Thrombin Injection into the Pulmonary Circulation to Create a Novel Swine Model of Acute Pulmonary Embolism
Travis J. Vowels, MD, Luis F. Gomez, MD, Muhammad M. Zubair, MD, Eric K. Peden, MD.
Houston Methodist Hospital, Houston, TX, USA.
OBJECTIVE: Despite the high risk of intracranial and fatal bleeding, systemic thrombolysis is still indicated for massive and submassive pulmonary embolism (PE). Catheter-directed techniques provide promising alternatives to the high morbidity and mortality associated with systemic thrombolysis and open pulmonary embolectomy, but randomized data is lacking. Previously described PE models include injection of ex vivo thrombus and embolization of caval thrombus. We aim to develop a simple in vivo swine model of acute PE to aid in the development and application of catheter-directed therapies.
METHODS: We strictly adhered to the protocol and standards set forth by the Institutional Animal Care and Use Committee. Five adult male Yorkshire swine and 2 Yucatan swine, weight 67±4 kg (mean±stdev), were placed under general anesthesia. We monitored vital signs and placed two 8 French venous sheaths. After pulmonary angiography, we inflated a 7 Fogarty Embolectomy Catheter (Edwards Lifesciences) in the left main pulmonary artery (PA). We then injected recombinant thrombin through the catheter until effective thrombus formation assessed by serial venography (Figure 1). Five of the swine were immediately euthanized for the acute PE experiment and clot burden was grossly assessed at necropsy; two were kept alive to assess the feasibility of a subacute or chronic PE model.
RESULTS: We created acute PE extending from the left main PA to the subsegmental branches in all swine using this method. Three exhibited hypotension upon injection which resulted in unexpected death in one who received 10000 units of thrombin over 1 minute. The other two recovered after temporarily halting injection. The amount of thrombin injected ranged from 8000 to 20000 units and rate of injection ranged from 1000 to 10000 units per minute. Two swine were survived for a week and repeat pulmonary angiogram showed complete or near complete resolution of the clot burden, confirmed at necropsy.
CONCLUSIONS: A swine model of acute PE can be created in vivo by controlled injection of thrombin directly into the pulmonary circulation to aid in the development of catheter-directed therapies. Further research is needed to delineate a swine model for subacute or chronic PE using this technique.
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