The Self-Expandable Impella CP (ECP) as a Mechanical Resuscitation Device.

The survival rate of cardiac arrest (CA) can be improved by utilizing percutaneous left ventricular assist devices (pLVADs) instead of conventional chest compressions. However, existing pLVADs require complex fluoroscopy-guided placement along a guidewire and suffer from limited blood flow due to their cross-sectional area. The recently developed self-expandable Impella CP (ECP) pLVAD addresses these limitations by enabling guidewire-free placement and increasing the pump cross-sectional area. This study evaluates the feasibility of resuscitation using the Impella ECP in a swine CA model. Eleven anesthetized pigs (73.8 ± 1.7 kg) underwent electrically induced CA, were left untreated for 5 min and then received pLVAD insertion and activation. Vasopressors were administered and defibrillations were attempted. Five hours after the return of spontaneous circulation (ROSC), the pLVAD was removed, and animals were monitored for an additional hour. Hemodynamics were assessed and myocardial function was evaluated using echocardiography. Successful guidewire-free pLVAD placement was achieved in all animals. Resuscitation was successful in 75% of cases, with 3.5 ± 2.0 defibrillations and 1.8 ± 0.4 mg norepinephrine used per ROSC. Hemodynamics remained stable post-device removal, with no adverse effects or aortic valve damage observed. The Impella ECP facilitated rapid guidewire-free pLVAD placement in fibrillating hearts, enabling successful resuscitation. These findings support a broader clinical adoption of pLVADs, particularly the Impella ECP, for CA.

A Novel Swine Model for Inducing Functional Tricuspid Valve Regurgitation.

Functional tricuspid regurgitation (FTR) is the most common TR, although experimental models to effectively study it are scarce; therefore, this study aimed to establish a robust experimental swine model. A swine FTR model was developed using radiofrequency ablation, atrial septostomy, and right atrial volume overload. The baseline and follow-up echocardiography was performed to evaluate the progression FTR and changes in the heart. Autopsy was employed to verify the anatomy of tricuspid valve. One-month post intervention, among the subjects, one (8.3%) exhibited severe FTR, eight (66.7%) exhibited moderate TR, and three (25%) exhibited mild FTR. Each pig developed an atrial septal defect (diameter, 1.5 ± 0.5 cm). The tricuspid annular diameter significantly increased with enlargement of right heart (P < 0.05). No significant difference was found on left heart size and mitral regurgitation. We successfully developed a novel swine FTR model, providing a reliable and effective platform for further research on FTR.

Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

Growth capacity of a Wharton's Jelly derived mesenchymal stromal cells tissue engineered vascular graft used for main pulmonary artery reconstruction in piglets.

Background: Surgical treatment of congenital heart defects affecting the right ventricular outflow tract (RVOT) often requires complex reconstruction and multiple reoperations due to structural degeneration and lack of growth of currently available materials. Hence, alternative approaches for RVOT reconstruction, which meet the requirements of biocompatibility and long-term durability of an ideal scaffold, are needed. Through this full scale pre-clinical study, we demonstrated the growth capacity of a Wharton's Jelly derived mesenchymal stromal cells (WJ-MSC) tissue engineered vascular graft used in reconstructing the main pulmonary artery in piglets, providing proof of biocompatibility and efficacy. Methods: Sixteen four-week-old Landrace pigs were randomized to undergo supravalvar Main Pulmonary Artery (MPA) replacement with either unseeded or WJ-MSCs-seeded Small Intestinal Submucosa-derived grafts. Animals were followed up for 6 months by clinical examinations and cardiac imaging. At termination, sections of MPAs were assessed by macroscopic inspection, histology and fluorescent immunohistochemistry. Results: Data collected at 6 months follow up showed no sign of graft thrombosis or calcification. The explanted main pulmonary arteries demonstrated a significantly higher degree of cellular organization and elastin content in the WJ-MSCs seeded grafts compared to the acellular counterparts. Transthoracic echocardiography and cardiovascular magnetic resonance confirmed the superior growth and remodelling of the WJ-MSCs seeded conduit compared to the unseeded. Conclusion: Our findings indicate that the addition of WJ-MSCs to the acellular scaffold can upgrade the material, converting it into a biologically active tissue, with the potential to grow, repair and remodel the RVOT.

