An overview of mechanical circulatory support in single-ventricle patients

The population of people with a single-ventricle is continually increasing due to improvements across the spectrum of medical care. Unfortunately, a proportion of these patients will develop heart failure. Often, for these patients, mechanical circulatory support (MCS) represents the only available treatment option. While single-ventricle patients currently represent a small proportion of the total number of patients who receive MCS, as the single-ventricle patient population increases, this number will increase as well. Outcomes for these complex single-ventricle patients who require MCS has begun to be evaluated. When considering the entire population, survival to hospital discharge is 30-50%, though this must be considered with the significant heterogeneity of the single-ventricle patient population. Patients with a single-ventricle have unique anatomy, mechanisms of failure, indications for MCS and the type of support utilized. This has made the interpretation and the generalizability of the limited available data difficult. It is likely that some subsets will have a significantly worse prognosis and others a better one. Unfortunately, with these limited data, indications of a favorable or poor outcome have not yet been elucidated. Though currently, a database has been constructed to address this issue. While the outcomes for these complex patients is unclear, at least in some situations, they are poor. However, significant advances may provide improvements going forward, including new devices, computer simulations and 3D printed models. The most important factor, however, will be the increased experience gained by the heart failure team to improve patient selection, timing, device and configuration selection and operative approach

High glucose concentration in cell culture medium does not acutely affect human mesenchymal stem cell growth factor production or proliferation

Optimizing the function and proliferative capacity of stem cells is essential to maximize their therapeutic benefits. High glucose concentrations are known to have detrimental effects on many cell types. We hypothesized that human mesenchymal stem cells (hMSCs) cultured in high glucose-containing media would exhibit diminished proliferation and attenuated production of VEGF, hepatocyte growth factor (HGF), and FGF2 in response to treatment with TNF-α, LPS, or hypoxia. hMSCs were plated in medium containing low (5.5 mM) and high (20 mM or 30 mM) glucose concentrations and treated with TNF-α, LPS, or hypoxia. Supernatants were collected at 24 and 48 h and assayed via ELISA for VEGF, HGF, and FGF2. In addition, hMSCs were cultured on 96-well plates at the above glucose concentrations, and proliferation at 48 h was determined via bromo-2′-deoxy-uridine (BrdU) incorporation. At 24 and 48 h, TNF-α, LPS, and hypoxia-treated hMSCs produced significantly higher VEGF, HGF, and FGF2 compared with control. Hypoxia-induced VEGF production by hMSCs was the most pronounced change over baseline. At both 24 and 48 h, glucose concentration did not affect production of VEGF, HGF, or FGF2 by untreated hMSCs and those treated with TNF-α, LPS, or hypoxia. Proliferation of hMSCs as determined via BrdU incorporation was unaffected by glucose concentration of the media. Contrary to what has been observed with other cells, hMSCs may be resistant to the short-term effects of high glucose. Ongoing efforts to characterize and optimize ex vivo and in vivo conditions are critical if the therapeutic benefits of MSCs are to be maximized

Estrogen receptor β mediates increased activation of PI3K/Akt signaling and improved myocardial function in female hearts following acute ischemia

Females have a lower incidence of heart failure and improved survival after myocardial ischemia-reperfusion (I/R) compared with males. Although estrogen-suppressed cardiomyocyte apoptosis may be mediated through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, it is unclear whether this action is mediated via estrogen receptor β (ERβ). Therefore, we hypothesized that ERβ mediates estrogen-induced cardioprotection through PI3K/Akt and antiapoptotic signaling in females but not in males. Isolated male and female hearts from ERβ knockout (ERβKO) and wild-type (WT) mice (n = 5 mice/group) were subjected to 20-min ischemia followed by 60-min reperfusion (Langendorff). Ablation of ERβ significantly decreased postischemic recovery of left ventricular developed pressure in female, but not male, hearts. Reduced activation of PI3K and Akt was noted in female ERβKO hearts, which was associated with increased expression of caspase-3 and -8, as well as decreased Bcl-2 levels compared with WT. However, myocardial STAT3, SOCS3 (suppressor of cytokine signaling 3), VEGF, and TNF receptors 1 and 2 levels did not change in ERβKO of either sex following I/R. Furthermore, deficiency of ERβ increased myocardial JNK activation in females but increased ERK1/2 activity in males during acute I/R. We conclude that ERβ mediates myocardial protection via upregulation of PI3K/Akt activation, decreased caspase-3 and -8, and increased Bcl-2 in female hearts following I/R. These findings provide evidence of ERβ-mediated PI3K/Akt and antiapoptotic signaling in the myocardium and may lend insight into the mechanistic pathways behind the observed variation in clinical outcomes between males and females after myocardial infarction