152 
CARDIAC MODELS 
in animals with severe depression of ventricular 
performance. From these studies in the intact 
ventricle of normal, hypertrophied and failing 
hearts, it is concluded that the observations 
made in the isolated papillary muscle were also 
true for the intact ventricles of these animals. 
There was obvious depression of myocardial 
function both in isolated muscle and intact ven- 
tricles of animals with hypertrophy but without 
overt heart failure in which the cardiac output 
was normal. Thus, it is appax'ent that depres- 
sion of the cardiac output is a late finding in 
congestive heart failure. 
SUMMARY 
Pulmonary artery constriction in the cat has 
been and continues to be an excellent model for 
investigation of ventricular hypertrophy and 
congestive heart failure. By this method some 
aspects of the pathophysiology and the clinical 
syndrome of congestive heart failure have been 
elucidated. It has been found that the contrac- 
tile state of isolated cardiac muscle in both the 
hypertrophied and failing heart is severely re- 
duced. It is also apparent that there is severe 
depression of the contractile state of the intact 
ventricle of experimental animals in which 
there is hypertrophy but no overt congestive 
heart failure and in which the cardiac output is 
normal at rest. It has become increasingly im- 
portant to determine the contractile state of the 
myocardium in cardiac disease, since its proper 
understanding provides the basis for the appre- 
ciation of the compensatory mechanisms neces- 
sary to maintain cardiac output in the face of 
severely reduced myocardial contractility. 
Also this cat pulmonary constriction heart 
failure model has provided tissue for investiga- 
tion of the biochemical abnormalities associated 
with the failing heart. Disorders of lipid sub- 
strate utilization, myofibrillar ATPase, and the 
sarcoplasmic reticulum-calcium system have 
been demonstrated or implied, and several 
potential lesions have been excluded. Both sym- 
pathetic nervous system function and cardiac ca- 
techolamine metabolism are strikingly altered 
in ventricular hypertrophy and in congestive 
heart failure. The depletion of myocardial ca- 
techolamine results in the impairment of a 
potential compensatory mechanism. In this sit- 
uation, however, circulating catecholamine rep- 
resents an important support for the failing 
heart, which is supersensitive to the effects of 
exogenous norepinephrine, a fact that explains 
the deleterious effect that may occur when 
beta-adrenergic receptor blocking agents are 
administered to patients with depressed cardiac 
function. 
In addition to the changes in the central cir- 
culation, there are important changes in the pe- 
ripheral arterial and venous beds in heart failure 
that aid in the maintenance of circulatory 
function. The cardiac compensatory mecha- 
nisms that help maintain circulation in the face 
of the depressed intrinsic state of the myocar- 
dium can be considered in terms of the resul- 
tant symptoms that they produce. The principal 
compensations are by myocardial hypertrophy, 
the Frank-Starling mechanism, and altered 
sympathetic nervous system activity to the 
heart, arterial and venous beds. Each compen- 
satory mechanism has a built-in set of limita- 
tions that, when exceeded, produce signs and 
symptoms, such as dyspnea, pulmonary edema 
and systemic venous congestion. A reduction in 
resting cardiac output is a relatively late mani- 
festation of the failing heart ; when the compen- 
satory mechanisms are no longer sufficient to 
overcome the intrinsic depression of the con- 
tractile state, the cardiac output fails even at 
rest, and the end stages of congestive heart fail- 
ure are apparent in weakness, mental confu- 
sion, oliguria and hypotension. 
REFERENCES 
1. Barger, a. C, Richardson, G. S., Roe, B. B. A 
method for producing chronic cardiac failure in 
dogs. Proc. Soc. Exp. Biol. & Med. 73:113, 1950. 
2. Gertler, M. M. Production of experimental con- 
gestive heart failure in the guinea pig. Proc. Soc. 
Exp. Biol. & Med. 102:396, 1959. 
3. Alexander, N., Edmonson, H. A., Druary, D. R. 
The production of experimental congestive heart 
failure in rabbits. Circ. Res. 1:491, 1953. 
4. Nadeau, R. A., COLEBATCH, J. J. H. Normal respir- 
atory and circulatory values in the cat. Appl. Phy- 
siol. 20:863, 1965. 
5. Sonnenblick, E. H. Implications of muscle me- 
chanics in the heart. Fed. Proc. 21:975, 1962. 
