Cardiovascular control and time domain granger causality: Insights from selective autonomic blockade

We studied causal relations among heart period (HP), systolic arterial pressure (SAP) and respiration (R) according to the definition of Granger causality in the time domain. Autonomic pharmacological challenges were used to alter the complexity of cardiovascular control. Atropine (AT), propranolol and clonidine (CL) were administered to block muscarinic receptors, β-adrenergic receptors and centrally sympathetic outflow, respectively.We found that: (i) at baseline, HP and SAP interacted in a closed loop with a dominant causal direction from HP to SAP; (ii) pharmacological blockades did not alter the bidirectional closedloop interactions between HP and SAP, but AT reduced the dominance of the causal direction from HP to SAP; (iii) at baseline, bidirectional interactions between HP and R were frequently found; (iv) the closed-loop relation between HP and R was unmodified by the administration of drugs; (v) at baseline, unidirectional interactions from R to SAP were often found; and (vi) while AT induced frequently an uncoupling between R and SAP, CL favoured bidirectional interactions. These results prove that time domain measures of Granger causality can contribute to the description of cardiovascular control by suggesting the temporal direction of the interactions and by separating different causality schemes (e.g. closed loop versus unidirectional relations).