Cross correlation is a mathematical function whereby spectral analysis is used to describe the relationship between heart-rate fluctuations (256 R-R intervals) and respiration (simultaneously obtained by pneumotachograph). To assess its usefulness for testing autonomic integrity, cross correlation and deep breathing were compared in 141 diabetic subjects (aged 39 ± 14 yr) and in 77 control subjects (aged 33 ± 13 yr). To characterize patients, Valsalva maneuver, 30:15 ratio, tilt, and handgrip tests were performed in 96 of these patients; 23 had two or more abnormal tests (group A), 28 had one (group B), and 45 had none (group C). Sensitivity to parasympathetic withdrawal was compared in 9 control subjects (aged 26 ± 4 yr) by four sequential 0.01-mg/kg i.v. atropine administrations. Reproducibility was compared in 11 control subjects (aged 25 ± 2 yr) by repeating the tests four times for 2 consecutive days. Considering all 141 patients, cross correlation and deep breathing were <2SD of the mean of control subjects in 64 and 36 subjects, respectively. Considering patients who also performed other tests of autonomic function, cross correlation and deep breathing were <2SD of the mean of controls in 42 and 30 subjects, respectively (group A, 20 and 15; group B, 12 and 9; group C, 10 and 6). Cross correlation had better reproduciblity than deep breathing (C.V. 10.3 vs. 30.6% at 6 breaths/min) and greater sensitivity to atropine (after the 1st injection, cross correlation and deep breathing decreased to 34.6 and 48.2% of baseline values, respectively; P < .05). These data support the use of cross correlation to improve the diagnostic approach to cardiac autonomic damage.

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