Modification of some components of the cardiac beta-adrenergic system along the experimental Trypanosoma cruzi infection

LO PRESTI, M.S.; RIVAROLA, H.W.; FERNANDEZ, A.R.; ENDERS, J.E.; LEVIN, G.; COMAY, D.F.; PAGLINI-OLIVA, P.A.

Bs As

Congreso; World Congress of Cardiology; 2008

World Heart Federation

Chagas’ disease is one of the most important determinants of congestive heart failure and sudden death in Latin America. It has been demonstrated that the cardiac beta-adrenergic signal transduction system is altered somewhere along it’s pathway in Trypanosoma cruzi infected hearts and the study of this system would therefore be important for the understanding of the disease pathophysiology. In the present work, we studied some components of the cardiac beta-adrenergic system in mice hearts infected with T. cruzi, Tulahuen strain, along the experimental infection: acute phase (30 days post infection –d.p.i.), indeterminate chronic form (75 d.p.i.), early cardiac chronic form (135 d.p.i) and late cardiac chronic form (365 d.p.i). We determined: the primary messenger (epinephrine and norepinephrine) levels in plasma by RF-HPLC; the cardiac beta-receptor density and affinity by binding with trited dihidroalprenolol; the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the activation of protein kinase A and the consequent phosphorylation of the proteins involved in cardiac contraction; and the cardiac contractility and functional studies of the beta-ARs as a response to the ligand binding to the receptor. Plasma catecholamines levels diminished with the evolution of the infection when compared to the uninfected controls (p<0.05). The beta-receptor’s affinity also decreased with the evotution of the infection when compared to the uninfected mice (p<0.05), while their density remained unchanged at the beggining of the infection and started to decrease in the early cardiac chronic form (p<0.05). cAMP levels were higher in the infected group (p<0.01) relative to the controls in all phases of the infection and increasing significantly increasing in the late cardiac chronic form. However, the basal contractile force remained unchanged, and the response to catecholamines increased only in the chronic indeterminate form of the experimental infection (p<0.05). The alterations in the signaling pathways of the cardiac beta-adrenergic system start in the acute phase and progress with the evolution of the experimental infection. These results point to alterations at different levels of the system: 1) between catecholamines and the beta1-receptors; 2) between the receptors activation and the adenylyl-cyclase activation; and/or 3) between cAMP and the contractile response. Since this system is the most powerful regulator of cardiac function, these alterations could be responsible for inducing the progressive cardiopathy.