Safety evaluation of the Guardian device on the common carotid artery in sheep.

Background: Pulse pressure intensity in middle-aged adults is a risk factor for dementia. The Guardian device (The Brain Protection Company, Sydney, Australia) has been developed to reduce pulse pressure, as a potential therapy. Objectives: The aim of this study was to evaluate the safety of the Guardian, a novel pulse modulation device designed to reduce the intensity of the pulse pressure that penetrates into the cerebral small vessels. The Guardian is a helix that gently wraps around the common carotid artery (CCA) to slightly change its shape, to absorb pulsatility, without lowering flow. Methods: The Guardian was implanted bilaterally on the CCAs of 10 mature sheep for chronic implant periods of 3, 6 or 8 months. The ratio of internal device diameter to outer diameter of the CCA varied from 63% to 92% (n = 20). The implant position on the vessel was marked surgically at implant. Gross pathology and histopathology of the CCA were examined at 3- and 6-months post explant. Most devices were explanted using open surgery, however minimally invasive surgical explant techniques were examined in 2 animals to assess the potential of this approach for explant in humans if required. Results: The Guardian was successfully implanted with no adverse events, and minimally invasive explant appeared to be viable for removal. Following implant, the device was surrounded by a thin fibrous capsule, with similar pathology at 3- and 6-months. Minimal or no movement was observed. CCA sections appeared histologically normal, with no evidence of thrombosis, stenosis, fibrosis, chronic inflammatory response, or vessel degeneration. Conclusions: The feasibility of surgical implantation and biomaterial safety of the Guardian was confirmed over 8 months. Minimally invasive explant of the Guardian has the potential to be viable. Further work is required to demonstrate efficacy in vitro and/or in vivo before evaluation in humans.

The common carotid artery provides significant pressure wave dampening in the young adult sheep.

BACKGROUND: It has been established that the central elastic arteries of the mammalian circulation dampen the high pulse pressure emanating from the left ventricle, so that the pulsations in distal arterioles, such as in the cerebral circulation, are of lower amplitude than more centrally. However, the contribution of the common carotid artery (CCA) to protection of the cerebral microvasculature from high pulse pressure is not known, specifically to what extent viscoelastic energy dissipation in the arterial wall might contribute to the shock absorbing function of the large conduit arteries. METHODS: Young adult sheep (n = 6) were anaesthetised and their CCAs (n = 7) exposed. Pressure catheters were inserted 10-15 cm apart, proximally and distally in the CCA; a flow probe was placed proximally on the vessel. RESULTS: The median dp/dtmax on the pressure rise of the arterial wave upstroke for the proximal CCA was 619 mm Hg/s and for the distal CCA it was significantly lower, at 197 mm Hg/s (p = 0.0156; n = 7). The median pulse pressure of the proximal CCA was 24 mm Hg/s; distal pulse pressure was significantly lower, at 18 mm Hg/s (p = 0.0156; n = 7). The median flow rate was 0.97 L/min with an interquartile range from 0.51 to 1.15 L/min. CONCLUSIONS: The native CCA in the young adult sheep is an effective "pressure dampener" in the arterial circulation, reducing both pressure slope and pulse pressure, most likely via viscous dampening in the arterial wall.