Kristin Haraldsdottir

Impaired autonomic function in adolescents born preterm

Preterm birth temporarily disrupts autonomic nervous system (ANS) development, and the long‐term impacts of disrupted fetal development are unclear in children. Abnormal cardiac ANS function is associated with worse health outcomes, and has been identified as a risk factor for cardiovascular disease. We used heart rate variability (HRV) in the time domain (standard deviation of RR intervals, SDRR; and root means squared of successive differences, RMSSD) and frequency domain (high frequency, HF; and low frequency, LF) at rest, as well as heart rate recovery (HRR) following maximal exercise, to assess autonomic function in adolescent children born preterm. Adolescents born preterm (less than 36 weeks gestation at birth) in 2003 and 2004 and healthy age‐matched full‐term controls participated. Wilcoxon Rank Sum tests were used to compare variables between control and preterm groups. Twenty‐one adolescents born preterm and 20 term‐born controls enrolled in the study. Preterm‐born subjects had lower time‐domain HRV, including SDRR (69.1 ± 33.8 vs. 110.1 ± 33.0 msec, respectively, P = 0.008) and RMSSD (58.8 ± 38.2 vs. 101.5 ± 36.2 msec, respectively, P = 0.012), with higher LF variability in preterm subjects. HRR after maximal exercise was slower in preterm‐born subjects at 1 min (30 ± 12 vs. 39 ± 9 bpm, respectively, P = 0.013) and 2 min (52 ± 10 vs. 60 ± 10 bpm, respectively, P = 0.016). This study is the first report of autonomic dysfunction in adolescents born premature. Given prior association of impaired HRV with adult cardiovascular disease, additional investigations into the mechanisms of autonomic dysfunction in this population are warranted.

Early Pulmonary Vascular Disease in Young Adults Born Preterm

Rationale: Premature birth affects 10% of live births in the United States and is associated with alveolar simplification and altered pulmonary microvascular development. However, little is known about the long‐term impact prematurity has on the pulmonary vasculature. Objectives: Determine the long‐term effects of prematurity on right ventricular and pulmonary vascular hemodynamics. Methods: Preterm subjects (n = 11) were recruited from the Newborn Lung Project, a prospectively followed cohort at the University of Wisconsin‐Madison, born preterm with very low birth weight (≤1,500 g; average gestational age, 28 wk) between 1988 and 1991. Control subjects (n = 10) from the same birth years were recruited from the general population. All subjects had no known adult cardiopulmonary disease. Right heart catheterization was performed to assess right ventricular and pulmonary vascular hemodynamics at rest and during hypoxic and exercise stress. Measurements and Main Results: Preterm subjects had higher mean pulmonary arterial pressures (mPAPs), with 27% (3 of 11) meeting criteria for borderline pulmonary hypertension (mPAP, 19‐24 mm Hg) and 18% (2 of 11) meeting criteria for overt pulmonary hypertension (mPAP ≥ 25 mm Hg). Pulmonary vascular resistance and elastance were higher at rest and during exercise, suggesting a stiffer vascular bed. Preterm subjects were significantly less able to augment cardiac index or right ventricular stroke work during exercise. Among neonatal characteristics, total ventilatory support days was the strongest predictor of adult pulmonary pressure. Conclusions: Young adults born preterm demonstrate early pulmonary vascular disease, characterized by elevated pulmonary pressures, a stiffer pulmonary vascular bed, and right ventricular dysfunction, consistent with an increased risk of developing pulmonary hypertension.

In-Season Changes in Heart Rate Recovery Are Inversely Related to Time to Exhaustion but not Aerobic Capacity in Rowers

To determine if in‐season changes in heart rate recovery (HRR) are related to aerobic fitness and performance in collegiate rowers. Twenty‐two female collegiate rowers completed testing before and after their competitive season. Body fat percentage (BF%) was determined by dual‐energy X‐ray absorptiometry. Maximal aerobic capacity (VO2max) and time to exhaustion (Tmax) were determined during maximal rowing ergometer testing followed by 1 minute of recovery. HRR was expressed absolutely and as a percentage of maximal HR (HRR%1 min). Variables were compared using paired Wilcoxon tests. Multivariable regression models were used to predict in‐season changes in HRR using changes in VO2max and Tmax, while accounting for changes in BF%. From preseason to post‐season, VO2max and BF% decreased (3.98±0.42 vs 3.78±0.35 L/min, P=.002 and 23.8±3.4 vs 21.3±3.9%, P<.001, respectively), while Tmax increased (11.7±1.3 vs 12.6±1.3 min, P=.002), and HRR%1 min increased (11.1±2.7 vs 13.8±3.8, P=.001). In‐season changes in VO2max were not associated with HRR%1 min (P>.05). In‐season changes in Tmax were related to changes in HRR%1 min (β=−1.67, P=.006). In‐season changes in BF% were not related to changes in HRR (P>.05 for all). HRR1 min and HRR%1 min were faster preseason to post‐season, although the changes were unrelated to VO2max. Faster HRR%1 min post‐season was inversely related to changes in Tmax. This suggests that HRR should not be used as a measure of aerobic capacity in collegiate rowers, but is a promising measure of training status in this population.

