Swimming behavior indicates stress and adaptations to exercise.

Introduction: Behaviors of swimming rodents are not uniform, exhibiting large variations, which may underlie the individual differences in swimming exercise-induced benefits. The study aimed to monitor individualized swimming behavior and evaluate its biological significance. Methods: A swimming tank which can monitor individualized rodent swimming behavior during exercise was established. A total of 45 mice were subjected to swimming training for 1 month (1 h per day) and the swimming behaviors of each mouse were recorded. Results: The swimming behaviors of mice displayed considerable variations in aspects of distance, velocity, and area preference. For example, nearly one-third of mice preferred to swim in central area and most of the mice exhibited an even area distribution. Long-term exercise training improved cardiac systolic function and decreased blood pressure in mice, but hardly changed swimming behaviors. Analyses of the relationship between swimming behavior and cardiovascular adaptations to exercise training revealed that swimming behavior indicated the biological effects of swimming training. Specifically, mice which preferred swimming at the central zone or were trainable in behavior during 1-month training exhibited better outcomes in cardiac function and blood pressure post long-term exercise. Mechanistically, a centralized swimming behavior indicated a smaller stress during exercise, as evidenced by a milder activation of hypothalamic-pituitary-adrenal axis. Discussion: These results suggest that swimming behavior during training indicates individualized adaptations to long-term exercise, and highlight a biological significance of swimming behavior monitoring in animal studies.

The athlete's heart: allometric considerations on published papers and relation to cardiovascular variables.

To evaluate the morphology of the "athlete's heart", left ventricular (LV) wall thickness (WT) and end-diastolic internal diameter (LVIDd) at rest were addressed in publications on skiers, rowers, swimmers, cyclists, runners, weightlifters (n = 927), and untrained controls (n = 173) and related to the acute and maximal cardiovascular response to their respective disciplines. Dimensions of the heart at rest and functional variables established during the various sport disciplines were scaled to body weight for comparison among athletes independent of body mass. The two measures of LV were related (r = 0.8; P = 0.04) across athletic disciplines. With allometric scaling to body weight, LVIDd was similar between weightlifters and controls but 7%-15% larger in the other athletic groups, while WT was 9%-24% enlarged in all athletes. The LVIDd was related to stroke volume, oxygen pulse, maximal oxygen uptake, cardiac output, and blood volume (r = ~ 0.9, P < 0.05), while there was no relationship between WT and these variables (P > 0.05). In conclusion, while cardiac enlargement is, in part, essential for the generation of the cardiac output and thus stroke volume needed for competitive endurance exercise, an enlarged WT seems important for the development of the wall tension required for establishing normal arterial pressure in the enlarged LVIDd.

Mitral and Tricuspid Valve Disease in Athletes.

Observing mitral or tricuspid valve disease in an athlete raises many considerations for the clinician. Initially, the etiology must be clarified, with causes differing depending on whether the athlete is young or a master. Notably, vigorous training in competitive athletes leads to a constellation of structural and functional adaptations involving cardiac chambers and atrioventricular valve systems. In addition, a proper evaluation of the athlete with valve disease is necessary to evaluate the eligibility for competitive sports and identify those requiring more follow-up. Indeed, some valve pathologies are associated with an increased risk of severe arrhythmias and potentially sudden cardiac death. Traditional and advanced imaging modalities help clarify clinical doubts, allowing essential information about the athlete's physiology and differentiating between primary valve diseases from those secondary to training-related cardiac adaptations. Remarkably, another application of multimodality imaging is evaluating athletes with valve diseases during exercise to reproduce the sport setting and better characterize the etiology and valve defect mechanism. This review aims to analyze the possible causes of atrioventricular valve diseases in athletes, focusing primarily on imaging applications in diagnosis and risk stratification.

Longitudinal maternal cardiac function in hypertensive disorders of pregnancy.

