The 38th Annual Meeting of the Academy of Surgical Research: Summary of Presentations, Labs, and Workshops, Focusing on Experimental Surgery, La Jolla, CA, USA, 14–16 September 2022

Abstract

The 38th Annual Meeting of the Academy of Surgical Research took place in La Jolla, CA, USA, on 14–16 September 2022. For more than 40 years, the Academy has promoted the advancement of professional and academic standards in education and research in the arts and sciences of experimental surgery. The diverse membership includes technicians, veterinarians, medical doctors, and biomedical researchers from industry, academia, and complementary disciplines supporting discovery and translational research. At the annual meeting, this experimental surgery community shared the latest in research and surgical techniques, along with professional development that included cutting-edge lectures, hands-on training, and qualification exams for certifications. Over 130 participants from 26 different states and 3 countries were in attendance for the scientific program and social events. Two scientific tracks featuring three keynotes were presented together with a poster session. Participants could practice hands-on surgical techniques in dry and wet labs that ranged from applied surgical anesthesia to minimally invasive surgical skills, followed by in-depth discussion roundtables focused on improving study design and best practices in anesthesia and analgesia. The social program provided participants the opportunity to connect in person with potential mentors and collaborators. We present the highlights from this meeting in this report, together with selected abstracts that illustrate the diverse scientific expertise of the Academy and promising new surgical research.

1. Introduction

On 14–16 September 2022, the meeting of the Academy of Surgical Research (ASR) was held in La Jolla, CA, USA. The meeting, organized by program chair Amy Martunas together with the ASR program committee and Association Solutions, hosted more than 130 attendees from 26 different states and 3 countries representing organizations across industries, academia, and more. Attendees were welcomed by ASR president Leslie Stoll, who opened the meeting by warmly welcoming back the Academy members for the first in-person meeting following pandemic restrictions. She encouraged members to really take advantage of the opportunity to create connections between those starting out as well as seasoned individuals as an opportunity to grow and lead by building meaningful one-on-one mentoring relationships, highlighting the unique Academy of Surgical Research Mentorship program. She wished success to members taking certification exams, a rigorous accreditation process that sets standards for proper training in experimental anesthesia and surgery with independent assessment. She highlighted the new partnership with MDPI Publishing to position ‘Surgeries’ as the Academy’s official journal to provide both our members and the research community with a fully open access (OA) journal and shared the Academy’s enthusiasm for the shared mission with Surgeries to advance surgical sciences for the benefit of society at large! This decision to move to an open-access journal reflects the commitment of ASR to make research openly available, maximize visibility, and accelerate our scientific discoveries. Surgeries (ISSN 2673-4095) is an international, peer-reviewed, open-access journal offering a platform for all content related to findings and developments in experimental surgery. The journal promotes scholarly communication and interactions among scientists, clinicians, and technologists whose primary interests focus on theoretical, clinical, and experimental research and advances in all fields of surgery, including state-of-the-art surgical innovations, postoperative therapy, and surgery-preventing strategies. To kick off this special partnership, we have launched a special issue, “Interdisciplinary Experimental Surgical Research and Technologies, Featured by the Academy of Surgical Research” where you can both submit and view articles of special interest to the Academy “https://www.mdpi.com/journal/surgeries/special_issues/ASR (accessed on 15 June 2023)”.

Keynote and scientific breakout sessions focused on education and research related to experimental surgery models, technical best practices, and cutting-edge surgical innovations and refinements. A selection of abstracts from this meeting is presented in this report. Meeting participants advanced their technical skills by attending dry and wet labs that provided practice with hands-on surgical techniques that ranged from applied surgical anesthesia to minimally invasive surgical skills. This was followed by in-depth discussion roundtables focused on improving study design and best practices in anesthesia and analgesia. Finally, awards were presented in honor of key contributors to the Academy and their contributions to the field. The Academy of Surgical Research has a social program that is unmatched, providing participants with the unique opportunity to network with peers, potential mentors, collaborators, and friends in a casual and fun setting. The annual meeting is supported by generous exhibitors and corporate sponsors, providing the members with opportunities for social networking events and access to the latest commercial technologies to advance research goals.

