DIAPHRAGM MICROGEOMETRY AND FUNCTION--IMPACT OF DISEASE

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In respiratory disease, the degree of ventilatory and physical impairment is related, in part to diaphragm function. Treatment of chronic respiratory diseases e.g., emphysema is dependent on understanding diaphragm function in health and how this normal function is impacted by the disease state. Interrelationships between diaphragm structure and microcirculatory function have not been studies. Knowledge of sarcomere length during acute respiratory maneuvers and chronic diseases (e.g., emphysema, fibrosis) provide insights into muscle contractile function, energetic demands, regional fiber deformation, microvascular function and O2 exchange potential of the capillary bed. However, there are almost no measurements of sarcomere length in the in situ diaphragm. Thee investigations will test the hypothesis that the diaphragm operates over a "right-shifted" range of sarcomere lengths such that lengths sufficiently short to substantially impair tension development (i.e., lessor 2.3 microns) are not attained, even at total lung capacity (TLC). Thus, at lung volumes below TLC (i.el, diaphragm sarcomere length greater than 2.3 microns) vessels will be stretched, their diameter decreased and slow dynamics and O2 delivery capacity impaired. The competing hypothesis is that sarcomere length will become sufficiently short at a high lung volumes to potentially limit tension development, but at volumes lessor TLC the microvasculature will not be stretched. Chronic diseases i.e., fibrosis, emphysema and hypoxemia are expected to change specific aspects of diaphragm capillary to fiber geometrical relationships. Reduced lung volumes in fibrosis will increase sarcomere length and stretch the capillary bed thereby impairing flow, increasing flow heterogeneity and reducing O2 deliver. In emphysema, neither microvascular flow nor capillary surface area would be expected to change. However, intrafiber diffusion distances will increase due to fiber hypertrophy. Recently developed morphometric techniques and novel physiologic approaches (i.e., microvascular PO2 determination by phosphorescence quenching, diaphragm intravital microscopy) will be employed to identify acute and chronic change in diaphragm capillary and fiber geometry and test their effect on microvascular flow and PO2 and also provide data necessary for modelling O2 exchange and PO2. The ultimate goal of these investigations is to provide a better understanding of the interrelationships between diaphragm fiber geometry and muscular and microvascular function in health and disease.