BACKGROUND: Compared with gestational hypertension, preeclampsia has traditionally been considered the worse end of the spectrum of hypertensive disorders of pregnancy. It is associated with worse pregnancy outcomes and future cardiovascular morbidities. Both hypertensive disorders may be associated with cardiac maladaptation in pregnancy. However, previous studies were limited by small numbers and a paucity of longitudinal data and unaccounted for the contribution of maternal characteristics that can affect hemodynamics. OBJECTIVE: This study aimed to assess, in an unselected population, the maternal cardiac adaptation in normotensive and hypertensive pregnancies after controlling for important maternal characteristics that affect maternal cardiac function and the interaction among these covariates. STUDY DESIGN: This was a prospective, multicenter longitudinal study of maternal hemodynamics, assessed by a noninvasive bioreactance technology, measured at 11 0/7 to 13 6/7, 19 0/7 to 24 0/7, 30 0/7 to 34 0/7, and 35 0/7 to 37 0/7 weeks of gestation in 3 groups of women. Group 1 was composed of women with preeclampsia (n=45), group 2 was composed of women with gestational hypertension (n=61), and group 3 was composed of normotensive women (n=1643). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables controlling for maternal age, height, weight, weight gain, race, previous obstetrical history, and birthweight. RESULTS: After adjusting for confounders that significantly affect maternal hemodynamics, both group 1 and group 2, compared with group 3, had pathologic cardiac adaptation. Group 1, compared with group 3, demonstrated hyperdynamic circulation with significantly higher cardiac output driven by greater stroke volume in the first trimester of pregnancy. As the pregnancies progressed to after 20 0/7 weeks of gestation, this hyperdynamic state transitioned to hypodynamic state with low cardiac output and high peripheral vascular resistance. Group 2, compared with group 3, had no significant differences in cardiac output, stroke volume, and heart rate before 20 0/7 weeks of gestation but thereafter demonstrated a continuous decline in cardiac output and stroke volume, similar to group 1. Both groups 1 and 2, compared with group 3, had persistently elevated mean arterial pressure and uterine artery pulsatility index throughout pregnancy. CONCLUSION: After adjusting for confounders that affect maternal hemodynamics in an unselected pregnant population, women with preeclampsia and gestational hypertension, compared with normotensive women, demonstrated similar cardiac maladaptation. This pathologic profile was evident after 20 0/7 weeks of gestation and at least 10 weeks before the clinical manifestation of the disease.

Autologous Umbilical Cord Blood-Derived Mononuclear Cell Therapy Promotes Cardiac Proliferation and Adaptation in a Porcine Model of Right Ventricle Pressure Overload.

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

Echocardiographic Characterization of Left Heart Morphology and Function in Highly Trained Male Judo Athletes.

The long-term practice of judo can lead to various changes in the heart including increased dimensions of the left ventricle in diastole and thickening of the interventricular septum and the posterior wall of the left ventricle. This study aimed to assess left ventricular morphology and function in elite male judokas. A comparative cross-sectional study was conducted that included a total of 20 subjects, 10 judokas, and 10 healthy non-athletes aged 24 ± 2.85 years. Demographic and anthropometric data were analyzed. All subjects underwent a medical examination and a two-dimensional transthoracic echocardiogram. Different parameters of left ventricular morphology and function were measured and compared between athletes and non-athletes. Left ventricle mass and LV mass index were higher in judokas than in non-athletes (p < 0.05), as well as PW thickness (9.78 ± 0.89 mm vs. 8.95 ± 0.76 mm). A total of six (n = 6) of athletes had eccentric hypertrophy, while others had normal heart geometry. LVEDd, LVEDs, LVEDd/BSA, and LVEDs/BSA were significantly higher in judokas (p < 0.05). LVEDd in athletes ranged from 48 to 62 mm. These values, combined with normal diastolic function, ejection fraction, and shortening fraction, indicate that the judokas' cardiac adaptation was physiological rather than pathological.

Hallmarks of exercised heart.

The benefits of exercise in humans on the heart have been well recognized for many years. Long-term endurance exercise training can induce physiologic cardiac hypertrophy with normal or enhanced heart function, and provide protective benefits in preventing heart failure. The heart-specific responses that occur during exercise are complex and highly variable. This review mainly focuses on the current understanding of the structural and functional cardiac adaptations to exercise as well as molecular pathways and signaling proteins responsible for these changes. Here, we summarize eight tentative hallmarks that represent common denominators of the exercised heart. These hallmarks are: cardiomyocyte growth, cardiomyocyte fate reprogramming, angiogenesis and lymphangiogenesis, mitochondrial remodeling, epigenetic alteration, enhanced endothelial function, quiescent cardiac fibroblast, and improved cardiac metabolism. A major challenge is to explore the underlying molecular mechanisms for cardio-protective effects of exercise, and to identify therapeutic targets for heart diseases.