2. Summary of Keynotes, Breakout Sessions, Posters, Labs, and Workshops

2.1. Keynotes

Dr. Kat Reed from the San Diego Zoo presented her remarkable experiences performing surgery in zoo and wildlife settings: From the Outback to Balboa Park (Figure 1). She discussed the unique challenges that zoo and wildlife settings present to surgeons and anesthetists, from a wide array of anatomic and physical challenges to the n = 1 conundrum. Dr. Reed shares cases she encountered during her career in Australian wildlife hospitals, aquaria, and now in a large American zoo. She presented one-of-a-kind cases involving avian orthopedic fracture repair, approaches to surgery, and postoperative care in nontraditional species that included invertebrates, fish, large carnivores, and even megavertebrates!

Dr. Jose Antonio Diaz, Research Associate Professor of Surgery and Director of the Division of Surgical Research at Vanderbilt University presented a lecture on deep vein thrombosis. He shared his unique expertise in preclinical modeling, having authored the first consensus paper in preclinical models of venous thrombosis that provided information on model standardization, discussed advantages and disadvantages of each model, and included a model selection algorithm that allows investigators and grant reviewers to choose the most appropriate preclinical model based on the research question. Dr. Diaz explored the mechanisms of blood clot formation, associated inflammation, and their influence on various approaches to treatment, both medical and surgical.

Dr. Tony Yaksh, Professor and Vice Chairman for Research in Anesthesiology and Pharmacology at the University of California San Diego, shared his scientific journey that formed the basis for understanding the pharmacology of spinal and dorsal root ganglion gating of pain. He presented an overview of intrathecal analgesics, the relevance of epidural versus intrathecal delivery, and side effect profiles. Dr. Yaksh’s expertise in spinal drug kinetics and safety was a perfect fit for an audience of anesthetists and surgeons keen to refine practices using the latest neuraxial anesthesia techniques, and ASR was proud to award him the 2022 ASR Jacob Markowitz Award for his significant and long-standing contributions to anesthesia, surgery, and medicine.

2.2. Breakout Sessions and Posters

Attendees were able to attend track breakout sessions and poster viewing that focused on major areas that included general surgery, technique, and new model development, infusion and ports, cardiovascular surgical models and medical devices, and anesthesia and analgesia refinements. The Michael DeLeo Award winning poster, “The Use of Injection Ports for Intrathecal Administration: The Mouse Ommaya (the Top Hat Port).” was presented by Michele Danielson. This winning abstract, together with selected abstracts from each area, are highlighted herein.

2.3. Interactive Wet Labs

Academy members with deep expertise in small and large animal anesthesia and surgery instructed wet labs at the UC San Diego School of Medicine, Center for the Future of Surgery, La Jolla, CA, USA (Figure 2). Owing to their popularity, each wet lab was provided twice, providing the opportunity for participants to join more than one lab.

Jose Negron-Garcia instructed minimally invasive surgical techniques in the swine model. Participants had the opportunity to perform endoscopic, laparoscopic, and fluoroscopy-guided endovascular procedures. The instructors mentored anesthesia and proper handling of the equipment and instruments needed to perform these procedures, along with specific techniques and tips for each. This wet lab was possible thanks to a generous donation from Premier BioSource.

Andree Lapierre provided training on vascular catheterization in rodents in a unique and state-of-the-art facility. In addition to sharing surgical tips and tricks for success, the instructors reviewed updates on surgical and anesthetic processes, surgical instruments, and postoperative recommendations for achieving long-term patency in catheterized rodents. The wet labs allowed participants to have hands-on experiences with the Instech Vascular Access Button.

