[Clinical, laboratory and morphological comparisons in cellular alteration under conditions of hypoxia].

Objective: To compare structural changes in tissues with clinical and laboratory parameters and immunohistochemical determination of proteins HIF1α, HIF2α, caspase-3 during cellular alteration under conditions of hypoxia in the liver and kidneys in an experiment on pigs.

Material And Methods: Laboratory parameters related to the state of gas exchange (decrease in partial pressure of arterial blood oxygen (PaO2), arterial blood saturation, lactate level, kidney function (creatinine, urea) and liver (ALT, AST, bilirubin) in 18 animals were analyzed in comparison with the results of a morphological study. Histological examination evaluated alterative and inflammatory tissue changes of varying severity, and also determined the expression of transcription factors HIF1α and HIF2α and a marker of apoptosis - caspase-3.

Lack of neuropathological changes in rats administered tedizolid phosphate for nine months.

Tedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.

Nonclinical and pharmacokinetic assessments to evaluate the potential of tedizolid and linezolid to affect mitochondrial function.

Prolonged treatment with the oxazolidinone linezolid is associated with myelosuppression, lactic acidosis, and neuropathies, toxicities likely caused by impairment of mitochondrial protein synthesis (MPS). To evaluate the potential of the novel oxazolidinone tedizolid to cause similar side effects, nonclinical and pharmacokinetic assessments were conducted. In isolated rat heart mitochondria, tedizolid inhibited MPS more potently than did linezolid (average [± standard error of the mean] 50% inhibitory concentration [IC50] for MPS of 0.

STP position paper: Recommended practices for sampling and processing the nervous system (brain, spinal cord, nerve, and eye) during nonclinical general toxicity studies.

The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central nervous system (CNS) and peripheral nervous system (PNS) in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be weighed and trimmed similarly for all animals in a study. Certain structures should be sampled regularly: caudate/putamen, cerebellum, cerebral cortex, choroid plexus, eye (with optic nerve), hippocampus, hypothalamus, medulla oblongata, midbrain, nerve, olfactory bulb (rodents only), pons, spinal cord, and thalamus.

An oral developmental neurotoxicity study of decabromodiphenyl ether (DecaBDE) in rats.

Background: Decabromodiphenyl ether (DecaBDE; CASRN 1163-19-5) is a flame retardant used in a variety of manufactured products. A single oral dose of 20.1 mg/kg administered to mice on postnatal day 3 has been reported to alter motor activity at 2, 4, and 6 months of age.

Developmental neurotoxicity study of dietary bisphenol A in Sprague-Dawley rats.

This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F(1) offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity.

A 90-day repeated dose oral (gavage) toxicity study of perfluorohexanoic acid (PFHxA) in rats (with functional observational battery and motor activity determinations).

Possible toxic effects of perfluorohexanoic acid (PFHxA) were evaluated when administered orally by gavage to rats at levels up to 200mg/kg/day for 90 days. Lower body weight gains were noted in the 10, 50 and 200mg/kg/day group males (not dose-responsive) throughout dosing. Other changes included lower red blood cell parameters, higher reticulocyte counts and lower globulin in the 200mg/kg/day group males and females, higher liver enzymes in males at 50 and 200mg/kg/day, lower total protein and higher albumin/globulin ratio, and lower cholesterol, calcium in males at 200mg/kg/day.

Inhalation carcinogenicity study with nickel metal powder in Wistar rats.

Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.

28-Day oral (gavage) toxicity studies of green tea catechins prepared for beverages in rats.

The beneficial health effects associated with drinking green tea are widely considered to be due primarily to tea catechins. Heat treatment of marketed green tea beverages for sterilization causes epimerization and/or polymerization of tea catechins. Safety studies on heat-treated tea catechins are limited.

Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain.

Dextromethorphan is a widely used antitussive agent, also showing increased recreational abuse. Dextromethorphan and its metabolite dextrorphan are non-competitive antagonists at the N-methyl-d-aspartate (NMDA) receptor ion channel. Single doses of some NMDA receptor antagonists produce neuropathologic changes in neurons of the retrosplenial/posterior cingulate cortices (RS/PC), characterized by vacuolation or neurodegeneration.

Critical time window for intra-arrest cooling with cold saline flush in a dog model of cardiopulmonary resuscitation.

Background: Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation (CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model.

Developmental neurotoxicity study of styrene by inhalation in Crl-CD rats.

This study was conducted to assess potential adverse functional and/or morphological effects of styrene on the neurological system in the F2 offspring following F0 and F1 generation whole-body inhalation exposures. Four groups of male and female Crl:CD (SD)IGS BR rats (25/sex/group) were exposed to 0, 50, 150, and 500 ppm styrene for 6 hr daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure continued for the F0 and F1 females throughout mating and through gestation day 20.

Suspended animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs.

Background: We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (suspended animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom suspended animation may buy time for resuscitative surgery and delayed resuscitation.

Mild hypothermia during prolonged cardiopulmonary cerebral resuscitation increases conscious survival in dogs.

Objective: Therapeutic hypothermia during cardiac arrest and after restoration of spontaneous circulation enables intact survival after prolonged cardiopulmonary cerebral resuscitation (CPCR). The effect of cooling during CPCR is not known. We hypothesized that mild to moderate hypothermia during CPCR would increase the rate of neurologically intact survival after prolonged cardiac arrest in dogs.

Survival without brain damage after clinical death of 60-120 mins in dogs using suspended animation by profound hypothermia.

Objectives: This study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60-120 mins, with preservation (suspended animation) induced immediately after the start of exsanguination cardiac arrest.

