Biomedical subjects

Soren Schenk

Publications and source records attributed to Soren Schenk.

5 recordsLinked to original sources

PubMed2004

Effects of T cell frequency and graft size on transplant outcome in mice.

The features that determine whether graft-reactive T lymphocytes develop into effector cells capable of mediating organ destruction are not well understood. To investigate potential factors involved in this process, we first confirmed that female recipient mice acutely rejected minor Ag-disparate male skin, but not heart transplants. Despite this difference in outcome, heart and skin transplantation induced antidonor T cell responses of similar magnitude, specificity, and cytokine profile. The heart-graft-primed T cells transiently infiltrated the graft and ultimately induced the development of chronic transplant vasculopathy. Increasing the frequency of donor-reactive T cells by presensitization or by using TCR (CD8+ antimale)-transgenic recipients did not mediate acute rejection but accelerated the pace and severity of the vasculopathy. Surprisingly, decreasing the tissue mass of the donor heart by 50% resulted in acute rejection of these smaller grafts without increasing the frequency of antidonor effector T cells in the recipients. In complementary studies, placement of one or two male skin grafts on a single recipient did not affect the frequency or cytokine profile of the induced antimale T cell repertoire. Nonetheless, the recipients of single grafts acutely rejected the transplanted skin while the recipients of two skin grafts did not. These results provide new insight into the pathogenesis of transplant vasculopathy and provide an explanation for the difference in outcome between murine skin and heart transplants by highlighting the novel concept that the efficiency of transplant-reactive T cell immunity is heavily influenced by the tissue burden it encounters at the effector stage.

Acute Disease↗

PubMed2003

Ventricular reshaping with devices.

Device-based left ventricular reshaping to facilitate reverse remodeling in cases of congestive heart failure represents an innovative surgical strategy. Originating from experiences gained with partial left ventriculectomy and dynamic cardiomyoplasty, the Myocor Myosplint device and the Acorn CorCap Cardiac Support Device are intended to improve left ventricle function through left ventricular shape change by means of wall stress reduction and passive diastolic support, respectively. Encouraging experimental and early clinical results with both devices support these novel concepts. Careful patient selection and a combined approach integrating adjunct surgical and medical treatments are crucial factors for the success of ventricular reshaping.

Animals↗

PubMed2002

Myosplint implant and shape-change procedure: intra- and peri-operative safety and feasibility.

BACKGROUND: In patients with dilated cardiomyopathy (DCM), the heart enlarges, leading to a corresponding increase in ventricular wall stress. To reduce the stress, transventricular tension members (Myosplint, Myocor, Inc.) were implanted to change the left ventricle (LV) effective radius and to reduce the LV wall stress by 20%. We conducted this study to evaluate the intra- and peri-operative safety and feasibility of LV-shape change therapy. METHODS: In 7 patients, all diagnosed with DCM, Myosplints were implanted. New York Heart Association class ranged from III-IV, and LV end-diastolic diameter ranged from 70 to 102 mm. Mitral valve regurgitation was classified as mild in 3 and moderate in 4 cases. Four patients underwent mitral valve annuloplasty. RESULTS: We observed no significant device-related complications, such as thromboembolism, bleeding, device instability, or vascular damage, at 90 days. Early indications in a small patient population demonstrate some improvements in clinical parameters. CONCLUSIONS: From this initial experience, one may conclude that placement of the Myosplint devices can be safely performed without early, significant adverse events. In patients with significant mitral valve incompetence, concomitant mitral valve repair is indicated to realize the full benefit of the procedure. This study also suggests that Myosplints can be safely implanted in combination with mitral valve repair. The long-term effect of each procedure on cardiac function and survival will require further evaluation.

Adult↗

PubMedDate not supplied

Device-based left ventricular geometry change for heart failure treatment: developmental work and current status.

BACKGROUND: Device-based left ventricular (LV) geometry change is a new concept in the treatment of heart failure that reduces LV wall stress and improves cardiac function by reducing effective LV radius. Ventricular geometry change is achieved by placement of three Myosplint devices to bisect the LV and to create two smaller LV chambers. METHODS AND RESULTS: Since the first animal experiment in June 1997, the Myosplint has been tested extensively in a series of animal studies using a pacing-induced, canine dilated cardiomyopathy model. Device-based LV geometry change decreased LV wall stress, improved systolic function, and maintained diastolic function, resulting in an improvement in myocardial energetics. An acute human feasibility study during heart transplant surgery was started in July 1999. While awaiting the arrival of the donor heart, the Myosplint was implanted in the recipient LV in 5 patients. The device was easily applied on a beating heart without complications related to the device or the procedure in any of the patients. LV wall stress was significantly decreased after tightening of the device. Clinical safety studies with chronic Myosplint implantation were begun in Germany in June 2000 and in the United States in February 2001. There have been a total of 21 patients receiving the implant without evidence of bleeding, muscle tearing, severe arrhythmia, or thrombus formation associated with the implant. CONCLUSIONS: Device-based geometry change has been demonstrated to be practical, effective, and safe.

Animals↗

PubMedDate not supplied

In vivo performance and biocompatibility of the MagScrew ventricular assist device.

Currently available ventricular assist devices (VADs) have limitations in long-term durability and blood compatibility. We evaluated a prototype of a pulsatile MagScrew VAD for in vivo hemodynamic performance and biocompatibility. The device is composed of an actuator, blood pump housing, diaphragm, pusher plate, and bioprosthetic valves. Its protein-coated ("biolized") blood-contacting surface inhibits clot formation. Forces between moving parts of the actuator are transmitted magnetically, eliminating a primary source of friction and wear. The pump fills passively and is highly preload sensitive. The device was implanted into three calves for 90, 10, and 57 days, respectively. No anticoagulants were given postoperatively. The device functioned without technical problems during the entire course of each experiment, with mean device flow ranging between 5.4 and 9.0 L/min. Autopsy of the first two calves revealed no sign of embolization and clean blood-contacting surfaces of the devices. The third experiment was complicated by a prosthetic valve endocarditis with infectious embolization, and a few small depositions were found in the pump. In conclusion, the MagScrew VAD has demonstrated a high level of performance and biocompatibility in three calves studied for 10-90 days. Vigorous development is in progress to bring this device to preclinical readiness and thus provide surgeons with the VAD of choice for permanent implantation.

Animals↗