This proposal will attempt to provide a better understanding of certain physical phenomena that influence the coronary circulation. The phenomena of capacitance, vascular waterfalls, critical closure, zero-flow pressure intercepts will be analyzed from a theoretical and experimental approach. Simple models of the physiologic preparations will be scrutinized for possible experimental insights. Specific projects include: 1) Capacitive Phenomena. The arterial and total vascular compliance of the coronary vasculature will be quantitated and tested for linearity. The influence of capacitance on pressure-flow relationships will be assessed in terms of coronary conductance and zero-flow intercepts. The beneficial effects of increased compliance on the delivery of collateral blood flow will be explored. A re-examination of the critical closure phenomenon will be performed in terms of capacitive effects. The possible curvilinear shape of pressure-flow relationships will be assessed and explained in terms of vascular compliance. 2) Waterfall Phenomena. Regional variations in pressure-flow relationships will be examined using the microsphere technique at the very low driving pressure range. The beneficial effects of lowered preload will be explained in terms of collateral conductance and collateral waterfalls. The physical basis for """"""""reverse coronary steal"""""""" will be described in terms of physical alterations. The hypothesis of an intramyocardial pump as the basis for systolic inhibiton of coronary flow will be critically tested. 3) An Arterial Vascular Hierarchy. Using sequential embolization of the microvasculature, the arterial branching pattern can be mapped. Transmural differences in vascularity at different levels of the arterial tree will be determined from """"""""physiologic"""""""" and morphometric techniques. 4) The Non-Blood Flow Basis for Subendocardial Vulnerability. The wavefront phenomenon of myocardial necrosis is not due to a gradient of blood flow! It is likely that a transmural variation in myocardial metabolism dictates this phenomenon. These findings will be confirmed in models of ischemia where the transmural gradient of blood flow is abolished. The uniformly blood flow depleted myocardium provides a critical test of the significance of metabolic gradients. The role of blood flow in modulating the rate of necrosis will be explored.
| Dolgilevich, S M; Siri, F M; Atlas, S A et al. (2001) Changes in collagenase and collagen gene expression after induction of aortocaval fistula in rats. Am J Physiol Heart Circ Physiol 281:H207-14 |
