Force Frequency Relationship of the Human Ventricle Increases During Early Postnatal Development

Wiegerinck, Rob F.; Cojoc, Anca; Zeidenweber, Carlo M.; Ding, Guoliang; Shen, Ming; Joyner, Ronald W.; Fernandez, Janet D.; Kanter, Kirk R.; Kirshbom, Paul M.; Kogon, Brian; Wagner, Mary B.

doi:10.1203/pdr.0b013e318199093c

Cited by 73 publications

(69 citation statements)

References 38 publications

(61 reference statements)

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“…We speculate that the observed early enhancement of negative dP/dt likely contributed to NPs' maintenance of LVO. This is supported by the findings of an in vitro study of human ventricular muscle strips from neonates with congenital heart disease, which suggests preserved acceleration of relaxation (39) in neonatal hearts.…”

Section: Discussionsupporting

confidence: 56%

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Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment

Fortin-Pellerin

Khoo

Mills

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Fortin-Pellerin E, Khoo NS, Mills L, Coe JY, Serrano-Lomelin J, Cheung PY, Hornberger LK. Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment. Am J Physiol Heart Circ Physiol 310: H598 -H607, 2016. First published December 30, 2015; doi:10.1152/ajpheart.00595.2015-Doppler studies at rest suggest left ventricular (LV) diastolic function rapidly improves from the neonate to infant. Whether this translates to its response to hemodynamic challenges is uncertain. We sought to explore the impact of early LV maturation on its ability to tolerate atrial tachycardia. As tachycardia reduces filling time, we hypothesized that the neonatal LV would be less tolerant of atrial tachycardia. Landrace cross piglets of two age groups (1-3 days; NPs; 14 -17 days, YPs; n ϭ 7/group) were instrumented for an atrial pacing protocol (from 200 to 300 beats/min) and assessed by invasive monitoring and echocardiography. NPs maintained their LV output and blood pressure, whereas YPs did not. Although negative dP/dt in NPs at baseline was lower than that of YPs (Ϫ1,599 Ϯ 83 vs. Ϫ2,470 Ϯ 226 mmHg/s, respectively, P ϭ 0.007), with increasing tachycardia negative dP/dt converged between groups and was not different. Both groups had similar preload reduction during tachycardia; however, NPs maintained shortening fraction while YPs decreased (NPs: 35.4 Ϯ 1.4 vs. 31.8 Ϯ 2.2%, P ϭ 0.35; YPs: 31.4 Ϯ 0.8 vs. 22.9 Ϯ 0.8%, P Ͻ 0.001). Contractility measures did not differ between groups. Peak LV twist and untwisting rate also did not differ; however, NPs tended to augment LV twist through increased apical rotation and YPs through increasing basal rotation (P ϭ 0.009). The NPs appear more tolerant of atrial tachycardia than the YPs. They have at least similar diastolic performance, enhanced systolic performance, and different LV twist mechanics, which may contribute to improved tachycardia tolerance of NPs. HEMODYNAMIC MANAGEMENT OF the critically ill term newborn is complex. Understanding the functional nature of the neonatal myocardium and how it evolves through the first few weeks and months after birth is key to optimizing care. Although many authors have provided their opinions regarding clinical management strategies (1, 12, 32), more translational and clinical studies are needed to provide insight into the functional capacity of the early postnatal heart. In particular, changes in diastolic reserve during the first few weeks and months of life in relation to the known disproportionate left ventricular (LV) growth (3, 27) have been poorly explored.In human infants, most of our understanding of the evolution of diastolic function has been derived from noninvasive Doppler-based studies (16,26,31). These investigations have suggested that the neonatal LV myocardium has less robust diastolic relaxation (16) with greater dependency on atrial contraction for filling, much like that of the diseased adult heart with diastolic dysfunction (15). In the first few mo...

