had subclinical patent ductus arteriosus. They received either indomethacin or placebo at a mean age of 2.9 days. Among the 25 infants weighing more than 1000 g, a hemodynamically important ductus shunt developed in only four of the 14 given placebo. The incidence of important shunts, the number of surgical ligations, and the duration of oxygen therapy were not appreciably different between the study groups. In contrast, among the 22 infants who weighed 1000 g or less, a major ductus shunt developed in 10 of the 12 given placebo. In the smaller infants indomethacin therapy was associated with a significantly lower incidence of major shunts, fewer surgical ligations, a decreased duration of oxygen therapy, and fewer days necessary to regain birth weight. We conclude that prophylactic indomethacin therapy in infants weighing under 1000 g prevents the later development of large ductus shunts and decreases morbidity.

Clinical Trials as Topic↗
PubMed1982

Increased shunt through the patent ductus arteriosus after surfactant replacement therapy.

Instillation of surfactant into the trachea of preterm infants with respiratory distress syndrome is associated with a 90% incidence of patent ductus arteriosus. We studied the effects of surfactant therapy on the ductus arteriosus in 12 preterm lambs. Flow across the ductus arteriosus and systemic blood flow were calculated from radioactive microsphere injections. All developed respiratory failure (pH less than 7.1, Paco2 greater than 60) by 30 minutes after birth. Between 30 and 60 minutes after birth, six lambs were treated with tracheal instillation of 50 mg/kg surfactant lipid. By two hours after birth, treated lambs differed significantly from controls in pH (7.27 +0.02 vs 6.97 +0.08) and Paco2 (43.3 +4.1 vs 85 + 15). There were no differences in Pao2 or PGE2 concentrations or ductus arteriosus resistance, but there was a significantly larger shunt through the ductus arteriosus in treated lambs. This increased shunt resulted from the significant drop in pulmonary vascular resistance and not from a change in patency of the ductus arteriosus. Surfactant replacement may require interventions directed specifically at the patent ductus arteriosus in sick preterm infants.

Animals↗