Andrew Wisneski

Biomechanical Properties of Human Ascending Thoracic Aortic Aneurysms

BACKGROUND Surgical management of ascending thoracic aortic aneurysms (aTAAs) relies on maximum diameter, growth rate, and presence of connective tissue disorders. However, dissection and rupture do occur in patients who do not meet criteria for surgical repair. This study investigated the mechanical properties of aTAAs compared with normal human ascending aortas for eventual development of biomechanical aTAA risk models. METHODS aTAA specimens (n = 18) were obtained from patients undergoing surgical aneurysm repair, and fresh, healthy ascending aortas (n = 19) as controls were obtained from the transplant donor network. Biaxial stretch testing was performed to obtain tissue mechanical properties. Patient-specific aTAA physiologic stress was calculated based on preoperative computed tomography diameter. aTAA and ascending aorta tissue stiffness at respective physiologic stress were determined. RESULTS Physiologic stress of aTAA was significantly greater (241.6 ± 59.4 kPa) than the 74 kPa for normal controls. Tissue stiffness of aTAAs was significantly greater than that of the ascending aortas at their respective physiologic stresses in the circumferential (3041.4 ± 1673.7 vs 905.1 ± 358.9 kPa, respectively; p < 0.001) and longitudinal (3498.2 ± 2456.8 vs 915.3 ± 368.9 kPa, respectively; p < 0.001) directions. Tissue stiffness of aTAAs positively correlated with aTAA diameter but did not correlate with patient age. No correlation was found between aTAA physiologic stress level and maximum aTAA diameter. CONCLUSIONS aTAAs are much stiffer than normal ascending aortas at their respective physiologic stress, which was also significantly greater in ATAAs than ascending aortas. Patient-specific physiologic stress did not correlate with maximum aTAA diameter, and patient-specific aTAA wall stress may be a useful variable to predict adverse aTAA events.

Myocardial survival signaling in response to stem cell transplantation.

BACKGROUND Experimental human stem cell transplantation to the heart has begun, but the mechanisms underlying benefits seen in preclinical models, both at the site of cell injection and at more distant regions, remain uncertain. We hypothesize that these benefits can be best understood first at the level of key intracellular signaling cascades in the host myocardium, which can be responsible for functional and structural preservation of the heart. STUDY DESIGN Western blot and ELISA were used to assess key pathways that regulate cardiac myocyte survival and hypertrophy in both the infarct/borderzone and remote myocardium of C57/B6 mouse hearts subjected to coronary artery ligation, with subsequent injection of either vehicle or bone marrow-derived adult mesenchymal stem cells (MSC). RESULTS Improved left ventricular function with MSC transplantation was associated with a relative preservation of Akt phosphorylation (activation) and of phosphorylation of downstream mediators of cell survival and hypertrophy. There was no substantial difference in activation of mitogen-activated protein kinase p38, and activation of the antiapoptotic mitogen-activated protein kinase extracellular signal-regulated kinase was lower at 1 week after MSC treatment, but rose beyond controls by week 2. Similar changes were observed in both the infarct/borderzone and the remote myocardium. CONCLUSION Stem cell transplantation in the post-MI murine myocardium is associated with preservation of Akt signaling. Together with a possible later increase in extracellular signal-regulated kinase activation, this signaling change might be responsible for cardioprotection. Additional focused investigation might identify elements in transplantation regimens that optimize this mechanism of benefit, and that can increase the likelihood of human clinical success.

Material properties of CorCap passive cardiac support device.

BACKGROUND Myocardial function deteriorates during ventricular remodeling in patients with congestive heart failure (HF). Ventricular restraint therapy using a cardiac support device (CSD) is designed to reduce the amount of stress inside the dilated ventricles, which in turn halts remodeling. However, as an open mesh surrounding the heart, it is unknown what the mechanical properties of the CSD are in different fiber orientations. METHODS Composite specimens of CorCap (Acorn Cardiovascular, Inc, St. Paul, MN) CSD fabric and silicone were constructed in different fiber orientations and tested on a custom-built biaxial stretcher. Silicone controls were made and stretched to detect the parameters of the matrix. CSD coefficients were calculated using the composite and silicone matrix stress-strain data. Stiffness in different fiber orientations was determined. RESULTS Silicone specimens exerted a linear behavior, with stiffness of 2.57 MPa. For the composites with 1 fiber set aligned with respect to the stretch axes, stiffness in the direction of the aligned fiber set was higher than that in the cross-fiber direction (14.39 MPa versus 5.66 MPa), indicating greater compliance in the cross-fiber direction. When the orientation of the fiber sets in the composite were matched to the expected clinical orientation of the implanted CorCap, the stiffness in the circumferential axis (with respect to the heart) was greater than in the longitudinal axis (10.55 MPa versus 9.70 MPa). CONCLUSIONS The mechanical properties of the CorCap demonstrate directionality with greater stiffness circumferentially than longitudinally. Implantation of the CorCap clinically should take into account the directionality of the biomechanics to optimize ventricular restraint.

Tsinghua-Johns Hopkins Joint Center for Biomedical Engineering Research: Scientific and cultural exchange in undergraduate engineering

A model for an international undergraduate biomedical engineering research exchange program is outlined. In 2008, the Johns Hopkins University in collaboration with Tsinghua University in Beijing, China established the Tsinghua-Johns Hopkins Joint Center for Biomedical Engineering Research. Undergraduate biomedical engineering students from both universities are offered the opportunity to participate in research at the overseas institution. Programs such as these will not only provide research experiences for undergraduates but valuable cultural exchange and enrichment as well. Currently, strict course scheduling and rigorous curricula in most biomedical engineering programs may present obstacles for students to partake in study abroad opportunities. Universities are encouraged to harbor abroad opportunities for undergraduate engineering students, for which this particular program can serve as a model.