Transverse lipid organization dictates bending fluctuations in model plasma membranes.

Membrane undulations play a vital role in many biological processes, including the regulation of membrane protein activity. The asymmetric lipid composition of most biological membranes complicates theoretical description of these bending fluctuations, yet experimental data that would inform any such a theory is scarce. Here, we used neutron spin-echo (NSE) spectroscopy to measure the bending fluctuations of large unilamellar vesicles (LUV) having an asymmetric transbilayer distribution of high- and low-melting lipids. The asymmetric vesicles were prepared using cyclodextrin-mediated lipid exchange, and were composed of an outer leaflet enriched in egg sphingomyelin (ESM) and an inner leaflet enriched in 1-palmitoyl-2-oleoyl-phosphoethanolamine (POPE), which have main transition temperatures of 37 °C and 25 °C, respectively. The overall membrane bending rigidity was measured at three temperatures: 15 °C, where both lipids are in a gel state; 45 °C, where both lipids are in a fluid state; and 30 °C, where there is gel-fluid co-existence. Remarkably, the dynamics for the fluid asymmetric LUVs (aLUVs) at 30 °C and 45 °C do not follow trends predicted by their symmetric counterparts. At 30 °C, compositional asymmetry suppressed the bending fluctuations, with the asymmetric bilayer exhibiting a larger bending modulus than that of symmetric bilayers corresponding to either the outer or inner leaflet. We conclude that the compositional asymmetry and leaflet coupling influence the internal dissipation within the bilayer and result in membrane properties that cannot be directly predicted from corresponding symmetric bilayers.

Maladaptive aortic properties after the Norwood procedure: An angiographic analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial.

OBJECTIVES: Aortic arch reconstruction in children with single ventricle lesions may predispose to circulatory inefficiency and maladaptive physiology leading to increased myocardial workload. We sought to describe neoaortic anatomy and physiology, risk factors for abnormalities, and impact on right ventricular function in patients with single right ventricle lesions after arch reconstruction. METHODS: Prestage II aortic angiograms from the Pediatric Heart Network Single Ventricle Reconstruction trial were analyzed to define arch geometry (Romanesque [normal], crenel [elongated], or gothic [angular]), indexed neoaortic dimensions, and distensibility. Comparisons were made with 50 single-ventricle controls without prior arch reconstruction. Factors associated with ascending neoaortic dilation, reduced distensibility, and decreased ventricular function on the 14-month echocardiogram were evaluated using univariate and multivariable logistic regression. RESULTS: Interpretable angiograms were available for 326 of 389 subjects (84%). Compared with controls, study subjects more often demonstrated abnormal arch geometry (67% vs 22%, P < .01) and had increased ascending neoaortic dilation (Z score 3.8 ± 2.2 vs 2.6 ± 2.0, P < .01) and reduced distensibility index (2.2 ± 1.9 vs 8.0 ± 3.8, P < .01). Adjusted odds of neoaortic dilation were increased in subjects with gothic arch geometry (odds ratio [OR], 3.2 vs crenel geometry, P < .01) and a right ventricle-pulmonary artery shunt (OR, 3.4 vs Blalock-Taussig shunt, P < .01) but were decreased in subjects with aortic atresia (OR, 0.7 vs stenosis, P < .01) and those with recoarctation (OR, 0.3 vs no recoarctation, P = .04). No demographic, anatomic, or surgical factors predicted reduced distensibility. Neither dilation nor distensibility predicted reduced right ventricular function. CONCLUSIONS: After Norwood surgery, the reconstructed neoaorta demonstrates abnormal anatomy and physiology. Further study is needed to evaluate the longer-term impact of these features.

Prior Innominate Vein Occlusion Does Not Preclude Successful Bidirectional Superior Cavopulmonary Connection.

BACKGROUND: Low superior vena cava (SVC) blood flow has recently been identified as a marker for bidirectional superior cavopulmonary connection (SCPC) failure and death. Prior innominate vein occlusion is considered a significant anatomic risk factor for SCPC failure. We therefore evaluated the outcomes of infants who underwent SCPC with known upper-body venous obstruction. METHODS: Between February 1995 and June 2014, SCPC was carried out in 8 patients who had either a single SVC with known prior occlusion of the innominate vein (n = 6) or bilateral SVCs without a bridging vein with occlusion of one SVC (n = 2). The cause of the occlusion was an indwelling catheter in 5 patients. These patients were compared with 8 patients with normal upper-body venous drainage who underwent SCPC. Patients were evaluated for preoperative risk factors (including SVC size, pulmonary artery size, Nakata index, pulmonary vascular resistance), operative factors, and clinical outcomes to determine the impact of prior upper-body venous occlusion on SCPC failure or death. RESULTS: There were no significant differences in preoperative risk factors between the two groups, except for a significantly lower Nakata index in the study group with a trend toward smaller pulmonary artery branch size. There were no SCPC takedowns or mortalities. There was no significant difference in postoperative length of stay (median of 7 days [range, 5 to 32 days] versus 5 days [range, 4 to 32 days]; p = 0.17. Study patients had a lower mean systemic oxygen saturation at discharge, 81% versus 85% (p = 0.05). In the study group, at a median follow-up of 42 months, 3 patients underwent successful Fontan completion and 5 are still awaiting Fontan completion. CONCLUSIONS: Although patients with prior upper-body venous obstruction may have lower systemic oxygen saturations at hospital discharge, they do not demonstrate an increased SCPC failure or mortality rate. Innominate vein occlusion or its equivalent in patients with bilateral SVCs should not preclude the performance of SCPC. Physiologic rather than anatomic evaluation of preoperative systemic venous return may be more useful to predict outcome after SCPC.

Feasibility and utility of three-dimensional color flow echocardiography of the aortic arch: The "echocardiographic angiogram".

Two-dimensional transthoracic echocardiography (2DE) is the most commonly used diagnostic modality to evaluate congenital and acquired abnormalities of the aortic arch. However, 2DE is frequently limited in this ability due to the three-dimensional character of the arch and its interrelationships with other vascular structures. Recently, three-dimensional echocardiography (3DE) with 3D color flow Doppler became commercially available. We examined the feasibility and utility of 3DE with 3D color Doppler in the evaluation of patients with congenital (native and postoperative) abnormalities of the aortic arch. We found that 3DE color flow provides important diagnostic information in patients with aortic arch anomalies, in a manner that is quick and user-friendly. In addition, 17 of the 26 patients had their 3DE findings confirmed by additional modalities, providing reasonably significant validation for our findings with 3DE.