Biomedical subjects
Publications and source records attributed to J E Lock.
6-Keto-PGE1 is a potent direct dilator of the pulmonary and systemic circulations of the newborn lamb under both normoxic and hypoxic conditions. Its threshold dose is similar to that of PGI2 and PGE1. Under hypoxia, 6-keto-PGE1 appears equally effective on the pulmonary and systemic circulations, while under normoxia it predominantly affects the systemic circulation.
The pulmonary vascular effects of tolazoline were studied in unsedated newborn lambs during normal oxygenation and hypoxia. Direct and indirect pulmonary vascular responses were analyzed separately. During normal oxygenation, tolazoline (1 mg/kg) given into a branch pulmonary artery increased cardiac output while decreasing systemic and pulmonary resistances. Pulmonary flow distribution did not change, suggesting that the fall in pulmonary resistance was due to an indirect rather than a direct action of the drug. Tolazoline had similar effects on systemic and pulmonary resistances in the hypoxic lamb; however, there was a shift in blood flow toward the injected lung, indicating local pulmonary vasodilation induced by the drug. In either case, tolazoline did not alter the resistance ratio between the injected lung and the systemic circulation. We conclude that tolazoline is a direct pulmonary vasodilator in the hypoxic lamb, but does not appear to lower the pulmonary to systemic resistance ratio.
We determined alterations in plasma and red-cell electrolyte concentrations associated with digoxin administration in 11 children in heart failure, 24 nontoxic patients receiving maintenance digoxin and 11 children in whom digoxin toxicity developed. Twenty normal children served as controls. Digoxin therapy was associated with a mean (+/- S.E.M.) increase in red-cell sodium from a pretreatment level of 6.2 +/- 0.7 meq per liter to 11.9 +/- 1.2 meq per liter and a decrease in red-cell potassium from 105.4 +/- 1.4 to 99.5 +/- 1.9 meq per liter (P less than 0.001). The red-cell sodium levels of toxic patients exceeded those of nontoxic patients whereas the potassium concentrations were lower (P less than 0.001). Toxic patients manifested significantly higher ratios of red-cell sodium to red-cell potassium (0.213 +/- 0.003) than nontoxic patients (0.085 +/- 0.008; P less than 0.001). Changes in red-cell electrolytes are sensitive indicators of digoxin affects.
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An 11-year-old girl was found to have completely obstructed left pulmonary veins eight years following corrective surgery for transposition of the great arteries. The patient was acyanotic and asymptomatic. Retrograde flow of arterial blood from the affected left lung accounted for an angiographic appearance that mimicked occlusion of the left pulmonary artery and resulted from a failure of systemic venous development. Pulmonary venous anatomy could only be demonstrated by pulmonary arterial wedge angiographic studies. This experience emphasizes that complete unilateral pulmonary venous obstruction may occur in an asymptomatic patient and underlines the importance of investigating pulmonary venous anatomy in any patient with gross inequality of the distribution of pulmonary blood flow.
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Glycine concentrations were measured in plasma and cerebrospinal fluid of five patients in different types of hyperglycinemia to determine why severe neurologic deterioration is confined to the so-called nonketotic form of hyperglycinemia. Glycine content and glycine-cleavage enzyme activity were also determined in brain obtained in autopsy from three of these patients. Spinal-fluid glycine concentrations were 15 to 30 times above normal in patients with nonketotic hyperglycinemia, but were normal in those with hyperglycinemias of undetermined type who had comparable elevations of plasma glycine. Glycine content was two to four times above normal in several brain regions, and brain glycine cleavage enzyme activity was absent in two patients dying of nonketotic hyperglycinemia. By contrast, glycine content was normal and glycine cleavage activity present in the brain of an infant who died of hyperglycinemia of unknown cause. These results suggest that elevated glycine levels may be harmless in blood, but lethal in brain.
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Anatomic evidence suggests that leu5-enkephalin (Leu5-enk) may be involved in the physiologic control of pulmonary vascular tone. Information regarding its pulmonary vascular effect is limited; we therefore studied its effect on the immature pulmonary circulation. Normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around the right and left pulmonary arteries were used. Leu5-enk was injected into one pulmonary artery only, so that any direct effect of the peptide on the pulmonary vessels could be determined by measuring changes in the ratio of blood flow to the injected versus the non-injected lung. Leu5-enk caused a small but significant increase in pulmonary artery pressure without increasing cardiac output or left atrial pressure (threshold = 1 microgram/kg); it is therefore a pulmonary vasoconstrictor. At a dose of 10 micrograms/kg, Leu5-enk also raised pulmonary artery pressure (20.6 mmHg to 23.9 mmHg; F(8,36) = 15.1 p less than 0.001) and calculated PAR (14.6 to 16.1 units; NS). However, the ratio of blood flow to the two lungs did not change; thus, Leu5-enk does not appear to directly act on pulmonary vessels, but rather through an intermediary to produce pulmonary vasoconstriction. This indirect pulmonary vasoconstriction was blocked by pretreatment with naloxone (3 mg/kg). We conclude that Leu5-enk is a pulmonary vasoconstrictor, albeit a weak one, in the lamb and may therefore play a role in pulmonary vascular homeostasis. This vasoconstriction does not seem to be due to a direct effect on pulmonary vessels by Leu5-enk, but may be effected through a neural or hormonal intermediary.
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Bombesin-, calcitonin-, and serotonin-immunoreactive pulmonary neuroendocrine cells (PNEC) were quantitated in the lungs of infants dying of hyaline membrane disease (HMD) and bronchopulmonary dysplasia (BPD). When compared with the lungs of age-matched control infants dying of noncardiopulmonary causes, infants who had HMD demonstrated a decrease in the numbers of bombesin-, calcitonin-, and serotonin-immunoreactive PNECs, while infants who had BPD demonstrated an increase. This difference was most pronounced at 2 months of age, when infants with BPD had a threefold increase in bombesin-, a tenfold increase in calcitonin-, and a 34-fold increase in serotonin-immunoreactive cells. In both control infants and infants who had acute and chronic lung disease, a consistent relationship was found between numbers of the three cell types: bombesin greater than calcitonin greater than serotonin. Radioimmunoassay of lung tissue from infants dying of HMD and BPD confirmed low levels of bombesin immunoreactivity in HMD and increased levels in BPD. Circulating plasma bombesin levels in neonates, as measured by radioimmunoassay, were significantly higher than levels found in adults. Though these findings are intriguing, the documentation of a causal relationship between observed alterations in PNEC and the vascular and gas exchange abnormalities known to be associated with HMD and BPD must await further studies.