Steve Kreuser instructed a hands-on wet lab in anesthesia technique in mice and rats. Participants were instructed in proper technique for intubation and procedures for successful mechanical ventilation in rodents. Participants learned the identification of the appropriate anatomy, suitable supplies, and equipment for rodent intubation, including the use of Kent Scientific’s endotracheal kits, including their intubation stands, fiber optic lights, vaporizers, and ventilators. Instructors shared several approaches along with troubleshooting tips and tricks learned over many years of trial and error. Participants gained the skills necessary to add to their resumes. Recognizing efficient rodent intubation allows for the expansion of capabilities and the ability to perform complex rodent surgeries, as well as intratracheal dosing for specific therapeutic targets.

Delphine Bouard and Bertrand Lussier instructed a hands-on dry lab in basic microsurgery. During this workshop, we will learn the principles of basic microsurgery to provide an overview of microscope settings, a description of basic instrumentation, and the principles of basic microsurgical procedures. Participants performed multiple procedures on latex models through directed exercises that included performing simple interrupted sutures, performing a purse string suture after the insertion of a catheter through a stab incision and then realizing a Chinese finger trap around the catheter, and closure using a simple continuous pattern, Ford interlocking pattern.

2.4. Workshops

The “What do I do now?” roundtable moderated by Jose Negron-Garcia and Heather Bogie and the “Anesthesia and Analgesia” roundtable moderated by Amy Martunas and Justin Hartman provided attendees the opportunity to bring their most challenging cases and complex questions to their peers and panel experts and offered opportunities to share best practices, challenges, new techniques, and form connections between individuals and teams with mutual interests. “Curious George goes to the podium—Coaching and encouragement for future ASR presenters” led Steven Kreuser and Leslie Stoll and provided attendees the opportunity to practice method sharing with a small supportive group that provided feedback and tips for making this a rewarding experience.

3. Awards for the 38th ASR Annual Meeting

The Barry Sauer Award was presented to Brittany Pavlinsky for attaining the highest Surgical Research Anesthetist exam score, to Daniel Turner for attaining the highest Surgical Research Technician exam score, and to Stephanie Caron and Renee Hlavka Lock for attaining the highest Surgical Research Specialist exam scores.

The Michael DeLeo Award was presented to Michele Danielson for the highest-scoring poster presentation, “The Use of Injection Ports for Intrathecal Administration: The Mouse Ommaya (the Top Hat Port).

Melanie Graham, MPH, PhD, a Professor of Surgery at the University of Minnesota, was presented with the Andreas von Recum Award, which honors members for their outstanding service to the members of ASR. She has been dedicated to ASR, has served on the Board of Directors, and has led the Academy’s academic website to provide members unprecedented access to ASR resources.

Tony L. Yaksh, PhD., a distinguished professor at the School of Medicine at the University of California, was presented the Jacob Markowitz Award for his outstanding contributions to the art, science, and technology of experimental surgery. The Academy recognized Dr. Yaksh’s contributions to the mechanisms of pain and analgesia. His work provided the first description of the specific analgesic actions of spinally delivered drugs, such as opiates and alpha-2 agonists, and the complexity of spinal agents in specifically altering pain processing, with more than 150 papers detailing this work.

ASR-2022 38th Annual Meeting Selected Abstracts from Breakout and Poster Sessions

• (ASR-22-1) Regional Function Change After Endomyocardial Gene Delivery in a Pig MI Model: Echo Strain Analysis
• Ke Li, Shijie Liu, Sui Zhang, James Martin, and Emerson Perin

Introduction: The Hippo pathway, an inhibitory kinase cascade, represses adult cardiomyocyte (CM) proliferation. We developed an Adeno-Associated Virus 9 (AAV9) gene therapy that can knock down this pathway on a pig model. Our previous results have shown that this therapy can improve a pig’s global heart function. This study continued to explore how this therapy can improve regional heart function.

