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.
Barthel
H
H
Klinik für Anaesthesiologie, Universitätklinikum Düsseldorf, Postfach 10 10 07, D-40001 Düsseldorf, Germany.
Ebel
D
D
Müllenheim
J
J
Obal
D
D
Preckel
B
B
Schlack
W
W
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D008012:Lidocaine