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.

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

CONTEXT: Methyl 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. RESULTS: We 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). CONCLUSION: We conclude that cobinamide could potentially serve as a CH3SH antidote.