Stuart Berger

Prostaglandin levels: Predictors of indomethacin responsiveness

SummaryPretreatment plasma dilator prostaglandin levels were measured in 16 premature infants with patent ductus arteriosus in an attempt to correlate abnormally elevated levels with clinical responsiveness to indomethacin therapy. Nine of the 16 infants responded well to indomethacin, with complete disappearance of their murmurs by 48 h. Eight of these nine infants had elevated baseline 6 keto PGF1α levels (>500 pg/ml).In contrast, seven of the 16 infants did not respond to indomethacin, and six of these had 6 keto PGF1α within the normal range (<500 pg/ml). PGE2 levels varied in the same general direction, but lacked the specificity and sensitivity of the 6 keto PGF1α levels. Thus, 6 keto PGF1α levels seem to correlate with, and may eventually be helpful in predicting, clinical indomethacin responsiveness in the premature neonate with patency of the ductus arteriosus.

Acute Liver Injury after Protracted Seizures in Children

Three children were observed to have extensive liver injury following protracted seizures. Two recovered with supportive care and one died from central nervous system complications. When first measured, the levels of aminotransferases were minimally elevated, but they increased to 250 to 8,000 times normal within 12 to 24 h after the seizure episode. They fell to near normal over the next 8 to 11 days in the survivors, and to one sixth of the peak level by 4 days in the patient who died. A percutaneous liver biopsy from one child demonstrated centrolobular necrosis consistent with severe ischemic injury. Common causes for liver dysfunction, including viral hepatitis, drug hepatitis, and Reye syndrome, were excluded on clinical, serologic, and histologic grounds. We reason that hepatic injury resulted from ischemia. We speculate that prior treatment with anticonvulsants, which are capable of inducing mixed-function oxidases in the liver, aggravated the ischemia-reperfusion injury by increasing the production of reactive oxygen intermediates and reducing cytoprotective mechanisms. Prevention of such injury should be directed toward control of seizures and early respiratory support when seizures occur, not restructuring medication regimens.

The Pathophysiology and Treatment of Canine Kerosene Pulmonary Injury: Effects of Plasmapheresis and Positive End-Expiratory Pressure

Hydrocarbon aspiration is a relatively common cause of pulmonary injury in the pediatric age group. We evaluated the pathophysiology of kerosene aspiration in 18 anesthetized dogs during the first hour after injury and then compared the effects of treatments by plasmapheresis (n = 6) and positive end-expiratory pressure (PEEP) of 10 cm H2O (n = 6) with the results obtained in untreated control dogs (n = 6) over the next four hours. A group of uninjured control dogs (n = 3) confirmed that surgical preparation and saline sham injury did not cause acute lung injury like that due to kerosene. The untreated control dogs with a stable pulmonary capillary wedge pressure (Ppw) of 10 torr received 0.5 mL/kg of intratracheal kerosene. Although Ppw was maintained at 10 torr for five hours post-injury in these dogs, there was a wide range of lung edema (wet lung weight to body weight ratios from 16.4 to 61.1 g/kg; median of 41.4 g/kg). Between one and five hours, extravascular thermal volume (ETV) increased by 19.1 mL/kg, associated with a median increase in venous admixture (Ova/ Qt) of 28.5% and a median reduction in lung compliance of 12.7 mL/cm H2O. Another group of dogs was similarly injured, but underwent batch plasmapheresis one hour after injury to reduce Ppw to a target value of 5 torr for the remainder of the protocol. Plasmapheresis was associated with a smaller change in ETV (0.8 mL/kg, P < .05 compared with injured animals, Kruskall-Wallis). Gravimetric analysis of edema from lungs excised at five hours confirmed the in vivo findings that reduced Ppw was associated with a lower median wet weight to body weight ratio (20.5 g/kg) than in the untreated group (P < .06, Kruskall-Wallis). Similarly, progressive increases in Qva/Qt (2.6%, P < .06) and decreases in lung compliance (3.7 mL/cm H2O, P < .05) were prevented by plasmapheresis. A third group of dogs with transmural Ppw maintained at 10 torr underwent identical injury but were treated from one hour with 10 cm H2O PEEP. In this group, Qva/Qt was also stabilized (median decrease of 2.5%): but edema formation continued (median ETV increase of 28.5 mL/kg). Cardiac output and oxygen delivery were adequately maintained in both treatment groups so that oxygen consumption was not reduced. We conclude that kerosene aspiration caused pulmonary vascular leaks of varied severity and that plasmapheresis reduced pulmonary edema and its adverse effects on gas exchange and lung mechanics in this model. PEEP also reduced Qva/Qt, but did not reduce edema or lung stiffness and so necessitated the use of higher inflation pressures. Because plasmapheresis did not adversely affect systemic oxygen delivery and consumption, this canine study supports a therapeutic approach to early hydrocarbon pneumonitis of seeking the lowest vascular volume or Ppw associated with an adequate cardiac output and oxygen transport.

