A novel swine model of subarachnoid hemorrhage-induced cerebral vasospasm.

OBJECTIVE: One of the most serious complications following subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI) secondary to symptomatic vasospasm. An animal model mimicking post SAH vasospasm is essential for enabling the translation of newer technologies from the conceptual phase to animal studies, and eventually to clinical trials. Various animal models of DCI following SAH have been reported, with canine models being the most common. Due to the similarity of the swine cardiovascular system and its dimensions to the human's system, the main objective of this study was to establish a consistent and quantitatively representative model of SAH-induced vasospasm in swine. MATERIALS AND METHODS: Twelve female swines (57 ± 3 kg) were injected twice (with a 2-day interval between injections) with autologous blood into the subarachnoid space at the level of C2-3 vertebrae. Different volumes were injected to identify clinical and radiological changes. The effect of volume variations on hematoma size and vasospasm intensity in the circle of Willis arteries were studied 7-14 days after the first injection using ascending pharyngeal angiographic measurements of vessel diameter. Neurological outcome using a modified scoring table based on clinical parameters (e.g., appetite, behavior, walking, posture, and eye movement) was recorded. RESULTS: Our results demonstrate that between volume combinations, intrathecal injection of 12 ml followed by 15 ml, with a 2-day interval in between, resulted in the most extensive angiographically-assessed vasospasm 12 ± 2 days following the first injection. The degree of vasospasm in the intracranial internal carotid artery was 22% and 16% for the left and right sides, respectively. Vasoconstriction of the anterior cerebral artery was 34% and 27% for the left and right sides, respectively. The vasoconstriction was not associated with either overt clinical signs or clinical outcome, which is indicative of an ischemic event. CONCLUSIONS: The relative scarcity of swine models for SAH-induced vasospasm motivated us to develop and quantify a straightforward protocol for producing consistent mild-to-moderate vasospasm following SAH. As swine is commonly used in translational cardiovascular research, we believe that this study constitutes an important phase in the study of SAH and in developing pharmacological agents and medical devices for interventions.

Fluid structure interaction with contact surface methodology for evaluation of endovascular carotid implants for drug-resistant hypertension treatment.

Drug-resistant hypertensive patients may be treated by mechanical stimulation of stretch-sensitive baroreceptors located in the sinus of carotid arteries. To evaluate the efficacy of endovascular devices to stretch the carotid sinus such that the induced strain might trigger baroreceptors to increase action potential firing rate and thereby reduce systemic blood pressure, numerical simulations were conducted of devices deployed in subject-specific carotid models. Two models were chosen--a typical physiologic carotid and a diminutive atypical physiologic model representing a clinically worst case scenario--to evaluate the effects of device deployment in normal and extreme cases, respectively. Based on the anatomical dimensions of the carotids, two different device sizes were chosen out of five total device sizes available. A fluid structure interaction (FSI) simulation methodology with contact surface between the device and the arterial wall was implemented for resolving the stresses and strains induced by device deployment. Results indicate that device deployment in the carotid sinus of the physiologic model induces an increase of 2.5% and 7.5% in circumferential and longitudinal wall stretch, respectively, and a maximum of 54% increase in von Mises arterial stress at the sinus wall baroreceptor region. The second device, deployed in the diminutive carotid model, induces an increase of 6% in both circumferential and longitudinal stretch and a 50% maximum increase in von Mises stress at the sinus wall baroreceptor region. Device deployment has a minimal effect on blood-flow patterns, indicating that it does not adversely affect carotid bifurcation hemodynamics in the physiologic model. In the smaller carotid model, deployment of the device lowers wall shear stress at sinus by 16% while accelerating flow entering the external carotid artery branch. Our FSI simulations of carotid arteries with deployed device show that the device induces localized increase in wall stretch at the sinus, suggesting that this will activate baroreceptors and subsequently may control hypertension in drug-resistant hypertensive patients, with no consequential deleterious effects on the carotid sinus hemodynamics.

A novel endovascular device for emboli rerouting: part I: evaluation in a Swine model.