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Section: Discussionsupporting

confidence: 56%

“…has been shown to decrease with maturation (37,39). A larger number of NCX in the very young may allow for more efficient clearing of cytosolic calcium, and may favor NP LV relaxation performance during chronotropic stress, when compared with YPs.…”

Section: Discussionmentioning

confidence: 99%

Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment

Fortin-Pellerin

Khoo

Mills

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…The reasons are multifactorial but include the limited physiologic reserve of cardiac and other organ systems, smaller cardiac structures, greater procedural complexity, the potential for exaggerated interactions between the blood components and the cardiopulmonary bypass circuit, and the susceptibility to infection. 11,12 Previous investigations have identified risk factors for mortality among neonatal cardiac surgical patients. The preoperative risk factors include lower gestational age at birth and lower weight at surgery and the presence of major noncardiac anomalies and genetic syndromes.…”

Section: Discussionmentioning

confidence: 99%

Unplanned reinterventions are associated with postoperative mortality in neonates with critical congenital heart disease

Mazwi

Brown

Marshall

et al. 2013

The Journal of Thoracic and Cardiovascular Surgery

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Objective Neonates with critical congenital heart disease remain at risk of adverse outcomes after cardiac surgery. Residual or undiagnosed anatomic lesions might be contributory. The present study aimed to describe the incidence and type of cardiac lesions that lead to early, unplanned cardiac reintervention, identify the risk factors for unplanned reintervention, and explore the associations between unplanned reinterventions and hospital mortality. Methods The present single-center retrospective cohort study included 943 consecutive neonates with critical congenital heart disease who underwent cardiac surgery from 2002 to 2008. An unplanned cardiac reintervention was defined as a cardiac reoperation or interventional cardiac catheterization performed during the same hospitalization as the initial operation. Multivariate logistic regression analyses were used to identify the risk factors for unplanned cardiac reintervention and hospital mortality. Results Of the 943 neonates, 104 (11%) underwent an unplanned cardiac reintervention. The independent predictors of unplanned reintervention included prenatal diagnosis, lower birth weight, need for mechanical ventilation before the initial cardiac operation, lower attending surgeon experience, and greater Risk Adjustment in Congenital Heart Surgery, version 1, category. Those who underwent reintervention had increased hospital mortality (n = 33/104, 32%) relative to those who did not (n = 31/839, 4%; adjusted odds ratio, 8.6; 95% confidence interval, 4.7 to 15.6; P < .001). The mortality rates among patients undergoing surgical reintervention (23/66, 35%) or transcatheter reintervention (4/16, 25%), or both (6/22, 27%) were similar (P = .66). Conclusions The need for unplanned cardiac reintervention in neonates with critical congenital heart disease is strongly associated with increased mortality. Early unplanned reinterventions might be an important covariate in outcomes studies and useful as a quality improvement measure.

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“…one of them would be the greater availability of cytosolic Ca 2+ to be taken up by sERCA not only because of the greater Ca 2+ influx but also due to less Ca 2+ extrusion by the nCX, the main sarcolemmal transporter that removes Ca 2+ from the cytosol. This may be particularly important in the neonatal myocardium, where nCX expression is higher and the exchanger plays a greater role in cytosolic Ca 2+ clearance than in the adult [4,27,29]. We estimate that increasing [Ca 2+ ] o to 2 mM would cause a 10 mv negative shift of the nCX reversal potential, which should decrease diastolic Ca 2+ efflux and possibly favor transport in the Ca 2+ influx mode during sarcolemmal depolarization.…”

Section: Discussionmentioning

confidence: 87%

Blood Calcium Levels in Immature Rats: Influence of Extracellular Calcium Concentration on Myocardial Calcium Handling

et al. 2012

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Abstract:Calcium ions play an important role in several cell functions, from fertilization to cell death. from 1.2 to 2 mM, which also increased the Ca 2+ content in the sarcoplasmic reticulum (SR), and changed the pattern of competition between the main transporters that remove Ca 2+ from the cytosol (SR Ca 2+ -ATPase and Na + /Ca 2+ exchanger). These observations stress the importance of using physiological [Ca 2+ ] o values for reliability of results. It is expected that the present calcemia data, reported for the first time in immature rats, may contribute to the refinement of in vitro experiments with neonatal rat preparations.

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Force Frequency Relationship of the Human Ventricle Increases During Early Postnatal Development

Cited by 73 publications

References 38 publications

Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment

Postnatal neonatal myocardial adaptation is associated with loss of tolerance to tachycardia: a simultaneous invasive and noninvasive assessment

Unplanned reinterventions are associated with postoperative mortality in neonates with critical congenital heart disease

Blood Calcium Levels in Immature Rats: Influence of Extracellular Calcium Concentration on Myocardial Calcium Handling

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