Athlete Heart in Children and Young Athletes. Echocardiographic Findings in 331 Cases.

The changes of the athlete's heart are not well defined and characterized in children. We aimed to describe the morphological changes of the heart related to sport in young athletes. We evaluated a group of 331 young athletes under 18 years (mean 11.9 ± 3.2) who practice tennis: 58 (16.52%), football: 118 (33.62%), basketball: 16 (4.56%), athletics: 40 (11.4%), and swimming: 99 (28.21%). Type of sport, years of practice, and duration of the training were collected. All children underwent echocardiography with the following M-mode parameters: left atrium diameter (LAD), interventricular septum (IVS), and left ventricle posterior Wall (LVPW), diastolic diameter of the left ventricle (LVDD), and right ventricle outflow tract (RVOT). The major finding of our study was that 20% of the children had a Z score > 2 for the IVS and that increased to 30% for the children playing tennis or swimming. Also, other changes like LA and RVOT dilatation were observed in about 10 and 14% of the cases, respectively. Taken together, these figures indicate that cardiac remodeling is frequent in children. Further studies are needed to establish consensus-based criteria of athlete's heart in young children.

Cardiac dysfunction after preeclampsia; an overview of pro- and anti-fibrotic circulating effector molecules.

Preeclampsia (PE) is strongly associated with heart failure (HF) later in life. The aberrant cardiac remodelling is likely initiated or amplified during preeclamptic pregnancy. Aberrant remodelling often persists after delivery and is known to relate strongly to cardiac fibrosis. This review provides an overview of pro- and anti- fibrotic circulating effector molecules that are involved in cardiac fibrosis and their association with PE. Women with PE complicated pregnancies show increased ANG-II sensitivity and elevated levels of the pro-fibrotic factors IL-6, TNF-α, TGs and FFAs compared to uncomplicated pregnancies. In the postpartum period, PE pregnancies compared to uncomplicated pregnancies have increased ANG-II sensitivity, elevated levels of the pro-fibrotic factors IL-6, TNF-α, LDL cholesterol and leptin, as well as decreased levels of the anti-fibrotic factor adiponectin. The review revealed several profibrotic molecules that associate to cardiac fibrosis during and after PE. The role that these fibrotic factors have on the heart during and after PE may improve the understanding of the link between PE and HF. Furthermore they may provide insight into the pathways in which the relation between both diseases can be understood as potential mechanisms which interfere in the process of cardiovascular disease (CVD). Unravelling the molecular mechanism and pathways involved might bring the diagnostic and therapeutic abilities of those factors a step closer.

Uncomplicated Monochorionic Twins: Two Normal Hearts Sharing One Placenta.

Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography was performed at 26-30 weeks gestation and cord blood B-type natriuretic peptide (BNP) was measured at delivery. In both groups, z-scores for echocardiographic parameters were within normal ranges; however the monochorionic group had larger atrial areas (mean (standard deviation) right atria-to-heart ratio: 17.0 (2) vs. 15.9 (1); p = 0.018; left atria-to-heart ratio: 17.0 (3) vs. 15.8 (2); p < 0.001) and signs of concentric hypertrophy (right relative wall thickness: 0.66 (0.12) vs. 0.56 (0.11); p < 0.001; left relative wall thickness: 0.69 (0.14) vs. 0.58 (0.12); p < 0.001). Longitudinal function was increased in twins, leading to higher tricuspid annular plane systolic excursion (6.9 mm (0.9) vs. 5.9 mm (0.7); p < 0.001) and mitral annular plane systolic excursion (4.9 mm (0.8) vs. 4.4 mm (1.1); p < 0.001. BNP levels at birth were also higher in MCDA twins (median [interquartile range]: 20.81 pg/mL [16.69-34.01] vs. 13.14 pg/mL [9.17-19.84]; p < 0.001). Thus, uncomplicated MCDA fetuses have normal cardiac shape and function, but signs of cardiac adaptation were identified by echocardiographic and biochemical parameters, when compared with singletons.

