Evaluation of Left Ventricular Outflow Gradients During Staged Exercise Stress Echocardiography Helps Differentiate Pediatric Patients With Hypertrophic Cardiomyopathy From Athletes and Normal Subjects.

BACKGROUND: Elevated left ventricular outflow tract (LVOT) gradients during exercise can occur in patients with hypertrophic cardiomyopathy (HCM) as well as in athletes and normal controls. The authors' staged exercise protocol calls for imaging at rest and during each stage of exercise to evaluate the mechanism of LVOT obstruction at each stage. They investigated whether this staged approach helps differentiate HCM from athletes and normal controls. METHODS: They reviewed pediatric exercise stress echocardiograms completed between January 2009 and October 2017 at their center and identified those with gene-positive HCM, athlete's heart, and normal controls. Children with inducible obstruction (those with no LVOT gradient at rest who developed a LVOT peak gradient > 25 mm Hg during exercise) were included. LVOT peak gradient, velocity time integral, acceleration time, and deceleration time were measured at rest, submaximal stages, and peak exercise. RESULTS: Compared with athletes, HCM patients had significantly higher LVOT peak gradients at rest (P = .019), stage 1 of exercise (P = .002), and peak exercise (P = .051), as well as a significantly higher change in LVOT peak gradient from rest to stage 1 (P = .016) and from rest to peak (P = .038). The acceleration time/deceleration time ratio of the LVOT Doppler was significantly lower in HCM patients compared with normal controls at peak exercise. CONCLUSIONS: The HCM patients who develop elevated LVOT gradients at peak exercise typically manifest early obstruction in the submaximal stages of exercise, which helps to differentiate them from athletes and normal controls.

The Miniaturized Multiplane Micro-Transesophageal Echocardiographic Probe: A Comparative Evaluation of Its Accuracy and Image Quality.

BACKGROUND: The initial experience with the miniaturized multiplane micro-transesophageal echocardiographic probe (MTEE) reported high-quality diagnostic imaging in small infants. The aim of this study was to compare the diagnostic accuracy and image quality of the intraoperative MTEE with the pediatric multiplane transesophageal echocardiographic probe (PTEE). METHODS: Infants weighing <5 kg who underwent intraoperative transesophageal echocardiography were identified. Studies using the MTEE were matched 1:1 with those using the PTEE by cardiac diagnosis. The postoperative transesophageal echocardiograms, obtained using either probe, were reviewed for the presence of 11 cardiac abnormalities. Postoperative transesophageal echocardiograms were compared with predischarge transthoracic echocardiograms to assess accuracy. Using receiver operating characteristic curves, the areas under the curve for the MTEE and PTEE were compared. Two pediatric cardiologists scored six image quality metrics on equal numbers of studies obtained with the MTEE and the PTEE. Composite scores from both reviewers were used to compare image quality. RESULTS: The study included 110 transesophageal echocardiograms per probe type. The mean weight for the MTEE was lower than for the PTEE (3.15 ± 0.58 vs 3.70 ± 0.52 kg, P < .001). There was no significant difference in the diagnostic accuracy of the MTEE and PTEE using receiver operating characteristic curves. The numbers of residual anatomic lesions missed by the MTEE and PTEE were similar (19 vs 22, respectively). The composite image quality score was worse for the MTEE compared with the PTEE (81% vs 92%, respectively, P < .0001). CONCLUSIONS: Although the image quality of the MTEE is inferior compared with the PTEE, its diagnostic accuracy in infants weighing <5 kg is comparable.

Lowbush blueberries inhibit scavenger receptors CD36 and SR-A expression and attenuate foam cell formation in ApoE-deficient mice.

