A MODEL OF CHRONIC ISCHEMIC HEART FAILURE

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The purpose of the proposed research is to investigate the role of discretionary, sequential electrothrombogenesis (ETG) in the creation of a practical model of chronic (3-month) ischemic left ventricular failure. Nearly all reported models either accomplish too little--the heart undergoes no lasting change--or too much--the animal dies. In the proposed technique 8 electrodes whose ends will be exteriorized will be implanted in the lumina of left coronary artery branches in each of 60 dogs. In 25 conscious dogs that have recovered from thoracotomy (Group A), anodal current will be applied to the LAD near its origin for 6 hours to induce a thrombus (i.e., electrothrombogenesis, or ETG). After the dog's recovery, branches of the circumflex (CX) will be obstructed by ETG one by one until the pulmonary capillary wedge pressure (PCWP) is greater than 15 mm Hg. The dog will then be kept in failure for 3 months, receiving medical treatment when the PCWP is greater than 20 mm Hg. Documentation of the dog's response to each ETG will include cardiac output and PCWP measurement during graded treadmill exercise, and standard clinical observations. Left coronary cineangiography will be performed after recovery from thoracotomy and just before sacrifice. Comparison of left ventricular function curves and evaluation of clinical data will define the most practical protocol. The same procedure will be followed in 25 Group B animals, except that the first ETG will be applied to the CX and succeeding ones to the branches of the LAD. Five Group C dogs will serve as controls. A simplified protocol will be developed on the basis of the Group A and B results and followed in 5 Group D dogs to confirm its practicality. Since the dog represents the most difficult case for establishment of a chronic failure model, the protocol, if successful, is expected to be readily transferred to larger species, such as those used in study of mechanical circulatory assist devices.