Reduced threshold for myocardial cell calcium intolerance in the rat heart with aging.
To determine whether advancing age is accompanied by a reduced Ca2+ tolerance, we measured Ca(2+)-dependent diastolic pressure, prolonged relaxation and systolic functional deterioration, spontaneous sarcoplasmic reticulum (SR)-generated Ca2+ oscillations [detected as scattered laser light intensity fluctuations (SLIF)], aftercontractions, and ventricular fibrillation in isolated, isovolumic, atrioventricular-blocked intact hearts from 24- to 26-mo (old) and 6- to 8-mo (young) male Wistar rats. In enzymatically isolated single cardiac myocytes, the likelihood of the occurrence of spontaneous contractile waves driven by spontaneous SR Ca2+ release was also determined. In response to stepwise increase in perfusate Ca2+ concentration (Cao), a reduction in the maximum developed pressure accompanied by an elevation in end-diastolic pressure and a prolonged contraction duration was observed at lower Cao in old vs. young hearts (P < 0.01 for each parameter). Furthermore, Ca(2+)-dependent ventricular fibrillation occurred during pacing in six old but in no young hearts (P < 0.01), aftercontractions were observed in seven old vs. one young heart (P < 0.01), and SLIF increased to a greater extent in old vs. young hearts. In single cardiac myocytes, spontaneous contractile waves occurred more frequently with increasing age (P < 0.01). These results indicate that aging is associated with an increased likelihood for the occurrence of SR-generated Ca2+ oscillations and functional abnormalities that result from these oscillations.
Hano
O
O
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Bogdanov
K Y
KY
Sakai
M
M
Danziger
R G
RG
Spurgeon
H A
HA
Lakatta
E G
EG
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004056:Differential Threshold; D004351:Drug Resistance; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D014693:Ventricular Fibrillation / Q000503:physiopathology
D002118:Calcium