Drug Distribution After Intravitreal Injection: A Mathematical Model.

Purpose: Intravitreal injection of drugs is commonly used for treatment of chorioretinal ocular pathologies, such as age-related macular degeneration. Injection causes a transient increase in the intraocular volume and, consequently, of the intraocular pressure (IOP). The aim of this work is to investigate how intravitreal flow patterns generated during the post-injection eye deflation influence the transport and distribution of the injected drug. Methods: We present mathematical and computational models of fluid motion and mass transport in the vitreous chamber during the transient phase after injection, including the previously unexplored effects of globe deflation as ocular volume decreases. Results: During eye globe deflation, significant fluid velocities are generated within the vitreous chamber, which can possibly contribute to drug transport. Pressure variations within the eye globe are small compared to IOP. Conclusions: Even if significant fluid velocities are generated in the vitreous chamber after drug injection, these are found to have negligible overall effect on drug distribution.

A mechanical model of ocular bulb vibrations and implications for acoustic tonometry.

In this study, we propose a comprehensive mechanical model of ocular bulb vibrations and discuss its implications for acoustic tonometry. The model describes the eye wall as a spherical, pre-stressed elastic shell containing a viscoelastic material and accounts for the interaction between the elastic corneoscleral shell and the viscoelastic vitreous humor. We investigate the natural frequencies of the system and the corresponding vibration modes, expanding the solution in terms of scalar and vector spherical harmonics. From a quantitative point of view, our findings reveal that the eyebulb vibration frequencies significantly depend on IOP. This dependency has two origins: "geometric" stiffening, due to an increase of the pre-stress, and "material" stiffening, due to the nonlinearity of the stress-strain curve of the sclera. The model shows that the second effect is by far dominant. We also find that the oscillation frequencies depend on ocular rigidity, but this dependency is important only at relatively large values of IOP. Thus close to physiological conditions, IOP is the main determinant of ocular vibration frequencies. The vitreous rheological properties are found to mostly influence vibration damping. This study contributes to the understanding of the mechanical behavior of the eye under dynamic conditions and thus has implications for non-contact intraocular pressure measurement techniques, such as acoustic tonometry. The model can also be relevant for other ocular pathological conditions, such as traumatic retinal detachment, which are believed to be influenced by the dynamic behavior of the eye.

Myopic macular schisis: Insights into distinct morphological subtypes and novel biomechanical hypothesis.

PURPOSE: To analyze the features of myopic macular schisis (MMS) in different retinal layers and to explore the role of Müller cells in the pathophysiology of such condition. METHODS: Spectral-domain optical coherence tomography (SD-OCT) images of myopic eyes with staphyloma and macular schisis were reviewed. The morphological features of MMS were analyzed and correlated with their geographical location in the parafoveal and perifoveal region. A biomechanical model was adopted to explain MMS morphological differences. The effect of the different schisis subtypes with best corrected visual acuity (BCVA) was also explored. RESULTS: A total of 36 eyes from 26 patients were included in this study. MMS was classified into inner, middle and outer retinal subtypes. The prevalence of middle retinal schisis was significantly lower in the parafovea, within a central 3 mm-diameter circle (p < 0.001) centered at the fovea . The prevalence of inner retinal schisis was significantly higher outside the central 3-mm diameter circle, in the perifoveal region (p < 0.001). No significant differences were noted in the prevalence of outer retinal schisis for these two locations (p = 0.475). The presence of middle retinal schisis within the central 3-mm diameter circle showed a weak association with lower BCVA (p = 0.058). The presence of outer retinal schisis within the central 3-mm diameter circle was significantly related with lower BCVA (p = 0.024). CONCLUSION: Three major forms of MMS are distinguished: inner, middle and outer retinal schisis. This classification may have clinical importance as only the outer grade of schisis was associated with vision loss.

A Mathematical Model of Aqueous Humor Production and Composition.

