Porcine Model Research Articles

Acute intracardiac electrogram changes and their relation to pulsed field ablation dose in porcine left ventricle

Abstract Background Pulsed field ablation (PFA) is an emerging cardiac ablation modality based on irreversible electroporation with promising preclinical and clinical results. Acute reduction of intracardiac electrograms (bipolar iEGMs) is consistently observed, similar to other ablation modalities, e.g. radiofrequency ablation. We and others have previously reported lesion size dependence on PFA dosing. However, the relevance of iEGM changes and their dependence on the PFA dose is not established. Furthermore, our study shows that unipolar iEGM signals may contain additional information about the effects of PFA in cardiac tissue. Purpose To quantify the effect of different PFA dosing on changes observed in bipolar and unipolar iEGMs within 5 minutes after the ablation. Methods In total, PFA was applied endocardially at 40 sites in the left ventricles of 8 pigs via a 5 mm tip catheter using a modified decapolar catheter in the inferior vena cava for current return (all electrodes). The following PFA doses (voltage and number of pulse trains) were used: 1000 V, 4 trains; 1300 V, 4 trains; 1500 V, 1 train; 1500 V, 4 trains; 1500 V, 8 trains; and 1500 V, 16 trains. For standard bipolar iEGMs (30 Hz – 500 Hz) the reduction in peak-to-peak amplitude after PFA was considered as a measure of the effect. In addition, unipolar iEGMs (0.5 Hz – 500 Hz) were decomposed into non-overlapping frequency sub-bands with Daubechies order 6 discrete wavelet transform (Figure 1A) allowing separate analysis in high-frequency (HF) and low-frequency (LF) ranges (63 Hz – 500 Hz and 0.5 Hz – 8 Hz, respectively). Results In total, 30 standard bipolar and 35 unipolar iEGMs (with at least 3.5 minutes of artefact-free post-ablation duration) were analysed. No dose dependency was observed for standard bipolar iEGMs within 5 minutes post-ablation (data not shown). However, the HF and LF content of unipolar iEGMs revealed opposing effects: a decrease in the HF and an increase in the LF content. Correlation with the dose was clearer in the LF content 3.5 minutes post-ablation, the difference being significant (p<0.05) between the lowest and the highest doses (Figure 1B and C). Discussion The decrease in HF content could reflect electrical silencing, ie. stunning of locally affected cardiomyocytes, most likely caused by irreversibly electroporated (ablated) cells located close to the catheter tip and by reversibly electroporated or otherwise temporarily silenced cells in adjacent tissue. The increase in LF content could reflect the current-of-injury effect, which is a broader area phenomenon derived from electrical potential differences between affected (reversibly and irreversibly electroporated) and non-affected regions. Conclusion Unipolar iEGMs acquired with a broadened frequency range and decomposed into HF and LF content provide new insight into the effects of PFA and correlate with PFA dosing in this pre-clinical porcine model.

Autonomous precision resuscitation during ground and air transport of an animal hemorrhagic shock model

We tested the ability of a physiologically driven minimally invasive closed-loop algorithm, called Resuscitation based on Functional Hemodynamic Monitoring (ReFit), to stabilize for up to 3 h a porcine model of noncompressible hemorrhage induced by severe liver injury and do so during both ground and air transport. Twelve animals were resuscitated using ReFit to drive fluid and vasopressor infusion to a mean arterial pressure (MAP) > 60 mmHg and heart rate < 110 min−1 30 min after MAP < 40 mmHg following liver injury. ReFit was initially validated in 8 animals in the laboratory, then in 4 animals during air (23nm and 35nm) and ground (9 mi) to air (9.5nm and 83m) transport returning to the laboratory. The ReFit algorithm kept all animals stable for ~ 3 h. Thus, ReFit algorithm can diagnose and treat ongoing hemorrhagic shock independent to the site of care or during transport. These results have implications for treatment of critically ill patients in remote, austere and contested environments and during transport to a higher level of care.