Methods: A total of 11 of 18 domestic pigs were in the treatment group and 7 were in the control group. On day 0, they all underwent a 90-min percutaneous balloon-induced LAD occlusion, which was located between D1 and D2 branches, to create the myocardial infarction (MI). On day 14, they received NOGA EP mapping to delineate the scar and border zone based on unipolar voltages, followed by 10–15 endomyocardial injections in the border zone in each pig. The treatment group received AAV9-sav-shRNA injections, while the controls received AAV9-GFP injections. The transthoracic echocardiography was performed on days 0, 14, and 104, and strain data was analyzed offline using the GE EchoPAC Workstation. All pigs were sacrificed on day 104.

Results: Among the injections the treatment group received, 70% were in the middle section, and 40% were in the septal segments. Accordingly, the anteroseptal segment in the middle section of the treatment group had major improvements: both radial and circumferential strains significantly increased. Their radial strain also increased in other middle section segments, except for the anterior segment (the least injected place). For LV synchrony analysis, among all middle section segments in the treatment group, their standard deviation of the time to peak radial strain and the time difference between anteroseptal and posterior segments were significantly shorter than in the control group. There were no significant regional improvements in the basal and apex sections.

Conclusions: Suppressing the Hippo pathway in the pig MI model improved regional mechanical function and synchrony. This regional function change was consistent with endocardial injection distribution: the area with more injections recovered better. This finding provides a solid base for designing a precise endomyocardial gene therapy strategy for MI patients based on their infarction distribution.

• (ASR-22-2) Baseline Hemodynamics, including Aortic and Pulmonary Blood Flow in a Chronic Bovine Model
• Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Kelly Handy, Gil Costas, and O.H. Frazier

Introduction: The use of large animal models in preclinical studies has provided invaluable data for evaluating the safety and efficacy of new therapies and devices and has facilitated the development and clinical application of cardiovascular innovations. With an increasingly valuable role, the implementation of large animal models has expanded, serving to bridge the translation of physiologic and economic aspects of animal research into the successful treatment of human heart failure. In this study, we report normal hemodynamic values, including aortic and pulmonary blood flow, in a bovine model at rest and during exercise after a control procedure.

Methods: An 8-month-old calf weighing 80.9 kg underwent a left lateral thoracotomy. Fluid-filled pressure lines (aortic pressure [AoP], right atrial pressure [RAP], left atrial pressure [LAP], and pulmonary artery pressure [PAP]) and left and right flow probe lines were implanted. Flow probes were then placed on the aorta and pulmonary arteries. The calf was continuously monitored throughout the postoperative period. Physiologic pressures, animal vital signs, aortic and pulmonary flows, and pulmonary and systemic vascular resistance were recorded hourly. Treadmill exercise evaluations were conducted, and pressures (AoP, RAP, LAP, and PAP) and flows (aortic and pulmonary) were monitored to determine the animal’s hemodynamic response to exercise.

Results: The animal thrived throughout the postoperative course, gaining a total of 68.5 lbs. The clinical pathology values were in an acceptable range and showed no sign of infection or end-organ dysfunction. Hemodynamic data, including the parameters obtained while the animal was at rest in our laboratory’s intensive care unit (e.g., heart rate, pressure, flows, and vascular resistances), was collected to characterize pressures and flow rates at baseline and during treadmill trials. The average treadmill trial duration was 22.5 min, with an average distance walked of 2213.16 ft (674.5 m). When pressures and flow rates at baseline and during treadmill trials were compared, we observed a physiologic response to exercise similar to that seen in humans, with a sympathetic discharge that increased systolic blood pressure. However, the rise in mean arterial pressure was much lower due to an overall decrease in vascular resistance, which increased blood flow.

Conclusions: This study provides investigators, device engineers, and manufacturers with normal bovine cardiovascular physiology data that can be used for technical consideration during device development for preclinical trials.

