Microdialysis and CO2 sensors detect pancreatic ischemia in a porcine model

Background: Pancreatic transplantation is associated with a high rate of early postoperative graft thrombosis. If a thrombosis is detected in time, a potentially graft-saving intervention can be initiated. Current postoperative monitoring lacks tools for early detection of ischemia. The aim of this study was to investigate if microdialysis and tissue pCO2 sensors detect pancreatic ischemia and whether intraparenchymal and organ surface measurements are comparable. Methods: In 8 anaesthetized pigs, pairs of lactate monitoring microdialysis catheters and tissue pCO2 sensors were simultaneously inserted into the parenchyma and attached to the surface of the pancreas. Ischemia was induced by sequential arterial and venous occlusions of 45-minute duration, with two-hour reperfusion after each occlusion. Microdialysate was analyzed every 15 minutes. Tissue pCO2 was measured continuously. We investigated how surface and parenchymal measurements correlated and the capability of lactate and pCO2 to discriminate ischemic from non-ischemic periods. Results: Ischemia was successfully induced by arterial occlusion in 8 animals and by venous occlusion in 5. During all ischemic episodes, lactate increased with a fold change of 3.2–9.5 (range) in the parenchyma and 1.7–7.6 on the surface. Tissue pCO2 increased with a fold change of 1.6–3.5 in the parenchyma and 1.3–3.0 on the surface. Systemic lactate and pCO2 remained unchanged. The area under curve (AUC) for lactate was 0.97 (95% confidence interval (CI) 0.93–1.00) for parenchymal and 0.90 (0.83–0.97) for surface (p<0.001 for both). For pCO2 the AUC was 0.93 (0.89–0.96) for parenchymal and 0.85 (0.81–0.90) for surface (p<0.001 for both). The median correlation coefficients between parenchyma and surface were 0.90 (interquartile range (IQR) 0.77–0.95) for lactate and 0.93 (0.89–0.97) for pCO2. Conclusions: Local organ monitoring with microdialysis and tissue pCO2 sensors detect pancreatic ischemia with adequate correlation between surface and parenchymal measurements. Both techniques and locations seem feasible for further development of clinical pancreas monitoring.publishedVersio

Assessment of Intestinal Ischemia–Reperfusion Injury Using Diffuse Reflectance VIS-NIR Spectroscopy and Histology

A porcine model was used to investigate the feasibility of using VIS-NIR spectroscopy to differentiate between degrees of ischemia–reperfusion injury in the small intestine. Ten pigs were used in this study and four segments were created in the small intestine of each pig: (1) control, (2) full arterial and venous mesenteric occlusion for 8 h, (3) arterial and venous mesenteric occlusion for 2 h followed by reperfusion for 6 h, and (4) arterial and venous mesenteric occlusion for 4 h followed by reperfusion for 4 h. Two models were built using partial least square discriminant analysis. The first model was able to differentiate between the control, ischemic, and reperfused intestinal segments with an average accuracy of 99.2% with 10-fold cross-validation, and the second model was able to discriminate between the viable versus non-viable intestinal segments with an average accuracy of 96.0% using 10-fold cross-validation. Moreover, histopathology was used to investigate the borderline between viable and non-viable intestinal segments. The VIS-NIR spectroscopy method together with a PLS-DA model showed promising results and appears to be well-suited as a potentially real-time intraoperative method for assessing intestinal ischemia–reperfusion injury, due to its easy-to-use and non-invasive nature.publishedVersio

Assessing ischemic injury in human intestine ex vivo with electrical impedance spectroscopy