Neural control of ventricular electrophysiology: the role of the posterior descending ganglionated plexus

Abstract Background The autonomic nervous system plays an integral role in cardiac physiology. While the atrially located ganglionated plexus have been studied in several species, there is limited knowledge regarding the functional characterization of ventricular ganglionated plexus. Purpose The aim of the present study was to assess the role of the posterior descending ganglionated plexus (PD-GP) for neural control of ventricular electrophysiology. Methods First, to investigate whether the mouse may be useful as an animal model, a review of whole-mount immunohistological stained murine hearts (n=43) was conducted. Second, functional studies were performed in an ex-vivo retrograde-perfused porcine model (n=3) at baseline (pacing with a cycle length of 600 ms), during PD-GP high-frequency and local nicotine stimulation (Figure 1A). Wave propagation characteristics were determined by epicardial activation mapping. Activation recovery intervals (ARIs) were analyzed with a multi-electrode sock placed around the epicardium (Figure 1B). Finally, morphological analysis of explanted human hearts was conducted to determine the potential of translation into clinical practice. Results In murine hearts, ventricular ganglionated plexus were present in only 10% of hearts. In porcine hearts, dispersion of conduction velocity was increased during PD-GP high-frequency (8.52±2.24 radian vs. 2.79±0.89 radian; p=0.018) and nicotine stimulation (19.79±6.49 radian vs. 2.79±0.89 radian; p=0.044) compared to paced rhythm (Figure 1C). High-frequency stimulation prolonged ARIs in the posterior (257.8±6.7 ms vs. 244.8±1.9 ms; p=0.044) and basal (258.1±4.2 ms vs. 244.8±1.9 ms; p=0.039) right ventricle compared to the posterior left ventricle, while nicotine did not affect ARIs (right ventricle: 255.7±29.0 ms vs. left ventricle: 245.0±29.3 ms; p=0.677) (Figure 1D). Analysis of explanted human hearts confirmed the presence of the PD-GP in close relationship to the posterior descending coronary artery within epicardial adipose tissue (Figure 2). Conclusions While we demonstrate functional relevance of the PD-GP in explanted porcine hearts, important species-related differences might exist.Ex-vivo retrograde-perfused swine modelAnalysis of explanted human hearts

Optimizing Resuscitation of the Donation after Circulatory Death Heart by Mitochondrial Protection in a Female Porcine Model.

Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP). Hearts of female pigs (45.0 ± 4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N = 5) or presence (treated, N = 5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for an additional 300 min in working mode for a total perfusion time of 6 h. Oxidative capacity and detailed left ventricular mechanical function under an increasing workload (left atrial pressure, 6 to 12 mmHg) were assessed hourly. Left ventricular tissue was snap-frozen at the end of ESHP and used for molecular analyses. Left ventricular inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax = 440 mmHg/s; P = 0.009). Treated DCD hearts exhibited persistently higher left ventricular stroke work index during the 6-h period of ESHP, whereas untreated DCD hearts displayed a significant decline (change in left ventricular stroke work index = -3.10 ml · mmHg/g; P(time within untreated group) < 0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2 = 3.11 ml O2 · min-1 · 100 g-1; P = 0.004) and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, whereas untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates; reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage. A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts.

All-suture anchor size and drill angle influence load to failure in a porcine model of subpectoral biceps tenodesis, a biomechanical study

