ANIMAL MODELS OF MYOCARDIAL INFARCTION: 
CURRENT LIMITATIONS AND FUTURE PROMISE 
W. B. Hood, Jr. and J. C. Norman* 
Our laboratories have been engaged for four years in 
developing myocardial infarction models in the dog, 
pig, and calf. Initially open-chest, acute occlusions of 
individual major coronary arteries were effected in all 
three species. Subsequently this methodology was ex- 
tended to intact conscious animals utilizing single and 
multiple implantable coronary artery balloon-cuff 
occluders. With this approach discrete areas of the my- 
ocardium can be rendered temporarily ischemic or per- 
manently infarcted. Approximately two hundred ani- 
mals have been studied. Transient, acute occlusion of a 
major coronary artery with subsequent release within 
two minutes in the open-chest or awake, unanesthetized 
dog, pig or calf results in immediate, but reversible 
electrocardiographic changes of ischemia and hemo- 
dynamic alterations of moderate ventric ilar failure. 
Permanent occlusion of a major coronary trtery in the 
awake, unanesthetized animal results in persistent and 
progressive electrocardiographic, hemodynamic and en- 
zymatic alterations. Dogs develop significant hemodyn- 
amic changes, frequently without fatal dysrhythmias, 
whereas pigs and calves almost invariably fibrillate. No 
obvious pain reaction occurs in any of the species. Sur- 
viving dogs develop multifocal ventricular tachycardia 
in the period from 4 to 72 hours following permanent 
single vessel occlusion. Permanent multiple vessel oc- 
clusion is followed by progressive and unstable hemo- 
dynamic deterioration ; such animals are not suitable for 
studies of steady-state cardiac failure. Thus far, no 
completely satisfactory model of stable, severe, persist- 
ent cardiac failure has been evolved. In the most suit- 
able model, i.e., the dog, hemodynamic patterns of left 
ventricular failure are complicated by ventricular dys- 
rhythmias. The absence of pain reactions in all three 
species in the awake state suggests inherent differences 
from clinical myocardial infarction. Promising areas of 
future study include the production of severe failure 
by the staged complete occlusion of the left anterior de- 
scending followed by partial occlusion of the circum- 
flex coronary artery and observations on the pain-con- 
ditioned primate. 
INTRODUCTION** 
The recent resurgence of interest in the clini- 
cal entity of acute myocardial infarction has 
stimulated a search for improved models of 
acute coronary occlusion in animals. Models are 
being sought which will simulate the disease as 
it occurs in a clinical setting, which will prove 
suitable for evaluating the effects of medical 
therapy, and which will permit evaluation of 
newer methods of surgical intervention, includ- 
ing circulatory assist devices. 
The methods which have heretofore been 
available for inducing acute myocardial infarc- 
tion in animals have been manifold, and each 
possesses inherent advantages and disadvan- 
tages (Table I). To date, the most widely used 
methods have included direct ligation of a sin- 
gle large coronary vessel,^ placement of ame- 
roid constrictors about major coronary vessels,^ 
and embolization of coronary vessels with 
microspheres.^ The first method allows exact 
timing of infarction, but must be performed in 
the anesthetized open-chest animal, and has a 
considerable incidence of ventricular fibrilla- 
tion. The second method also requires thoraco- 
tomy, but animals usually develop infarction 
after recovery from surgery, and the method is 
therefore suitable for chronic studies ; the time 
of onset of infarction is unpredictable. The 
third method can be carried out in unoperated 
animals, but produces diffuse rather than focal 
myocardial damage, and therefore fails to simu- 
late clinical myocardial infarction. Newer meth- 
ods included insertion of a plug into a major 
coronary artery using a catheter-tipped device,* 
multiple ligation of small coronary vessels,^ in- 
duction of coronary arterial thrombosis by a 
catheter tipped electrode,*' embolization of the 
coronaries with metallic mercury,'^ and the in- 
duction of thrombosis by placing a magnesium 
* Thorndike Memorial and Sears Surgical Laboratories and the 
Boston University Medical Service, Boston City Hospital, the De- 
partments of Medicine and Surgery, Harvard Medical School, and 
the Department of Medicine, Boston University Medical School. 
** Supported by NIH Grants PH 43-68-684, AO 71-2498, HE 5244, 
HE 10539, HE 14294, SF-57-111, Grant 71-1016 from the American 
Heart Association, the John A. Hartford Foundation, the John and 
Mary R. Markle Foundation, and the Charles E. Merrill Trust. 
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