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The Impact of Blood Rheology on Drug Transport in Stented Arteries: Steady Simulations.

Vijayaratnam PR, O'Brien CC, Reizes JA, Barber TJ, Edelman ER - PLoS ONE (2015)

Bottom Line: Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model.Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection.The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology.

View Article: PubMed Central - PubMed

Affiliation: School of Mechanical and Manufacturing Engineering, the University of New South Wales, Sydney, New South Wales, Australia.

ABSTRACT

Background and methods: It is important to ensure that blood flow is modelled accurately in numerical studies of arteries featuring drug-eluting stents due to the significant proportion of drug transport from the stent into the arterial wall which is flow-mediated. Modelling blood is complicated, however, by variations in blood rheological behaviour between individuals, blood's complex near-wall behaviour, and the large number of rheological models which have been proposed. In this study, a series of steady-state computational fluid dynamics analyses were performed in which the traditional Newtonian model was compared against a range of non-Newtonian models. The impact of these rheological models was elucidated through comparisons of haemodynamic flow details and drug transport behaviour at various blood flow rates.

Results: Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model. Another model possessing the viscosity and density of blood plasma was also implemented to account for near-wall red blood cell losses and yielded recirculation length increases of up to 59%. However, the deviation from the average drug concentration in the tissue obtained with the Newtonian model was observed to be less than 5% in all cases except one. Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection.

Conclusions/significance: These results may be used to guide blood rheological model selection in future numerical studies. The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology. Furthermore, the finding that flow separation regions formed downstream of the stent struts diminish drug uptake may be of interest to device designers.

No MeSH data available.


Related in: MedlinePlus

Contour plots of the non-Newtonian drug concentration difference factor, ID.These contours display the degree to which a rheological model’s predicted drug concentration departs from that associated with the traditional Newtonian model. The regions highlighted in red (ID>0) depict where the non-Newtonian blood model predicts a greater drug concentration, whilst the blue regions (ID<0) show where the Newtonian model predicts a higher drug concentration. The plasma case (a) is different from the other cases examined in that its larger distal recirculation zone resulted in a less concentrated distal drug pool than that of the Newtonian model. This larger pool allowed a greater region of the lumen-tissue interface to be exposed to recirculating drug; however, no significant positive ID values were observed in the tissue. In contrast, the larger proximal drug pool of the Newtonian model did facilitate significant negative ID values in the proximal sections of the tissue. In contrast, cases b-h show that the smaller recirculation lengths of the non-Newtonian models enable the formation of higher concentration drug pools than the Newtonian model. Although significant negative ID values were again observed in the proximal aspects of the tissue, significant positive ID values were also observed in the distal tissue aspects in some models. The non-Newtonian blood rheological models therefore typically produced much higher tissue drug concentrations than the Newtonian model in the distal regions and significantly lower concentrations in the proximal regions.
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pone.0128178.g008: Contour plots of the non-Newtonian drug concentration difference factor, ID.These contours display the degree to which a rheological model’s predicted drug concentration departs from that associated with the traditional Newtonian model. The regions highlighted in red (ID>0) depict where the non-Newtonian blood model predicts a greater drug concentration, whilst the blue regions (ID<0) show where the Newtonian model predicts a higher drug concentration. The plasma case (a) is different from the other cases examined in that its larger distal recirculation zone resulted in a less concentrated distal drug pool than that of the Newtonian model. This larger pool allowed a greater region of the lumen-tissue interface to be exposed to recirculating drug; however, no significant positive ID values were observed in the tissue. In contrast, the larger proximal drug pool of the Newtonian model did facilitate significant negative ID values in the proximal sections of the tissue. In contrast, cases b-h show that the smaller recirculation lengths of the non-Newtonian models enable the formation of higher concentration drug pools than the Newtonian model. Although significant negative ID values were again observed in the proximal aspects of the tissue, significant positive ID values were also observed in the distal tissue aspects in some models. The non-Newtonian blood rheological models therefore typically produced much higher tissue drug concentrations than the Newtonian model in the distal regions and significantly lower concentrations in the proximal regions.

Mentions: The effect of blood rheology on the distribution of drug in the artery wall was ascertained by a comparison of the ID plots at the three flow rates investigated. The results of this study are shown in Fig 8. Once again, only the results corresponding with a flow rate of are displayed, as this is where non-Newtonian effects were generally most pronounced. The regions highlighted in red (ID>0) depict where the non-Newtonian blood model predicts a greater drug concentration, whilst the blue regions (ID<0) show where the Newtonian model predicts a higher drug concentration. Regions in which /ID/ >0.06 were deemed to correlate with regions in which the non-Newtonian model’s spatial distribution of drug matter departed significantly from that of the Newtonian model.


