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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., Competing Interests: Conflict of Interest L.P.C., A.P., C.S.G., D.D., Y.H.D., D.R.J., A.L., K.R.G., R.K., and D.F.K. have no conflict or competing interest to declare. S.R. and T.K. are investors and hold share in NeuroSave Inc. K.H. is a paid consultant and holds share in NeuroSave Inc. Relevant patents: US-8308787. Rapid cooling of body and/or brain by irrigation with a cooling liquid. US-9320644 Noninvasive systems, devices, and methods for selective brain cooling., (Thieme. All rights reserved.)

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.

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.

We propose a model to measure both regional ventilation (V) and perfusion (Q) in which the regional radiodensity (RD) in the lung during xenon (Xe) washin is a function of regional V (increasing RD) and Q (decreasing RD). We studied five anesthetized, paralyzed, mechanically ventilated, supine sheep. Four 2.5-mm-thick computed tomography (CT) images were simultaneously acquired immediately cephalad to the diaphragm at end inspiration for each breath during 3 min of Xe breathing. Observed changes in RD during Xe washin were used to determine regional V and Q. For 16 mm(3), Q displayed more variance than V: the coefficient of variance of Q (CV(Q)) = 1.58 +/- 0.23, the CV of V (CV(V)) = 0.46 +/- 0.07, and the ratio of CV(Q) to CV(V) = 3.5 +/- 1.1. CV(Q) (1.21 +/- 0.37) and the ratio of CV(Q) to CV(V) (2.4 +/- 1.2) were smaller at 1,000-mm(3) scale, but CV(V) (0.53 +/- 0.09) was not. V/Q distributions also displayed scale dependence: log SD of V and log SD of Q were 0.79 +/- 0.05 and 0.85 +/- 0.10 for 16-mm(3) and 0.69 +/- 0.20 and 0.67 +/- 0.10 for 1,000-mm(3) regions of lung, respectively. V and Q measurements made with CT and Xe also demonstrate vertically oriented and isogravitational heterogeneity, which are described using other methodologies. Sequential images acquired by CT during Xe breathing can be used to determine both regional V and Q noninvasively with high spatial resolution.

Hyperventilation with mixtures of O2 and CO2 has long been known to enhance carbon monoxide (CO) elimination at low HbCO levels in animals and humans. The effect of this therapy on oxygen delivery (DO2) has not been studied. Isocapnic hyperventilation utilizing mechanical ventilation may decrease cardiac output and therefore decrease DO2 while increasing CO elimination. We studied the effects of isocapnic hyperventilation on five adult mechanically ventilated sheep exposed to multiple episodes of severe CO poisoning. Five ventilatory patterns were studied: baseline minute ventilation (RR. VT), twice (2. RR) and four times (4. RR) baseline respiratory rate, and twice (2. VT) and four times (4. VT) baseline tidal volume. The mean carboxyhemoglobin (HbCO) washout half-time (t1/2) was 14.3 +/- 1.6 min for RR. VT, decreasing to 9.5 +/- 0.9 min for 2. RR, 8.0 +/- 0.5 min for 2. VT, 6.2 +/- 0.5 min for 4. RR, and 5.2 +/- 0.5 min for 4. VT. DO2 was increased during hyperventilation compared with baseline ventilation for 2. VT, 4. RR, and 4. VT ventilatory patterns. Isocapnic hyperventilation, in our animal model, did not alter arterial or pulmonary blood pressures, arterial pH, or cardiac output. Isocapnic hyperventilation is a promising therapy for CO poisoning.

Two patients with chronic, severe, episodic dyspnea underwent prolonged, extensive, and invasive evaluations without a diagnosis being made. Both were subsequently diagnosed with fibromyalgia, and therapy directed at this condition resulted in resolution of their symptoms. Fibromyalgia is rarely included in the differential diagnosis of dyspnea, and timely diagnosis and treatment may be delayed. However, this condition must be considered because it can only be established by seeking the appropriate history and physical findings.