Sanguinate's effect on pial arterioles in healthy rats and cerebral oxygen tension after controlled cortical impact.

Sanguinate, a polyethylene glycol-conjugated carboxyhemoglobin, was investigated for cerebral vasoactivity in healthy male Sprague-Dawley rats (Study 1) and for its ability to increase brain tissue oxygen pressure (PbtO2) after controlled cortical impact (CCI) - traumatic brain injury (TBI) (Study 2). In both studies ketamine-acepromazine anesthetized rats were ventilated with 40% O2. In Study 1, a cranial window was used to measure the diameters of medium - (50-100µm) and small-sized (<50µm) pial arterioles before and after four serial infusions of Sanguinate (8mL/kg/h, cumulative 16mL/kg IV), volume-matched Hextend, or normal saline. In Study 2, PbtO2 was measured using a phosphorescence quenching method before TBI, 15min after TBI (T15) and then every 10min thereafter for 155min. At T15, rats received either 8mL/kg IV Sanguinate (40mL/kg/h) or no treatment (saline, 4mL/kg/h). Results showed: 1) in healthy rats, percentage changes in pial arteriole diameter were the same among the groups, 2) in TBI rats, PbtO2 decreased from 36.5±3.9mmHg to 19.8±3.0mmHg at T15 in both groups after TBI and did not recover in either group for the rest of the study, and 3) MAP increased 16±4mmHg and 36±5mmHg after Sanguinate in healthy and TBI rats, respectively, while MAP was unchanged in control groups. In conclusion, Sanguinate did not cause vasoconstriction in the cerebral pial arterioles of healthy rats but it also did not acutely increase PbtO2 when administered after TBI. Sanguinate was associated with an increase in MAP in both studies.

[Effects of low concentration carbon monoxide on human physiological function].

Human volunteers were exposed to various low concentrations of carbon monoxide (CO) in a closed cabin. The results showed that 35 mg/m3 of CO caused slight subjective symptoms and reduction in contrast vision, operating efficiency and T-wave of ECG. At 80 mg/m3 and 115 mg/m3 the above changes were more severe and a rise in hearing threshold level was observed. It demonstrated that an inhibitory effect on the CNS and heart were caused by low concentrations of CO. According to the absorption curves for human exposed to CO, it is suggested that the sense effect level and vision effect level for CO are 7% COHb, and the hearing effect level is 9% COHb.

National Association of Medical Examiners Pediatric Toxicology (PedTox) Registry Report 3. Case submission summary and data for acetaminophen, benzene, carboxyhemoglobin, dextromethorphan, ethanol, phenobarbital, and pseudoephedrine.

Data are presented from the National Association of Medical Examiners' (St. Louis, MO, U.S.A.) Pediatric Toxicology (PedTox) Registry. A total of 839 case reports have been submitted to the registry. Reported here are the concentrations of several drugs and potentially toxic substances observed in children who have died of various causes, often non-drug-related. Except for carbon monoxide, for each of the substances addressed in this report, there is insufficient information in the literature to distinguish "lethal" from "non- or sublethal" concentrations in children, and the data are presented only to provide a working frame of reference. For 30 infants whose deaths were attributed to causes other than phenobarbital, the median blood phenobarbital concentration was 7.8 mg/L, with a range of 0.1-22.4 mg/L. For eight infants whose deaths were not attributed to ethanol, the mean blood ethanol concentration was 0.029 gm/dl and ranged from 0.011 gm/dl to 0.050 gm/dl. Blood dextromethorphan concentrations in seven infants showed a mean of 0.38 mg/L and ranged from 0.10 mg/L to 0.95 mg/L. In 15 infants, blood pseudoephedrine concentrations ranged between 0.07 mg/L and 13.0 mg/L, with a mean concentration of 3.55 mg/L. Blood carboxyhemoglobin saturations for 38 children aged < or = 5 years, who died in fires and were dead on the scene and not resuscitated, ranged between 29% and 94%, with a mean saturation of 64%. Blood benzene concentrations in eight children aged < or = 6 years who died in fires and were dead on the scene showed a mean concentration of 2.3 mg/L and a range of 0.2-4.9 mg/L. For 33 children aged < or = 5 years whose deaths were attributed to nondrug causes, the mean blood acetaminophen concentration was 9.9 mg/L, and the range was 1.0-34.5 mg/L. These data are not well controlled in terms of testing methodology or cause of death determinations and should not be used as the sole source of information when assessing whether or not a death is caused by one of these substances. Further data and controlled studies are needed to work toward establishing lethal concentrations of certain drugs and toxic substances in children, and the reporting of cases to the PedTox Registry is encouraged.