Calcium sparks in human ventricular cardiomyocytes from patients with terminal heart failure

Cardiomyocytes from terminally failing hearts display significant abnormalities in e-c-coupling, contractility and intracellular Ca2+ handling. This study is the first to demonstrate the influence of end-stage heart failure on specific properties of Ca2+ sparks in human ventricular cardiomyocytes. We investigated the frequency and characteristics of spontaneously arising Ca2+ sparks in single isolated human myocytes from terminally failing (HF) and non-failing (NF) control myocardium by using the Ca2+ indicator Fluo-3. The Ca2+ sparks were recorded by line-scan images along the longitudinal axis of the myocytes at a frequency of 250 Hz. After loading the sarcoplasmic reticulum (SR) with Ca2+ by repetitive field stimulation (10 pulses at 1 Hz) the frequency of the Ca2+ sparks immediately after stimulation (t = 0 s) was reduced significantly in HF compared to NF (4.15 +/- 0.42 for NF vs. 2.81 +/- 0.20 for HF sparks s(-1), P < 0.05). This difference was present constantly in line-scan recordings up to 15 s duration (t = 15 s: 2.75 +/- 0.65 for NF vs. 1.36 +/- 0.34 for HF sparks s(-1), P < 0.05). The relative amplitude (F/F-0) of Ca2+ sparks was also significantly lower in H F cardiomyocytes (1.33 +/- 0.015 NF vs. 1.19+/-0.003 HF, t = 0 s) and during subsequent recordings of 15 s. Significant differences between HF and NF were also present in calculations of specific spark properties. The time to peak was estimated at 25.75 +/- 0.88 ms in HF and 18.68+/-0.45 ms in NF cardiomyocytes (P<0.05). Half-time of decay was 66.48 +/- 1.89 ms (HF) vs. 44.15 +/- 1.65 ms (NF, P<0.05), and the full width at half-maximum (FWHM) was 3.99+/-0.06 mum (HF) vs. 3.5+/-0.07 mum (NF, P<0.05). These data support the hypothesis that even in the absence of cardiac disease, Ca2+ sparks from human cardiomyocytes differ from previous results of animal studies with respect to the time-to-peak, half-time of decay and FWHM. The role of elevated external Ca2+ in HF was studied by recording Ca2+ sparks in HF cardiomyocytes with 10 mmol external Ca2+ concentration. Under these conditions, the average spark amplitude was increased from 1.119+/-0.003 (F/F-0, 2 mmol Ca2+) to 1.26+/-0.01 (F/F-0, 10 mmol Ca2+). We conclude that human heart failure causes distinct changes in Ca2+ spark frequency and characteristics comparable to results established in animal models of heart failure. A reduced Ca2- load of the SR alone is unlikely to account for the observed differences between HF and NF and additional alterations in intracellular Ca2+ release mechanisms must be postulated. (C) 2002, Elsevier Science Ltd. All rights reserved.