Anesthetized Swine Model Research Articles

Electromuscular Incapacitation Current Induced Neuromuscular Tissue Injury.

Electrical stun devices (ESDs) serve a basic role in law enforcement and provide an alternative to lethal options for target control by causing electromuscular incapacitation (EMI). A fundamental concern is the adverse health consequences associated with their use. The capability of EMI electric field pulses to disrupt skeletal muscle cells (i.e. rhabdomyolysis) was investigated over the operational range commonly used in commercial EMI devices. Functional and structural alteration and recovery of muscle and nerve tissue were assessed. In an anesthetized swine model, the left thigh was exposed to 2 min of electrical pulses, using a commercially available ESD or a custom-made EMI signal power amplifier. Serum creatinine phosphokinase (CPK), troponin, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels were monitored intermittently for 6 h post-EMI exposure. A standard external cardiac defibrillator served as a positive control. Muscle and nerve tissue histology adjacent to the EMI contacts were examined. Post-EMI shock skeletal muscle function was evaluated by analyzing the compound muscle action potentials (CMAPs) of the rectus femoris muscle. Maximal energy cardiac defibrillator pulses resulted in rhabdomyolysis and marked elevation of CPK, LDH, and AST 6 h post-shock. EMI field pulses resulted in the animals developing transient acidosis. CMAP amplitudes decreased approximately 50% after EMI and recovered to near-normal levels within 6 h. Within 6 h post-EMI exposure, blood CPK was mildly increased, LDH was normal, and no arrhythmia was observed. Minimal rhabdomyolysis was produced by the EMI pulses. These results suggest that EMI exposure is unlikely to cause extremity rhabdomyolysis in normal individuals. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Novel Doppler-guided subxyphoid approach to avoid coronary artery damage during left ventricular epicardial lead placement or ablation.

Subxyphoid active left ventricular epicardial (LVE) lead implants or VT ablation are attractive but remain a challenge due to concerns of coronary artery damage. We aimed to see if Doppler-guided positioning could permit safe LVE lead placement without coronary angiography. We evaluated the feasibility of a Doppler flow-guided subxyphoid epicardial screw-in lead fixation in a swine model. Acute subxyphoid access to the pericardial space was performed in an anesthetized swine model using a deflectable sheath and a modified needle-derived Doppler flow meter. The audio signal and visual display from the Doppler flow meter were recorded. Coronary angiography was performed to verify the catheter location. A SelectSecure Model 3830 lead (Medtronic) was used to assess pacing in the procedure. In both of two swine, the deflectable catheter was inserted into pericardial space via subxyphoid access. The tip of the deflectable catheter with the Doppler was directed to several locations, from quiet (no nearby coronary artery expected) to typical rhythmic pulsatile sound locations which were maximal when superimposed on a coronary artery. Repeated coronary angiograms confirmed the expected findings. A 3830 active lead was fixed into a quiet location for LVE pacing, and confirmed by angiography as distant from a coronary artery. Doppler-guided subxyphoid epicardial screw-in lead placement is feasible once the catheter tip is directed and stabilized in a desired LVE location. This obviates the need for repeated (or any) coronary angiography. The Doppler-guided subxyphoid epicardial procedure may also be applicable for epicardial ventricular arrhythmia ablation procedures.

Controlled progressive elevation rather than an optimal angle maximizes cerebral perfusion pressure during head up CPR in a swine model of cardiac arrest

Aim of the StudyElevation of the head and thorax (HUP) during cardiopulmonary resuscitation (CPR) has been shown to double brain blood flow with increased cerebral perfusion pressures (CerPP) after active compression-decompression (ACD) CPR with an impedance threshold device (ITD). However, the optimal angle for HUP CPR is unknown. MethodsIn Study A, different angles were assessed (20°, 30°, 40°), each randomized over 5-min periods of ACD + ITD CPR, after 8 min of untreated ventricular fibrillation in an anesthetized swine model. Based upon Study A, Study B was performed, where animals were randomized to 1 of 2 sequences: 20°, 30°, 40° or 40°, 30°, 20° with a similar protocol. The primary endpoint was CerPP for both studies. ResultsIn Study A, no optimal HUP angle was observed in 18 pigs. CerPPs for 30° and 40° (mmHg, mean ± SD) were equivalent (44 ± 22 and 47 ± 26, p = 0.18). However, CerPP appeared higher when 40° HUP was performed during the last 5-min of CPR, suggestive of a sequence effect. For Study B, after 17 min of CPR, CerPP (mmHg) were higher with the 20°, 30°, 40° sequence: 60 ± 17 versus 33 ± 18 (p = 0.035). ConclusionsNo optimal HUP CPR angle was observed. However, controlled progressive elevation of the head and thorax during CPR is more beneficial than an absolute angle or height to maximize CerPP. Further studies are needed to determine the optimal rate of rise during HUP ACD + ITD CPR. Institutional Protocol Number17-06.