Design: Prospective experimental comparison of three arrest times, without randomization.

Setting: University research laboratory.

Antioxidant Tempol enhances hypothermic cerebral preservation during prolonged cardiac arrest in dogs.

The authors are systematically exploring pharmacologic preservation for temporarily unresuscitable exsanguination cardiac arrest in dogs. They hypothesized that the antioxidant Tempol improves cerebral outcome when added to aortic saline flush at the start of cardiac arrest. In study A, no drug (n = 8), Tempol 150 mg/kg (n = 4), or Tempol 300 mg/kg (n = 4) was added to 25 mL/kg saline flush at 24 degrees C (achieving mild cerebral hypothermia) at the start of 20-minute cardiac arrest.

Fructose-1,6-bisphosphate and MK-801 by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 min in dogs. An exploratory study.

In our exsanguination cardiac arrest (CA) outcome model in dogs we are systematically exploring suspended animation (SA), i.e. preservation of brain and heart immediately after the onset of CA to enable transport and resuscitative surgery during CA, followed by delayed resuscitation.

Thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs. An exploratory study.

We are systematically exploring in our exsanguination cardiac arrest (CA) outcome model in dogs suspended animation (SA), i.e. immediate preservation of brain and heart for resuscitative surgery during CA, with delayed resuscitation.

Peritoneal ventilation with oxygen improves outcome after hemorrhagic shock in rats.

Objective: In experimental pulmonary consolidation with hypoxemia in rabbits, peritoneal ventilation (PV) with 100% oxygen (PV-O2) improved PaO2. We hypothesized that PV-O2 could improve outcome after hemorrhagic shock (HS) with normal lungs, by mitigating dysoxia of the abdominal viscera.

Design: Randomized, controlled, laboratory animal study.

Rapid hypothermic aortic flush can achieve survival without brain damage after 30 minutes cardiac arrest in dogs.

Background: Neither exsanguination to pulselessness nor cardiac arrest of 30 min duration can be reversed with complete neurologic recovery using conventional resuscitation methods. Techniques that might buy time for transport, surgical hemostasis, and initiation of cardiopulmonary bypass or other resuscitation methods would be valuable. We hypothesized that an aortic flush with high-volume cold normal saline solution at the start of exsanguination cardiac arrest could rapidly preserve cerebral viability during 30 min of complete global ischemia and achieve good outcome.

Rapid induction of mild cerebral hypothermia by cold aortic flush achieves normal recovery in a dog outcome model with 20-minute exsanguination cardiac arrest.

Objectives: Resuscitation attempts in trauma victims who suffer cardiac arrest (CA) from exsanguination almost always fail. The authors hypothesized that an aortic arch flush with cold normal saline solution (NSS) at the start of exsanguination CA can preserve cerebral viability during 20-minute no-flow.

Methods: Twelve dogs were exsanguinated over 5 minutes to CA of 20-minute no-flow, resuscitated by cardiopulmonary bypass, followed by post-CA mild hypothermia (34 degrees C) continued to 12 hours, controlled ventilation to 20 hours, and intensive care to 72 hours.

Suspended animation for delayed resuscitation from prolonged cardiac arrest that is unresuscitable by standard cardiopulmonary-cerebral resuscitation.

Standard cardiopulmonary-cerebral resuscitation fails to achieve restoration of spontaneous circulation in approximately 50% of normovolemic sudden cardiac arrests outside hospitals and in essentially all victims of penetrating truncal trauma who exsanguinate rapidly to cardiac arrest. Among cardiopulmonary-cerebral resuscitation innovations since the 1960s, automatic external defibrillation, mild hypothermia, emergency (portable) cardiopulmonary bypass, and suspended animation have potentials for clinical breakthrough effects. Suspended animation has been suggested for presently unresuscitable conditions and consists of the rapid induction of preservation (using hypothermia with or without drugs) of viability of the brain, heart, and organism (within 5 mins of normothermic cardiac arrest no-flow), which increases the time available for transport and resuscitative surgery, followed by delayed resuscitation.

Thiopental combination treatments for cerebral resuscitation after prolonged cardiac arrest in dogs. Exploratory outcome study.

We postulate that mitigating the multifactorial pathogenesis of postischemic encephalopathy requires multifaceted treatments. In preparation for expensive definitive studies, we are reporting here the results of small exploratory series, compared with historic controls with the same model. We hypothesized that the brain damage mitigating effect of mild hypothermia after cardiac arrest can be enhanced with thiopental loading, and even more so with the further addition of phenytoin and methylprednisolone.

Adenosine by aortic flush fails to augment the brain preservation effect of mild hypothermia during exsanguination cardiac arrest in dogs - an exploratory study.

Most trauma cases with rapid exsanguination to cardiac arrest (CA) in the field, as well as many cases of normovolemic sudden cardiac death are 'unresuscitable' by standard cardiopulmonary-cerebral resuscitation (CPCR). We are presenting a dog model for exploring pharmacological strategies for the rapid induction by aortic arch flush of suspended animation (SA), i.e.

Hypothermic aortic arch flush for preservation during exsanguination cardiac arrest of 15 minutes in dogs.

Background: Trauma victims rarely survive cardiac arrest from exsanguination. Survivors may suffer neurologic damage. Our hypothesis was that a hypothermic aortic arch flush of 500 mL of isotonic saline solution at 4 degrees C, compared with 24 degrees C (room temperature), administered at the start of prolonged exsanguination cardiac arrest (CA) would improve functional neurologic outcome in dogs.