Fractal dynamics of heart beat interval fluctuations in corticotropin-releasing factor receptor subtype 2 deficient mice

Non-linear fractal analysis of cardiac interbeat time series was performed in corticotropin-releasing factor receptor subtype 2 (CRFR2) deficient mice. Heart rate dynamics in mice constitutes a self-similar, scale-invariant, random fractal process with persistent intrinsic long-range correlations and inverse power-law properties. We hypothesized that the sustained tachycardic response elicited by intraperitoneal (ip) injection of human/rat CRF (h/rCRF) is mediated by CRFR2. In wildtype control animals, heart rate was increased to about maximum levels (~ 750 bpm) while in CRFR2-deficient animals baseline values were retained (~ 580 bpm). The tachycardic response elicited by ip-application is mediated by CRFR2 and is interpreted to result from sympathetic stimulation. However, the functional integrity of CRFR2 would not present a prerequisite to maintaining the responsiveness and resiliency of cardiac control to external environmental perturbations experimentally induced by extrinsic ip-application of h/rCRF or under physiological conditions that may be associated with an increased peripheral release of CRF. Under stressful physiological conditions achieved by novelty exposure, CRFR2 is not involved in the cardiodynamic regulation to external short-term stress. While the hypothesis of involvement of CRFR2 in cardiac regulation upon pharmacological stimulation cannot be rejected, the present findings suggest that the mechanism of action is by sympathetic stimulation, but would not unambiguously allow to draw any conclusions as to the physiological role of CRFR2 in the control of cardiac dynamics.