A mouse model of carcinoid syndrome and heart disease.
BACKGROUND
Carcinoid heart disease occurs in over 65% of patients with the carcinoid syndrome and is characterized by fibrous thickening of cardiac valves, leading to heart failure. Whether serotonin is directly responsible for these cardiac abnormalities is unknown. Therefore, to further understand the etiology and pathophysiology of carcinoid heart disease, we developed an animal model of the carcinoid syndrome.


METHODS
Seventeen nude mice underwent intrasplenic injection of human pancreatic carcinoid BON cells (10(7)) and then were euthanized 9 weeks later. Murine livers were analyzed by immunohistochemistry. Murine hearts were sectioned and the surface area of the right heart valves determined. Blood was also collected and analyzed for platelet serotonin by ELISA.


RESULTS
Sixty-five percent of the mice developed gross carcinoid liver metastases demonstrated by chromogranin-A-staining lesions within the liver. Mice with carcinoid liver metastases had elevated platelet serotonin levels (1058 +/- 529 ng/ml versus 123 +/- 52 ng/ml, P = 0.002) when compared to the controls. Animals with carcinoid liver metastases also had a trend toward greater tricuspid valvular surface areas (242 +/- 24 versus 174 +/- 25 microm, P = 0.08). On histological examination, this increase in tricuspid surface area in mice with liver metastases appeared to be due to fibrosis of the valvular tissues, consistent with the pathologic findings of carcinoid heart disease.


CONCLUSIONS
Using this novel animal model of carcinoid syndrome, the tricuspid valve thickening resembling carcinoid heart disease could be due to exposure to factors such as serotonin secreted by carcinoid tumor cells.
Musunuru
Sandeepa
S
Department of Surgery, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
Carpenter
Jennifer E
JE
Sippel
Rebecca S
RS
Kunnimalaiyaan
Muthusamy
M
Chen
Herbert
H
D000818:Animals; D002275:Carcinoid Heart Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D012701:Serotonin / Q000096:biosynthesis
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid