Prophylactic lidocaine: concentrations in plasma and myocardial tissue and antifibrillatoric efficacy during early ischemia in dogs and pigs.
We investigated the antifibrillatoric efficacy of lidocaine and the time courses of lidocaine concentrations in plasma and nonischemic (NIM) and ischemic myocardium (IM) during early myocardial ischemia in anesthetized dogs and pigs. Lidocaine (2 or 3 mg/kg bolus + 50, 100, 150, or 500 micrograms/kg.min) was administered over 30 min to 29 dogs and 15 pigs. The left anterior descending coronary artery (LAD) was occluded 2 min after bolus application. Blood and myocardial biopsies were sampled for analysis by high-performance liquid chromatography (HPLC) up to 40 min. In 19 dogs and 6 pigs, we determined the ventricular fibrillation threshold (VFT) with and without lidocaine during acute LAD occlusion for 7-13 min. Dosages leading to therapeutic plasma levels (1.6-4.2 micrograms/ml) resulted in lidocaine concentrations always highest in the IM (IM greater than NIM greater than plasma). Under identical dosages, all lidocaine levels were higher in pigs than in dogs. The IM concentrations decreased less in the pigs. Lidocaine prevented the ischemic drop in VFT and spontaneous fibrillation only at persistent IM concentrations greater than 8 micrograms/g. With therapeutic dosages, this was achieved only in pigs, occluding the LAD as early as 2 or 10 min after bolus application. Lidocaine prophylaxis with clinically recommended dosages in humans will hardly result in myocardial concentrations sufficiently high to be antifibrillatorically effective during early acute ischemia.
Vogt
B
B
Department of Pathophysiology, University of Essen, Federal Republic of Germany.
Martin
C
C
Meesmann
W
W
D000818:Animals; D000889:Anti-Arrhythmia Agents; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008012:Lidocaine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine