Reduction of myocardial infarct size in rabbits and inhibition of activation of rabbit and human neutrophils by lidocaine.
Myocardial reperfusion is associated with increased influx of activated neutrophils and intracellular accumulation of sodium in the ischemic zone. Lidocaine is a sodium channel blocker that also inhibits several neutrophil functions. We investigated the effect of lidocaine on infarct size in rabbits undergoing 30 minutes of ischemia and 48 hours of reperfusion. Animals randomly received lidocaine (10 mg/kg, n = 11) or saline (n = 11) during occlusion. The area of necrosis (AN) was measured histologically and expressed as a percentage of the area at risk (AR). Myocardial oxygen consumption and the perfusion bed at risk were similar in the two groups. Lidocaine reduced infarct size compared with control (AN/AR = 30% +/- 4% vs 61% +/- 5%, respectively; p = 0.0001). This reduction was associated with a significant decrease in neutrophil infiltration and in the degree of hemorrhage in the reperfused myocardium. Lidocaine also significantly inhibited superoxide anion production by rabbit and human neutrophils in whole blood. Therefore, lidocaine treatment results in a significant reduction in infarct size in the rabbit model, partly through reduction of neutrophil-mediated injury to viable cells, suggesting that lidocaine may be useful to enhance myocardial salvage in patients undergoing pharmacologic or mechanical reperfusion.
Vitola
J V
JV
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0111, USA.
Forman
M B
MB
Holsinger
J P
JP
Atkinson
J B
JB
Murray
J J
JJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology*; D008163:Luminescent Measurements; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D018375:Neutrophil Activation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D026941:Sodium Channel Blockers
D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D008012:Lidocaine