The Impact of Blood Rheology on Drug Transport in Stented Arteries: Steady Simulations.

Vijayaratnam PR, O'Brien CC, Reizes JA, Barber TJ, Edelman ER - PLoS ONE (2015)

Contour plots of the non-Newtonian drug concentration difference factor, ID.These contours display the degree to which a rheological model’s predicted drug concentration departs from that associated with the traditional Newtonian model. The regions highlighted in red (ID>0) depict where the non-Newtonian blood model predicts a greater drug concentration, whilst the blue regions (ID<0) show where the Newtonian model predicts a higher drug concentration. The plasma case (a) is different from the other cases examined in that its larger distal recirculation zone resulted in a less concentrated distal drug pool than that of the Newtonian model. This larger pool allowed a greater region of the lumen-tissue interface to be exposed to recirculating drug; however, no significant positive ID values were observed in the tissue. In contrast, the larger proximal drug pool of the Newtonian model did facilitate significant negative ID values in the proximal sections of the tissue. In contrast, cases b-h show that the smaller recirculation lengths of the non-Newtonian models enable the formation of higher concentration drug pools than the Newtonian model. Although significant negative ID values were again observed in the proximal aspects of the tissue, significant positive ID values were also observed in the distal tissue aspects in some models. The non-Newtonian blood rheological models therefore typically produced much higher tissue drug concentrations than the Newtonian model in the distal regions and significantly lower concentrations in the proximal regions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466567&req=5

pone.0128178.g008: Contour plots of the non-Newtonian drug concentration difference factor, ID.These contours display the degree to which a rheological model’s predicted drug concentration departs from that associated with the traditional Newtonian model. The regions highlighted in red (ID>0) depict where the non-Newtonian blood model predicts a greater drug concentration, whilst the blue regions (ID<0) show where the Newtonian model predicts a higher drug concentration. The plasma case (a) is different from the other cases examined in that its larger distal recirculation zone resulted in a less concentrated distal drug pool than that of the Newtonian model. This larger pool allowed a greater region of the lumen-tissue interface to be exposed to recirculating drug; however, no significant positive ID values were observed in the tissue. In contrast, the larger proximal drug pool of the Newtonian model did facilitate significant negative ID values in the proximal sections of the tissue. In contrast, cases b-h show that the smaller recirculation lengths of the non-Newtonian models enable the formation of higher concentration drug pools than the Newtonian model. Although significant negative ID values were again observed in the proximal aspects of the tissue, significant positive ID values were also observed in the distal tissue aspects in some models. The non-Newtonian blood rheological models therefore typically produced much higher tissue drug concentrations than the Newtonian model in the distal regions and significantly lower concentrations in the proximal regions.
Mentions: The effect of blood rheology on the distribution of drug in the artery wall was ascertained by a comparison of the ID plots at the three flow rates investigated. The results of this study are shown in Fig 8. Once again, only the results corresponding with a flow rate of are displayed, as this is where non-Newtonian effects were generally most pronounced. The regions highlighted in red (ID>0) depict where the non-Newtonian blood model predicts a greater drug concentration, whilst the blue regions (ID<0) show where the Newtonian model predicts a higher drug concentration. Regions in which /ID/ >0.06 were deemed to correlate with regions in which the non-Newtonian model’s spatial distribution of drug matter departed significantly from that of the Newtonian model.

Bottom Line: Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model.Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection.The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology.

View Article: PubMed Central - PubMed

Affiliation: School of Mechanical and Manufacturing Engineering, the University of New South Wales, Sydney, New South Wales, Australia.

ABSTRACT

Background and methods: It is important to ensure that blood flow is modelled accurately in numerical studies of arteries featuring drug-eluting stents due to the significant proportion of drug transport from the stent into the arterial wall which is flow-mediated. Modelling blood is complicated, however, by variations in blood rheological behaviour between individuals, blood's complex near-wall behaviour, and the large number of rheological models which have been proposed. In this study, a series of steady-state computational fluid dynamics analyses were performed in which the traditional Newtonian model was compared against a range of non-Newtonian models. The impact of these rheological models was elucidated through comparisons of haemodynamic flow details and drug transport behaviour at various blood flow rates.

Results: Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model. Another model possessing the viscosity and density of blood plasma was also implemented to account for near-wall red blood cell losses and yielded recirculation length increases of up to 59%. However, the deviation from the average drug concentration in the tissue obtained with the Newtonian model was observed to be less than 5% in all cases except one. Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection.

Conclusions/significance: These results may be used to guide blood rheological model selection in future numerical studies. The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology. Furthermore, the finding that flow separation regions formed downstream of the stent struts diminish drug uptake may be of interest to device designers.

No MeSH data available.


Related in: MedlinePlus