This proposal will test the hypothesis that temporary extracorporeal circulatory assistance (TECA) can accelerate recovery of left ventricular function, reduce infarct size, and thereby improve survival by reducing circumferential and regional myocardial wall stresses after acute myocardial infarction (AMI) with or without reperfusion of the obstructed coronary artery. Centrifugal pump perfusion systems will be modified for use in AMI by developing techniques for peripheral, percutaneous cannulation, cannulation of the left atrium without thoracotomy, pulsatile perfusion, and perfusion with low dose or no heparin. Seven perfusion system combinations, suitable for use in AMI, will then be evaluated for their ability to reduce left ventricular wall stress in poorly contractile, pentobarbital-suppressed sheep hearts. Left atrial-to-femoral artery and veno-arterial bypass systems with both continuous and timed pulsatile flow with and without intra-aortic balloon counterpulsation will be studied. One system, which maximally reduces left ventricular wall stress and which is most practical for use in AMI, will be chosen for AMI studies. The ability of TECA to accelerate recovery of well-perfused, poorly contractile ventricular segments and to reduce infarct size will be evaluated in sheep with occlusion of the circumflex coronary artery. Myocardial regional wall shortening, wall thickness and short and long axis diameters will be measured by sonomicrometry in addition to aortic flow and cardiac chamber pressures. Awake sheep will be perfused for 96 hours using the chosen TECA system and compared to unperfused control animals. Calculated estimates of regional wall stresses will be made, and after euthanasia, size of the infarcted area will be determined. The effects of reperfusion of reversibly and irreversibly ischemic myocardium on regional wall motion, calculated estimates of regional wall stress, and overall ventricular function with and without TECA will be determined in the sheep model of circumflex coronary artery occlusion. The data obtained will define the role, if any, of TECA in AMI and will quantitate changes in regional wall motion, calculated estimates of regional wall stress, and overall ventricular performance after no, early, and late reperfusion of an obstructed coronary artery. This information may influence current management of patients with large acute myocardial infarctions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL036308-01
Application #
3351218
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1986-04-01
Project End
1990-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Gorman 3rd, Joseph H; Gorman, Robert C; Jackson, Benjamin M et al. (2003) Annuloplasty ring selection for chronic ischemic mitral regurgitation: lessons from the ovine model. Ann Thorac Surg 76:1556-63
Jackson, Benjamin M; Gorman 3rd, Joseph H; Salgo, Ivan S et al. (2003) Border zone geometry increases wall stress after myocardial infarction: contrast echocardiographic assessment. Am J Physiol Heart Circ Physiol 284:H475-9
Wilson, Eric M; Moainie, Sina L; Baskin, Julia M et al. (2003) Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling. Circulation 107:2857-63
Jackson, Benjamin M; Gorman, Joseph H; Moainie, Sina L et al. (2002) Extension of borderzone myocardium in postinfarction dilated cardiomyopathy. J Am Coll Cardiol 40:1160-7; discussion 1168-71
Salgo, Ivan S; Gorman 3rd, Joseph H; Gorman, Robert C et al. (2002) Effect of annular shape on leaflet curvature in reducing mitral leaflet stress. Circulation 106:711-7
Moainie, Sina L; Gorman 3rd, Joseph H; Guy, T Sloane et al. (2002) An ovine model of postinfarction dilated cardiomyopathy. Ann Thorac Surg 74:753-60
Moainie, Sina L; Guy, T Sloane; Gorman 3rd, Joseph H et al. (2002) Infarct restraint attenuates remodeling and reduces chronic ischemic mitral regurgitation after postero-lateral infarction. Ann Thorac Surg 74:444-9; discussion 449
Bowen, F W; Hattori, T; Narula, N et al. (2001) Reappearance of myocytes in ovine infarcts produced by six hours of complete ischemia followed by reperfusion. Ann Thorac Surg 71:1845-55
Bowen, F W; Jones, S C; Narula, N et al. (2001) Restraining acute infarct expansion decreases collagenase activity in borderzone myocardium. Ann Thorac Surg 72:1950-6
Kelley, S T; Malekan, R; Gorman 3rd, J H et al. (1999) Restraining infarct expansion preserves left ventricular geometry and function after acute anteroapical infarction. Circulation 99:135-42

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