Alterations of ventricular function following a myocardial infarction result from a complex interaction of changes in regional wall properties, global chamber geometry, and fiber architecture. Understanding of the contribution and interplay of these changes has been limited by the lack of load insensitive measures of global and regional function, and the frequent absence of regional shortening data encorporating a complete characterization of three dimensional strain. The purose of this proposal is to define the mechanisms by which alterations in regional wall strain following myocardial infarction are related to global ventricular pressure-volume behavior, and compensatory adjustments to ischemic injury. The study will combine the simultaneous measurement of in situ pressure-volume (P-V) relationships, using a conductance-volume catheter, and regional strain and pressure-strain relationships by tracking the motion of multiple implanted radiopaque markers. Dogs will be instrumented, and following control study of both the global P-V relationships and regional wall strain, will be subjected to a transmural myocardial infarction. Chronic study of the regional and global ventricular responses will be made. Tensor analysis of the strain data will define alterations in principal strain directions and amplitudes. Regional pressure-strain relationships will define changes in diastolic and systolic properties, while chamber P-V relationships will assess the net effects on global ventricular performance. Finally, examination of the chronically infarcted ventricle in an isolated supported heart preparation will help define changes in the mechanics and energetics of the remaining functional myocardium. Understanding the mechanisms of myocardial compensation after infarction has important implications to the clinical management of ischemic heart disease. A better appreciation of the nature and limitations of this compensation will provide insight into the pathophysiology and potential therapy of ischemic cardiomyopathy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (K11)
Project #
5K11HL001820-04
Application #
3087379
Study Section
(SRC)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
4
Fiscal Year
1989
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
Kass, D A; Wolff, M R; Ting, C T et al. (1993) Diastolic compliance of hypertrophied ventricle is not acutely altered by pharmacologic agents influencing active processes. Ann Intern Med 119:466-73
De Tombe, P P; Jones, S; Burkhoff, D et al. (1993) Ventricular stroke work and efficiency both remain nearly optimal despite altered vascular loading. Am J Physiol 264:H1817-24
Liu, C P; Ting, C T; Lawrence, W et al. (1993) Diminished contractile response to increased heart rate in intact human left ventricular hypertrophy. Systolic versus diastolic determinants. Circulation 88:1893-906
Wolff, M R; de Tombe, P P; Harasawa, Y et al. (1992) Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure. Circ Res 70:516-29
Kelly, R P; Ting, C T; Yang, T M et al. (1992) Effective arterial elastance as index of arterial vascular load in humans. Circulation 86:513-21
Kass, D A; Kelly, R P (1992) Ventriculo-arterial coupling: concepts, assumptions, and applications. Ann Biomed Eng 20:41-62
Kass, D A; Beyar, R (1991) Evaluation of contractile state by maximal ventricular power divided by the square of end-diastolic volume. Circulation 84:1698-708
Kass, D A; Midei, M; Brinker, J et al. (1990) Influence of coronary occlusion during PTCA on end-systolic and end-diastolic pressure-volume relations in humans. Circulation 81:447-60
Lankford, E B; Kass, D A; Maughan, W L et al. (1990) Does volume catheter parallel conductance vary during a cardiac cycle? Am J Physiol 258:H1933-42
Kass, D A; Grayson, R; Marino, P (1990) Pressure-volume analysis as a method for quantifying simultaneous drug (amrinone) effects on arterial load and contractile state in vivo. J Am Coll Cardiol 16:726-32

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