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As a result of epigenetic changes, children conceived by assisted reproduction may be at risk of premature cardiovascular aging with notably increased blood pressures. Their cardiovascular autonomic nervous function is unknown. Therefore, this study investigated the cardiovascular autonomic nervous function in 8-12-yr-old children (51% girls) conceived naturally (n = 33) or by assisted reproduction with frozen (n = 34) or fresh (n = 38) embryo transfer by evaluating heart rate variability, during rest; from provocation maneuvers; and from baroreflex function. Heart rate and blood pressure response to provocation maneuvers and baroreflex function were comparable between children conceived naturally or by assisted reproduction. The mean RR-interval and high-frequency component of heart rate variability were lower in children conceived by assisted reproduction than in children conceived naturally. Children conceived by fresh embryo transfer had -17% lower heart rate-corrected standard deviation of normal-to-normal R-R intervals; -22% lower heart rate-corrected square root of the mean of the squared difference between successive R-R intervals; and -37% higher low-frequency/high-frequency ratio than naturally conceived children. Children conceived by assisted reproduction still had lower heart rate variability and vagal modulation than naturally conceived children after adjustment for confounders. Thus, these results raise the possibility of sympathetic predominance in children conceived by assisted reproduction. Therefore, it is important to reproduce these results in larger and older cohorts as sympathetic predominance relates with cardiovascular and metabolic diseases. [ABSTRACT FROM AUTHOR]

Experimental studies using 38 adult rabbits help determine the relation between the degree of alveolar inflation and amount of actively transported alveolar liquid. Separation of active and passive liquid clearance enables the determination of passive hydraulic conductance of the alveolar epithelium. Active sodium transport reverses the secretion of liquid into the alveoli at low lung inflation, while at high lung inflation active sodium transport does not contribute to transepithelial flow. Experimental data reveal the degradation of liquid clearance due to pulmonary inflation.

Windkessel function is governed by conductance artery compliance that is associated with cardiovascular disease in adults independently of other risk factors. Sex-related differences in conductance artery compliance partly explain the sex-related differences in risk of cardiovascular disease. Studies on sex-related differences in conductance artery function in prepubertal children are few and inconclusive. This study determined the conductance artery compliance and cardiac function by magnetic resonance imaging in 150 healthy children (75 girls) aged 7-10 yr. Any sex-related difference in conductance artery function was determined with correction for other potential predictors in multivariable linear regression models. Our data showed that ascending [crude mean difference 1.11 95% confidence interval (CI) (0.22; 2.01)] and descending [crude mean difference 1.10 95% CI (0.09; 1.91)] aortic distensibility were higher in girls, but differences disappeared after adjustment for pubertal status and other identified potential predictors. Systolic and diastolic blood pressure, cardiac output, left ventricle (LV) systolic function, and total peripheral resistance did not differ between the sexes. In girls, heart rate was 7 beats/min higher, whereas pulse pressure (by 2 mmHg), LV end-diastolic volume index (by 7 mL), and stroke volume (by 5 mL) were lower. LV peak filling rate indexed to LV end-diastolic volume was 0.5 s -1 higher in girls. In conclusion, prepubertal girls and boys have equal conductance artery function. Thus, the well-known sex difference in adult conductance artery function seems to develop after the onset of puberty with girls initially increasing aortic distensibility. NEW & NOTEWORTHY Although it has been suggested that sex differences in conductance artery function may exist early in childhood, this study demonstrates that the well-known, sex-related difference in conductance artery stiffness (hence Windkessel function) in adulthood is not established before puberty. Thus, healthy prepubertal girls and boys have comparable conductance artery compliance. In contrast to previous studies, our study suggests that pubertal girls develop a more distensible aorta than prepubertal children.

Myocardial function and exercise reserve are important determinants of outcome in pulmonary arterial hypertension (PAH) but are incompletely understood. For this study, we performed subject-specific computer simulations, based on invasive measurements and cardiac magnetic resonance imaging (CMR), to investigate whole circulation properties in PAH at rest and exercise and determinants of exercise reserve. CMR and right heart catheterization were performed in nine patients with idiopathic PAH, and CMR in 10 healthy controls. CMR during exercise was performed in seven patients with PAH. A full-circulation computer model was developed, and model parameters were optimized at the individual level. Patient-specific simulations were used to analyze the effect of right ventricular (RV) inotropic reserve on exercise performance. Simulations achieved a high consistency with observed data. RV contractile force was increased in patients with PAH (127.1 ± 28.7 kPa vs. 70.5 ± 14.5 kPa, P < 0.001), whereas left ventricular contractile force was reduced (107.5 ± 17.5 kPa vs. 133.9 ± 10.3 kPa, P = 0.002). During exercise, RV contractile force increased by 1.56 ± 0.17, P = 0.001. In silico experiments confirmed RV inotropic reserve as the important limiting factor for cardiac output. Subject-specific computer simulation of myocardial mechanics in PAH is feasible and can be used to evaluate myocardial performance. With this method, we demonstrate marked functional myocardial adaptation to PAH in the resting state, primarily composed of increased contractile force development by RV myofibers, and we show the negative impact of reduced RV inotropic reserve on cardiac output during exercise. NEW & NOTEWORTHY Computer simulations of the myocardial mechanics and hemodynamics of rest and exercise were performed in nine patients with pulmonary arterial hypertension and 10 control subjects, with the use of data from invasive catheterization and from cardiac magnetic resonance. This approach allowed a detailed analysis of myocardial adaptation to pulmonary arterial hypertension and showed how reduction in right ventricular inotropic reserve is the important limiting factor for an increase in cardiac output during exercise.

