This grant will test the hypothesis that resistance of the myocardial fiber to shortening-determines the energy cost of contraction. In post-ischemic myocardial dysfunction (stunning), we have observed that end-diastolic length and also the delay that occurs from the onset of local force-development to the beginning of segment shortening are markedly prolonged, and can be shortened by isoproterenol. Under various conditions, efficiency of myocardial contraction (regional segment work / regional myocardial oxygen consumption) varies over a range of at least 100-150%. It is proposed that the relative elastance of each myocardial segment largely controls local myocardial efficiency, and determines the extent of global energy loss. Experiments will be performed and a mathematical model will be constructed to test this hypothesis by producing local and global changes in elastance (passive and time- varying) and observing the effect on local and global myocardial efficiency. In open-chest anesthetized dogs, local segment length and developed force will be measured simultaneously in myocardium supplied by the left anterior descending and circumflex coronary arteries respectively. LV pressure and volume will also be measured. Regional and global LV work will be calculated on-line by integration of the length-force and volume-pressure loops during systole. Regional and total LV coronary blood flow will be measured with radioactive microspheres, and microspectrophotometric determination of regional O2 saturations as well as coronary sinus oximetry will be used to calculate regional and global MVO2 respectively. The effects of induced changes in end-diastolic volume, contractility, and heart rate during regional and global ischemia and reperfusion of varying durations on these parameters will be measured. A mathematical model of regionally impaired ventricular contraction will consist of normal and impaired regions. Each region will have a prescribed dynamic pressure- volume relationship and will be permitted to interact with each other, the arterial load, and a filling reservoir. The purpose of the model will be to help explain and suggest basic relationships for the observed data. Information obtained from this study will provide a quantitative understanding of factors controlling oxygen cost of local contraction, and may lead to management of coronary insufficiency by treatment aimed at increasing efficiency.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL049138-01A2
Application #
2225245
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1994-05-01
Project End
1997-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Physiology
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
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LaBruno, S; Naim, K L; Li, J K et al. (1998) Beta-adrenergic stimulation of reperfused myocardium after 2-hour ischemia. J Cardiovasc Pharmacol 32:535-42
Wang, J J; Drzewiecki, G; Li, J K et al. (1997) Novel design of a regional myocardial force transducer. Biomed Instrum Technol 31:155-63
Naim, K L; Weiss, H R; Guo, X et al. (1997) Local inotropic stimulation by methylene blue does not improve mechanical dysfunction due to myocardial stunning. Res Exp Med (Berl) 197:23-35
Scholz, P M; Kedem, J; Cheinberg, B V et al. (1996) The oxygen wasting effect of isoproterenol is altered by chemical denervation and cardiac hypertrophy. Basic Res Cardiol 91:308-18
Wang, J J; Li, J K; Drzewiecki, G (1996) Analysis of effect of two concurrent ischaemic zones on left ventricular function. Med Biol Eng Comput 34:477-80
Guo, X; Kedem, J; Weiss, H R et al. (1996) Effect of cyclic GMP reduction on regional myocardial mechanics and metabolism in experimental left ventricular hypertrophy. J Cardiovasc Pharmacol 27:392-400
Drzewiecki, G; Wang, J J; Li, J K et al. (1996) Modeling of mechanical dysfunction in regional stunned myocardium of the left ventricle. IEEE Trans Biomed Eng 43:1151-63
Guo, X; Kedem, J; Scholz, P M et al. (1996) Action of acetylcholine on regional myocardial work and metabolism in vivo: association with cyclic GMP. Can J Physiol Pharmacol 74:73-9

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