Effects of adrenergic agonists on the growth and gene expression of the transplanted heart

Cardiac growth occurs in response to changes in hemodynamic demand and results primarily from cellular hypertrophy without cellular hyperplasia. In addition to changes in cardiac work, various reports have demonstrated that adrenergic stimulation, specifically of the alpha 1 adrenergic receptor of cultured myocytes, can produce changes in cardiac-specific gene expression and increases in protein synthesis and cell growth. To study the effects of adrenergic stimulation in the absence of alterations in cardiac work we have used the model of the heterotopically transplanted heart, which is a spontaneously beating, vascularly perfused, and histologically normal heart that is hemodynamically unloaded. Seventy-two hours after transplantation, the hemodynamically unloaded transplanted heart had decreased in size by 20% when compared with the control host heart that was growing in situ. Treatment with either the alpha-adrenergic agonist phenylephrine (2.5 mg/kg/day) or the beta-adrenergic agonist isoproterenol (250 micrograms/kg/day) while increasing the spontaneous heart rate had no effect on the size of the transplanted heart. Simultaneous measurements demonstrated that both of these drugs produced a 10% increase in weight of the corresponding hemodynamically loaded host heart. We previously demonstrated that cardiac unloading caused a change in the expression of the myosin heavy chain (MHC) genes with a significant increase in the beta MHC isoform. In the present studies treatment with either isoproterenol or phenylephrine did not alter MHC gene expression either in the in situ host or transplanted hearts.(ABSTRACT TRUNCATED AT 250 WORDS)