Men and women are known to react differently to stress. Thus, stress cardiomyopathy almost solely strikes women. Stress cardiomyopathy is suggested to relate to sex differences in catecholamine reaction. Left heart function during dobutamine stress is well described, but sex-specific inotropic and lusitropic response to abrupt termination of dobutamine stress is not. We aimed to investigate sex differences in left ventricular (LV) and atrial (LA) function during and after dobutamine stress. We enrolled 20 healthy elderly subjects (60-70 yr, 10 females) and measured their LV and LA volumes throughout the cardiac cycle by cardiac magnetic resonance imaging at rest, during dobutamine stress (15 μg·kg(-1)·min(-1)), 15 min after termination (T15), and 30 min after termination (T30) of dobutamine stress. We calculated LV ejection fractions, LV stroke volumes, LV peak filling rates, and LA passive, active, and conduit volumes. Sex differences were not observed at rest or during dobutamine stress. Compared with prestress values, at T15 a rebound decrease in LV peak filling rate was observed in women (-22 ± 3%, P < 0.001) but not in men. This was reflected in reduced LA passive emptying volume (-40 ± 3%, P < 0.001) and a corresponding increase in LA active emptying volume (36 ± 2%, P < 0.001). At T30 there were no differences between the sexes. We conclude that dobutamine causes greater stress to the female heart. This is revealed after termination of dobutamine stress where the left heart recovers in men, whereas women experience rebound LV stiffening with reduced diastolic relaxation. This is the first report of a sex-specific transient rebound phenomenon in cardiovascular response to catecholamines.

Positive-pressure ventilation (PPV) is widely used for treatment of acute cardiorespiratory failure, occasionally at the expense of compromised cardiac function and arterial blood pressure. The explanation why has largely rested on interpretation of intracardiac pressure changes. We evaluated the effect of PPV on the central circulation by studying cardiac chamber volumes with cardiac magnetic resonance imaging (CMR). We hypothesized that PPV lowers cardiac output (CO) mainly via the Frank-Starling relationship. In 18 healthy volunteers, cardiac chamber volumes and flow in aorta and the pulmonary artery were measured by CMR during PPV levels of 0, 10, and 20 cmH2O applied via a respirator and a face mask. All cardiac chamber volumes decreased in proportion to the level of PPV. Following 20-cmH2O PPV, the total diastolic and systolic cardiac volumes (±SE) decreased from 605 (±29) ml to 446 (±29) ml (P < 0.001) and from 265 (±17) ml to 212 (±16) ml (P < 0.001). Left ventricular stroke volume decreased by 27 (±4) ml/beat; heart rate increased by 7 (±2) beats/min; and CO decreased by 1.0 (±0.4) l/min (P < 0.001). From 0 to 20 cmH2O, right and left ventricular peak filling rates decreased by -146 (±32) and -187 (±64) ml/s (P < 0.05) but maximal emptying rates were unchanged. Cardiac filling and output decrease with increasing PPV in healthy volunteers. The decrease is seen even at low levels of PPV and should be taken into account when submitting patients to mechanical ventilation with positive pressures. The decrease in CO is fully explained by the Frank-Starling mechanism.

The aim of this study is to describe phasic volume changes of the left atrium (LA) in healthy young and elderly subjects at rest and during pharmacological stress (PS). LA maximum size is related to cardiovascular mortality. LA has passive, active, and conduit function for left ventricular (LV) filling. We hypothesized that changes in LV compliance from normal aging are reflected in LA volume changes and that PS will augment these differences. We enrolled twenty young (20-30 yr) and twenty elderly (60-70 yr) healthy subjects and measured their LV and LA volumes by cardiac magnetic resonance imaging at rest and during dobutamine and glycopyrrolate stress. We identified LA minimum, maximum, and middiastolic volumes and the volume before atrial contraction. LA emptying volumes were calculated as LA passive and active emptying volumes and LA conduit volume. We also calculated LV peak filling rates (LVPFRs). Both at rest and during PS, LA maximum and minimum volumes were similar in the groups, whereas middiastolic volume was higher in the elderly. During PS, a marked decrease in LA passive emptying function and a corresponding increase in LA active emptying function were seen in the elderly but not in the young. At rest, LVPFR was lower in the elderly, and during PS this difference was augmented. The aging heart has reduced LVPFR, which is reflected in reduced LA passive and compensatory increased LA active volumetric contribution to LV stroke volume. These age-related differences are evident at rest and highly augmented during both dobutamine and glycopyrrolate stress.