Reply to Rescigno et al.

We appreciate the sensitivities of Rescigno et al. [1] in their letter questioning the justification for animal experiments, suggesting a careful and selective approach in choosing a canine model in science. In their comment, Rescigno et al. referred to the use of dogs, which was described in our study [2]. They assert that we should not have used dogs, because we were not studying a totally new device but a modification of an existing device, and they allege that our studies could have been done in cadavers or cell cultures. We respectfully disagree.

Prior to establishing this study protocol, the study investigators and study consultants carefully considered potential alternatives to animal use (e.g. in silico, in vitro and in cadavers). It has been determined [and the University of Minnesota’s Institutional Animal Care and Use Committee (IACUC) concurred] that animals (in this case, dogs) were necessary to achieve the study’s specific objectives to (i) evaluate safety because the device approach/deployment differed with the new device design and new fabric; (ii) explore system performance (implantability scores) in a beating heart with normal blood volumes in the heart chambers (impossible with cadavers); complete appendage occlusion without device migration over time had to be evaluated in live animals; and (iii) assess biocompatibility and possible complications, also in live animals; cell cultures could not yield such assessments.

Canines were used because their cardiac size and anatomy resemble those of humans; the dog’s left atrial appendage is human-like in morphology, size and tissue thickness, making the canine model optimal for evaluating occlusion efficacy. Atrial appendage exclusion and atrial fibrillation have been widely studied in canine models, with results published in medical journals [3–6]. One of our greatest concerns with the new clip was the possibility of occluding the circumflex artery. That artery is also similar in dogs and humans, making dogs an ideal test subject. In sheep, the circumflex is in a different location. In pigs, it is at a different site, and the appendage is significantly different from that of humans. We believe that our animal selection was necessary and appropriate, as approved by the IACUC. As cardiovascular investigators, we acknowledge that in vivo studies using research animals must inevitably take place if medicine is to progress.

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