Prostaglandins and echocardiography in the assessment of patent ductus arteriosus

Prostaglandin (PG) levels and M-mode echocardiography were used to evaluate the severity of patent ductus arteriosus (PDA) in 19 premature infants. Mean 6-keto-PGF1α levels in infants with more severe left-to-right shunting were significantly higher than those in infants with a moderate level of shunting (1335 ± 763 vs. 504 ± 348 pg/ml, respectively). Furthermore, there was a significant correlation between this elevation and a decrease in the left ventricular systolic time interval, suggesting that both reflect the severity of ductal shunting. Although other echocardiographic measurements of cardiovascular function generally showed some tendency to vary with 6-keto-PGF1α levels, none was as closely correlated with the extent of PG elevation. Levels of PGE2 also seemed to vary with PDA severity; however, this correlation was not as significant.

Congenital left atrial aneurysm in an infant

Congenital left atrial aneurysm, without associated cardiac abnormalities, is a rare defect. We report the case of a large left atrial aneurysm filling almost the entire left hemothorax. This is the first report of this anomaly occurring in an infant less than 1 year of age.

Defect in fatty acid oxidation: Laboratory and pathologic findings in a patient

The clinical, laboratory, and pathologic findings in a patient with a previously undescribed deficiency in fatty acid oxidation are summarized. The patient had a fatal defect in fatty acid metabolism profoundly affecting heart, skeletal muscle, liver, and kidney. Oxidation of palmitate was 38-51% of controls. Complementation assays demonstrated that the patients fibroblasts complemented fibroblast lines from all known defects in fatty acid oxidation except long-chain acyl-CoA dehydrogenase deficiency. Urine and serum carnitine profiles also were indicative of a defect in the oxidation of long-chain substrate; however, the palmitoyl-CoA dehydrogenase activity was actually increased. This finding indicates that the patient had a defect that was distinct from, but possibly related to, long-chain acyl-CoA dehydrogenase deficiency. This patient demonstrates the laboratory and pathologic findings in defects in fatty acid oxidation and how they differ from those in Reye syndrome.

1408 PROSTAGLANDINS AND SYSTOLIC TIME INTERVALS (LVSTI) IN THE DIAGNOSIS OF PATENT DUCTUS ARTERIOSUS (PDA)

The ductus arteriosus of the premature neonate is exquisitely sensitive to prostaglandins. Dilator prostaglandins 6 keto PGF1α, a stable metabolite of prostacyclin, and PGE2 were measured by a RIA in 15 infants with PDA. Left ventricular systolic time intervals (LVSTI) were measured by M-mode echocardiography. LVSTI ≤ 0.30 are associated with clinically significant ductal shunting. Mean 6 keto PGF1α levels in infants with more severe shunting (LVSTI≤0.30) were significantly higher than in those with a moderate level of shunting (776 ± 432 vs. 302 ± 115 pg/ml; p<0.05). Furthermore, a significant correlation was found between the extent of elevation of 6 keto PGF, and of decrease in LVSTI suggesting that both reflect the severity of left to right shunting. Elevated PGE2 levels and LA/Ao ratios, on the otheY hand, were not correlated with PDA severity.

Response of Primitive Veins of Chick Embryos to Experimental Transection

A recent microangiographic study on chick embros at very early stages of development (H-H stages 14–22) confirmed the existence of two intracardiac streams prior to and during early cardiac septation [1]. Methylene blue injection into eight peripheral vitelline vein sites demonstrated a different pattern of intracardiac streaming than is traditionally seen. Previous reports have described a right stream and a left stream within the primitive atrium and ventricle that spiraled within the bulboventricular region [2]. Unlike these previous reports, we observed craniocaudal relationships of the two streams within the atrium and atrioventricular canal. Within the ventricle and conus, we noted dorsoventral relationships of the two venous streams. Both streams assumed a parallel course and did not spiral within the conus. In addition, there was longitudinal separation of the streams at and beyond the branchial arches, as well as within the dorsal aorta. These findings argued against the “flow-molding” concept of Bremer, which assumed that bulboventricular and truncal septation was a consequence of and determined by intracardiac flow streaming [2].

THROMBOXANE B2 LEVELS IN NEONATES WITH PERSISTENT FETAL CIRCULATION

Plasma levels of Thromboxane B2 (TxB2) were determined by radioimmunoassay in seven infants with persistent fetal circulation (PFC) of various etiologies. The levels were found to be quite elevated as compared with those of seven neonates with other cardiorespiratory problems, but without PFC:All of the infants with PFC, except one, had TxB2 levels >300pg/ml, while all of the controls had levels of <300pg/ml. These differences are significant (p <0.05).Of the PFC infants, two had β strep sepsis, four had meconium aspiration pneumonia and two were prematures with HMD. Within the PFC group, however, the type of primary lung disease did not seem to make a difference in TxB2 levels. Two of the infants were thrombocytopenic; although, this in itself was not associated with higher TxB2 levels. Both infants with TxB2 levels >2,000 pg/ml subsequently expired.TxB2 is a potent vasoconstrictor which is noted to be elevated in some infants with PFC, with and without sepsis. This increased vasoconstrictor tone may play a role in the pathophysiology of PFC, and may have prognostic implications.