5 Comparative Cardiac Anatomy ALEXANDER J. HILL, PhD AND PAUL A. IAIZZO, PhD CONTENTS HISTORICAL PERSPECTIVE OF ANATOMY AND ANIMAL RESEARCH IMPORTANCE OF ANATOMY AND ANIMAL RESEARCH LARGE MAMMALIANCOMPARATIVE CARDIAC ANATOMY REFERENCES 1. HISTORICAL PERSPECTIVE the dominion of man and, although worthy of respect, could be OF ANATOMY AND ANIMAL RESEARCH used to obtain information if it was for a "higher" purpose (2). Anatomy is one of the oldest branches of medicine, with his- Descartes described humans and other animals as complex torical records dating back at least as far as the 3rd century BC; machines, with the human soul distinguishing humans from animal research dates back equally as far. Aristotle (384-322 BC) all other animals. This beast-machine concept was important studied comparative animal anatomy and physiology, and for early animal researchers because, if animals had no souls, Erasistratus of Ceos (304-258 BC) studied live animal anatomy it was thought that they could not suffer pain. Furthermore, the and physiology (1). Galen of Pergamum (129-199 AD) is prob- reactions of animals were thought to be the response of auto- ably the most notable early anatomist who used animals in mata and not reactions of pain (2). research to attempt to understand the normal structure and The concept of functional biomedical studies can probably function of the body (2). He continuously stressed the cen- be attributed to another great scientist and anatomist, William trality of anatomy and made an attempt to dissect every day Harvey (1578-1657 AD). He is credited with one of the most because he felt it was critical to learning (3). His most notable outstanding achievements in science and medicine: a demon- work was De Anatomicis Administrationibus (On Anatomical stration of the circulation of blood, which was documented in Procedures), which when rediscovered in the 16th century, his publication Exercitatio Anatomica De Motu Cordis et San- renewed interest in anatomy and scientific methods (2). guinis in Animalibus (De Motu Cordis) in 1628. His work ush- The Renaissance was a period of great scientific discovery ered in a new era in science, in which a hypothesis was and included advances in our understanding of human and formulated and then tested through experimentation (4). Many animal anatomy. Andreas Vesalius (1514-1564 AD) was argu- great anatomists emerged during this period and made innu- ably the greatest anatomist of the era (4). He performed public merable discoveries; many of these discoveries were named nonhuman dissections at the University of Padua in Italy to after the individuals who described them, including several teach anatomy and is credited with creating the field of mod- researchers who studied cardiac anatomy such as the eustachian ern anatomy (2). His immediate successors at Padua were valve (Bartolomeo Eustachio), the Thebesian valve and The- Matteo Realdo Colombo (1510-1559 AD), who described pul- besian veins (Thebesius), and the sinus of Valsalva (Antonio monary circulation and the atrial and ventricular cavities, and Maria Valsalva). Gabriele Falloppio (1523-1562 AD), who is credited with the It should be noted that, during this time period, in addition to discovery of the Fallopian tubes among other things (4). Ani- animal dissection, dissections on deceased human bodies were mal research flourished during this period because of a num- performed, but not to the degree that they are today. In fact, it ber of popular ideas launched by the Christian church and is written that, in general, during the post-Renaissance era there Rene Descartes. The church asserted that animals were under was a serious lack of human bodies available for approved dis- section. Often, bodies were obtained in a clandestine manner, From: Handbook of Cardiac Anatomy, Physiology, and Devices Edited by: P. A. Iaizzo © Humana Press Inc., Totowa, NJ such as grave robbing, or the bodies of executed criminals were 81 82 PART I1: ANATOMY / HILL AND IAIZZO provided for dissection. In spite of the lack of bodies for study, were employed as the primary animal model in numerous stud- most structures in the human body, including microscopic ones, ies aimed at identifying potential pharmacological therapies for were described by various anatomists and surgeons between the reducing infarct size. However, a detailed understanding of the 15th and early 19th centuries. coronary arterial anatomy was either lacking or overlooked at Early in the 19th century, the first organized opposition to the time; subsequently, it was shown that dogs have a much animal research occurred. In 1876, the Cruelty to Animals Act more extensive coronary collateral circulation relative to hu- was passed in Britain. It was followed in the United States by mans (Fig. 1). Thus, even when major coronary arteries were the Laboratory Animal Welfare Act of 1966, which was occluded, reliable