Purpose: We develop a mathematical model that predicts aqueous humor (AH) production rate by the ciliary processes and aqueous composition in the posterior chamber (PC), with the aim of estimating how the aqueous production rate depends on the controlling parameters and how it can be manipulated. Methods: We propose a compartmental mathematical model that considers the stromal region, ciliary epithelium, and PC. All domains contain an aqueous solution with different chemical species. We impose the concentration of all species on the stromal side and exploit the various ion channels present on the cell membrane to compute the water flux produced by osmosis, the solute concentrations in the AH and the transepithelial potential difference. Results: With a feasible set of parameters, the model predictions of water flux from the stroma to the PC and of the solute concentrations in the AH are in good agreement with measurements. Key parameters which impact the aqueous production rate are identified. A relevant role is predicted to be played by cell membrane permeability to \(\text{K}^+\) and \(\text{Cl}^-\), by the level of transport due to the Na+-H+ exchanger and to the co-transporter of Na+/K+/2Cl-; and by carbonic anhydrase. Conclusions: The mathematical model predicts the formation and composition of AH, based on the structure of the ciliary epithelium. The model provides insight into the physical processes underlying the functioning of drugs that are adopted to regulate the aqueous production. It also suggests ion channels and cell membrane properties that may be targeted to manipulate the aqueous production rate.

Dynamic Pressure Measurements During Vitrectomy in a Model of the Eye.

Purpose: To accurately evaluate pressure changes during vitrectomy in a rigid model of the vitreous chamber and to test the efficiency of the EVA phacovitrectomy system (Dutch Ophthalmic Research Center) in terms of compensation of intraocular pressure variations. Methods: We tested 23-, 25-, and 27-gauge double-blade vitreous cutters in both vented global pressure control and automatic infusion compensation (AIC) modes in a vitreous chamber model, mimicking the real surgical procedure. Balanced salt solution and artificial vitreous, similar to the real vitreous body, were used. We tested both standard-flow (SF) and high-flow (HF) infusion systems, varying the infusion pressure between 20 and 40 mm Hg. In each experiment, flow rate was also measured. Results: Pressure drop was rapidly and efficiently compensated when 23- and 25-gauge cutters were used in AIC mode, with infusion pressures ranging between 30 and 55 mm Hg. The 27-gauge cutter was less efficient in compensating pressure variations. Pressure fluctuations related to the high-frequency motion of the cutter blade were small compared to the overall pressure variations. The use of the HF infusion system resulted in larger flow rates and lower pressure changes compared to the SF infusion system. Conclusions: Despite the rigid material of the model, the present pressure measurements are in line with previous studies performed on porcine eye. The use of AIC mode compensates intraoperative pressure drops efficiently, with both 23- and 25-gauge cutters. The HF infusion system is more efficient than the SF infusion system. Translational Relevance: The AIC infusion mode efficiently compensates intraoperative pressure drops, in both 23- and 25-gauge experimental vitrectomy. The HF infusion system resulted in larger flow rate and lower pressure changes.

Biocompatibility of intraocular liquid tamponade agents: an update.

Intraocular liquids tamponade agents, such as perfluorocarbon liquids (PFCLs), semifluorinated alkanes (SFAs), silicone oils (SOs) and heavy silicone oils (HSOs), are a crucial intraoperative and/or postoperative tool in vitreoretinal surgery, in particular for the management of complex vitreoretinal diseases. However, their use is not without complications, which are potentially severe. Consequently, a growing interest has been devoted to the biocompatibility of these compounds and the adequacy of current regulations that should guarantee their safety. Obviously, an updated knowledge on research findings and potential risks associated to the use of intraocular liquid compounds is essential, not only for vitreoretinal surgeons, but also for any ophthalmologist involved in the management of patients receiving intraocular liquid tamponades. In light of this, the review provides a comprehensive characterisation of intraocular liquid tamponades, in terms of physical and chemical properties, current clinical use and possible complications. Moreover, this review focuses on the safety profile of these compounds, summarising the existing regulation and the available evidence on their biocompatibility.

TWENTY-THREE-GAUGE HYPERSONIC VITRECTOMY: Real-World Surgical Evidence.

