Glycans as receptors for influenza pathogenesis

Influenza A viruses, members of the Orthomyxoviridae family, are responsible for annual seasonal influenza epidemics and occasional global pandemics. The binding of viral coat glycoprotein hemagglutinin (HA) to sialylated glycan receptors on host epithelial cells is the critical initial step in the infection and transmission of these viruses. Scientists believe that a switch in the binding specificity of HA from Neu5Acα2-3Gal linked (α2-3) to Neu5Acα2-6Gal linked (α2-6) glycans is essential for the crossover of the viruses from avian to human hosts. However, studies have shown that the classification of glycan binding preference of HA based on sialic acid linkage alone is insufficient to establish a correlation between receptor specificity of HA and the efficient transmission of influenza A viruses. A recent study reported extensive diversity in the structure and composition of α2-6 glycans (which goes beyond the sialic acid linkage) in human upper respiratory epithelia and identified different glycan structural topologies. Biochemical examination of the multivalent HA binding to these diverse sialylated glycan structures also demonstrated that high affinity binding of HA to α2-6 glycans with a characteristic umbrella-like structural topology is critical for efficient human adaptation and human-human transmission of influenza A viruses. This review summarizes studies which suggest a new paradigm for understanding the role of the structure of sialylated glycan receptors in influenza virus pathogenesis.National Institute of General Medical Sciences (U.S.) (Glue Grant U54 GM62116)National Institutes of Health (U.S.) (Grant GM57073)Singapore-MIT Alliance for Research and Technolog

Accuracy of tissue Doppler estimation of the right atrial pressure in anesthetized, paralyzed, and mechanically ventilated patients

The ratio of tricuspid peak early inflow velocity to peak early diastolic velocity of the lateral tricuspid annulus (the E/Ea ratio) measured by transthoracic echocardiography has been reported to correlate with right atrial (RA) pressure. In this study, the correlation between the E/Ea ratio and RA pressure was tested in 44 anesthetized, paralyzed, and mechanically ventilated patients by transesophageal echocardiography. Mean RA pressure and the following echocardiographic data were recorded simultaneously: tricuspid peak early inflow velocities by Doppler echocardiography, peak early diastolic velocity of the lateral tricuspid annulus by tissue Doppler imaging, and right ventricular and left ventricular end-diastolic areas. Linear regression did not indicate a correlation between the E/Ea ratio and RA pressure (r = -0.11, p = 0.48) or between the E/Ea ratio and the right or left ventricular end-diastolic area index; it revealed a weak correlation between RA pressure and the inspiratory plateau pressure and body mass index. In conclusion, the E/Ea ratio failed to predict RA pressure or planimetric indexes of ventricular preload in anesthetized, paralyzed, and mechanically ventilated patients. In these patients, RA pressure was largely influenced by extracardiac factors. (c) 2006 Elsevier Inc. All rights reserved

Effects of on-pump versus off-pump coronary artery bypass graft surgery on right ventricular function

Objectives: Right ventricular dysfunction is a possible cause of cardiac failure after coronary surgery. The use of cardiopulmonary bypass is regarded as a major cause for its occurrence, and it has been postulated that performing coronary surgery without cardiopulmonary bypass might reduce ventricular dysfunction. Therefore, this prospective, randomized, controlled study tested the hypothesis that off-pump coronary surgery would better preserve right ventricular systolic and diastolic function than conventional bypass surgery. Methods: Fifty patients scheduled for elective coronary artery bypass surgery were randomly assigned to conventional or off-pump surgery. Right ventricular function was assessed by intraoperative transesophageal echocardiography immediately before and after coronary surgery. Right ventricular ejection fraction was used as a marker of global systolic function and tricuspid early/late ( atrial) ratio as a marker of the global diastolic function. Peak systolic and early diastolic velocities of the lateral tricuspid annulus were studied to assess systolic and diastolic function in the area of the right ventricular free wall. Results: Surgery was completed according to randomization in 48 of 50 patients. Preoperative characteristics were similar in both groups. Intraoperative differences between the two groups included a higher volume of allogeneic blood transfusion in the conventional surgery group. At the end of surgery, global systolic right ventricular function was similarly maintained and diastolic function similarly impaired in both groups. There were no significant intergroup differences in any of the echocardiographic markers of right ventricular function. Conclusions: Off-pump surgery did not better preserve right ventricular systolic and diastolic function than did conventional coronary surgery