Arrhythmogenicity of the hypertrophied and senescent heart and relationship to membrane proteins involved in the altered calcium handling.
The high incidence of arrhythmias in human left ventricular hypertrophy has been well established but the mechanisms of arrhythmias are not well defined. In attempt to clarify these mechanisms, we tried to determine if a relationship might exist in the hypertrophied or senescent hearts between the incidence of arrhythmias and alterations in the gene expression of the main membrane proteins involved in the regulation of calcium movements. Holter monitoring was used in young and senescent rats where hypertrophy had been induced by aortic stenosis and hyperthyroidism (young rats) or by DOCA-salt treatment (senescent rats). Different types of spontaneous arrhythmias were detected. In the aortic stenosis group, the heart rate and the number of supraventricular premature beats were increased significantly, whereas the number of ventricular premature beats was increased in some animals but not in all. In senescent rats, the numbers of ventricular and supraventricular premature beats and the incidence of atrioventricular block were very high. At the cellular level, the density of calcium channels from the sarcolemma and of the alpha 1 subunit of the Na+/K(+)-ATPase were unchanged in the hypertrophied and senescent hearts but most of the proteins involved in the regulation of calcium movements (calcium release channel and Ca(2+)-ATPase from the sarcoplasmic reticulum, Na+/Ca2+ exchange, and beta adrenergic and muscarinic receptors from the sarcolemma) have a decreased density or activity. These changes might account for the slowing of the maximum shortening velocity and the impaired contractility of the hypertrophied and senescent hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Carré
F
F
INSERM U127, Hôpital Lariboisière, Paris, France.
Rannou
F
F
Sainte Beuve
C
C
Chevalier
B
B
Moalic
J M
JM
Swynghedauw
B
B
Charlemagne
D
D
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats
D008565:Membrane Proteins; D002118:Calcium