Antenatal dexamethasone treatment transiently alters diastolic function in the mouse fetal heart.

Endogenous glucocorticoid action is important in the structural and functional maturation of the fetal heart. In fetal mice, although glucocorticoid concentrations are extremely low before E14.5, glucocorticoid receptor (GR) is expressed in the heart from E10.5. To investigate whether activation of cardiac GR prior to E14.5 induces precocious fetal heart maturation, we administered dexamethasone in the drinking water of pregnant dams from E12.5 to E15.5. To test the direct effects of glucocorticoids upon the cardiovascular system we used SMGRKO mice, with Sm22-Cre-mediated disruption of GR in cardiomyocytes and vascular smooth muscle. Contrary to expectations, echocardiography showed no advancement of functional maturation of the fetal heart. Moreover, litter size was decreased 2 days following cessation of antenatal glucocorticoid exposure, irrespective of fetal genotype. The myocardial performance index and E/A wave ratio, markers of fetal heart maturation, were not significantly affected by dexamethasone treatment in either genotype. Dexamethasone treatment transiently decreased the myocardial deceleration index (MDI; a marker of diastolic function), in control fetuses at E15.5, with recovery by E17.5, 2 days after cessation of treatment. MDI was lower in SMGRKO than in control fetuses and was unaffected by dexamethasone. The transient decrease in MDI was associated with repression of cardiac GR in control fetuses following dexamethasone treatment. Measurement of glucocorticoid levels in fetal tissue and hypothalamic corticotropin-releasing hormone (Crh) mRNA levels suggest complex and differential effects of dexamethasone treatment upon the hypothalamic-pituitary-adrenal axis between genotypes. These data suggest potentially detrimental and direct effects of antenatal glucocorticoid treatment upon fetal heart function.

[Conduction disorders at multiple levels during the acute phase of a myocardial infarct: an electrophysiological study]. / Trastornos de conducción a niveles múltiples durante la fase aguda del infarto del miocardio: estudio electrofisiológico.

Forty patients with a diagnosis of acute myocardial infarction (anterior 24, and inferior 16) were studied. Of these patients, 37.5% manifested second and third degree atrioventricular (AV) block as a complication; another 30% showed complete right bundle branch and left anterior hemiblock. Right bundle branch and left posterior hemiblock were evidenced in 12.5% of the subjects. There was 20% with complete left bundle branch block. Electrophysiologic studies were performed in all patients to assess the site of block. A direct relation was found between the surface ECG and the His bundle electrogram studies in patients with an inferior myocardial infarction and AV block, both procedures located the conduction disturbances at the AV node (suprahisian block), in contrast to patients with anteroseptal myocardial infarction whose surface ECG only showed bundle branch block or fascicular block. The His bundle electrogram registered multiple levels of AV block, 70% with troncular and infrahisian block that gave way to sudden AV block. The mechanism responsible for this block was considered to be a functional longitudinal dissociation of conduction system due to an acute ischemic injury of the His bundle, more than a sudden and simultaneous failure of all the bundle branch of His. We conclude that electrophysiologic studies are a useful procedure for identification of a group of patients with multiple AV conduction disturbances that have a less favorable prognosis than those with only suprahisian level of block.