Abstract Electrical impedance spectroscopy is a well-established tool for monitoring changes in the electrical properties of tissue. Most tissue and organ types have been investigated in various studies. As for the small intestine, there are several published studies conducted on pig and rat models. This study investigates the changes in passive electrical properties of the complete wall of the human intestine non-invasively during ischemia. We aim to use the passive electrical properties to assess intestinal viability. The bioimpedance measurements were performed using a two-electrode set-up with a Solartron 1260 Impedance/gain-phase analyser. The small intestinal samples were resected from patients who underwent pancreaticoduodenectomy. Impedance measurements were conducted following resection by placing the electrodes on the surface of the intestine. A voltage was applied across the intestinal sample and the measured electrical impedance was obtained in the ZPlot software. Impedance data were further fitted into a Cole model to obtain the Cole parameters. The P y value was calculated from the extracted Cole parameters and used to assess the cell membrane integrity, thus evaluate the intestinal viability. Eight small intestinal segments from different patients were used in this study and impedance measurements were performed once an hour for a ten-hour period. One hour after resection, the impedance decreased, then increased the next two hours, before decreasing until the end of the experiment. For all the intestinal segments, the P y values first increased and reached a plateau which lasted for 1 - 2 hours, before it decreased irreversibly. The time interval where P y value reached the maximum is consistent with reported viable/non-viable limits from histological analysis

Quantification of aerosol dispersal from suspected aerosol-generating procedures

Background Oxygen-delivering modalities like humidified high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV) are suspected of generating aerosols that may contribute to transmission of disease such as coronavirus disease 2019. We sought to assess if these modalities lead to increased aerosol dispersal compared to the use of non-humidified low-flow nasal cannula oxygen treatment (LFNC). Methods Aerosol dispersal from 20 healthy volunteers using HFNC, LFNC and NIV oxygen treatment was measured in a controlled chamber. We investigated effects related to coughing and using a surgical face mask in combination with the oxygen delivering modalities. An aerodynamic particle sizer measured aerosol particles (APS3321, 0.3–20 µm) directly in front of the subjects, while a mesh of smaller particle sensors (SPS30, 0.3–10 µm) was distributed in the test chamber. Results Non-productive coughing led to significant increases in particle dispersal close to the face when using LFNC and HFNC but not when using NIV. HFNC or NIV did not lead to a statistically significant increase in aerosol dispersal compared to LFNC. With non-productive cough in a room without air changes, there was a significant drop in particle levels between 100 cm and 180 cm from the subjects. Conclusions Our results indicate that using HFNC and NIV does not lead to increased aerosol dispersal compared to low-flow oxygen treatment, except in rare cases. For a subject with non-productive cough, NIV with double-limb circuit and non-vented mask may be a favourable choice to reduce the risk for aerosol spread

Machine learning for intraoperative prediction of viability in ischemic small intestine

Objective: Evaluation of intestinal viability is essential in surgical decision-making in patients with acute intestinal ischemia. There has been no substantial change in the mortality rate (30-93%) of patients with acute mesenteric ischemia (AMI) since the 1980’s. As the accuracy from the first laparotomy alone is 50%, the gold standard is a second-look laparotomy, increasing the accuracy to 87-89%. This study investigates the use of machine learning to classify intestinal viability and histological grading in pig jejunum, based on multivariate time-series of bioimpedance sensor data. Approach: We have previously used a bioimpedance sensor system to acquire electrical parameters from perfused, ischemic and reperfused pig jejunum (7 + 15 pigs) over 1-16 hours of ischemia and 1-8 hours of reperfusion following selected durations of ischemia. In this study we compare the accuracy of using end-point bioimpedance measurements with a feedforward neural network (FNN), versus the accuracy when using a recurrent neural network with long short-term memory units (LSTM-RNN) with bioimpedance data history over different periods of time. Main results: Accuracies in the range of what has been reported clinically can be achieved using FNN’s on a single bioimpedance measurement, and higher accuracies can be achieved when employing LSTM-RNN on a sequence of data history. Significance: Intraoperative bioimpedance measurements on intestine of suspect viability combined with machine learning can increase the accuracy of intraoperative assessment of intestinal viability. Increased accuracy in intraoperative assessment of intestinal viability has the potential to reduce the high mortality and morbidity rate of the patients

