Can baroreflex measurements with spontaneous sequence analysis be improved by also measuring breathing and by standardization of filtering strategies?

Baroreflex sensitivity (BRS) is known to be attenuated by inspiration and all the original BRS methodologies took this into account by measuring only in expiration. Spontaneous sequence analysis (SSA) is a non-invasive clinical tool widely used to estimate BRS in Man but does not take breathing into account. We have therefore modified it to test whether it too can detect inspiratory attenuation. Traditional SSA is also entangled with issues of distinguishing causal from random relationships between blood pressure and heart period and of the optimum choice of data filter settings. We have also tested whether the sequences our modified SSA rejects do behave as random relationships and show the limitations of the absence of filter standardization. SSA was performed on eupneic data from 1 h periods in 20 healthy subjects. Applying SSA traditionally produced a mean BRS of 23 ± 3 ms mmHg(-1). After modification to measure breathing, SSA detected significant inspiratory attenuation (11 ± 1 ms mmHg(-1)), and the mean expiratory BRS was significantly higher (26 ± 5 ms mmHg(-1)). Traditional SSA therefore underestimates BRS by an amount (3 ms mmHg(-1)) as big as the major physiological and clinical factors known to alter BRS. We show that the sequences rejected by SSA do behave like random associations between pressure and period. We also show the minimal effect of the r(2) filter and the biases that some pressure and heart period filters can introduce. We discuss whether SSA might be improved by standardization of filter settings and by also measuring breathing.