Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.
Objective We have previously demonstrated that human abdominal aortic aneurysm (AAA) rupture occurs in zones of low wall shear stress where flow recirculation and intraluminal thrombus (ILT) deposition are increased. Matrix metalloproteinase-9 (MMP-9) is involved in the pathogenesis of AAA via its lytic effect on collagen and elastin. We hypothesize that flow-mediated ILT deposition promotes increased local inflammatory and MMP-9 activity that leads to AAA wall degeneration. The purpose of this study was to examine the correlation between predicted pulsatile flow dynamics and regional differences in MMP-9, elastin, collagen, and ILT deposition in human AAA. Methods Full-thickness aortic tissue samples were collected from 24 patients undergoing open AAA repair. Control infrarenal aortic tissue was obtained from 6 patients undergoing aortobifemoral bypass. Full-thickness aortic tissue and ILT were assessed for MMP-9 levels using a cytokine array assay. Histologic and immunohistochemical assessment of inflammation, collagen and elastin content, and MMP-9 levels were also measured. Three-dimensional AAA geometry was generated from computed tomography angiogram (CTA) images using Mimics software and computational fluid dynamics was used to predict pulsatile aortic blood flow. Results The majority of AAA showed eccentric ILT deposition which was correlated with predicted recirculation blood flow (R 2 = –0.17; P < .05). The regions of high ILT were associated with significant increases in inflammation and loss of elastin and collagen compared with regions of low ILT, or with control tissue. MMP-9 was significantly higher in areas of high ILT deposition compared with areas devoid of ILT. Tissue MMP-9 was correlated with the thickness of ILT deposition (R 2 = 0.46; P < .05), and was also present in high levels in thick compared with thin ILT. Conclusions We have shown a correlation between flow-mediated ILT deposition with increased tissue levels of MMP-9 activity, increased inflammatory infiltrate, and decreased elastin and collagen content in stereotactically sampled human AAA, suggesting that ILT deposition is associated with local increases in proteolytic activity that may preferentially weaken and promote rupture at selected regions.
Ischemia Reperfusion (I/R) injury is a consequence of reperfusion of the ischemic myocardium when reperfusion is carried out beyond a certain time period of the ischemic insult. The I/R injury is associated with impaired heart function as well as myocardial cell damage and is generally seen to occur during coronary angioplasty, cardiac by-pass surgery, cardiac transplantation and thrombolytic therapy. Several mechanisms including the occurrence of oxidative stress, activation of inflammatory processes, development of intracellular Ca 2+ -overload, depletion of high energy stores and increased activities of proteolytic enzymes have been suggested to explain the I/R-induced cardiac dysfunction. While contractile failure, apoptosis and necrosis in the heart may be due to cationic redistribution and metabolic alterations as a consequence of oxidative stress and intracellular Ca 2+ -overload, marked alterations in cardiac gene expression and translation mechanisms may play a critical role in attenuating the recovery of ischemic myocardium. This article therefore is focused on understanding changes in the metabolic and molecular processes occurring in the heart due to I/R injury. Furthermore, current and potential pharmacologic as well as non-pharmacologic interventions are indicated for preventing the I/R injury in the heart.
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