Caride V J, Twickler J, Zaret B L
J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):996-1005.
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.
为研究脂质体在实验性心肌梗死区域沉积的机制和动力学，测定了阳性和阴性脂质体在心肌中的分布情况，作为局部心肌血流和给药后时间的函数。该研究在实验性心肌梗死后1小时和24小时的犬类中进行。冠状动脉闭塞24小时后，阳性和阴性脂质体的初始心肌分布（2分钟）与局部心肌血流成正比。随着时间的推移，所有心肌区域中与阴性脂质体相关的放射性示踪剂均减少（p<0.01）。相反，在血流中度和重度减少的区域，包封或掺入阳性脂质体中的示踪剂逐渐积累。这种增加在120分钟时变得显著（p<0.005）。在冠状动脉闭塞1小时后进行的研究中也观察到了类似的结果。使用双标记脂质体[（3H]胆固醇和[99mTc]二亚乙基三胺五乙酸）研究正常和缺血心肌中脂质体的完整性。冠状动脉闭塞1小时后，观察到阳性脂质体的水相和脂质标记物有明显解离。在24小时心肌梗死模型中，也观察到缺血心肌中水相和脂质标记物的解离。这种现象在阳性脂质体中比在阴性脂质体中更明显（p<0.02）。示踪剂从脂质体中的泄漏可能是由于磷脂酶、分解代谢产物的作用以及局部环境变化导致缺血心肌中脂质体的不稳定或破坏。这种作用对阴性脂质体不太明显。脂质体的使用改善了示踪剂在梗死组织中的区域分布。然而，输送到心肌的示踪剂绝对量低于游离形式所达到的量。
