E. B. STINSON, P. L. TECKLENBERG, J. F. HOLLINGS WORTH AND K. W. JONES 
685 
ferent from that present at the time of post- 
operative recovery. 
Both peak systolic rate of diameter shorten- 
ing (-dD/dt) and normalized circumferential 
shortening rate (Vcf) decreased significantly 
(p < .05) with acute rejection (to 43 
mm/second and 1.9 circs/second, respectively) 
(Figure 1). Percent systolic shortening of the 
transverse diameter also declined, from a mean 
value of 28% recorded at the time of recovery 
to 23.5% (p < .05) (Figure 1). 
Maximum systolic -dD/dt and Vcf deter- 
mined at the point of peak wall tension in one 
animal decreased during graft rejection to final 
measured values of 30 mm/second and 1.1 
circs/second, respectively. 
In all four grafts in which transverse left 
ventricular diameter was serially studied strik- 
ing changes in the pattern of diastolic filling de- 
veloped during rejection. The early, rapid phase 
of diastolic filling, which at the time of post- 
operative recovery accounted for 60 to 70% of 
the total diastolic increment in diameter, ac- 
counted for a progressively increasing propor- 
tion of total diastolic filling with advancing 
rejection (p < .01) (Figure 3). In other words, 
during late rejection little or no increase in left 
ventricular diameter occurred after the rapid 
filling phase, despite the persistence of donor 
atrial systole. The resulting records of left ven- 
tricular diameter were characteristically "flat- 
topped." Representative serial recordings of 
left ventricular diameter throughout the post- 
operative course of one animal are shown in Fig- 
ure 4. Concurrently, the average rate of diame- 
ter lengthening during the rapid filling phase of 
diastole decreased significantly (Figure 3). 
Mean rapid filling dD/dt for the four animals 
decreased from 71.3 mm/second at the time of 
postoperative recovery to 54 mm/second during 
rejection (p < .01). 
DISCUSSION 
These studies indicate that in the unmodified 
canine recipient hemodynamic function of an 
orthotopic cardiac graft is relatively well-main- 
tained at rest until late in the course of immu- 
nologic rejection. Detectable impairment of 
pumping performance developed only during 
the terminal 24 to 36 hours. In contrast, histo- 
logic observations have demonstrated a pro- 
gressive immune response appearing as early as 
24 to 48 hours after transplantation.® The earli- 
est such changes consist of mononuclear cell 
margination, endothelial cell damage, edema 
formation, and then progressive perivascular 
and interstitial mononuclear cell infiltration." It 
is apparent from the present studies that in the 
initial stages of rejection these changes are not 
expressed in demonstrable deterioration of he- 
modynamic or mechanical function of the trans- 
planted left ventricle. Late in the course of 
rejection, i.e., 24 to 48 hours prior to terminal 
failure of the graft, morphologic lesions include 
widespread foci of myocyte necrosis, and, in 
some cases, areas of frank myocardial infarc- 
tion involving especially the left ventricular 
subendocardial region and papillary muscles. 
Also at this stage, edema of the ventricular 
walls is strikingly severe, and the ventricular 
myocardium is grossly firm, rubbery, and dus- 
ky-red. 
During this interval, progressive diminution 
of cardiac output, due almost entirely to in- 
POSTOP RECOVERY REJECTION 
Figure 3. — Changes in the percent of rapid diastolic 
filling (% R.F.) (see text) and average dD/dt dur- 
ing rapid filling in four grafts (time periods same as 
in Figure 1). 