Changes in glial cell activation and extracellular vesicles production precede the onset of disease symptoms in transgenic hSOD1G93A pigs.

SOD1 gene is associated with progressive motor neuron degeneration in the familiar forms of amyotrophic lateral sclerosis. Although studies on mutant human SOD1 transgenic rodent models have provided important insights into disease pathogenesis, they have not led to the discovery of early biomarkers or effective therapies in human disease. The recent generation of a transgenic swine model expressing the human pathological hSOD1G93A gene, which recapitulates the course of human disease, represents an interesting tool for the identification of early disease mechanisms and diagnostic biomarkers. Here, we analyze the activation state of CNS cells in transgenic pigs during the disease course and investigate whether changes in neuronal and glial cell activation state can be reflected by the amount of extracellular vesicles they release in biological fluids. To assess the activation state of neural cells, we performed a biochemical characterization of neurons and glial cells in the spinal cords of hSOD1G93A pigs during the disease course. Quantification of EVs of CNS cell origin was performed in cerebrospinal fluid and plasma of transgenic pigs at different disease stages by Western blot and peptide microarray analyses. We report an early activation of oligodendrocytes in hSOD1G93A transgenic tissue followed by astrocyte and microglia activation, especially in animals with motor symptoms. At late asymptomatic stage, EV production from astrocytes and microglia is increased in the cerebrospinal fluid, but not in the plasma, of transgenic pigs reflecting donor cell activation in the spinal cord. Estimation of EV production by biochemical analyses is corroborated by direct quantification of neuron- and microglia-derived EVs in the cerebrospinal fluid by a Membrane Sensing Peptide enabled on-chip analysis that provides fast results and low sample consumption. Collectively, our data indicate that alteration in astrocytic EV production precedes the onset of disease symptoms in the hSODG93A swine model, mirroring donor cell activation in the spinal cord, and suggest that EV measurements from the cells first activated in the ALS pig model, i.e. OPCs, may further improve early disease detection.

Modulation of Inflammatory Response by Electromagnetic Field Stimulation in Traumatic Brain Injury in Yucatan Swine.

Traumatic brain injury is a leading cause of disability and death worldwide and represents a high economic burden for families and national health systems. After mechanical impact to the head, the first stage of the damage comprising edema, physical damage, and cell loss gives rise to a second phase characterized by glial activation, increased oxidative stress and excitotoxicity, mitochondrial damage, and exacerbated neuroinflammatory state, among other molecular calamities. Inflammation strongly influences the molecular events involved in the pathogenesis of TBI. Therefore, several components of the inflammatory cascade have been targeted in experimental therapies. Application of Electromagnetic Field (EMF) stimulation has been found to be effective in some inflammatory conditions. However, its effect in the neuronal recovery after TBI is not known. In this pilot study, Yucatan miniswine were subjected to TBI using controlled cortical impact approach. EMF stimulation via a helmet was applied immediately or two days after mechanical impact. Three weeks later, inflammatory markers were assessed in the brain tissues of injured and contralateral non-injured areas of control and EMF-treated animals by histomorphometry, immunohistochemistry, RT-qPCR, Western blot, and ELISA. Our results revealed that EMF stimulation induced beneficial effect with the preservation of neuronal tissue morphology as well as the reduction of inflammatory markers at the transcriptional and translational levels. Immediate EMF application showed better resolution of inflammation. Although further studies are warranted, our findings contribute to the notion that EMF stimulation could be an effective therapeutic approach in TBI patients.

Recovery of extracorporeal lungs using cross-circulation with injured recipient swine.

OBJECTIVE: Lung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia. METHODS: Swine donor lungs (n = 6) were stored at 4 °C for 24 hours while recipient swine (n = 6) underwent gastric aspiration injury before cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation. RESULTS: Recipient swine lung injury resulted in sustained, impaired oxygenation (arterial oxygen tension/inspired oxygen fraction ratio 205 ± 39 mm Hg vs 454 ± 111 mm Hg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, arterial oxygen tension/inspired oxygen fraction ratio 138 ± 28.2 mm Hg; 24 hours, 539 ± 156 mm Hg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours. CONCLUSIONS: We demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease who are candidates for this clinical application.

Limitation of cerebral blood flow by increased venous outflow resistance in elevated ICP.

