Perfluorochemicals (PFC) have extensive clinical application because these compounds have shown to be effective in transporting oxygen and carbon dioxide. We will assess the effects of PFC therapy on myocardial infarction (MI), ventricular function and ventricular arrhythmias following temporary and permanent coronary artery occlusion at 1, 3 nd 7 days post MI. Dogs will undergo left anterior descending coronary artery occlusion and will be divided into 3 groups. Group I will receive Fluosol-DA (40 ml/Kg) while a similar volume of blood is withdrawn. Group II, sham dogs, will receive a similar volume of their own heparinized blood. Both these groups will be ventilated with 100% O2. Group III, control dogs, will undergo coronary occlusion but no infusion or withdrawal of blood. These dogs will be ventilated with room air. Dogs will be studied 24 hrs after myocardial infarction to determine and characterize the location of ventricular arrhythmias. Ventricular fibrillation threshold (VFT) will be determined and programmed electrical stimulation (PES) will be performed before and 3 and 7 days after infarction to determine what effects PFC may have on these indicies of ventricular vulnerability. Myocardial function will be evaluated by radionuclide ventriculography 1 day before and 1, 3 and 7 days after myocardial infarction. Dogs will be sacrificed at 1, 3 and 7 days and the vascular slices. The area of central necrosis and the border or marginal zones will be defined by light microscopy, mapped and measured. These areas will be compared in each of the groups and correlated with inducibility of ventricular arrhythmias. The mechanism of action of PFC's is not well understood and is probably multifunctional. To elucidate complement as a possible mechanism C1 C3, C4, C5 and CH50 will be measured before and 1,2,6 and 24 hours after myocardial infarction and will be correlated with the extent of inflammatory response seen in the area of infarction. It is postulated that if perfluorochemical, Fluosol-DA treatment, leads to uniform reduction in infarct size, then sustained ventricular tachycardia and/or ventricular fibrillation may be more difficult to induce. However, if perfluorochemical treatment promotes or enhances the marginal zone of infarction in an evolving myocardial infarct, then inducibility of sustained ventricular tachycardia may enhanced. It is anticipated that the results of this study will further our long-term goal to understand the complex relationships which exists between infarct size, infarct metamorphosis and susceptibility to life-threatening ventricular arrhythmias. Our data should provide important information needed for the rational use of perfluorochemical, Fluosol-DA, as clinical therapy in myocardial infarction.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034079-02
Application #
3346664
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1984-09-30
Project End
1987-09-29
Budget Start
1985-09-30
Budget End
1986-09-29
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
American Registry of Pathology, Inc.
Department
Type
DUNS #
114400633
City
Washington
State
DC
Country
United States
Zip Code
20306
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Forman, M B; Puett, D W; Wilson, B H et al. (1987) Beneficial long-term effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model. J Am Coll Cardiol 9:1082-90
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