Magnetic resonance spectroscopy in congenital heart disease.

OBJECTIVE: To determine the feasibility of studying myocardial and skeletal muscle bioenergetics using 31P magnetic resonance spectroscopy (MRS) in babies and young children with congenital heart disease. SUBJECTS: 16 control subjects aged 5 months to 24 years and 18 patients with CHD, aged 7 months to 23 years, of whom 11 had cyanotic CHD, five had cardiac failure, and two had had a Senning procedure. DESIGN: 31P MRS was carried out using a 1.9 Tesla horizontal 65 cm bore whole body magnet to study the myocardium in 10 patients and skeletal muscle (gastrocnemius) in 14 patients, eight of whom were exercised, together with appropriate controls. RESULTS: In hypoxaemic patients, in skeletal muscle at rest intracellular pH (pHi) was abnormally high [7.06 (SEM 0.04) v 7.04 (0.05), P < 0.01] and showed a positive correlation with haemoglobin (P < 0.03). On exercise, hypoxaemic patients fatigued more quickly but end-exercise pHi and phosphocreatine recovery were normal, implying that an equivalent but smaller amount of work had been performed. End-exercise ADP concentration was lower. On recovery, the initial rate of phosphocreatine resynthesis was low. Skeletal muscle bioenergetics were within normal limits in those in heart failure. In the myocardium, the phosphocreatine/ATP ratio was similar in controls and hypoxaemic subjects, but low in those in heart failure. CONCLUSIONS: In heart failure, the myocardial phosphocreatine/ATP ratio was reduced, as in adults, while resting skeletal muscle studies were normal. By contrast, hypoxaemic children had normal myocardial bioenergetics, but showed skeletal muscle alkalinity, and energy reserves were more readily depleted on exercise. On recovery, the initially slow phosphocreatine resynthesis rate reflects a low rate of mitochondrial ATP synthesis, probably due to an inadequate oxygen supply. 31P MRS offers a safe, non-invasive method of studying myocardial and skeletal muscle bioenergetics in children as young as 5 months.

Thromboxane A2 and prostacyclin biosynthesis in children and adolescents with pulmonary vascular disease.

BACKGROUND: The pathogenesis of pulmonary vascular disease in children with congenital heart disease is incompletely understood. Thromboxane (TX) A2 and prostacyclin (PGI2) have opposing effects on platelet aggregation and pulmonary vascular smooth muscle. An imbalance in their biosynthesis could contribute to the progressive increase in pulmonary vascular resistance seen in older untreated patients with pulmonary hypertensive congenital heart disease and the thrombotic complications they may develop. METHODS AND RESULTS: We investigated TXA2 and PGI2 biosynthesis in 15 young children (0.2 to 2.25 years old) with congenital heart disease with increased pulmonary blood flow and potentially reversible pulmonary vascular disease by measuring urinary excretion of 2,3-dinor-TXB2 and 2,3-dinor-6-oxoprostaglandin (PG) F1 alpha and compared the findings with those in 16 healthy children (0.5 to 2.8 years old). 2,3-Dinor-TXB2 excretion was greater in the patients than in control subjects (1253 +/- 161 versus 592 +/- 122 ng/g creatinine; P < .001). Excretion of 2,3-dinor-6-oxo-PGF1 alpha was 452 +/- 54 compared with 589 +/- 95 ng/g creatinine in control subjects. In 5 patients who underwent successful cardiac surgery > or = 1 year later excretion of 2,3-dinor-TXB2 decreased from 1100 +/- 298 to 609 +/- 131 ng/g creatinine (P < .05), a value comparable to those in 5 healthy children of similar age (749 +/- 226 ng/g creatinine). We also compared 15 patients (11 to 23 years old) with advanced irreversible pulmonary vascular disease with 19 healthy control subjects (10 to 23 years old). The ratio of TX to PGI2 metabolite excretion was greater in the patients than in control subjects (3.5 +/- 0.6 versus 2.0 +/- 0.3; P < .05). CONCLUSIONS: There is increased 2,3-dinor-TXB2 excretion in children with congenital heart disease and a high pulmonary blood flow that may reflect an imbalance in biosynthesis of TXA2 and PGI2 in the pulmonary vascular bed. The imbalance may contribute to the progressive development of increased pulmonary vascular resistance and persists in older patients whose heart defects are uncorrected.