• (ASR-22-3) Multichannel radio telemetry in a unilaterally lesioned rat model of Parkinson’s disease enables bilateral assessment of EEG and EMG readouts
• James Destefano, Russell Port, Anitha Manohar, Ioan Petrescu, Tasha Gray, Michael Marino, and Jason Cassaday

Introduction: Parkinson’s disease (PD) is a movement disorder caused by dopaminergic neurodegeneration, with bradykinesia as a core motor symptom. PD patients are known to have abnormal brain waves, and it is believed that beta oscillatory activity in the cortico-striatal-thalamic loop of the brain is dramatically increased in PD. The source of this increased beta is considered to be the subthalamic nucleus (STN). We have developed a robust wireless rat telemetry model to record both the electroencephalogram (EEG), specifically beta oscillations from the motor cortex, and the electromyogram (EMG) from hemiparkinsonian rats during behavioral assays.

Methods: Rats underwent a preliminary surgery where a potent neurotoxin, 6-hydroxydopamine (6-OHDA), a hydroxylated analog of dopamine, was unilaterally injected into the substantia nigra (SN), a region of the brain that produces dopamine. This intracerebral infusion causes a significant destruction of nigrostriatal dopaminergic neurons and a selective neurodegeneration that recapitulates key aspects of PD. Successful models were subjected to subsequent surgery to implant a multichannel telemetry device, allowing EEG and EMG analysis ipsilateral and contralateral to the brain lesion.

Results: Postsurgery, animals underwent signal quality control and were acclimated to a forced walking treadwheel. Chronic home cage recordings from these animals showed selectively increased power in the high beta range (30–50 Hz) of the motor cortex ipsilateral (as opposed to contralateral) to the lesion (STN). This activity is not evident when the animals are in an inattentive rest state, but it can be stably induced and monitored in the motor cortex when they are engaged in an ongoing activity such as treadwheel walking. Rats were dosed with vehicle or a combination of L-DOPA and benserazide hydrochloride, and one hour postdose, they were placed in a treadwheel cylinder with an affixed telemetry receiver to walk for five minutes. Data were analyzed, and signal quality provided confidence in the characterization of beta oscillations.

Conclusions: Our new model was a novel in-house combination of multichannel wireless telemetry, the 6-OHDA rat model, and behavioral assays. Study results indicate that this model is sensitive, durable, reproducible, and will support the screening of compounds used to desynchronize beta oscillations pharmacologically.

• (ASR-22-4) Liver Regeneration Model in Cynomolgus Monkeys
• Randy Pielemeier, Ben Olthoff, Alexandra Schultz, Cody Resendez, Janelle Gesaman, Shelby Powers, and Amanda Klenoski

Introduction: Approximately 41,260 new cases (28,600 in men and 12,660 in women) of liver cancer will be diagnosed in 2022, according to the American Cancer Society website. A model resecting approximately 60% of the liver by weight in Cynomolgus monkeys is valuable in evaluating potential therapies that encourage natural regrowth of the liver postresection in human patients.

Methods: Spanning three separate studies, a laparotomy was performed on a total of 26 animals, resecting approximately 60% of the total liver volume (by weight) of each animal’s liver. Liver volume was calculated based on historical organ (liver) weights measured at necropsy and determined to be approximately 2% of the animal’s total body weight. The right and left median lobes were resected across the liver using a bipolar generator with a Covidien Ligasure™ hand piece. Using conventional dissection and duct ligation techniques, the left lateral lobe was resected with silk ligatures. The right lateral lobe was left intact. Liver biopsies were collected from each animal either under ultrasound guidance or laparoscopically.

Results: Post liver resection, one animal was euthanized with potential hepatic encephalopathy. Several days postoperative, transient inappetence was observed. Due to complications in dissection, while attempting to laparoscopically collect the biopsy from the cut/regenerating edge of the liver, two animals were required to be euthanized. Significant adhesions were seen on the left and right median liver lobe cut edges, and/or between the stomach, mesentery, and diaphragm. In later animals, resection of the right medial lobe was modified to reduce biopsy complications.

Conclusions: Postoperative recovery was manageable with additional enrichment foods to encourage appetite along and pain management based on pain scoring. Inappetence and pain were likely caused by painful and reduced peristalsis in the stomach due to the formation and breakdown of adhesions. An ultrasound-guided needle biopsy had minimal complications except for one kidney injury. Modifications to the resection of the right medial lobe, by curving the resection away from the diaphragm on the right edge of the right medial lobe, mitigated laparoscopic biopsy complications in later cases. This alteration led to better access and fewer adhesions to the liver.