Sex-Specific Skeletal Muscle Fatigability and Decreased Mitochondrial Oxidative Capacity in Adult Rats Exposed to Postnatal Hyperoxia

Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth. The objective of this study was to evaluate whether postnatal hyperoxia exposure in rats could recapitulate the skeletal and metabolic phenotype of premature birth, and to characterize the subcellular metabolic changes associated with postnatal hyperoxia exposure, with a secondary aim to evaluate sex differences in this model. Compared to control rats, male rats exposed to 14 days of postnatal hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability, lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and higher glycolytic enzyme expression. These differences were not present in female rats with the same postnatal hyperoxia exposure. This study demonstrates detrimental mitochondrial and muscular outcomes in the adult male rat exposed to postnatal hyperoxia. Given that young adults born premature also demonstrate skeletal muscle dysfunction, future studies are merited to determine whether this dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial oxidative capacity and metabolic dysfunction.

In-season changes in ventricular morphology and systolic function in adolescent female athletes

Abstract Purpose: To evaluate the influence of physical maturity on the changes in ventricular morphology and function with sport training in female youth athletes. Methods: Thirty-two female athletes (age 13–18 years) underwent height and weight measurement and 2-D echocardiographic evaluation immediately prior to, and following, a 20-week soccer season. Pre- and post-season left ventricular end-diastolic diameter (LVEDD), end-diastolic volume (LVEDV), ejection fraction (LVEF), stroke volume (LVSV), mass (LVM), and posterior wall thickness (LVPWT), right ventricular end-diastolic diameter (RVEDD), end-diastolic area (RVEDA), and fractional area change (RVFAC), and interventricular septal thickness (IVST) were compared. In-season change in each variable was compared across pre-season hours of vigorous physical activity (0–1, 2–3, >3 hours). Results: Significant increases were identified in LVEDV (51.3 ± 10.4 v 56.4 ± 9.6 ml/m2, p = 0.001) and RVEDA (10.5 ± 1.9 v 11.3 ± 2.5 cm2/m2, p = 0.040), but not LVEDD, LVM, LVPWT, LVSV, RVEDD, RVEDA, RVFAC, or IVST (p > 0.05 for all). In-season changes in echocardiographic variables did not differ across hours of pre-season vigorous physical activity (p > 0.05 for all). Conclusion: Among female adolescent soccer players, in-season training elicits changes in resting ventricular volume, but not wall thickness or systolic function. These adaptations do not appear to be influenced by pre-season physical activity level.

Altered Right Ventricular Mechanical Properties Are Afterload Dependent in a Rodent Model of Bronchopulmonary Dysplasia

Infants born premature are at increased risk for development of bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), and ultimately right ventricular (RV) dysfunction, which together carry a high risk of neonatal mortality. However, the role alveolar simplification and abnormal pulmonary microvascular development in BPD affects RV contractile properties is unknown. We used a rat model of BPD to examine the effect of hyperoxia-induced PH on RV contractile properties. We measured in vivo RV pressure as well as passive force, maximum Ca2+ activated force, calcium sensitivity of force (pCa50) and rate of force redevelopment (ktr) in RV skinned trabeculae isolated from hearts of 21-and 35-day old rats pre-exposed to 21% oxygen (normoxia) or 85% oxygen (hyperoxia) for 14 days after birth. Systolic and diastolic RV pressure were significantly higher at day 21 in hyperoxia exposed rats compared to normoxia control rats, but normalized by 35 days of age. Passive force, maximum Ca2+ activated force, and calcium sensitivity of force were elevated and cross-bridge cycling kinetics depressed in 21-day old hyperoxic trabeculae, whereas no differences between normoxic and hyperoxic trabeculae were seen at 35 days. Myofibrillar protein analysis revealed that 21-day old hyperoxic trabeculae had increased levels of beta-myosin heavy chain (β-MHC), atrial myosin light chain 1 (aMLC1; often referred to as essential light chain), and slow skeletal troponin I (ssTnI) compared to age matched normoxic trabeculae. On the other hand, 35-day old normoxic and hyperoxic trabeculae expressed similar level of α- and β-MHC, ventricular MLC1 and predominantly cTnI. These results suggest that neonatal exposure to hyperoxia increases RV afterload and affect both the steady state and dynamic contractile properties of the RV, likely as a result of hyperoxia-induced expression of β-MHC, delayed transition of slow skeletal TnI to cardiac TnI, and expression of atrial MLC1. These hyperoxia-induced changes in contractile properties are reversible and accompany the resolution of PH with further developmental age, underscoring the importance of reducing RV afterload to allow for normalization of RV function in both animal models and humans with BPD.

In-season Changes In Heart Rate Recovery Are Related To Time To Exhaustion, But Not Aerobic Capacity In Collegiate Rowers: 1016 Board #332 June 1, 2: 00 PM - 3: 30 PM.

Methods: 22 female collegiate varsity rowers completed testing immediately before and after their competitive fall season. Lean body mass (LBM) and body fat percentage (BF%) were determined by dual energy xray absorptiometry (DXA). VO2max and time to exhaustion (Tmax) were determined during maximal rowing ergometer testing followed by 3 minutes of active recovery at 70W. Heart rate was measured continuously and HRR was expressed absolutely at 1, 2 and 3 minutes after test completion (HRR1min, HRR2min, HRR3min, respectively). Pre and postseason variables were compared using paired t-tests. Multivariable regression models were used to predict inseason changes in HRR at each time point using in-season changes in 1) VO2max and BF% and 2) Tmax and BF% as covariates.