Downregulated expression of microRNAs associated with cardiac hypertrophy and fibrosis in physiological pregnancy and the association with echocardiographically-evaluated myocardial function.

The aim of the present study was to analyze the profiles of cardiac microRNAs (miRNAs/miRs) in healthy pregnant women and non-pregnant controls. A total of 61 healthy women >18 years of age with singleton pregnancies in the third trimester were compared with 19 non-pregnant controls. Specifically, expression of miRNAs associated with cardiac hypertrophy (miR-1, miR-17-5, miR-22, miR-34a, miR-124, miR-133a, miR-195, miR-199a-3p, miR-199b, miR-210, miR-222 and miR-1249) and miRNAs associated with cardiac hypertrophy and fibrosis (miR-15b, miR-21, miR-26a, miR-29-a, miR-29c, miR-30c, miR-101, miR-146a, miR-191, miR-208a-5p and miR-328) were analyzed and compared with echocardiographic examination results. Both groups had similar cardiac miRNA expression profiles, but differed in quantitative evaluation. Women in the third trimester of physiological pregnancy exhibited downregulation of certain profibrotic miRNAs (miR-21, miR-30c and miR-328), decreased expression of a hypertrophic and antimetabolic miRNAs (miR-146a), downregulation of an antifibrotic miRNA (miR-222), and downregulation of a hypertrophic miRNA (miR-195). In pregnant women, the indices of systolic function were associated with miR-195 expression, and an interplay between miR-17-5p and diastolic function was observed. While the profiles of cardiac miRNAs expressed in healthy pregnant women and healthy non-pregnant controls were similar, these two groups differed in terms of expression of specific miRNAs. In the third trimester of physiological pregnancy, a downregulation of miR-17-5p, miR-21, miR-30c, miR-146a, miR-195, miR-222 and miR-328 was observed. The differences in the association between echocardiographic indices with miRNAs in pregnant and non-pregnant women suggest that miRNAs regulate both the structure and function of the pregnant heart, influencing cardiac muscle thickness as well as systolic and diastolic function.

The Impact of Ethnicity on Cardiac Adaptation.

Regular intensive exercise is associated with a plethora of electrical, structural and functional adaptations within the heart to promote a prolonged and sustained increase in cardiac output. Bradycardia, increased cardiac dimensions, enhanced ventricular filling, augmentation of stroke volume and high peak oxygen consumption are recognised features of the athlete's heart. The type and magnitude of these adaptations to physical exercise are governed by age, sex, ethnicity, sporting discipline and intensity of sport. Some athletes, particularly those of African or Afro-Caribbean (black) origin reveal changes that overlap with diseases implicated in sudden cardiac death. In such instances, erroneous interpretation has potentially serious consequences ranging from unfair disqualification to false reassurance. This article focuses on ethnic variation in the physiological cardiac adaption to exercise.

Acute impact of changes to hemodynamic load on the left ventricular strain-volume relationship in young and older men.

Chronic changes in left ventricular (LV) hemodynamics, such as those induced by increased afterload (i.e., hypertension), mediate changes in LV function. This study examined the proof of concept that 1) the LV longitudinal strain (ε)-volume loop is sensitive to detecting an acute increase in afterload, and 2) these effects differ between healthy young versus older men. Thirty-five healthy male volunteers were recruited, including 19 young (24 ± 2 yr) and 16 older participants (67 ± 5 yr). Tests were performed before, during, and after 10-min recovery from acute manipulation of afterload. Real-time hemodynamic data were obtained and LV longitudinal ε-volume loops were calculated from four-chamber images using two-dimensional echocardiography. Inflation of the anti-gravity (anti-G) suit resulted in an immediate increase in heart rate, blood pressure, and systemic vascular resistance and a decrease in stroke volume (all P < 0.05). This was accompanied by a decrease in LV peak ε, slower slope of the ε-volume relationship during early diastole, and an increase in uncoupling (i.e., compared with systole; little change in ε per volume decline during early diastole and large changes in ε per volume decline during late diastole) (all P < 0.05). All values returned to baseline levels after recovery (all P > 0.05). Manipulation of cardiac hemodynamics caused comparable effects in young versus older men (all P > 0.05). Acute increases in afterload immediately change the diastolic phase of the LV longitudinal ε-volume loop in young and older men. This supports the potency of the LV longitudinal ε-volume loop to provide novel insights into dynamic cardiac function in humans in vivo.