• (ASR-22-5) Coronary Sinus Dosing in Swine: Anatomical Considerations in Comparison to Human Anatomy
• Randy Pielemeier, Jennifer DeVries, and Scott Wilson

Introduction: Routine cardiac catheterization for angioplasty and stenting has created a large population of patients with cardiac damage and subsequent long-term heart failure. Cardiac therapies are often administered directly to the heart by methods such as coronary sinus retrograde infusion. Understanding the differences in human and swine coronary sinus anatomy is crucial in preclinical safety studies, particularly for biodistribution evaluation. Contrast/Dye studies aid in determining coronary sinus anatomy and catheter placement in the heart.

Methods: Under general anesthesia, a 9F or greater sheath was placed via jugular vein cutdown on three Landrace/Duroc and two Yucatan swine. Using fluoroscopic guidance, a balloon was placed into the great cardiac vein. Placing the balloon into the coronary sinus leaves the azygous vein open, allowing the dose to travel into the azygous vein instead of the coronary sinus. Therefore, the dose was delivered retrogradely into the left ventricle, the typical site of reperfusion injury in the swine model. In humans, the balloon is normally placed in the coronary sinus, dosing the left and right ventricles. Infusions of iodinated contrast or Evans blue at 1 or 5 mL per minute up to 80 mL were used to evaluate the distribution of potential therapies.

Results: A 50-mL infusion of the contrast/saline mixture into the great cardiac vein at 5 mL/min generated satisfactory fluoroscopic images of left ventricle perfusion. Anatomical distribution in the left ventricle was verified by hand injecting 9 mL of Evans blue while taking serial photos. Gross necropsies showed significant petechial hemorrhage on the surface of the heart associated with the capillary beds in the animals dosed with contrast. Animals dosed with only saline exhibited no petechial hemorrhage. No acute mortality resulted from this study’s procedures.

Conclusions: When dosing via retrograde infusion into the great cardiac vein of swine, 50 mL of material adequately exposes the entire left ventricle, and up to 80 mL can be delivered with minimal complication. The osmolality of the contrast agent residing in the capillary beds during infusion likely caused the petechial hemorrhage observed in the contrast groups. A 2-balloon method occluding the azygous vein and the coronary sinus replicates the human dose methodology and allows perfusion of both the left and right ventricles in swine. However, in previous studies using the left anterior descending artery reperfusion model, dosing the damaged tissue of just the left ventricle has been a suitable model for preclinical safety evaluation.

• (ASR-22-6) The Use of Injection Ports for Intrathecal Administration: The Mouse Ommaya (the Top Hat Port)
• Michele Danielson, Mary Jane Perkins, Margi Baldwin, Tiffany Razaboudski, Vincent Law, and Peter Forsyth

Introduction: In this poster, we will describe a novel technique and device called the Mouse Ommaya, designed for performing multiple single doses of intrathecal (IT) treatments over a period of time. The device is essentially a permanent access port that allows novice targets such as chemical agents, antibodies, or cells that would have limited penetration due to the blood-brain barrier to now be delivered directly into cerebral spinal fluid (CSF). The port also increases the efficiency of injection by minimizing the dead space, which allows for the least amount of volume in microliters of drug targets needed.

Methods: The mouse was anesthetized under isoflurane inhalant anesthesia and placed in stereotactic apparatus, and a small incision (3 mm) was created, followed by blunt dissection of the underlying subcutaneous tissue to expose the skull. The skull is dried with hydrogen peroxide-soaked cotton-tip applicator sticks. A burr hole is drilled into the skull “x” mm anterior “x” mm lateral of the bregma with a 0.9 mm burr to expose the dura mater. “x” measurement is provided by the lab and specific to strain, age/size of mouse. The drill is moved aside, and the port is affixed to the skull using glue, followed by suturing around the port using nonabsorbable suture in a purse string pattern or simple interrupted pattern.

