Quantitative assessment of chlorine gas inhalation injury based on endoscopic OCT and spectral encoded interferometric microscope imaging with deep learning.

Chlorine exposure can cause severe airway injuries. While the acute effects of chlorine inhalation are well-documented, the structural changes resulting from the post-acute, high-level chlorine exposure remain less understood. Airway sloughing is one of the standards for doctors to evaluate the lung function. Here, we report the application of a high-resolution swept-source optical coherence tomography system to investigate the progression of injury based on airway sloughing evaluation in a chlorine inhalation rabbit model. This system employs a 1.2 mm diameter flexible fiberoptic endoscopic probe via an endotracheal tube to capture in vivo large airway anatomical changes before and as early as 30 min after acute chlorine exposure. We conducted an animal study using New Zealand white rabbits exposed to acute chlorine gas (800 ppm, 6 min) during ventilation and monitored them using optical coherence tomography (OCT) for 6 h. To measure the volume of airway sloughing induced by chlorine gas, we utilized deep learning for the segmentation task on OCT images. The results showed that the volume of chlorine induced epithelial sloughing on rabbit tracheal walls initially increased, peaked around 30 min, and then decreased. Furthermore, we utilized a spectral encoded interferometric microscopy system to study ex vivo airway cilia beating dynamics based on Doppler shift, aiding in elucidating how chlorine gas affects cilia beating function. Cilia movability and beating frequency were decreased because of the epithelium damage. This quantitative approach has the potential to enhance the diagnosis and monitoring of injuries from toxic gas inhalation and to evaluate the efficacy of antidote treatments for these injuries

Characterizing tourniquet induced hemodynamics during total knee arthroplasty using diffuse optical spectroscopy.

Tourniquet use creates a reduced blood surgical field during total knee arthroplasty (TKA), however, prolonged ischemia may cause postoperative tourniquet complications. To understand the effects of tourniquet-induced ischemia, we performed a prospective observational study using quantitative broadband diffuse optical spectroscopy (DOS) to measure tissue hemodynamics and water and lipid concentrations before, during, and after tourniquet placement in subjects undergoing TKA. Data was collected for 6 months and, of the total subjects analyzed (n = 24), 22 were primary TKAs and 2 were revision TKA cases. We specifically investigated tourniquet-induced hemodynamics based upon subject-specific tissue composition and observed a significant relationship between the linear rate of deoxygenation after tourniquet inflation and water/lipid ratio (W/L, p < 0.0001) and baseline somatic tissue oxygen saturation, StO2 (p = 0.05). Subjects with a low W/L ratio exhibited a lower tissue metabolic rate of oxygen consumption, (tMRO2 ) (p = 0.008). Changes in deoxyhemoglobin [HbR] (p = 0.009) and lipid fraction (p = 0.001) were significantly different between high and low W/L subject groups during deoxygenation. No significant differences were observed for hemodynamics during reperfusion and total tourniquet time was neither significantly related to the hemodynamic hyperemic response (p = 0.73) nor the time to max StO2 after tourniquet release (p = 0.57). In conclusion, we demonstrate that DOS is capable of real-time monitoring of tissue hemodynamics distal to the tourniquet during TKA, and that tissue composition should be considered. DOS may help surgeons stratify hemodynamics based upon tissue composition and eventually aid the preoperative risk assessment of vascular occlusions from tourniquet use during TKA

Intratracheal cobinamide (vitamin B12 analog) administration increases survivability in rabbits exposed to a lethal dose of inhaled hydrogen sulfide

BackgroundHydrogen sulfide is a highly toxic, flammable, and colorless gas. Hydrogen sulfide has been identified as a potential terrorist chemical threat agent in mass-casualty events. Our previous studies showed that cobinamide, a vitamin B12 analog, effectively reverses the toxicity from hydrogen sulfide poisoning. In this study, we investigate the effectiveness of intratracheally administered cobinamide in treating a lethal dose hydrogen sulfide gas inhalation and compare its performance to saline control administration.MethodsA total of 53 pathogen-free New Zealand White rabbits were used for this study. Four groups were compared: (i) received no saline solution or drug intratracheally (n = 15), (ii) slow drip saline intratracheally (n = 15), (iii) fast drip saline intratracheally (n = 15), and (iv) slow drip cobinamide intratracheally (n = 8). Blood pressure was continuously monitored, and deoxy- and oxyhemoglobin concentration changes were monitored in real-time in vivo using continuous wave near-infrared spectroscopy.ResultsThe mean (± standard deviation) weight for all animals (n = 53) was 3.87 ± 0.10 kg. The survival rates of the slow cobinamide and the fast saline groups were 75 percent and 60 percent, respectively, while the survival rates in the slow saline and control groups were 26.7 percent and 20 percent, respectively. A log-rank (Mantel-Cox) test showed that survival in fast saline and slow cobinamide groups were significantly greater than those of no saline control and slow saline groups (P < 0.05). The slow and no saline control groups were not significantly different (P = 0.59). The slow cobinamide group did significantly better than the slow saline group (P = 0.021).DiscussionThe ability to use intratracheal cobinamide as an antidote to hydrogen sulfide poisoning is a novel approach to mass-casualty care. The major limitations of this study are that it was conducted in a single species at a single inhaled hydrogen sulfide concentration. Repeated investigations in other species and at varying levels of hydrogen sulfide exposure will be needed before any definitive recommendations can be made.ConclusionsWe demonstrated that intratracheal cobinamide and fast saline drip improved survival for hydrogen sulfide gas inhalation in rabbit models. Although further study is required, our results suggest that intratracheal administration of cobinamide and fast saline may be useful in hydrogen sulfide mass-casualty events

Methyl mercaptan gas: mechanisms of toxicity and demonstration of the effectiveness of cobinamide as an antidote in mice and rabbits

ContextMethyl mercaptan (CH3SH) is a colorless, toxic gas with potential for occupational exposure and used as a weapon of mass destruction. Inhalation at high concentrations can result in dyspnea, hypoventilation, seizures, and death. No specific methyl mercaptan antidote exists, highlighting a critical need for such an agent. Here, we investigated the mechanism of CH3SH toxicity, and rescue from CH3SH poisoning by the vitamin B12 analog cobinamide, in mammalian cells. We also developed lethal CH3SH inhalation models in mice and rabbits, and tested the efficacy of intramuscular injection of cobinamide as a CH3SH antidote.ResultsWe found that cobinamide binds to CH3SH (Kd = 84 µM), and improved growth of cells exposed to CH3SH. CH3SH reduced cellular oxygen consumption and intracellular ATP content and activated the stress protein c-Jun N-terminal kinase (JNK); cobinamide reversed these changes. A single intramuscular injection of cobinamide (20 mg/kg) rescued 6 of 6 mice exposed to a lethal dose of CH3SH gas, while all six saline-treated mice died (p = 0.0013). In rabbits exposed to CH3SH gas, 11 of 12 animals (92%) treated with two intramuscular injections of cobinamide (50 mg/kg each) survived, while only 2 of 12 animals (17%) treated with saline survived (p = 0.001).ConclusionWe conclude that cobinamide could potentially serve as a CH3SH antidote