The long-term objective is to evolve a new approach to acute myocardial infarction (AMI) to reduce substantially the disappointing 10-I5% CCU mortality resulting from current medical treatment. Hypothesis: The fate of ischemic myocardium is determined by the conditions under which blood supply is restored (reperfusion) rather than how quickly it is re-established. Methods: Using a dog model of acute coronary occlusion, the structural, functional, metabolic consequences of cardiac damage which can be avoided by controlling re-perfu-sate conditions (i.e., pressure, f)ow, LV venting) and composition (i.e., substrates, 02 radicals) will be characterized. These studies will: a. show all AMI patients can be helped by controlled reperfusion, even after time intervals thought previously to produce irreversible damage (> 6 hrs). b. demonstrate that controlled reperfusion (i.e., blood cardioplegia on total bypass) can be delivered in the cath lab or operating room and produce immediate recovery of contractility in jeopardized muscle. c. present a new method of instituting percutaneous total vented bypass and regional reperfusion without thoracotomy that is applicable in the catheterization lab. d. show that complications of AMI (i.e., intractable fibrillation, shock extension) are due to previously unrecognized problems in remote (non-ischemic) muscle that can be treated successfully by directing medical and surgical efforts towards remote rather than infarcting muscle. e. develop a new """"""""intravenous IV substrate infusion"""""""" to treat cariogenic shock and postoperative low output which corrects specific metabolic deficiencies that cause myocardial dysfunction, and limits inotropic drug requirements. f. apply reperfusion principles to allow: a) safe cardiac surgery in energy-depleted hearts (i.e., ischemia, hypoxia, hypertrophy) and b) storage for prolonged intervals (48-72 hours) and permit organ bank development for transplantation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL016292-17
Application #
3335162
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1979-01-01
Project End
1992-02-28
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
17
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Acar, C; Partington, M T; Buckberg, G D (1991) Studies of controlled reperfusion after ischemia. XIX. Reperfusate composition: benefits of blood cardioplegia over fluosol DA cardioplegia during regional reperfusion--importance of including blood components in the initial reperfusate. J Thorac Cardiovasc Surg 101:284-93
Julia, P L; Buckberg, G D; Acar, C et al. (1991) Studies of controlled reperfusion after ischemia. XXI. Reperfusate composition: superiority of blood cardioplegia over crystalloid cardioplegia in limiting reperfusion damage--importance of endogenous oxygen free radical scavengers in red blood cells. J Thorac Cardiovasc Surg 101:303-13
Kofsky, E R; Julia, P L; Buckberg, G D et al. (1991) Studies of controlled reperfusion after ischemia. XXII. Reperfusate composition: effects of leukocyte depletion of blood and blood cardioplegic reperfusates after acute coronary occlusion. J Thorac Cardiovasc Surg 101:350-9
Acar, C; Partington, M T; Buckberg, G D (1990) Studies of controlled reperfusion after ischemia. XVII. Reperfusion conditions: controlled reperfusion through an internal mammary artery graft--a new technique emphasizing fixed pressure versus fixed flow. J Thorac Cardiovasc Surg 100:724-36
Acar, C; Partington, M T; Buckberg, G D (1990) Studies of controlled reperfusion after ischemia. XVIII. Reperfusion conditions: attenuation of the regional ischemic effect by temporary total vented bypass before controlled reperfusion. J Thorac Cardiovasc Surg 100:737-44
Beyersdorf, F; Acar, C; Buckberg, G D et al. (1989) Studies on prolonged acute regional ischemia. III. Early natural history of simulated single and multivessel disease with emphasis on remote myocardium. J Thorac Cardiovasc Surg 98:368-80
Allen, B S; Rosenkranz, E; Buckberg, G D et al. (1989) Studies on prolonged acute regional ischemia. VI. Myocardial infarction with left ventricular power failure: a medical/surgical emergency requiring urgent revascularization with maximal protection of remote muscle. J Thorac Cardiovasc Surg 98:691-702;discussion 702-3
Beyersdorf, F; Acar, C; Buckberg, G D et al. (1989) Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure. J Thorac Cardiovasc Surg 98:567-79
Partington, M T; Acar, C; Buckberg, G D et al. (1989) Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries. J Thorac Cardiovasc Surg 97:605-12
Beyersdorf, F; Acar, C; Buckberg, G D et al. (1989) Studies on prolonged acute regional ischemia. IV. Aggressive surgical treatment for intractable ventricular fibrillation after acute myocardial infarction. J Thorac Cardiovasc Surg 98:557-66

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