Mechanism of cardioventilatory coupling: insights from cardiac pacing, vagotomy, and sinoaortic denervation in the anesthetized rat

Cardioventilatory coupling (CVC), a temporal alignment between the heartbeat and inspiratory activity, is a major determinant of breath-to-breath variation in observed respiratory rate (f(o)). The cardiac-trigger hypothesis attributes this to adjustments of respiratory timing by baroreceptor afferent impulses to the central respiratory pattern generator. A mathematical model of this hypothesis indicates that apparent CVC in graphical plots of ECG R wave vs. inspiratory time is dependent on the heart rate (HR), the rate of the intrinsic respiratory oscillator (f(i)), and the strength of the hypothetical cardiovascular afferent impulse. Failure to account for HR and f(i) may explain the inconsistent results from previous attempts to identify the neural pathways involved in CVC. Cognizant of these interactions, we factored in the HR-to-f(i) ratio in our examination of the role of the vagus nerve and arterial baroreceptors in CVC by cardiac pacing 29 anesthetized Sprague-Dawley rats and incrementally changing the HR. With the assumption of a relatively constant f(i), CVC could be examined across a range of HR-to-f(o) ratios before and after vagotomy, sinoaortic denervation, and vagotomy + sinoaortic denervation. We confirmed the relation between CVC, HR-to-f(o) ratio, and breath-to-breath respiratory period variability and demonstrated the loss of these relations after baroreceptor elimination. Sham experiments (n = 8) showed that these changes were not due to surgical stress. Our data support the notion that inspiratory timing can be influenced by cardiac afferent activity. We conclude that the putative cardiovascular input arises from the arterial baroreceptors and that the vagus nerve is not critical for CVC.