Screening for glucose-6-phosphate dehydrogenase deficiency.
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Glucosephosphate Dehydrogenase Deficiency↗
Biomedical subjects
C Hammerman
Publications and source records attributed to C Hammerman.
Plasma thromboxane and pulmonary artery pressure in neonates treated with extracorporeal membrane oxygenation.
To examine whether neonates with persistent pulmonary hypertension are subject to a thromboxane-mediated exacerbation of their pulmonary hypertension during extracorporeal membrane oxygenator therapy (a form of partial cardiopulmonary bypass), we performed serial measurements of plasma thromboxane B2 and pulmonary artery pressure before, during, and after extracorporeal membrane oxygenation. Pulmonary artery pressure was high before extracorporeal membrane oxygenation, did not increase after the start of this therapy, but began to decrease after 48 hours of extracorporeal membrane oxygenation. During the course of extracorporeal membrane oxygenation, mean pulmonary artery pressure decreased by 50% and mean plasma thromboxane B2 levels decreased by 70%. In addition, serial plasma thromboxane B2 levels were significantly correlated with pulmonary artery pressures in individual infants with a primary diagnosis of meconium aspiration (r = 0.965 to 0.723). We speculate that the decrease in pulmonary artery pressure and plasma thromboxane B2 levels over time may reflect resolution of acute lung injury and that thromboxane B2 may play a role in regulating pulmonary artery pressure in infants with meconium aspiration.
Echocardiography↗
Variations in local PGE levels: a potential factor in therapeutic responsiveness?
It was hypothesized that it is the concentration of PGE in the plasma which actually reaches the ductus arteriosus which determines ductal response to PGE administration. Therefore, site specific PGE levels were studied in two infants with ductus dependent congenital heart lesions who were receiving PGE1 infusions. PGE levels were found to vary in a fashion related to the infusion site and the specific cardiac anatomy and hemodynamics of each patient. One of our patients, for instance, had a double outlet right ventricle with high pulmonary vascular resistance and right to left ductal shunting. This infant was given an intraarterial infusion of PGE. The plasma concentrations of PGE in the ductal blood of the infant were negligible. Assuming that ductal site specific PGE levels are critical in mediating the therapeutic response, hemodynamics and infusion site are factors that should be considered when initiating a PGE infusion, or in evaluating a therapeutic failure of PGE.
Alprostadil↗
Effects of hyperventilation on prostacyclin formation and on pulmonary vasodilation after group B beta-hemolytic streptococci-induced pulmonary hypertension.
Prostacyclin is released during hyperventilation (HV); however, its role as mediator of HV-induced pulmonary vasodilation remains controversial. We have investigated this by studying the effects of HV on pulmonary artery pressure (PAP) in otherwise normal lungs versus lungs vasoconstricted with group B streptococci (GBS), with and without prior prostacyclin synthesis inhibition. Two- to 3-wk-old piglets were given tranylcypromine, a prostacyclin synthetase inhibitor (n = 6), or placebo (n = 6). Animals were mechanically ventilated normally, then hyperventilated (PCO2 1.5 +/- 0.2 kPa) and then returned to normal ventilation. After each 30-min segment, plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (prostacyclin hydrolysis product) levels and PAP were measured. Then GBS infusions were administered to both groups to induce pulmonary hypertension. With GBS, the normal ventilation/hyperventilation/normal ventilation protocol was repeated as above.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Ketoprostaglandin F1 alpha↗
Plasma prostanoids in neonatal extracorporeal membrane oxygenation. Influence of meconium aspiration.
