This research is directed at the development of a noninvasive, rapid and reliable method utilizing ultrasonic backscatter from myocardium for early detection of acute graft rejection following cardiac transplantation alone or in conjunction with M-mode and 2-D echocardiography. The acute rejection crises can be controlled with appropriate immunosuppressive therapy only if it can be detected sufficiently early. The early histological signs of acute cardiac rejection are interstitial infiltration of monocytes, vascular engorgement and/or edema. As a result, it is very likely that echogenicity (echo generating capability) or backscatter of the graft myocardium may be used as an early indicator for acute rejection since it has been suggested that the echogenicity of biological tissues is related to their biological composition. In the initial phase of the project, we propose to study whether ultrasonic backscatter can be used as a measure to detect acute cardiac rejection in vitro with canine models. This will be achieved by comparing the backscatter from tissues excised from canine grafts in rejection crisis as demonstrated by myocardial biopsy to that from normal canine myocardium. Subsequently, serial changes in ultrasonic backscatter from exposed homografts following cardiac transplantation with acute rejection, no rejection, and persistent rejection will be collected. Finally, in vivo experimentation on closed-chest dogs will be pursued. During this phase, the significance of the ultrasonic backscatter results alone or supplemented by data obtained by M-mode or 2-D echocardiography such as posterior left ventricular wall thickness and left ventricular mass in predicting acute cardiac rejection will be determined by correlating them to myocardial biopsy. It is hoped that the results obtained in this research can be utilized to facilitate the development of a noninvasive, reliable, rapid and independent method for the detection of cardiac rejection at its inception. The need for such a technique is accentuated by the fact that there is no appreciate change in EKG voltages during rejection crisis in patients treated with cyclosporin A, a new immunosuppressive drug, which has been found to be less toxic and more effective then conventional therapy.