Extensive investigation and modeling efforts have been dedicated to cerebral pressure autoregulation, which is primarily regulated by the ability of the cerebral arterioles to change their resistance and modulate cerebral blood flow (CBF). However, the mechanisms by which elevated intracranial pressure (ICP) leads to increased resistance to venous outflow have received less attention. We modified our previously described model of intracranial fluid interactions with a newly developed model of a partially collapsed blood vessel, which we termed the "flow control zone" (FCZ). We sought to determine the degree to which ICP elevation causing venous compression at the FCZ becomes the main parameter limiting CBF. The FCZ component was designed using nonlinear functions representing resistance as a function of cross-sectional area and the pressure-volume relations of the vessel wall. We used our previously described swine model of cerebral edema with graduated elevation of ICP to calculate venous outflow resistance and a newly defined parameter, the cerebral resistance index (CRI), which is the ratio between venous outflow resistance and cerebrovascular resistance. Model simulations of cerebral edema and increased ICP led to increased venous outflow resistance. There was a close similarity between model predictions of venous outflow resistance and experimental results in the swine model (cross-correlation coefficient of 0.97, a mean squared error of 0.087, and a mean absolute error of 0.15). CRI was strongly correlated to ICP in the swine model (r2 = 0.77, P = 0.00012, 95% confidence interval [0.15, 0.45]). A CRI value of 0.5 was associated with ICP values above clinically significant thresholds (24 mmHg) in the swine model and a diminished capacity of changes in arteriolar resistance to influence flow in the mathematical model. Our results demonstrate the importance of venous compression at the FCZ in determining CBF when ICP is elevated. The cerebral resistance index may provide an indication of when compression of venous outflow becomes the dominant factor in limiting CBF following brain injury.NEW & NOTEWORTHY The goal of this study was to investigate the effects of venous compression caused by elevated intracranial pressure (ICP) due to cerebral edema, validated through animal experiments. The flow control zone model highlights the impact of cerebral venous compression on cerebral blood flow (CBF) during elevated ICP. The cerebral venous outflow resistance-to-cerebrovascular resistance ratio may indicate when venous outflow compression becomes the dominant factor limiting CBF. CBF regulation descriptions should consider how arterial or venous factors may predominantly influence flow in different clinical scenarios.

Corrigendum: Effect of high-fat and low-fat dairy products on cardiometabolic risk factors and immune function in a low birthweight swine model of diet-induced insulin resistance.

[This corrects the article DOI: 10.3389/fnut.2022.923120.].

A Swine Model of Neural Circuit Electromagnetic Fields: Effects of Immediate Electromagnetic Field Stimulation on Cortical Injury.

Background Neurologic diseases have profound disability, mortality, and socioeconomic effects worldwide. Treatment of these disorders varies but is largely limited to unique factors associated with neural physiology. Early studies have evaluated alterations in electromagnetic fields (EMF) due to neural disorders with subsequent modulation of EMF as a potential treatment modality. Swine models have begun to be evaluated as translational models in this effect. Methods EMF measurements of a Yucatan miniswine were recorded using proprietary non-contact, non-invasive induction sensors with a dual layer Mu-metal and interlaced copper mesh helmet. The swine then underwent controlled cortical impact (CCI) to simulate traumatic brain injury (TBI). Twenty minutes post-injury after surgical wound closure, the swine underwent targeted EMF signal modulation using a signal generator to stimulate the swine's injured cortical circuit using a sinusoidal wave individualized at 2.5 Hz with a 500mV positive offset at 1V. After 10 days of stimulation, settings were modified to another individualized frequency of 5.5 Hz, 500mV positive offset and 1V for stimulation. Behavioral patterns in swine were evaluated, and EMF measurements were recorded daily prior to, during, and after stimulation. Artificial intelligence (AI) models evaluated patterns in EMF signals. Histology of the stimulated swine cortex was evaluated using hematoxylin and eosin staining and pentachrome staining and compared to a control swine without stimulation and a swine that had received stimulation two days post-injury in a delayed fashion. Serial serum specimens and tissue at the time of euthanasia were obtained for assessment of neuron-specific enolase (NSE) concentration. Results Pre-operative and post-stimulation measurements demonstrated differences in patterns and activity early on. There was an identified peak at 1.6Hz, not frequently seen pre-operatively. There were convergent frequencies in both data sets at 10.5 Hz and 3.9 Hz. Plateaus and decreased variability of changes in slope were identified early in the post-injury phase. AI modeling identified early similarities in pre-operative and post-stimulation measurements through the patterns of peaks with similarities on postoperative day 10 and similarities in the valleys on postoperative day 17. Histologic specimens identified increased degrees of apoptosis and cellular death in the non-stimulated control compared to the stimulated swine. Similarly, the immediately stimulated swine had less apoptosis and increased histologic viability at the site of injury compared to the two-day delayed stimulation swine. There were increased levels of NSE noted in the stimulated swine at the site of injury compared to non-injured sites and the control swine. Conclusions Cortical function was appropriately measured through induction sensors and shielding in the form of a helmet and electromagnetic field channels. Early stimulation resulted in the early and durable recovery of neuronal circuit-driven electromagnetic field patterns. Histology identified increased viability of neurons with fewer apoptotic neurons and glial cells in stimulated swine with early stimulation identifying the best effect compared to a non-stimulated subject. This recovery identifies change and recovery at the circuit, cellular, and subcellular levels that potentiate the need for further study of EMF modulation as a treatment modality in neurological disorders.

