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.

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 focal, proximal left anterior descending artery stenosis in the setting of unstable angina and positive stress testing.⁶ This constituted the invention of the field of interventional cardiology as we know it today, demonstrating the vital role of the preclinical lab.

Since that time, the preclinical interventional cardiology lab has become a mainstay in the vertical integration of the device-based innovation process. The flow from idea to engineering to bench top testing to reengineering to animal lab testing to reengineering and finishing with further animal lab testing was demonstrated by Gruentzig; it has since flourished worldwide.

With foundations in the preclinical lab, many significant device-based contributions to the field of cardiovascular medicine have been developed, ranging from vascular, to hemodynamic, to structural, to electrophysiologic. Given the continuously evolving field of invasive cardiology and the ethos of innovation in the field, preclinical labs have had to evolve in lock step with technologic advancement. For example, some preclinical labs have been focused mainly on coronary disease models, and their accompanying diagnostics and interventions. However, with the rise in structural interventions such as transcatheter aortic valve replacement, mitral interventions, and ventricular assist devices, the expertise of the lab must evolve to meet the demands of both the new disease models and the new diagnostics/therapeutics to be assessed.

There are currently a number of preclinical interventional cardiology labs across the world. Most either currently operate within or had roots in the academic medical setting. Given the interdisciplinary demands of the type of work done in the interventional cardiology preclinical lab, the academic environment is naturally conducive to it. Innovators can brainstorm with colleagues from different specialties and capitalize on diverse expertise by collaborating across different departments, such as engineering and chemistry. Additionally, university-based administrative groups can assist with management of regulatory issues and contracts.

However, the infrastructure and often bureaucratic nature of the academic setting has not traditionally been designed to function optimally under conditions in which entrepreneurial hands are involved. Specifically, most academic settings have not evolved to provide services to those who comprise the majority of “customers” to the interventional cardiology preclinical lab—often small and large industry partners.