Thromboxane B2 may be a mediator of neonatal persistent pulmonary hypertension. Elevated levels of plasma thromboxane and prostacyclin have been described previously in hypoxic newborn infants with neonatal pulmonary hypertension. We measured serial plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin) in 21 newborn infants with severe respiratory failure and pulmonary hypertension who required extracorporeal membrane oxygenation support. We sought to study (1) the evolution of plasma prostanoids in pulmonary hypertensive infants treated with extracorporeal membrane oxygenation and (2) whether different pulmonary hypertensive diagnostic subgroups have distinctive prostanoid profiles. Our data indicated that infants with meconium aspiration had significantly lower levels of plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha while receiving extracorporeal membrane oxygenation than did infants with persistent pulmonary hypertension but no meconium aspiration. Levels of all infants decreased progressively as extracorporeal membrane oxygenation support continued.
6-Ketoprostaglandin F1 alpha↗
Plasma prostanoids in neonates with pulmonary hypertension treated with conventional therapy and with extracorporeal membrane oxygenation.
Thromboxane may be a mediator of pulmonary hypertension in the neonate. Acute thromboxane-mediated pulmonary hypertension has been described in sheep receiving extracorporeal membrane oxygenation, which raises concerns about a potential thromboxane-mediated exacerbation of pulmonary hypertension in human neonates with severe pulmonary hypertension who are treated with extracorporeal membrane oxygenation. We measured plasma levels of thromboxane, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in infants with pulmonary hypertension, some of whom were treated medically and some of whom were treated with extracorporeal membrane oxygenation. Plasma levels of all three prostanoids were elevated in infants with pulmonary hypertension and decreased with time, whether the neonates were treated with extracorporeal membrane oxygenation or with medical management alone. In infants treated with extracorporeal membrane oxygenation, we collected samples simultaneously from preoxygenator sites, postoxygenator sites, and umbilical artery catheter. We could demonstrate no significant difference in plasma prostanoid levels across the oxygenator. In two patients, plasma thromboxane and prostaglandin F2 alpha levels measured shortly after a platelet transfusion were distinctly higher in the umbilical artery catheter than in venous samples.
6-Ketoprostaglandin F1 alpha↗
Prostanoid inhibition and group B hemolytic streptococci (GBS) induced neutropenia in newborn piglets.
GBS (Group B Hemolytic Streptococci) cause pulmonary hypertension with associated neutropenia. We investigated whether there is a correlation between the neutropenia of sepsis and GBS-induced pulmonary vasoconstriction, through study of the effects of inhibiting pulmonary vasoconstriction on the neutropenia of GBS in newborn piglets. Fifteen piglets were infused with GBS. After one hour, animals were given either a thromboxane inhibitor (DAZ), a combined cyclooxygenase/lipoxygenase inhibitor, BW755C, or placebo. With GBS infusion, WBC and PMN counts dropped steadily, from similar baselines, to 2250 +/- 570, 3300 +/- 500 and 5400 +/- 1100 cells/mm3 respectively (p less than 0.05; DAZ and BW vs. placebo). PMN's dropped similarly to 710 +/- 320, 2390 + 1240 and 3130 +/- 1050 cells/mm3 respectively (p less than 0.05; DAZ vs. BW and placebo). The drop in WBC's predominantly resulted from proportional decreases in PMN's (DAZ: r = 0.98; BW: r = 0.88; placebo r = 0.93). Compared to GBS alone, DAZ reduced pulmonary vasoconstriction, but exacerbated the granulocytopenia. BW755C similarly reduced pulmonary hypertension: however, it ameliorated the exacerbation of GBS induced neutropenia described above. These data imply that there is no direct correlation between GBS induced granulocytopenia and pulmonary hypertension.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
Prolonged indomethacin therapy for the prevention of recurrences of patent ductus arteriosus.
We tested the hypothesis that prolonged maintenance indomethacin therapy would allow more effective closure of patent ductus arteriosus (PDA) and thereby decrease the recurrence rate. Thirty-nine low birthweight neonates (less than 1500 gm) with confirmed PDA were randomly assigned in a double-blind fashion to receive standard indomethacin therapy (three doses), followed either by maintenance indomethacin therapy (0.2 mg/kg/day) for 5 days or by an equivalent volume of placebo for 5 days. Of the 20 infants who received maintenance indomethacin therapy, two (10%) required additional therapy and one of these required surgical ligation. Of the 19 infants who received only the first three indomethacin doses, nine (47%) required additional therapy for PDA (p less than 0.05) and seven of these had a ligation (p less than 0.05). We conclude that maintenance indomethacin therapy, in comparison with short-term indomethacin therapy, decreases the incidence of surgical PDA ligations, eliminates most PDA recurrences, and does not increase toxic effects of indomethacin in the low birth weight infant with PDA.