A Swine Model of Changes in the Neuronal Electromagnetic Field After Traumatic Brain Injury: A Pilot Study.

Background Traumatic brain injury (TBI) is a global cause of disability and mortality. Treatment depends on mitigation of secondary injury resulting in axonal injury, necrosis, brain dysfunction, and disruption of electrical and chemical signaling in neural circuits. To better understand TBI, translational models are required to study physiology, diagnostics, and treatments in homologous species, such as swine. Electromagnetic fields (EMFs) from altered neural circuits can be measured and historically have been reliant on expensive shielding and supercooling in magnetoencephalography. Using proprietary induction sensors, it has been found that a non-invasive, non-contact approach with an engineered Mu-metal and copper mesh-shielded helmet effectively measures EMFs. This has not yet been investigated in swine models. We wished to evaluate the efficacy of this technology to assess TBI-dependent EMF changes in swine to describe the efficacy of these sensors and this model using a gravity-dependent controlled cortical impact (CCI). Methods A Yucatan miniswine was evaluated using non-contact, non-invasive proprietary induction sensors with an engineered dual-layer Mu-metal and interlaced copper mesh helmet with sensors within EMF channels connected to a helmet. Swine EMF recordings were obtained prior to induced gravity-dependent CCI followed by post-TBI measurements. Behavioral changes and changes in EMF measurements were assessed. EMF measurements were evaluated with an artificial intelligence (AI) model. Results Differences between room "noise" EMF measurements and pre-TBI swine electromagnetic field measurements were identified. Morphological characteristics between pre-injury and post-injury measurements were noted. AI modeling differentiated pre-injury and post-injury patterns in the swine EMF. Frequently identified frequencies seen post-injury were peaks at 2.5 Hz and 6.5 Hz and a valley at 11 Hz. The AI model identified less changes in the slope and thus decreased variation of EMF measurements post-TBI between 4.5 Hz and 7 Hz. Conclusions For the first time, it was identified that cortical function in a swine can be appropriately measured using novel induction sensors and shielding isolated to a helmet and EMF channels. The swine model can be appropriately differentiated from the external noise signal with identifiably different pre-injury and post-injury EMFs. Patterns can be recognized within the post-injury EMF due to altered neural circuits that can be measured using these sensors continuously, non-invasively, and in real time.

A Swine Model of Traumatic Brain Injury: Effects of Neuronally Generated Electromagnetic Fields and Electromagnetic Field Stimulation on Traumatic Brain Injury-Related Changes.

