Potential preservation of """"""""border zone"""""""" myocardium at the lateral margins of the ischemic area has received considerable attention, but recent studies have demonstrated that the lateral borders of an infarcted area are well demarcated (in terms of myocardial blood flow distribution, NADH fluorscence, biochemistry or histology), and unlikely to be substantially altered with different interventions. Several lines of evidence, however, suggest that damaged myocardium is surrounded by a zone of normally perfused but functionally impaired myocardium. This type of border zone may begin and the relatively abrupt ischemic perfusion boundary and extend laterally into (apparently) nonischemic myocardium. The size and determinants of this area, termed the """"""""functional border zone"""""""", are yet to be established. Therefore, the objective of the proposal is characterization of the functional border zone using the microsphere technique to precisely delineate the ischemic-nonischemic perfusion boundary and sonomicrometers to provide high resolution measurement of regional myocardial performance at and around the perfusion boundary. Experiments are proposed to: 1.) Determine the size of the functional """"""""border zone"""""""". 2.) Establish whether its dimensions may vary depending on the extent, severity, and transmural distribution of acute ischemia or infarction. 3.) Examine if function in this area is modified by altering hemodynamic conditions. 4.) Determine the changes that occur with time after myocardial infarction. The existence of a functional border zone, its dimensions, and the potential for altering it acutely or chronically, are important issues for the correct interpretation of most methods used clinically and experimentally to measure regional myocardial function. For example, abnormal wall motion has proven to be a valuable diagnostic indicator of the presence and severity of coronary artery disease, but echocardiographic studies suggest this modality consistently overestimates the size of an acutely ischemic or infarcted area. Detailed study of the hypofunctional, but potentially nonischemic areas of myocardium will enable realistic assessment of such clinically relevant issues by addressing the fundamental question of how adjacent regions of ischemic and nonischemic myocardium affect each other in terms of contractile function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL001420-04
Application #
3073768
Study Section
Cardiovascular Study Section (CVA)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Schott, R J; Nao, B S; McClanahan, T B et al. (1989) F(ab')2 fragments of anti-Mo1 (904) monoclonal antibodies do not prevent myocardial stunning. Circ Res 65:1112-24
Simpson, P J; Mickelson, J; Fantone, J C et al. (1988) Reduction of experimental canine myocardial infarct size with prostaglandin E1: inhibition of neutrophil migration and activation. J Pharmacol Exp Ther 244:619-24