BACKGROUND AND PURPOSE: The feasibility and safety of a novel endovascularly delivered tubular mesh designed to reroute emboli away from a critical artery as a means of ischemic stroke prevention was tested in vitro and in vivo. METHODS: Emboli rerouting efficacy was assessed in vitro. Perfusion through the external femoral artery that was jailed by the device, cellular proliferation rate over the jailing mesh, and the resulting tissue coverage of the orifice were assessed in the swine iliofemoral bifurcation. Device-induced embolization was assessed in a swine kidney model. RESULTS: In vitro experiments demonstrated that particles as small as 60% of the pore dimension can be rerouted by the device, although at low efficacy, and rerouting efficacy approached 100% as the particle size approached the pore dimension. Repeat assessment of flow preimplantation and at various follow-up times by Doppler ultrasound showed no significant changes in the perfusion ratio of the jailed branch to the parent artery or the jailed branch to the naive contralateral artery either as a result of device implantation or at the follow-up times. Tissue coverage over the jailed ostium was limited to approximately 12% after stabilization. Cellular proliferation rate gradually decreased to diminishing level approximately 22 weeks postimplantation. The devices implanted across the renal arteries did not demonstrate any device-induced embolization after 1 month. CONCLUSIONS: It is proposed that this device could be used to reroute emboli away from important intracranial vessels as a means of stroke prevention.

A novel carotid device for embolic diversion: lessons learned from a "first in man" trial in patients with atrial fibrillation.

PURPOSE: This study was designed to investigate a novel device that was developed to direct emboli away from the internal carotid artery to the external carotid artery to prevent embolic stroke while avoiding the necessity for anticoagulation with warfarin. METHODS: A stent-like, self-expandable filter was developed consisting of fine cobalt alloy mesh. After promising preclinical animal testing, the device was implanted into the common carotid artery extending into the external carotid artery in three patients with atrial fibrillation, each of whom were at high-risk for cerebral emboli and were suboptimal candidates for anticoagulation. Follow-up was performed clinically and with carotid duplex ultrasound. RESULTS: The implantation was successful in all three patients. Unrestricted flow through the filter was demonstrated in each patient at 6 months by duplex sonography. However, at 7 months ultrasound demonstrated occlusion of the internal carotid artery filter in one patient, which was subsequently confirmed by angiography. Subtotal filter occlusion occurred in a second patient at 14 months. Neither patient had clinical symptoms. Both internal carotid arteries were successfully recanalized using standard angioplasty techniques without complication. The third patient had completely normal carotid blood flow at 29 months follow-up. CONCLUSIONS: Implantation of a novel device intended to divert emboli away from the internal carotid artery was feasible, but resulted in occlusive neointimal proliferation in two of three patients. These results demonstrate a discrepancy from the findings of preclinical animal studies and human investigation.

Similarity of the swine vasculature to the human carotid bifurcation: analysis of arterial diameters.

PURPOSE: We assessed the similarities of the iliac bifurcation in two breeds of swine to the known human carotid bifurcation, in order to assess its applicability as a preclinical model of the human carotid bifurcation. MATERIALS AND METHODS: Mixed-Landrace crossbreed (domestic; n = 66) and Yucatan miniswine (Yucatan; n = 13) were studied. The diameters of the iliac bifurcation arteries were measured from angiographic pictures, the relations between the arterial diameters and the animal's weight assessed, and diametrical ratios calculated. Findings were compared with the known human carotid bifurcation. RESULTS: The external iliac diameter (approximately 6-7mm) in the lower weight swine was similar to the known human common carotid artery. The best similarity was found between the diametrical ratios of the human internal to common carotid artery (mean 0.63) to the swine profunda to external iliac (means 0.68 and 0.65 for the domestic and Yucatan, respectively). The arterial diameters of the domestic swine were highly correlated with their weight that increased considerably with time, while in the Yucatan group, arterial diameters did not change with increasing weight and the average weight increase rate was low. Thus, the estimated arterial diameter increase rate over time was high in the domestic while minor in the Yucatan group. CONCLUSIONS: Similarities were found between the swine iliac bifurcation arteries to the human carotid bifurcation in terms of diameters, diametrical ratios and angle. The swine iliac bifurcation may be used for preclinical endovascular research of devices intended to the human carotid bifurcation, with miniswine strains a preferable model for long-term studies.