Birth Weight↗
Lipoxygenase and cyclooxygenase blockade by BW755C does not prevent the secondary phase of septic pulmonary hypertension.
The infusion of Group B beta hemolytic streptococci (GBS) in newborn animals generates a dual phase pulmonary hypertensive response. The initial, acute phase responds to cyclooxygenase or thromboxane inhibition, and appears to be thromboxane mediated. The second phase is characterized by a more moderate rise in pulmonary vascular resistance, accompanied by an increase in microvascular permeability. It has been speculated that this phase may be leukotriene mediated. In an attempt to clarify this, we have studied and compared the effects of the thromboxane synthetase inhibitor, Dazmegrel (DAZ), and the combined cyclooxygenase/lipoxygenase inhibitor, BW755C, on the cardiopulmonary hemodynamics of the secondary phase of GBS induced pulmonary hypertension in newborn piglets. Ten piglets were infused with GBS, and all animals developed a significant increase in pulmonary artery pressure (to 39 +/- 5 and 36 +/- 5 mmHg for DAZ and BW755C animals respectively). After one hour of GBS, either DAZ or BW755C was administered. Data were collected for another two hours following drug administration. GBS infusion was continued throughout. Both DAZ and BW755C were associated with transient, acute reductions in pulmonary artery pressure (to 22 +/- 5 and 22 +/- 8 mmHg, respectively). However, after 60 minutes, PAP again began to rise in both groups (PAP 30 +/- 5 and 30 +/- 11 mmHg respectively by 240 minutes). There were no differences between the groups at any time. These data do not support a significant role for lipoxygenase products in mediating the secondary phase of septic pulmonary hypertension.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
Intravenous lipids in newborn lungs: thromboxane-mediated effects.
Lipid infusions can interfere with oxygenation and cause pulmonary hypertension. We studied the effects of iv lipid infusions on pulmonary hemodynamics and oxygen transport to investigate whether the vasoconstrictor, thromboxane (Tx), mediates resulting changes. Newborn piglets were instrumented to observe cardiopulmonary hemodynamics, blood gases, and oxygen contents. Oxygen delivery (DO2), oxygen consumption, and extraction ratios were calculated. All piglets received continuous 1-g/kg.h iv lipid infusions. After one hour, and as the lipid infusion continued, six piglets were given placebo (PL) and six others were given the Tx antagonist SQ 29548 (SQ). Pulmonary vasoconstriction occurred in both groups after one hour of lipid infusion (pulmonary artery pressure [PAP] 28 +/- 6 mm Hg in the PL piglets and to 31 +/- 13 mm Hg in the SQ piglets. After intervention, PAP remained elevated only in the PL group (32 +/- 2 vs. 23 +/- 8 mm Hg) (p less than .02). PaO2 and DO2 fell significantly with iv lipid and improved after intervention in SQ animals only (p less than .02). TxB2 increased in all animals with iv lipid (276 +/- 295 to 1481 +/- 716 in PL; 228 +/- 110 to 1402 +/- 580 in SQ), and fell with intervention in the SQ animals only (2632 +/- 1236 vs. 964 +/- 305, respectively; p less than .02). In conclusion, interference with DO2 associated with pulmonary hypertension and increased TxB2 occurred with iv lipid infusion in piglets. Tx antagonism ameliorated these changes.
Animals↗
Prostaglandin E1 selectively reduces group B beta-hemolytic streptococci-induced pulmonary hypertension in newborn piglets.
