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The effect of cardiac hypertrophy on changes in cytosolic free calcium concentration during ischemia
P J del Nido1, H Nakamura, E Jimenez
1Department of Surgery, University of Pittsburgh, Pa.
Insights
Newborn and hypertrophied hearts show lower intracellular calcium (Cai) during ischemia, leading to poorer cardiac function recovery. This impaired calcium regulation may stem from irreversible binding to contractile proteins.
Area of Science:
- Cardiology
- Physiology
- Biochemistry
Background:
- Chronic ventricular hypertrophy is a risk factor in congenital cardiac surgery.
- Calcium regulates contractile protein interaction in the heart.
- Altered calcium handling in myocytes may affect cardiac function during ischemia.
Purpose of the Study:
- To investigate the regulation of free cytosolic calcium (Cai) during ischemia in newborn, adult control, and hypertrophied rabbit hearts.
- To determine the relationship between Cai levels and cardiac function recovery after ischemia.
Main Methods:
- Isolated retroperfused rabbit hearts were loaded with the fluorescent probe Fura-2 to measure Cai.
- Experiments involved inducing ischemia at 37°C for up to 50 minutes.
- Cardiac function was assessed by measuring peak developed pressure during ischemia and reperfusion.
Main Results:
- Hypertrophied and newborn hearts exhibited significantly lower Cai levels during ischemia compared to adult control hearts.
- Recovery of peak developed pressure was reduced in newborn (85%) and hypertrophied (67%) hearts post-ischemia.
- Cai levels declined during ischemia in newborn and hypertrophied hearts, unlike in control hearts where they increased.
Conclusions:
- Newborn and hypertrophied hearts demonstrate impaired intracellular calcium regulation during ischemia.
- Lower Cai levels during ischemia are associated with worse cardiac function recovery.
- Irreversible binding of calcium to contractile proteins might explain the reduced Cai in hypertrophied and newborn hearts.
Abstract:
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.