Results: The top hat port allowed flexibility to adjust drug concentrations, dosing frequencies, and duration of study according to interest. We could administer a single microliter volume into the brain and decrease the amount of drug preparation. The mice that were “cured” of CNS metastases in the immunotherapy study remained bright, alert, and responsive. We also found the mice tolerated the port well, so there was no need to replace it. We found that with this port, there was no dead space, which minimized the waste of agents. Direct-targeted treatment had increased the overall survival period.

Conclusions: The placement of this port has allowed researchers to utilize a targeted area with multiple single doses of treatment over a period of time. It has allowed researchers to adjust dosages to be minimal in volume.

• (ASR-22-7) Ameroid Band Constrictor-Induced Arterial Occlusion Simulates Peripheral Vascular Disease in a Porcine Model
• Heidi Philips, Wawrzyniec Dobrucki, Somaye Babaei, and Michael Insana

Introduction: Gradually tightening vascular occluders such as ameroid constrictors are used to model chronic ischemia and may recapitulate human ischemic disease pathophysiology and atherosclerotic plaque progression better than acute ligation. Ultrasonic power doppler (US-PD) imaging uses doppler sampling and filtering techniques that significantly increase the sensitivity and specificity of routine sonographic instruments for imaging spatially disorganized patterns of peripheral perfusion without contrast enhancement.

Objective: To compare the sensitivity of US-PD with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) techniques for measuring endothelial function and determining vascular perfusion.

Methods: Four 6-month-old, castrated male Yucatan mini-pigs were operated on. A~9 cm incision was conducted in the skin and subcutaneous tissues of the right hindlimb from the inguinal ligament toward the stifle, preserving the femoral artery and vein. The superficial femoral artery was isolated using blunt and sharp dissection, and a 3.5-mm ameroid band constrictor was placed proximally. A single interrupted suture of 3-0 PDS was placed through the pectineus fascia and lumen of the ring to secure the ring proximally and prevent slippage distally. The surgical wound was closed in three layers. Animals were imaged by US-PD and DCE-MRI at 1, 2, 3, and 4 weeks following ameroid placement.

Results: All pigs recovered from anesthesia and healed from surgery without incident. Flow through the superficial femoral artery was substantially decreased by 3–4 weeks in all pigs; however, DCE-MRI revealed minimal decreases in muscle perfusion. Prior to euthanasia, all pigs were injected with fluorescent microspheres, and arterial blood samples were obtained. Following euthanasia,

Conclusions: Ameroid constrictors provide gradual occlusion of arteries and can be reliably used in translational studies using animal models designed to mimic chronic progressive vascular occlusion.

• (ASR-22-8) Pharmacokinetics of Methadone in Cynomolgus Macaques
• Steven Kreuser, Jan Bernal, and Amy Martunas

Introduction: Methadone, a synthetic opioid, has gained popularity as an analgesic for surgical procedures as it provides a longer effective duration compared to common opioids for moderate-to-severe pain. Pharmacokinetic (PK) data in dogs and humans demonstrate therapeutic duration for 12–14 h. This study investigates the pharmacokinetics of methadone at two dose levels in Cynomolgus Macaques for use as an extended-duration opioid for surgical procedures involving moderate-to-severe pain postoperatively.

Methods: Eight Mauritius-origin Cynomolgus Macaques were administered 0.2 mg/kg and 0.5 mg/kg of methadone hydrochloride intramuscularly (IM), and plasma and urine were collected at predetermined time points and analyzed. Average mean total plasma concentration at 15 min postadministration: 37.7 ng/mL. Average mean total plasma concentration at 8 h: 4.48 ng/mL

Results: After IM administration, 0.2 mg/kg dose terminal half-life was 3.61 h and in therapeutic range for 8 h; 0.5 mg/kg dose terminal half-life was 21.3 h and in therapeutic range for a minimum of 12 h. Time points between 12 and 16 h should be considered to determine when levels begin to decrease (plan to investigate this in a future study).

