Abhijit Sinha Roy

Hemodynamic wall shear stress profiles influence the magnitude and pattern of stenosis in a pig AV fistula

Venous stenosis is a significant problem in arteriovenous fistulae, likely due to anatomical configuration and wall shear stress profiles. To identify linkages between wall shear stress and the magnitude and pattern of vascular stenosis, we produced curved and straight fistulae in a pig model. A complete wall stress profile was calculated for the curved configuration and correlated with luminal stenosis. Computer modeling techniques were then used to derive a wall shear stress profile for the straight arteriovenous fistula. Differences in the wall shear stress profile of the curved and straight fistula were then related to histological findings. There was a marked inverse correlation between the magnitude of wall shear stress within different regions of the curved arteriovenous fistula and luminal stenosis in these same regions. There were also significantly greater differences in wall shear stress between the outer and inner walls of the straight as compared to curved arteriovenous fistula, which translated into a more eccentric histological pattern of intima-media thickening. Our results suggest a clear linkage between anatomical configuration, wall shear stress profiles, and the pattern of luminal stenosis and intima-media thickening in a pig model of arteriovenous fistula stenosis. These results suggest that fistula failure could be reduced by using computer modeling prior to surgical placement to alter the anatomical and, consequently, the wall shear stress profiles in an arteriovenous fistula.

Functional and anatomical diagnosis of coronary artery stenoses.

BACKGROUND Functional/physiological evaluation of coronary artery stenoses may be more important than anatomical measurements of severity. Optimization of thresholds for stenosis intervention and treatment endpoints depend on coupling functional hemodynamic and anatomical data. We sought to develop a single prognostic parameter correlating stenosis-specific anatomy, pressure gradient, and velocities that could be measured during catheterization. MATERIALS AND METHODS In vivo Experiments were performed in six swine (41 +/- 3 kg). The lumen area of the left anterior descending coronary artery was measured with intravascular ultrasound. An angioplasty balloon was inflated to create the desired intraluminal area obstructions. Fractional flow reserve (FFR), coronary flow reserve (CFR), and hyperemic-stenosis-resistance index were measured distal to the balloon at peak hyperemia with 10 mg intracoronary papaverine. A functional index:pressure drop coefficient (CDP) and a combined functional and anatomical index:lesion flow coefficient (LFC) were calculated from measured hyperemic pressure gradient, velocity, and percentage area stenosis. P < 0.05 was considered statistically significant. RESULTS The CDP and LFC correlated linearly and significantly with FFR and CFR. The CDP (R(2) = 0.72, P < 0.0001) correlated better than LFC (R(2) = 0.19, P < 0.003) with hyperemic-stenosis-resistance index. When LFC was correlated simultaneously with FFR and CFR, R(2) improved to 0.82 (P < 0.0001). Inclusion of percentage area stenoses concurrently with FFR and CFR marginally improved the correlation with LFC. CONCLUSIONS A dimensionless parameter combining measured pressure gradient, velocity, and area reduction data can optimally define the severity of coronary stenoses based on our preliminary results and could prove useful clinically.

In Vitro Pressure Flow Relationship in Model of Significant Coronary Artery Stenosis

Simultaneous measurement of pressure and flow rate has been found to be helpful in evaluating the physiologic significance of obstructive coronary artery disease and in the diagnosis of microvascular disease. This experimental study seeks to find important pressure-flow relationship in an in-vitro model of significant coronary artery stenoses using a non-Newtonian liquid, similar to blood showing a shear thinning behavior, using significant stenotic in-vitro model (minimal area stenosis = 90%). The geometry for the stenotic model is based on data provided in an in vivo study by Wilson et al., (1988). For 90% area stenosis, the maximum recorded pressure drop for steady flow rate of 55, 79 and 89 are 14, ~24 and ~32 mmHg respectively. The maximum pressure drop at flow rate of 115 ml/min (the physiological limit) is 50.3 mmHg respectively. Using a power law curve fit, the maximum pressure drop (in mmHg) related with flow rate (in ml/min) provided a power law index of 1.72. Shorter distal length than required in the in-vitro model did not allow the recording of complete pressure recovery. This preliminary data provides reference values for further experimentation both in vitro with pulsatile flow as in physiological conditions, and in vivo.Copyright

Comparison of Convective Transport of Drug Between Intravitreal Injection and Controlled Release Implant

It is important to know the drug distribution following administration of drug in order to properly treat with adequate dosage and thus, avoid damage to tissues due to excessive high concentrations. A computer model was developed to determine drug distribution by convective-diffusive transport processes in a rabbit eye. When compared with pure diffusion within vitreous, the ratio of the amount of a model compound, fluorescein, reaching the retina to that cleared by aqueous outflow increased by 93% and 84% for intravitreal injection and implant, respectively, with maximum vitreous outflow (glaucomatous eye). The result shows that the combined “convective” effect due to the vitreous outflow and “wash out” effect by aqueous outflow has significant impact on drug distribution for both intravitreal injection and implant. These two effects should be considered in the design of drug delivery strategies.Copyright