Finding the ideal biomaterial for aortic valve repair with ex vivo porcine left heart simulator and finite element modeling

OBJECTIVES: Aortic valve (AV) repair (AVr) has become an attractive alternative to AV replacement for the correction of aortic insufficiency; however, little clinical evidence exists in determining which biomaterial at AVr would be optimal. Cusp replacement in AVr has been associated with increased long-term AVr failure. We measured the hemodynamic and biomaterial properties using an ex vivo porcine AVr model with clinically relevant biomaterials and generated a finite element model to ascertain which materials would be best suited for valve repair. METHODS: Porcine aortic roots with intact AVs were placed in a left heart simulator mounted with a high-speed camera for baseline valve assessment. The noncoronary cusp was excised and replaced with autologous porcine pericardium, glutaraldehyde-fixed bovine pericardial patch (Synovis), extracelluar matrix scaffold (CorMatrix), or collagen-impregnated Dacron (Hemashield). The hemodynamic parameters were measured for a range of cardiac outputs (2.5-6.5 L/min) after repair. The biomaterial properties and St Jude Medical pericardial patch were determined using pressurization experiments. Finite element models of the AV and root complex were constructed to determine the hemodynamic characteristics and leaflet stresses. RESULTS: The geometric orifice areas after repair were significantly reduced in the Hemashield (P<.05) and CorMatrix (P=.0001) groups. Left ventricular work increased with increasing cardiac output (P=.001) in unrepaired valves, as expected, and was similar among all biomaterial groups. Finite element modeling of the biomaterials displayed differences in the percentage of changes in total Von Mises stress for both replaced (noncoronary cusp) and nonreplaced left and right cusps with the St Jude Medical pericardial patch (+4%, +24%) and autologous porcine pericardium (+5, +26%), with a lower percentage of changes than for the bovine pericardial patch (+12%, +27%), Hemashield (+30%, +9%), and CorMatrix (+13%, +32%). Conclusions: The present study has shown that postrepair left ventricular work did not increase despite a decrease in geometric orifice areas in the Hemashield and CorMatrix groups. The autologous porcine pericardium and St Jude Medical pericardial patch had the closest profile to normal AVs; therefore, either biomaterial might be best suited. Finally, the increased stresses found in the bovine pericardial patch, Hemashield, and CorMatrix groups might, after prolonged tensile exposure, be associated with late repair failure

The extracellular matrix controls gap junction protein expression and function in postnatal hippocampal neural progenitor cells

BACKGROUND:Gap junction protein and extracellular matrix signalling systems act in concert to influence developmental specification of neural stem and progenitor cells. It is not known how these two signalling systems interact. Here, we examined the role of ECM components in regulating connexin expression and function in postnatal hippocampal progenitor cells.RESULTS:We found that Cx26, Cx29, Cx30, Cx37, Cx40, Cx43, Cx45, and Cx47 mRNA and protein but only Cx32 and Cx36 mRNA are detected in distinct neural progenitor cell populations cultured in the absence of exogenous ECM. Multipotential Type 1 cells express Cx26, Cx30, and Cx43 protein. Their Type 2a progeny but not Type 2b and 3 neuronally committed progenitor cells additionally express Cx37, Cx40, and Cx45. Cx29 and Cx47 protein is detected in early oligodendrocyte progenitors and mature oligodendrocytes respectively. Engagement with a laminin substrate markedly increases Cx26 protein expression, decreases Cx40, Cx43, Cx45, and Cx47 protein expression, and alters subcellular localization of Cx30. These changes are associated with decreased neurogenesis. Further, laminin elicits the appearance of Cx32 protein in early oligodendrocyte progenitors and Cx36 protein in immature neurons. These changes impact upon functional connexin-mediated hemichannel activity but not gap junctional intercellular communication.CONCLUSION:Together, these findings demonstrate a new role for extracellular matrix-cell interaction, specifically laminin, in the regulation of intrinsic connexin expression and function in postnatal neural progenitor cells.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Predictive factors, management, and clinical outcomes of coronary obstruction following transcatheter aortic valve implantation: insights from a large multicenter registry

This study sought to evaluate the main baseline and procedural characteristics, management, and clinical outcomes of patients from a large cohort of patients undergoing transcatheter aortic valve implantation (TAVI) who suffered coronary obstruction (CO). Very little data exist on CO following TAVI. This multicenter registry included 44 patients who suffered symptomatic CO following TAVI of 6,688 patients (0.66%). Pre-TAVI computed tomography data was available in 28 CO patients and in a control group of 345 patients (comparisons were performed including all patients and a cohort matched 1:1 by age, sex, previous coronary artery bypass graft, transcatheter valve type, and size). Baseline and procedural variables associated with CO were older age (p < 0.001), female sex (p < 0.001), no previous coronary artery bypass graft (p = 0.043), the use of a balloon-expandable valve (p = 0.023), and previous surgical aortic bioprosthesis (p = 0.045). The left coronary artery was the most commonly involved (88.6%). The mean left coronary artery ostia height and sinus of Valsalva diameters were lower in patients with obstruction than in control subjects (10.6 ± 2.1 mm vs. 13.4 ± 2.1 mm, p < 0.001; 28.1 ± 3.8 mm vs. 31.9 ± 4.1 mm, p < 0.001). Differences between groups remained significant after the case-matched analysis (p < 0.001 for coronary height; p = 0.01 for sinus of Valsalva diameter). Most patients presented with persistent severe hypotension (68.2%) and electrocardiographic changes (56.8%). Percutaneous coronary intervention was attempted in 75% of the cases and was successful in 81.8%. Thirty-day mortality was 40.9%. After a median follow-up of 12 (2 to 18) months, the cumulative mortality rate was 45.5%, and there were no cases of stent thrombosis or reintervention. Symptomatic CO following TAVI was a rare but life-threatening complication that occurred more frequently in women, in patients receiving a balloon-expandable valve, and in those with a previous surgical bioprosthesis. Lower-lying coronary ostium and shallow sinus of Valsalva were associated anatomic factors, and despite successful treatment, acute and late mortality remained very high, highlighting the importance of anticipating and preventing the occurrence of this complication