Background and objective Traumatic brain injury (TBI) has been associated with aberrations in neural circuitry attributable to the pathology resulting in electromagnetic field (EMF) changes. These changes have been evaluated in a variety of settings including through novel induction sensors with an ultra-portable shielded helmet and EMF channels with differences identified by comparing pre-injury and post-injury states. Modulation of the EMF has undergone cursory evaluation in neurologic conditions but has not yet been fully evaluated for clinical effects in treatment. Target EMF stimulation using EMF-related changes preoperatively to postoperatively has not yet been attempted and has not been completed using induction sensor technology. Our objectives in this study were twofold: we wanted to test the hypothesis that targeted stimulation using an EMF signal generator and stimulator to abnormal thresholds identified by real-time measurement of EMFs may enable early resolution of EMF changes and treatment of the TBI as modeled through controlled cortical impact (CCI); we also aimed to assess the feasibility of attempting this using real-time measurements with an EMF shielded helmet with EMF channels and non-contact, non-invasive induction sensors with attached EMF transmitters in real-time. Methods A singular Yucatan miniswine was obtained and baseline EMF recordings were obtained. A CCI of TBI and postoperative assessment of cortical EMF in a non-invasive, non-contact fashion were completed. Alterations in EMF were evaluated and EMF stimulation using those abnormal frequencies was completed using multiple treatments involving three minutes of EMF stimulation at abnormal frequencies. Stimulation thresholds of 2.5 Hz, 3.5 Hz, and 5.5 Hz with 1 V signal intensity were evaluated using sinusoidal waves. Additionally, stimulation thresholds using differing offsets to the sine wave at -500 mV, 0 mV, and 500 mv were assessed. Daily EMF and post-stimulation EMF measurements were recorded. EMF patterns were then assessed using an artificial intelligence (AI) model. Results AI modeling appropriately identified differences in EMF signal in pre-injury, post-injury, and post-stimulation states. EMF stimulation using a positive offset of 500 mV appeared to have maximal beneficial effects in return to baseline. Similarly targeted stimulation using thresholds of 2.5 Hz and 5.5 Hz with a positive 500 mV offset at 1 V allowed for recovery of EMF patterns post-injury towards patterns seen in baseline EMF measurements on stimulation day seven (postoperative day 17). Conclusion Stimulation of neural circuits with targeted EMF in a sinusoidal pattern with targeted thresholds after measurement with induction sensors with shielding isolated to a Mu-metal and copper mesh helmet and EMF channels is efficacious in promoting neuronal circuit recovery to preoperative baselines in the TBI miniswine model. Similarly, our findings confirm the appropriateness of this translational model in the evaluation of brain neuronal circuit EMF and that preoperative and post-trauma differences can be appropriately assessed with this technology.

Impaired cardiac glycolysis and glycogen depletion are linked to poor myocardial outcomes in juvenile male swine with metabolic syndrome and ischemia.

Obesity continues to rise in the juveniles and obese children are more likely to develop metabolic syndrome (MetS) and related cardiovascular disease. Unfortunately, effective prevention and long-term treatment options remain limited. We determined the juvenile cardiac response to MetS in a swine model. Juvenile male swine were fed either an obesogenic diet, to induce MetS, or a lean diet, as a control (LD). Myocardial ischemia was induced with surgically placed ameroid constrictor on the left circumflex artery. Physiological data were recorded and at 22 weeks of age the animals underwent a terminal harvest procedure and myocardial tissue was extracted for total metabolic and proteomic LC/MS-MS, RNA-seq analysis, and data underwent nonnegative matrix factorization for metabolic signatures. Significantly altered in MetS versus. LD were the glycolysis-related metabolites and enzymes. In MetS compared with LD Glycogen synthase 1 (GYS1)-glycogen phosphorylases (PYGM/PYGL) expression disbalance resulted in a loss of myocardial glycogen. Our findings are consistent with the concept that transcriptionally driven myocardial changes in glycogen and glucose metabolism-related enzymes lead to a deficiency of their metabolite products in MetS. This abnormal energy metabolism provides insight into the pathogenesis of the juvenile heart in MetS. This study reveals that MetS and ischemia diminishes ATP availability in the myocardium via altering the glucose-G6P-pyruvate axis at the level of metabolites and gene expression of related enzymes. The observed severe glycogen depletion in MetS coincides with disbalance in expression of GYS1 and both PYGM and PYGL. This altered energy substrate metabolism is a potential target of pharmacological agents for improving juvenile myocardial function in MetS and ischemia.

Detection of Myocardial Ischemia Using Cardiovascular MRI Stress T1 Mapping: A Miniature-Swine Validation Study.

