Publications by Author: Tarek Shazly

We propose a relatively simple two-dimensional mathematical model for maladaptive inward remodeling of resistive arteries in hypertension in terms of vascular solid mechanics. The main premises are: (i) maladaptive inward remodeling manifests as a reduced increase in the arterial mass compared to the case of adaptive remodeling under equivalent hypertensive pressures and (ii) the pressure-induced circumferential stress in the arterial wall is restored to its basal target value as happens in the case of adaptive remodeling. The rationale for these assumptions is the experimental findings that elevated tone in association with sustained hypertensive pressure down-regulate the normal differentiation of vascular smooth muscle cells from contractile to synthetic phenotype and the data for the calculated hoop stress before and after completion of remodeling. Results from illustrative simulations show that as the hypertensive pressure increases, remodeling causes a nonmonotonic variation of arterial mass, a decrease in inner arterial diameter, and an increase in wall thickness. These findings and the model prediction that inward eutrophic remodeling is preceded by inward hypertrophic remodeling are supported by published observations. Limitations and perspectives for refining the mathematical model are discussed.

Strategic delivery of hydrogels to the newly formed myocardial infarction (MI) is an area of active investigation and offers high target specificity for releasing a small molecule therapeutic payload. This study examined the effects of delayed post-MI delivery (pigs, 3 days post-MI) of a shear-thinning hydrogel which encapsulated and released a small molecule matrix metalloproteinase inhibitor. The results demonstrated the feasibility and efficacy of targeted delivery of a shear-thinning injectable hydrogel containing a small molecule matrix metalloproteinase inhibitor to attenuate post-MI remodeling.

Purpose

Premature coronary artery bypass graft (CABG) failure has been linked to geometric, mechanical, and compositional discrepancies between host and graft tissues. Acute hemodynamic disturbances and the introduction of wall stress gradients trigger a myriad of mechanobiological processes at the anastomosis that can be associated with restenosis and graft failure. Although the origins of coronary artery disease dictate the anastomotic target, an opportunity exists for graft-vessel optimization through rationale graft selection.

Methods

Here we explored the four distinct regions of the left (L) and right (R) ITA (1 = proximal, 2 = submuscular, 3 = middle, 4 = distal), and four common target vessels in the coronary circulation including the proximal and distal left anterior descending (PLAD & DLAD), right coronary (RCA), and left circumflex (LCX) arteries. Benchtop biaxial mechanical data was used to acquire constitutive model parameters of these tissues and enable vessel-specific computational models to elucidate the mechanical consequences of 32 unique graft-target combinations.

Results

Simulations revealed the maximum principal wall stresses for the PLAD, RCA, and LCX occurred when anastomosed with LITA₁, and the maximum flow-induced shear stress occurred with LITA₄. The DLAD, on the other hand, reached stress maximums when anastomosed to LITA₄. Using a normalized objective function of simulation output variables, we found LITA₂ to be the best graft choice for both LADs, RITA₃ for the RCA, and LITA₃ for the LCX.

Conclusion

Although mechanical compatibility is just one of many factors determining bypass graft outcomes, our data suggests improvements can be made to the grafting process through vessel-specific regional optimization.

Endothelial dysfunction, defined as a reduction in the bioavailability of nitric oxide (NO), is a risk factor for the occurrence and progression of various vascular diseases. This study investigates the effect of endothelial dysfunction on age-related changes in aortic extracellular matrix (ECM) microstructure and the relationship between microstructural adaptation and the mechanical response. Here, we used groups of NOS3 knockout (KO), NOS3 heterozygotes (Het), and wild-type (WT) B6 mice (controls) to study changes in hemodynamic parameters, collagen fiber organization, and both active and passive aortic mechanics using biaxial pressure myography over a time course from 1.5 to 12 mo. Our results show that homeostatic levels of passive circumferential stress and stretch were preserved in KO mice by remodeling adventitial collagen fibers toward a more predominantly circumferential direction with age, rather than by increased fibrosis, in response to hypertension induced by endothelial dysfunction. However, passive aortic stiffness in KO mice was significantly increased owing to geometrical changes, including significant increases in wall thickness and decreases in inner diameter, as well as by ECM microstructural reorganization, during this maladaptive vascular remodeling. Furthermore, long-term NO deficiency significantly increased smooth muscle cell (SMC) contractility initially, but this effect was attenuated with age. These findings improve our understanding of microstructural and mechanical changes during the maladaptive vascular remodeling process, demonstrating a role for adventitial collagen fiber re-orientation in the response to hypertension

Described herein are devices and methods for performing automated and minimally invasive intramyocardial injections for cardiac repair that eliminate the need for opening the chest cavity for injections of therapeutics to the heart muscle to address heart attack, cardiomyopathy or myocardial diseases and can detect diseased tissue and deliver a specified volume of a therapeutic injectate to the region of interest.