Cardiac muscle contraction is one of the major influences on coronary flow -- flow decreases, dramatically during contraction. Despite this well-known observation, however, the precise underlying mechanisms are not well understood. Delineating the mechanisms is difficult in the intact heart partly because it is difficult to precisely measure the pertinent parameters and partly because there are transmural gradients of these parameters. Moreover, the phasic nature of cardiac contraction adds additional complications. The overall goal of this proposal is to delineate the mechanical effects of the muscle and surrounding tissue on coronary pressure flow relations.
The specific aims of the proposal are to test the following hypotheses:
Specific Aim # l: The passive effect of mechanical stretching on P-F relations of the vasodilated bed in cardiac muscular tissue is influenced by the extent and direction of stretching.
Specific Aim #2 : The effects of both phasic and steady (tetanized) contractions on P-F relations of the vasodilated bed are influenced by the level of contractility, the extent and direction of stretching, but not by the afterload.
Specific Aim #3 : The interaction between vessels and surrounding tissue is influenced by the interstitial fluid volumes.
Specific Aim #4 : The interaction between vessels and surrounding tissue is modulated by the presence of vessel tone.
Specific Aim #5 : The interaction between vessels and surrounding tissue is modulated by the curvature of the tissue with the effect being greater in active than passive states. By using the specific expertise of two laboratories these aims will be addressed using isolated microvessels, perfused rat papillary muscles, perfused isolated dog interventricular septum, and isolated supported hearts. By progressing from the very simple to the very complex and utilizing the advantages of each preparation to answer a question for which it is ideally suited, a better understanding of this important field will emerge.
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