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The effect of the cold pressor test on autonomic cardiovascular control was studied non-invasively by means of spectrum analysis of periodic heart rate and blood pressure fluctuations in ten normal subjects. Fast Fourier Transform algorithm based on a 256-point time series (sampling rate 2 Hz, i.e. 2-min and 8-s) was used to estimate the amplitude spectra of heart rate and blood pressure rhythmicity at the low frequency (70-140 mHz) and respiration related frequency (230-270 mHz) band. Respiration rate was controlled at 250 mHz. Auto- and cross-spectral techniques were used to determine the complex relationship between systolic blood pressure and heart rate fluctuations in the frequency domain. The spectral pattern of systolic and diastolic blood pressure showed a marked increment of the absolute and relative (100 multiplied with absolute value/total area under the curve of the amplitude spectrum from 15-500 mHz) low frequency component: control vs. cold pressor test--systolic blood pressure--absolute values (in [mmHg/Hz1/2]): 634.4 +/- 48.9 vs. 827.4 +/- 69.9*; relative values (in [%]): 26 +/- 2 vs. 32 +/- 2*; diastolic blood pressure--absolute values: 433.2 +/- 42.3 vs. 537.2 +/- 45.8*; relative values: 35 +/- 3 vs. 40 +/- 2*, (average +/- SEM, *P < 0.05). The cold pressor test induced no change in average heart rate; the absolute low frequency component in heart rate spectra increased clearly during the test: low frequency component (in [bpm/Hz1/2]): 586.9 +/- 89.9 vs. 712.0 +/- 91.4*, while the relative low frequency component did not change: 29 +/- 3 vs. 30 +/- 3.(ABSTRACT TRUNCATED AT 250 WORDS)

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The proposed strategy offers a possible answer to a major question raised by the community of safety pharmacology. By allowing a more automated analysis of the signals, our approach could contribute to promote the technology based on MEA and hiPSC-CMs and, therefore, improve reliability and efficiency of drug screening.

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