Purpose: To assess the efficacy of cardiac MRI stress T1 mapping in detecting ischemic and infarcted myocardium in a miniature-swine model, using pathologic findings as the reference standard. Materials and Methods: Ten adult male Chinese miniature swine, with coronary artery stenosis induced by an ameroid constrictor, and two healthy control swine were studied. Cardiac 3-T MRI rest and adenosine triphosphate stress T1 mapping and perfusion images, along with resting and late gadolinium enhancement images, were acquired at baseline and weekly up to 4 weeks after surgery or until humanely killed. A receiver operating characteristic analysis was used to analyze the performance of T1 mapping in the detection of myocardial ischemia. Results: In the experimental group, both the infarcted myocardium (ΔT1 = 10 msec ± 2 [SD]; ΔT1 percentage = 0.7% ± 0.1) and ischemic myocardium (ΔT1 = 10 msec ± 2; ΔT1 percentage = 0.9% ± 0.2) exhibited reduced T1 reactivity compared with the remote myocardium (ΔT1 = 53 msec ± 7; ΔT1 percentage = 4.7% ± 0.6) and normal myocardium (ΔT1 = 56 msec ± 11; ΔT1 percentage = 4.9% ± 1.1). Receiver operating characteristic analysis demonstrated high diagnostic performance of ΔT1 in detecting ischemic myocardium, with an area under the curve (AUC) of 0.84 (P < .001). Rest T1 displayed high diagnostic performance in detecting infarcted myocardium (AUC = 0.95; P < .001). When rest T1 and ΔT1 were combined, the diagnostic performance for both ischemic and infarcted myocardium were improved (AUCs, 0.89 and 0.97, respectively; all P < .001). The collagen volume fraction correlated with ΔT1, ΔT1 percentage, and Δ extracellular volume percentage (r = -0.70, -0.70, and -0.50, respectively; P = .001, .001, and .03, respectively). Conclusion: Using histopathologic validation in a swine model, noninvasive cardiac MRI stress T1 mapping demonstrated high performance in detecting ischemic and infarcted myocardium without the need for contrast agents.Keywords: Coronary Artery Disease, MRI, Myocardial Ischemia, Rest T1 Mapping, Stress T1 Mapping, Swine Model Supplemental material is available for this article. © RSNA, 2023See also commentary by Burrage and Ferreira in this issue.

Characterization of Green Fluorescent Protein in Heart Valves of a Transgenic Swine Model for Partial Heart Transplant Research.

A transgenic strain of pigs was created to express green fluorescent protein (GFP) ubiquitously using a pCAGG promoter. Here, we characterize GFP expression in the semilunar valves and great arteries of GFP-transgenic (GFP-Tg) pigs. Immunofluorescence was performed to visualize and quantify GFP expression and colocalization with nuclear staining. GFP expression was confirmed in both the semilunar valves and great arteries of GFP-Tg pigs compared to wild-type tissues (aorta, p = 0.0002; pulmonary artery, p = 0.0005; aortic valve; and pulmonic valve, p < 0.0001). The quantification of GFP expression in cardiac tissue allows this strain of GFP-Tg pigs to be used for future research in partial heart transplantation.

Intracranial electrophysiological recordings on a swine model of mesial temporal lobe epilepsy.