PURPOSE: To evaluate the safety, effectiveness, and the best parameters setup of hypersonic vitrectomy. METHODS: A prospective, multicentric, interventional study on 50 eyes that had undergone hypersonic vitrectomy because of various vitreoretinal diseases. We primarily assessed the effectiveness of vitreous removal, intraoperative complications, and surgical setup. Secondarily, we evaluated single-surgery anatomical success and postoperative best-corrected visual acuity. RESULTS: Intraoperative complications occurred in 5 eyes (10%), whereas technical problems were detected in 23 eyes (46%), resulting in conversion to guillotine vitrectomy in 15 cases. The most common finding related to the technical problems was an inadequate vitreous liquefaction with the formation of vitreous strands and consequent inadequate vitreous outflow, sometimes complicated by vitreous incarceration in the vitrectomy probe. The best settings were considered a stroke of 60 µm and vacuum of 40 mmHg for both core and peripheral vitrectomy. At 3-month follow-up, primary anatomical success was achieved in 49 eyes (98%) and the mean best-corrected visual acuity overall improved. CONCLUSION: The availability of hypersonic vitrectomy in the current surgical practice opens a new era in vitreoretinal surgery. Despite the potential advantages in fluidics, the performance of hypersonic vitrectomy system needs to be further optimized, mainly for the occurrence of inadequate vitreous liquefaction and vitreous strands formation.

Experimental assessment of the performance of vitreous cutters with fluids with different rheological properties.

PURPOSE: To assess the influence of rheological properties of an artificial vitreous (AV) on the performance of double-blade (DB) and single-blade (SB) guillotine vitreous cutters, with 23-, 25-, and 27-gauge (G) probes. METHODS: We evaluate the aspiration flow rate, using an optical method, based on image processing. Experiments are conducted using ten viscoelastic vitreous phantoms, with different properties that are measured with rheological tests. RESULTS: Aspiration rate strongly varies with fluid properties. Regardless of cutter geometry and operational conditions, the flow rate significantly decreases as vitreous viscosity and elasticity increase. CONCLUSIONS: All tested vitreous probes are very sensitive to changes in fluid rheology. SB cutters produce smaller flow rates compared with DB ones of the same caliber; however, they are less sensitive to fluid properties at low aspiration pressures. The use of vitreous substitutes for test performance guarantees comparability between flow rate results achieved with different vitrectomy systems operating in different media. This outcome is further confirmed by the low values of estimated flow rate relative errors.

The Role of Endogenous Proteins on the Emulsification of Silicone Oils Used in Vitreoretinal Surgery.

The present work is aimed at investigating the chemicophysical properties of the interface between silicone oils (SOs) used in vitreoretinal surgery and aqueous solutions, in the presence of surfactant biomolecules. Such molecules are thought to play an important role in the formation of SO emulsions in vitrectomised eyes, in which the natural vitreous body has been replaced with a SO. In particular, we have measured the interfacial tension (IT) and the interfacial dilational viscoelasticity (DV) of the interface between SO (Siluron 1000) and serum proteins (albumin and γ-globulins) at various concentrations in a Dulbecco alkaline buffer. The equilibrium IT value is relevant for the onset of emulsification, and the DV influences the stability of an emulsion, once formed. The study is complemented by preliminary emulsification tests. The experimental results show that, when proteins are dissolved in the aqueous solution, the rheological properties of the interface change. The IT decreases significantly for physiological protein concentrations, and the DV modulus achieves high values, even for small protein concentrations. The emulsification tests confirm that, in the presence of proteins, emulsions are stable on the time scale of months. We conclude that the measured values of IT in the presence of serum proteins are compatible with the promotion of droplet formation, which, in addition, are expected to be stable against coalescence. Adsorption of biomolecules at the interface with the SO is, therefore, likely to play an important role in the generation of an emulsion in eyes subjected to vitrectomy. These findings are relevant to identify strategies to avoid or control the formation of emulsions in eyes.

Fluid Dynamic Assessment of Hypersonic and Guillotine Vitrectomy Probes in Viscoelastic Vitreous Substitutes.