BackgroundTenodesis of the long head of the biceps tendon is frequently performed in shoulder surgery, and all-suture anchors have become more popular as fixation methods. However, uncertainty still exists regarding the ultimate load to failure of all-suture anchors and the best insertion angle at a cortical humeral insertion point.PurposeThe purpose of this study was to compare the biomechanical characteristics of three types of all-suture anchors frequently used for biceps tenodesis. In addition, the influence of two different insertion angles was observed in a porcine humeri model.MethodsThe ultimate load to failure and failure mode of three types of all-suture anchors (1.6 FiberTak®, 1.9 FiberTak®, 2.6 FiberTak®, Arthrex®) applicable for subpectoral biceps tenodesis were evaluated at 90° and 45° insertion angles in 12 fresh-frozen porcine humeri. The anchors were inserted equally alternated in a randomized manner at three different insertion sites along the bicipital groove, and the suture tapes were knotted around a rod for pullout testing. In total, 36 anchors were evaluated in a universal testing machine (Zwick & Roell).ResultsThe 2.6 FiberTak® shows higher ultimate loads to failure with a 90° insertion angle (944.0 N ± 169.7 N; 537.0 N ± 308.8 N) compared to the 1.9 FiberTak® (677.8 N ± 57.7 N; 426.3 N ± 167.0 N, p-value: 0.0080) and 1.6 FiberTak® (733.0 N ± 67.6 N; 450.0 N ± 155.8 N, p-value: 0.0018). All anchor types show significantly higher ultimate loads to failure and smaller standard deviations at the 90° insertion angle than at the 45° insertion angle. The major failure mode was anchor pullout. Only the 2.6 FiberTak® anchors showed suture breakage as the major failure mode when placed with a 90° insertion angle.ConclusionsAll three all-suture anchors are suitable fixation methods for subpectoral biceps tenodesis. Regarding our data, we recommend 90° as the optimum insertion angle.Clinical relevanceThe influence of anchor size and insertion angle of an all-suture anchor should be known by the surgeon for optimizing ultimate loads to failure and for achieving a secure fixation.

Twenty-four-hour Normothermic Ex Vivo Heart Perfusion With Low Flow Functional Assessment in an Adult Porcine Model.

Cold static storage and normothermic ex vivo heart perfusion are routinely limited to 6 h. This report describes intermittent left atrial (LA) perfusion that allows cardiac functional assessment in a working heart mode. Using our adult porcine model, general anesthesia was induced and a complete cardiectomy was performed following cardioplegic arrest. Back-table instrumentation was completed and normothermic ex vivo heart perfusion (NEHP) was initiated in a nonworking heart mode (Langendorff). After 1 h of resuscitation and recovery, LA perfusion was initiated and the heart was transitioned to a coronary flow-only working heart mode for 30 min. Baseline working heart parameters were documented and the heart was returned to nonworking mode. Working heart assessments were performed for 30 min every 6 h for 24 h. Twenty-four-hour NEHP on 9 consecutive hearts (280 ± 42.1 g) was successful and no significant differences were found between working heart parameters at baseline and after 24 h of perfusion. There was no difference between initial and final measurements of LA mean pressures (5.0 ± 3.1 versus 9.0 ± 6.5 mm Hg, P = 0.22), left ventricular systolic pressures (44.3 ± 7.2 versus 39.1 ± 9.0 mm Hg, P = 0.13), mean aortic pressures (30.9 ± 5.8 versus 28.1 ± 8.1 mm Hg, P = 0.37), and coronary resistance (0.174 ± 0.046 versus 0.173 ± 0.066 mL/min/g, P = 0.90). There were also no significant differences between lactate (2.4 ± 0.5 versus 2.6 ± 0.4 mmol/L, P = 0.17) and glucose (173 ± 75 versus 156 ± 70 mg/dL, P = 0.37). A novel model using intermittent LA perfusion to create a coronary flow-only working heart mode for assessment of ex vivo cardiac function has been successfully developed.

