Key result
Pheochromocytoma cell implantation in rodents increased left ventricular dilation by 35±6% in rats and reduced fractional shortening by 20±3% compared to norepinephrine alone.
Why the study?
Do pheochromocytoma secretory factors in combination with catecholamines induce greater cardiac damage than catecholamines alone in animal models?
Do pheochromocytoma secretory factors in combination with catecholamines induce greater cardiac damage than catecholamines alone in animal models?
Pheochromocytoma-induced cardiomyopathy is driven by a synergistic effect of catecholamines and other tumor-secreted factors, rather than catecholamines alone.
Pheochromocytoma factors may synergize with catecholamines to worsen rodent cardiomyopathy; leaves open human translation.
BACKGROUND: Pheochromocytomas are rare tumors derived from the chromaffin cells of the adrenal medulla. Although these tumors have long been postulated to induce hypertension and cardiomyopathy through the hypersecretion of catecholamines, catecholamines alone may not fully explain the profound myocardial remodeling induced by these tumors. We sought to determine whether changes in myocardial function in pheochromocytoma-induced cardiomyopathy result solely from catecholamines secretion or from multiple pheochromocytoma-derived factors. METHODS AND RESULTS: Isolated cardiomyocytes incubated with pheochromocytoma-conditioned growth media contracted at a higher frequency than cardiomyocytes incubated with norepinephrine (NE) only. Sprague-Dawley rats and black-6 mice were implanted with agarose-encapsulated pheochromocytoma (PC12) cells, dihydroxyphenylalanine decarboxylase knock-out PC12 cells deficient in NE (PC12-KO), or NE-secreting pumps. PC12 cell implantation increased left ventricular dilation by 35+/-6% and 9.6+/-1.4% and reduced left ventricular fractional shortening by 20+/-3% and 28+/-4% in rats and mice compared with animals dosed only with NE, respectively. Elimination of NE secretion in PC12-KO cells induced neither cardiac dilation (3.9%+/-1.8% increase versus control) nor changes in (1.9%+/-0.4% reduction) fractional shortening compared to controls. CONCLUSIONS: Pheochromocytomas induce a greater degree of cardiomyopathy than equivalent doses of NE, suggesting pheochromocytoma-induced cardiomyopathy is not solely mediated by NE, rather pheochromocytoma secretory factors in combination with catecholamines act synergistically to induce greater cardiac damage than catecholamines alone.
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Mobine et al. (2009) studied Pheochromocytoma-induced cardiomyopathy. Agarose-encapsulated pheochromocytoma (PC12) cells vs. Norepinephrine (NE)-secreting pumps and NE-deficient PC12-KO cells was evaluated on Left ventricular dilation and fractional shortening. Pheochromocytoma cell implantation in rodents increased left ventricular dilation by 35±6% in rats and reduced fractional shortening by 20±3% compared to norepinephrine alone.
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