We investigated whether autonomic nervous system imbalance imposed by pharmacologic blockades and associated with acute myocardial infarction (AMI) is manifested as modifications of the nonlinear interactions in heart rate variability signal using a statistically-based bispectrum method. The statistically-based bispectrum method is an ideal approach for identifying nonlinear couplings in a system and overcomes the previous limitation of determining in an ad hoc way the presence of such interactions. Using the improved bispectrum method we found significant nonlinear interactions in healthy young subjects, which were abolished by administration of atropine, but were still present after propanolol adiminstration. Complete de-coupling of nonlinear interactions was obtained with double pharmacological blockades. Nonlinear couplings were found to be the strongest for healthy young subjects followed by degradation with old age, and a complete absence of such couplings for the old age-matched AMI subjects. Our results suggest that the presence of nonlinear couplings is largely driven by the parasympathetic nervous system regulation, and that the often-reported autonomic nervous system imbalance seen in AMI subjects is manifested as the absence of nonlinear interactions between the sympathetic and parasympathetic nervous regulations.