Endothelin-1, cardiac morphology, and heart failure: the MESA angiogenesis study.

BACKGROUND: Circulating levels of endothelin-1 (ET1) are elevated in heart failure and predict poor prognosis. However, it is not clear whether ET1 elevation is an adaptive response, maladaptive response, or an epiphenomenon of heart failure. In this study, we evaluated the relationships between ET1, cardiac morphology, and incident heart failure or cardiovascular death in participants with no evidence of clinical cardiovascular disease at the time ET1 was measured. METHODS AND RESULTS: ET1 was measured in 1,361 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis Sub-Study. As suggested by linear regression, participants with lower circulating ET1 levels tended to be older, non-white, more likely to have smoked heavily, and less likely to report intentional exercise. Participants with higher ET1 levels had smaller left ventricular end-diastolic volumes (8.9 ml smaller per log increase in ET1, 95% confidence interval 17.1-0.7, p = 0.03) with an increased left ventricular ejection fraction (2.8% per log increase in ET1, 95% confidence interval 0.5%-5.2%, p = 0.02). As suggested by Cox Proportional Hazards estimates, participants with higher ET1 levels had a lower risk for the composite outcome of heart failure or cardiovascular death in models that were unadjusted or had limited adjustment (p = 0.03 and p = 0.05, respectively). Lower risk for heart failure with higher ET1 levels could not be clearly shown in a model including health behaviors. CONCLUSIONS: These results suggest, but do not confirm, that elevated levels of circulating ET1 are associated with a more favorable cardiac phenotype. The relationship between ET1 and outcomes was not fully independent of one or more covariates.

Cardiac adaptation to exercise training in health and disease.

The heart is the primary pump that circulates blood through the entire cardiovascular system, serving many important functions in the body. Exercise training provides favorable anatomical and physiological changes that reduce the risk of heart disease and failure. Compared with pathological cardiac hypertrophy, exercise-induced physiological cardiac hypertrophy leads to an improvement in heart function. Exercise-induced cardiac remodeling is associated with gene regulatory mechanisms and cellular signaling pathways underlying cellular, molecular, and metabolic adaptations. Exercise training also promotes mitochondrial biogenesis and oxidative capacity leading to a decrease in cardiovascular disease. In this review, we summarized the exercise-induced adaptation in cardiac structure and function to understand cellular and molecular signaling pathways and mechanisms in preclinical and clinical trials.

Left ventricular torsional mechanics in term fetuses and neonates.

OBJECTIVE: Left ventricular (LV) torsion is an important aspect of cardiac mechanics and is fundamental to normal ventricular function. The myocardial mechanics of the fetal heart and the changes that occur during the transition to the neonatal period have not been explored previously. The aim of this study was to evaluate perinatal changes in LV torsion and its relationship with myocardial function. METHODS: This was a prospective study of 36 women with an uncomplicated term pregnancy. Fetal and neonatal conventional, spectral tissue Doppler and two-dimensional (2D) speckle tracking echocardiography were performed a few days before and within hours after delivery to measure cardiac indices including LV rotational parameters derived from short-axis views at the base and apex of the heart. Linear regression analysis was used to examine the relationship between LV rotational parameters and cardiac geometric and functional indices in term fetuses and neonates. Perinatal changes in LV rotational parameters were assessed. RESULTS: There were three patterns of LV twist in term fetuses: those with reversed-apex-type LV twist had the lowest median values of LV torsion (0.1°/cm), with higher values (1.6°/cm) in those with infant-type LV twist and the highest values (4.4°/cm) in those with adult-type LV twist. LV torsion was associated significantly with cardiac geometric and functional indices. Perinatal evaluation revealed a significant increase in LV torsion following delivery in fetuses exhibiting reversed-apex-type LV twist (increase of 2.8°/cm, P = 0.009) and a significant decrease in those with adult-type LV twist (decrease of 3.2°/cm, P = 0.008). CONCLUSIONS: This study demonstrates the feasibility of 2D speckle tracking imaging for accurate assessment of rotational cardiac parameters in term fetuses. There are unique perinatal patterns of LV twist that demonstrate different values of LV torsion, which was found to correlate with indices of ventricular geometry and myocardial function. Differences in patterns of LV twist may therefore reflect differences in compensatory myocardial adaptation to the physiological environment/loading conditions in late gestation in fetuses and postnatal cardiac adjustment to the acute loading changes that occur at delivery. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

One year of exercise training promotes distinct adaptations in right and left ventricle of female Sprague-Dawley rats.

