In SHR, hypertension induces early subcellular LA myocyte Ca2+ remodelling during compensated LV hypertrophy. In basal conditions, atrial myocyte CaTs are not changed. At increased stimulation frequency, however, SHR atrial myocytes become more prone to arrhythmogenic Ca2+ alternans, suggesting a link between hypertension, atrial Ca2+ homeostasis, and development of atrial tachyarrhythmias.

Female Wistar rats were injected intravenously with tracer levels of 210Pb, alone or combined with carrier Pb(NO3)2 at 5 or 25 mg/kg body weight at 9 or 15 days of gestation (dg). Tissue 210Pb distribution and retention, and lead excretion, were measured several times during the first 30 h and at 20 dg. Toxic effects following the administration of 25 mg/kg (a teratogenic dose) included an early decrease in hematocrit, hematuria, gastrointestinal hemorrhage, and diarrhea, as well as an eventual loss of body weight and an increase in spleen and kidney weights. The stage of pregnancy at injection did not affect the retention and distribution of lead in major organs other than the reproductive system. Following injection of the 25-mg/kg dose, deposition of lead in the liver, kidney, spleen, and lung was elevated. Disproportionately high plasma lead levels were also observed at early times after the injection of the 25-mg/kg dose, and may act as a significant factor in placental lead transfer and subsequent malformations or fetal mortality.

Lead metabolism was studied in the fetoplacental unit (FPU) of Wistar rats during the genesis of developmental abnormalities and embryonic death. Female rats were injected iv with tracer 210Pb(NO3)2, alone or in combination with 5 or 25 mg Pb(NO3)2/kg, at 9 or 15 days of gestation (dg). The distribution of lead and its effects were determined in the FPUs during the ensuing 30-h period and at 20 dg. Hemorrhage of the egg cylinder was noted as early as 6 h postinjection of 25 mg/kg at 9 dg. By 20 dg, fetuses exhibited characteristic stunting and external malformations (gastroschisis and severe skeletal defects). Administration of this dose at 15 dg produced petechial hemorrhage in fetal brain within 90 min; more massive hemorrhage was a consistent observation by 24 h. At 20 dg, embryo mortality was 44% in rats injected with 25 mg/kg at 9 dg and 100% in those injected at 15 dg. At 90 min after injection, lead content of 15-dg FPUs was 10 times that of the 9-dg FPUs, but the weights of the 15-dg FPUs were 16 times greater. Values remained relatively constant in 15-dg FPUs for 30 h, but early clearance was observed after injection at 9 dg, with a return to 90-min values by 20 dg. In the 15-dg FPUs, placental clearance was followed by fetal lead incorporation, which reached a maximum at 6 h. Fetal lead values were constant from 6 to 30 h after injection at tracer and 5-mg/kg dose levels, but values increased progressively at 25 mg/kg. Both temporal and quantitative relationships of fetal lead metabolism were disrupted by the 25-mg/kg dose, but the nature of the effect was determined by the stage of fetal development at exposure.

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BackgroundThe most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency (CAH). Both men and women with classic CAH have lower fertility rates than the general population, and an increased rate of miscarriages has been reported in affected women. There are no data on the incidence rate of miscarriages in families with an offspring that have classic CAH.MethodsWe studied families with a history of classic CAH. The families came from different parts of Germany and attended the annual meeting of the German CAH support group for parents and patients which was held in Hamburg in September 2014. The data was collected anonymously by a paper-based questionnaire which was completed by the families at home. The families also accepted the responsibility to address this question to their siblings. In all, the data of 50 families with at least one child with classic CAH, and the data of 164 parental siblings were available for evaluation. Miscarriage rates were calculated in relation to the reported pregnancies.ResultsTwenty-two miscarriages were reported from 19 families. At least one miscarriage occurred in 38% of the families, three families experienced two miscarriages and 16 families had one miscarriage each. The mean miscarriage rate was 15.8%. The heterozygous mothers had a total of 90 siblings (41 m, 49 f), while 74 siblings (33 m, 41 f) were reported from the heterozygous fathers. The miscarriage rate was 10.1% in the families of the mothers` siblings, and 11.4% in the families of the fathers` siblings. The genotype was known in all parents that have an offspring with classic CAH, but not defined in 82% of the maternal siblings, and in 86% of the paternal siblings. No child with classic CAH has been diagnosed in any of the sibling’s families to date.ConclusionOur data show that the miscarriage rate in German families with a child with classic CAH is not elevated.Electronic supplementary materialThe online version of this article (10.1186/s12884-018-2091-8) contains supplementary material, which is available to authorized users.