RESUMEN
Disturbance in ionic gradient across sarcolemma may lead to arrhythmias. Because Na(+)-K(+)-ATPase regulates intracellular Na(+) and K(+) concentrations, and therefore intracellular Ca(2+) concentration homeostasis, our aim was to determine whether changes in the Na(+)-K(+)-ATPase alpha-isoforms in guinea pigs during transition from compensated (CLVH) to decompensated left ventricular hypertrophy (DLVH) were concomitant with arrhythmias. After 12- and 20-mo aortic stenosis, CLVH and DLVH were characterized by increased mean arterial pressure (30% and 52.7%, respectively). DLVH differed from CLVH by significantly increased end-diastolic pressure (34%), decreased sarco(endo)plasmic reticulum Ca(2+)-ATPase (-75%), and increased Na(+)/Ca(2+) exchanger (25%) mRNA levels and by the occurrence of ventricular arrhythmias. The alpha-isoform (mRNA and protein levels) was significantly lower in DLVH (2.2 +/- 0.2- and 1. 4 +/- 0.15-fold, respectively, vs. control) than in CLVH (3.5 +/- 0. 4- and 2.2 +/- 0.13-fold, respectively) and was present in sarcolemma and T tubules. Changes in the levels of alpha(1)- and alpha(3)-isoform in CLVH and DLVH appear physiologically irrelevant. We suggest that the increased level of alpha(2)-isoform in CLVH may participate in compensation, whereas its relative decrease in DLVH may enhance decompensation and arrhythmias.
Asunto(s)
Adaptación Fisiológica/fisiología , Insuficiencia Cardíaca , Hipertrofia Ventricular Izquierda/fisiopatología , Isoenzimas/metabolismo , Miocardio/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Femenino , Cobayas , Hipertrofia Ventricular Izquierda/metabolismo , Isoenzimas/genética , ARN Mensajero/metabolismo , Ratas , ATPasa Intercambiadora de Sodio-Potasio/genéticaRESUMEN
The sinoatrial (SA) node is the cardiac pacemaker and changes in its adrenergic-muscarinic phenotype have been postulated as a determinant of age-associated modifications in heart rate variability. To address this question, right atria were microdissected, the SA node area was identified by acetylcholinesterase staining, and, using a RT-PCR method, the accumulation of mRNA molecules encoding beta1- and beta2-adrenergic (beta1- and beta2-AR) and muscarinic (M2-R) receptor was quantified to define the proportion between beta-AR and M2-R mRNAs within the sinoatrial area of adult (3 months) and senescent (24 months) individual rat hearts. In adult hearts, the highest M2-R/beta-AR mRNA ratio was observed within the sinoatrial area compared with adjacent atrial myocardium, while in the senescent hearts, no difference was observed between sinoatrial and adjacent areas. This change was specific of the sinoatrial area since adult and senescent whole atrial or ventricular myocardium did not differ in their M2-R/beta-AR mRNA ratio, and was associated with a fragmentation of acetylcholinesterase staining of the senescent SA node. Quantitative changes in the expression of genes encoding proteins involved in heart rate regulation specifically affect the sinoatrial area of the senescent heart.
Asunto(s)
Envejecimiento/metabolismo , Miocardio/metabolismo , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Receptores Muscarínicos/genética , Nodo Sinoatrial/metabolismo , Animales , Corazón/anatomía & histología , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero , Ratas , Ratas Wistar , Receptor Muscarínico M2 , Sensibilidad y Especificidad , Nodo Sinoatrial/anatomía & histologíaRESUMEN
BACKGROUND: Although severe arrhythmias are still a major problem in patients with left ventricular hypertrophy (LVH), the relationship between ventricular remodeling and its regression or prevention, and the prevalence of ventricular premature beats (VPB) or more sustained arrhythmias are still poorly explored in hypertensive heart disease. METHODS AND RESULTS: Holter monitoring was used to quantify supraventricular premature beats and VPB and heart rate (HR) in middle-aged spontaneously hypertensive rats (SHR) and Wistar rats treated for 3 months with trandolapril (ACE inhibitor, 0.3 mg/kg per day). Hypertrophy and fibrosis were morphometrically determined. Statistical analysis was performed with the use of simple regression and multivariate data analysis (cluster and correspondence analysis). SHR have higher cardiac mass and fibrosis, more VPB, and a decreased HR. Cluster analysis demonstrated that trandolapril was only effective in SHR. Trandolapril significantly reduced cardiac hypertrophy, fibrosis, and VPB incidence and increased the HR. Simple regression analysis showed that VPB incidence correlated to both hypertrophy and fibrosis. Correspondence analysis evidenced a strong correlation between hypertrophy, fibrosis, and VPB, but only for severe hypertrophy, and the correlation disappeared for moderate hypertrophy. CONCLUSIONS: After trandolapril treatment, the regression of VPB incidence not only is linked to hypertrophy and fibrosis, but additional causal factors also are involved including the myocardial phenotype and new calcium metabolism. Our model of Holter monitoring in conscious middle-aged SHR and multivariate data analysis might be useful in correlating myocardial structural modifications and ectopic activity.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Complejos Cardíacos Prematuros/prevención & control , Indoles/uso terapéutico , Envejecimiento , Animales , Complejos Cardíacos Prematuros/epidemiología , Complejos Cardíacos Prematuros/etiología , Electrocardiografía Ambulatoria/métodos , Electrocardiografía Ambulatoria/veterinaria , Fibrosis Endomiocárdica/etiología , Fibrosis Endomiocárdica/prevención & control , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/prevención & control , Incidencia , Masculino , Análisis Multivariante , Prevalencia , Ratas , Ratas Endogámicas SHR , Ratas WistarRESUMEN
Reduced heart rate variability (HRV) has a strong predictive value in terms of sudden death, as compared to other prognostic criteria, but it has never been previously studied in experimental models of cardiac hypertrophy and failure. However, it has been quantified in rats using Holter monitoring and the peak and trough method of analysis. In normal rats, as in humans, short and long oscillations, sensitive, respectively, to atropine and propranolol were detected. Both correlate with heart rate. Cardiothyrotoxicosis was characterized by tachycardia and, independently, by a pronounced alteration in long oscillations. HRV was normal in compensatory cardiac hypertrophy due to aortic stenosis, but in this model the normal correlation existing between HRV and heart rate had disappeared. It is suggested that the main determinants of the above modifications of HRV are the changes in the new myocardial phenotype observed in terms of beta-adrenoceptor and muscarinic densities.