Lung vascular cell heterogeneity: endothelium, smooth muscle, and fibroblasts

The pulmonary circulation represents a unique vascular bed, receiving 100% of the cardiac output while maintaining low blood pressure. Multiple different cell types, including endothelium, smooth muscle, and fibroblasts, contribute to normal vascular function, and to the vascular response to injury. Our understanding of the basic cell biology of these various cell types, and the roles they play in vascular homeostasis and disease, remains quite limited despite several decades of study. Recent advances in approaches that enable the mapping of cell origin and the study of the molecular basis of structure and function have resulted in a rapid accumulation of new information that is essential to vascular biology. A recent National Institutes of Health workshop was held to discuss emerging concepts in lung vascular biology. The findings of this workshop are summarized in this article.     

Interventricular delay interval optimization in cardiac resynchronization therapy guided by echocardiography versus guided by electrocardiographic QRS interval width

Present devices for cardiac resynchronization therapy offer the possibility of tailoring the hemodynamic effect of biventricular pacing by optimization of the interventricular delay (VV) beyond atrioventricular (AV)-interval optimization. It was not yet defined whether a QRS width-based strategy may be a helpful tool for echocardiography for device programming. The aim of the study was to investigate the relation between VV-interval optimization guided by echocardiography and guided by QRS interval width. One hundred six patients with a cardiac resynchronization therapy device for > or =3 months were enrolled. All patients underwent echocardiographic AV and VV delay optimization. The AV interval was optimized according to the E wave-A wave (EA) interval and left ventricular filling time. At the optimal AV delay, VV optimization was performed by measuring the aortic velocity time integral at 5 different settings: simultaneous right and left ventricle output, left ventricle pre-excitation (left ventricle + 40 and 80 ms, respectively), and right ventricle pre-excitation (right ventricle + 40 and 80 ms, respectively). A 12-lead electrocardiogram was recorded and QRS duration was measured in the lead with the greatest QRS width. The electrocardiographic (ECG)-optimized VV interval was defined according to the narrowest achievable QRS interval among 5 VV intervals. The echocardiographic-optimized VV interval was left ventricle + 40 ms in 28 patients, left ventricle + 80 ms in 15 patients, simultaneous in 46 patients, right ventricle + 40 ms in 14 patients, and right ventricle + 80 ms in 3 patients. Significant concordance (kappa = 0.69, p <0.001) was found between the echocardiographic- and ECG-optimized VV interval. In conclusion, significant concordance appeared to exist during biventricular pacing between VV programming based on the shortest QRS interval at 12-lead ECG pacing and echocardiographic-guided VV-interval optimization. A combined ECG- and echocardiographic approach could be a less time-consuming solution in performing this operation.     

Measurement of long‐term iron absorption and loss during iron supplementation using a stable isotope of iron (57Fe)

We report the first measurements of long‐term iron absorption and loss during iron supplementation in African children using a stable isotope of iron (⁵⁷Fe). After uniform labelling of body iron with ⁵⁷Fe, iron absorption is proportional to the rate of decrease in the ⁵⁷Fe tracer concentration, while iron loss is proportional to the rate of decrease in the ⁵⁷Fe tracer amount. Anaemic Gambian toddlers were given 2 mg ⁵⁷Fe orally to equilibrate with total body iron over 8–11 months. After assignment to the positive control arm of the HIGH study, 22 toddlers consumed a micronutrient powder containing 12 mg iron for 12 weeks followed by 12 weeks without iron supplementation. Their daily iron absorption increased 3·8‐fold during the iron supplementation period compared to the control period [median (interquartile range, IQR): 1·00 (0·82; 1·28) mg/day vs. 0·26 (0·22; 0·35) mg/day; P = 0·001]. Unexpectedly, during the supplementation period, daily iron loss also increased by 3·4‐fold [0·75 (0·55; 0·87) mg/day vs. 0·22 (0·19; 0·29) mg/day; P = 0·005]. Consequently, most (~72%) of the absorbed iron was lost during supplementation. Long‐term studies of iron absorption and loss are a promising and accurate method for assessing and quantifying long‐term iron balance and may provide a reference method for evaluating iron intervention programs in vulnerable population groups. This study was registered as ISRCTN 0720906.