Evaluation of the use of a heparin dose-response test in dogs to determine the optimal heparin dose during intravascular procedures and assessment of the in vitro heparin response in healthy dogs.

BACKGROUND: No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. OBJECTIVES: To evaluate an activated clotting time (ACT)-based heparin dose-response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin - ACT and in vitro heparin - factor anti-Xa activity (anti-Xa) relationships in dogs. METHODS: Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0-0.5-1-2-4 international unit (IU)/mL) was prepared and ACT and anti-Xa were determined using whole blood and frozen plasma, respectively. RESULTS: The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti-Xa increased significantly with increasing blood heparin concentration. Heparin - ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin - anti-Xa remained linear throughout the tested range. CONCLUSIONS: The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin - ACT relationship, as observed in vitro. Anti-Xa is a promising alternative for ACT; however, unavailability as a point-of-care test and lack of in vivo target values restrict its current use.

Evaluation of resuscitative endovascular balloon occlusion of the aorta catheter placement and comparison to resuscitative thoracotomy with aortic clamping in cadaver dogs.

OBJECTIVE: To describe placement of an aortic occlusion catheter in aortic zone 1 (Z1) and aortic zone 3 (Z3) in dogs and to compare time to placement in these zones with and without external chest compressions (ECC). Additional evaluations of time to placement in Z1 with time for resuscitative thoracotomy with aortic clamping (RT-AC) were performed. DESIGN: Prospective ex vivo study. SETTING: University teaching hospital. ANIMALS: Ten canine cadavers. INTERVENTIONS: Ten cadaver dogs were obtained from client donation after euthanasia. Cadavers were randomized to have balloon catheter placement into the right or left femoral artery via cutdown, with or without ECC. The xiphoid was used as an external anatomical landmark for Z1, and the spinous process of the 5th lumbar vertebra was used for Z3. Balloon placement was confirmed with radiography. Time to balloon placement in Z1 and Z3 and time to RT-AC were recorded. MEASUREMENTS AND MAIN RESULTS: Median body weight was 23.5 kg (9-40 kg). Median time to Z1 placement was 6.6 minutes (4.6-12.4 minutes) with ECC and 6.9 minutes (3.3-13.1 minutes) without ECC and was not statistically different (P = 0.5). Median time to RT-AC was 1 minute (0.6-1.4 minutes), which was significantly faster than time to balloon placement in Z1 with or without ECC (P = 0.004 and P = 0.002, respectively). CONCLUSIONS: Endovascular balloon occlusion of the aorta can be achieved by cutdown with and without ECC, but RT-AC is faster. Successful balloon position in Z1 could be achieved with knowledge of external anatomical landmarks, but landmarks for Z3 need further study.

Biopsy of an intracardiac paraganglioma in a dog using a fluoroscopically guided endovascular technique.

A 10-year-old female spayed mixed breed dog was evaluated for diarrhea and vomiting. Diagnostic imaging demonstrated the presence of an intracardiac mass. A modified Seldinger technique was used to access the right jugular vein, and an endomyocardial biopsy forceps was introduced through a sheath to obtain several biopsies. Histopathology and immunohistochemistry demonstrated a paraganglioma. The dog underwent 1 fraction of radiotherapy and l-asparaginase chemotherapy and was discharged. The dog developed a pulmonary thromboembolism 2 days after radiotherapy and chemotherapy, and the owner elected humane euthanasia. Although long-term assessment of treatment response was unable to be performed, this novel diagnostic option could be considered for similar cases due to success in obtaining a histopathologic diagnosis, which is essential in developing a disease-specific treatment plan. This report also describes the use of radiotherapy for primary treatment of an intracardiac neoplasm, which can be a consideration in the future.

Long-Term Management of Vascular Access Ports in Nonhuman Primates Used in Preclinical Efficacy and Tolerability Studies.

