Although innovators brainstorm ideas for novel therapies often while working in the clinical setting, these ideas see the earliest translation into reality in the preclinical laboratory. The goal of the preclinical lab is to provide hands-on testing in the animal model to guide focused revisions of a new device or treatment. This is the realm in which devices and treatments move beyond basic prototype, into early versions of an eventual finished product for clinical use in patients. These early versions get tested, revamped, and retested, with the goal of evaluating feasibility, safety, and efficacy. The preclinical lab is also a common ground where interventional cardiologists, engineers, veterinarians, scientists, and industry can meet to collaborate.
The goal of this chapter is to review some of the important requirements of a preclinical laboratory and suggest insights into what makes a preclinical lab successful in the current landscape of translational cardiovascular research.
HISTORICAL FOUNDATIONS OF THE INTERVENTIONAL PRECLINICAL LABORATORY
Although animal studies have historical roots over millennia, the field of interventional cardiology and the vital role of the preclinical interventional cardiology lab can be directly traced back to Andreas Gruentzig, the first interventional cardiologist. Gruentzig developed percutaneous coronary balloon angioplasty, building on the work of Mason Sones, Charles Dotter, and Melvin Judkins. In 1958 during an aortogram, Mason Sones inadvertently cannulated and performed an angiogram of the right coronary artery, ultimately demonstrating the diagnostic potential of coronary angiography.1
Subsequently, Charles Dotter in 1963 inadvertently recanalized an occluded right iliac artery when he was obtaining access to the abdominal aorta for an aortagram in a patient with renal artery stenosis, demonstrating the potential for transluminal angioplasty.2 In 1964, Judkins (Dotter’s trainee) and Dotter conducted the first intentional and successful transluminal angioplasty of a short superficial femoral artery stenosis for a patient with a gangrenous toe and nonhealing ulcer who refused surgical intervention.3 After learning the Dotter technique, Gruentzig added balloons to the Dotter catheters (ultimately iterating until he developed a polyvinylchloride-based double lumen catheter). Between 1972 and 1975, he performed peripheral balloon angioplasty in animals and then transitioned to humans.4 By 1976, Gruentzig had revised his device to a size appropriate for coronary intervention and continued to demonstrate feasibility, safety, and efficacy of his prototype in the preclinical lab. Specifically, Gruentzig performed a partial ligation of the circumflex artery via thoracotomy in a canine model. He then performed angiography to demonstrate the stenosis as well as to measure the transstenotic pressure gradient. He positioned his balloon at the stenosis and intervened on it by inflating the balloon until he broke the ligature, ultimately resolving the stenosis and the transstenotic pressure gradient. These results were presented at the American College of Cardiology meeting in 1976 in Miami, Florida (Fig. 67-1).5 By 1977, Gruentzig successfully performed the first human use of coronary angioplasty in a 38-year-old patient with ...