Group B beta-hemolytic streptococci (GBS)-induced pulmonary hypertension was generated in ten newborn piglets. Intravenous infusions of either prostaglandin E1 (PGE1) (n = 5) or placebo (n = 5) were begun after 60 minutes of stable pulmonary hypertension. The effects of these interventions on cardiopulmonary hemodynamics were studied. Pulmonary artery pressure (PAP) increased similarly in both groups during the first 60 minutes of GBS infusion. By two hours after intervention, PAP was significantly lower in the animals given PGE1 (20 +/- 4 vs 32 +/- 5 mm Hg for PGE1 vs placebo). The ratio of pulmonary to systemic vascular resistance followed a pattern analogous to PAP, increasing with the GBS infusion, indicating selective pulmonary vasoconstriction. The pulmonary vascular resistance/systemic vascular resistance ratio decreased after intervention in the group given PGE1 only (0.25 +/- 0.08 vs 0.50 +/- 0.12 for PGE1 vs placebo), indicating selective pulmonary vasodilation. Transient systemic hypotension was noted at one hour after initiation of PGE1 infusion. Prostaglandin E1 infusion selectively improved GBS-induced pulmonary hypertension and hypoxemia in newborn piglets with only transient systemic hypotension.
Alprostadil↗
Persistent pulmonary hypertension of the newborn. Managing the unmanageable?
Persistent pulmonary hypertension of the newborn is a complex syndrome with multiple causes, which retains a high morbidity and mortality. This article presents pathophysiologic and diagnostic foundations and then focuses the discussion on management issues.
Extracorporeal Membrane Oxygenation↗
Hypoxic vs septic pulmonary hypertension. Selective role of thromboxane mediation.
Pulmonary hypertension was generated in 11 newborn piglets, via either infusion of group B beta-hemolytic streptococci (n = 5) or induction of isocapnic hypoxia (n = 6), to study the contributions of thromboxane metabolite thromboxane B2 levels to different types of pulmonary hypertension. After 30 minutes of stable pulmonary hypertension, mean (+/- SD) pulmonary artery pressure increased similarly from 16 +/- 4 to 33 +/- 5 mm Hg (hypoxic), and from 14 +/- 2 to 34 +/- 6 mm Hg (septic). All other measured hemodynamic variables were similar. Despite these hemodynamic similarities, there were significant differences in thromboxane B2 levels. After 60 minutes of pulmonary hypertension, thromboxane B2 levels were 760 +/- 253 pg/mL (hypoxic), and 3103 +/- 1083 pg/mL (septic). These data demonstrate that, while thromboxane appears to be crucial in mediating septic pulmonary hypertension in the piglet, it is not associated with hypoxic pulmonary hypertension, implying that different types of pulmonary hypertension are probably mediated by different biochemical agents.
Animals↗
Decreased lipid intake reduces morbidity in sick premature neonates.
For an investigation of the clinical sequelae of parenteral lipid infusions during the first week of life, 42 neonates (less than 1750 gm birth weight) were randomly assigned to receive parenteral alimentation with (IL) (Vitrum) or without a parenteral lipid infusion (NL) for 5 days. Follow-up clinical status was monitored and compared, and plasma prostaglandin levels were analyzed. Chronic lung disease was increased in duration and tended to be more severe after lipid administration. The number of days of mechanical ventilation (37 +/- 35 vs 21 +/- 18) and supplemental oxygen therapy (51 +/- 39 vs 28 +/- 23) was significantly increased in the IL group. Five IL infants developed stage 3 bronchopulmonary dysplasia, in comparison with none of the NL infants. Seven IL infants were discharged on a regimen of supplemental oxygen therapy versus none of the NL infants. Thromboxane B2 levels were significantly increased in the babies receiving Vitrum. We conclude that early administration of Vitrum in the premature neonate is associated with increased respiratory difficulty in the ensuing weeks of life.
6-Ketoprostaglandin F1 alpha↗
Oxygen transport in newborn piglets with pulmonary hypertension.
