Intramuscular cobinamide as an antidote to methyl mercaptan poisoning.

BACKGROUND: Methyl mercaptan occurs naturally in the environment and is found in a variety of occupational settings, including the oil, paper, plastics, and pesticides industries. It is a toxic gas and deaths from methyl mercaptan exposure have occurred. The Department of Homeland Security considers it a high threat chemical agent that could be used by terrorists. Unfortunately, no specific treatment exists for methyl mercaptan poisoning. METHODS: We conducted a randomized trial in 12 swine comparing no treatment to intramuscular injection of the vitamin B12 analog cobinamide (2.0 mL, 12.5 mg/kg) following acute inhalation of methyl mercaptan gas. Physiological and laboratory parameters were similar in the control and cobinamide-treated groups at baseline and at the time of treatment. RESULTS: All six cobinamide-treated animals survived, whereas only one of six control animals lived (17% survival) (p = 0.0043). The cobinamide-treated animals returned to a normal breathing pattern by 3.8 ± 1.1 min after treatment (mean ± SD), while all but one animal in the control group had intermittent gasping, never regaining a normal breathing pattern. Blood pressure and arterial oxygen saturation returned to baseline values within 15 minutes of cobinamide-treatment. Plasma lactate concentration increased progressively until death (10.93 ± 6.02 mmol [mean ± SD]) in control animals, and decreased toward baseline (3.79 ± 2.93 mmol [mean ± SD]) by the end of the experiment in cobinamide-treated animals. CONCLUSION: We conclude that intramuscular administration of cobinamide improves survival and clinical outcomes in a large animal model of acute, high dose methyl mercaptan poisoning.

Use of an oxygen-carrying blood substitute to improve intravascular optical coherence tomography imaging.

Optical coherence tomography (OCT) is a catheter-based imaging technology with powerful resolution capable of identifying vulnerable plaques and guiding coronary intervention. However, a significant limitation of intravascular OCT imaging is its attenuation by blood. We propose that the use of an oxygen-carrying blood substitute could potentially optimize OCT image quality. Surgical isolation of the descending thoracic aorta of six rabbits is performed, followed by intravascular OCT imaging of the abdominal aorta. Perfluorodecalin (PFD) is oxygenated using a bubble-through technique with 100% oxygen. OCT imaging is performed and compared using three different flushing modalities: PFD; saline; and blood. OCT imaging of the rabbit abdominal aorta is successful in all of the subjects. In each of the six studied subjects, flushing with PFD consistently provides dramatically better imaging of the vessel wall tissue structures. OCT image quality is highly dependent on the ability of the flushing modality to remove blood from the imaging field. From this proof-of-concept study, we demonstrate that endovascular flushing with an oxygen-carrying blood substitute (PFD) is optically superior to saline flushing for intravascular imaging.

Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography.

Optical coherence tomography (OCT) is a noninvasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures.

In vivo endoscopic optical coherence tomography by use of a rotational microelectromechanical system probe.

A novel endoscopic optical coherence tomography probe was designed and constructed with a 1.9-mm microelectromechanical system (MEMS) motor. The new MEMS endoscopic probe design eliminates the need to couple the rotational energy from the proximal to the distal end of the probe. Furthermore, the endoscopic probe's sheath and fiber have the advantages of having a much smaller diameter and being more flexible than traditional endoscopes since no reinforcement is needed to couple the rotational torque. At the distal end, a prism mounted on a micromotor deflects the light rays to create a transverse circular-scanning pathway. Because our MEMS scanner does not require the coupling of a rotational single-mode fiber, a high scanning speed is possible while eliminating unstable optical signals caused by nonuniform coupling.