Like engineered materials, an artery's biomechanical behavior and function depend on its microstructure. Glycation is associated with both normal aging and diabetes and has been shown to increase arterial stiffness. In this study we examined the direct effect of glycation on the mechanical response of intact arteries and on the mechanical response and structure of elastin isolated from the arteries. Samples of intact arteries and isolated elastin were prepared from porcine aortas and glycated. The mechanical response of all samples was completed using a uniaxial material test system. Glycation levels were measured using ELISA. A confocal microscope was used to image differences in the structure of the glycated and untreated elastin fibers. We found that, under the conditions used in this study, glycation led to decreased stiffness of elastin isolated from arteries, which was associated with a thinning of elastin fibers as imaged by confocal microscopy. We observed no effect of glycation on collagen fibers under our treatment conditions. These results suggest that glycation leads to weakening of the elastin component of arteries that could contribute to vascular defects seen in diabetes and aging. Prevention of glycation reactions may be an important consideration for vascular health later in life.
Reactive oxygen species (ROS), a product of many cellular functions, has been implicated in many age-related pathophysiological processes, including cardiovascular disease. The arterial proteins collagen and elastin may also undergo structural and functional changes due to damage caused by ROS. This study examined the effect of oxidation on the mechanical response of porcine aortas and aorta elastin and the associated changes in structural protein ultrastructure as a step in exploring the role of molecular changes in structural proteins with aging on elastic artery function. We examined the change in mechanical properties of aorta samples after various oxidation times as a first step in understanding how the oxidative environment associated with aging could impact mechanical properties of arterial structural proteins. We used confocal microscopy to visualize how the microstructure of isolated elastin changed with oxidation. We find that short term oxidation of elastin isolated from aortas leads to an increase in material stiffness, but also an increase in the fiber diameter, increase in void space in the matrix, and a decrease in the fiber orientation, possibly due to fiber cross-linking. The short term effects of oxidation on arterial collagen is more complex, with increase in material stiffness seen in the collagen region of the stress stretch curve at low extents of oxidation, but not at high levels of oxidation. These results may provide insight into the relationship between oxidative damage to tissue associated with aging and disease, structure of the arterial proteins elastin and collagen, and arterial mechanical properties and function.
The purpose of this study was to design and evaluate a system to test the mechanical behavior of pacemaker and defibrillator leads. Over 300,000 pacemaker and implantable cardioverter defibrillator (ICD) procedures are performed every year in the U.S. for the treatment of cardiac arrhythmias, ventricular dysrhythmias, and congestive heart failure. These procedures require implanting transvenous leads into the interior wall of the heart. A serious and sometimes fatal complication that may occur during or after lead implantation is perforation of the lead tip through the heart wall. The factors that lead to perforation are not fully understood. This illustrates that the mechanical interactions between the lead tip and the cardiac tissue need to be further investigated to improve the outcome for pacemaker and ICD patients. To improve the performance of lead tips, the testing protocols must reproduce physiological and clinically relevant tip-tissue interactions. As a first step toward this goal, testing parameters that influence those interactions must be identified. We investigated the effect of test system parameters, which reproduce potentially critical physiological constraints, on the load experienced at the distal tip of thirteen pacemaker and defibrillator active-fixation leads. We evaluated the use of a constraint to simulate the effect of the right ventricle (RV constraint) in vivo, how and where the lead was fixed in the test configuration, location of the load cell in the test system, rotation and frequency of the test protocol, and the effect of stylets. Results showed the RV constraint and load cell placement had the largest impact on lead tip load, while rotation of the test setup and test frequency had a minimal impact. Recommendations are made for a test system and protocol for in vitro testing of leads that take into consideration in vivo conditions. Better approximations of the in vivo environment may lead to improved product development. The potential of this system to more effectively evaluate new pacemaker and defibrillator lead designs will require further study.
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