Purpose: To assess the fluidics of 23-gauge (G) large-port (L) and tear drop-port (TD) hypersonic vitrectomy probes (HVPs) compared with guillotine vitrectomy probes (GVPs) of various calibers (23G, 25G, and 27G) and geometries (single and double blades). Also, to identify the working parameters that provide the best balance between acceleration and flow rate, and, for HVPs, to measure temperature variations in the fluid. Methods: We used particle image velocimetry to measure flow fields in balanced salt solution and viscoelastic artificial vitreous. We analyzed acceleration, kinetic energy, and volumetric flux. The parameters considered were vacuum pressure, ultrasound stroke, and cut rate. Temperature measurements were taken using an infrared thermal camera. Results: The flow rate was significantly higher for HVPs than GVPs. With both probes, flow rate and acceleration increased with vacuum pressure. Flow rate depended weakly on the ultrasound stroke or cut rate. In HVPs, the acceleration peaked at a stroke of 30 µm, whereas in GVPs it peaked at a cutting rate of 4000 to 5000 cuts per minute (cpm). The HPV/TD combination generated higher flow rates and lower accelerations than did HPV/L. The increase in temperature was small. Conclusions: Under the present experimental setup and medium, HVPs offered better fluidics compared with GVPs in terms of flow and acceleration; however, the flow structure for HVPs is more complicated and unsteady. The HPV/TD combination produced larger flows than did the HPV/L combination and slightly smaller accelerations. HPVs generated a small temperature increase. Translational Relevance: In the tested artificial vitreous, HVPs were found to be more efficient in terms of generating lower acceleration for a given flow rate. The slight increase in temperature observed with HVPs is unlikely to be clinically significant.

A mechanical model of posterior vitreous detachment and generation of vitreoretinal tractions.

We propose a mechanical model of generation of vitreoretinal tractions in the presence of posterior vitreous detachment (PVD). PVD is a common occurrence with aging, and it consists in the separation of the vitreous body from the retina at the back pole of the eye, due to progressive shrinking of the vitreous gel. During this separation process, vitreoretinal tractions are generated at regions of high adhesion between the vitreous and the retina. Such tractions are mainly responsible for the creation of retinal tears, which can lead to retinal detachment. We describe the PVD evolution developing a continuum model of a shrinking soft body, representing the vitreous humor gel phase. In the model, the vitreous is surrounded by a membrane, stiffer than the bulk, the vitreous cortex, and it is contained within a rigid spherical domain, the vitreous chamber. The membrane is attached to the spherical wall and the adhesion strength is spatially non-uniform, increasing from the back to the front of the chamber, according to clinical observations. During the shrinking process, the vitreous undergoes elastic distortions, owing to the spatially variable adhesion on the wall, and this produces boundary tractions. We also consider the clinically relevant case of anomalous PVD, in which regions of focal adhesion between the vitreous and the retina exist, leading to the generation of strong, localized tractions. The model reproduces a PVD evolution in good qualitative agreement with clinical observations and makes it possible to correlate the shape of the detached vitreous with the intensity of vitreoretinal tractions.

Fluid and solute transport across the retinal pigment epithelium: a theoretical model.

The retina is composed of two main layers-the neuroretina and the retinal pigment epithelium (RPE)-that are separated by a potential gap termed the sub-retinal space (SRS). Accumulation of fluid in the SRS may result in a retinal detachment. A key function of the RPE is to prevent fluid accumulation in the SRS by actively pumping fluid from this space to the choroid. We have developed a mathematical model of this process that incorporates the transport of seven chemical species: Na+, K+, Cl-, HCO3-, H+, CO2 and H2CO3. This allows us to estimate solute and water fluxes and to understand the role of the different membrane ion channels. We have performed a global sensitivity analysis using the extended Fourier amplitude sensitivity test to investigate the relative importance of parameters in generating the model outputs. The model predicts that flow across the RPE is driven by an osmotic gradient in the cleft gap between adjacent cells. Moreover, the model estimates how water flux is modified in response to inhibition of membrane ion channels and carbonic anhydrase (CA). It provides a possible explanation for how CA inhibitors, which are used clinically to prevent fluid accumulation in the SRS, may be acting.

The role of Müller cells in tractional macular disorders: an optical coherence tomography study and physical model of mechanical force transmission.

