Polyethylene glycol conjugated bovine hemoglobin containing 15% MetHb plays approving effect in exchange transfusion rabbit model.

PEG-bHb was developed by Kaizheng Biotech (Beijing, China), and pre-clinical research was completed. The objective of this study was to investigate the safe concentration of MetHb in PEG-bHb. The study was accomplished by examining the effects of PEG-bHb containing 5%, 8%, 15%, and 25% methemoglobin (MetHb), respectively, on cardiovascular system, blood chemistry, pathology of liver and kidney in rabbits following a 50% exchange transfusion. The results showed that PEG-bHb containing 5%, 8%, 15%, and 25% MetHb could keep four groups of experimental rabbits (5/5) alive until the 8th day after 50% exchange infusion as autologous whole blood did, and were superior to dextran 40 (2/5). MetHb concentration in PEG-bHb, no more than 25%, did not affect the PEG-bHb function on resuscitation of hemorrhaged rabbits by physiological measurements and blood chemistry assays. Histology study using optic and electron microscopy showed that there were slight pathological changes in hepatocytes and renal tubule epithelia in rabbits, which were infused by PEG-bHb containing 5%, 8%, and 15% MetHb. Partial organelles collapse was observed in rabbits resuscitated by PEG-bHb containing 25% MetHb. In conclusion, PEG-bHb is safe and effective when the MetHb concentration is at or below 15%.

Failure of intravenous N-acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial.

STUDY OBJECTIVE: To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in human volunteers. METHODS: We conducted a randomized, control crossover trial with each subject serving as his own control. Methemoglobinemia was induced with intravenous sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0. At time 30 minutes, subjects were randomly assigned to treatment with intravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg per hour for 40 minutes) or administration of an equal volume of 5% dextrose in water. Each subject received the alternative treatment after an interval of at least 1 week. Blood methemoglobin concentrations were measured by multiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minutes. Area under the methemoglobin concentration-time curve (AUC) between 30 and 130 minutes was compared between groups using a 2-tailed, paired t test. RESULTS: There were no statistically significant differences in the control and treatment groups with respect to baseline hemoglobin or methemoglobin concentrations, as well as nitrite-induced methemoglobin concentrations at the initiation of treatment (0.85+/-0.06 g/dL, 0.88+/-0.04 g/dL; mean+/-SEM; P =.31). Mean AUC for the control group (77.1+/-5.7 g x min/dL) was significantly lower than the mean AUC for the treatment group (84.5+/-4.7 g x min/dL); P =.01). CONCLUSION: Intravenous NAC failed to enhance methemoglobin reduction in this model.

Cyanide and methemoglobin kinetics in smoke inhalation victims treated with the cyanide antidote kit.

STUDY OBJECTIVE: To evaluate serial cyanide, methemoglobin, and carbon monoxide levels in smoke inhalation patients. SETTING: Regional poison center and regional toxicology treatment center. PARTICIPANTS: Seven critically ill smoke inhalation patients referred to the regional poison center. INTERVENTIONS: Peak level and half-life were determined by obtaining serial carboxyhemoglobin, cyanide, and methemoglobin levels. RESULTS: The mean observed half-life of cyanide was 3.0 +/- 0.6 hours. Methemoglobinemia was evaluated in four patients after sodium nitrite administration. The peak measured methemoglobin levels (mean, 10.5% +/- 2%; range, 7.9% to 13.4%) did not occur until a mean of 50 minutes (range, 35 to 70 minutes) following administration of sodium nitrite. The total oxygen-carrying capacity reduced by the combination of carboxyhemoglobin and methemoglobin was never more than 21% (range, 10% to 21%) in this series. CONCLUSION: The administration of sodium nitrite to smoke inhalation patients in the presence of concomitant carbon monoxide poisoning may be relatively safe.

Extravascular arteriovenous oxygen shunting in the cat stomach.

Venous appearance of oxygen and red cells labelled with methaemoglobin was compared in the gastric vascular bed. At 'resting' gastric blood flow the red cells appeared earlier than oxygen after simultaneous close i.a. injection, as would be expected from the intravascular laminar flow profile. However, when lowering arterial inflow pressure to the stomach by partially occluding the coeliac trunk, oxygen often appeared earlier than the red blood cells. When arterial pressure was lower than 50 mmHg this was always the case. This observation is taken to indicate that during these experimental conditions an extravascular shunting of oxygen occurs. It is suggested that this may occur in the submucosal vascular network and/or in the mucosa. The functional implications of such a mechanism are tentatively discussed.

Exogenous methemoglobin as a cyanide antidote in rats.

The effects of the administration of methemoglobin (MetHb) prepared in vitro were evaluated in Sprague-Dawley rats given increasing doses of potassium cyanide (KCN). Median lethal dose (LD50) studies were conducted by giving intraperitoneal injections of KCN (in 0.3- to 0.5-ml volumes), then 2 min later administering intravenous (iv) doses of 1000, 1500, or 2500 mg/kg of MetHb through the tail vein. Control rats received an equivalent volume of saline. The resulting LD50 values for KCN were 7.4 +/- 1.1, 11.7 +/- 1.1, 13.9 +/- 1.0, and 14.2 +/- 1.0 mg/kg (mean +/- SD) for the control (no MetHb) and 1000-, 1500-, and 2500-mg/kg dose groups, respectively. Additional groups of rats were given 1000, 1500, or 2500 mg/kg MetHb and submitted for necropsy. The gross finding of darkened kidneys was present in both dose groups, but became consistent and more prominent in the 2500-mg/kg dose group. Evidence of pathologic changes was not present in other organs. Single-dose pharmacokinetic studies were conducted using iv doses of 1600 and 2500 mg/kg MetHb. The elimination half-life was similar in both doses (62.6 min), but the volume of distribution (95.3 +/- 7.2 and 126.3 +/- 5.2 ml/kg, mean +/- SE) and clearance (1.1 +/- 0.1 and 1.5 +/- 0.1 ml/min/kg) were significantly different (P less than 0.05) for the 1600- and 2500-mg/kg dose groups, respectively. From these data we conclude that although MetHb is cleared from the vascular system rapidly, it may be an effective and nontoxic antidote for doses of cyanide up to twice that of the control LD50.