Changes in fetal cardiac axis between 8 and 15 weeks' gestation.

OBJECTIVES: To document changes in the normal embryonic/fetal cardiac axis in the late first and early second trimesters of pregnancy. METHODS: Images from 188 fetal echocardiograms performed prospectively between 8 and 15 weeks' gestation in 166 healthy pregnancies and in 10 pregnancies with severe fetal heart disease were reviewed. For each echocardiogram, three measurements of the cardiac axis were taken in the axial plane at the level of the four-chamber view. Differences in mean embryonic/fetal cardiac axis at different gestational ages in the healthy pregnancies were compared. RESULTS: The mean ± SD embryonic/fetal cardiac axis was 25.5 ± 11.5° from 8 + 0 to 9 + 6 weeks (Group 1), 40.4 ± 9.2° from 10 + 0 to 11 + 6 weeks (Group 2), 49.2 ± 7.4° from 12 + 0 to 12 + 6 weeks (Group 3), 50.6 ± 5.7° from 13 + 0 to 13 + 6 weeks (Group 4) and 48.6 ± 7.3° from 14 + 0 to 14 + 6 weeks (Group 5). Groups 1 and 2 were significantly different from each other and all other groups (P < 0.05). The results for 22 cases with repeat measurements from 8 + 0 to 11 + 6 and 12 + 0 to 14 + 6 weeks confirmed that the embryonic/fetal cardiac axis increased significantly (P < 0.001). In the cases with severe congenital heart disease, the cardiac axis was > 90th centile in four cases and < 10th centile in two cases. CONCLUSIONS: The embryonic cardiac axis is relatively midline at 8 weeks and levorotates in the late first trimester. By 12 weeks' gestation, the normal leftward fetal cardiac axis is established and remains stable until at least 14 + 6 weeks. Observation of an abnormal cardiac axis in some cases of severe congenital heart disease prior to 15 weeks' gestation may assist in prenatal detection.

Evolution of heart disease in utero.

Cardiac embyogenesis occurs in the first 6 to 7 weeks of human development. Although it is during this time that many of the major cardiovascular defects develop, many of these lesions continue to evolve and others develop in the latter half of gestation. There may be development or progression of ventricular inflow or outflow tract and arch obstruction, and ventricular or great artery hypoplasia. There may be progressive antrioventricular or semi-lunar valve regurgitation which can compromise the fetal circulation. There may be development of dysrhythmias, primary myocardial disease and heart failure. The fetal shunts, the foramen ovale and ductus arteriosus, may change in form and function. Finally, cardiac tumors may develop, grow, or regress. Knowledge of the mechanisms of and potential for progression in fetal heart disease is critical for counseling regarding prognosis and for planning of prenatal and neonatal management.

L-carnitine attenuates doxorubicin-induced lipid peroxidation in rats.

Doxorubicin (DOX) was administered intraperitoneally to rats in six equal, 2.5 mg/kg doses over a 2-week period with or without L-carnitine. Injury was monitored by echocardiography, release of myosin light chain-1 (MLC-1), and by measurement of aldehydic lipid peroxidation products. General observation revealed that DOX alone caused more ascites than DOX plus L-carnitine. Animals sacrificed 2 h after the sixth dose had significantly higher aldehyde concentrations than 2 h after a single dose of DOX. Aldehydes in plasma and heart remained elevated for 3 weeks after the final dose of DOX, whereas L-carnitine prevented or attenuated the DOX-induced increases in lipid peroxidation. The increase in MLC-1 2 h after the sixth dose of DOX was greater than after a single dose, suggesting cumulative damage. Echocardiography did not detect either early injury or the protective effects of L-carnitine. These data indicate that lipid peroxidation following DOX occurs early, and parallels the cumulative characteristics of DOX-induced cardiotoxicity. The protective effects of L-carnitine may be due to improved cardiac energy metabolism and reduced lipid peroxidation.

Doxorubicin-induced acute changes in cytotoxic aldehydes, antioxidant status and cardiac function in the rat.

Doxorubicin (DOX)-induced cardiotoxicity is thought to be caused by free radical-mediated mechanisms. An in vivo rat model was developed to investigate the DOX-induced cascade of early biochemical changes focusing on the central role of the aldehydic lipid peroxidation products. Antioxidant status was evaluated by glutathione measurements. Creatine Kinase (CK) activity was measured as an index of cardiac injury. Development of functional abnormalities were documented by echocardiography. The results showed that aldehydes in rat plasma and heart tissues increased significantly following DOX treatment. The changes occurred early, peaked around 2 h after DOX administration, and the levels declined or returned to baseline value within 8-24 h. Toxic aldehyde levels including malondialdehyde, hexanal and 4-hydroxy-non-2-enal also increased. Acyloin levels, metabolic products of aldehydes, increased early and then decreased in plasma, and there was a significant decrease in heart tissues after DOX treatment. GSH levels decreased early, then increased by 24 h, while GSSG levels decreased initially, then increased after DOX treatment, suggesting early depletion of GSH and a later rebound phenomenon. CK levels were elevated after treatment. The functional abnormalities were documented by stress echocardiography in some rats although the changes were not consistent at such an early stage following treatment. Our data confirmed the involvement of free radicals, and suggested that the cytotoxic aldehydes play a central role in initiating the steps that lead to functional impairment of the myocardium following DOX administration. Scavengers and the metabolic removal of some of the aldehydes also play a role in protecting the myocardium against injury.