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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044399-02
Application #
3363130
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1992-04-09
Project End
1997-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Versluis, J Pieter; Heslinga, Johannes W; Sipkema, Pieter et al. (2004) Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy. Am J Physiol Heart Circ Physiol 286:H979-84
Versluis, J P; Heslinga, J W; Sipkema, P et al. (2001) Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 microm. Am J Physiol Heart Circ Physiol 281:H1913-8
Cornelissen, A J; Spaan, J A; Dankelman, J et al. (2001) Evidence for stretch-induced resistance increase of proximal coronary microcirculation. Am J Physiol Heart Circ Physiol 281:H2687-96
Spaan, J A; Cornelissen, A J; Chan, C et al. (2000) Dynamics of flow, resistance, and intramural vascular volume in canine coronary circulation. Am J Physiol Heart Circ Physiol 278:H383-403
Yamamoto, S; Sipkema, P; Yin, F C (1999) Effect of vasoconstriction on coronary artery resistance changes caused by stretching surrounding myocardial tissue. Heart Vessels 14:9-14
Heslinga, J W; Allaart, C P; Yin, F C et al. (1997) Effects of contraction, perfusion pressure, and length on intramyocardial pressure in rat papillary muscle. Am J Physiol 272:H2320-6
Dijkman, M A; Heslinga, J W; Allaart, C P et al. (1997) Reoxygenated effluent of Tyrode-perfused heart affects papillary muscle contraction independent of cardiac perfusion. Cardiovasc Res 33:45-53
Dijkman, M A; Heslinga, J W; Sipkema, P et al. (1997) Perfusion-induced changes in cardiac contractility and oxygen consumption are not endothelium-dependent. Cardiovasc Res 33:593-600
Sipkema, P; Yamada, H; Yin, F C (1996) Coronary artery resistance changes depend on how surrounding myocardial tissue is stretched. Am J Physiol 270:H924-34
Dijkman, M A; Heslinga, J W; Sipkema, P et al. (1996) Perfusion-induced changes in cardiac O2 consumption and contractility are based on different mechanisms. Am J Physiol 271:H984-9

Showing the most recent 10 out of 14 publications