Liposome kinetics in infarcted canine myocardium.
To study the mechanisms and kinetics of liposome deposition in the region of the experimental myocardial infarction, the myocardial distribution of positive and negative liposomes was determined as a function of regional myocardial blood flow and time after administration. The study was performed in dogs at 1 and 24 h following experimental myocardial infarction. Twenty-four hours after coronary artery occlusion, the initial myocardial distribution of positive and negative liposomes (2 min) is directly proportional to regional myocardial blood flow. With time, there is reduction of the radiotracer associated with negative liposomes from all myocardial regions (p less than 0.01). In contrast, in areas of moderate and severe blood flow reduction, there is progressive accumulation of tracers entrapped or incorporated in positive liposomes. This increment becomes significant in 120 min (p less than 0.005). Similar findings are observed in studies performed 1 h after coronary artery occlusion. Dual-label liposomes [( 3H]cholesterol and [99mTc]diethylenetriamine pentaacetic acid) were used to study the integrity of liposomes in normal and ischemic myocardium. Significant dissociation of the aqueous and lipid labels of positive liposomes is observed 1 h following coronary artery occlusion. In the 24-h myocardial infarction model, dissociation of the aqueous and lipid labels in ischemic myocardium is also observed. This phenomenon is more pronounced with positive than with negative liposomes (p less than 0.02). The leakage of tracers from liposomes may result from destabilization or destruction of liposomes in the ischemic myocardium by the action of phospholipases, catabolites, and local environmental changes. This effect is less marked for negative liposomes. The use of liposomes improved the regional distribution of the tracer in infarcted tissue. However, the absolute amount of tracer delivered to the myocardium is less than that achieved with the free form.
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003326:Coronary Circulation; D004285:Dogs; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism*; D008863:Microspheres; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D004369:Pentetic Acid; D013667:Technetium; D016284:Technetium Tc 99m Pentetate
D008081:Liposomes; D013667:Technetium; D004369:Pentetic Acid; D002784:Cholesterol; D016284:Technetium Tc 99m Pentetate