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Objective: Septic shock (SS) patients often show elevated heart rate (HR) despite resuscitation, and this condition is considered an early manifestation of myocardial dysfunction due to an impairment of autonomic nervous system (ANS). We aimed at proposing a mathematical model to assess the autonomic control of ventricular contractility (VC) and HR to track changes in heart functionality during an experimental animal model of SS and resuscitation. Methods: SS was induced in six adult swine by polymicrobial peritonitis. We analyzed the beat-to-beat variability of the maximum positive time derivative of left ventricular pressure (dP/dt max), heart period (HP), and aortic blood pressure (ABP). We identified the transfer functions relating fluctuations in ABP and HP to dP/dt max to characterize the static and dynamic properties of the arterial baroreflex and the force-frequency relation mechanisms, respectively. Standard indices of autonomic dysfunction have also been considered as HR variability (HRV) and baroreflex sensitivity (BRS). Results: During baseline, the baroreflex is predominant in controlling VC with a gain value of -5.8 (-7.5,-3) s<sup>-1</sup>, compared to -1.2 (-1.9,-0.5) mmHg/s ms<sup>-1</sup> of the force-frequency autoregulation. During shock, both mechanisms increase their extent in VC control (higher gains and slightly faster dynamics for the baroreflex). After resuscitation, the physiological control of VC is not restored and all the animals still exhibit high HR and reduced HRV and BRS. Conclusion: A condition of cardiovascular inefficiency is persistent after resuscitation and this could be due to autonomic dysfunction. Significance: The ANS in SS is crucial to restore homeostasis. Our model could be used to evaluate the efficacy of treatments on VC and related control mechanisms.

A Mathematical Model of dP/dt Max for the Evaluation of the Dynamic Control of Heart Contractility in Septic Shock