Intravenous Dabigatran Provides Adequate Anticoagulation for Cardiopulmonary Bypass Using a Rabbit Model.

BACKGROUND: Heparin anticoagulation has been used successfully for cardiopulmonary bypass (CPB). However, an alternative anticoagulant approach is desirable due to the cases of heparin-induced thrombocytopenia. Dabigatran provides anticoagulation for an in vitro model of simulated CPB. The current analysis tests the hypothesis that dabigatran provides sufficient anticoagulation for CPB in intact rabbits. METHODS: Nonlinear mixed effects models were used to estimate dabigatran parameters for a two-compartment pharmacokinetic model in 10 New Zealand White rabbits. A dabigatran infusion designed to maintain a plasma concentration of 90 µg/ml was run throughout CPB based on the pharmacokinetics. Animals were subjected to sternotomy and anticoagulated with IV dabigatran (six animals) or heparin (four animals). Rabbits were cannulated centrally using the right atrium and ascending aorta and CPB was maintained for 120 min. Measurement of activated clotting time, thromboelastometric reaction time, and blood gases were performed during CPB. Then, the animals were euthanized, and the brain and one kidney were removed for histology. Sections of the arterial filters were inspected using electron microscopy. RESULTS: The observed dabigatran concentrations during CPB were greater than the target concentration, ranging from 137 ± 40 µg/ml at 5 min of CPB to 428 ± 150 µg/ml at 60 min, and 295 ± 35 µg/ml at 120 min. All rabbits completed 2 h of CPB without visible thrombosis. In the two groups, reaction time values were elevated, reaching 10,262 ± 4,198 s (dabigatran group) and 354 ± 141 s (heparin group) at 120 min of CPB. Brains and kidneys showed no evidence of thrombosis or ultrastructural damage. Sections of the arterial line filter showed minimal or no fibrin. There was no significant difference in outcomes between dabigatran- and heparin-treated animals. CONCLUSIONS: In this first-use, proof-of-concept study, the authors have shown that dabigatran provides acceptable anticoagulation similar to heparin to prevent thrombosis using a rabbit CPB model.

A modified LVAD technique to augment caval and pulmonary arterial blood flow in the "failing Fontan" circulation.

BACKGROUND: There are minimal circulatory support options for patients with a failing Fontan. The Heartmate II (HMII) left ventricular assist device (Thoratec, Bedford, MA) in its packaged state cannot augment caval/pulmonary arterial blood flow. AIM: We hypothesized that a modified HMII pump could augment caval and pulmonary arterial blood flow. METHODS: A bifurcated ringed Gore-Tex graft (W. L. Gore & Associates, Flagstaff, AZ) was sewn to the HMII inflow, and the outflow graft transected and tapered from 16 mm to 8 mm in diameter. In three sheep, the inflow and outflow grafts were anastomosed end-to-side to both cava and the pulmonary artery. RESULTS: Following baseline measurements, the pump speed was increased to 8000 revolutions per minute (RPMs). Compared to baseline, at 8000 RPMs, there were no significant differences in mean arterial, central venous, or pulmonary arterial pressure. However, there was a significant decrease in right ventricular diastolic diameter (3.1 ± 0.1 vs. 1.8 ± 0.2 cm, R = 0.6, p = 0.02) and similarly a decrease in pulmonary arterial pulse pressure (8.5 ± 2.1 vs. 2.1 ± 2.9 mmHg, p = 0.01). As pump speed increased, there was a corresponding increase in pump flow and power, with a decrease in pulsatility index. CONCLUSIONS: These findings suggest that the HMII may be modified to provide caval/pulmonary circulatory support for the failing Fontan circulation.

Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits.

OBJECTIVE: To determine the clinical effectiveness and safety of a compounded sustained-release formulation of buprenorphine, compared with effects of regular buprenorphine, for postoperative analgesia in rabbits. DESIGN: Blinded randomized controlled clinical trial. ANIMALS: 24 purpose-bred adult male New Zealand White rabbits. PROCEDURES: Rabbits received titanium implants in each tibia as part of another study. Immediately prior to surgery, each rabbit received regular buprenorphine hydrochloride (0.02 mg/kg [0.009 mg/lb], SC, q 12 h for 3 days) or 1 dose of a compounded sustained-release formulation of buprenorphine (0.12 mg/kg [0.055 mg/lb], SC) followed by an equal volume of saline (0.9% NaCl) solution (SC, q 12 h for 3 days) after surgery. For 7 days after surgery, rabbits were evaluated for signs of pain by means of rabbit grimace and activity scoring and for adverse effects. RESULTS: No significant differences were identified between treatment groups in grimace and activity scores at any point. No major adverse effects were detected for either drug. However, 3 rabbits that received regular buprenorphine had pain scores suggestive of moderate to severe pain by the time dose administration was due (ie, within the 12-hour administration interval). No clinically important differences were detected in intraoperative anesthetic or postoperative recovery variables. CONCLUSIONS AND CLINICAL RELEVANCE: Sustained-release buprenorphine administered SC at 0.12 mg/kg was at least as effective as regular buprenorphine in providing analgesia for rabbits following orthopedic surgery without any major adverse effects. This sustained-release formulation represents an important alternative for rabbit analgesia with potential to improve rabbit welfare over existing analgesic standards.

Sheep (Ovis aries) as a model for cardiovascular surgery and management before, during, and after cardiopulmonary bypass.

Because of its similarity to humans in important respects, sheep (Ovis aries) are a common animal model for translational research in cardiovascular surgery. However, some unique aspects of sheep anatomy and physiology present challenges to its use in these complicated experiments. In this review, we discuss relevant anatomy and physiology of sheep and discuss management before, during, and after procedures requiring cardiopulmonary bypass to provide a concise source of information for veterinarians, technicians, and researchers developing and implementing protocols with this model.