Vascular access ports (VAPs) are an essential tool for long-term vascular access in preclinical studies and disease modeling in non-human primates (NHPs). We retrospectively reviewed central (inferior vena cava, IVC) and portal VAP implantation with the maintenance at our center from 15 January 2010 to 31 January 2018. In total, 209 VAPs were implanted for long-term drug administration and sampling. Patency was >95% at 6 months and >80% at 1 year for IVC VAPs and >90% at 6 months and >85% at 1 year for portal VAPs. The majority of animals had no complications and access was generally durable with device use ranging up to 7 years. In IVC, VAPs loss of patency occurred in 13% (0.035/100 d), surgical site infection in 2.9% (0.097/100 d), port pocket infection in 2.2% (0.004/100 d), erosion in 2.9%, 0.008/100 d), and mechanical failure in 4.3% (0.012/100 d). In portal, VAPs loss of patency occurred in 11.3% (0.028/100 d) and port pocket infection in 1.4% (0.003/100 d). About 12% of VAPs were removed as a result of complications.This study confirms VAP implant and maintenance is a beneficial and safe practice in NHPs resulting in favorable outcomes. High patency rates and low complication rates are comparable to the clinical setting. In addition to enabling comprehensive data collection, VAPs increase satisfaction and well-being by minimizing interference with daily routines and fostering cooperation. VAP implantation, together with an effective maintenance regimen and co-operative handling, is a reliable and convenient refined method for drug administration and blood sampling.Keywords: Vascular access port; nonhuman primates; refinement; central vascular access; portal vascular access; surgical technique; experimental surgery; animal model.

Placement of a balloon for resuscitative endovascular balloon occlusion of the aorta without fluoroscopic guidance in canine cadavers.

OBJECTIVE: To determine whether a balloon for resuscitative endovascular balloon occlusion of the aorta (REBOA) could be accurately placed in the descending aorta between the left subclavian and celiac arteries (zone I) by using external anatomic landmarks in dogs. STUDY DESIGN: Cadaver study. SAMPLE POPULATION: Fifteen canine cadavers of 3 weight categories (10-20, 20-30, and ≥ 30 kg). METHODS: Percutaneous catheterization of the femoral artery was attempted under ultrasonographic guidance; when unsuccessful, an arterial cutdown was performed to place an introducer sheath. Distance was measured between the introducer sheath and the target region, located ventral to the epaxial muscles at the level of the 12th thoracic vertebra. The balloon was advanced the measured distance, and placement was confirmed with fluoroscopy. The volume of iohexol solution required to inflate balloons was recorded. Histopathology was performed on the aortas of the first 5 dogs. RESULTS: Three catheters were placed under ultrasonographic guidance. Balloons were successfully placed into zone I in 15 of 15 cadavers. Balloons were inflated with a median 0.4 mL/kg (range, 0.21-0.67) of iohexol solution. Minor changes were identified in 2 of 5 dogs examined with histopathology (linear defects in 1 dog, small focal dissection in the other). CONCLUSION: A balloon for REBOA was consistently placed in the target zone I without fluoroscopic guidance. CLINICAL SIGNIFICANCE: Fluoroscopy may not be required for zone I REBOA in dogs. Additional studies are warranted to evaluate the feasibility of REBOA in clinical dogs with hemoperitoneum.

Location is everything: The hemodynamic effects of REBOA in Zone 1 versus Zone 3 of the aorta.

OBJECTIVES: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging technology to augment proximal blood pressure during the resuscitation of patients with noncompressible torso hemorrhage. Currently, placement choice, supraceliac (Zone 1) versus infrarenal (Zone 3) aorta, depends on injury patterns, but remains a highly debated topic. We sought to compare the proximal hemodynamic support provided by Zone 1 versus Zone 3 REBOA placement and the degree of hemodynamic instability upon reperfusion following intervention. METHODS: Eighteen anesthetized swine underwent controlled hemorrhage of 25% total blood volume, followed by 45 minutes of Zone 1 REBOA, Zone 3 REBOA, or no intervention (control). They were then resuscitated with shed blood, aortic balloons were deflated, and 5 hours of critical care ensued prior to euthanasia. Physiologic parameters were recorded continuously, and blood was drawn for analysis at specified intervals. Significance was defined as p < 0.05. RESULTS: There were no significant differences between groups at baseline or during the initial 30 minutes of hemorrhage. During the intervention period, average proximal MAP was significantly greater in Zone 1 animals when compared with Zone 3 animals (127.9 ± 1.3 vs. 53.4 ± 1.1 mm Hg) and greater in Zone 3 animals when compared with control animals (42.9 ± 0.9 mm Hg). Lactate concentrations were significantly higher in Zone 1 animals (9.6 ± 0.4 mmol/L) when compared with Zone 3 animals (5.1 ± 0.3 mmol/L) and control animals (4.2 ± 0.8 mmol/L). CONCLUSIONS: In our swine model of hemorrhagic shock, Zone 3 REBOA provided minimal proximal hemodynamic support when compared with Zone 1 REBOA, albeit with less ischemic burden and instability upon reperfusion. In cases of impending hemodynamic collapse, Zone 1 REBOA placement may be more efficacious regardless of injury pattern, whereas Zone 3 should be reserved only for relatively stable patients with ongoing distal hemorrhage.

