Pulsed Laser-Induced Liquid Jet Microcatheter System for Rapid and Reliable Fibrinolysis in Acute Cerebral Embolisms: Experiments on Safety and Preliminary Application in Porcine Cranial Vessels

Abstract

The authors have incorporated a holmium: YAG laser-induced liquid jet (LILJ) within a microcatheter for rapid, safe, and reliable fibrinolysis, and reported its effectiveness in vitro. The purpose of this study is to evaluate an appropriate operation mode to minimize debris size and to apply the system in in vivo experiments using a porcine cranial artery model. Evaluation of debris size: The relationships between laser energy and the size of the debris have been evaluated in in vitro experiments. Pulsed LILJ (3 Hz for 60 seconds) were applied to the artificial thrombi (made out of human blood taken from healthy volunteers) in a teflon tube (internal diameter: 4 mm) in the following operation modes: firstly, the laser energy was set at 0.6, 0.8, 1.0, 1.2, 1.4 W, and urokinase (UK) solution (12000 IU/mL) was supplied at rate of 40 mL/hour. In the 0.8 W operation, the concentrations of UK were changed between 0, 1200, 6000, and 12000 lU/mL. Immediately after application of LILJ, the remnant debris were collected and fixed with formaldehyde, and the size and numbers of debris were evaluated under a light microscope. Application in a porcine cranial artery model: The acute embolic models were made using four pigs: the artificial thrombi were made of porcine blood and 1 mL of embolus was used to occlude the left lingual artery via a catheter. After occlusion of lingual artery for 30 minutes, the LILJ microcatheter system was brought to the occlusion site via a guiding catheter and with the assistance of guide-wire. After every 2.5 minutes application of LILJ, angiographies were performed to evaluate the recanalization of the occluded vessels. Cold UK (1200 IU/mL) solution (4 degrees C) was supplied at the rate of 40 mL/hour with laser operation (2 pigs) and without laser operation (2 pigs: control). The pigs were decapitated, and vessels at the laser irradiation sites were obtained to evaluate the damage to the vessel wall. Evaluation of debris size: After application of UK solution by the LILJ (12000 lU/mL), 48.7 (1.0 W) to 72.0% (0.8 W) of debris were under 200 microm in size, while 3.7 (0.8 W) to 17.0% (1.2 W) of them exceeded 600 microm, and the 0.8 W operation mode had a tendency to be the better operation mode. During the 0.8 W operation mode, 58 (without UK) to 72% (12000 lU/mi) of debris were under 200 microm in size, while 3.5 (12000 lU/mL) to 8.5% (without UK) of them exceeded 600 microm. Application in a porcine cranial artery model: Recanalization of the occluded vessels was obtained at 15 and 20 minutes in the treatment group. Histological specimens showed neither apparent mechanical nor thermal damage. Although an additional system to collect debris, which cannot be dealt with in the pharmacological effect of fibrinolytics in the short-term, should be developed, the present results show the possibility of the LILJ microcatheter system to become a useful assistant device for the mechanical fragmentation of embolus and the enhancement of fibrinolytics.