The effect of cardiac hypertrophy on changes in cytosolic free calcium concentration during ischemia.
Chronic ventricular hypertrophy caused by pressure overload is a common associated risk factor in congenital cardiac surgery. Because calcium controls contractile protein interaction, we postulated that inducing ventricular hypertrophy from birth alters the way myocytes are able to regulate free cytosolic calcium (Cai) during ischemia. In this study we measured Cai with a recently developed intracellular fluorescent probe trapped inside myocytes by deesterification. The probe shifts its fluorescence spectra (from 380 to 340 nm; fluorescence measured at 510 nm) when it binds to calcium in direct relation to Cai. We studied the effects of ischemia at 37 degrees C (up to 50 minutes) on Cai in newborn (3 to 5 days), adult control (2 to 4 months old), and hypertrophied (2 months old; aortic banding done at 10 days) isolated retroperfused rabbit hearts loaded with Fura-2. In a separate group of hearts (n = 6 per group) we measured isovolumic peak developed pressure with an intracavity balloon in hearts subjected to 30 minutes of ischemia at 37 degrees C and 30 minutes of reperfusion. The recovery of peak developed pressure (percent of preischemic control) was 101% +/- 6% in control, 85% +/- 4% (p less than 0.05 vs control) in newborn, and 67% +/- 7% (p less than 0.05 vs control) in hypertrophied hearts. Cai-dependent fluorescence rose to 160% +/- 30% of preischemic baseline levels by 30 minutes of ischemia in control versus a decline to 55% +/- 7% (p less than 0.05 vs control) in newborn and 51% +/- 2% (p less than 0.05 vs control) in hypertrophied hearts by 30 minutes of ischemia. We conclude that hypertrophied and newborn hearts have a lower Cai during ischemia compared with adult hearts, and this is associated with a worse recovery of cardiac function. The lower Cai may be the result of irreversible binding of calcium to contractile proteins.
del Nido
P J
PJ
Department of Surgery, University of Pittsburgh, Pa.
Nakamura
H
H
Jimenez
E
E
Sarin
M
M
Feinberg
H
H
Levitsky
S
S
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology; D003600:Cytosol / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D009200:Myocardial Contraction; D009994:Osmolar Concentration; D011817:Rabbits
D001572:Benzofurans; D005456:Fluorescent Dyes; D002118:Calcium; D016257:Fura-2