Average Diameter of Fibrous Bundles Connecting the Optic Nerve to the Optic Sheath Decreases with Increased Intracranial Pressure

ObjectiveThe objective of this study was to evaluate the effect of increased intracranial pressure (ICP) on the fiber bundles connecting the optic nerve to the optic sheath in a swine model.MethodsIncreased ICP was induced in an anesthetized swine model by passing a catheter through a drilled opening into the epidural space. ICP was monitored continuously. Post euthanasia and enucleation of the swine eyes, a section of optic nerve sheath, with the intact nerve, was removed from both the control and experimental swine model. The tissue was fixed overnight in paraformaldehyde and glutaraldehyde in a sodium cacodylate buffer, postfixed in osmium tetroxide in a sodium cacodylate buffer, dehydrated with a graded ethanol series, and critical point dried with carbon dioxide. The dried control and experimental model sections were mounted and imaged using a scanning electron microscope (SEM). Images of the trabecular meshwork were taken radially around the optic nerve at several magnifications. The images were segmented and analyzed using the ImageJ plug‐in DiameterJ. Segmentation quality was confirmed using image subtraction of the original image from the segmented image and vice versa. All images had false positive and false negative total percentages of less than 5% of all pixels. Image overlays of the segmented and original images confirmed this qualitatively.ResultsMean and median fiber bundle diameters were recorded for a total of 61 images. 30 (49.1%) of the images analyzed were from the control sample and 31 (50.9%) were from the experimental sample. An analysis of variance found that both the mean (.52 μm) and median (.62 μm) fibrous bundle diameters were significantly different (smaller) for the experimental model as compared to the control (.73 μm and .85 μm) respectively (p<.0001). The relationship between mean and median fibrous bundle diameters and sample (control or experimental) was not significantly correlated to radial location (relative to the optic nerve) or magnification of the image based on analyses of covariance.ConclusionThis research demonstrates that in a swine model the fibrous bundles of the optic sheath's connections to the optic nerve are statistically different (smaller) after exposure to increased ICP. Future research will evaluate if the thinning is caused by increased ICP, by increasing the sample size and using other methods to induce increased ICP. Future research may impact the current understanding of traumatic brain injury.Support or Funding InformationMedical Scholars Program, Medical College of Georgia at Augusta University, Summer 2017This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.

Sulfur mustard (HD) is a vesicating and alkylating agent widely used on the battlefield during World War I and more recently in the Iran-Iraq War. It targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function; early acute effects lead to long-term consequences. However, it is the effects on the lungs that drive morbidity and eventual mortality. The temporal postexposure response to HD within lung tissue raises the question of whether toxicity is driven by the alkylating properties of HD on critical homeostatic pathways. We have established an anesthetized swine model of inhaled HD vapor exposure to investigate the toxic effects of HD 12 h postexposure. Large white female swine were anesthetized and instrumented prior to exposure to air, 60 (sublethal) or 100 μg·kg-1 (∼LD40) doses of HD (10 min). Physiological parameters were continuously assessed. Data indicate that exposure to 100 μg·kg-1 HD lowered arterial blood oxygenation and increased shunt fraction and lavage protein compared with those of air-exposed controls and the 60 μg·kg-1 dose of HD. Histopathology showed an increased total pathology score between the 100 μg·kg-1 HD group and air-exposed controls. Principal component analysis of differentially expressed genes demonstrated a distinct and separable response of inhaled HD between air-exposed controls and the 60 and 100 μg·kg-1 doses of HD. Canonical pathway analysis demonstrated changes in acute phase response signaling, aryl hydrocarbon receptor signaling, NRF-2 mediated oxidative stress, and zymosterol biosynthesis in the 60 and 100 μg·kg-1 HD dose group. Transcriptional changes also indicated alterations in immune response, cancer, and cell signaling and metabolism canonical pathways. The 100 μg·kg-1 dose group also showed significant changes in cholesterol biosynthesis. Taken together, exposure to inhaled HD had a significant effect on physiological responses coinciding with acute changes in gene expression and lung histopathology. In addition, transcriptomics support the observed beneficial effects of N-acetyl-l-cysteine for treatment of acute inhalation HD exposure.

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

IntroductionDeep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. MethodsA multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. ResultsHemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. ConclusionsThe present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop.

