Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy : Insights From Wave Intensity Analysis and Magnetic Resonance

Background: Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. Objectives: Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. Methods: Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. Results: Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). Conclusions: Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment

"Choice set" for health behavior in choice-constrained settings to frame research and inform policy : examples of food consumption, obesity and food security

ABSTRACT: Objectives: Using the nexus between food consumption, food security and obesity, this paper addresses the complexity of health behavior decision-making moments that reflect relational social dynamics in context-specific dialogues, often in choice-constrained conditions. Methods: A pragmatic review of literature regarding social determinants of health in relation to food consumption, food security and obesity was used to advance this theoretical model. Results and discussion: We suggest that health choice, such as food consumption, is based on more than the capacity and volition of individuals to make "healthy" choices, but is dialogic and adaptive. In terms of food consumption, there will always be choice-constrained conditions, along a continuum representing factors over which the individual has little or no control, to those for which they have greater agency. These range from food store geographies and inventories and food availability, logistical considerations such as transportation, food distribution, the structure of equity in food systems, state and non-government food and nutrition programs, to factors where the individual exercises a greater degree of autonomy, such as sociocultural foodways, family and neighborhood shopping strategies, and personal and family food preferences. At any given food decision-making moment, many factors of the continuum are present consciously or unconsciously when the individual makes a decision. These health behavior decision-making moments are mutable, whether from an individual perspective, or within a broader social or policy context. We review the construct of "choice set", the confluence of factors that are temporally weighted by the differentiated and relationally-contextualized importance of certain factors over others in that moment. The choice transition represents an essential shift of the choice set based on the conscious and unconscious weighting of accumulated evidence, such that people can project certain outcomes. Policies and interventions should avoid dichotomies of "good and bad" food choices or health behaviors, but focus on those issues that contribute to the weightedness of factors influencing food choice behavior at a given decision-making moment and within a given choice set

Expression and Localization of Angiogenic Growth Factors in Developing Porcine Mesonephric Glomeruli

The development and growth of renal glomeruli is regulated by specific angiogenic growth factors, including vascular endothelial growth factor (VEGF) and the angiopoietins (ANGPT1 and ANGPT2). The expression of these factors has already been studied during metanephric glomerulogenesis, but it remains to be elucidated during the development of the embryonic mesonephros, which can function as an interesting model for glomerular development and senescence. In this study, the presence of the angiogenic growth factors was studied in developing porcine mesonephroi, using IHC and real-time RT-qPCR on laser capture microdissected glomeruli. In addition, mesonephric glomerular growth was measured by using stereological methods. ANGPT2 remained upregulated during maturation of glomeruli, which may be explained by the continuous growth of the glomeruli, as observed by stereological examination. The mRNA for VEGFA was expressed in early developing and in maturing glomeruli. The VEGF receptor VEGFR1 was stably expressed during the whole lifespan of mesonephric glomeruli, whereas VEGFR2 mRNA was only upregulated in early glomerulogenesis, suggesting that VEGFR2 is important for the vascular growth but that VEGFR1 is important for the maintenance of endothelial fenestrations. (J Histochem Cytochem 58:1045–1056, 2010