190 
PULMONARY MODELS 
sized membrane enclosed droplets. The thick- 
ened endocardium of the right ventricle was 
attributed to edema, focal hemorrhage and a de- 
cided subendothelial proliferation of fibrous 
connective tissue. 
The arteries throughout the right ventricle 
were also affected. Their entire walls were ede- 
matous, components were widely separated, and 
extravasated blood cells were prevalent 
throughout the wall. Fractures in the endo- 
thelial lining were apparent in some of these ves- 
sels. 
The hyperplastic bone marrow of the infant 
monkeys displayed numerous megakaryocytes 
and erythroid and myeloid elements. The gen- 
eral morphological features of the livers were 
fairly well maintained with the exception of iso- 
lated areas of vascular occlusion involving the 
small hepatic veins. The development of exten- 
sive hepatic scarring and the formation of en- 
dothelial lined sinuses so prevalent in older 
monocrotaline intoxicated monkeys^"^ was in- 
apparent in the livers of the infant animals. 
DISCUSSION 
Infant Macaca aretoides monkeys develop ex- 
tensive pulmonary vascular lesions following 
the administration of the pyrrolizidine alkaloid, 
monocrotaline. Pulmonary hypertension, car- 
diac hypertrophy, and right heart dilatation are 
aftermaths of the vascular changes. When adult 
monkeys are given similar doses of monocrota- 
line, only minor changes are noticed in the 
lungs; however, extensive liver lesions 
develop.i-3 This variation in response is attrib- 
uted to the means by which the alkaloid is metab- 
olized by the hepatic microsomal enzymes of 
the two age groups.^ It has been demonstrated 
that the microsomes from infant livers do not 
have the ability to convert monocrotaline into 
pyrroles (the liver toxin) as readily as micro- 
somes from adolescent or adult livers. It has 
been postulated that metabolites other than the 
pyrroles may give rise to the lung lesions,'^ and 
the enzymes responsible for these metabolic al- 
terations are more active in the microsomes of 
the younger animals. Regardless of the exact 
mechanism associated with the age dependent 
response, infant monkeys must be employed if 
acute pulmonary vascular lesions are desired. 
Cor pulmonale, liver necrosis, and hepatic 
and pulmonary vascular lesions, similar to those 
seen in primates, have been reported in rodents 
given monocrotaline. ■'■^ The major difficulty in 
employing these animals as experimental mod- 
els to study pulmonary or hepatic vascular le- 
sions is related to the inability of the investiga- 
tor to predict which of the two organs will be 
affected most severely under a given set of cir- \ 
cumstances. Rats of similar breeding, weight, 
and sex may develop pulmonary lesions when 
injected on one day and hepatic lesions when , 
litter mates are injected on the following day. It j 
is also difficult to predict the survival rates of i 
rats with acute pulmonary lesions. Pulmonary | 
edema and hemorrhage likely related to altered | 
vascular permeability, invariably present com- 
plications during the initial phases of monocro- 
taline intoxication and are largely responsible 
for heavy mortality. Such complications do not 
arise when subhuman primates are employed as 
experimental animals. By varying the age of 
the monkey, the specific lesions produced by 
monocrotaline can be accurately predicted and 
promptly developed in the absence of mortali- 
ties. 
SUMMARY 
Monocrotaline intoxicated monkeys offer a 
readily produced experimental model to study 
pulmonary hypertension and right heart failure 
in an animal having similar tissue responses 
and closely related phylogenetically to man. 
ACKNOWLEDGMENTS 
The authors express appreciation to Dr. J. A. 
Will for his assistance in the determinations of 
pulmonary artery and right heart pressures. 
REFERENCES 
1. Allen, J. R., Cakstens, L. A., and Olson, B. E. 
Veno-occlusive disease in Macaca speciosa mon- 
keys. Amer. J. Path. 50:653, 1967. 
2. Allen, J. R., Carstens, L. A., and Katagiri, G. J. 
Sequential ultrastructural changes in hepatic veins 
of monkeys with veno-occlusive disease. Arch. Path. 
87:279, 1969. 
