The decade of the 1990s has seen considerable progress toward the development of innovative ventricular assist blood pump systems suitable for the chronic support of adult patients in refractory cardiac failure. Particularly noteworthy are the centrifugal and axial flow rotary blood pumps which are now undergoing long-term animal testing in anticipation of the first U.S. clinical trials. Several of these pump systems are also currently being tested overseas in humans in acute implant trials. One long-standing question remains unanswered regarding these rotary blood pumps relates to the chronic effect of a non- physiologic flow pulse on the anatomy and physiology of the host. This question is assuming considerable clinical importance as these rotary pump systems approach the clinical application for which they are intended, namely long-term total cardiac support. Consequently, the proposed study is being undertaken to investigate chronic non-pulsatile flow from the point of view of physiologic endpoints which are known to be important in the clinical setting of left ventricular and biventricular assistance. To that end, we will complete a series of in vivo (calf) experiments in which diminished pulse flow or totally non- pulsatile flow is generated for either 30 days or 180 days duration via implantation of an axial flow blood pump system. Using this well-validated animal model and robust pump system, we will evaluate the effects of diminished pulsatility and non- pulsatile flow on vasomotor response, arterial microstructure, biomechanical properties of the carotid arteries, and tissue capillary flow. From these experiments, we believe that we will provide significant new information regarding tissue perfusion and arterial adaptation to, and possible impairment from, diminished or non-existent flow pulse.
| Kilic, Ahmet; Li, Tieluo; Nolan, Timothy D C et al. (2006) Strain-related regional alterations of calcium-handling proteins in myocardial remodeling. J Thorac Cardiovasc Surg 132:900-8 |
