Low-frequency blood flow oscillations in congestive heart failure and after beta1-blockade treatment

Abstract

Laser Doppler flowmetry (LDF) of forearm skin blood flow, combined with iontophoretically-administered acetylcholine and sodium nitroprusside and wavelet spectral analysis, was used for noninvasive evaluation of endothelial function in 17 patients newly diagnosed with New York Heart Association class II-III congestive heart failure (CHF). After 20+/-10 weeks' treatment with a beta(1)-blocker (Bisoprolol), the measurements were repeated. Measurements were also made on an age- and sex-matched group of healthy controls (HC). In each case data were recorded for 30 min. In HC, the difference in absolute spectral amplitude of LDF oscillations between the two vasodilators manifests in the frequency interval 0.005-0.0095 Hz (p<0.01); this difference is initially absent in patients with CHF, but appears following the beta(1)-blocker treatment (p<0.01). For HC, the difference between the two vasodilators also manifests in normalised spectral amplitude in 0.0095-0.021 Hz (p<0.05). This latter difference is absent in CHF patients and is unchanged by treatment with beta(1)-blockers. It is concluded that there are two oscillatory skin blood flow components associated with endothelial function. Both are reduced in CHF. Activity in the lower frequency interval is restored by beta(1)-blocker treatment, confirming the association between CHF and endothelial dysfunction but suggesting the involvement of two distinct mechanisms.

Fig. 1

Simultaneously measured LDF signals showing how blood flow changes in response to iontophoresis with the two vasodilators. (a) Timing of the 100 μA iontophoresis current pulses; (b) blood flow in response to ACh; and (c) in response to SNP.

Fig. 2

(a) The wavelet transform of an LDF skin blood flow signal, illustrating the presence of distinct spectral peaks whose frequencies and amplitudes vary in time. The wavelet coefficients, presented in the time–frequency domain, were calculated from the basal flow of a healthy subject at rest. Only a short time section of the transform is presented. (b) A time-average of the wavelet transform showing the division of the frequency scale into six intervals.

Fig. 3

Summary of heart and respiration frequencies (a and c) and their variability (b and d) for the three subject groups. 0.01 < p < 0.05 is indicated by ⁎ and p < 0.01 by ⁎⁎. For an explanation of data presentation and error bars, see text (subsection on statistical analysis and presentation).

Fig. 4

The effects of ACh and SNP on the mean value of the blood flow signal and the average spectral amplitude for the CHF and HC subject groups. p < 0.01 is indicated by ⁎⁎. For an explanation of data presentation and error bars, see text (subsection on statistical analysis and presentation).

Fig. 5

The effects of ACh and SNP on the individual oscillatory components in blood flow for the CHF and HC subject groups. (a) Effect of ACh on the absolute spectral amplitude; (b) its effect on the normalised spectral amplitude; (c) effect of SNP on the absolute spectral amplitude; (d) its effect on normalised spectral amplitude. 0.01 < p < 0.05 is indicated by ⁎ and p < 0.01 by ⁎⁎. For an explanation of data presentation and error bars, see text (subsection on statistical analysis and presentation).

Fig. 6

Effect of β1-blockers. The absolute spectral amplitude (upper row) and normalised spectral amplitude (lower row) are plotted for: (a, d) the HC group; (b, e) the CHF group prior to treatment; (c, f) the CHF group after treatment with β₁-blockers. 0.01 < p < 0.05 is indicated by ⁎ and p < 0.01 by ⁎⁎. For an explanation of data presentation and error bars, see text (subsection on statistical analysis and presentation).

Fig. 7

Comparison of the three subject groups (HC, CHF and CHF-β) in terms of their ACh and SNP responses. Absolute spectral amplitudes are presented in intervals V and VI for (a) ACh response and (b) SNP response. 0.01 < p < 0.05 is indicated by ⁎ and p < 0.01 by ⁎⁎. For an explanation of data presentation and error bars, see text (subsection on statistical analysis and presentation).