Matching supply to demand: relating local structural adaptation to global function

The heart and microvasculature have characteristics of a complex adaptive system. Extreme challenges faced by these organ systems cause structural changes which lead to global adaptation. To assess the impact of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. With chronic edema, the primary form of collagen changed from type I to III and left ventricular chamber compliance significantly increased. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus, preserving cardiac function over a wide range of interstitial fluid pressures. To asses the effect of microvascular occlusions, we reintroduced the Pallid bat wing model and developed a novel mathematical model. We hypothesized that microvessels can switch from predominantly pressure-mediated to shear-mediated responses to ensure dilation during occlusions. Arterioles of unanesthetized Pallid bats were temporarily occluded upstream (n=8) and parallel (n=4) to vessels of interest (20-65 mm). In both cases, the vessels of interest rapidly dilated (36+24 %, 37+33 %), illustrating that they responded appropriately to either decreased pressure or increased shear stress. The model not only reproduced this switching behavior, but reveals its origin as the nonlinear shear-pressure-radius relationship. The properties of the heart and microvasculature were extended to characterize a ?Research-Intensive Community? (RIC) model, to provide a feasible solution consistent with the Boyer Commission, to create a sustainable physiology research program. We developed and implemented the model with the aim of aligning diverse goals of participants while simultaneously optimizing research productivity. While the model radically increases the number of undergraduate students supported by a single faculty member, the inherent resilience and scalability of this complex adaptive system enables it to expand without formal institutionalization.