Ventricular suction, the phenomenon whereby the ventricle assists its own filling by contracting to below its equilibrium volume and thereby generating restoring forces, has been recognized for many years. Its physiologic importance and mechanism remain uncertain, however, due to the difficulty of studying suction in the absence of the confounding influence of other determinants of filling, especially those related to the properties of the atrium. Recent studies in which a prosthetic mitral valve was used to clamp left ventricular (LV) volume at the end- systolic (ES) value suggest that suction is a major component of filling under physiologic conditions. To study this phenomenon in the Intact LV, we have designed a servo motor system which allows abrupt clamping of left atrial pressure (LAP) at a constant value during a single diastole. By clamping LAP below LV minimum pressure, a non- filling diastole (identical to an ES volume clamp) can be produced which in turn allows delineation of the positive and negative, fully- relaxed pressure-volume relation (PVR) of the LV. The position of the negative PVR Is a measure of the magnitude of restoring forces. In addition, the system can be used to produce zero source pressure conditions for filling, in which LAP = LV external pressure. With a zero source pressure, filling can only occur via suction. This allows study of suction in the absence of the effects of other determinants of filling. In this project, to be performed in open-chest pericardiectomlzed dogs, we propose to exploit this unique approach to accomplish four specific aims: 1) determine the Importance of suction as a mechanism of filling over a wide range of preload, afterload, heart rate and contractility; 2) delineate the features of normal regional contraction responsible for generation of restoring forces and how they are modified by alterations in regional function; 3) relate restoring forces/suction to LV """"""""twist""""""""; and 4) determine the relationship between LV restoring forces and right ventricular performance. These studies should provide improved understanding of an important aspect of LV filling.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL051201-02
Application #
2227796
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1994-01-14
Project End
1996-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Wu, Yiming; Bell, Stephen P; Trombitas, Karoly et al. (2002) Changes in titin isoform expression in pacing-induced cardiac failure give rise to increased passive muscle stiffness. Circulation 106:1384-9
Wu, Yiming; Labeit, Siegfried; Lewinter, Martin M et al. (2002) Titin: an endosarcomeric protein that modulates myocardial stiffness in DCM. J Card Fail 8:S276-86
Bell, S P; Nyland, L; Tischler, M D et al. (2000) Alterations in the determinants of diastolic suction during pacing tachycardia. Circ Res 87:235-40
Bell, S P; Fabian, J; LeWinter, M M (1998) Effects of dobutamine on left ventricular restoring forces. Am J Physiol 275:H190-4
LeWinter, M M; Fabian, J; Bell, S P (1998) Left ventricular restoring forces: modulation by heart rate and contractility. Basic Res Cardiol 93 Suppl 1:143-7
Bell, S P; Fabian, J; Watkins, M W et al. (1997) Decrease in forces responsible for diastolic suction during acute coronary occlusion. Circulation 96:2348-52
Watkins, M W; Higashiyama, A; Chen, Z et al. (1996) Rapid shortening during relaxation increases activation and improves systolic performance. Circulation 94:1475-82