Effect of lidocaine on ischaemic preconditioning in isolated rat heart.

BACKGROUND: Lidocaine is frequently used as an agent to treat ventricular arrhythmias associated with acute myocardial ischaemia. Lidocaine is a potent blocker not only of sodium channels, but also of ATP-sensitive potassium channels. The opening of these channels is a key mechanism of ischaemic preconditioning. We investigated the hypothesis that lidocaine blocks the cardioprotection induced by ischaemic preconditioning. METHODS: Isolated rat hearts (n=60) were subjected to 30 min of no-flow ischaemia and 60 min of reperfusion. Control hearts (CON) underwent no further intervention. Preconditioned hearts (PC) received two 5-min periods of ischaemia separated by 10 min of reflow before the 30 min ischaemia. In three groups, lidocaine was infused at concentrations of 2, 10 or 20 microg ml(-1) for 5 min before the preconditioning ischaemia. Left ventricular developed pressure (LVDP) and infarct size (IS) (triphenyltetrazolium choride staining) were measured as variables of ventricular function and cellular injury, respectively. RESULTS: PC reduced IS from 24.8 (sem 4.1) % to 4.0 (0.7) % of the area at risk (P<0.05). Adding 2 or 10 microg ml(-1) lidocaine had no effect on IS compared with PC alone (3.7 (0.7) %, 6.9 (1.8) %). Adding 20 microg ml(-1) lidocaine increased IS to 14.1 (2.5) % compared with PC (P<0.05). Baseline LVDP was similar in all groups (111.4 (2.1) mm Hg). Compared with CON, PC improved functional recovery (after 60 min of reperfusion; 52.3 (5.9) mm Hg vs 16.0 (4.0) mm Hg, P<0.01). The improved ventricular function was not influenced by addition of 2 or 10 microg ml(-1) lidocaine (47.3 (5.7) mm Hg, not significant; 45.3 (7.3) mm Hg, not significant), but was blocked by the infusion of 20 microg ml(-1) lidocaine (22.5 (8.0) mm Hg, P<0.01 vs PC). CONCLUSIONS: Lidocaine blocks the cardioprotection induced by ischaemic preconditioning only at supratherapeutic concentrations.