To date, the mechanism underlying ventricular suction is unknown, and its role in maintaining physiological diastolic function is unproven. Ventricular suction is thought to play an important role in the almost explosive character of the early, rapid filling phase of the cardiac cycle (when much of ventricular inflow occurs); to contribute greatly to the diastolic filling necessary for efficient operation of the heart at rapid heart rates and with exercise; and to increase the overall efficiency of the heart by applying part of the mechanical energy of systole to power diastole. A failure of ventricular suction has been implicated in the excessively high left atrial pressures in the failing heart. The long range goal of the work described in this application is to determine the mechanical and structural basis for ventricular suction and elucidate the importance of diastolic suction to left ventricular filling under both physiological and pathophysiological conditions. This goal is now attainable due to three recent advances in our laboratories: First, the ability to acquire, by automated computerized analysis of stereo videoradiograms of implanted radiopaque markers, hundreds of simultaneous three-dimensional strains throughout the entire left ventricular myocardium; Second, a new experimental technique for left atrial pressure clamping and left ventricular volume clamping (servo-controlled) which shows promise in preliminary tests of revealing, for the first time, the mechanical correlates of left ventricular suction; and Third, a new computer graphics approach to visualization of large numbers of simultaneous instantaneous regional strains and shears allowing recognition of patterns, both spatial and temporal, not otherwise recognizable in the myriad of data arising from studies such as these. The proposed studies address the following questions: (1) What is the range of suction pressures which can be developed in the presence of a normal mitral valvular apparatus? (2) What is the importance of the contribution of suction to left ventricular filling? (3) Is elastic energy stored in myocardial torsional deformation, transmural compression, in-plane strains, or combinations of these shears and strains? (4) What are the regional distributions of elastic recoil and the sequence of regional energy release during diastole and how do these influence gradients of pressure within the LV? (5) What fraction of total LV filling can be accounted for by the mitral valve engulfing blood as it recoils toward the left atrium? (6) What are the effects of the pathophysiological conditions accompanying (a) volume overload hypertrophy and (b) pressure overload hypertrophy on regional diastolic mechanics, the storage of elastic energy during systole and its release during diastole, and the capability of the LV to develop suction? and (7) In what sequence and what proportion is energy stored in and released from the connective tissue matrix and the myocytes to aid filling? The answers to these questions should provide important new information regarding these fundamental aspects of diastolic function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL048837-02
Application #
3368008
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1992-08-12
Project End
1997-06-30
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Palo Alto Medical Foundation Research Institute
Department
Type
DUNS #
622276137
City
Palo Alto
State
CA
Country
United States
Zip Code
94301
Timek, Tomasz A; Lai, David T; Bothe, Wolfgang et al. (2015) Geometric perturbations in multiheaded papillary tip positions associated with acute ovine ischemic mitral regurgitation. J Thorac Cardiovasc Surg 150:232-7
Rodriguez, Filiberto; Green, G Randall; Dagum, Paul et al. (2006) Left ventricular volume shifts and aortic root expansion during isovolumic contraction. J Heart Valve Dis 15:465-73
Timek, T A; Nielsen, S L; Green, G R et al. (2001) Influence of anterior mitral leaflet second-order chordae on leaflet dynamics and valve competence. Ann Thorac Surg 72:535-40; discussion 541
Dagum, P; Timek, T; Green, G R et al. (2001) Three-dimensional geometric comparison of partial and complete flexible mitral annuloplasty rings. J Thorac Cardiovasc Surg 122:665-73
Timek, T; Dagum, P; Lai, D T et al. (2001) The role of atrial contraction in mitral valve closure. J Heart Valve Dis 10:312-9
Timek, T; Glasson, J R; Dagum, P et al. (2000) Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia. J Thorac Cardiovasc Surg 119:774-83
Dagum, P; Timek, T A; Green, G R et al. (2000) Coordinate-free analysis of mitral valve dynamics in normal and ischemic hearts. Circulation 102:III62-9
Dagum, P; Green, G R; Glasson, J R et al. (1999) Potential mechanism of left ventricular outflow tract obstruction after mitral ring annuloplasty. J Thorac Cardiovasc Surg 117:472-80
Green, G R; Dagum, P; Glasson, J R et al. (1999) Restricted posterior leaflet motion after mitral ring annuloplasty. Ann Thorac Surg 68:2100-6
Dagum, P; Green, G R; Timek, T A et al. (1999) Functional evaluation of the medtronic stentless porcine xenograft mitral valve in sheep. Circulation 100:II70-7

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