Acute effect of simultaneous discharge of TASER X26TASER X26 on anesthetized swine model

The safety of Conducted energy weapons is under debate [1]. The patient's condition and the delivered energy are ones of the affecting factors to the safety [2]. Repeated or long-duration exposure related to the delivered energy can lead to cardiac arrest, apnea, hypotension or academia [3].

Repetitive TASER X26 Discharge Resulted in Adverse Physiologic Events with a Dose–Response Relationship Related to the Duration of Discharge in Anesthetized Swine Model

The objectives of our study were to investigate the dose-response relationship of the TASER X26 discharge duration in an anesthetized swine model. Fourteen swines were anesthetized and then exposed to TASER X26 discharge for 5 sec (n = 5) or for 10 sec (n = 6). The sham control group (n = 3) was anesthetized and studied using the same protocol except TASER X26 discharges during the experiments. Hemodynamic parameters were obtained. Blood pressure and total peripheral resistance decreased significantly after TASER discharge and returned to baseline value at 15 min after 5 sec of TASER discharge but did not return to baseline values during the 30-min observation period after 10 sec of TASER discharge. Repetitive TASER X26 discharge resulted in adverse physiologic events with a dose-response relationship related to the duration of TASER X26 discharge in an anesthetized swine model.

Abstract 284: Real Time Blood Pressure Dynamics During Fluid Resuscitation Predict 6-Hour Survival in a Swine Model of Polytrauma with Uncontrolled Hemorrhage

Objective: Blood pressure responses to fluid resuscitation during trauma can reflect blood loss and shock severity. We examine early blood pressure responses to fluid resuscitation to test the hypothesis that rapid blood pressure dynamics during trauma resuscitation may also predict longer-term survival. Methods: Mean arterial pressure (MAP) during the initial fluid resuscitation was abstracted from a study using an anesthetized swine model of traumatic brain injury and catheter/free hemorrhage by aortic tear. Animals were hemorrhaged to MAP=30mmHg for 15 minutes prior to resuscitation. Lactated Ringers (LR, 20ml/kg) or a Hemoglobin-based Oxygen Carrier (HBOC, 10ml/kg) was then given over 10 minutes and repeated every 15 minutes thereafter for MAP < 60mmHg for up to 105 minutes. The aortic tear was then repaired and the animal further resuscitated using Normal Saline and shed blood to predefined criteria for up to 6 hours. Serial invasive MAP measurements recorded in 5 minute intervals over the first 15 minutes of fluid infusion were correlated with blood loss and survival time. MAP dynamics as predictors of 6 hour survivorship were examined by nominal logistic regression. Results: 50% of animals (7/14) survived to 6 hours. There were no differences in initial MAP responses between LR and HBOC groups (p=0.85). Survivors demonstrated a more rapid and prolonged positive blood pressure response to the initial fluid bolus by a higher MAP at 5 minutes of fluid infusion (43.1 mmHg vs. 34.7 mmHg in nonsurvivors, T-test, p value=0.04) and a faster rate of increase (survivors = 3.0 mmHg/min vs. nonsurvivors= 1.4mmHg/min, Wilcoxon p value= 0.0008). MAP was sustained in survivors after the initial fluid infusion ended, but immediately declined in nonsurvivors. MAP increase was associated with total survival time (R=0.77, p=0.0012). A MAP rate of increase of at least 2.2mmHg/min over the first 5 minutes of fluid resuscitation predicted survival to 6 hours with 100% sensitivity and 75% specificity (AUC= 0.93, p< 0.0001). There was no association between blood pressure response and intraperitoneal hemorrhage volume. Conclusion: In this swine model, very early resuscitation MAP dynamics predicted longer-term survival and may reflect retained physiological reserve.

254 Comparison of Chest Position and Distance to the Heart in the Induction of Cardiac Stimulation From an Electronic Control Device Using Steel versus Carbon Fiber Darts in Pigs

254 Comparison of Chest Position and Distance to the Heart in the Induction of Cardiac Stimulation From an Electronic Control Device Using Steel versus Carbon Fiber Darts in Pigs

An Animal Model to Investigate Effectiveness and Safety of Conducted Energy Weapons (Including TASER® Devices)*

Conducted energy weapons (CEWs) are used by law-enforcement personnel to incapacitate individuals quickly and effectively, without causing lethality. CEWs have been deployed for relatively long or repeated exposures during law-enforcement operations. The purpose of this technical note is to describe, in detail, some aspects of an anesthetized swine model used in our laboratory and to answer specific questions related to the model. In particular, tiletamine/zolazepam-induced, propofol-maintained anesthesia appears to be a useful technique for studying effects of CEW applications on muscle contraction and blood factors such as muscle enzymes. Because effects of CEWs on breathing have not been fully elucidated, a spontaneously breathing model is preferable to one in which mechanical ventilation is supplied. Placement of the swine in a supine position may facilitate measurement of muscle contractions, without compromising other physiological parameters.