#598 Successful application of allo-hemodialysis in a porcine model of embolization-induced acute kidney injury

Abstract Background and Aims Annually, millions of kidney patients, primarily in low- and low-middle income nations, die prematurely due to the lack of affordable kidney replacement therapy. We propose a novel, low-cost alternative dialysis modality called allo-hemodialysis (alloHD), where blood of a patient with kidney failure flows counter-current to the blood of a healthy subject (“buddy”) through the dialyzer [1]. Uremic solutes and excess fluid are then excreted by the buddy's healthy kidneys. We have already demonstrated the technical feasibility of alloHD in pigs with acute kidney injury (AKI) induced by renal artery ligation [2]. In this study, we explored alloHD in a less invasive porcine model of AKI induced by renal artery embolization. Method The protocol was approved by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), New Delhi, India. We studied two female Yorkshire pigs (weight 80-90 kg) with central venous catheter as vascular access. AKI was induced by embolization of both kidneys by transcatheter deployment of Contour™ Poly Vinyl Alcohol particles (Boston Scientific, Marlborough, MA, USA). The AKI pig and the buddy pig were connected to the dialysate and blood compartments, respectively, of a Nipro Cellentia 17H dialyzer. The AKI pig was then dialyzed for 4 hours against the healthy buddy pig. During alloHD, both pigs were anticoagulated with heparin (5,000 IU/h) and the buddy pig was sedated with 1-2% isoflurane gas. Blood samples were collected before, during, and after alloHD for measurements of blood urea nitrogen (BUN) and creatinine. Results We performed nine alternate day alloHD sessions with the same pair of pigs. During alloHD, BUN and Creatinine levels declined in the AKI pig (Fig. 1) and increased—as expected—transiently above baseline in the buddy pig and then trended towards baseline post-dialysis (Fig. 1). We found no indication of hemolysis or coagulation of the extracorporeal circuit in any of the nine alloHD sessions. The animals were sacrificed after the 9th session. Conclusion We demonstrated the feasibility of alloHD in a porcine embolization AKI model. This study corroborates and complements our previous experience with alloHD in a porcine model of AKI induced by renal artery ligation. Given these promising results, we are investigating the potential for advancing to a clinical trial.

Development of a two-hit lethal liver injury model in swine.

Noncompressible truncal hemorrhage remains a leading cause of preventable death in the prehospital setting. Standardized and reproducible large animal models are essential to test new therapeutic strategies. However, existing injury models vary significantly in consistency and clinical accuracy. This study aims to develop a lethal porcine model to test hemostatic agents targeting noncompressible abdominal hemorrhages. We developed a two-hit injury model in Yorkshire swine, consisting of a grade IV liver injury combined with hemodilution. The hemodilution was induced by controlled exsanguination of 30% of the total blood volume and a 3:1 resuscitation with crystalloids. Subsequently, a grade IV liver injury was performed by sharp transection of both median lobes of the liver, resulting in major bleeding and severe hypotension. The abdominal incision was closed within 60s from the injury. The endpoints included mortality, survival time, serum lab values, and blood loss within the abdomen. This model was lethal in all animals (5/5), with a mean survival time of 24.4 ± 3.8min. The standardized liver resection was uniform at 14.4 ± 2.1% of the total liver weight. Following the injury, the MAP dropped by 27 ± 8mmHg within the first 10min. The use of a mixed injury model (i.e., open injury, closed hemorrhage) was instrumental in creating a standardized injury while allowing for a clinically significant hemorrhage. This novel highly lethal, consistent, and clinically relevant translational model can be used to test and develop life-saving interventions for massive noncompressible abdominal hemorrhage.

The effect of anatomic location on porcine models of burn injury and wound healing.

Porcine models are frequently used for burn healing studies; however, factors including anatomic location and lack of standardised wound methods can impact the interpretation of wound data. The objectives of this study are to examine the influence of anatomical locations on the uniformity of burn creation and healing in porcine burn models. To optimise burn parameters on dorsal and ventral surfaces, ex vivo and in situ euthanized animals were first used to examine the location-dependence of the burn depth and contact time relationship. The location-dependent healing in vivo was then examined using burn and excisional wounds at dorsal, ventral, caudal and cranial locations. Lactate dehydrogenase (LDH) and H&E were used to assess burn depth and wound re-epithelialization. We found that burn depth on the ventral skin was significantly deeper than that of the dorsal skin at identical thermal conditions. Compared with burns created ex vivo, burns created in situ immediately post-mortem were significantly deeper in the ventral location. In live animals, 2 out of 12 burn wounds were fully re-epithelialized after 14 days in contrast to complete re-epithelialization of all excisional wounds. Among the burn wounds, those at the cranial-dorsal site exhibited faster healing than at the caudal-dorsal site. This study showed that anatomical location is an important consideration for the consistency of burn depth creation and healing. These data support symmetric localization of treatment and control for comparative assessment of burn healing in porcine models to prevent misinterpretation of results and increase the translatability of findings to humans.