Small intestinal ischemia and reperfusion - Bioimpedance measurements

Objective: Trans-intestinal bioimpedance measurements have previously been used to investigate changes in electrical parameters during 6h of ischemia in the small intestine. Knowledge is lacking regarding the time course of trans-intestinal bioimpedance parameters during reperfusion. As reperfusion is an important part in the clinical treatment of intestinal ischemia, we need to know how it affects the bioimpedance measurements. Approach: We performed bioimpedance measurements, using a two-electrode setup on selected segments of the jejunum in 15 pigs. A controlled voltage signal was applied while measuring the resulting current. In each pig, five or six 30 cm segments of the jejunum were made ischemic by clamping the mesenteric arteries and veins creating segments with ischemia from 1–16h duration. Reperfusion was initiated at selected time intervals of ischemia, and measured for 5–15h afterwards. Main results: The tan δ parameter (loss tangent) was different (p < 0.016) comparing ischemic and control tissue for the duration of the experiment (16h). Comparing the control tissue 30 cm from the ischemic area with the control tissue 60 cm from the ischemic tissue, we found that the mean tan δ amplitude in the frequency range (3900–6300 Hz) was significantly higher (p < 0.036) in the proximal control after 10h of experiment duration. After reperfusion, the time development of tanδm (loss tangent maximum over a frequency range) amplitude and frequency overlapped and periodically increased above the tanδm in the ischemic intestine. Dependent on the ischemic duration pre-reperfusion, the initial increase in tan δ stabilizes or increases drastically over time, compared to the tan δ amplitude of the ischemic tissue. Significance: As during ischemia, the electrical parameters during reperfusion also follow a characteristic timecourse, depending on the ischemic exposure before pre-reperfusion. The temporal changes in electrical parameters during small intestinal ischemia followed by reperfusion provides important information for assessment of tissue injury

Cerebral perfusion and metabolism with mean arterial pressure 90 vs. 60 mmHg in a porcine post cardiac arrest model with and without targeted temperature management

Aim To determine whether targeting a mean arterial pressure of 90 mmHg (MAP90) would yield improved cerebral blood flow and less ischaemia compared to MAP 60 mmHg (MAP60) with and without targeted temperature management at 33 °C (TTM33) in a porcine post-cardiac arrest model. Methods After 10 min of cardiac arrest, 41 swine of either sex were resuscitated until return of spontaneous circulation (ROSC). They were randomised to TTM33 or no-TTM, and MAP60 or MAP90; yielding four groups. Temperatures were managed with intravasal cooling and blood pressure targets with noradrenaline, vasopressin and nitroprusside, as appropriate. After 30 min of stabilisation, animals were observed for two hours. Cerebral perfusion pressure (CPP), cerebral blood flow (CBF), pressure reactivity index (PRx), brain tissue pCO2 (PbtCO2) and tissue intermediary metabolites were measured continuously and compared using mixed models. Results Animals randomised to MAP90 had higher CPP (p < 0.001 for both no-TTM and TTM33) and CBF (no-TTM, p < 0.03; TH, p < 0.001) compared to MAP60 during the 150 min observational period post-ROSC. We also observed higher lactate and pyruvate in MAP60 irrespective of temperature, but no significant differences in PbtCO2 and lactate/pyruvate-ratio. We found lower PRx (indicating more intact autoregulation) in MAP90 vs. MAP60 (no-TTM, p = 0.04; TTM33, p = 0.03). Conclusion In this porcine cardiac arrest model, targeting MAP90 led to better cerebral perfusion and more intact autoregulation, but without clear differences in ischaemic markers, compared to MAP60

Utilization of dielectric properties for assessment of liver ischemia-reperfusion injury in vivo and during machine perfusion

Abstract There is a shortage of donor livers and patients consequently die on waiting lists worldwide. Livers are discarded if they are clinically judged to have a high risk of non-function following transplantation. With the aim of extending the pool of available donor livers, we assessed the condition of porcine livers by monitoring the microwave dielectric properties. A total of 21 livers were divided into three groups: control with no injury (CON), biliary injury by hepatic artery occlusion (AHEP), and overall hepatic injury by static cold storage (SCS). All were monitored for four hours in vivo, followed by ex vivo plurithermic machine perfusion (PMP). Permittivity data was modeled with a two-pole Cole–Cole equation, and dielectric properties from one-hour intervals were analyzed during in vivo and normothermic machine perfusion (NMP). A clear increasing trend in the conductivity was observed in vivo in the AHEP livers compared to the control livers. After four hours of NMP, separations in the conductivity were observed between the three groups. Our results indicate that dielectric relaxation spectroscopy (DRS) can be used to detect and differentiate liver injuries, opening for a standardized and reliable point of evaluation for livers prior to transplantation