Running title: Enhanced feedforward mechanism in post infarction

The interactions between systolic arterial pressure (SAP) and RR interval fluctuations after acute myocardial infarction (AMI) were investigated by measures of synchronization separating the feedback from the feedforward control and capturing both linear and nonlinear contributions. The causal synchronization, evaluating the ability of RR to predict SAP (χ s/t) or vice versa (χ t/s), and the global synchronization (χ), were estimated at rest and after head-up tilt in 35 post-AMI patients, 20 Young and 12 Old. Significance and nonlinearity of the coupling were assessed by surrogate data analysis. Tilting increased the number of Young subjects in which RR-SAP link was significant (from 17 to 19) and linear (from 11 to 18). In AMI, both significance and linearity of the coupling were low at rest (26 significant, 24 nonlinear) and further reduced after tilt (17 significant, 16 nonlinear). Old showed a partial recovery of linearity after tilt (rest: 1 linear out of 7 significant; tilt: 5 linear out of 8 significant). In Young, the causal synchronization indexes were balanced and increased from rest (χ t/s =0.072±0.037, χ s/t =0.054±0.028) to tilt (χ t/s =0.125±0.071, χ s/t =0.108±0.053). On the contrary, in Old and AMI the feedforward was prevalent to the feedback coupling at rest (Old: χ t/s =0.041±0.023, χ s/t =0.069±0.042; AMI: χ t/s =0.050±0.030, χ s/t =0.089±0.053). Tilting blunted the unbalance in Old (χ t/s =0.065±0.052, χ s/t =0.069±0.044) but not in AMI (χ t/s =0.040±0.019, χ s/t =0.060±0.040). Thus, after AMI nonlinear mechanisms are elicited in RR-SAP interactions. Further, the neural regulation of the cardiovascular system resulted unbalanced as a consequence of impaired feedback and enhanced feedforward control mechanisms.