Cardio-ventilatory coupling in young healthy resting subjects

Abstract

In this work, cardio-ventilatory coupling (CVC) refers to the statistical relationship between the onset of either inspiration (I) or expiration (E) and the timing of heartbeats (R-waves) before and after these respiratory events. CVC was assessed in healthy, young (<45 yr), resting, supine subjects (n = 19). Four intervals were analyzed: time from I-onset to both the prior R-wave (R-to-I) and the following R-wave (I-to-R), as well as time from E-onset to both the prior R-wave (R-to-E) and following R-wave (E-to-R). The degree of coupling was quantified in terms of transformed relative Shannon entropy (tRSE), and χ(2) tests based on histograms of interval times from 200 breaths. Subjects were studied twice, from 5 to 27 days apart, and the test-retest reliability of CVC measures was computed. Several factors pointed to the relative importance of the R-to-I interval compared with other intervals. Coupling was significantly stronger for the R-to-I interval, coupling reliability was largest for the R-to-I interval, and only tRSE for the R-to-I interval was correlated with height, weight, and body surface area. The high test-retest reliability for CVC in the R-to-I interval provides support for the hypothesis that CVC strength is a subject trait. Across subjects, a peak ~138 ms prior to I-onset was characteristic of CVC in the R-to-I interval, although individual subjects also had earlier peaks (longer R-to-I intervals). CVC for the R-to-I interval was unrelated to two separate measures of respiratory sinus arrhythmia (RSA), suggesting that these two forms of coupling (CVC and RSA) are independent.

Fig. 1.

Illustration of the steps involved in setting up the binning schemes. The first step is to create an R-to-R interval histogram (A). Next, a cumulative density distribution is created from 0 to the 99.75 percentile of the R-to-R interval histogram (B). Then this distribution was inverted and normalized to a maximum of 1.0 (C). This final distribution is the expected distribution of R-to-I intervals (or any interval between an R wave and the immediately following or preceding I- or E-onset) assuming no coupling (chance). For transformed Relative Shannon Entropy (tRSE), the distribution from 0 to the 0.25 percentile of the R-R distribution (the flat part of the chance distribution) was divided into 20 bins (C). For the −log₁₀(P) analysis, almost the entire distribution (up to 99.75 percentile of the R-R distribution) was divided into 27 equal bins (D). Because the sum of the expected counts in bins 23–27 was often quite small, these bins were combined into a single 23rd bin.

Fig. 2.

The 27-bin interval histograms for 2 subjects (#12 and #20) showing strong CVC (1 subject per row). The first 2 columns present the data from the first visit and the second 2 columns present the data from the second visit. The histograms are centered on either onset of inspiration (I-onset; columns 1 and 3) or expiration (E-onset; columns 2 and 4). I-onset and E-onset occur at time 0, and 27 bins are shown before and after time 0. The number below each histogram is the bin width in ms. The alphabet marks and associated arrows (e.g., a, f) are discussed in Sample Interval Histograms.

Fig. 3.

Composite 27-bin histograms for all four intervals based on a sum across subjects and visits. All histograms, regardless of statistical significance, are included in these composites. The numbers below each bar represent the average bin center, in ms, across subjects and visits. The average bin width was 39.58 ms.

Fig. 4.

Histograms of tRSE values by interval type along with gamma function fits.

Fig. 5.

Histograms of −log₁₀(P) values by interval type along with negative binomial fits.

Fig. 6.

Scatter plot relating rank body surface area (BSA) to rank tRSE for the R-to-I interval. ♀Female subjects.

Fig. 7.

R-to-R intervals before, after and spanning I-onset. Values are means (±SE) for all subjects and visits, after controlling for differences in median heart rate.