Conclusions: Established dosing ranges and duration for methadone in NHPs to effectively address moderate-to-severe pain. The half-life increases significantly at a higher dose. Based on clinical application, 0.5 mg/kg methadone can be effectively dosed in NHPs at 12-h intervals for moderate-severe pain; doses may need to be adjusted for chronic administration due to cumulative effects.

• (ASR-22-9) Cerebral oxygenation monitoring in rats under isoflurane anesthesia
• Melissa Sugiura, Ardy Wong, Jeffrey Rothman, Benjamin Franco, Eden Alamaw, KambizPourrezai, Cholawat Pacharinsak, Zeinab Barati, and Kelly Drew

Introduction: Although monitoring vital signs in small lab animals is critical to successful anesthetic outcomes, reliable measurement of the vital signs is challenging due to their size. To this end, we are developing a miniaturized optical imaging device based on the near infrared spectroscopy (NIRS) technique for noninvasive measurement of the brain and peripheral tissue oxygenation and perfusion. Our goal is to develop a device to support safe and reliable anesthesia monitoring in small lab animals to improve animal welfare, ensure successful outcomes, and create reproducible research, which will ultimately aide in better knowledge of the living systems to enhance health, lengthen life, and reduce illness and disability burden worldwide.

Methods: All procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals, 8th edition. The NIRS device consisted of a controller module and an optical sensor with two LED light sources and two photodiodes, making up two parallel channels for monitoring the left and right cerebral hemispheres. Optical intensity measurements were converted to deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2) changes relative to a 2-min window after induction and at the beginning of 1.5% isoflurane.

Three male Sprague Dawley rats (325–400 g) were anesthetized with a mixture of isoflurane vaporized in 100% 02 delivered at 1.5 L/min. After 10–15 min at 1.5% isoflurane, the level of isoflurane was increased to 3% and then 5%.

Results: The concentration of Hb slightly decreased as the level of isoflurane increased, whereas the concentration of HbO2 significantly increased at 3% and 5% isoflurane compared to 1.5%.

Conclusions: These preliminary studies demonstrate the promise of improving anesthesia monitoring in small laboratory animals and highlight the need to better understand the relationship between arterial blood gas measurements, cardiovascular parameters, peripheral tissue, and cerebral oxygenation to enable effective and reliable early detection of adverse events during anesthesia in small lab animals.

4. Sponsors

The Academy of Surgical Research Annual Meeting is supported by a number of generous sponsors, many of whom are long-term supporters [1,2,3]. Especially platinum sponsors, Bristol-Myers Squibb, Charles River, Envigo, Fine Science Tools, Kent Scientific, NAMSA, Neurosite Consulting, LLC, Northern Biomedical Research, Pfizer, and VetEquip; gold level sponsors, Becton Dickinson, BRAD, and insidescientific; and bronze level sponsor, UID Identification Solutions. Avante Scientific, Jan Bernal, Colonial Medical Supply Co., Inc., Instech Laboratories, Steve Kreuser, Marshall BioResources, Neurosite Consulting, LLC, and SAI Infusion Technologies each hosted various social and networking events during the meeting. Wet lab sponsors included Charles River, Fine Science Tools, Instech Laboratories, Medline, and Premier BioSource.

5. Closing Remarks

The 38th Academy of Surgical Research Annual Meeting successfully concluded a year celebrating connections and coming back together in the Academy. This year we launched our new journal affiliation with ‘Surgeries’ in an effort to best support members and expand the reach of our research. We congratulate the individuals who completed the requirements for and successfully passed their certification exams to be awarded the designation of Surgical Research Anesthetist (SRA), Surgical Research Technician (SRT), and/or Surgical Research Specialist (SRS) by the Academy. We are looking forward to welcoming everyone to the next meeting, the 39th Academy of Surgical Research Annual Meeting, on 10–12 October 2023, in Nashville, TN, USA.