Objective: To test the feasibility and reliability of intracranial electrophysiological recordings in an acute status epilepticus model on laboratory swine. Method: Intrahippocampal injection of kainic acid (KA) was performed on 17 male Bama pigs (Sus scrofa domestica) weighing between 25 and 35 kg. Two stereoelectroencephalography (SEEG) electrodes with a total of 16 channels were implanted bilaterally along the sensorimotor cortex to the hippocampus. Brain electrical activity was recorded 2 h daily for 9-28 days. Three KA dosages were tested to evaluate the quantities capable of evoking status epilepticus. Local field potentials (LFPs) were recorded and compared before and after the KA injection. We quantified the epileptic patterns, including the interictal spikes, seizures, and high-frequency oscillations (HFOs), up to 4 weeks after the KA injection. Test-retest reliability using intraclass correlation coefficients (ICCs) were performed on interictal HFO rates to evaluate the recording stability of this model. Results: The KA dosage test suggested that a 10 µl (1.0 µg/µl) intrahippocampal injection could successfully evoke status epilepticus lasting from 4 to 12 h. At this dosage, eight pigs (50% of total) had prolonged epileptic events (tonic-chronic seizures + interictal spikes n = 5, interictal spikes alone n = 3) in the later 4 weeks of the video-SEEG recording period. Four pigs (25% of total) had no epileptic activities, and another four (25%) had lost the cap or did not complete the experiments. Animals that showed epileptiform events were grouped as E + (n = 8) and the four animals showing no signs of epileptic events were grouped as E- (n = 4). A total of 46 electrophysiological seizures were captured in the 4-week post-KA period from 4 E + animals, with the earliest onset on day 9. The seizure durations ranged from 12 to 45 s. A significant increase of hippocampal HFOs rate (num/min) was observed in the E+ group during the post-KA period (weeks 1, 2,4, p < 0.05) compared to the baseline. But the E-showed no change or a decrease (in week 2, p = 0.43) compared to their baseline rate. The between-group comparison showed much higher HFO rates in E + vs. E - (F = 35, p < 0.01). The high ICC value [ICC (1, k) = 0.81, p < 0.05] quantified from the HFO rate suggested that this model had a stable measurement of HFOs during the four-week post-KA periods. Significance: This study measured intracranial electrophysiological activity in a swine model of KA-induced mesial temporal lobe epilepsy (mTLE). Using the clinical SEEG electrode, we distinguished abnormal EEG patterns in the swine brain. The high test-retest reliability of HFO rates in the post-KA period suggests the utility of this model for studying mechanisms of epileptogenesis. The use of swine may provide satisfactory translational value for clinical epilepsy research.

Effect of SAM junctional tourniquet on respiration when applied in the axilla: A swine model.

PURPOSE: SAM junctional tourniquet (SJT) has been applied to control junctional hemorrhage. However, there is limited information about its safety and efficacy when applied in the axilla. This study aims to investigate the effect of SJT on respiration when used in the axilla in a swine model. METHODS: Eighteen male Yorkshire swines, aged 6-month-old and weighing 55 - 72 kg, were randomized into 3 groups, with 6 in each. An axillary hemorrhage model was established by cutting a 2 mm transverse incision in the axillary artery. Hemorrhagic shock was induced by exsanguinating through the left carotid artery to achieve a controlled volume reduction of 30% of total blood volume. Vascular blocking bands were used to temporarily control axillary hemorrhage before SJT was applied. In Group I, the swine spontaneously breathed, while SJT was applied for 2 h with a pressure of 210 mmHg. In Group II, the swine were mechanically ventilated, and SJT was applied for the same duration and pressure as Group I. In Group III, the swine spontaneously breathed, but the axillary hemorrhage was controlled using vascular blocking bands without SJT compression. The amount of free blood loss was calculated in the axillary wound during the 2 h of hemostasis by SJT application or vascular blocking bands. After then, a temporary vascular shunt was performed in the 3 groups to achieve resuscitation. Pathophysiologic state of each swine was monitored for 1 h with an infusion of 400 mL of autologous whole blood and 500 mL of lactated ringer solution. Tb and T0 represent the time points before and immediate after the 30% volume-controlled hemorrhagic shock, respectively. T30, T60, T90 and T120, denote 30, 60, 90, and 120 min after T0 (hemostasis period), while T150, and T180 denote 150 and 180 min after T0 (resuscitation period). The mean arterial pressure and heart rate were monitored through the right carotid artery catheter. Blood samples were collected at each time point for the analysis of blood gas, complete cell count, serum chemistry, standard coagulation tests, etc., and thromboelastography was conducted subsequently. Movement of the left hemidiaphragm was measured by ultrasonography at Tb and T0 to assess respiration. Data were presented as mean ± standard deviation and analyzed using repeated measures of two-way analysis of variance with pairwise comparisons adjusted using the Bonferroni method. All statistical analyses were processed using GraphPad Prism software. RESULTS: Compared to Tb, a statistically significant increase in the left hemidiaphragm movement at T0 was observed in Groups I and II (both p < 0.001). In Group III, the left hemidiaphragm movement remained unchanged (p = 0.660). Compared to Group I, mechanical ventilation in Group II significantly alleviated the effect of SJT application on the left hemidiaphragm movement (p < 0.001). Blood pressure and heart rate rapidly increased at T0 in all three groups. Respiratory arrest suddenly occurred in Group I after T120, which required immediate manual respiratory assistance. PaO2 in Group I decreased significantly at T120, accompanied by an increase in PaCO2 (both p < 0.001 vs. Groups II and III). Other biochemical metabolic changes were similar among groups. However, in all 3 groups, lactate and potassium increased immediately after 1 min of resuscitation concurrent with a drop in pH. The swine in Group I exhibited the most severe hyperkalemia and metabolic acidosis. The coagulation function test did not show statistically significant differences among three groups at any time point. However, D-dimer levels showed a more than 16-fold increase from T120 to T180 in all groups. CONCLUSION: In the swine model, SJT is effective in controlling axillary hemorrhage during both spontaneous breathing and mechanical ventilation. Mechanical ventilation is found to alleviate the restrictive effect of SJT on thoracic movement without affecting hemostatic efficiency. Therefore, mechanical ventilation could be necessary before SJT removal.

