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Location-dependent coronary artery diffusive and convective mass transport properties of a lipophilic drug surrogate measured using nonlinear microscopy

机译:使用非线性显微镜测量的亲脂性药物替代物的位置依赖性冠状动脉扩散和对流传质

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Purpose: Arterial wall mass transport properties dictate local distribution of biomolecules or locally delivered dugs. Knowing how these properties vary between coronary artery locations could provide insight into how therapy efficacy is altered between arterial locations. Methods: We introduced an indocarbocyanine drug surrogate to the lumens of left anterior descending and right coronary (LADC; RC) arteries from pigs with or without a pressure gradient. Interstitial fluorescent intensity was measured on live samples with multiphoton microscopy. We also measured binding to porcine coronary SMCs in monoculture. Results: Diffusive transport constants peaked in the middle sections of the LADC and RC arteries by 2.09 and 2.04 times, respectively, compared to the proximal and distal segments. There was no statistical difference between the average diffusivity value between LADC and RC arteries. The convection coefficients had an upward trend down each artery, with the RC being higher than the LADC by 3.89 times. Conclusions: This study demonstrates that the convective and diffusive transport of lipophilic molecules changes between the LADC and the RC arteries as well as along their length. These results may have important implications in optimizing drug delivery for the treatment of coronary artery disease.
机译:目的:动脉壁的传质特性决定了生物分子的局部分布或局部输送的挖掘物。了解这些特性在冠状动脉位置之间如何变化可以洞悉治疗效果如何在动脉位置之间改变。方法:我们将吲哚并花菁药物替代物引入到有或没有压力梯度的猪的左前降支和右冠状动脉(LADC; RC)管腔。用多光子显微镜在活样品上测量间质荧光强度。我们还测量了在单一培养物中与猪冠状动脉SMC的结合。结果:与近端和远端段相比,LADC和RC动脉中段的扩散转运常数分别达到2.09和2.04倍的峰值。 LADC和RC动脉之间的平均扩散率值之间无统计学差异。对流系数沿每条动脉向下呈上升趋势,RC比LADC高3.89倍。结论:这项研究表明,亲脂性分子的对流和扩散运输在LADC和RC动脉之间以及沿其长度变化。这些结果可能对优化治疗冠状动脉疾病的药物输送具有重要意义。

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