Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass

Abstract

Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β, β-adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β and β receptors and GRK-2, suggesting that this is one of the mechanisms responsible for the exacerbated response of cardiomyocytes to circulating catecholamines. These alterations could explain the irreversible myocardial damage and lipid peroxidation of membranes classically attributed to catecholamine excess, observed in some infants who develop heart failure and postoperative death. Although other factors may be involved, this study confirms that CPB acts as a potent inducer of increased gene expression of β- adrenergic receptors and GRK-2, making the myocardium of these infants more susceptible to the effects of circulating endogenous catecholamines, which may contribute to the development of irreversible myocardial damage and death.

Atrial Strain by Feature-Tracking Cardiac Magnetic Resonance Imaging in Takotsubo Cardiomyopathy. Features, Feasibility, and Reproducibility

“…As a matter of fact, the number of beta adrenoreceptors present at atrial level is the same as at ventricles. 21,22 In the present study, we found an impairment of RA conduit phase (RA e e ) in TS patients in comparison with control groups. RA e e represents passive filling of blood from systemic veins during ventricular diastole.…”

“…As a matter of fact, the number of beta adrenoreceptors present at atrial level is the same as at ventricles. 21,22…”

β2-Adrenoceptors and GRK2 as Potential Biomarkers in Patients With Chronic Pulmonary Regurgitation

“…As far as we know, our study is the first to analyze the behavior of β-ARs and GRKs in patients with congenital heart disease or with right ventricle disease in a stable situation. Only, one paper has been published analyzing alterations in the expression of GRK2 and ARs in atrial myocytes of patients with congenital heart disease operated on with cardiopulmonary bypass (Oliveira et al, 2017) but, in this case, the alterations were related to the vulnerability of the myocardium to catecholamine levels in an acute surgical context. These findings, although interesting, are not comparable to the situation of our patients, since post-RVP extraction has been performed in a stable situation, at least one year after surgery.…”

Calenduloside E suppresses calcium overload by promoting the interaction between L-type calcium channels and Bcl2-associated athanogene 3 to alleviate myocardial ischemia/reperfusion injury

“…Once restored at room temperature, the sections were blocked with BSA and incubated with primary antibody overnight at 4 °C. The next day, the sections were incubated with secondary antibody at 37 °C in the dark for 1 h, and nuclei were stained with DAPI [20] , [21] . The fluorescent images were acquired by Tissue Gnostics AX10 analysis system (Vienna, Austria).…”