PULMONARY HYPERTENSION IN YOUNG MACACA ARCTOIDES 
MONKEYS: A SEQUELA TO MONOCROTALINE INTOXICATION 
J. R. Allen, J. M. Jenny and C. F. Chesney* 
Infant Macaca arctoides monkeys (stumptail) were 
given injections of the plant alkaloid monocrotaline 
(CioHsoOoN) on four occasions during a Gix month 
period. Within the terminal month or two of the experi- 
ment, there was an increase in hemoglobin, hematocrit, 
red cell volume and arterial pCOa and a decrease in ar- 
terial pOs and pH. Increases in right heart and pul- 
monary artery pressures were also indicative of changes 
in the pulmonary vasculature. Prior to death, the least 
exertion by these animals produced marked cyanosis. 
Grossly, the major changes noticed at necropsy were 
related to the heart and lungs. There was hypertrophy 
of the myocardium and a decided right heart dilatation. 
The lungs were uniformly firm and failed to collapse 
readily when exposed to atmospheric pressure. Micro- 
scopically, there were extensive modifications in the pul- 
monary vasculature. Platelet and fibrin thrombi oc- 
cluded numerous interalveolar capillaries. The walls of 
many arterioles and small muscular arteries were hy- 
alinized while in others there was hypertrophy of the 
smooth muscle and endothelium, both of which pro- 
duced partial or complete occlusion of the lumens. 
Fractured endothelial linings of the larger pulmonary 
arteries predisposed to the accumulation of blood com- 
ponents throughout the wall and to the development of 
fibrin thrombi within the lumen of the affected vessels. 
The myocardium of the right heart was edematous, the 
endocardium fibrotic and the arterial vessel walls dis- 
rupted. 
INTRODUCTION** 
It has been established that subhuman pri- 
mates offer the most ideal experimental model 
to evaluate two maladies of man, Budd-Chiari 
syndrome and veno-occlusive disease. Within 
a few months following the administration 
of the pyrrolizidine alkaloid, monocrotaline 
(C16H26O6N) to adult M. arctoides monkeys, 
segments of the hepatic venous system were 
obstructed.i-3 The animals developed ascites, 
portal hypertension, varices, hepatic fibrosis 
♦ Department of Pathology and Wisconsin Regional Primate Re- 
search Center, University of Wisconsin Madison, Wisconsin 
•* Supported in part by U.S. Public Health Service Grants 
HE10941, RR00167 and 1F02-ES46357 
and peliosis hepatis. However, cardiorespir- 
atory lesions in these animals were not appar- 
ent. The present communication is concerned 
with modifications in the above experimental 
procedure whereby similar doses of monocrota- 
line produce sufficient alteration in the pulmon- 
ary vascular bed of monkeys to facilitate 
interalveolar fibrosis, pulmonary hypertension, 
cardiac hypertrophy, and a right heart dilata- 
tion (cor pulmonale) . It is suggested that mono- 
crotaline intoxicated monkeys having cardio- 
respiratory lesions offer a readily produced 
experimental model to study human respiratory 
and cardiac maladies related to hypertension. 
MATERIALS AND METHODS 
Twelve Macaca arctoides monkeys, 30 days of 
age, weighing approximately 650 grams, and of 
both sexes, were employed in this study. Follow- 
ing a complete blood study which included hem- 
oglobins (Hb), hematocrits (Hct), white blood 
cell counts (WBC), differential counts, serum 
bilirubins, serum glutamic oxalacetic transami- 
nase (SGOT), total serum protein (TP), and 
electrophoretic patterns of the serum proteins, 
the animals were subcutaneously injected ini- 
tially with 30 mg of monocrotaline per kg of 
body weight. They were subsequently given 60 
mg of monocrotaline per kg of body weight on 
the second, fourth, and sixth month of the exper- 
iment. When the animals developed respira- 
tory symptoms and displayed a relative increase 
in circulating erythrocytes as determined by 
blood Hcts and an absolute increase as deter- 
mined by red cell volume,^ the arterial and ven- 
ous blood was analyzed for its hydrogen ion 
concentration, PCO2 and PO2,*** and right 
heart and pulmonary artery pressures were de- 
termined via cardiac catheterization. 
♦*♦ Radiometer (Astrup method) Blood Gas Analyzer, type AMEl, 
The London Co., Westlake, Ohio. 
187 