Blueberries have recently been reported to reduce atherosclerotic lesion progression in apoE deficient (apoE(-/-)) mice. However, the underlying mechanisms are not fully understood. The objective of this study was to determine whether lowbush blueberries altered scavenger receptor expression and foam cell formation in apoE(-/-) mice. ApoE(-/-) mice were fed AIN-93 diet (CD) or CD formulated to contain 1% freeze-dried lowbush blueberries (BB) for 20 weeks. Gene expression and protein levels of scavenger receptor CD36 and SR-A in aorta and thioglycollate-elicited peritoneal macrophages (PM) were lower in mice fed BB (P < 0.05). In the second experiment, apoE(-/-) mice were fed CD or BB for 5 weeks. PM were collected and cultured. Gene expression and protein levels of CD36 and SR-A were found to be lower in PM of BB fed mice (P < 0.05). In PM from BB fed mice, fewer oxLDL-induced foam cells were formed compared to those from mice fed CD. Gene expression and protein levels of PPARγ were lower in the PM of BB fed mice (P < 0.05). Detectable isomers of hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acid (HETEs) were also lower in the PM of BB fed mice (P < 0.05 or P < 0.01). In conclusion, BB inhibited expression of the two major scavenger receptors CD36 and SR-A in PM of apoE(-/-) mice, at least in part through down-regulating PPARγ and reducing its endogenous ligands HODEs and HETEs. We proposed that BB mediated reduction of scavenger receptor expression and attenuation of oxLDL-induced foam cell formation in PM of apoE(-/-) mice are important mechanisms of the athero-protective effects of BB.

Blueberries reduce pro-inflammatory cytokine TNF-α and IL-6 production in mouse macrophages by inhibiting NF-κB activation and the MAPK pathway.

Blueberries (BB) have been reported to attenuate atherosclerosis in apoE-deficient (ApoE(-/-) ) mice. The aim of this study was to evaluate the effects of BB in reducing pro-inflammatory cytokine production in mouse macrophages. ApoE(-/-) mice were fed AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried BB for 5 wk. TNF-α and IL-6 were lower in serum of BB-fed mice and TNF-α expression in aorta was down-regulated with BB feeding. Protein level and mRNA expression of TNF-α and IL-6 were significantly lower in the peritoneal macrophages from mice fed BB without or with LPS or oxLDL stimulation. RAW264.7 macrophages were treated with polyphenol-enriched extracts made from the sera of rats fed CD (SEC) or CD containing 10% BB (SEB). SEB significantly inhibited LPS-induced mRNA expression and protein levels of TNF-α and IL-6. Furthermore, SEB inhibited the phosphorylation of IκB, NF-κB p65, MAPK p38 and JNK. All of these are important signaling pathways involved in the production of TNF-α and IL-6.

Açaí juice attenuates atherosclerosis in ApoE deficient mice through antioxidant and anti-inflammatory activities.

OBJECTIVE: Açaí fruit pulp has received much attention because of its high antioxidant capacity and potential anti-inflammatory effects. In this study, athero-protective effects of açaí juice were investigated in apolipoprotein E deficient (apoE(-/-)) mice. METHODS AND RESULTS: ApoE(-/-) mice were fed AIN-93G diet (CD) or CD formulated to contain 5% freeze-dried açaí juice powder (AJ) for 20 weeks. The mean lesion areas in the aorta for apoE(-/-) mice fed AJ were 58% less (P<0.001) compared to that for CD fed mice. HDL-cholesterol was higher in AJ fed mice. Biomarkers of lipid peroxidation, including F(2)-isoprostanes and isomers of hydroxyoctadecadienoic acids and hydroxyeicosatetraenoic acids were significantly lower in serum and in liver of AJ fed mice. Expression of the two antioxidant enzyme genes, Gpx3 and Gsr, were significantly up-regulated in the aorta from AJ fed mice. The activity of GPX, GSR and PON1 increased in serum and/or liver of mice fed AJ. In the second experiment, ApoE(-/-) mice were fed CD or AJ for 5 weeks. Serum levels, gene expression and protein levels of the two proinflammatory cytokines TNF-α and IL-6 in the resident macrophages with or without LPS stimulation were lower in mice fed AJ. SEAP reporter assay determined that AJ reduced NF-κB activation. CONCLUSION: Reducing lipid peroxidation through boosting antioxidant enzymes and inhibiting pro-inflammatory cytokine production are proposed as major underlying mechanisms for the athero-protective effects of the açaí juice tested in these experimental in vivo models.

Coronary artery spasm during angiography in a pediatric heart transplant recipient: subsequent prevention by intracoronary nitroglycerin administration.

Coronary artery spasm can occur during coronary angiography in pediatric heart transplant recipients. The angiographic appearance can suggest allograft vasculopathy. We report coronary artery spasm in a pediatric heart transplant recipient in whom intracoronary nitroglycerin administration prevented a repetition of spasm upon subsequent diagnostic coronary angiography. Additional studies of dose response, particularly in cardiac transplant recipients, may help determine whether lower doses of intracoronary nitrates, such as that administered to our patient, can be effective in preventing coronary artery vasospasm in pediatric heart transplant recipients.