Differential Effects of Intra-Abdominal Hypertension and ARDS on Respiratory Mechanics in a Porcine Model.

Background and Objectives: Intra-abdominal hypertension (IAH) and acute respiratory distress syndrome (ARDS) are common concerns in intensive care unit patients with acute respiratory failure (ARF). Although both conditions lead to impairment of global respiratory parameters, their underlying mechanisms differ substantially. Therefore, a separate assessment of the different respiratory compartments should reveal differences in respiratory mechanics. Materials and Methods: We prospectively investigated alterations in lung and chest wall mechanics in 18 mechanically ventilated pigs exposed to varying levels of intra-abdominal pressures (IAP) and ARDS. The animals were divided into three groups: group A (IAP 10 mmHg, no ARDS), B (IAP 20 mmHg, no ARDS), and C (IAP 10 mmHg, with ARDS). Following induction of IAP (by inflating an intra-abdominal balloon) and ARDS (by saline lung lavage and injurious ventilation), respiratory mechanics were monitored for six hours. Statistical analysis was performed using one-way ANOVA to compare the alterations within each group. Results: After six hours of ventilation, end-expiratory lung volume (EELV) decreased across all groups, while airway and thoracic pressures increased. Significant differences were noted between group (B) and (C) regarding alterations in transpulmonary pressure (TPP) (2.7 ± 0.6 vs. 11.3 ± 2.1 cmH2O, p < 0.001), elastance of the lung (EL) (8.9 ± 1.9 vs. 29.9 ± 5.9 cmH2O/mL, p = 0.003), and elastance of the chest wall (ECW) (32.8 ± 3.2 vs. 4.4 ± 1.8 cmH2O/mL, p < 0.001). However, global respiratory parameters such as EELV/kg bodyweight (-6.1 ± 1.3 vs. -11.0 ± 2.5 mL/kg), driving pressure (12.5 ± 0.9 vs. 13.2 ± 2.3 cmH2O), and compliance of the respiratory system (-21.7 ± 2.8 vs. -19.5 ± 3.4 mL/cmH2O) did not show significant differences among the groups. Conclusions: Separate measurements of lung and chest wall mechanics in pigs with IAH or ARDS reveals significant differences in TPP, EL, and ECW, whereas global respiratory parameters do not differ significantly. Therefore, assessing the compartments of the respiratory system separately could aid in identifying the underlying cause of ARF.

Tacrolimus-loaded Drug Delivery Systems in Vascularized Composite Allotransplantation: Lessons and Opportunities for Local Immunosuppression.

Long-term systemic immunosuppression is needed for vascularized composite allotransplantation (VCA). The high rate of acute rejection episodes in the first posttransplant year, the development of chronic rejection, and the adverse effects that come along with this treatment, currently prevent a wider clinical application of VCA. Opportunistic infections and metabolic disturbances are among the most observed side effects in VCA recipients. To overcome these challenges, local immunosuppression using biomaterial-based drug delivery systems (DDS) have been developed. The aim of these systems is to provide high local concentrations of immunosuppressive drugs while reducing their systemic load. This review provides a summary of recently investigated local DDS with different mechanisms of action such as on-demand, ultrasound-sensitive, or continuous drug delivery. In preclinical models, ranging from rodent to porcine and nonhuman primate models, this approach has been shown to reduce systemic tacrolimus (TAC) load and adverse effects, while prolonging graft survival. Localized immunosuppression using biomaterial-based DDS represents an encouraging approach to enhance graft survival and reduce toxic side effects of immunosuppressive drugs in VCA patients. Preclinical models using TAC-releasing DDS have demonstrated high local immunosuppressive effects with a low systemic burden. However, to reduce acute rejection events in translational animal models or in the clinical reality, the use of additional low-dose systemic TAC treatment may be envisaged. Patients may benefit through efficient graft immunosuppression and survival with negligible systemic adverse effects, resulting in better compliance and quality of life.

