The evaluation of left ventricular (LV) performance remains a difficult problem in clinical practice and physiologic investigation. Data from isolated canine hearts suggest that the LV behaves as an elastic structure that stiffens in a predictable manner during systole, thus, it can be described as a time-varying elastance. The goals of this project are to test the ability of this hypothesis to describe the relation between LV systolic pressure and volume in the in situ heart; and to investigate two new methods of evaluating LV performance that we have derived from the time varying elastance hypothesis. The first method involves the relation between the peak rate of LV pressure rise (dP/dt-max) and the LV end-diastolic volume. We will test the hypothesis, supported by our preliminary data, that this relation is linear, insensitive to alterations in loading conditions, and very sensitive to inotropic state. Secondly, we will evaluate a new method of calculating E-max, the slope of the LV end-systolic pressure-volume relation, using a relation derived from the time-varying elastance hypothesis and supported by preliminary date. This relation describes E-max as a function of dP/dt-max, the LV end-systolic and end-diastolic volumes, and the time to end-systole. Thus E-max can be determined from measurements under a single set of conditions, avoiding the need to alter loading conditions to produce a range of LV end-systolic pressure-volume points. These studies will be carried out in dogs chronically instrumented with a micromanometer to measure LV pressure, and 3 pairs of ultrasonic crystals to determine LV volume. Aortic flow will be measured with an electromagnetic flow probe. LV pressure and volume will be varied by caval occlusions. Inotropic state will be altered by dobutamine infusion, while loading conditions will be varied by infusion of methoxamine and dextran and by transient occlusions of the descending aorta. Isovolumic beats will be produced by transient complete occlusion of the ascending aorta. These studies will provide new information on the descriptors of LV systolic function in the in situ heart and two new methods of evaluating LV performance that may be independent of loading conditions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037324-02
Application #
3352885
Study Section
(SSS)
Project Start
1986-04-01
Project End
1990-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Little, W C; Cheng, C P (1994) Coupling of the left ventricular and arterial system. Med Biol Eng Comput 32:205-9
Cheng, C P; Noda, T; Nozawa, T et al. (1993) Effect of heart failure on the mechanism of exercise-induced augmentation of mitral valve flow. Circ Res 72:795-806
Cheng, C P; Igarashi, Y; Klopfenstein, H S et al. (1993) Effect of vasopressin on left ventricular performance. Am J Physiol 264:H53-60
Little, W C; Cheng, C P (1993) Effect of exercise on left ventricular-arterial coupling assessed in the pressure-volume plane. Am J Physiol 264:H1629-33
Cheng, C P; Igarashi, Y; Little, W C (1992) Mechanism of augmented rate of left ventricular filling during exercise. Circ Res 70:9-19
Cheng, C P; Igarashi, Y; Pettersson, K et al. (1991) Effect of felodipine on left ventricular performance in conscious dogs: assessment by left ventricular pressure-volume analysis. J Pharmacol Exp Ther 257:163-9
Little, W C; Cheng, C P (1991) Left ventricular-arterial coupling in conscious dogs. Am J Physiol 261:H70-6
Igarashi, Y; Cheng, C P; Little, W C (1991) Left ventricular ejection activation in the in situ heart. Am J Physiol 260:H1495-500
Little, W C; Downes, T R (1990) Clinical evaluation of left ventricular diastolic performance. Prog Cardiovasc Dis 32:273-90
Applegate, R J; Santamore, W P; Klopfenstein, H S et al. (1990) External pressure of undisturbed left ventricle. Am J Physiol 258:H1079-86

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