Design of an endovascular morcellator for the surgical treatment of equine Cushing's disease.

BACKGROUND: A new paradigm of surgical treatment of equine Cushing's disease has been developed using the vascular system combined with a flexible morcellation instrument to reach the pituitary gland. OBJECTIVE: The goal was twofold: (1) to design, prototype, and test an instrument that can reach the pituitary gland using the vascular system unique to equids and (2) to test the feasibility of the endovascular approach. ANIMALS AND METHODS: The morcellator consists of a radial rotating cutting blade for tissue resection, a flexible shaft incorporating a cable drive for flexible actuation, and central morcellated tissue transportation lumen. The morcellator prototype was tested on a horse's cadaver head for the validation of the cutting blade design, actuator design, and feasibility of the endovascular approach. RESULTS: The overall assembled length of the morcellator tip was 13.9 mm, allowing for non-traumatic steering through the vascular system from the proximal end. The radially rotating cutting blade (barrel of Ø 4 and 4.4 mm width) incorporated multiple cutting edges to deliver the action force during resection and provides the necessary grasping force to draw the tissue towards the second cutting edge of the morcellator incorporated inside the blunted cuboidal static tip element (5 mm square and wall-thickness of 0.3 mm). In the tests, the morcellator was successfully guided towards the pituitary and managed to sample pituitary tissue. CONCLUSION AND CLINICAL IMPORTANCE: Continued development of the prototype and the endovascular approach may in time improve the outcome and quality of life of horses suffering from Cushing's disease.

Endovascular evaluation and treatment of intrahepatic portosystemic shunts in dogs: 100 cases (2001-2011).

OBJECTIVE: To evaluate short- and long-term outcome following endovascular treatment of intrahepatic portosystemic shunts in dogs. DESIGN: Retrospective case series. ANIMALS: 100 dogs. PROCEDURES: All patients had angiographic evaluation with or without endovascular shunt attenuation. The medical records were reviewed for pertinent data, complications, outcome, and survival time. RESULTS: 95 dogs with congenital intrahepatic portosystemic shunts received 111 procedures (83% [79/95] had 1 treatment, and 17% [16/95] had > 1 treatment; 5 dogs had no treatment because of excessive portal venous pressure-central venous pressure gradients). Angiography identified 38 right, 33 left, and 19 central divisional single shunts (n = 90) and 10 complex or multiple shunts. Partial shunt attenuation was performed in 92 dogs by means of caval stent placement and insertion of thrombogenic coils within the shunt, and 3 had complete acute shunt occlusion. Major intraoperative complications (3/111 [3%]) included temporary severe portal hypertension in 2 dogs and gastrointestinal hemorrhage in 1 dog. Major postoperative (< 1 week after surgery) complications (14/111 [13%]) included seizures or hepatoencephalopathy (7/111 [6%]), cardiac arrest (2/111 [2%]), jugular site bleeding (2/111 [2%]), pneumonia (1/111 [1%]), suspected portal hypertension (1/111 [1%]), and acute death (1/111 [1%]). Median follow-up time was 958 days (range, 0 to 3,411 days). Median survival time for treated dogs was 2,204 days (range, 0 to 3,411 days). Outcome was considered excellent (57/86 [66%]) or fair (13/86 [15%]) in 70 of 86 (81%) treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that endovascular treatment of intrahepatic shunts in dogs may result in lower morbidity and mortality rates, with similar success rates, compared with previously reported outcomes for open surgical procedures. Gastrointestinal ulceration was a common finding among this population of dogs, and lifelong gastroprotectant medications are now recommended.