Early Left Ventricular Dysfunction Elicits Activation of Sympathetic Drive and Attenuation of Parasympathetic Tone in the Paced Canine Model of Congestive Heart Failure

Abstract

Background Although autonomic imbalance is known to be characteristic of patients with clinically overt symptomatic congestive heart failure, it is currently unknown whether this autonomic response arises early in the course of left ventricular dysfunction or is restricted to the later stages of circulatory failure. Methods and Results This investigation utilized the technique of spectral analysis of heart rate variability in a paced canine model of congestive heart failure that permits an examination of autonomic activity at the earliest stages of ventricular dysfunction to determine whether early systolic dysfunction in congestive heart failure is characterized by autonomic imbalance, which may contribute to subsequent myocardial and vascular dysfunction. The results indicate that autonomic imbalance as reflected in an abnormal pattern of heart rate variability evolves early in the course of ventricular systolic dysfunction consisting of both a significant increase in sympathetically influenced low-frequency heart rate variability and a significant reduction of parasympathetically mediated high-frequency variability. This was quantified by a marked and significant increase in the area under the low-frequency region from 0.053±0.037 (beats per minute) 2 at baseline to 0.182±0.143 (beats per minute) 2 at 48 hours to 0.253± 0.202 (beats per minute) 2 after 7 days of pacing (ANOVA, P <.04). The area under the high-frequency region of the curve showed a decrease from a baseline value of 0.945±0.037 (beats per minute) 2 to 0.811±0.152 (beats per minute) 2 at 48 hours to 0.733±0.197 (beats per minute) 2 after 7 days of pacing (ANOVA, P <.03). This resulted in a shift in autonomic balance away from parasympathetic tone and toward augmented sympathetic drive as reflected by the ratio of high- to low-frequency areas from a baseline value of 15.2±9.6 to 10.1±6.89 at 48 hours and 0.004±0.001 at 7 days (ANOVA, P <.01). Conclusions The results indicate that autonomic imbalance as reflected in an abnormal pattern of heart rate variability evolves early in the course of ventricular systolic dysfunction consisting of both a significant increase in sympathetically influenced low-frequency heart rate variability and a significant reduction of parasympathetically mediated high-frequency variability. The early appearance of these autonomic abnormalities suggests that autonomic imbalance plays a significant role in promoting the progression of circulatory failure.