and consistent myocardial infarcts were dif- amended in 1970, 1976, and 1985. These two acts began a ficult to create. This led to false claims about the efficacy of new era in how laboratory animals were treated and utilized in many drugs in reducing infarct size; when tested in humans, experimental medicine. Nevertheless, the necessity of animal these drugs usually did not produce the same results as those research is still great; therefore, animals continue to be used observed in the canine experiments (5). for a variety of scientific purposes, including cardiovascular 3. LARGE MAMMALIAN device research. COMPARATIVE CARDIAC ANATOMY 2. IMPORTANCE OF ANATOMY In general, the hearts of large mammals share many similari- AND ANIMAL RESEARCH ties, and yet the sizes, shapes, and positions of the hearts in the Anatomy remains as quite possibly one of the most impor- thoracic cavities can vary considerably between species (6). tant branches of medicine. To diagnose and treat medical con- Typically, the heart is located in the lower ventral part of the ditions, normal structure and function must be known because mediastinum in large mammals (7). Most quadruped mammals it is the basis for determining what is abnormal. Furthermore, tend to have a less-pronounced left-sided orientation and a more structure typically has a great impact on the function of an organ, ventrally tilted long axis of the heart compared to humans (7) such as with the heart. For instance, a stenotic aortic valve will (Fig. 2). In addition, hearts of most quadruped mammals tend to usually cause functional impairment of the left ventricle and be elongated and have a pointed apex, with the exception of lead to further pathological conditions (e.g., hypertrophy). Thus, (1) dogs, which tend to have an ovoid heart with a blunt apex knowledge of anatomy and pathology is fundamental in under- (7); (2) sheep, which may have a somewhat blunt apex (8); and standing not only how the body is organized, but also how the (3) pigs, which have a blunt apex that is oriented medially (8). body works and how disease processes can affect it. Comparatively, human hearts typically have a trapezoidal shape Likewise, animal research has been fundamental for much of (9) with a blunt apex. However, the apices of normal dog, pig, the progress made in medicine. Most, if not all, of what we sheep, and human hearts are all formed entirely by the left ven- know about the human body and biology in general has been tricles (8-11) (Fig. 3). initially made possible through animal research. A 1989 Ameri- Differences exist in the ratios of heart weight to body weight can Medical Association publication, cited in ref. 2, listed medi- reported for large mammals. It is generally accepted that adult cal advances that had emanated from animal research, including sheep and adult pigs have smaller ratios of heart weight to studies on acquired immunodeficiency syndrome (AIDS), body weight than those of adult dogs. It has been reported that anesthesia, cardiovascular disease, diabetes, hepatitis, and adult dogs have as much as twice the heart weight to body Parkinson's disease, to name only a few. weight ratio (6.95:7 g/kg) as pigs (2.89:2.5 g/kg) and sheep Currently, animal research is fundamental in developing (3.13:3 g/kg) (12,13). The normal ratio of the adult human new therapies aimed at improving the quality of life for patients heart weight to body weight has been reported as 5 g/kg, which with cardiovascular disease. Furthermore, early cardiac device is similar to that of young pigs (animals 25-30 kg) (14). prototype testing is commonly performed utilizing animal All large mammalian hearts are enclosed by the pericardium, models, both with and without cardiovascular disease. More which creates the pericardial cavity surrounding the heart. The specifically, before an invasively used device (a class III medi- pericardium is fixed to the great arteries at the base of the heart cal device) can be tested in humans, the Food and Drug Admin- and is attached to the sternum and diaphragm in all mammals, istration requires sufficient data obtained from animal research although the degree of these attachments to the diaphragm var- indicating that the device functions in the desired and appropri- ies between species (6,7). Specifically, the attachment to the ate manner. Importantly, it is also critical to extrapolate subse- central tendinous aponeurosis of the diaphragm is firm and quently that a given device will be safe when used in humans; broad in humans and pigs, the phrenopericardial ligament is the that is, it will behave in humans in a manner similar to its only pericardial attachment in dogs, and the caudal portion of determined function in the animal models. This extrapolation the pericardium is attached via the strong sternopericadial liga- of animal data to the human condition requires that the animal ment in sheep (6,7).