BackgroundBreast milk nutrient content varies with prematurity and postnatal age. Our aims were to conduct a meta-analysis of preterm and term breast milk nutrient content (energy, protein, lactose, oligosaccharides, fat, calcium, and phosphorus); and to assess the influence of gestational and postnatal age. Additionally we assessed for differences by laboratory methods for: energy (measured vs. calculated estimates) and protein (true protein measurement vs. the total nitrogen estimates).MethodsSystematic review results were summarized graphically to illustrate the changes in composition over time for term and preterm milk. Since breast milk fat content varies within feeds and diurnally, to obtain accurate estimates we limited the meta-analyses for fat and energy to 24-hour breast milk collections.ResultsForty-one studies met the inclusion criteria: 26 (843 mothers) preterm studies and 30 (2299 mothers) term studies of breast milk composition. Preterm milk was higher in true protein than term milk, with differences up to 35% (0.7 g/dL) in colostrum, however, after postnatal day 3, most of the differences in true protein between preterm and term milk were within 0.2 g/dL, and the week 10–12 estimates suggested that term milk may be the same as preterm milk by that age. Colostrum was higher than mature milk for protein, and lower than mature milk for energy, fat and lactose for both preterm and term milk. Breast milk composition was relatively stable between 2 and 12 weeks. With milk maturation, there was a narrowing of the protein variance. Energy estimates differed whether measured or calculated, from −9 to 13%; true protein measurement vs. the total nitrogen estimates differed by 1 to 37%.ConclusionsAlthough breast milk is highly variable between individuals, postnatal age and gestational stage (preterm versus term) were found to be important predictors of breast milk content. Energy content of breast milk calculated from the macronutrients provides poor estimates of measured energy, and protein estimated from the nitrogen over-estimates the protein milk content. When breast milk energy, macronutrient and mineral content cannot be directly measured the average values from these meta-analyses may provide useful estimates of mother’s milk energy and nutrient content.

The cardiac action potential (AP) is critical for initiating and coordinating myocyte contraction. In particular, the early repolarization period of the AP (phase 1) strongly influences the time course and magnitude of the whole‐cell intracellular Ca2+ transient by modulating trans‐sarcolemmal Ca2+ influx through L‐type Ca2+ channels (ICa,L) and Na‐Ca exchangers (ICa,NCX). The transient outward potassium current (Ito) has kinetic properties that make it especially effective in modulating the trajectory of phase 1 repolarization and thereby cardiac excitation‐contraction coupling (ECC). The magnitude of Ito varies greatly during cardiac development, between different regions of the heart, and is invariably reduced as a result of heart disease, leading to corresponding variations in ECC. In this article, we review evidence supporting a modulatory role of Ito in ECC through its influence on ICa,L, and possibly ICa,NCX. We also discuss differential effects of Ito on ECC between different species, between different regions of the heart and in heart disease.

Background-We have recently shown that genetic inactivation of phosphoinositide 3-kinase ␥ (PI3K␥), the isoform linked to G-protein-coupled receptors, results in increased cardiac contractility with no effect on basal cell size. Signaling via the G-protein-coupled ␤-adrenergic receptors has been implicated in cardiac hypertrophy and heart failure, suggesting that PI3K␥ might play a role in the pathogenesis of heart disease. Methods and Results-To determine the role for PI3K␥ in hypertrophy induced by G-protein-coupled receptors and cardiomyopathy, we infused isoproterenol, a ␤-adrenergic receptor agonist, into PI3K␥-deficient mice. Compared with controls, isoproterenol infusion in PI3K␥-deficient mice resulted in an attenuated cardiac hypertrophic response and markedly reduced interstitial fibrosis. Intriguingly, chronic ␤-adrenergic receptor stimulation triggered impaired heart functions in wild-type mice, whereas PI3K␥-deficient mice retained their increased heart function and did not develop heart failure. The lack of PI3K␥ attenuated the activation of Akt/protein kinase B and extracellular signal-regulated kinase 1/2 signaling pathways in cardiac myocytes in response to isoproterenol. ␤ 1 -and ␤ 2 -adrenergic receptor densities were decreased by similar amounts in PI3K␥-deficient and control mice, suggesting that PI3K␥ isoform plays no role in the downregulation of ␤-adrenergic receptors after chronic ␤-adrenergic stimulation. Conclusions-Our data show that PI3K␥ is critical for the induction of hypertrophy, fibrosis, and cardiac dysfunction function in response to ␤-adrenergic receptor stimulation in vivo. Thus, PI3K␥ may represent a novel therapeutic target for the treatment of decreased cardiac function in heart failure.