Acute hibernation decreases myocardial pyruvate carboxylation and citrate release.

In the well-perfused heart, pyruvate carboxylation accounts for 3-6% of the citric acid cycle (CAC) flux, and CAC carbon is lost via citrate release. We investigated the effects of an acute reduction in coronary flow on these processes and on the tissue content of CAC intermediates. Measurements were made in an open-chest anesthetized swine model. Left anterior descending coronary artery blood flow was controlled by a extracorporeal perfusion circuit, and flow was decreased by 40% for 80 min to induce myocardial hibernation (n = 8). An intracoronary infusion of [U-(13)C(3)]lactate and [U-(13)C(3)]pyruvate was given to measure the entry of pyruvate into the CAC through pyruvate carboxylation from the (13)C-labeled isotopomers of CAC intermediates. Compared with normal coronary flow, myocardial hibernation resulted in parallel decreases of 65% and 79% in pyruvate carboxylation and net citrate release by the myocardium, respectively, and maintenance of the CAC intermediate content. Elevation of the arterial pyruvate concentration by 1 mM had no effect. Thus a 40% decrease in coronary blood flow resulted in a concomitant decrease in pyruvate carboxylation and citrate release as well as maintenance of the CAC intermediates.

Hepatic and renal blood flow responses to a clinical dose of intravenous cyclosporine in the pig

The immunosuppressant Cyclosporine A (CsA) is considered to induce nephrotoxicity in part by causing vasoconstriction of the glomerular afferent arterioles. Although CsA is widely used in hepatic transplantation, little is known concerning its effects on hepatic blood flow. We used ultrasonic flow probes in an anesthetized swine model to measure the effects of a single 60 min infusion of a clinically comparable dose of CsA (5 mg/kg per h) on hepatic, renal, and supraceliac descending aortic blood flows (n = 7 swine). To account for any changes in systemic output or systemic vascular resistance during the 60 min CsA infusion that may non-specifically affect hepatic and renal blood flows, the total hepatic (portal vein plus hepatic artery) and renal blood flows were reported relative to the supraceliac descending aortic blood flow (termed ‘fractional’ total hepatic and renal blood flows). The fractional total hepatic blood flow decreased significantly (p < 0.05) by 40 min of CsA infusion vs baseline, and continued to decrease throughout the infusion (baseline = 0.38 ± 0.03 units vs 0.28 ± 0.05 units by 60 min of CsA infusion). During the recovery period, the fractional total hepatic blood flow increased to a value which was not different from baseline (recovery = 0.38 ± 0.03 units). Fractional right renal artery blood flow did not change significantly from baseline at any time during the CsA infusion or during the recovery period. We conclude that a single, clinically comparable dose of CsA results in a significant decrease in total hepatic blood flow, and that this decrease is greater than that seen in renal blood flow.

Coronary Blood Flow Autoregulation and Flow Heterogeneity in the Stunned Heart.

We used an anesthetized swine model of regionally "stunned" myocardium to determine the effect of stunning on coronary autoregulation and blood flow heterogeneity. In 18 domestic swine, stunning was accomplished by reducing blood flow to the left anterior descending coronary artery (LAD) by approximately 75% of baseline for 15 min and restoring it to normal for 1 hour. We quantified coronary autoregulation using both the slope of coronary pressure-flow curves and an autoregulation index. We quantified blood flow heterogeneity using radioactive microspheres to determine the variability in flow (dispersion index) among forty 200 mg segments of myocardium from the center of the stunned, LAD-perfused left ventricle. Before and after stunning, we measured autoregulation, myocardial blood flow and flow heterogeneity, as well as hemodynamic indices of myocardial oxygen demand. Fifteen min of ischemia and 1 hour of reperfusion produced both a 46% reduction in mechanical function, and a 7% drop in systemic arterial pressure, but not change in heart rate or rate pressure product. Myocardial oxygen consumption was 15% reduced and myocardial blood flow 16% reduced in the stunned myocardium when measured at one hour of reperfusion. Fifteen min after reperfusion, the slope of the coronary pressure flow plots and the coronary venous oxygenation were increased whereas the autoregulation index decreased. These findings all indicate reduced autoregulation during early reperfusion. However, after one hour of reperfusion, the slope of the coronary pressure-flow relation (0.41 +/- 0.19 vs. 0.48 +/- 0.26 ml.100 g-1.min-1.mmHg-1) and the autoregulation index (0.43 +/- 0.16 vs. 0.30 +/- 0.32) were unchanged from control measurements (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)