| Autor: |
Sipido, Karin R, Stankovicova, Tania, Flameng, Willem, Vanhaecke, Johan, Verdonck, Fons |
| Zdroj: |
Cardiovascular Research; Feb1998, Vol. 37 Issue 2, p478-488, 11p |
| Abstrakt: |
Objectives: Human cardiac muscle from failing heart shows a decrease in active tension development and a rise in diastolic tension at stimulation frequencies above 50–60 beats/min due to both systolic and diastolic dysfunction. We have investigated underlying changes in cellular [Ca2+]i regulation. Methods: Single ventricular myocytes were isolated enzymatically from the explanted hearts of transplant recipients with ischemic cardiomyopathy (nhearts=5, ncells=15) or dilated cardiomyopathy (nhearts=6, ncells=19). Cells were studied during whole-cell patch clamp with fluo-3 and fura-red as [Ca2+]i indicators (36±1°C). Results: In current clamp mode (action potential recording), the amplitude of Ca2+ release from the sarcoplasmic reticulum (SR) decreased at stimulation frequencies above 0.5 Hz; this decrease was more pronounced for cells from dilated cardiomyopathy. Diastolic [Ca2+]i increased at 1 and 2 Hz for both groups. Action potential duration (APD90) decreased with frequency in all cells; in addition there was a drop in plateau potential of 10±1 mV for cells from ischemic cardiomyopathy and of 13±2 mV for cells from dilated cardiomyopathy. In voltage clamp mode the L-type Ca2+ current showed reversible decrease during stimulation at 1 and 2 Hz. Recovery from inactivation during a double pulse protocol was slow (75±3% at 500 ms, 89±3% at 1000 ms) and followed the decay of the [Ca2+]i transient. Conclusions: The negative force-frequency relation of the failing human heart is due to a decrease in Ca2+ release of the cardiac myocytes at frequencies ≥0.5 Hz, more pronounced in dilated than in ischemic cardiomyopathy. Inhibition of ICaL at higher frequencies, at least partially related to an increase in diastolic [Ca2+]i, will contribute to this negative staircase because of a decrease in the trigger for Ca2+ release, and of decreased loading of the SR. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
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