Response to dopamine and dobutamine in the preterm infant less than 30 weeks gestation.

Mean arterial pressure (MAP) and heart rate (HR) were studied in 12 hypotensive preterm neonates given dopamine. A significant, although temporary, elevation in MAP (8 +/- 3 mm Hg; p less than .01) occurred in five neonates in response to 5 micrograms/kg.min, but an increase in MAP was found in all infants (11 +/- 6 mm Hg; p less than .01) when the infusion rate was doubled. This elevation was sustained only in five who previously showed some response to the slower infusion. HR was unaffected except for an increase of 22 +/- 12 beat/min (p less than .01) in the five showing sustained MAP elevation with 10 micrograms/kg.min. Dobutamine failed to raise MAP in the seven who relapsed, and refractory shock resulted. We conclude that time should not be wasted when starting dopamine at less than 10 micrograms/kg.min in hypotensive preterm infants, as lower rates are unlikely to produce a response and delay may cause further compromise.

Blood pressure fluctuation and intraventricular hemorrhage in the preterm infant of less than 31 weeks' gestation.

A total of 22 infants of less than 31 weeks' gestation who were mechanically ventilated for a minimum of 12 hours for respiratory distress syndrome were studied. The coefficient of variation of direct systolic pressure was measured each minute from six to 36 hours of age and averaged per hour after birth with a microcomputer-based system of data collection. At the start of recording, the ultrasound scan appeared normal in each infant, but intraventricular hemorrhage developed in ten infants less than 36 hours of age. Twelve infants remained free of intraventricular hemorrhages. BP fluctuation was greater for a longer proportion of measured time in infants in whom intraventricular hemorrhage did not develop compared with those in whom it did develop P less than .05). These findings do not support a causal relationship between BP fluctuation and intraventricular hemorrhage within the range of coefficient of variation studied.

Effect of pancuronium and pethidine on heart rate and blood pressure in ventilated infants.

To investigate cardiovascular effects in 32 ventilated neonates, given either pancuronium or pethidine, computer based data were analysed for five minutes preceding and for 20 minutes after administration of the drugs. Heart rate and direct mean arterial pressure remained unchanged but arterial pressure variability decreased with each drug.

Mean arterial blood pressure and neonatal cerebral lesions.

Computerised continuous measurement of mean arterial blood pressure (MAP) and serial cranial ultrasonography in 33 infants of less than 31 weeks' gestation showed that a MAP of less than 30 mm Hg for over an hour was significantly associated with severe haemorrhage, ischaemic cerebral lesions, or death within 48 hours. No severe lesions developed with a MAP greater than or equal to mm Hg.

Peripheral arteriovenous fistula as a cause of neonatal cardiac failure.

A newborn infant presented with cardiac failure secondary to a peripheral cavernous haemangioma. She was successfully treated surgically but was later diagnosed as having GM1 gangliosidosis.

Effects of microinjections of 5,7-dihydroxytryptamine in the suprachiasmatic nuclei of the rat on serotonin reuptake and the circadian variation of corticosterone levels.

The role of the 5-hydroxytryptamine (5-HT) terminals in the suprachiasmatic nucleus (SCN) in the production of the circadian variation of corticosterone secretion was investigated by lesioning the 5-HT inputs to the SCN with 5,7-dihydroxytryptamine (5,7-DHT). Vehicle-injected animals showed a normal circadian variation of corticosterone levels. In contrast, the mean corticosterone levels of the 5,7-DHT-lesioned group were intermediate between control peak and trough values, and although the individual rats showed fluctuations, no significant circadian variation was present in the group as a whole. 3H-5-HT reuptake in the SCN was reduced to 38% of the mean control level in the 5,7-DHT-lesioned group, but ventromedial hypothalamic 3H-5-HT reuptake was only decreased to 82% of control. These results indicated that the SCN 5-HT terminals may play an important role in the synchronization of the circadian variation of corticosterone secretion.