Dietary blueberries attenuate atherosclerosis in apolipoprotein E-deficient mice by upregulating antioxidant enzyme expression.

Protective effects of blueberries (BB) against atherosclerosis and potential underlying mechanisms in reducing oxidative stress were examined in apoE-deficient (apoE(-/-)) mice. ApoE(-/-) mice were fed an AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried whole BB for 20 wk. The mean lesion area for apoE(-/-) mice fed BB was reduced by 39% (P < 0.001) in the aorta sinus and 58% (P < 0.001) in the descending aorta compared with CD-fed mice. These atheroprotective effects were independent of the serum lipid profile or total antioxidant capacity (as measured by oxygen radical absorbance capacity). The concentration of a biomarker of lipid peroxidation, F(2)-isoprostane, was lower in liver of BB-fed mice (P < 0.05). Genes analyzed by RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin reductase 1] were upregulated in BB-fed mice. Enzyme activities of SOD and GSR were greater (P < 0.05) in liver and/or serum of BB-fed mice than those of CD-fed mice. In addition, serum paraoxonase 1 activity in serum of BB-fed mice was also greater than that of CD-fed mice (P < 0.05) at the end of the study. These results suggest a protective effectiveness of BB against atherosclerosis in this apoE(-/-) mouse model. The potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation and enhancement of antioxidant defense.

Results of intravascular stent placement for fibrosing mediastinitis.

OBJECTIVE: Fibrosing mediastinitis is a rare disorder characterized by an excessive fibrotic reaction in the mediastinum which can result in compromise of mediastinal structures. We sought to evaluate short- and midterm results of intravascular thoracic vessel stent placement for patients with fibrosing mediastinitis. DESIGN: We reviewed all records of fibrosing mediastinitis patients who were referred for stent placement to treat mediastinal vascular compression over a 7-year period. Catheterization reports and digital angiography were assessed to determine vessel dimension and stent characteristics. PATIENTS: Thirteen catheterizations were performed in six patients (five females, mean age 39 years, range 23-63) with a range of 1-4 per patient. INTERVENTIONS: Four patients were treated with intravascular stents placed percutaneously. One patient underwent surgical intravascular stent placement, and one patient declined surgical therapy. The right pulmonary artery was treated in three patients, the superior vena cava was treated in one patient, and three pulmonary veins were treated in one patient. OUTCOME MEASURES: Pertinent vessel and hemodynamics including immediate short-, and mid-term results were assessed. Procedural complications, midterm follow-up (up to 7 years), and overall survival were determined. RESULTS: Each intervention resulted in hemodynamic improvement with subsequent clinical improvement. Reintervention was required within 12 months in two of four percutaneously treated patients. One death occurred 4 days after cutting balloon angioplasty in a preexisting pulmonary vein stent. CONCLUSIONS: Percutaneous therapy for vessel compression secondary to fibrosing mediastinitis is an option that is effective in improving short-term vascular patency. In-stent stenosis was a frequent complication in patients with fibrosing mediastinitis, particularly when pulmonary veins were involved. Short- and midterm success can be achieved, but progressive fibrosing mediastinitis remains a difficult clinical problem with repeat dilation of stents and/or additional stent placement necessary to maintain optimal stent patency and improvement in clinical symptomatology.

Agouti signaling protein stimulates cell division in "viable yellow" (A(vy)/a) mouse liver.

Enhanced linear growth, hyperplasia, and tumorigenesis are well-known characteristics of "viable yellow" agouti A(vy)/- mice (Wolff GL, Roberts DW, Mountjoy KG. Physiol Genomics 1:151-163, 1999); however, the functional basis for this aspect of the phenotype is unknown. In the present study, we ascertained whether agouti signaling protein (ASIP) levels in A(vy)/a or a/a livers are associated with hepatocyte proliferation as a possible factor in promotion of hepatocellular tumor formation. Proliferating cell nuclear antigen (PCNA) assays and quantitative real-time reverse transcriptase polymerase chain reaction assays were performed on liver samples from mottled yellow A(vy)/a, pseudoagouti A(vy)/a, and black a/a VY mice to determine mitotic indices and expression levels of A(vy )and a in relation to the expression level of the housekeeping gene hprt. We found that ASIP levels were approximately 100-fold higher in yellow than in pseudoagouti or black mice and that the proportion of PCNA-positive hepatocytes was greater (P < 0.001) in yellow than in pseudoagouti or black mice.