BACKGROUND: To explore the role of foveal and parafoveal Müller cells in the morphology and pathophysiology of tractional macular disorders with a mathematical model of mechanical force transmission. METHODS: In this retrospective observational study, spectral-domain optical coherence tomography images of tractional lamellar macular holes and patients with myopic foveoschisis were reviewed and analysed with a mathematical model of force transmission. Parafoveal z-shaped Müller cells were modelled as a structure composed of three rigid rods, named R1, R2 and R3. The angle formed between the rods was referred to as θ . R1, R2 and R3 lengths as well as the variation of the angle θ were measured and correlated with best corrected visual acuity (BCVA). RESULTS: In tractional lamellar macular holes, there was a significant reduction of the angle θ towards the foveal centre (p<0.001). By contrast, there were no significant differences in θ in myopic foveoschisis (p=0.570). R2 segments were more vertical in myopic foveoschisis. There was a significant association between lower θ angles at 200 µm temporal and nasal to the fovea and lower BCVA (p<0.001 and p=0.005, respectively). The stiffness of parafoveal Müller cells was predicted to be function of the angle θ , and it grew very rapidly as the θ decreased. CONCLUSION: Parafoveal Müller cells in the Henle fibre layer may guarantee structural stability of the parafovea by increasing retinal compliance and resistance to mechanical stress. Small values of the angle θ were related to worse BCVA possibly due to damage to Müller cell processes and photoreceptor's axons.

Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions.

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight.

A Mathematical Model of Corneal Metabolism in the Presence of an Iris-Fixated Phakic Intraocular Lens.

Purpose: Corneal endothelial cell loss is one of the possible complications associated with phakic iris-fixated intraocular lens (PIOL) implantation. We postulate that this might be connected to the alteration of corneal metabolism secondary to the lens implantation. Methods: A mathematical model of transport and consumption/production of metabolic species in the cornea is proposed, coupled with a model of aqueous flow and transport of metabolic species in the anterior chamber. Results: Results are presented both for open and closed eyelids. We showed that, in the presence of a PIOL, glucose availability at the corneal endothelium decreases significantly during sleeping. Conclusions: Implantation of a PIOL significantly affects nutrient transport processes to the corneal endothelium especially during sleep. It must still be verified whether this finding has a clinical relevance.

Fluidics of Single and Double Blade Guillotine Vitrectomy Probes in Balanced Salt Solution and Artificial Vitreous.

PURPOSE: To assess the fluidics of double-vitreous cutter blade (DB) compared with single-blade (SB) guillotine with 23-, 25-, and 27-gauge vitrectomy probes. To assess flow characteristics and flow rates in viscous and viscoelastic fluids. METHODS: We used Particle Image Velocimetry to measure the flow field close to the tip of each cutter probe and we derived kinematic quantities of interest, such as kinetic energy and acceleration. We performed measurements both on a balanced salt solution (BSS) and on a viscoelastic artificial vitreous (AV). RESULTS: The flow rate is significantly higher with DB than SB vitrectomy probes, for a given pumping pressure and cutting rate. The fluid flow observed is very different between BSS and AV tests. CONCLUSIONS: The DB has more efficient fluidics than SB vitrectomy probe in all tested conditions. Fluid acceleration depends on the cutting frequency, especially in the case of measurements in AV. The flow rate strongly depends on the pressure and it is little affected by the cutting frequency, in a range of clinical interest. The 27-G DB produces flow rates similar to the 23- and 25-G SB, with significantly smaller acceleration. The flow induced in the AV is different from that in BSS and oscillates at different frequencies. TRANSLATIONAL RELEVANCE: DB cutters prove to be more efficient in terms of lower acceleration for a given flow rate. The latter is mainly controlled by aspiration pressure and less by cut rates. The influence of vitreous rheology deserves further investigations.

Osmotic and electroosmotic fluid transport across the retinal pigment epithelium: A mathematical model.

The retinal pigment epithelium (RPE) is the outermost cell layer of the retina. It has several important physiological functions, among which is removal of excess fluid from the sub-retinal space by pumping it isotonically towards the choroid. Failure of this pumping leads to fluid accumulation, which is closely associated with several pathological conditions, such as age-related macular degeneration, macular oedema and retinal detachment. In the present work we study mechanisms responsible for fluid transport across the RPE with the aim of understanding how fluid accumulation can be prevented. We focus on two possible mechanisms, osmosis and electroosmosis, and develop a spatially resolved mathematical model that couples fluid and ion transport across the epithelium, accounting for the presence of Na+,K+ and Cl- ions. Our model predicts spatial variability of ion concentrations and the electrical potential along the cleft gap between two adjacent cells, which osmotically drives the flow across the lateral membranes. This flow is directed from the sub-retinal space to the choroid and has a magnitude close to measured values. Electroosmosis is subdominant by three orders of magnitude to osmosis and has an opposite direction, suggesting that local osmosis is the main driving mechanism for water transport across the RPE.