Intracoronary Administration of Microencapsulated HGF in a Reperfused Myocardial Infarction Swine Model.

Therapy microencapsulation allows minimally invasive, safe, and effective administration. Hepatocyte growth factor (HGF) has angiogenic, anti-inflammatory, anti-apoptotic, and anti-fibrotic properties. Our objective was to evaluate the cardiac safety and effectiveness of intracoronary (IC) administration of HGF-loaded extended release microspheres in an acute myocardial infarction (AMI) swine model. An IC infusion of 5 × 106 HGF-loaded microspheres (MS+HGF, n = 7), 5 × 106 placebo microspheres (MS, n = 7), or saline (SAL, n = 7) was performed two days after AMI. TIMI flow and Troponin I (TnI) values were assessed pre- and post-treatment. Cardiac function was evaluated with magnetic resonance imaging (cMR) before injection and at 10 weeks. Plasma cytokines were determined to evaluate the inflammatory profile and hearts were subjected to histopathological evaluation. Post-treatment coronary flow was impaired in five animals (MS+HGF and MS group) without significant increases in TnI. One animal (MS group) died during treatment. There were no significant differences between groups in cMR parameters at any time (p > 0.05). No statistically significant changes were found between groups neither in cytokines nor in histological analyses. The IC administration of 5 × 106 HGF-loaded-microspheres 48 h post-AMI did not improve cardiac function, nor did it decrease inflammation or cardiac fibrosis in this experimental setting.

TNF ΔARE Pigs: A Translational Crohn's Disease Model.

BACKGROUND AND AIMS: Crohn's disease [CD] is a major subtype of inflammatory bowel diseases [IBD] with increasing incidence and prevalence. Results of studies using available small and large animal models are often poorly translatable to patients, and few CD models show small intestinal pathology. Due to its similarities to humans, the pig has emerged as a highly suitable translational disease model, particularly for testing novel nutritional and technological interventions. Our goal was to develop a physiologically relevant porcine CD model to facilitate translation of findings and interventions towards the clinic. METHODS: We generated pigs bearing a 93-bp deletion of the adenosine-uracil-rich element [ARE] and a constitutive-decay element within the 3' untranslated region of the TNF gene. Comparative analysis of physiological, molecular, histological and microbial characteristics was performed between wild-type, TNFΔARE/+ and TNFΔARE/ΔARE animals. Alterations in the microbiome were compared to the TNFΔARE mouse model and IBD patients. RESULTS: TNF ΔARE pigs recapitulate major characteristics of human CD, including ulcerative transmural ileocolitis, increased abundance of proinflammatory cytokines, immune cell infiltration and dysbiotic microbial communities. 16S rRNA gene amplicon sequencing revealed enrichment in members belonging to Megasphaera, Campylobacter, Desulfovibrio, Alistipes and Lachnoclostridum in faecal or mucosa-associated bacteria compared to wild-type littermates. Principal components analysis clustering with a subset of TNFΔARE/+ mice and human IBD patients suggests microbial similarity based on disease severity. CONCLUSIONS: We demonstrate that the TNFΔARE pig resembles a CD-like ileocolitis pathophenotype recapitulating human disease. The ability to conduct long-term studies and test novel surgical procedures and dietary interventions in a physiologically relevant model will benefit future translational IBD research studies.

Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy.

Millions of people suffer from end-stage refractory diseases. The ideal treatment option for terminally ill patients is organ transplantation. However, donor organs are in absolute shortage, and sadly, most patients die while waiting for a donor organ. To date, no technology has achieved long-term sustainable patient-derived organ generation. In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology.