686 
PHYSIOLOGY 
creasing restriction of stroke volume, develops 
and eventually results in death of the host. Un- 
commonly, a fatal arrhythmia (most often asys- 
tole, not ventricular fibrillation) is the terminal 
event. It is important to note that parallel aug- 
mentation of peripheral vascular resistance in 
the recipient results in relatively stable preser- 
vation of arterial blood pressure (and thus, 
parenthetically, in conjunction with the availa- 
ble data on ventricular diameter, maintenance 
of left ventricular afterload) until terminal col- 
lapse. 
Of the primary determinants of cardiac out- 
put, i.e., ventricular preload, afterload, heart 
rate, and contractile state, it is the latter v^^hich 
would appear to be the critically limiting factor 
during advanced rejection. The small changes 
which did occur in end-diastolic fiber length 
(diameter) were directionally opposite to those 
which would tend to decrease stroke volume, ac- 
cording to the Frank-Starling principle. How- 
ever, these changes were sufficiently slight as to 
not significantly increase ventricular afterload. 
Heart rate changes were generally minimal. 
The observed alterations in maximum sys- 
tolic -dD/dt, VcF, VcE, and percent systolic 
shortening of diameter (and thus by extrapola- 
tion, ejection fraction) , in the absence of signif- 
icant variations of preload, afterload, heart 
rate, and direct neural stimulation (denervated 
heart) , suggest a decay in contractility. Several 
previously demonstrated pathologic findings, in 
addition to actual myocyte necrosis, are availa- 
ble for correlation with this conclusion. For ex- 
ample, Kosek and coworkers^ have shown, in 
cardiac allografts undergoing acute rejection, 
abnormalities in subcellular structures such as 
mitochondria, the sarcotubular system, and en- 
doplasmic reticulum. Such changes would be ex- 
pected to be associated with derangement of 
electromechanical coupling and energy transfer. 
At the present time, however, the precise patho- 
physiologic implications of these morphologic 
alterations in acute graft rejection are un- 
known. 
In addition to the changes recorded in donor 
left ventricular systolic performance during 
acute rejection, significant alterations in the 
configuration of diastolic filling were also ob- 
served. With advancing rejection the rapid. 
early phase of ventricular diastolic filling ac- 
counted for an increasing proportion of the 
total increment of diameter during diastole. Be- 
cause of the limited augmentation of diameter 
during diastasis and atrial systole, the resulting 
records of left ventricular diameter assumed a 
"flat-topped" appearance (Figure 4), reminis- 
cent of the "square root" sign of ventricular 
DAY 3 
DAY 4 
DAY 5 
DAY 6 
HR 100 
DAY 6 
HR 145 
Sec 
DAY 0 I 
HR 147 Q 20- 
> 
lOL 
30 r 
DAY I 
HR 135 20 
10 
-AAAAAT 
30 r 
20- 
10- 
30- 
20- 
10- 
30 
20 
10 
30r 
20- 
10- 
30r 
20- 
10- 
r~\r 
Figure 4. — Serial recordings of left ventricular internal 
transverse diameter (in mm) throughout the post- 
operative course in one recipient. 