Aerobic exercise training induces a unique cardioprotective phenotype, but it is becoming clear that it does not promote the same structural, functional, and molecular adaptations in both ventricles. In the present study, we aimed to better characterize and compare the molecular pathways involved in the exercise-induced remodeling of both ventricles. Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Animals in the exercise group were submitted to low-intensity treadmill exercise for 54 weeks. After the experimental period, biventricular hemodynamic analysis was performed and right and left ventricles were harvested for morphological and biochemical analyses. Data showed that long-term low-intensity exercise training improves cardiac function, especially left ventricular diastolic function; however, the expression of connexin-43, CCAAT-enhancer binding protein ß, and c-kit did not change in none of the ventricles. In the right ventricle, long-term exercise training induced an increase of manganese superoxide dismutase and sirtuin 3 protein expression, suggestive of improved antioxidant capacity. Our results also support that long-term aerobic exercise training imposes greater metabolic remodeling to the right ventricle, mainly by increasing mitochondrial ability to produce ATP, with no association to estrogen-related receptor α regulation.

Changes in dynamic left ventricular function, assessed by the strain-volume loop, relate to reverse remodeling after aortic valve replacement.

Aortic valve replacement (AVR) leads to remodeling of the left ventricle (LV). Adopting a novel technique to examine dynamic LV function, our study explored whether post-AVR changes in dynamic LV function and/or changes in aortic valve characteristics are associated with LV mass regression during follow-up. We retrospectively analyzed 30 participants with severe aortic stenosis who underwent standard transthoracic echocardiographic assessment before AVR [88 (IQR or interquartile range: 22-143) days], post-AVR [13 (6-22) days], and during follow-up [455 (226-907) days]. We assessed standard measures of LV structure, function, and aortic valve characteristics. Novel insight into dynamic LV function was provided through a four-chamber image by examination of the temporal relation between LV longitudinal strain (ε) and volume (ε-volume loops), representing the contribution of LV mechanics to volume change. AVR resulted in immediate changes in structural valve characteristics, alongside a reduced LV longitudinal peak ε and improved coherence between the diastolic and systolic part of the ε-volume loop (all P < 0.05). Follow-up revealed a decrease in LV mass (P < 0.05) and improvements in LV ejection fraction and LV longitudinal peak ε (P < 0.05). A significant relationship was present between decline in LV mass during follow-up and post-AVR improvement in coherence of the ε-volume loops (r = 0.439, P = 0.03), but not with post-AVR changes in aortic valve characteristics or LV function (all P > 0.05). We found that post-AVR improvements in dynamic LV function are related to long-term remodeling of the LV. This highlights the potential importance of assessing dynamic LV function for cardiac adaptations in vivo.NEW & NOTEWORTHY Combining temporal measures of left ventricular longitudinal strain and volume (strain-volume loop) provides novel insights in dynamic cardiac function. In patients with aortic stenosis who underwent aortic valve replacement, postsurgical changes in the strain-volume loop are associated with regression of left ventricular mass during follow-up. This provides novel insight into the relation between postsurgery changes in cardiac hemodynamics and long-term structural remodeling, but also supports the potential utility of the assessment of dynamic cardiac function.

Postnatal cardiovascular adaptation.

The heart undergoes rapid transformations in function during the transition to extrauterine life. Our understanding of the adaptive physiology underlying this process is able to inform the clinical management of infants who are struggling to complete this complex transition. Much of our knowledge of the cardiac transition is derived from the preterm infant in whom the preparative adaptations are incomplete and clinical sequelae all too common. This review will re-examine the cardiac transition highlighting the physiology that drives it and suggest appropriate clinical intervention to support the process.

Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

BACKGROUND: Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. METHODS: Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO2~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). RESULTS: Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. CONCLUSIONS: The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile and bio-energetic homeostasis.