A Study of the Mechanical Forces on Aphakic Iris-Fixated Intraocular Lenses.

Iris-fixated aphakic intraocular lenses (IFIOL) are used in cataract surgery when more common intraocular lenses (IOL) cannot be adopted because of the absence of capsular bag support. These lenses can be implanted on either the posterior or the anterior surface of the iris. In this work, we study whether one of these options is preferable over the other from the mechanical point of view. In particular, we focus on the forces that the IFIOL transmits to the iris, which are associated with the risk of lens dislocation. We study the problem numerically and consider aqueous flow induced by saccadic rotations in the cases of an IFIOL in the anterior and posterior sides of the iris. The considered IFIOL is the Artisan Aphakia +30.0 D lens (IFIOL) produced by Ophtec BV. We perform the simulations in openfoam. We find that the forces transmitted by the aphakic IFIOL to the iris are significantly higher in the case of posterior implantation. This suggests that lens implantation on the posterior surface of the iris might be associated with a higher risk of lens dislocation, when an inadequate amount of iris tissue is enclavated during implantation.

Flow in the anterior chamber of the eye with an implanted iris-fixated artificial lens.

Flow in the aqueous humour that fills the anterior chamber of the eye occurs in response to the production and drainage of the aqueous humour, and also due to buoyancy effects produced by thermal gradients. Phakic intraocular lenses are manufactured lenses that are surgically inserted in the eyes of patients to correct refractive errors. Their presence has a dramatic effect on the circulation of the aqueous humour, resulting a very different flow in the anterior chamber, the effects of which have not been extensively investigated. In this article we use a simplified mathematical model to analyse the flow, in order to assess the effect of the implanted lens on the pressure drop required to drive the flow and also on the wall shear stress experienced by the corneal endothelial cells and the cells of the iris. A high pressure drop could result in an increased risk of glaucoma, whilst raised shear stress on the cornea could result in a reduction in the density of endothelial cells there, and on the iris it could result in the detachment of pigment cells, which block the outflow of the eye, also leading to glaucoma. Our results confirm those of previous fully numerical studies, and show that, although the presence of the lens causes significant differences in the flow topology and direction, the typical magnitudes of the shear stress are not significantly changed from the natural case. Our semi-analytical solution allows us to perform a thorough study of the dependence of the results on the controlling parameters and also to understand the basic physical mechanisms underlying flow characteristics.

A mathematical model for the vessel recruitment in coronary microcirculation in the absence of active autoregulation.

This paper proposes a mathematical model for vessel recruitment in the microvascular coronary network. The model is based on microvascular network units (MVNUs), where we define a MVNU as a portion of the microvascular network comprising seven generations of identical, parallel-arranged vessels (upstream arteries, large and small arterioles, capillaries, small and large venules, and downstream veins). The model implements a new mechanism to describe the variation in the number of MVNU in response to sudden variations of the local input pressure. In particular, it describes a recruitment mechanism dependent on distal pressure which operates in the coronary microcirculatory network even in maximally dilated conditions. We apply the model to interpret data from 29 patients who underwent revascularization by percutaneous coronary intervention (PCI). Treated vessels were the left anterior descending coronary artery, the left circumflex and the right coronary artery in 26, 2 and 1 patients, respectively. Following intracoronary adenosine administration, distal coronary pressure and blood flow were 48 ± 18 mmHg and 45 ± 30 ml/min before PCI, respectively, and significantly increased afterwards to 80 ± 17 mmHg and 68 ± 32 ml/min (p<0.001). The model predicts an increase in MVNU number in patients with preserved wall motion in the myocardial region which underwent PCI. On the contrary, a decrease in MVNU number is predicted by the model in patients with regional dysfunction and implies a relatively lower response of maximal flow to revascularization.