© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Effects of sustained low-flow ischemia on myocardial function and calcium-regulating proteins in adult and senescent rat hearts1
aGroupe de Physiopathologie Cellulaire Cardiaque, ESA CNRS 5077, Université Joseph Fourier, 38000 Grenoble, France
bService de Cardiologie, Hôpital Bichat-Claude Bernard, 75018 Paris, France
cINSERM Unité 127, IFR Circulation, Hôpital Lariboisière, 75010 Paris, France
dLaboratoire de Biophysique Moléculaire et Cellulaire, CEA-DBMS, URA CNRS 520, 38000 Grenoble, France
eURA CNRS 1131, Université Paris-Sud, 91405 Orsay, France
fFaculté de Pharmacie, Université Aix-Marseille II, 13000 Marseille, France
* Corresponding author. Tel. (+33) 4 76 51 46 71; Fax (+33) 4 76 51 26 59.
Objective: Both aging and myocardial ischemia are associated with alterations of calcium-regulating proteins. We investigated the effects of graded levels of low-flow ischemia on myocardial function and on SR Ca2+-ATPase (SERCA2), Na+-Ca2+ exchanger (NCx) and ryanodine receptor (RyR2), at mRNA and protein levels in both adult and senescent myocardium. Methods: Isolated hearts from 4 and 24 month old (mo) rats were retrogradely perfused during 180 min at 100% (100% CF, n=11 and n=11 respectively), 30% (30% CF, n=10 and n=12) or 15% (15% CF, n=13 and n=8) of their initial coronary flow, and active tension and coronary resistance (in % of their baseline value) were recorded. After 180 min of perfusion, NCx, RyR2 and SERCA2 mRNAs (in % of age-matched 100% CF group value) and protein levels were quantitated in the left ventricles by slot blot and Western blot analysis, respectively. Results: In 24 mo hearts, low-flow ischemia induced a greater fall in active tension (–65±7% vs. –40±4% in 4 mo 30% CF, p<0.01 and –82±2% vs. –60±5% in 4 mo 15% CF groups, p<0.05 after 15 min of ischemia) and a greater increase in coronary resistance (+357±44% vs. +196±39% in 4 mo 30% CF, p<0.05 and +807±158% vs. +292±61% in 4 mo 15% CF groups, p<0.001 after 15 min of ischemia). An increased accumulation of SERCA2 (+36%) and NCx (+46%) transcripts, but not RyR2, already occurred in 24 mo 30% CF group while the 3 transcripts accumulated in 24 mo 15% CF group. In 4 mo rats SERCA2 (+26%), NCx (+35%) and RyR2 (+81%) mRNA levels only increased in the 15% CF group. Corresponding calcium-regulating protein levels were unaltered whatever the degree of flow reduction in both 4 mo and 24 mo hearts. Conclusion: Low-flow ischemia does not induce calcium-regulating protein loss in both adult and senescent hearts. The increase in mRNAs coding for calcium-handling proteins and the impairment of myocardial function which occur at a lesser degree of coronary flow reduction in senescent hearts, indicate a higher vulnerability to low-flow ischemia during aging.
KEYWORDS Aging; Ischemia; Contractility; Sarcoplasmic reticulum; Calcium; Rat
1 Presented in part at the XVIIIth Congress of the European Society of Cardiology, Birmingham, UK, 1996 and at the 69th Scientific Sessions of the American Heart Association, New Orleans, USA, 1996.
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