Differential Effects of Pharmacologic and Mechanical Support on Right-Left Ventricular Coupling.

Percutaneous ventricular assist devices are increasingly relied on to maintain perfusion for cardiogenic shock patients. Optimal medical management strategies however remain uncertain from limited understanding of interventricular effects. This study analyzed the effects of pharmacologic and left-sided mechanical support on right ventricular function. A porcine model was developed to assess biventricular function during bolus pharmacologic administration before and after left-sided percutaneous ventricular assist and in cardiogenic shock. The presence of mechanical support increased right ventricular load and stress with respect to the left ventricle. This shifted and exaggerated the relative effects of commonly used vasoactive agents. Furthermore, induction of cardiogenic shock led to differential pulmonary vascular and right ventricular responses. Left ventricular ischemia and mechanical support altered interventricular coupling. Resulting impacts of pharmacologic agents indicate differential right heart responses and sensitivity to treatments and the need for further study to optimize biventricular function in shock patients.

Arterial Blood Flow and Effects on Limb Tissue Perfusion During Endoshunting of the Common Iliac Artery in an Experimental Porcine Model

Arterial Blood Flow and Effects on Limb Tissue Perfusion During Endoshunting of the Common Iliac Artery in an Experimental Porcine Model

Optical coherence tomography for the detection of electrothermal ureteral injury in an ex-vivo porcine model

Optical coherence tomography for the detection of electrothermal ureteral injury in an ex-vivo porcine model

Assessment of Autoregulation of the Cerebral Circulation during Acute Lung Injury in a Neonatal Porcine Model.

In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain's adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO2 was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO2 and PvO2; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO2 and SvO2. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO2 steps, but predominantly by hypoxemia at FiO2 < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO2 steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia.

Optical coherence tomography for the detection of electrothermal ureteral injury in an ex-vivo porcine model

Optical coherence tomography for the detection of electrothermal ureteral injury in an ex-vivo porcine model

Noninvasive Assessment of Aortic Biomechanics using 4D Flow and Cardiovascular Magnetic Resonance in a Porcine Model of Aortic Coarctation

Noninvasive Assessment of Aortic Biomechanics using 4D Flow and Cardiovascular Magnetic Resonance in a Porcine Model of Aortic Coarctation

Quantitative assessment of the troCarWash™ system for automated laparoscopic camera cleaning.

Soilage of the surgical endoscope occurs frequently during minimally invasive surgery. The resultant impairment of visualization of the surgical field compromises patient safety, prolongs operative times, and frustrates surgeons. The standard practice for cleaning the surgical camera involves a disruption in the conduct of surgery by completely removing the endoscope from the field, manually cleaning its lens, treating it with a surfactant, and reinserting it into the patient; after which the surgeon resumes the procedure. We developed an automated solution for in vivo endoscope cleaning in minimally invasive surgery- a port that detects the position of the endoscope in its distal lumen, and precisely and automatically delivers a pressurized mist of cleaning solution to the lens of the camera. No additions to the scope and minimal user interaction with the port are required. We tested the efficacy of this troCarWash™ device in a porcine model of laparoscopy. Four board-certified general surgeons were instructed to soil and then clean the laparoscope using the device. Representative pre- and post-clean images were exported from the surgical video and clarity was graded (1) digitally by a canny edge detection algorithm, and (2) subjectively by 3 blinded, unbiased observers using a semi-quantitative scale. We observed statistically significant improvements in clarity by each method and for each surgeon, and we noted significant correlation between digital and subjective scores. Based on these data, we conclude that the troCarWash™ effectively restored impaired visualization in a large animal model of laparoscopy.

