Role of the autonomic nervous system in cardioprotection by remote preconditioning in isoflurane-anaesthetized dogs

Aims Remote ischaemic preconditioning (rIPC) protects cardiac and non-cardiac tissues against ischaemic injury. Although there is increased demand to investigate its potential clinical applicability, fundamental mechanisms responsible for rIPC-mediated protection remain unresolved. We examined in isoflurane-anaesthetized dogs whether an intact cardiac nervous system was necessary to mediate rIPC protection against ischaemic injury. Methods and results Dogs were randomly allocated to six groups: 1, control (CON, no-rIPC); 2, rIPC (4 x 5 min renal artery occlusion/reperfusion); 3, autonomic ganglionic blockade with hexamethonium (HEX, no-rIPC; 20 mg/kg iv); 4, HEX + rIPC; 5, cardiac decentralization by surgical ablation of extracardiac nerves (DCN, no-rIPC); and 6, DCN + rIPC. All dogs underwent 60 min coronary occlusion and 180 min reperfusion; cardiac haemodynamic parameters were monitored. Regional blood flow (microspheres) in the heart and kidneys was assessed. Necrotic tissue was visualized using triphenyltetrazolium staining and related to anatomic risk zone size (area at risk; P = NS between groups) and coronary collateral blood flow. Infarct size (% AAR) was 29 +/- 5 (mean +/- 1 SD) in CON and 15 +/- 4 in rIPC dogs (P = 0.001 vs. CON); 24 +/- 3 in HEX vs. 12 +/- 2 in HEX + rIPC (P 0.001 vs. HEX); and 20 +/- 2 in DCN vs. 12 +/- 4 in DCN + rIPC (P 0.001 vs. DCN). In CON dogs, infarct size was inversely related to coronary collateral flow; this relation was shifted downwards in all groups pre-treated with rIPC. Conclusion We report robust myocardial protection by rIPC against ischaemic injury in canines that was not abrogated by either pharmacological or surgical decentralization of cardiac nerves.