Unexpected Course of Nonlinear Cardiac Interbeat Interval Dynamics during Childhood and Adolescence

The fluctuations of the cardiac interbeat series contain rich information because they reflect variations of other functions on different time scales (e.g., respiration or blood pressure control). Nonlinear measures such as complexity and fractal scaling properties derived from 24 h heart rate dynamics of healthy subjects vary from childhood to old age. In this study, the age-related variations during childhood and adolescence were addressed. In particular, the cardiac interbeat interval series was quantified with respect to complexity and fractal scaling properties. The R-R interval series of 409 healthy children and adolescents (age range: 1 to 22 years, 220 females) was analyzed with respect to complexity (Approximate Entropy, ApEn) and fractal scaling properties on three time scales: long-term (slope β of the power spectrum, log power vs. log frequency, in the frequency range 10−4 to 10−2 Hz) intermediate-term (DFA, detrended fluctuation analysis, α2) and short-term (DFA α1). Unexpectedly, during age 7 to 13 years β and ApEn were higher compared to the age <7 years and age >13 years (β: −1.06 vs. −1.21; ApEn: 0.88 vs. 0.74). Hence, the heart rate dynamics were closer to a 1/f power law and most complex between 7 and 13 years. However, DFA α1 and α2 increased with progressing age similar to measures reflecting linear properties. In conclusion, the course of long-term fractal scaling properties and complexity of heart rate dynamics during childhood and adolescence indicates that these measures reflect complex changes possibly linked to hormonal changes during pre-puberty and puberty

Post-Weaning Protein Malnutrition Increases Blood Pressure and Induces Endothelial Dysfunctions in Rats

Malnutrition during critical periods in early life may increase the subsequent risk of hypertension and metabolic diseases in adulthood, but the underlying mechanisms are still unclear. We aimed to evaluate the effects of post-weaning protein malnutrition on blood pressure and vascular reactivity in aortic rings (conductance artery) and isolated-perfused tail arteries (resistance artery) from control (fed with Labina®) and post-weaning protein malnutrition rats (offspring that received a diet with low protein content for three months). Systolic and diastolic blood pressure and heart rate increased in the post-weaning protein malnutrition rats. In the aortic rings, reactivity to phenylephrine (10−10–3.10−4 M) was similar in both groups. Endothelium removal or L-NAME (10−4 M) incubation increased the response to phenylephrine, but the L-NAME effect was greater in the aortic rings from the post-weaning protein malnutrition rats. The protein expression of the endothelial nitric oxide isoform increased in the aortic rings from the post-weaning protein malnutrition rats. Incubation with apocynin (0.3 mM) reduced the response to phenylephrine in both groups, but this effect was higher in the post-weaning protein malnutrition rats, suggesting an increase of superoxide anion release. In the tail artery of the post-weaning protein malnutrition rats, the vascular reactivity to phenylephrine (0.001–300 µg) and the relaxation to acetylcholine (10−10–10−3 M) were increased. Post-weaning protein malnutrition increases blood pressure and induces vascular dysfunction. Although the vascular reactivity in the aortic rings did not change, an increase in superoxide anion and nitric oxide was observed in the post-weaning protein malnutrition rats. However, in the resistance arteries, the increased vascular reactivity may be a potential mechanism underlying the increased blood pressure observed in this model

Age and gender dependent heart rate circadian model development and performance verification on the proarrhythmic drug case study

BACKGROUND: There are two main reasons for drug withdrawals at the various levels of the development path – hepatic and cardiac toxicity. The latter one is mainly connected with the proarrhythmic potency and according to the present practice is supposed to be recognized at the pre-clinical (in vitro and animal in vivo) or clinical level (human in vivo studies). There are, although, some limitations to all the above mentioned methods which have led to novel in vitro – in vivo extrapolation methods being introduced. With the use of in silico implemented mathematical and statistical modelling it is possible to translate the in vitro findings into the human in vivo situation at the population level. Human physiology is influenced by many parameters and one of them which needs to be properly accounted for is a heart rate which follows the circadian rhythm. We described such phenomenon statistically which enabled the improved assessment of the drug proarrhythmic potency. METHODS: A publicly available data set describing the circadian changes of the heart rate of 18 healthy subjects, 5 males (average age 36, range 26–45) and 13 females (average age 34, range 20–50) was used for the heart rate model development. External validation was done with the use of a clinical research database containing heart rate measurements derived from 67 healthy subjects, 34 males and 33 females (average age 33, range 17–72). The developed heart rate model was then incorporated into the ToxComp platform to simulate the impact of circadian variation in the heart rate on QTc interval. The usability of the combined models was assessed with moxifloxacin (MOXI) as a model drug. RESULTS: The developed heart rate model fitted well, both to the training data set (RMSE = 128 ms and MAPE = 12.3%) and the validation data set (RMSE = 165 ms and MAPE = 17.1%). Simulations performed at the population level proved that the combination of the IVIVE platform and the population variability description allows for the precise prediction of the circadian variation of drugs proarrhythmic effect. CONCLUSIONS: It can be concluded that a flexible and practically useful model describing the heart rate circadian variation has been developed and its performance was verified

Atherosclerosis lifestyle risk factors in children with congenital heart disease.

OBJECTIVE: To assess lifestyle risk factors for atherosclerotic cardiovascular disease in children with congenital heart disease. MATERIALS AND METHODS: Surveys were distributed to 329 unselected cardiac children. RESULTS: Many patients were taking an unhealthy diet and did not eat fruit (68%), vegetables (60%) or low-fat milk products (60%) every day, whereas 41% drank sweetened beverages and 89% ate foods high in fats at least three times a week. Only 15% spent half an hour daily involved in after-school physical activity, whereas 7.6% were overweight, 4.3% had arterial hypertension, 50% were passive smokers and 12% of teenagers were active smokers. CONCLUSION: Most cardiac children have modifiable cardiovascular risk factors. This highlights the importance of enhancing actions to promote a healthy lifestyle addressed to that population