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Abstract Circulation of perfluorocarbon (PFC) through corporeal cavities has received interest by virtue of its potential to supplement oxygenation via mechanical ventilation. However, the technology is not mature enough for clinical application, due to the knowledge gaps regarding the limiting factors hampering oxygen transport from PFC to blood. In this paper, we investigate a novel hypothesis that hypothermic peritoneal perfusion of cold oxygenated PFC may improve oxygenation of blood by facilitating the diffusion of oxygen from PFC to blood. Our hypothesis originates from physics-inspired insights that both hypothermia and PFC cooling may increase PFC-to-blood oxygen tension gradient: (i) hypothermia may decrease venous oxygen tension while (ii) cooling PFC may increase oxygen tension therein by increasing its oxygen solubility. Using a physics-based mathematical model capable of simulating oxygen tension responses to mechanical ventilation and peritoneal PFC perfusion under normothermic and hypothermic conditions, we analyzed the effect of hypothermic peritoneal cold PFC perfusion on blood oxygenation. The results predicted that peripheral oxygen saturation may be improved by 5%-10% by peritoneal perfusion of oxygenated 15°C PFC at 32°C body temperature compared with peritoneal perfusion of oxygenated 37.5°C PFC at 37.5°C body temperature. The results also predicted that cooling PFC may play a more meaningful role than hypothermia. Pending the investigation of adverse impact of hypothermia and cold PFC on homeostasis, hypothermic cold PFC perfusion may improve peritoneal oxygenation by facilitating diffusion. 

OBJECTIVES/GOALS: Patients suffering from respiratory failure have few options to support oxygenation and carbon dioxide removal aside from mechanical ventilation. Our objective was to test a novel extrapulmonary mechanism of gas exchange via peritoneal oxygenated perfluorocarbon (PFC) in a large animal model. METHODS/STUDY POPULATION: Using two 50 kg swine, hypoxia was modeled with subatmospheric oxygen and hypercarbia induced with acute hypoventilation. Through a midline laparotomy, cannulas were placed into the peritoneal space to allow for PFC infusion and circulation. After abdominal closure, these cannulas were connected to a device capable of draining, oxygenating, and infusing PFC. One animal was subjected to acute hypoxia (12% FiO2) and another animal to acute hypoventilation (4 breaths per minute). Primary outcomes were times for SpO2 to reach 75 mmHg, respectively. Trials were performed without PFC and with PFC dwelling or circulating through the peritoneal space, during which abdominal and bladder pressures were monitored and maintained under 20 mmHg by regulation of the PFC volume contained in the animal. RESULTS/ANTICIPATED RESULTS: In the animal subjected to acute hypoxia (12% FiO2), survival time improved from 5:55 to 20:00 (min:sec) after 2.5 liters of oxygenated PFC was instilled in the peritoneal space. Oxygen percent saturation of PFC before and after dwelling in the peritoneal space was measured at 100% before and 70% after dwelling in the animal during this hypoxic period corresponding with a gas transfer of 300 mL of oxygen over the 20-minute trial (i.e., 15 mL/min). Continual PFC circulation did not further extend the survival time during hypoxic conditions over PFC dwelling in the abdomen. In the animal that was acutely hypoventilated, there were no detectable differences in the rate of CO2 accumulation as measured by EtCO2 or direct blood pCO2 measurements with PFC dwelling or circulating through the peritoneal space. DISCUSSION/SIGNIFICANCE: Oxygenated PFC dwelling in the peritoneal space increased the duration of systemic arterial blood saturation remaining greater than 50% during normobaric hypoxic (12% FiO2) conditions but did not appreciably clear blood carbon dioxide during hypoventilation. Future experiments will focus on maximizing the rate of systemic oxygen uptake. 

Abstract This paper presents an experimentally parameterized model of the dynamics of oxygen transport in a laboratory animal that simultaneously experiences: (i) a reduction in inspired oxygen plus (ii) an increase in intra-abdominal pressure. The goal is to model the potential impact of elevated intra-abdominal pressure on oxygen transport dynamics. The model contains three compartments, namely, the animal’s lungs, lower body vasculature, and upper body vasculature. The model assumes that intra-abdominal pressure affects the split of cardiac output among the two vasculature compartments and that aerobic metabolism in each compartment diminishes with severe hypoxia. Fitting this model to a laboratory experiment on an adult male Yorkshire swine using a regularized nonlinear least-squares approach furnishes both physiologically plausible parameter values plus a reasonable quality of fit. 

OBJECTIVES/GOALS: For patients suffering from respiratory failure there are limited options to support gas exchange aside from mechanical ventilation. Our goal is to design, investigate, and refine a novel device for extrapulmonary gas exchange via peritoneal perfusion with perfluorocarbons (PFC) in an animal model. METHODS/STUDY POPULATION: Hypoxic respiratory failure will be modeled using 50 kg swine mechanically ventilated with subatmospheric (10-12%) oxygen. Through a midline laparotomy, two cannulas, one for inflow and one for outflow, will be placed into the peritoneal space. After abdominal closure, the cannulas will be connected to a device capable of draining, oxygenating, regulating temperature, filtering, and pumping perfluorodecalin at a rate of 3-4 liters per minute. During induced hypoxia, the physiologic response to PFC circulation through the peritoneal space will be monitored with invasive (e.g. arterial and venous blood gases) and non-invasive measurements (e.g. pulse oximetry). RESULTS/ANTICIPATED RESULTS: We anticipate that the initiation of oxygenated perfluorocarbons perfusion through the peritoneal space during induced hypoxia will create an increase in hemoglobin oxygen saturation and partial pressure of oxygen in arterial blood. As we expect gas exchange to be occurring in the microvascular beds of the peritoneal membrane, we expect to observe an increase in the venous blood oxygen content sampled from the inferior vena cava. Using other invasive hemodynamic measures (e.g. cardiac output) and blood samples taken from multiple venous sites, a quantifiable rate of oxygen delivery will be calculable. DISCUSSION/SIGNIFICANCE: Peritoneal perfluorocarbon perfusion, if able to deliver significant amounts of oxygen, would provide a potentially lifesaving therapy for patients in respiratory failure who are unable to be supported with mechanical ventilation alone, and are not candidates for extracorporeal membrane oxygenation.