Selective brain hypothermia: feasibility and safety study of a novel method in five patients.

BACKGROUND/OBJECTIVE: Reduction of brain temperature remains the most common method of neuroprotection against ischemic injury employed during cardiac surgery. However, cooling delivered via the cardiopulmonary bypass circuit is brief and cooling the body core along with the brain has been associated with a variety of unwanted effects. This study investigated the feasibility and safety of a novel selective brain cooling approach to induce rapid, brain-targeted hypothermia independent of the cardiopulmonary bypass circuit. METHODS: This first-in-human feasibility study enrolled five adults undergoing aortic valve replacement with cardiopulmonary bypass support. During surgery, the NeuroSave system circulated chilled saline within the pharynx and upper esophagus. Brain and body core temperature were continuously monitored. Adverse effects, cardiopulmonary function, and device function were noted. RESULTS: Patient 1 received cooling fluid for an insignificant period, and Patients 2-5 successfully underwent the cooling procedure using the NeuroSave system for 56-89 minutes. Cooling fluid was 12°C for Patients 1-3, 6°C for Patient 4, and 2°C for Patient 5. There were no NeuroSave-related adverse events and no alterations in cardiopulmonary function during NeuroSave use. Brain temperature decreased by 3°C within 15 minutes and remained at least 3.5°C colder than the body core. During a brief episode of hypotension in one patient, the brain cooled an additional 4°C in 2 minutes, briefly reaching 27.4°C. CONCLUSION: The NeuroSave system can induce rapid brain-targeted hypothermia and simultaneously maintain a favorable body-brain temperature gradient, even during hypotension. Further studies are required to evaluate the function of the system during longer periods of use.

Novel Focal Therapeutic Hypothermia Device for Treatment of Acute Neurologic Injury: Large Animal Safety and Efficacy Trial.

Objective Therapeutic hypothermia is a potentially powerful and controversial clinical tool for neuroprotection following acute neurologic pathology, particularly vascular injury. Indeed, therapeutic hypothermia remains a standard of care for postcardiac arrest ischemia and acute neonatal hypoxic-ischemic encephalopathy, improving both survival and outcomes. Although therapeutic hypothermia remains promising for cellular and systems-based neuronal protection in other neurologic injury states, the systemic side effects have limited clinical utility, confounded analysis of potential neurologic benefits, and precluded the completion of meaningful clinical trials. Methods To address such limitations, we developed and tested a novel, minimally invasive, neurocritical care device that employs continuous circulation of cold saline through the pharyngeal region to deliver focal cerebrovascular cooling. We conducted a preclinical safety and efficacy trial in six adult porcine animals to assess the validity and functionality of the NeuroSave device, and assess cooling potential following middle cerebral artery occlusion ( n = 2). Results NeuroSave consistently lowered brain parenchymal temperature by a median of 9°C relative to core temperature within 60 minutes of initiation, including in ischemic cerebral parenchyma. The core body temperature experienced a maximal reduction of 2°C, or 5% of body temperature, with no associated adverse effects identified. Conclusion The present study uses a large animal preclinical model to demonstrate the safety and efficacy of a novel, noninvasive device for the induction of robust and systemically safe hypothermia within the brain.

The spatial and temporal heterogeneity of regional ventilation: comparison of measurements by two high-resolution methods.

High-resolution estimates of ventilation distribution in normal animals utilizing deposition of fluorescent microsphere aerosol (FMS technique) demonstrate substantial ventilation heterogeneity, but this finding has not been confirmed by an independent method. Five supine anesthetized sheep were used to compare the spatial and temporal heterogeneity of regional ventilation measured by both the FMS technique and by a ventilation model utilizing the data from computed tomography images of xenon gas washin (CT/Xe technique). An aerosol containing 1 microm fluorescent microspheres (FMS) was administered via a mechanical ventilator delivering a 2-s end-inspiration hold during each breath. Following the aerosol administration, sequential CT images of a transverse lung slice were acquired during each end-inspiration hold during washin of a 65% Xenon/35% oxygen gas mixture (CT/Xe technique). Four paired FMS and CT/Xe measurements were done at 30 min intervals, after which the animals were sacrificed. The lungs were extracted, air-dried and sliced in 1cm transverse sections. The lung section corresponding to the CT image was cut into 1 cm3 cubes, with notation of spatial coordinates. The individual cubes were soaked in solvent and the four fluorescent signals were measured with a fluorescence spectrophotometer. The color signals were normalized by the mean signal for all pieces and taken as the FMS estimate of ventilation heterogeneity. The CT images were clustered into 1 cm3 voxels and the rate of increase in voxel density was used to calculate voxel ventilation utilizing the model of . The regional ventilation voxel measurements were normalized by the mean value to give a CT/Xe estimate of ventilation heterogeneity comparable to the normalized FMS measurements. The overall of heterogeneity of ventilation at the 1 cm3 level of resolution was comparable by both techniques, with substantial differences among animals (coefficient of variation ranging from 37% to 74%). The repeated within-animal measurements by both techniques gave consistent values. Both techniques showed comparable large-scale distribution of regional ventilation in the caudal lobes of the supine animals. There were appreciable differences in the temporal variability of ventilation among animals. This study provides an independent confirmation of the scale-dependent heterogeneity of ventilation described by previous FMS aerosol studies of ventilation heterogeneity.

Standardized qualitative evaluation of scar tissue properties in an animal wound healing model.

There is a great need to establish reproducible methods for evaluative studies of wound treatment and wound healing. Validation of the healing process through optical techniques, as well as histologic and immunohistochemical methodologies, have been improved and to some extent have become well-established assays. Data relating to biomechanical properties, e.g., evaluation of the tensile strength of scar tissue that forms in experimental wound treatment strategies, are less widely available. We chose the domestic pig as an animal model in which to examine epidermal wound healing. We implanted specially made chambers that served to isolate the wounds and prevent epidermal migration from the edges. We performed histologic and immunohistochemical analyses as well as evaluation of biomechanical qualities of scar tissue using laser tensiometry. Pig skin is well suited for wound healing studies, and wound creation, implantation of the chambers, and the regular changing of dressings could all be carried out in the operating theater. In addition to established macroscopic evaluation and microscopic documentation, the need for objective biomechanical assessment of scar tissue by measuring tensile strength has been met using laser tensiometry. By optimizing methods for measuring tensile strength, it is possible to evaluate the biomechanical quality of scar tissue formed following different courses of wound treatment, as well as histologic assessment.