Evaluating Acetate as a Renoprotective Agent After Kidney Ischemia in a Porcine Model.

Objective: Renoprotection from reperfusion injury appears to be conferred by HIF-2a activation, which can be stimulated by exogenous acetate administration. The study objective was to assess whether administration of acetate in a porcine model can mitigate kidney injury related to ischemia-reperfusion after renal hilar occlusion. Methods: A porcine single-kidney model was created by performing a laparoscopic nephrectomy followed by animal recovery. After 2 days, the animals underwent laparoscopic hilar dissection. Block randomization was used to assign pigs into one of four experimental groups. One treatment block of pigs received 150 mEq of sodium acetate intravenously during 90 minutes of en bloc occlusion of the renal hilum (herein noted as "cross-clamping"). Another block received 0.75 g/kg of oral sodium acetate for 3 days prior to cross-clamping. A third block received no acetate and underwent hilar dissection without cross-clamping (negative control). The final block received no acetate and underwent cross-clamping (positive control). Serum creatinine was used to estimate renal function post-nephrectomy. Results: A total of 16 animals (4 pigs in each group) completed the study protocol. Median pig weight was 34.6 kg. One pig receiving IV acetate was excluded from the final analysis because of unrecoverable renal failure after cross-clamping. There was a significantly lower mean serum creatinine for the IV acetate group compared with the positive control group 72 hours after cross-clamping (p = 0.012). The same effect was not observed for the pigs receiving oral acetate. By day 7, renal function had recovered without significant difference in all groups. Conclusions: We observed that the administration of intravenous acetate conferred a significant renoprotective benefit in our single kidney ischemia-reperfusion porcine model 72 hours after hilar occlusion. This work is hypothesis-generating, and further work in human subjects undergoing renal hilar occlusion during partial nephrectomy is warranted.

Catheter-based pulmonary vein isolation fails to prevent transient atrial arrhythmogenic changes related to acute obstructive respiratory events in a porcine model.

Pulmonary vein isolation (PVI) is the corner stone of modern rhythm control strategies in patients with atrial fibrillation (AF). Sleep-disordered breathing (SDB) is prevalent in more than 50% of patients undergoing AF ablation, and studies have indicated a greater recurrence rate after PVI in patients with SDB. Herein, we study the effect of catheter-based PVI on AF in a pig model for SDB. In 11 sedated spontaneously breathing pigs, obstructive apnoeas were simulated by 75 s of intermittent negative upper airway pressure (INAP) applied by a negative pressure device connected to the endotracheal tube. Intermittent negative upper airway pressures were performed before and after PVI. AF-inducibility and atrial effective refractory periods (aERPs) were determined before and during INAP by programmed atrial stimulation. Pulmonary vein isolation prolonged the aERP by 48 ± 27 ms in the right atrium (RA) (P < 0.0001) and by 40 ± 34 ms in the left atrium (LA) (P = 0.0004). Following PVI, AF-inducibility dropped from 28 ± 26% to 0% (P = 0.0009). Intermittent negative upper airway pressure was associated with a transient aERP-shortening (ΔaERP) in both atria, which was not prevented by PVI (INAP indued ΔaERP after PVI in the RA: -57 ± 34 ms, P = 0.0002; in the LA: -42 ± 24 ms, P < 0.0001). Intermittent negative upper airway pressure was associated with a transient increase in AF-inducibility (from 28 ± 26% to 69 ± 21%; P = 0.0008), which was not attenuated by PVI [INAP-associated AF-inducibility after PVI: 58 ± 33% (P = 0.5)]. Transient atrial arrhythmogenic changes related to acute obstructive respiratory events are not prevented by electrical isolation of the pulmonary veins, which partially explains the increased AF recurrence in patients with SDB after PVI procedures.