High-Frequency Fluctuation Intensity as a Predictor of Post-Stenotic Dilatation in Swine.

OBJECTIVE: To identify the turbulent components of blood flow facilitating aortic lumen dilatation in a post-stenotic dilatation (PSD) porcine model. METHODS: The porcine abdominal aorta (AA) was moderately coarctated to induce overt flow turbulence in the downstream region and to lead to dilatation in time periods between four and twelve weeks. We propose a new metric, fluctuation intensity (FI), to quantify turbulent fluctuations of pulsatile aortic flow measured within twenty minutes post-coarctation. Lumen perimeter ratio (LPR) of the distal-to-suprarenal AA was used to assess the degree of PSD. Using k-means clustering analysis, we first divided FI frequency spectrum into low- and high-frequency fluctuation intensity (LFFI and HFFI), and subsequently grouped animals with coarctation. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of the proposed metric to predict PSD. RESULTS: The frequency band of the FI spectrum in facilitating aortic lumen dilatation was identified to be 40∼200 Hz. Using sham group as the reference, pigs receiving coarctation were clustered into two groups with (group A) and without (group B) increases in HFFI values. Coarctation significantly increased LPR values in group A, but not in group B. Moreover, group A exhibited a high probability density distribution on severe elastic fiber fragmentation. ROC analysis indicated HFFI to be capable of predicting PSD with excellent sensitivity and specificity. CONCLUSION: High-intensity, high-frequency components of blood flow fluctuations induced by moderate coarctation promote elastic lamella degradation and aortic lumen dilatation. SIGNIFICANCE: HFFI application in flowmeter programs may provide a useful predictor of PSD.

Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model.

OBJECTIVE: Hemodynamic stress participates in the initiation and progression of aneurysmal degeneration. Coarctation increases flow-mediated stress on the aortic wall. We tested the hypothesis that prolonged coarctation of an infrarenal abdominal aorta (AA) segment leads to abdominal aortic aneurysm (AAA) formation in mini pigs. METHODS: An asymmetric, funnel-shaped flow path was created by constricting the infrarenal AA segment of Taiwanese Lanyu mini pigs (age, 7-10 months; male and female) wrapped with an 8-mm-wide expanded polytetrafluoroethylene Teflon strip for 4 weeks (4w), 8 weeks (8w), and 12 weeks (12w) (seven pigs per group). This mimics the tortuous aneurysm neck in human AAA, which increases downstream flow-mediated stress. Significant flow disturbance resulting from moderate coarctation was indicated by a pulsatility index reduced to one third the inherent levels. Sham control pigs received Teflon wrapping without coarctation. RESULTS: Aneurysm characterized by progressive medial degeneration occurred at the terminal AA after 12w coarctation. The outer dimension enlargement of the distal AA exceeded 50% compared with that of the proximal AA at 4w, 8w, and 12w postcoarctation (sham, 1.0; 4w, 1.7 ± 0.08; 8w, 1.5 ± 0.09; 12w, 1.7 ± 0.01). Lumen ratio of the distal-to-suprarenal AA increased time dependently, with 12w postcoarctation exhibiting significant increase (sham, 1.0 ± 0.05; 4w, 1.1 ± 0.11; 8w, 1.4 ± 0.20; 12w, 1.5 ± 0.09). In the distal AA, elastic lamellae exhibited fragmentation at 4w and more pronounced fragmentation with decreased density at 8w and 12w postcoarctation. Medial collagen density exhibited the trend to increase at 4w and 8w but was reversed at 12w postcoarctation. Smooth muscle exhibited disarray and nuclear density decrease at 8w and 12w postcoarctation (sham, 6966 ± 888/mm; 4w, 5747 ± 1340/mm; 8w, 4153 ± 323/mm; 12w, 4083 ± 465/mm). Gelatin zymography revealed that matrix metalloproteinase-9 activity markedly increased at 4w postcoarctation. CONCLUSIONS: Prolonged moderate coarctation caused regional hemodynamic stress and thereby induced degenerative AAA in the terminal AA.