Lidocaine protects from myocardial damage due to ischemia and reperfusion in mice by its antiapoptotic effects.
BACKGROUND
Perioperative myocardial ischemia poses a vital threat to surgical patients. Means to protect postischemic myocardium are clinically not available. Lidocaine has been demonstrated to exert antiinflammatory pleiotropic effects. The authors set out to test if lidocaine protects ischemic myocardium from reperfusion injury.


METHODS
A mouse model of transient coronary artery ligation (30 min) and reperfusion (24 h) was used with animal care committee approval. Infarct size and area-at-risk were determined. Leukocyte recruitment was quantified on immunohistochemical stainings. Apoptosis was assessed using enzyme-linked immunosorbent assay to detect histone modifications and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Lidocaine effects on leukocyte-endothelial interactions were assessed in vitro by using a parallel-plate flow chamber or static adhesion assays.


RESULTS
Infarct size per area-at-risk was reduced by 27% in mice treated with a lidocaine bolus (1 mg/kg) before a continuous infusion (0.6 mg . kg(-1) . h(-1)) during ischemia (P < 0.005). Neutrophil density in the infarct and periinfarct zone was not reduced by lidocaine, although the size of the infiltrated area was. Terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cardiomyocytes and endothelial cells were significantly reduced in the periinfarct zone by lidocaine. In vitro, no effect on leukocyte rolling or firm adhesion to resting or activated endothelium was demonstrable. In vitro, lidocaine reduced cardiomyocyte apoptosis induced by hypoxia and reoxygenation (3h/1h) significantly. Infarct size and in vitro cardiomyocyte apoptosis were likewise reduced when lidocaine bolus and infusion were administered after the ischemic insult.


CONCLUSIONS
Lidocaine exerts cardioprotective effects when administered before or after the ischemic insult. This effect is mediated through an antiapoptotic and not through an antiinflammatory pathway and may be therapeutically exploitable.
Kaczmarek
Dominik J
DJ
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany.
Herzog
Christine
C
Larmann
Jan
J
Gillmann
Hans-Jörg
HJ
Hildebrand
Reinhard
R
Schmitz
Martina
M
Westermann
Anik
A
Harendza
Thomas
T
Werdehausen
Robert
R
Osthaus
Alexander W
AW
Echtermeyer
Frank
F
Hahnenkamp
Klaus
K
Wollert
Kai C
KC
Theilmeier
Gregor
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008012:Lidocaine / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology
D002316:Cardiotonic Agents; D008012:Lidocaine