Combined treatment with naloxone and the alpha2 adrenoceptor antagonist atipamezole reversed brain hypoxia induced by a fentanyl-xylazine mixture in a rat model.

Xylazine, a veterinary tranquillizer known by drug users as "Tranq", is being increasingly detected in people who overdose on opioid drugs, indicating enhanced health risk of fentanyl-xylazine mixtures. We recently found that xylazine potentiates fentanyl- and heroin-induced brain hypoxia and eliminates the rebound-like post-hypoxic oxygen increases. Here, we used oxygen sensors coupled with high-speed amperometry in rats of both sexes to explore the treatment potential of naloxone plus atipamezole, a selective α2-adrenoceptor antagonist, in reversing brain (nucleus accumbens) and periphery (subcutaneous space) hypoxia induced by a fentanyl-xylazine mixture.

Xylazine effects on opioid-induced brain hypoxia.

Rationale: Xylazine has emerged in recent years as an adulterant in an increasing number of opioid-positive overdose deaths in the United States. Although its exact role in opioid-induced overdose deaths is largely unknown, xylazine is known to depress vital functions and cause hypotension, bradycardia, hypothermia, and respiratory depression.

Objectives: In this study, we examined the brain-specific hypothermic and hypoxic effects of xylazine and its mixtures with fentanyl and heroin in freely moving rats.

The pattern of brain oxygen response induced by intravenous fentanyl limits the time window of therapeutic efficacy of naloxone.

Opioids induce respiratory depression resulting in coma or even death during overdose. Naloxone, an opioid antagonist, is the gold standard reversal agent for opioid intoxication, but this treatment is often less successful for fentanyl. While low dosing is thought to be a factor limiting naloxone's efficacy, the timing between fentanyl exposure and initiation of naloxone treatment may be another important factor.

Basic metabolic and vascular effects of ketamine and its interaction with fentanyl.

Ketamine is a short-acting general anesthetic with hallucinogenic, analgesic, and amnestic properties. In addition to its anesthetic use, ketamine is commonly abused in rave settings. While safe when used by medical professionals, uncontrolled recreational use of ketamine is dangerous, especially when mixed with other sedative drugs, including alcohol, benzodiazepines, and opioid drugs.

Basic physiological effects of ketamine-xylazine mixture as a general anesthetic preparation for rodent surgeries.

Among the numerous general anesthetics utilized in rodent surgical procedures, the co-administration of ketamine and xylazine is the current standard for induction and maintenance of surgical planes of anesthesia and pain control. In contrast to classical GABAergic anesthetics, which act to inhibit CNS activity, inducing muscle relaxation, sedation, hypothermia, and brain hypoxia, ketamine and xylazine act through different mechanisms to induce similar effects while also providing potent analgesia. By using three-point thermorecording in freely moving rats, we show that the ketamine-xylazine mixture induces modest brain hyperthermia, resulting from increased intra-cerebral heat production due to metabolic brain activation and increased heat loss due to skin vasodilation.

Rapid fluctuations in brain oxygenation during glucose-drinking behavior in trained rats.

Proper inflow of oxygen into brain tissue is essential for maintaining normal neural functions. Although oxygen levels in the brain's extracellular space depend upon a balance between its delivery from arterial blood and its metabolic consumption, the use of high-speed electrochemical detection revealed rapid increases in brain oxygen levels elicited by various salient sensory stimuli. These stimuli also increase intrabrain heat production, an index of metabolic neural activation, but these changes are slower and more prolonged than changes in oxygen levels.

A Novel Virtual Reality Medical Image Display System for Group Discussions of Congenital Heart Disease: Development and Usability Testing.

Background: The complex 3-dimensional (3D) nature of anatomical abnormalities in congenital heart disease (CHD) necessitates multidisciplinary group discussions centered around the review of medical images such as magnetic resonance imaging. Currently, group viewings of medical images are constrained to 2-dimensional (2D) cross-sectional displays of 3D scans. However, 2D display methods could introduce additional challenges since they require physicians to accurately reconstruct the images mentally into 3D anatomies for diagnosis, staging, and planning of surgery or other therapies.

Novel, 3D Display of Heart Models in the Postoperative Care Setting Improves CICU Caregiver Confidence.

Background: Postoperative care delivered in the pediatric cardiac intensive care unit (CICU) relies on providers' understanding of patients' congenital heart defects (CHDs) and procedure performed. Novel, bedside use of virtual, three-dimensional (3D) heart models creates access to patients' CHD to improve understanding. This study evaluates the impact of patient-specific virtual 3D heart models on CICU provider attitudes and care delivery.

Registered 3-D ultrasound and digital stereotactic mammography for breast biopsy guidance.

Large core needle biopsy is a common procedure used to obtain histological samples when cancer is suspected in diagnostic breast images. The procedure is typically performed under image guidance, with freehand ultrasound and stereotactic mammography (SM) being the most common modalities used. To utilize the advantages of both modalities, a biopsy device combining three-dimensional ultrasound (3DUS) and digital SM imaging with computer-aided needle guidance was developed.