Because of the neonate's susceptibility to pulmonary hypertension (PHN) and his inefficiency in invoking the compensatory mechanisms often used by adults to maintain stable levels of O2 consumption (VO2) in the face of changes in O2 delivery (DO2) and metabolic demand, we have attempted to define the O2 handling capabilities of the newborn piglet affected with various types of pulmonary vasoconstriction. Hemodynamically similar levels of PHN were generated in 18 newborn piglets (six through group B beta-hemolytic Streptococci infusion; six through hypoxia; six through hypercarbia) and O2 transport was studied. At 60 min VO2 was similar in all groups, although DO2 was different (10.7 +/- 6.7, 7.2 +/- 1.6, and 21.7 +/- 8.9 ml/kg.min, in the septic, hypoxic, and hypercarbic groups, respectively). Extraction efficiency varied in an inverse fashion (43 +/- 12%, 72 +/- 12%, and 27 +/- 16%, in the septic, hypoxic, and hypercarbic groups, respectively). Supply dependency and a critical DO2 were observed in the septic and hypoxic PHN groups (18.4 and 12.2 ml/kg.min, respectively). Both of these were elevated as compared to healthy adult levels. Hypercarbic pulmonary hypertension was supply independent at the levels studied; however, DO2 remained elevated in these animals and may never have reached the critical DO2 level.
Animals↗
Unusual manifestations of arrhythmogenic right ventricular dysplasia as ventricular fibrillation, atrial paralysis, and hypoexcitable right ventricle.
Ventricular fibrillation occurred in an apparently healthy 19 year old man. The results of non-invasive and invasive studies suggested right ventricular dysplasia. Electrophysiological studies showed atrial paralysis, hypoexcitability of multiple areas of the right ventricle, and inducible poorly tolerated ventricular tachycardia.
Adult↗
Selective inhibition of thromboxane synthetase reduces group-B-beta-hemolytic-streptococci-induced pulmonary hypertension in piglets.
13 newborn piglets with group-B-beta-hemolytic-streptococci (GBS)-induced pulmonary hypertension were assigned to receive either placebo (group 1) or Dazmegrel, a thromboxane synthetase inhibitor (group 2). All piglets with pulmonary hypertension had increased thromboxane B2 (TxB2) and 6-keto PGF1 alpha levels. With continued GBS infusion, the placebo group demonstrated a continued elevation of pulmonary artery pressure (PAP) and of TxB2. The Dazmegrel piglets, however, despite continued GBS infusion, demonstrated a selective decrease in PAP associated with a significant decrease in TxB2 levels and stability of systemic pressure and cardiac output. These data demonstrate that thromboxane synthetase inhibition is effective therapeutically in selectively reducing PAP.
6-Ketoprostaglandin F1 alpha↗
Endogenous dilator prostaglandins in congenital heart disease.
Maintaining patency of the ductus arteriosus pending surgical intervention can be critical to the survival of the neonate with ductal dependent congenital heart disease. Spontaneously delayed ductal closure has been observed clinically and experimentally in newborns with critical pulmonic stenosis. Infants with ductal dependent congenital heart lesions were therefore studied to ascertain whether there was an endogenous increase in dilator prostaglandins prolonging ductal patency. Six neonates with cyanotic lesions (group 1) and six with left ventricular obstructive lesions (group 2) were studied. Circulating PGE2 was not increased in either group. The levels of plasma 6 keto PGF1 alpha, a stable hydrolysis product of prostacyclin, were found to be elevated, but only in the cyanotic group (3143 +/- 1844 vs 404 +/- 250 pg/ml; p less than 0.05; normal less than 500 pg/ml). As expected, PaO2's were also different (36 +/- 15 vs 72 +/- 34 mmHg; p less than 0.05). It is speculated, therefore, that increased synthesis and/or release of prostacyclin, possibly mediated by the hypoxia of the cyanotic ductal dependent lesion, contributes to persistent patency of the ductus arteriosus.
6-Ketoprostaglandin F1 alpha↗