Biphasic changes in spontaneous cardiovagal baroreflex sensitivity during passive hyperthermia

Figures

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  Figure 1. Core body temperature and haemodynamic changes during passive hyperthermia. Tracings during the first 60 min were recorded in the animals’ home cages at an air temperature (Ta) of 23 °C. Then, the rats were transferred to a climatic chamber with a Ta of 44 °C. Original data were averaged over 10-s intervals for plotting. Elevated Ta values induced gradual elevation in core body temperature, i.e., passive hyperthermia (a), and biphasic responses of heart rate (b), systolic (c), and pulse (d) pressures.

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  Figure 2. Time-course of changes in cardiovagal baroreflex sensitivity (BRS) during passive hyperthermia. BRS was estimated in 10-s windows and moved in 1-s steps as a transfer function modulus between systolic pressure and R-R interval fluctuations in the low frequency band of R-R interval oscillations (0.2–0.7 Hz) with a coherence limit of 0.5 and negative phase shift. BRS in the home cage and in the climatic chamber at an air temperature (Ta) of 23 °C (a). Cumulative sum of deviations of the actual BRS from the mean BRS (cusum ΔBRS) in the home cage at a Ta of 23 °C (b). BRS in the home cage at a Ta of 23 °C and in the climatic chamber at a Ta of 44 °C (c). Cusum ΔBRS at Ta values of 23 °C and 44 °C (d). Mean BRS values of 10-min bins (e) from data displayed in (a,c). A univariate test for repeated measures ANOVA with Greenhouse-Geisser correction was used to analyse the effects of time spent in the climatic chamber and of Ta on BRS. Interaction time vs. Ta: F(3.79, 34.14) = 21.303, p < 0.0000001, ε = 0.292, partial η2 = 0.703. Pairwise comparisons of BRS at Ta 23 °C vs. 44 °C with the Bonferroni test: *p < 0.0166. Panel (f) displays slopes of cusum ΔBRS curves from panels (b,d). The…

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  Figure 3. Effect of passive hyperthermia on cardiovagal baroreflex sensitivity (BRS) estimated with the sequence method. BRS of sequences of increased systolic pressure and prolonged R-R intervals (a). BRS of sequences of declining systolic pressure and shorter R-R intervals (b). Mean BRS values of 10-min bins (c) from data displayed in (a,b). Effect of time and ambient temperature (Ta) on BRS (up-up and down-down sequences together) was analysed with adjusted (Greenhouse-Geisser) univariate tests for repeated measures ANOVA: F(2.603, 28.624) = 34.558, p < 0.000001, ε = 0.2002, partial η2 = 0.759. Pairwise comparisons of BRS in the climatic chamber with the average BRS in the home cage were performed with the univariate test of significance for planned comparisons and the Bonferroni correction, *p < 0.00625. High-frequency (HF) power of heart rate variability (HRV), a surrogate measure of parasympathetic drive to the sinoatrial node (d).

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  Figure 4. Dependence of cardiovagal baroreflex sensitivity (BRS) on core body (Tc) and air (Ta) temperature. BRS before and during passive hyperthermia plotted against Tc (a). Cumulative sum of BRS deviations from the mean BRS in the climatic chamber at a Ta of 23 °C (cusum ΔBRS) plotted against Tc (b). Breakpoints in the trend of BRS values were identified with MARS. Breakpoint 1 coincides with placing animals into the climatic chamber heated to a Ta of 44 °C. The segment (1–2) corresponds to the period when the Tc of the animals was within the normal range, but BRS was higher than that at a Ta of 23 °C; during the segment (2–3), Tc is increasing and BRS is lower than that in the segment (1–2) but still above BRS at a Ta of 23 °C; after breakpoint 3, BRS is below the reference value; after breakpoint 4, BRS is near zero. Tc at structural breakpoints of the cusum ΔBRS curves (c). The numbers in brackets are standard deviations. Panel (d) shows slopes of segments of cusum ΔBRS curves from the panel (b). Significance of changes in the slopes of segments of cusum ΔBRS curves: F(4,6) = 16.0743, p = 0.002328, n = 10, partial η2 = 0.7272 (Wilks multivariate test for repeated measures). Pairwise…

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  Figure 5. Trend changes in haemodynamic parameters during passive hyperthermia. Systolic pressure (SP, a), heart rate (HR, b), rate-pressure product (RPP, c), pre-ejection time (PET, d) and cardiovagal baroreflex sensitivity (BRS) are plotted against the core body temperature (Tc), as a cumulative sum of deviations (cusum Δ) from the means estimated during the stay in the home cage at an air temperature (Ta) of 23 °C. Breakpoints on cusum curves (arrows, numbers in quadrilaterals) were identified with multivariate adaptive regression splines (n = 10). The period with elevated BRS values ended at a Tc of 38.8 (0.6) °C, and the period with baseline BRS values ended at a Tc of 40.9 (0.4) °C. Breakpoints on haemodynamic cusum curves denote the end of the initial period with approximate baseline values and the beginning of the period characterized by accelerated changes in haemodynamic parameters. The numbers in brackets are standard deviations. Tc values at which trend changes in BRS and haemodynamic parameters occurred were compared with multivariate tests for repeated measures (Wilks) separately for each haemodynamic parameter (e). Univariate tests of significance for planned comparison with…

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  Figure 6. Pharmacological cardiovagal baroreflex desensitization at a core body temperature (Tc) of 40 °C. Muscarinic blockade with oxyphenonium bromide (10 µmol.kg−1) via i.p. injection at a Tc of 40 °C caused abrupt reduction of cardiovagal baroreflex sensitivity (BRS) to values near zero (a). A corresponding shift in the distribution of BRS values (b). The cumulative frequency of BRS values estimated in the home cages at an ambient air temperature (Ta) of 23 °C was different from the BRS cumulative frequency curve in the climatic chamber at a Ta of 44 °C before muscarinic blockade (*p < 0.001, two-sample Kolmogorov-Smirnov test). Oxyphenonium administration caused a significant (#p < 0.001, two-sample Kolmogorov-Smirnov test) change in the distribution of BRS towards low values (b). Muscarinic blockade instantly elevated the heart rate (c) but had no effect on systolic pressure (d).