The heart pumps blood by cyclically filling and emptying. While this statement is simple, questions of how much and how fast the heart's chambers fill and empty are not. I will combine theoretical and experimental techniques to develop a better quantitative understanding of how the different chambers of the heart mechanically interact with each other, the pericardium and the lungs. I have developed a new description of the three-dimensional size and shape change the LV undergoes as it contracts and fills that avoids the assumptions about cavity size and shape necessary for other approaches. I will study hearts as they respond to chronic volume or pressure overload as well as during acute ischemia to assess how the contraction pattern changes as it adapts to changing conditions. My description of global contraction grew out of mathematical descriptions of regional contraction. Understanding the link between regional and global function is crucial to understanding the link between the heart's muscle (regional) and pump (global) function. I will develop this link and use it to understand the consequences of abnormal regional wall motion. In addition, this work will provide the theoretical base for an objective evaluation of the many competiting clinical techniques that have been proposed to quantify regional wall motion in patients suspected of having heart disease. The quantitative determinants of LV filling pressure and volume, including viscoelasticity of the heart muscle, slowed or incomplete relaxation from the previous beat, and negative intraventricular pressure due to systolic shortening to below the ventricle's rest volume, remains undefined. I will assess the relative importance of these factors, as well as the effects of the other cardiac chambers (so-called ventricular interaction), the pericardium, and the lungs on both diastolic and systolic function of the heart. Experiments will be conducted on dogs using two preparations: (1) Intact animals with radiopaque markers implanted in the heart muscle via a catheter introduced through an artery or vein, and (2) Open chest dogs with surgically implanted instruments to measure cardiac size, pressures, and flows. The first preparation has the advantage of being more physiologic but has the disadvantage of difficult data acquisition and reduction; the second preparation has the opposite advantages and drawbacks. The results of this project will help define how the heart functions in health and disease and help explain how some treatments work.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Mamudu, H M; Glantz, S A (2009) Civil society and the negotiation of the Framework Convention on Tobacco Control. Glob Public Health 4:150-68
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Solomon, S B; Barbier, P; Glantz, S A (1999) Changes in porcine transmitral flow velocity pattern and its diastolic determinants during partial coronary occlusion. J Am Coll Cardiol 33:854-66
Solomon, S B; Glantz, S A (1999) Regional ischemia increases sensitivity of left ventricular relaxation to volume in pigs. Am J Physiol 276:H1994-2005
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Tayama, M; Solomon, S B; Glantz, S A (1998) Effect of lidocaine on left ventricular pressure-volume curves during demand ischemia in pigs. Am J Physiol 274:H2100-9
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Takano, H; Glantz, S A (1995) Gadolinium attenuates the upward shift of the left ventricular diastolic pressure-volume relation during pacing-induced ischemia in dogs. Circulation 91:1575-87
Shintani, H; Glantz, S A (1994) Influence of filling on left ventricular diastolic pressure-volume curve during pacing ischemia in dogs. Am J Physiol 266:H1373-85
Nguyen, T N; Chagas, A C; Glantz, S A (1993) Left ventricular adaptation to gradual renovascular hypertension in dogs. Am J Physiol 265:H22-38

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