The chief goal of this proposal is construct a catheter-based interventional device containing an ultraviolet (UV) light-conducting glass optical fiber, which will be used to remove, from a common carotid artery (CCA) of a rat, an occlusive blood clot (thrombus) and to demonstrate, in particular, the effectiveness of this device against thrombi containing platelets only, or containing fibrin, red blood cells and platelets. The basis of this device's function is our newly patented (U.S. No. 6,539,944) process of ultraviolet (UV) laser-facilitated dethrombosis, defined as the dissolution of a platelet aggregate into individual platelets without the use of a thrombolytic agent. Thrombus dissociation is initiated by endoscopic UV laser irradiation of the interior surface of the arterial segment just proximal to the thrombus. This facilitates smooth muscle relaxation and thus dilation of the arterial segment, and most unusually, of the thrombus also. This allows for efficient penetration of blood into and throughout the thrombus and presages recanalization of the artery. UV laser irradiation proceeds sequentially through the thrombus, as one segment after another is recanalized. We will first construct a prototype single-lumen catheter, which can admit, via separate channels, an optical fiber to conduct the UV laser light and also infusion of solutions, such as saline, X-ray contrast fluid, or drugs. We will then insert the device via a femoral artery under X-ray fluoroscopy, first to examine the effectiveness of this device to dilate the rat CCA, and then to use these experimental parameters to begin dethrombosis of pure platelet (PP) or platelet-fibrin-red cell (FPE) occlusive thrombi. It may be possible to observe the progress of dethrombosis by fluoroscopy even during UV irradiation, owing to only moderate absorption of the UV light by the X-ray contrast fluid. For the PP and FPE thrombi we will determine the time taken to recanalize the CCA after endoscopic UV treatment and compare these dissolution times to the corresponding times when UV treatment is applied in conjunction with a special thrombolytic (tPA) drug, reteplase, and to those times resulting from drug treatment itself. Finally, we will examine by histologic staining and microscopy the treated portion of the CCA for residual thrombotic material.
