Contents

Introduction Protocol Development

Spontaneously Occurring Animal Models of Congenital Cardiac Disease

Alternatives to Whole Animal Models

Animal Models in Valve Disease

Animal Models in Myocardial Ischemia

Animal Models in Heart Failure and Transplantation

Animal Models for the Testing of Mechanical Devices

Cellular Cardiomyoplasty

Summary

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1. INTRODUCTION

The modern era of cardiac surgery is largely considered to have begun in the animal research laboratories. Today, animal models provide the ultimate preclinical assessment for the study of cardiovascular disease, pharmaceuticals, mechanical devices, and therapeutic procedures. This chapter was designed to provide readers and potential investigators crucial insights into the process of matching an experimental hypothesis to an animal species that will serve as the most appropriate model for specific cardiovascular diseases or for testing a given medical device. A review of the current animal models used in cardiac research is provided and arranged by disease state. Critical factors, including cost, reproducibility, and degree of similarity of the model to human disease are discussed; thus, this chapter can be utilized as a guide in planning research protocols.

2. PROTOCOL DEVELOPMENT

Several scientific governing bodies have developed guidelines in an effort to ensure that animals used in research are

From: Handbook of Cardiac Anatomy, Physiology, and Devices Edited by: P. A. Iaizzo © Humana Press Inc., Totowa, NJ

ethically and scientifically appropriate. Investigators who plan to utilize animal subjects in their research should first familiarize themselves with Guide for the Care and Use of Laboratory Animals (1). In addition, investigators should use these guidelines in conjunction with accepted scientific methods to develop a standardized protocol for each research project. It is standard procedure that, prior to commencing research, a detailed protocol must undergo review and approval by the local institutional governing body responsible for the safety and ethical use of animals in research. At the University of Minnesota, this is the Institutional Animal Care and Use Committee (see www.iacuc.umn.edu).

Both large and small animals have been extensively used in cardiovascular research. Yet, the choice of animal model should be primarily based on: (1) the scientific hypothesis; (2) the lab's capability to employ the model safely in the species chosen (i.e., appropriate animal housing and care, equipment, lab resources); and (3) the degree of the species' similarity to the human anatomy. Many of the best animal models can be expensive to establish and maintain; therefore, funding must be appropriate to complete the required number of animals to satisfy a pre-calculated statistical power.

Table 1

Naturally Occurring Animal Models of Cardiovascular Disease

Table 1

Naturally Occurring Animal Models of Cardiovascular Disease

Subaortic stenosis

Dog (Newfoundlands, golden retrievers, rottweilers, boxers, German shepherds, samoyeds);

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