Cardiomyopathy in a rat model of pheochromocytoma. Morphological and functional alterations.
To investigate the cardiac muscle damage observed in pheochromocytoma, New England Deaconness Hospital rats were implanted subcutaneously with a transplantable pheochromocytoma. The tumor was evident 4 weeks after transplantation. Approximately 5-6 weeks after transplant, systolic blood pressure was significantly increased in tumor-bearing animals (183 +/- 13 vs 119 +/- 7 in controls). At this time a cardiomyopathy with the following features was apparent in the tumor-bearing animals: multifocal lesions of enhanced interstitial and replacement fibrosis; granularity of the cytoplasm and contraction band necrosis; and mixed inflammatory infiltrates. Using a morphological scoring system from 0 (no cardiac damage) to 3 (complete involvement of the ventricular cross section studied), the pheochromocytoma animals had a cardiomyopathy score of 1.8 +/- 0.1, which is significantly greater than that found in age- and sex-matched controls: 0.4 +/- 0.1, p less than .001. A significant increase in the wet heart weights (1.28 +/- 0.07 vs. 1.12 +/- 0.04 in controls) was also observed in these animals, indicating the possibility of cardiac hypertrophy in the pheochromocytoma rats. There was a marked decrease in sensitivity to isoproterenol in isolated, electrically driven left atrial strips from pheochromocytoma rats. Isoproterenol's EC50 increased eightfold from 1.5 +/- 0.6 x 10(-8) M in controls to 1.3 +/- 0.4 x 10(-7) M in left atrial strips from the pheochromocytoma rats. However, there was no difference in maximal contractile response to isoproterenol in either the left atrial strips or in right or left ventricular papillary muscle strips. Also, there was no change in responsiveness of either left atrial or right ventricular muscle strips from pheochromocytoma hearts to contraction induced by 3.75 mM calcium chloride. However, the contractile response to calcium was enhanced in left ventricular papillary muscle from tumor-bearing animals (808 +/- 195 vs 372 +/- 101 mg tension in controls, p less than 0.05). These results demonstrate a catecholamine-induced cardiomyopathy in hearts from pheochromocytoma-bearing rats. Furthermore, the results demonstrate a functional beta-adrenergic receptor desensitization in isolated left atrial strips from tumor-bearing rats, whereas maximal contraction of heart muscle, induced by either isoproterenol or calcium chloride, remains intact.
Rosenbaum
J S
JS
Department of Medicine and Pathology, Stanford University, California.
Billingham
M E
ME
Ginsburg
R
R
Tsujimoto
G
G
Lurie
K G
KG
Hoffman
B B
BB
D000818:Animals; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000473:pathology* / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006984:Hypertrophy / Q000473:pathology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D010673:Pheochromocytoma / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines