Abdominal Positioning of the Next-Generation Intra-Aortic Fluid Entrainment Pump (Aortix) Improves Cardiac Output in a Swine Model of Heart Failure.

BACKGROUND: Acute heart failure refractory to medical therapy is a major cause of morbidity and mortality. The Aortix device (Procyrion Inc) is a percutaneously delivered entrainment pump positioned in the descending aorta. METHODS AND RESULTS: Using the newest generation Aortix device in 8 adult male Yorkshire swine, we tested the hypothesis that positioning in the abdominal aorta may provide superior hemodynamic effects than thoracic positioning in a swine model of postinfarct left ventricular injury.Abdominal activation generated significantly larger transaortic gradients (proximal minus distal mean aortic pressures) than thoracic positioning at all pump speeds. Compared with baseline values, activation in the abdominal, not thoracic, position significantly increased cardiac output, reduced arterial elastance, and systemic vascular resistance at low speeds. Compared with baseline values, abdominal activation also increased transpulmonary pressure gradients at medium and high speed, which was driven by trends toward higher mean pulmonary artery pressure and lower pulmonary capillary wedge pressure. CONCLUSIONS: This is the first report to determine that in contrast to thoracic positioning, abdominal positioning of the newest generation Aortix device reduces left ventricular afterload and increases cardiac output at low speeds. These findings have potentially important implications for the design of early clinical studies by suggesting that device position and speed are major determinants of improved hemodynamic efficacy.

Duodenal Cannulation in Pigs (Sus scrofa) as a Drug Delivery Method.

Currently available animal models for delivery of drug capsules and pharmacokinetic testing are limited by either intersubject variability in gastric emptying time or the need to sedate animals when using targeted delivery methods of drug capsules. With the increasing development of large-molecule biologics, better in vivo models for testing the pharmacokinetics of capsule-delivered drugs are urgently needed. To this end, we made engineering modifications to an existing bovine surgical cannula device, successfully implanted this modified cannula into pigs, and delivered drug capsules directly to the proximal duodenum. In our porcine model, capsule insertion and serial blood samples were all acquired without the use of sedatives. Furthermore, we were able to maintain cannulated pigs for weekly pharmacokinetic testing for more than 18 mo, with minimal postoperative complications. This study demonstrates a novel and effective porcine model of sedation-free drug delivery and blood collection that eliminates inconsistencies associated with models that require either gastric emptying or animal sedation.

M118, a novel low-molecular weight heparin with decreased polydispersity leads to enhanced anticoagulant activity and thrombotic occlusion in ApoE knockout mice.

Heparin and low-molecular weight heparin (LMWH) are complex, heterogeneous polysaccharides used in the treatment of arterial and venous thrombosis. M118 is a novel LMWH with low polydispersity and pronounced anti-Xa and anti-thrombin (IIa) activity as compared to current LMWHs. To determine if M118 is effective in preventing thrombosis in the setting of a vascular plaque, apolipoprotein E knockout mice fed a high fat diet were injected with M118, enoxaparin, unfractionated heparin, or saline control and examined for arterial thrombosis using a rose bengal laser induced carotid artery injury model. M118 significantly increased the time to occlusion as compared to control and unfractionated heparin but not compared to enoxaparin although fewer M118 treated animals had any vascular occlusion present at the time of protocol completion. Platelet-neutrophil aggregates were studied by flow cytometry and were found to be decreased with M118 as compared to enoxaparin. This is the first published report examining M118, a novel LMWH designed to have low polydispersity and enhanced anticoagulant activity. In an animal model of vascular plaque, M118 is a potent inhibitor of arterial thrombosis and, despite lower in vivo anti-Xa and anti-IIa activity levels, M118 was superior to UFH in the prevention of arterial thrombosis.